bluuebunny/crossref_metadata_2025_split huggingface dataset:
COLUMBIA-1: a randomised study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab in metastatic microsatellite-stable colorectal cancer
Authors: Segal Neil H. , Tie Jeanne , Kopetz Scott , Ducreux Michel , Chen Eric , Dienstmann Rodrigo , Hollebecque Antoine , Reilley Matthew J. , Elez Elena , Cosaert Jan , Cain Jason , Soo-Hoo Yee , Hewson Nicola , Cooper Zachary A. , Kumar Rakesh , Tabernero Josep 
Published: July 2024

Abstract
Background
To determine whether the addition of durvalumab (anti-PD-L1) and oleclumab (anti-CD73) to standard-of-care treatment (FOLFOX and bevacizumab) enhances the anti-tumour effect in patients with metastatic colorectal cancer (mCRC).

Methods
COLUMBIA-1 (NCT04068610) was a Phase Ib (feasibility; Part 1)/Phase II (randomised; Part 2) trial in patients with treatment-naïve microsatellite stable mCRC. Patients in Part 2 were randomised to receive standard-of-care (control arm) or standard-of-care plus durvalumab and oleclumab (experimental arm). Primary objectives included safety and efficacy.

Results
Seven patients were enrolled in Part 1 and 52 in Part 2 (n = 26 in each arm). Grade ≥3 treatment-emergent adverse events (TEAE) occurred in 80.8% and 65.4% of patients in the control and experimental arms of Part 2, respectively, with 26.9% and 46.3% experiencing serious TEAEs. The confirmed objective response rate (ORR) was numerically higher in the experimental arm compared with the control arm (61.5% [95% confidence interval (CI), 40.6–79.8] vs 46.2% [95% CI, 26.6–66.6]) but did not meet the statistically significant threshold in either arm.

Conclusion
The safety profile of FOLFOX and bevacizumab in combination with durvalumab and oleclumab was manageable; however, the efficacy results do not warrant further development of this combination in patients with microsatellite stable mCRC.

Registration
NCT04068610.
MORC2 regulates RBM39-mediated CDK5RAP2 alternative splicing to promote EMT and metastasis in colon cancer
Authors: He Yuxin , Shao Yangguang , Zhou Zhihui , Li Tingting , Gao Yunling , Liu Xue , Yuan Gang , Yang Gaoxiang , Zhang Lili , Li Feng 
Published: July 2024

AbstractColorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc finger 2 (MORC2) binds to RRM1 domain of RNA binding motif protein 39 (RBM39), and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, resulting in a splicing switch of cyclin-dependent kinase 5 regulatory subunit associated protein 2 (CDK5RAP2) L to CDK5RAP2 S. CDK5RAP2 S promotes invasion of colorectal cancer cells in vitro and metastasis in vivo. Mechanistically, CDK5RAP2 S specifically recruits the PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter. Moreover, CDK5RAP2 S, but not CDK5RAP2 L, is essential for the promotion of epithelial-mesenchymal transition induced by MORC2 or RBM39. Importantly, high protein levels of MORC2, RBM39 and Slug are strongly associated with metastasis and poor clinical outcomes of colorectal cancer patients. Taken together, our findings uncover a novel mechanism by which MORC2 promotes colorectal cancer metastasis, through RBM39-mediated pre-CDK5RAP2 alternative splicing and highlight the MORC2/RBM39/CDK5RAP2 axis as a potential therapeutic target for colorectal cancer.
Therapeutic strategy for spinal muscular atrophy by combining gene supplementation and genome editing
Authors: Hatanaka Fumiyuki , Suzuki Keiichiro , Shojima Kensaku , Yu Jingting , Takahashi Yuta , Sakamoto Akihisa , Prieto Javier , Shokhirev Maxim , Nuñez Delicado Estrella , Rodriguez Esteban Concepcion , Izpisua Belmonte Juan Carlos 
Published: July 2024

