bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease: a Mendelian randomization study
Authors: Huang Liang-Yu , Ou Ya-Nan , Yang Yu-Xiang , Wang Zuo-Teng , Tan Lan , Yu Jin-Tai 
Published: July 2023

AbstractPrevious observational studies reported that midlife clustering of cardiovascular risk factors and lifestyle behaviors were associated with neurodegenerative disease; however, these findings might be biased by confounding and reverse causality. This study aimed to investigate the causal associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease, using the two-sample Mendelian randomization design. Genetic variants for the modifiable risk factors and neurodegenerative disease were extracted from large-scale genome-wide association studies. The inverse-variance weighted method was used as the main analysis method, and MR-Egger regression and leave-one-out analyses were performed to identify potential violations. Genetically predicted diastolic blood pressure (DBP: OR per 1 mmHg, 0.990 [0.979–1.000]), body mass index (BMI: OR per 1 SD, 0.880 [0.825–0.939]), and educational level (OR per 1 SD, 0.698 [0.602–0.810]) were associated with lower risk of late-onset Alzheimer’s disease (LOAD), while genetically predicted low-density lipoprotein (LDL: OR per 1 SD, 1.302 [1.066–1.590]) might increase LOAD risk. Genetically predicted exposures (including LDL and BMI) applied to familial AD showed the same effect. The association of LDL was also found with Amyotrophic lateral sclerosis (ALS) (LDL: OR per 1 SD, 1.180 [1.080–1.289]). This MR analysis showed that LDL, BMI, BP, and educational level were causally related to AD; a significant association between LDL and ALS risk, as well as the potential effect of sleep duration on PD risk, were also revealed. Targeting these modifiable factors was a promising strategy of neurodegenerative disease prevention.
A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma
Authors: Lopez Juanita , Lai-Kwon Julia , Molife Rhoda , Welsh Liam , Tunariu Nina , Roda Desamparados , Fernández-García Paula , Lladó Victoria , McNicholl Adrian G. , Rosselló Catalina A. , Taylor Richard J. , Azaro Analía , Rodón Jordi , Sludden Julieann , Veal Gareth J. , Plummer Ruth , Urruticoechea Ander , Lahuerta Ainhara , Mujika Karmele , Escribá Pablo V. 
Published: July 2023

Abstract
Background
The first-in-class brain-penetrating synthetic hydroxylated lipid idroxioleic acid (2-OHOA; sodium 2-hydroxyoleate), activates sphingomyelin synthase expression and regulates membrane-lipid composition and mitochondrial energy production, inducing cancer cell autophagy. We report the findings of a multicentric first-in-human Phase 1/2A trial (NCT01792310) of 2-OHOA, identifying the maximum tolerated dose (MTD) and assessing safety and preliminary efficacy.

Methods
We performed an open-label, non-randomised trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumour activity of daily oral treatment with 2-OHOA monotherapy (BID/TID) in 54 patients with glioma and other advanced solid tumours. A dose-escalation phase using a standard 3 + 3 design was performed to determine safety and tolerability. This was followed by two expansion cohorts at the MTD to determine the recommended Phase-2 dose (RP2D).

Results
In total, 32 recurrent patients were enrolled in the dose-escalation phase (500–16,000 mg/daily). 2-OHOA was rapidly absorbed with dose-proportional exposure. Treatment was well-tolerated overall, with reversible grade 1–2 nausea, vomiting, and diarrhoea as the most common treatment-related adverse events (AEs). Four patients had gastrointestinal dose-limiting toxicities (DLTs) of nausea, vomiting, diarrhoea (three patients at 16,000 mg and one patient at 12,000 mg), establishing an RP2D at 12,000 mg/daily. Potential activity was seen in patients with recurrent high-grade gliomas (HGG). Of the 21 patients with HGG treated across the dose escalation and expansion, 5 (24%) had the clinical benefit (RANO CR, PR and SD >6 cycles) with one exceptional response lasting >2.5 years.

Conclusions
2-OHOA demonstrated a good safety profile and encouraging activity in this difficult-to-treat malignant brain-tumour patient population, placing it as an ideal potential candidate for the treatment of glioma and other solid tumour malignancies.

