bluuebunny/crossref_metadata_2025_split huggingface dataset:
A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration
Authors: San Gil Rebecca , Pascovici Dana , Venturato Juliana , Brown-Wright Heledd , Mehta Prachi , Madrid San Martin Lidia , Wu Jemma , Luan Wei , Chui Yi Kit , Bademosi Adekunle T. , Swaminathan Shilpa , Naidoo Serey , Berning Britt A. , Wright Amanda L. , Keating Sean S. , Curtis Maurice A. , Faull Richard L. M. , Lee John D. , Ngo Shyuan T. , Lee Albert , Morsch Marco , Chung Roger S. , Scotter Emma , Lisowski Leszek , Mirzaei Mehdi , Walker Adam K. 
Published: February 2024

AbstractUnderstanding the mechanisms that drive TDP-43 pathology is integral to combating amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases. Here we generated a longitudinal quantitative proteomic map of the cortex from the cytoplasmic TDP-43 rNLS8 mouse model of ALS and FTLD, and developed a complementary open-access webtool, TDP-map (https://shiny.rcc.uq.edu.au/TDP-map/). We identified distinct protein subsets enriched for diverse biological pathways with temporal alterations in protein abundance, including increases in protein folding factors prior to disease onset. This included increased levels of DnaJ homolog subfamily B member 5, DNAJB5, which also co-localized with TDP-43 pathology in diseased human motor cortex. DNAJB5 over-expression decreased TDP-43 aggregation in cell and cortical neuron cultures, and knockout of Dnajb5 exacerbated motor impairments caused by AAV-mediated cytoplasmic TDP-43 expression in mice. Together, these findings reveal molecular mechanisms at distinct stages of ALS and FTLD progression and suggest that protein folding factors could be protective in neurodegenerative diseases.
Stable water splitting using photoelectrodes with a cryogelated overlayer
Authors: Kang Byungjun , Tan Jeiwan , Kim Kyungmin , Kang Donyoung , Lee Hyungsoo , Ma Sunihl , Park Young Sun , Yun Juwon , Lee Soobin , Lee Chan Uk , Jang Gyumin , Lee Jeongyoub , Moon Jooho , Lee Hyungsuk 
Published: February 2024

AbstractHydrogen production techniques based on solar-water splitting have emerged as carbon-free energy systems. Many researchers have developed highly efficient thin-film photoelectrochemical (PEC) devices made of low-cost and earth-abundant materials. However, solar water splitting systems suffer from short lifetimes due to catalyst instability that is attributed to both chemical dissolution and mechanical stress produced by hydrogen bubbles. A recent study found that the nanoporous hydrogel could prevent the structural degradation of the PEC devices. In this study, we investigate the protection mechanism of the hydrogel-based overlayer by engineering its porous structure using the cryogelation technique. Tests for cryogel overlayers with varied pore structures, such as disconnected micropores, interconnected micropores, and surface macropores, reveal that the hydrogen gas trapped in the cryogel protector reduce shear stress at the catalyst surface by providing bubble nucleation sites. The cryogelated overlayer effectively preserves the uniformly distributed platinum catalyst particles on the device surface for over 200 h. Our finding can help establish semi-permanent photoelectrochemical devices to realize a carbon-free society.
Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial
Authors: Zhang Mina , Zhang Guowei , Niu Yuanyuan , Zhang Guifang , Ji Yinghua , Yan Xiangtao , Zhang Xiaojuan , Wang Qichuan , Jing Xiaohui , Wang Junsheng , Ma Zhiyong , Wang Huijuan 
Published: February 2024

AbstractThis was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0–not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2–NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.
Genetic influences on circulating retinol and its relationship to human health
Authors: Reay William R. , Kiltschewskij Dylan J. , Di Biase Maria A. , Gerring Zachary F. , Kundu Kousik , Surendran Praveen , Greco Laura A. , Clarke Erin D. , Collins Clare E. , Mondul Alison M. , Albanes Demetrius , Cairns Murray J. 
Published: February 2024

AbstractRetinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.
Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes
Authors: Bonciolini Stefano , Pulcinella Antonio , Leone Matteo , Schiroli Debora , Ruiz Adrián Luguera , Sorato Andrea , Dubois Maryne A. J. , Gopalakrishnan Ranganath , Masson Geraldine , Della Ca’ Nicola , Protti Stefano , Fagnoni Maurizio , Zysman-Colman Eli , Johansson Magnus , Noël Timothy 
Published: February 2024

AbstractIn contemporary drug discovery, enhancing the sp3-hybridized character of molecular structures is paramount, necessitating innovative synthetic methods. Herein, we introduce a deoxygenative cross-electrophile coupling technique that pairs easily accessible carboxylic acid-derived redox-active esters with aldehyde sulfonyl hydrazones, employing Eosin Y as an organophotocatalyst under visible light irradiation. This approach serves as a versatile, metal-free C(sp3)−C(sp3) cross-coupling platform. We demonstrate its synthetic value as a safer, broadly applicable C1 homologation of carboxylic acids, offering an alternative to the traditional Arndt-Eistert reaction. Additionally, our method provides direct access to cyclic and acyclic β-arylethylamines using diverse aldehyde-derived sulfonyl hydrazones. Notably, the methodology proves to be compatible with the late-stage functionalization of peptides on solid-phase, streamlining the modification of intricate peptides without the need for exhaustive de-novo synthesis.
Clinical application of next generation sequencing for Mendelian disease diagnosis in the Iranian population
Authors: Abolhassani Ayda , Fattahi Zohreh , Beheshtian Maryam , Fadaee Mahsa , Vazehan Raheleh , Ahangari Fatemeh , Dehdahsi Shima , Faraji Zonooz Mehrshid , Parsimehr Elham , Kalhor Zahra , Peymani Fatemeh , Mozaffarpour Nouri Maryam , Babanejad Mojgan , Noudehi Khadijeh , Fatehi Fatemeh , Zamanian Najafabadi Shima , Afroozan Fariba , Yazdan Hilda , Bozorgmehr Bita , Azarkeivan Azita , Sadat Mahdavi Shokouh , Nikuei Pooneh , Fatehi Farzad , Jamali Payman , Ashrafi Mahmoud Reza , Karimzadeh Parvaneh , Habibi Haleh , Kahrizi Kimia , Nafissi Shahriar , Kariminejad Ariana , Najmabadi Hossein 
Published: February 2024

AbstractNext-generation sequencing (NGS) has been proven to be one of the most powerful diagnostic tools for rare Mendelian disorders. Several studies on the clinical application of NGS in unselected cohorts of Middle Eastern patients have reported a high diagnostic yield of up to 48%, correlated with a high level of consanguinity in these populations. We evaluated the diagnostic utility of NGS-based testing across different clinical indications in 1436 patients from Iran, representing the first study of its kind in this highly consanguineous population. A total of 1075 exome sequencing and 361 targeted gene panel sequencing were performed over 8 years at a single clinical genetics laboratory, with the majority of cases tested as proband-only (91.6%). The overall diagnostic rate was 46.7%, ranging from 24% in patients with an abnormality of prenatal development to over 67% in patients with an abnormality of the skin. We identified 660 pathogenic or likely pathogenic variants, including 241 novel variants, associated with over 342 known genetic conditions. The highly consanguineous nature of this cohort led to the diagnosis of autosomal recessive disorders in the majority of patients (79.1%) and allowed us to determine the shared carrier status of couples for suspected recessive phenotypes in their deceased child(ren) when direct testing was not possible. We also highlight the observations of recessive inheritance of genes previously associated only with dominant disorders and provide an expanded genotype–phenotype spectrum for multiple less-characterized genes. We present the largest mutational spectrum of known Mendelian disease, including possible founder variants, throughout the Iranian population, which can serve as a unique resource for clinical genomic studies locally and beyond.
Flight test results for microgravity active vibration isolation system on-board Chinese Space Station
Authors: Liu Wei , Gao Yang , Zhang Long , Zou Tianji , Yu Mengxi , Zheng Tuo 
Published: February 2024