AbstractDefect in the SMN1 gene causes spinal muscular atrophy (SMA), which shows loss of motor neurons, muscle weakness and atrophy. While current treatment strategies, including small molecules or viral vectors, have shown promise in improving motor function and survival, achieving a definitive and long-term correction of SMA’s endogenous mutations and phenotypes remains highly challenging. We have previously developed a CRISPR-Cas9 based homology-independent targeted integration (HITI) strategy, enabling unidirectional DNA knock-in in both dividing and non-dividing cells in vivo. In this study, we demonstrated its utility by correcting an SMA mutation in mice. When combined with Smn1 cDNA supplementation, it exhibited long-term therapeutic benefits in SMA mice. Our observations may provide new avenues for the long-term and efficient treatment of inherited diseases.
Modeling short visual events through the BOLD moments video fMRI dataset and metadata
Authors: Lahner Benjamin , Dwivedi Kshitij , Iamshchinina Polina , Graumann Monika , Lascelles Alex , Roig Gemma , Gifford Alessandro Thomas , Pan Bowen , Jin SouYoung , Ratan Murty N. Apurva , Kay Kendrick , Oliva Aude , Cichy Radoslaw 
Published: July 2024

AbstractStudying the neural basis of human dynamic visual perception requires extensive experimental data to evaluate the large swathes of functionally diverse brain neural networks driven by perceiving visual events. Here, we introduce the BOLD Moments Dataset (BMD), a repository of whole-brain fMRI responses to over 1000 short (3 s) naturalistic video clips of visual events across ten human subjects. We use the videos’ extensive metadata to show how the brain represents word- and sentence-level descriptions of visual events and identify correlates of video memorability scores extending into the parietal cortex. Furthermore, we reveal a match in hierarchical processing between cortical regions of interest and video-computable deep neural networks, and we showcase that BMD successfully captures temporal dynamics of visual events at second resolution. With its rich metadata, BMD offers new perspectives and accelerates research on the human brain basis of visual event perception.
Sexual size dimorphism in mammals is associated with changes in the size of gene families related to brain development
Authors: Padilla-Morales Benjamin , Acuña-Alonzo Alin P. , Kilili Huseyin , Castillo-Morales Atahualpa , Díaz-Barba Karina , Maher Kathryn H. , Fabian Laurie , Mourkas Evangelos , Székely Tamás , Serrano-Meneses Martin-Alejandro , Cortez Diego , Ancona Sergio , Urrutia Araxi O. 
Published: July 2024

AbstractIn mammals, sexual size dimorphism often reflects the intensity of sexual selection, yet its connection to genomic evolution remains unexplored. Gene family size evolution can reflect shifts in the relative importance of different molecular functions. Here, we investigate the associate between brain development gene repertoire to sexual size dimorphism using 124 mammalian species. We reveal significant changes in gene family size associations with sexual size dimorphism. High levels of dimorphism correlate with an expansion of gene families enriched in olfactory sensory perception and a contraction of gene families associated with brain development functions, many of which exhibited particularly high expression in the human adult brain. These findings suggest a relationship between intense sexual selection and alterations in gene family size. These insights illustrate the complex interplay between sexual dimorphism, gene family size evolution, and their roles in mammalian brain development and function, offering a valuable understanding of mammalian genome evolution.
Efficient deep-blue electroluminescence from Ce-based metal halide
Authors: Yang Longbo , Du Hainan , Li Jinghui , Luo Yiqi , Lin Xia , Pang Jincong , Liu Yuxuan , Gao Liang , He Siwei , Kang Jae-Wook , Liang Wenxi , Song Haisheng , Luo Jiajun , Tang Jiang 
Published: July 2024

AbstractRare earth ions with d-f transitions (Ce3+, Eu2+) have emerged as promising candidates for electroluminescence applications due to their abundant emission spectra, high light conversion efficiency, and excellent stability. However, directly injecting charge into 4f orbitals remains a significant challenge, resulting in unsatisfied external quantum efficiency and high operating voltage in rare earth light-emitting diodes. Herein, we propose a scheme to solve the difficulty by utilizing the energy transfer process. X-ray photoelectron spectroscopy and transient absorption spectra suggest that the Cs3CeI6 luminescence process is primarily driven by the energy transfer from the I2-based self-trapped exciton to the Ce-based Frenkel exciton. Furthermore, energy transfer efficiency is largely improved by enhancing the spectra overlap between the self-trapped exciton emission and the Ce-based Frenkel exciton excitation. When implemented as an active layer in light-emitting diodes, they show the maximum brightness and external quantum efficiency of 1073 cd m−2 and 7.9%, respectively.
Climate resilience of European wine regions
Authors: Tscholl Simon , Candiago Sebastian , Marsoner Thomas , Fraga Helder , Giupponi Carlo , Egarter Vigl Lukas 
Published: July 2024

