bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification
Authors: Li Kang , Zhang Caihua , Zhou Ruoxing , Cheng Maosheng , Ling Rongsong , Xiong Gan , Ma Jieyi , Zhu Yan , Chen Shuang , Chen Jie , Chen Demeng , Peng Liang 
Published: April 2024

AbstractHead and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.
Phase II study of novel orally PI3Kα/δ inhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma
Authors: Wang Huaqing , Feng Jifeng , Liu Yanyan , Qian Zhengzi , Gao Da , Ran Xuehong , Zhou Hui , Liu Lihong , Wang Binghua , Fang Meiyun , Zhou Hebing , Huang Zhenqian , Tao Shi , Chen Zhuowen , Su Liping , Su Hang , Yang Yu , Xie Xiaobao , Wu Huijing , Sun Ping , Hu Guoyu , Liang Aibin , Li Zhiming 
Published: April 2024

AbstractThis registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3–93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.
Therapeutic role of PTEN in tissue regeneration for management of neurological disorders: stem cell behaviors to an in-depth review
Authors: Li Yue , Ma Ruishuang , Hao Xia 
Published: April 2024

AbstractPhosphatase and tensin homolog deleted on chromosome 10 (PTEN) represents the initial tumor suppressor gene identified to possess phosphatase activity, governing various cellular processes including cell cycle regulation, migration, metabolic pathways, autophagy, oxidative stress response, and cellular senescence. Current evidence suggests that PTEN is critical for stem cell maintenance, self-renewal, migration, lineage commitment, and differentiation. Based on the latest available evidence, we provide a comprehensive overview of the mechanisms by which PTEN regulates activities of different stem cell populations and influences neurological disorders, encompassing autism, stroke, spinal cord injury, traumatic brain injury, Alzheimer’s disease and Parkinson’s disease. This review aims to elucidate the therapeutic impacts and mechanisms of PTEN in relation to neurogenesis or the stem cell niche across a range of neurological disorders, offering a foundation for innovative therapeutic approaches aimed at tissue repair and regeneration in neurological disorders.
Outcomes of patients with Juvenile Polyposis-Hereditary Haemorrhagic Telangiectasia caused by pathogenic SMAD4 variants in a pan-Scotland cohort
Authors: Pearson Madeline , McGowan Ruth , Greene Philip , Lam Wayne , Miedzybrodzka Zofia , Berg Jonathan 
Published: April 2024

AbstractConstitutional loss of SMAD4 function results in Juvenile Polyposis-Hereditary Haemorrhagic Telangiectasia Overlap Syndrome (JP-HHT). A retrospective multi-centre case-note review identified 28 patients with a pathogenic SMAD4 variant from 13 families across all Scottish Clinical Genetics Centres. This provided a complete clinical picture of the Scottish JP-HHT cohort. Colonic polyps were identified in 87% (23/28) and gastric polyps in 67% (12/18) of screened patients. Complication rates were high: 43% (10/23) of patients with polyps required a colectomy and 42% (5/12) required a gastrectomy. Colorectal cancer occurred in 25% (7/28) of patients, at a median age of 33 years. Pulmonary arteriovenous malformations were identified in 42% (8/19) of screened patients. 88% (23/26) and 81% (17/21) of patients exhibited JP and HHT features respectively, with 70% (14/20) demonstrating features of both conditions. We have shown that individuals with a pathogenic SMAD4 variant are all at high risk of both gastrointestinal neoplasia and HHT-related vascular complications, requiring a comprehensive screening programme.
ATP-free in vitro biotransformation of starch-derived maltodextrin into poly-3-hydroxybutyrate via acetyl-CoA
Authors: Wei Xinlei , Yang Xue , Hu Congcong , Li Qiangzi , Liu Qianqian , Wu Yue , Xie Leipeng , Ning Xiao , Li Fei , Cai Tao , Zhu Zhiguang , Zhang Yi-Heng P. Job , Zhang Yanfei , Chen Xuejun , You Chun 
Published: April 2024

AbstractIn vitro biotransformation (ivBT) facilitated by in vitro synthetic enzymatic biosystems (ivSEBs) has emerged as a highly promising biosynthetic platform. Several ivSEBs have been constructed to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA). However, some systems are hindered by their reliance on costly ATP, limiting their practicality. This study presents the design of an ATP-free ivSEB for one-pot PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate. Stoichiometric analysis indicates this ivSEB can self-maintain NADP+/NADPH balance and achieve a theoretical molar yield of 133.3%. Leveraging simple one-pot reactions, our ivSEBs achieved a near-theoretical molar yield of 125.5%, the highest PHB titer (208.3 mM, approximately 17.9 g/L) and the fastest PHB production rate (9.4 mM/h, approximately 0.8 g/L/h) among all the reported ivSEBs to date, and demonstrated easy scalability. This study unveils the promising potential of ivBT for the industrial-scale production of PHB and other acetyl-CoA-derived chemicals from starch.
An optoacoustic field-programmable perceptron for recurrent neural networks
Authors: Becker Steven , Englund Dirk , Stiller Birgit 
Published: April 2024