Clinical trial registration
EudraCT registration number: 2012-001527-13; Clinicaltrials.gov registration number: NCT01792310.
Atopic allergic conditions and prostate cancer risk and survival in the Multiethnic Cohort study
Authors: Wang Anqi , Wan Peggy , Hebert James R. , Le Marchand Loic , Wilkens Lynne R. , Haiman Christopher A. 
Published: July 2023

Abstract
Background
Previous studies investigating relationship between atopic allergic conditions (AACs)—a highly reactive immune state—and prostate cancer (PCa) risk were inconclusive, and few have studied diverse racial/ethnic populations.

Methods
We analysed 74,714 men aged ≥45 years at enrollment in Multiethnic Cohort study. Using multivariable Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for self-reported AAC status on PCa outcomes.

Results
Through 2017, 8697 incident PCa and 1170 related deaths occurred. Twenty-one percent of men reported a history of AACs. AACs were not associated with incident PCa (HR = 0.98, 95% CI: 0.93–1.03) but were significantly inversely associated with PCa mortality (HR = 0.79, 95% CI: 0.67–0.92). This inverse association was consistently observed across all racial/ethnic groups (HR range: 0.60–0.90). Among men diagnosed with PCa, AACs were inversely associated with PCa-specific death (HR = 0.75, 95% CI: 0.63–0.89). Adjusting for potential confounding effect of PSA screening did not meaningfully change the results. No significant heterogeneity was observed in the effect of AACs on PCa incidence or mortality by Dietary Inflammatory Index.

Conclusions
Hyper-allergic conditions were not associated with PCa incidence but were inversely associated with PCa mortality, suggesting a potential role in reducing tumour progression. Further aetiological research is warranted to understand underlying mechanisms.
GANT-61 induces cell cycle resting and autophagy by down-regulating RNAP III signal pathway and tRNA-Gly-CCC synthesis to combate chondrosarcoma
Authors: Sun Yifeng , Fang Qiongxuan , Liu Wei , Liu Yi , Zhang Chunming 
Published: July 2023

AbstractChondrosarcoma is ineffective for conventional radiotherapy and chemotherapy with a poor prognosis. Hedgehog (Hh) signal pathway plays a crucial role in tumor growth and progression, which is constitutive activated in chondrosarcoma. GLI transcription factors as targets for new drugs or interference technology for the treatment of chondrosarcoma are of great significance. In this study, we indicated that the Hedgehog-GLI1 signal pathway is activated in chondrosarcoma, which further enhances the RNAP III signal pathway to mediate endogenous tRNA fragments synthesis. Downstream oncology functions of endogenous tRNA fragments, such as “cell cycle” and “death receptor binding”, are involved in malignant chondrosarcoma. The GANT-61, as an inhibitor of GLI1, could inhibit chondrosarcoma tumor growth effectively by inhibiting the RNAP III signal pathway and tRNA-Gly-CCC synthesis in vivo. Induced G2/M cell cycle resting, apoptosis, and autophagy were the main mechanisms for the inhibitory effect of GANT-61 on chondrosarcoma, which correspond with the above-described downstream oncology functions of endogenous tRNA fragments. We also identified the molecular mechanism by which GANT-61-induced autophagy is involved in ULK1 expression and MAPK signaling pathway. Thus, GANT-61 will be an ideal and promising strategy for combating chondrosarcoma.
Ferroptosis as a potential target for cancer therapy
Authors: Chen Zhen , Wang Weilong , Abdul Razak Siti Razila , Han Tao , Ahmad Nor Hazwani , Li Xiumin 
Published: July 2023

AbstractFerroptosis is a recently discovered essential type of cell death that is mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests that ferroptosis is a double-edged sword in human cancer. However, the precise underlying molecular mechanisms and their differential roles in tumorigenesis are unclear. Therefore, in this review, we summarize and briefly present the key pathways of ferroptosis, paying special attention to the regulation of ferroptosis as well as its dual role as an oncogenic and as a tumor suppressor event in various human cancers. Moreover, multiple pharmacological ferroptosis activators are summarized, and the prospect of targeting ferroptosis in cancer therapy is further elucidated.
A general model-based causal inference method overcomes the curse of synchrony and indirect effect
Authors: Park Se Ho , Ha Seokmin , Kim Jae Kyoung 
Published: July 2023