AbstractOver centuries, European vintners have developed a profound knowledge about grapes, environment, and techniques that yield the most distinguishable wines. In many regions, this knowledge is reflected in the system of wine geographical indications (GI), but climate change is challenging this historical union. Here, we present a climate change vulnerability assessment of 1085 wine GIs across Europe and propose climate-resilient development pathways using an ensemble of biophysical and socioeconomic indicators. Results indicate that wine regions in Southern Europe are among the most vulnerable, with high levels also found in Eastern Europe. Vulnerability is influenced by the rigidity of the GI system, which restricts grape variety diversity and thus contributes to an increased sensitivity to climate change. Contextual deficiencies, such as limited socioeconomic resources, may further contribute to increased vulnerability. Building a climate-resilient wine sector will require rethinking the GI system by allowing innovation to compensate for the negative effects of climate change.
Evidence of strong and mode-selective electron–phonon coupling in the topological superconductor candidate 2M-WS2
Authors: Li Yiwei , Xu Lixuan , Liu Gan , Fang Yuqiang , Zheng Huijun , Dai Shenghao , Li Enting , Zhu Guang , Zhang Shihao , Liang Shiheng , Yang Lexian , Huang Fuqiang , Xi Xiaoxiang , Liu Zhongkai , Xu Nan , Chen Yulin 
Published: July 2024

AbstractThe interaction between lattice vibrations and electrons plays a key role in various aspects of condensed matter physics — including electron hydrodynamics, strange metal behavior, and high-temperature superconductivity. In this study, we present systematic investigations using Raman scattering and angle-resolved photoemission spectroscopy (ARPES) to examine the phononic and electronic subsystems of the topological superconductor candidate 2M-WS2. Raman scattering exhibits an anomalous nonmonotonic temperature dependence of phonon linewidths, indicative of strong phonon–electron scattering over phonon–phonon scattering. The ARPES results demonstrate pronounced dispersion anomalies (kinks) at multiple binding energies within both bulk and topological surface states, indicating a robust and mode-selective coupling between the electronic states and various phonon modes. These experimental findings align with previous calculations of the Eliashberg function, providing a deeper understanding of the highest superconducting transition temperature observed in 2M-WS2(8.8 K) among all transition metal dichalcogenides as induced by electron–phonon coupling. Furthermore, our results may offer valuable insights into other properties of 2M-WS2and guide the search for high-temperature topological superconductors.
Human TMEFF1 is a restriction factor for herpes simplex virus in the brain
Authors: Chan Yi-Hao , Liu Zhiyong , Bastard Paul , Khobrekar Noopur , Hutchison Kennen M. , Yamazaki Yasuhiro , Fan Qing , Matuozzo Daniela , Harschnitz Oliver , Kerrouche Nacim , Nakajima Koji , Amin Param , Yatim Ahmad , Rinchai Darawan , Chen Jie , Zhang Peng , Ciceri Gabriele , Chen Jia , Dobbs Kerry , Belkaya Serkan , Lee Danyel , Gervais Adrian , Aydın Kürşad , Kartal Ayse , Hasek Mary L. , Zhao Shuxiang , Reino Eduardo Garcia , Lee Yoon Seung , Seeleuthner Yoann , Chaldebas Matthieu , Bailey Rasheed , Vanhulle Catherine , Lorenzo Lazaro , Boucherit Soraya , Rozenberg Flore , Marr Nico , Mogensen Trine H. , Aubart Mélodie , Cobat Aurélie , Dulac Olivier , Emiroglu Melike , Paludan Søren R. , Abel Laurent , Notarangelo Luigi , Longnecker Richard , Smith Greg , Studer Lorenz , Casanova Jean-Laurent , Zhang Shen-Ying 
Published: July 2024

