bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to verify the efficacy and safety of ansofaxine (LY03005) for major depressive disorder
Authors: Mi Weifeng , Di Xiaolan , Wang Yiming , Li Huafang , Xu Xiufeng , Li Lehua , Wang Huaning , Wang Guoqiang , Zhang Kerang , Tian Feng , Luo Jiong , Yang Chanjuan , Zhou Yunfei , Xie Shiping , Zhong Hua , Wu Bin , Yang Dong , Chen Zhenhua , Li Yi , Chen Jindong , Lv Shuyun , Yi Qizhong , Jiang Zhiwei , Tian Jingwei , Zhang Hongyan 
Published: May 2023

AbstractMajor depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice. Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need. A multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-week treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185). The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study. Safety indexes included adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG), and evaluation of suicide tendency and sexual function. Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, −20.0; 160 mg, −19.9) vs. placebo (−14.6; p < 0.0001). All doses of ansofaxine were generally well-tolerated. Treatment-emergent adverse events (TEAEs) were reported by 137 (74.46%) patients in ansofaxine 80 mg group, 144 (78.26%) patients in ansofaxine 160 mg and 125 (67.93%) patients in the placebo group. The incidence of treatment-related adverse events (TRAEs) was 59.2% (109 patients), 65.22% (120 patients) in the 80, 160 mg ansofaxine groups, and 45.11% (83 patients) in the placebo group. The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD. ClinicalTrials.gov Identifier: NCT04853407.
Temporal dynamics in mental health symptoms and loneliness during the COVID-19 pandemic in a longitudinal probability sample: a network analysis
Authors: Odenthal Michael , Schlechter Pascal , Benke Christoph , Pané-Farré Christiane A. 
Published: May 2023

AbstractFiguring out which symptoms are central for symptom escalation during the COVID-19 pandemic is important for targeting prevention and intervention. Previous studies have contributed to the understanding of the course of psychological distress during the pandemic, but less is known about key symptoms of psychological distress over time. Going beyond a pathogenetic pathway perspective, we applied the network approach to psychopathology to examine how psychological distress unfolds in a period of maximum stress (pre-pandemic to pandemic onset) and a period of repeated stress (pandemic peak to pandemic peak). We conducted secondary data analyses with the Understanding Society data (N = 17,761), a longitudinal probability study in the UK with data before (2019), at the onset of (April 2020), and during the COVID-19 pandemic (November 2020 & January 2021). Using the General Health Questionnaire and one loneliness item, we computed three temporal cross-lagged panel network models to analyze psychological distress over time. Specifically, we computed (1) a pre-COVID to first incidence peak network, (2) a first incidence peak to second incidence peak network, and (3) a second incidence peak to third incidence peak network. All networks were highly consistent over time. Loneliness and thinking of self as worthless displayed a high influence on other symptoms. Feeling depressed and not overcoming difficulties had many incoming connections, thus constituting an end-product of symptom cascades. Our findings highlight the importance of loneliness and self-worth for psychological distress during COVID-19, which may have important implications in therapy and prevention. Prevention and intervention measures are discussed, as single session interventions are available that specifically target loneliness and worthlessness to alleviate mental health problems.
Artificial Hsp104-mediated systems for re-localizing protein aggregates
Authors: Fischbach Arthur , Johns Angela , Schneider Kara L. , Hao Xinxin , Tessarz Peter , Nyström Thomas 
Published: May 2023

AbstractSpatial Protein Quality Control (sPQC) sequesters misfolded proteins into specific, organelle-associated inclusions within the cell to control their toxicity. To approach the role of sPQC in cellular fitness, neurodegenerative diseases and aging, we report on the construction of Hsp100-based systems in budding yeast cells, which can artificially target protein aggregates to non-canonical locations. We demonstrate that aggregates of mutant huntingtin (mHtt), the disease-causing agent of Huntington’s disease can be artificially targeted to daughter cells as well as to eisosomes and endosomes with this approach. We find that the artificial removal of mHtt inclusions from mother cells protects them from cell death suggesting that even large mHtt inclusions may be cytotoxic, a trait that has been widely debated. In contrast, removing inclusions of endogenous age-associated misfolded proteins does not significantly affect the lifespan of mother cells. We demonstrate also that this approach is able to manipulate mHtt inclusion formation in human cells and has the potential to be useful as an alternative, complementary approach to study the role of sPQC, for example in aging and neurodegenerative disease.
Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting
Authors: Ruffo Elisa , Butchy Adam A. , Tivon Yaniv , So Victor , Kvorjak Michael , Parikh Avani , Adams Eric L. , Miskov-Zivanov Natasa , Finn Olivera J. , Deiters Alexander , Lohmueller Jason 
Published: May 2023

AbstractChimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors are engineered cell-surface receptors that sense a target antigen and respond by activating T cell receptor signaling or a customized gene program, respectively. Here, to expand the targeting capabilities of these receptors, we develop “universal” receptor systems for which receptor specificity can be directed post-translationally via covalent attachment of a co-administered antibody bearing a benzylguanine (BG) motif. A SNAPtag self-labeling enzyme is genetically fused to the receptor and reacts with BG-conjugated antibodies for covalent assembly, programming antigen recognition. We demonstrate that activation of SNAP-CAR and SNAP-synNotch receptors can be successfully targeted by clinically relevant BG-conjugated antibodies, including anti-tumor activity of SNAP-CAR T cells in vivo in a human tumor xenograft mouse model. Finally, we develop a mathematical model to better define the parameters affecting universal receptor signaling. SNAP receptors provide a powerful strategy to post-translationally reprogram the targeting specificity of engineered cells.
Candida expansion in the gut of lung cancer patients associates with an ecological signature that supports growth under dysbiotic conditions
Authors: Seelbinder Bastian , Lohinai Zoltan , Vazquez-Uribe Ruben , Brunke Sascha , Chen Xiuqiang , Mirhakkak Mohammad , Lopez-Escalera Silvia , Dome Balazs , Megyesfalvi Zsolt , Berta Judit , Galffy Gabriella , Dulka Edit , Wellejus Anja , Weiss Glen J. , Bauer Michael , Hube Bernhard , Sommer Morten O. A. , Panagiotou Gianni 
Published: May 2023

AbstractCandida species overgrowth in the human gut is considered a prerequisite for invasive candidiasis, but our understanding of gut bacteria promoting or restricting this overgrowth is still limited. By integrating cross-sectional mycobiome and shotgun metagenomics data from the stool of 75 male and female cancer patients at risk but without systemic candidiasis, bacterial communities in high Candida samples display higher metabolic flexibility yet lower contributional diversity than those in low Candida samples. We develop machine learning models that use only bacterial taxa or functional relative abundances to predict the levels of Candida genus and species in an external validation cohort with an AUC of 78.6–81.1%. We propose a mechanism for intestinal Candida overgrowth based on an increase in lactate-producing bacteria, which coincides with a decrease in bacteria that regulate short chain fatty acid and oxygen levels. Under these conditions, the ability of Candida to harness lactate as a nutrient source may enable Candida to outcompete other fungi in the gut.
Mastering morphology of non-fullerene acceptors towards long-term stable organic solar cells
Authors: An Kang , Zhong Wenkai , Peng Feng , Deng Wanyuan , Shang Ying , Quan Huilei , Qiu Hong , Wang Cheng , Liu Feng , Wu Hongbin , Li Ning , Huang Fei , Ying Lei 
Published: May 2023

AbstractDespite the rapid progress of organic solar cells based on non-fullerene acceptors, simultaneously achieving high power conversion efficiency and long-term stability for commercialization requires sustainable research effort. Here, we demonstrate stable devices by integrating a wide bandgap electron-donating polymer (namely PTzBI-dF) and two acceptors (namely L8BO and Y6) that feature similar structures yet different thermal and morphological properties. The organic solar cell based on PTzBI-dF:L8BO:Y6 could achieve a promising efficiency of 18.26% in the conventional device structure. In the inverted structure, excellent long-term thermal stability over 1400 h under 85 °C continuous heating is obtained. The improved performance can be ascribed to suppressed charge recombination along with appropriate charge transport. We find that the morphological features in terms of crystalline coherence length of fresh and aged films can be gradually regulated by the weight ratio of L8BO:Y6. Additionally, the occurrence of melting point decrease and reduced enthalpy in PTzBI-dF:L8BO:Y6 films could prohibit the amorphous phase to cluster, and consequently overcome the energetic traps accumulation aroused by thermal stress, which is a critical issue in high efficiency non-fullerene acceptors-based devices. This work provides insight into understanding non-fullerene acceptors-based organic solar cells for improved efficiency and stability.
In situ continuous Dopa supply by responsive artificial enzyme for the treatment of Parkinson’s disease
Authors: Fang Xiao , Yuan Meng , Zhao Fang , Yu Aoling , Lin Qianying , Li Shiqing , Li Huichen , Wang Xinyang , Yu Yanbin , Wang Xin , Lin Qitian , Lu Chunhua , Yang Huanghao 
Published: May 2023