AbstractTo identify causation, model-free inference methods, such as Granger Causality, have been widely used due to their flexibility. However, they have difficulty distinguishing synchrony and indirect effects from direct causation, leading to false predictions. To overcome this, model-based inference methods that test the reproducibility of data with a specific mechanistic model to infer causality were developed. However, they can only be applied to systems described by a specific model, greatly limiting their applicability. Here, we address this limitation by deriving an easily testable condition for a general monotonic ODE model to reproduce time-series data. We built a user-friendly computational package, General ODE-Based Inference (GOBI), which is applicable to nearly any monotonic system with positive and negative regulations described by ODE. GOBI successfully inferred positive and negative regulations in various networks at both the molecular and population levels, unlike existing model-free methods. Thus, this accurate and broadly applicable inference method is a powerful tool for understanding complex dynamical systems.
Giant uniaxial negative thermal expansion in FeZr2 alloy over a wide temperature range
Authors: Xu Meng , Li Qiang , Song Yuzhu , Xu Yuanji , Sanson Andrea , Shi Naike , Wang Na , Sun Qiang , Wang Changtian , Chen Xin , Qiao Yongqiang , Long Feixiang , Liu Hui , Zhang Qiang , Venier Alessandro , Ren Yang , d’Acapito Francesco , Olivi Luca , De Souza Danilo Oliveira , Xing Xianran , Chen Jun 
Published: July 2023

AbstractNegative thermal expansion (NTE) alloys possess great practical merit as thermal offsets for positive thermal expansion due to its metallic properties. However, achieving a large NTE with a wide temperature range remains a great challenge. Herein, a metallic framework-like material FeZr2 is found to exhibit a giant uniaxial (1D) NTE with a wide temperature range (93-1078 K, $${\bar{\alpha }}_{l}=-34.01\times {10}^{-6}\,{{{{{{\rm{K}}}}}}}^{-1}$$

α

¯

l

=
−
34.01
×

10

−
6

K

−
1

). Such uniaxial NTE is the strongest in all metal-based NTE materials. The direct experimental evidence and DFT calculations reveal that the origin of giant NTE is the couple with phonons, flexible framework-like structure, and soft bonds. Interestingly, the present metallic FeZr2 excites giant 1D NTE mainly driven by high-frequency optical branches. It is unlike the NTE in traditional framework materials, which are generally dominated by low energy acoustic branches. In the present study, a giant uniaxial NTE alloy is reported, and the complex mechanism has been revealed. It is of great significance for understanding the nature of thermal expansion and guiding the regulation of thermal expansion.
Unlocking full and fast conversion in photocatalytic carbon dioxide reduction for applications in radio-carbonylation
Authors: Monticelli Serena , Talbot Alex , Gotico Philipp , Caillé Fabien , Loreau Olivier , Del Vecchio Antonio , Malandain Augustin , Sallustrau Antoine , Leibl Winfried , Aukauloo Ally , Taran Frédéric , Halime Zakaria , Audisio Davide 
Published: July 2023

AbstractHarvesting sunlight to drive carbon dioxide (CO2) valorisation represents an ideal concept to support a sustainable and carbon-neutral economy. While the photochemical reduction of CO2 to carbon monoxide (CO) has emerged as a hot research topic, the full CO2-to-CO conversion remains an often-overlooked criterion that prevents a productive and direct valorisation of CO into high-value-added chemicals. Herein, we report a photocatalytic process that unlocks full and fast CO2-to-CO conversion (<10 min) and its straightforward valorisation into human health related field of radiochemistry with carbon isotopes. Guided by reaction-model-based kinetic simulations to rationalize reaction optimisations, this manifold opens new opportunities for the direct access to 11C- and 14C-labeled pharmaceuticals from their primary isotopic sources [11C]CO2 and [14C]CO2.
Diversity-oriented synthesis of P-stereogenic and axially chiral monodentate biaryl phosphines enabled by C-P bond cleavage
Authors: Pang Liangzhi , Huang Zhan , Sun Qilin , Li Gen , Liu Jiaojiao , Li Baoli , Ma Congyue , Guo Jiaxu , Yao Chuanzhi , Yu Jie , Li Qiankun 
Published: July 2023

AbstractChiral monodentate biaryl phosphines (MOPs) have attracted intense attention as chiral ligands over the past decades. However, the creation of structurally diverse chiral MOPs with both P- and axial chirality is still in high demand but challenging. Here, we show a distinct strategy for diversity-oriented synthesis of structurally diverse MOPs containing both P- and axial chirality enabled by enantioselective C-P bond cleavage. The key chiral PdII intermediates, generated through the stereoselective oxidative addition of C-P bond, could be trapped by alkynes, R3Si-Bpin, diboron esters or reduced by H2O/B2pin2, leading to enantioenriched structurally diverse MOPs in excellent diastereo- and enantioselectivities. Based on the outstanding properties of the parent scaffolds, the P- and axially chiral monodentate biaryl phosphines serve as excellent catalysts in asymmetric [3 + 2] annulation of MBH carbonate affording the chiral functionalized bicyclic imide.
Drought exposure decreases altruism with salient group identities as key moderator
Authors: Döring Stefan , Hall Jonathan 
Published: July 2023