AbstractMost cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry. Genetic TMEFF1 deficiency allows HSV-1 to rapidly enter cortical neurons that are either patient specific or derived from CRISPR–Cas9-engineered human pluripotent stem cells, thereby enhancing HSV-1 translocation to the nucleus and subsequent replication. This cellular phenotype can be rescued by pretreatment with type I interferon (IFN) or the expression of exogenous wild-type TMEFF1. Moreover, ectopic expression of full-length TMEFF1 or its amino-terminal extracellular domain, but not its carboxy-terminal intracellular domain, impairs HSV-1 entry into NECTIN-1-expressing cells other than neurons, increasing their resistance to HSV-1 infection. Human TMEFF1 is therefore a host restriction factor for HSV-1 entry into cortical neurons. Its constitutively high abundance in cortical neurons protects these cells from HSV-1 infection, whereas inherited TMEFF1 deficiency renders them susceptible to this virus and can therefore underlie HSE.
A sequence of SVA retrotransposon insertions in ASIP shaped human pigmentation
Authors: Kamitaki Nolan , Hujoel Margaux L. A. , Mukamel Ronen E. , Gebara Edward , McCarroll Steven A. , Loh Po-Ru 
Published: July 2024

AbstractRetrotransposons comprise about 45% of the human genome1, but their contributions to human trait variation and evolution are only beginning to be explored2,3. Here, we find that a sequence of SVA retrotransposon insertions in an early intron of the ASIP (agouti signaling protein) gene has probably shaped human pigmentation several times. In the UK Biobank (n = 169,641), a recent 3.3-kb SVA insertion polymorphism associated strongly with lighter skin pigmentation (0.22 [0.21–0.23] s.d.; P = 2.8 × 10−351) and increased skin cancer risk (odds ratio = 1.23 [1.18–1.27]; P = 1.3 × 10−28), appearing to underlie one of the strongest common genetic influences on these phenotypes within European populations4–6. ASIP expression in skin displayed the same association pattern, with the SVA insertion allele exhibiting 2.2-fold (1.9–2.6) increased expression. This effect had an unusual apparent mechanism: an earlier, nonpolymorphic, human-specific SVA retrotransposon 3.9 kb upstream appeared to have caused ASIP hypofunction by nonproductive splicing, which the new (polymorphic) SVA insertion largely eliminated. Extended haplotype homozygosity indicated that the insertion allele has risen to allele frequencies up to 11% in European populations over the past several thousand years. These results indicate that a sequence of retrotransposon insertions contributed to a species-wide increase, then a local decrease, of human pigmentation.
Seroprevalence of Toxoplasma gondii and Neospora spp. in horse population of Tehran, Iran
Authors: Shams Farzane , Jokar Mohammad , Abdous Arman , Mohammadi Pardis , Abbassioun Aryan , Seuberlich Torsten , Rahmanian Vahid 
Published: July 2024

AbstractNeospora spp. and Toxoplasma gondii are two closely related protozoan parasites that are widely distributed throughout the world. Horses can act as intermediate hosts for both parasites and can acquire disease. Blood samples were taken from 487 clinically healthy horses from 17 different mechanized stables in Tehran, the capital of Iran, during September and November of 2022. IFAT and ELISA were employed to detect antibodies directed against Neospora spp. and T. gondii. The anti-N. caninum antibodies were detected in 52 of the horses (10.67%) based on IFAT and in 86 of the 487 horses (17.65%) based on the ELISA test. Also, antibodies against T. gondii were detected in 41 horses (8.42%) based on IFAT and in 63 of 487 horses (12.94%) based on the ELISA test. Also, in 6 of the horses (1.23%) based on IFAT and in 13 of the 487 horses (2.67%) based on the ELISA test, double positivity suggested co-infection with both parasites. Gender, age groups, and the presence of dogs for neosporosis, and age groups and the presence of cats for toxoplasmosis, could be considered factors having an influence on the seroprevalences (P < 0.05). The results proved the importance of the urgent implementation of stringent regulatory measures to prevent and control the spread of these parasites.
Seasonal characteristics of nosocomial infection in a psychiatric hospital in China with different nosocomial prevention and control backgrounds: a retrospective study
Authors: Zhou Yufang , Chen Shuili , Wang Youtian , Liang Jingyu , Li Huaijie , Shi Haishan , Miao Tianyang , Wu Shengwei , Xiao Aixiang , Ye Junrong , Zheng Xing 
Published: July 2024