AbstractOral dihydroxyphenylalanine (Dopa) administration to replenish neuronal dopamine remains the most effective treatment for Parkinson’s disease (PD). However, unlike the continuous and steady dopamine signaling in normal neurons, oral Dopa induces dramatic fluctuations in plasma Dopa levels, leading to Dopa-induced dyskinesia. Herein, we report a functional nucleic acid-based responsive artificial enzyme (FNA-Fe3O4) for in situ continuous Dopa production. FNA-Fe3O4can cross the blood-brain barrier and target diseased neurons relying on transferrin receptor aptamer. Then, FNA-Fe3O4responds to overexpressed α-synuclein mRNA in diseased neurons for antisense oligonucleotide treatment and fluorescence imaging, while converting to tyrosine aptamer-based artificial enzyme (Apt-Fe3O4) that mimics tyrosine hydroxylase for in situ continuous Dopa production. In vivo FNA-Fe3O4treatment results in recovery of Dopa and dopamine levels and decrease of pathological overexpressed α-synuclein in PD mice model, thus ameliorating motor symptoms and memory deficits. The presented functional nucleic acid-based responsive artificial enzyme strategy provides a more neuron friendly approach for the diagnosis and treatment of PD.
Unified theoretical framework for black carbon mixing state allows greater accuracy of climate effect estimation
Authors: Wang Jiandong , Wang Jiaping , Cai Runlong , Liu Chao , Jiang Jingkun , Nie Wei , Wang Jinbo , Moteki Nobuhiro , Zaveri Rahul A. , Huang Xin , Ma Nan , Chen Ganzhen , Wang Zilin , Jin Yuzhi , Cai Jing , Zhang Yuxuan , Chi Xuguang , Holanda Bruna A. , Xing Jia , Liu Tengyu , Qi Ximeng , Wang Qiaoqiao , Pöhlker Christopher , Su Hang , Cheng Yafang , Wang Shuxiao , Hao Jiming , Andreae Meinrat O. , Ding Aijun 
Published: May 2023

AbstractBlack carbon (BC) plays an important role in the climate system because of its strong warming effect, yet the magnitude of this effect is highly uncertain owing to the complex mixing state of aerosols. Here we build a unified theoretical framework to describe BC’s mixing states, linking dynamic processes to BC coating thickness distribution, and show its self-similarity for sites in diverse environments. The size distribution of BC-containing particles is found to follow a universal law and is independent of BC core size. A new mixing state module is established based on this finding and successfully applied in global and regional models, which increases the accuracy of aerosol climate effect estimations. Our theoretical framework links observations with model simulations in both mixing state description and light absorption quantification.
Nearly 100% selective and visible-light-driven methane conversion to formaldehyde via. single-atom Cu and Wδ+
Authors: Luo Lei , Han Xiaoyu , Wang Keran , Xu Youxun , Xiong Lunqiao , Ma Jiani , Guo Zhengxiao , Tang Junwang 
Published: May 2023

AbstractDirect solar-driven methane (CH4) reforming is highly desirable but challenging, particularly to achieve a value-added product with high selectivity. Here, we identify a synergistic ensemble effect of atomically dispersed copper (Cu) species and partially reduced tungsten (Wδ+), stabilised over an oxygen-vacancy-rich WO3, which enables exceptional photocatalytic CH4conversion to formaldehyde (HCHO) under visible light, leading to nearly 100% selectivity, a very high yield of 4979.0 μmol·g−1within 2 h, and the normalised mass activity of 8.5 × 106 μmol·g-1Cu·h−1of HCHO at ambient temperature. In-situ EPR and XPS analyses indicate that the Cu species serve as the electron acceptor, promoting the photo-induced electron transfer from the conduction band to O2, generating reactive •OOH radicals. In parallel, the adjacent Wδ+species act as the hole acceptor and the preferred adsorption and activation site of H2O to produce hydroxyl radicals (•OH), and thus activate CH4to methyl radicals (•CH3). The synergy of the adjacent dual active sites boosts the overall efficiency and selectivity of the conversion process.
Moist and warm conditions in Eurasia during the last glacial of the Middle Pleistocene Transition
Authors: Sánchez Goñi María Fernanda , Extier Thomas , Polanco-Martínez Josué M. , Zorzi Coralie , Rodrigues Teresa , Bahr André 
Published: May 2023