AbstractPrevious research on climate change impact regularly considers conflict outcomes, thereby disregarding cooperative behaviour such as altruism. Drought has the potential to fuel inter-ethnic cleavages, thus contributing to conflicts. Yet this runs against resilience arguments suggesting people who experience environmental hardship are more cooperative. Here we examine altruism in survey experiments in a natural setting among refugees from Syria and Iraq. We match survey responses to observational data on drought and socioeconomic variables. Our findings speak to both arguments. First, we show that drought exposure is associated with decreased altruism for survey respondents generally. We further show how group identity moderates the relationship between drought and altruism. Our results suggest a decrease in altruism due to drought is much larger when the target of altruism is presented as a member of an antagonistic ethno-religious outgroup.
Carbonate compensation depth drives abyssal biogeography in the northeast Pacific
Authors: Simon-Lledó Erik , Amon Diva J. , Bribiesca‐Contreras Guadalupe , Cuvelier Daphne , Durden Jennifer M. , Ramalho Sofia P. , Uhlenkott Katja , Arbizu Pedro Martinez , Benoist Noëlie , Copley Jonathan , Dahlgren Thomas G. , Glover Adrian G. , Fleming Bethany , Horton Tammy , Ju Se-Jong , Mejía-Saenz Alejandra , McQuaid Kirsty , Pape Ellen , Park Chailinn , Smith Craig R. , Jones Daniel O. B. 
Published: July 2023

AbstractAbyssal seafloor communities cover more than 60% of Earth’s surface. Despite their great size, abyssal plains extend across modest environmental gradients compared to other marine ecosystems. However, little is known about the patterns and processes regulating biodiversity or potentially delimiting biogeographical boundaries at regional scales in the abyss. Improved macroecological understanding of remote abyssal environments is urgent as threats of widespread anthropogenic disturbance grow in the deep ocean. Here, we use a new, basin-scale dataset to show the existence of clear regional zonation in abyssal communities across the 5,000 km span of the Clarion–Clipperton Zone (northeast Pacific), an area targeted for deep-sea mining. We found two pronounced biogeographic provinces, deep and shallow-abyssal, separated by a transition zone between 4,300 and 4,800 m depth. Surprisingly, species richness was maintained across this boundary by phylum-level taxonomic replacements. These regional transitions are probably related to calcium carbonate saturation boundaries as taxa dependent on calcium carbonate structures, such as shelled molluscs, appear restricted to the shallower province. Our results suggest geochemical and climatic forcing on distributions of abyssal populations over large spatial scales and provide a potential paradigm for deep-sea macroecology, opening a new basis for regional-scale biodiversity research and conservation strategies in Earth’s largest biome.
Climate change impacts on planned supply–demand match in global wind and solar energy systems
Authors: Liu Laibao , He Gang , Wu Mengxi , Liu Gang , Zhang Haoran , Chen Ying , Shen Jiashu , Li Shuangcheng 
Published: July 2023

AbstractClimate change modulates both energy demand and wind and solar energy supply but a globally synthetic analysis of supply–demand match (SDM) is lacking. Here, we use 12 state-of-the-art climate models to assess climate change impacts on SDM, quantified by the fraction of demand met by local wind or solar supply. For energy systems with varying dependence on wind or solar supply, up to 32% or 44% of non-Antarctic land areas, respectively, are projected to experience robust SDM reductions by the end of this century under an intermediate emission scenario. Smaller and more variable supply reduces SDM at northern middle-to-high latitudes, whereas reduced heating demand alleviates or reverses SDM reductions remarkably. By contrast, despite supply increases at low latitudes, raised cooling demand reduces SDM substantially. Changes in climate extremes and climate mean make size-comparable contributions. Our results provide early warnings for energy sectors in climate change adaptation.
Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial
Authors: Yin Jun , Yuan Jingnan , Li Yunjin , Fang Yong , Wang Ruoxi , Jiao Heng , Tang Han , Zhang Shaoyuan , Lin Siyun , Su Feng , Gu Jianmin , Jiang Tian , Lin Dong , Huang Zhiliang , Du Chaoxiang , Wu Kui , Tan Lijie , Zhou Qing 
Published: July 2023