AbstractRecurrent neural networks (RNNs) can process contextual information such as time series signals and language. But their tracking of internal states is a limiting factor, motivating research on analog implementations in photonics. While photonic unidirectional feedforward neural networks (NNs) have demonstrated big leaps, bi-directional optical RNNs present a challenge: the need for a short-term memory that (i) programmable and coherently computes optical inputs, (ii) minimizes added noise, and (iii) allows scalability. Here, we experimentally demonstrate an optoacoustic recurrent operator (OREO) which meets (i, ii, iii). OREO contextualizes the information of an optical pulse sequence via acoustic waves. The acoustic waves link different optical pulses, capturing their information and using it to manipulate subsequent operations. OREO’s all-optical control on a pulse-by-pulse basis offers simple reconfigurability and is used to implement a recurrent drop-out and pattern recognition of 27 optical pulse patterns. Finally, we introduce OREO as bi-directional perceptron for new classes of optical NNs.
Differentiation shifts from a reversible to an irreversible heterochromatin state at the DM1 locus
Authors: Handal Tayma , Juster Sarah , Abu Diab Manar , Yanovsky-Dagan Shira , Zahdeh Fouad , Aviel Uria , Sarel-Gallily Roni , Michael Shir , Bnaya Ester , Sebban Shulamit , Buganim Yosef , Drier Yotam , Mouly Vincent , Kubicek Stefan , van den Broek Walther J. A. A. , Wansink Derick G. , Epsztejn-Litman Silvina , Eiges Rachel 
Published: April 2024

AbstractEpigenetic defects caused by hereditary or de novo mutations are implicated in various human diseases. It remains uncertain whether correcting the underlying mutation can reverse these defects in patient cells. Here we show by the analysis of myotonic dystrophy type 1 (DM1)-related locus that in mutant human embryonic stem cells (hESCs), DNA methylation and H3K9me3 enrichments are completely abolished by repeat excision (CTG2000 expansion), whereas in patient myoblasts (CTG2600 expansion), repeat deletion fails to do so. This distinction between undifferentiated and differentiated cells arises during cell differentiation, and can be reversed by reprogramming of gene-edited myoblasts. We demonstrate that abnormal methylation in DM1 is distinctively maintained in the undifferentiated state by the activity of the de novo DNMTs (DNMT3b in tandem with DNMT3a). Overall, the findings highlight a crucial difference in heterochromatin maintenance between undifferentiated (sequence-dependent) and differentiated (sequence-independent) cells, thus underscoring the role of differentiation as a locking mechanism for repressive epigenetic modifications at the DM1 locus.
Mechanism and structural dynamics of sulfur transfer during de novo [2Fe-2S] cluster assembly on ISCU2
Authors: Schulz Vinzent , Steinhilper Ralf , Oltmanns Jonathan , Freibert Sven-A. , Krapoth Nils , Linne Uwe , Welsch Sonja , Hoock Maren H. , Schünemann Volker , Murphy Bonnie J. , Lill Roland 
Published: April 2024

AbstractMaturation of iron-sulfur proteins in eukaryotes is initiated in mitochondria by the core iron-sulfur cluster assembly (ISC) complex, consisting of the cysteine desulfurase sub-complex NFS1-ISD11-ACP1, the scaffold protein ISCU2, the electron donor ferredoxin FDX2, and frataxin, a protein dysfunctional in Friedreich’s ataxia. The core ISC complex synthesizes [2Fe-2S] clusters de novo from Fe and a persulfide (SSH) bound at conserved cluster assembly site residues. Here, we elucidate the poorly understood Fe-dependent mechanism of persulfide transfer from cysteine desulfurase NFS1 to ISCU2. High-resolution cryo-EM structures obtained from anaerobically prepared samples provide snapshots that both visualize different stages of persulfide transfer from Cys381NFS1 to Cys138ISCU2 and clarify the molecular role of frataxin in optimally positioning assembly site residues for fast sulfur transfer. Biochemical analyses assign ISCU2 residues essential for sulfur transfer, and reveal that Cys138ISCU2 rapidly receives the persulfide without a detectable intermediate. Mössbauer spectroscopy assessing the Fe coordination of various sulfur transfer intermediates shows a dynamic equilibrium between pre- and post-sulfur-transfer states shifted by frataxin. Collectively, our study defines crucial mechanistic stages of physiological [2Fe-2S] cluster assembly and clarifies frataxin’s molecular role in this fundamental process.
Distinct information conveyed to the olfactory bulb by feedforward input from the nose and feedback from the cortex
Authors: Zak Joseph D. , Reddy Gautam , Konanur Vaibhav , Murthy Venkatesh N. 
Published: April 2024

AbstractSensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical feedback projections numerically match sensory inputs. To unravel information carried by these two streams, we imaged the activity of olfactory sensory neurons (OSNs) and cortical axons in the mouse OB using calcium indicators, multiphoton microscopy, and diverse olfactory stimuli. Here, we show that odorant mixtures of increasing complexity evoke progressively denser OSN activity, yet cortical feedback activity is of similar sparsity for all stimuli. Also, representations of complex mixtures are similar in OSNs but are decorrelated in cortical axons. While OSN responses to increasing odorant concentrations exhibit a sigmoidal relationship, cortical axonal responses are complex and nonmonotonic, which can be explained by a model with activity-dependent feedback inhibition in the cortex. Our study indicates that early-stage olfactory circuits have access to local feedforward signals and global, efficiently formatted information about odor scenes through cortical feedback.
Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection
Authors: Liu Chang , Das Raksha , Dijokaite-Guraliuc Aiste , Zhou Daming , Mentzer Alexander J. , Supasa Piyada , Selvaraj Muneeswaran , Duyvesteyn Helen M. E. , Ritter Thomas G. , Temperton Nigel , Klenerman Paul , Dunachie Susanna J. , Paterson Neil G. , Williams Mark A. , Hall David R. , Fry Elizabeth E. , Mongkolsapaya Juthathip , Ren Jingshan , Stuart David I. , Screaton Gavin R. 
Published: April 2024

AbstractThe rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of BA.4/5 mAbs culminating in total loss of function with recent XBB.1.5.70 variants containing the so-called ‘FLip’ mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86.
Neoadjuvant tislelizumab plus stereotactic body radiotherapy and adjuvant tislelizumab in early-stage resectable hepatocellular carcinoma: the Notable-HCC phase 1b trial
Authors: Li Zhongchao , Liu Jing , Zhang Bo , Yue Jinbo , Shi Xuetao , Cui Kai , Liu Zhaogang , Chang Zhibin , Sun Zhicheng , Li Mingming , Yang Yue , Ma Zhao , Li Lei , Zhang Chengsheng , Sun Pengfei , Zhong Jingtao , Zhao Lei 
Published: April 2024

AbstractNotable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3$$\times $$
×
Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.
Robust compression and detection of epileptiform patterns in ECoG using a real-time spiking neural network hardware framework
Authors: Costa Filippo , Schaft Eline V. , Huiskamp Geertjan , Aarnoutse Erik J. , van’t Klooster Maryse A. , Krayenbühl Niklaus , Ramantani Georgia , Zijlmans Maeike , Indiveri Giacomo , Sarnthein Johannes 
Published: April 2024

AbstractInterictal Epileptiform Discharges (IED) and High Frequency Oscillations (HFO) in intraoperative electrocorticography (ECoG) may guide the surgeon by delineating the epileptogenic zone. We designed a modular spiking neural network (SNN) in a mixed-signal neuromorphic device to process the ECoG in real-time. We exploit the variability of the inhomogeneous silicon neurons to achieve efficient sparse and decorrelated temporal signal encoding. We interface the full-custom SNN device to the BCI2000 real-time framework and configure the setup to detect HFO and IED co-occurring with HFO (IED-HFO). We validate the setup on pre-recorded data and obtain HFO rates that are concordant with a previously validated offline algorithm (Spearman’s ρ = 0.75, p = 1e-4), achieving the same postsurgical seizure freedom predictions for all patients. In a remote on-line analysis, intraoperative ECoG recorded in Utrecht was compressed and transferred to Zurich for SNN processing and successful IED-HFO detection in real-time. These results further demonstrate how automated remote real-time detection may enable the use of HFO in clinical practice.
Ultrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device
Authors: Wang Yunxiang , Chen Hong , Lin Kai , Han Yongjun , Gu Zhixia , Wei Hongjuan , Mu Kai , Wang Dongfeng , Liu Liyan , Jin Ronghua , Song Rui , Rong Zhen , Wang Shengqi 
Published: April 2024