AbstractThis study aimed to investigate the relationship between various prevention and control measures for nosocomial infections (NIs) in psychiatric hospitals and patients with mental disorders. This study aimed to determine the characteristics of NIs in psychiatric hospitals and provide a reference for infection prevention and control in this setting. Data from the NI monitoring system of a psychiatric hospital in southeastern China were analysed. Patients who were hospitalized for mental disorders from January 1, 2016, to November 30, 2019, were classified into the non-COVID-19 containment group (NC19C group, n = 898), while those who were hospitalized from January 25, 2020, to November 30, 2022, were classified into the COVID-19 containment group (C19C group, n = 840). The data were analysed using SPSS version 22.0, and independent sample t tests, chi-square tests, correlation analyses, and multivariate logistic regression analyses were performed. A significance level of P < 0.0024 was applied. The incidence rate of NIs was higher in autumn in the NC19C group, while no seasonal difference was detected in the C19C group (P < 0.0024). Further analysis revealed that in the C19C group, the risk of hospitalized patients with mental disorders developing hospital-acquired pneumonia in spring was 0.362 times that in winter (OR = 0.362, 95% CI = 0.200 ~ 0.656, P = 0.001), and in summer, the risk was 0.342 times that in winter (OR = 0.342, 95% CI = 0.185 ~ 0.633 P = 0.001). Patients aged 18–44 years had a 4.260 times higher risk of developing hospital-acquired upper respiratory tract infections than did those aged 60 years and older (OR = 4.260, 95% CI = 2.143 ~ 8.470; P = 0.000). The risk of acquiring urinary tract infections in the hospital was 0.324 times greater among patients aged 18–44 years than for patients aged 60 years and older (OR = 0.324, 95% CI = 0.171–0.613; P = 0.001). The NC19C group did not exhibit the aforementioned differences. During the NC19C period, differences were observed in the diagnosis of hospital-acquired infections and sex (all P = 0.000). Psychiatric hospitals exhibit distinct nosocomial infection characteristics under the context of various infection control measures. Against the backdrop of strengthened infection control, the nosocomial infection characteristics of psychiatric hospitals may be associated with the features of mental disorders.
Relating the ultrasonic and aerosol filtration properties of filters
Authors: Alvarez-Arenas Tomás E. G. , Sipkens Timothy A. , Corbin Joel C. , Salso Patricia , Genovés Vicente 
Published: July 2024

AbstractNon-contact methods are useful to improve the quality control of particle filtration media. The purpose of this paper is to investigate the correlation between the filtration efficiency of a porous sheet and its ultrasonic properties obtained using a non-contact technique. An air-coupled ultrasonic technique is used to obtain rapid measurements without affecting the integrity of the material. High frequencies (from 0.1 to 2.5 MHz) are used to improve technique sensitivity, and transmitted waves are measured to probe the internal properties of the material. Measurements of transmission coefficient spectra (amplitude and phase) and the corresponding ultrasound velocity and attenuation coefficient at different frequencies are obtained for a set of filtration media with well-characterized properties. Results show that the ultrasonic properties of filtration media vary as a function of basis weight, and therefore filtration efficiency, for a given charge state. However, the effect of electrostatic charge on ultrasonic propagation is almost negligible, as expected. We conclude that ultrasonic transmission may provide a valuable tool for the continuous online monitoring of material quality during fabrication and as a method to tease apart mechanical and electrostatic contributions to particle filtration.
Unraveling the mechanism of small molecule induced activation of Staphylococcus aureus signal peptidase IB
Authors: Chen Shu-Yu , Fiedler Michaela K. , Gronauer Thomas F. , Omelko Olesia , von Wrisberg Marie-Kristin , Wang Tao , Schneider Sabine , Sieber Stephan A. , Zacharias Martin 
Published: July 2024

AbstractStaphylococcus aureussignal peptidase IB (SpsB) is an essential enzyme for protein secretion. While inhibition of its activity by small molecules is a well-precedented mechanism to kill bacteria, the mode of activation is however less understood. We here investigate the activation mechanism of a recently introduced activator, the antibiotic compound PK150, and demonstrate by combined experimental and Molecular Dynamics (MD) simulation studies a unique principle of enzyme stimulation. Mass spectrometric studies with an affinity-based probe of PK150 unravel the binding site of PK150 in SpsB which is used as a starting point for MD simulations. Our model shows the localization of the molecule in an allosteric pocket next to the active site which shields the catalytic dyad from excess water that destabilizes the catalytic geometry. This mechanism is validated by the placement of mutations aligning the binding pocket of PK150. While the mutants retain turnover of the SpsB substrate, no stimulation of activity is observed upon PK150 addition. Overall, our study elucidates a previously little investigated mechanism of enzyme activation and serves as a starting point for the development of future enzyme activators.