Abstract
The end of the Middle Pleistocene Transition (MPT, ~ 800-670 thousand years before present, ka) was characterised by the emergence of large glacial ice-sheets associated with anomalously warm North Atlantic sea surface temperatures enhancing moisture production. Still, the direction and intensity of moisture transport across Eurasia towards potential ice-sheets is poorly constrained. To reconstruct late MPT moisture production and dispersal, we combine records of upper ocean temperature and pollen-based Mediterranean forest cover, a tracer of westerlies and precipitation, from a subtropical drill-core collected off South-West Iberia, with records of East Asia summer monsoon (EASM) strength and West Pacific surface temperatures, and model simulations. Here we show that south-western European winter precipitation and EASM strength reached high levels during the Marine Isotope Stage 18 glacial. This anomalous situation was caused by nearly-continuous moisture supply from both oceans and its transport to higher latitudes through the westerlies, likely fuelling the accelerated expansion of northern hemisphere ice-sheets during the late MPT.
Confinement of unliganded EGFR by tetraspanin nanodomains gates EGFR ligand binding and signaling
Authors: Sugiyama Michael G. , Brown Aidan I. , Vega-Lugo Jesus , Borges Jazlyn P. , Scott Andrew M. , Jaqaman Khuloud , Fairn Gregory D. , Antonescu Costin N. 
Published: May 2023

AbstractThe epidermal growth factor receptor (EGFR) is a central regulator of cell physiology. EGFR is activated by ligand binding, triggering receptor dimerization, activation of kinase activity, and intracellular signaling. EGFR is transiently confined within various plasma membrane nanodomains, yet how this may contribute to regulation of EGFR ligand binding is poorly understood. To resolve how EGFR nanoscale compartmentalization gates ligand binding, we developed single-particle tracking methods to track the mobility of ligand-bound and total EGFR, in combination with modeling of EGFR ligand binding. In comparison to unliganded EGFR, ligand-bound EGFR is more confined and distinctly regulated by clathrin and tetraspanin nanodomains. Ligand binding to unliganded EGFR occurs preferentially in tetraspanin nanodomains, and disruption of tetraspanin nanodomains impairs EGFR ligand binding and alters the conformation of the receptor’s ectodomain. We thus reveal a mechanism by which EGFR confinement within tetraspanin nanodomains regulates receptor signaling at the level of ligand binding.
Highly host-linked viromes in the built environment possess habitat-dependent diversity and functions for potential virus-host coevolution
Authors: Du Shicong , Tong Xinzhao , Lai Alvin C. K. , Chan Chak K. , Mason Christopher E. , Lee Patrick K. H. 
Published: May 2023

AbstractViruses in built environments (BEs) raise public health concerns, yet they are generally less studied than bacteria. To better understand viral dynamics in BEs, this study assesses viromes from 11 habitats across four types of BEs with low to high occupancy. The diversity, composition, metabolic functions, and lifestyles of the viromes are found to be habitat dependent. Caudoviricetes species are ubiquitous on surface habitats in the BEs, and some of them are distinct from those present in other environments. Antimicrobial resistance genes are identified in viruses inhabiting surfaces frequently touched by occupants and in viruses inhabiting occupants’ skin. Diverse CRISPR/Cas immunity systems and anti-CRISPR proteins are found in bacterial hosts and viruses, respectively, consistent with the strongly coupled virus–host links. Evidence of viruses potentially aiding host adaptation in a specific-habitat manner is identified through a unique gene insertion. This work illustrates that virus–host interactions occur frequently in BEs and that viruses are integral members of BE microbiomes.
Multiplatform molecular profiling uncovers two subgroups of malignant peripheral nerve sheath tumors with distinct therapeutic vulnerabilities
Authors: Suppiah Suganth , Mansouri Sheila , Mamatjan Yasin , Liu Jeffrey C. , Bhunia Minu M. , Patil Vikas , Rath Prisni , Mehani Bharati , Heir Pardeep , Bunda Severa , Velez-Reyes German L. , Singh Olivia , Ijad Nazanin , Pirouzmand Neda , Dalcourt Tatyana , Meng Ying , Karimi Shirin , Wei Qingxia , Nassiri Farshad , Pugh Trevor J. , Bader Gary D. , Aldape Kenneth D. , Largaespada David A. , Zadeh Gelareh 
Published: May 2023