AbstractThe emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a single-step CRISPR-based diagnostic platform, termed SCOPE (Streamlined CRISPR On Pod Evaluation platform), for field-deployable ultrasensitive detection of MPXV in resource-limited settings. The viral nucleic acids are rapidly released from the rash fluid swab, oral swab, saliva, and urine samples in 2 min via a streamlined viral lysis protocol, followed by a 10-min single-step recombinase polymerase amplification (RPA)-CRISPR/Cas13a reaction. A pod-shaped vest-pocket analysis device achieves the whole process for reaction execution, signal acquisition, and result interpretation. SCOPE can detect as low as 0.5 copies/µL (2.5 copies/reaction) of MPXV within 15 min from the sample input to the answer. We validate the developed assay on 102 clinical samples from male patients / volunteers, and the testing results are 100% concordant with the real-time PCR. SCOPE achieves a single-molecular level sensitivity in minutes with a simplified procedure performed on a miniaturized wireless device, which is expected to spur substantial progress to enable the practice application of CRISPR-based diagnostics techniques in a point-of-care setting.
Nanoparticles as an antidote for poisoned gold single-atom catalysts in sustainable propylene epoxidation
Authors: Wang Qianhong , Sang Keng , Liu Changwei , Zhang Zhihua , Chen Wenyao , Ji Te , Li Lina , Lian Cheng , Qian Gang , Zhang Jing , Zhou Xinggui , Yuan Weikang , Duan Xuezhi 
Published: April 2024

AbstractThe development of sustainable and anti-poisoning single-atom catalysts (SACs) is essential for advancing their research from laboratory to industry. Here, we present a proof-of-concept study on the poisoning of Au SACs, and the antidote of Au nanoparticles (NPs), with trace addition shown to reinforce and sustain propylene epoxidation. Multiple characterizations, kinetics investigations, and multiscale simulations reveal that Au SACs display remarkable epoxidation activity at a low propylene coverage, but become poisoned at higher coverages. Interestingly, Au NPs can synergistically cooperate with Au SACs by providing distinct active sites required for H2/O2 and C3H6 activations, as well as hydroperoxyl radical to restore poisoned SACs. The difference in reaction order between C3H6 and H2 (nC3H6-nH2) is identified as the descriptor for establishing the volcano curves, which can be fine-tuned by the intimacy and composition of SACs and NPs to achieve a rate-matching scenario for the formation, transfer, and consumption of hydroperoxyl. Consequently, only trace addition of Au NPs antidote (0.3% ratio of SACs) stimulates significant improvements in propylene oxide formation rate, selectivity, and H2 efficiency compared to SACs alone, offering a 56-fold, 3-fold, and 22-fold increase, respectively, whose performances can be maintained for 150 h.
Direct conversion of methane to aromatics and hydrogen via a heterogeneous trimetallic synergistic catalyst
Authors: Zhu Pengxi , Bian Wenjuan , Liu Bin , Deng Hao , Wang Lucun , Huang Xiaozhou , Spence Stephanie L. , Lin Feng , Duan Chuancheng , Ding Dong , Dong Pei , Ding Hanping 
Published: April 2024

AbstractNon-oxidative methane dehydro-aromatization reaction can co-produce hydrogen and benzene effectively on a molybdenum-zeolite based thermochemical catalyst, which is a very promising approach for natural-gas upgrading. However, the low methane conversion and aromatics selectivity and weak durability restrain the realistic application for industry. Here, a mechanism for enhancing catalysis activity on methane activation and carbon-carbon bond coupling has been found to promote conversion and selectivity simultaneously by adding platinum–bismuth alloy cluster to form a trimetallic catalyst on zeolite (Pt-Bi/Mo/ZSM-5). This bimetallic alloy cluster has synergistic interaction with molybdenum: the formed CH3* from Mo2C on the external surface of zeolite can efficiently move on for C-C coupling on the surface of Pt-Bi particle to produce C2 compounds, which are the key intermediates of oligomerization. This pathway is parallel with the catalysis on Mo inside the cage. This catalyst demonstrated 18.7% methane conversion and 69.4% benzene selectivity at 710 °C. With 95% methane/5% nitrogen feedstock, it exhibited robust stability with slow deactivation rate of 9.3% after 2 h and instant recovery of 98.6% activity after regeneration in hydrogen. The enhanced catalytic activity is strongly associated with synergistic interaction with Mo and ligand effects of alloys by extensive mechanism studies and DFT calculation.