AbstractOverall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here, we reported the results of a phase 1b trial of neoadjuvant PD-L1 blockade with adebrelimab in resectable ESCC. Patients received two neoadjuvant doses of adebrelimab followed by surgery. The primary endpoints were safety and feasibility; secondary endpoints included pathologic complete response (pCR) and OS. Our data showed the primary endpoints of safety and feasibility had been met. Common treatment-related adverse events were anorexia (32%) and fatigue (16%), without grade 3 or more adverse events. Of the 30 patients enrolled in the trial, 25 underwent successful resection without surgery delay and 24% had major pathologic responses including a pCR rate of 8%. The 2-year OS was 92%. Responsive patients had an immune-enriched tumor microenvironment phenotype, whereas nonresponsive patients had greater infiltration of cancer-associated fibroblasts at baseline. Clonotypic dynamics of pre-existing intratumoral T cells was a hallmark of responsive patients. These findings provide a rational for neoadjuvant anti-PD-L1 monotherapy as a therapeutic strategy for patients with resectable ESCC. ClinicalTrials.gov identifier: NCT04215471.
GASP: a genetic algorithm for state preparation on quantum computers
Authors: Creevey Floyd M. , Hill Charles D. , Hollenberg Lloyd C. L. 
Published: July 2023

AbstractThe efficient preparation of quantum states is an important step in the execution of many quantum algorithms. In the noisy intermediate-scale quantum (NISQ) computing era, this is a significant challenge given quantum resources are scarce and typically only low-depth quantum circuits can be implemented on physical devices. We present a genetic algorithm for state preparation (GASP) which generates relatively low-depth quantum circuits for initialising a quantum computer in a specified quantum state. The method uses a basis set of$$R_x$$Rx,$$R_y$$Ry,$$R_z$$Rz, and CNOT gates and a genetic algorithm to systematically generate circuits to synthesize the target state to the required fidelity. GASP can produce more efficient circuits of a given accuracy with lower depth and gate counts than other methods. This variability of the required accuracy facilitates overall higher accuracy on implementation, as error accumulation in high-depth circuits can be avoided. We directly compare the method to the state initialisation technique based on an exact synthesis technique by implemented in IBM Qiskit simulated with noise and implemented on physical IBM Quantum devices. Results achieved by GASP outperform Qiskit’s exact general circuit synthesis method on a variety of states such as Gaussian states and W-states, and consistently show the method reduces the number of gates required for the quantum circuits to generate these quantum states to the required accuracy.
Anandamide modulates WNT-5A/BCL-2, IP3/NFATc1, and HMGB1/NF-κB trajectories to protect against mercuric chloride-induced acute kidney injury
Authors: Abdallah Dalaal M. , Kamal Mahmoud M. , Aly Nour Eldin S. , El-Abhar Hanan S. 
Published: July 2023

AbstractEndocannabinoid anandamide (AEA) has a physiological role in regulating renal blood flow, whereas its analogs ameliorated renal ischemia/reperfusion injury. Nonetheless, the role of AEA against mercuric chloride (HgCl2)-induced renal toxicity has not been unraveled. Rats were allocated into control, HgCl2, and HgCl2/AEA treated groups. The administration of AEA quelled the HgCl2-mediated increase in inositol trisphosphate (IP3) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). The endocannabinoid also signified its anti-inflammatory potential by turning off the inflammatory cascade evidenced by the suppression of high mobility group box protein-1 (HMGB1), receptor of glycated end products (RAGE), nuclear factor-κB p65 (NF-κB), and unexpectedly PPAR-γ. Additionally, the aptitude of AEA to inhibit malondialdehyde and boost glutathione points to its antioxidant capacity. Moreover, AEA by enhancing the depleted renal WNT-5A and reducing cystatin-C and KIM-1 (two kidney function parameters) partly verified its anti-apoptotic capacity, confirmed by inhibiting caspase-3 and increasing B-cell lymphoma-2 (BCL-2). The beneficial effect of AEA was mirrored by the improved architecture and kidney function evidenced by the reduction in cystatin-C, KIM-1, creatinine, BUN, and caspase1-induced activated IL-18. In conclusion, our results verify the reno-protective potential of AEA against HgCl2-induced kidney injury by its anti-inflammatory, antioxidant, and anti-apoptotic capacities by modulating WNT-5A/BCL-2, IP3/NFATC1, HMGB-1/RAGE/NF-κB, caspase-1/IL-18, and caspase-3/BCL-2 cues.