AbstractMalignant peripheral nerve sheath tumor (MPNST) is a highly aggressive sarcoma, and a lethal neurofibromatosis type 1-related malignancy, with little progress made on treatment strategies. Here, we apply a multiplatform integrated molecular analysis on 108 tumors spanning the spectrum of peripheral nerve sheath tumors to identify candidate drivers of MPNST that can serve as therapeutic targets. Unsupervised analyses of methylome and transcriptome profiles identify two distinct subgroups of MPNSTs with unique targetable oncogenic programs. We establish two subgroups of MPNSTs: SHH pathway activation in MPNST-G1 and WNT/ß-catenin/CCND1 pathway activation in MPNST-G2. Single nuclei RNA sequencing characterizes the complex cellular architecture and demonstrate that malignant cells from MPNST-G1 and MPNST-G2 have neural crest-like and Schwann cell precursor-like cell characteristics, respectively. Further, in pre-clinical models of MPNST we confirm that inhibiting SHH pathway in MPNST-G1 prevent growth and malignant progression, providing the rational for investigating these treatments in clinical trials.
Gesticulation in individuals with at risk mental states for psychosis
Authors: Lopes-Rocha Ana Caroline , de Paula Ramos Willian Henrique , Argolo Felipe , Gondim João Medrado , Mota Natalia Bezerra , Andrade Julio Cesar , Jafet Andrea Fontes , de Medeiros Matheus Wanderley , Serpa Mauricio Henriques , Cecchi Guillermo , Ara Anderson , Gattaz Wagner Farid , Corcoran Cheryl Mary , Loch Alexandre Andrade 
Published: May 2023

AbstractNonverbal communication (NVC) is a complex behavior that involves different modalities that are impaired in the schizophrenia spectrum, including gesticulation. However, there are few studies that evaluate it in individuals with at-risk mental states (ARMS) for psychosis, mostly in developed countries. Given our prior findings of reduced movement during speech seen in Brazilian individuals with ARMS, we now aim to determine if this can be accounted for by reduced gesticulation behavior. Fifty-six medication-naïve ARMS and 64 healthy controls were filmed during speech tasks. The frequency of specifically coded gestures across four categories (and self-stimulatory behaviors) were compared between groups and tested for correlations with prodromal symptoms of the Structured Interview for Prodromal Syndromes (SIPS) and with the variables previously published. ARMS individuals showed a reduction in one gesture category, but it did not survive Bonferroni’s correction. Gesture frequency was negatively correlated with prodromal symptoms and positively correlated with the variables of the amount of movement previously analyzed. The lack of significant differences between ARMS and control contradicts literature findings in other cultural context, in which a reduction is usually seen in at-risk individuals. However, gesture frequency might be a visual proxy of prodromal symptoms, and of other movement abnormalities. Results show the importance of analyzing NVC in ARMS and of considering different cultural and sociodemographic contexts in the search for markers of these states.
Contralateral bone conducted sound wave propagation on the skull bones in fresh frozen cadaver
Authors: Lee Jihyeon , Cho Wan-Ho , Kong Tae Hoon , Jung Sung-Soo , Han Woojae , Park Sihun , Seo Young Joon 
Published: May 2023

AbstractThe study aimed to investigate the efficient pathway for BC sound transmission by measuring vibrations on the opposite side of the skull bone, referred to as the mastoid position. The realistic contralateral transmission pathway of bone conduction (BC) vibrations is investigated through each osseous structure in the midlines of the fresh-frozen whole head. BC stimulation is applied to the mastoid using a bone vibrator, and acceleration responses are observed on the contralateral mastoid bone and seven midline points of skull bones using triaxial accelerometers. The study finds that the range showing the highest contralateral transmission efficiency of bone vibration is the intermediate frequency range with contralateral direction. Within this range, a significant amplitude of acceleration response is measured at the face-side points and the back and upper parts of the head. The thesis suggests that signal transmission from the specific midline to the mastoid can be more efficient than the conventional configuration of BC from the mastoid to the mastoid.