AbstractThe Fluid Physics Research Rack (FPR) is a research platform employed on-board the Chinese Space Station for conducting microgravity fluid physics experiments. The research platform includes the Microgravity Active Vibration Isolation System (MAVIS) for isolating the FPR from disturbances arising from the space station itself. The MAVIS is a structural platform consisting of a stator and floater that are monitored and controlled with non-contact electromagnetic actuators, high-precision accelerometers, and displacement transducers. The stator is fixed to the FPR, while the floater serves as a vibration isolation platform supporting payloads, and is connected with the stator only with umbilicals that mainly comprise power and data cables. The controller was designed with a correction for the umbilical stiffness to minimize the effect of the umbilicals on the vibration isolation performance of the MAVIS. In-orbit test results of the FPR demonstrate that the MAVIS was able to achieve a microgravity level of 1–30 μg0 (where g0 = 9.80665 m ∙ s−2) in the frequency range of 0.01–125 Hz under the microgravity mode, and disturbances with a frequency greater than 2 Hz are attenuated by more than 10-fold. Under the vibration excitation mode, the MAVIS generated a minimum vibration acceleration of 0.4091 μg0 at a frequency of 0.00995 Hz and a maximum acceleration of 6253 μg0 at a frequency of 9.999 Hz. Therefore, the MAVIS provides a highly stable environment for conducting microgravity experiments, and promotes the development of microgravity fluid physics.
Stretchable zein-coated alginate fiber for aligning muscle cells to artificially produce cultivated meat
Authors: Jeong Dayi , Jang Goo , Jung Woo Kyung , Park Yong Ho , Bae Hojae 
Published: February 2024

AbstractNumerous studies have explored the cultivation of muscle cells using non-animal materials for cultivated meat production. Achieving muscle cell proliferation and alignment using 3D scaffolds made from plant-based materials remains challenging. This study introduces a technique to culture and align muscle cells using only plant-based materials, avoiding toxic chemical modifications. Zein-alginate fibers (ZA fibers) were fabricated by coating zein protein onto alginate fibers (A fibers). Zein’s excellent cell compatibility and biodegradability enable high cell adhesion and proliferation rates, and the good ductility of the ZA fibers enable a high strain rate (>75%). We demonstrate mature and aligned myotube formation in ZA fibers, providing a simple way to align muscle cells using plant-based materials. Additionally, cultivated meat was constructed by assembling muscle, fat, and vessel fibers. This method holds promise for the future mass production of cultivated meat.
Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial
Authors: Kim Hyung-Don , Jung Seyoung , Lim Ho Yeong , Ryoo Baek-Yeol , Ryu Min-Hee , Chuah Samuel , Chon Hong Jae , Kang Beodeul , Hong Jung Yong , Lee Han Chu , Moon Deok-Bog , Kim Ki-Hun , Kim Tae Won , Tai David , Chew Valerie , Lee Jeong Seok , Finn Richard S. , Koh June-Young , Yoo Changhoon 
Published: February 2024

AbstractRegorafenib has anti-tumor activity in patients with unresectable hepatocellular carcinoma (uHCC) with potential immunomodulatory effects, suggesting that its combination with immune checkpoint inhibitor may have clinically meaningful benefits in patients with uHCC. The multicenter, single-arm, phase 2 RENOBATE trial tested regorafenib–nivolumab as front-line treatment for uHCC. Forty-two patients received nivolumab 480 mg every 4 weeks and regorafenib 80 mg daily (3-weeks-on/1-week-off schedule). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). ORR per RECIST version 1.1 was 31.0%, meeting the primary endpoint. The most common adverse events were palmar-plantar erythrodysesthesia syndrome (38.1%), alopecia (26.2%) and skin rash (23.8%). Median PFS was 7.38 months. The 1-year OS rate was 80.5%, and the median OS was not reached. Exploratory single-cell RNA sequencing analyses of peripheral blood mononuclear cells showed that long-term responders exhibited T cell receptor repertoire diversification, enrichment of genes representing immunotherapy responsiveness in MKI67+ proliferating CD8+ T cells and a higher probability of M1-directed monocyte polarization. Our data support further clinical development of the regorafenib–nivolumab combination as front-line treatment for uHCC and provide preliminary insights on immune biomarkers of response. ClinicalTrials.gov identifier: NCT04310709.
Generation of complex bone marrow organoids from human induced pluripotent stem cells
Authors: Frenz-Wiessner Stephanie , Fairley Savannah D. , Buser Maximilian , Goek Isabel , Salewskij Kirill , Jonsson Gustav , Illig David , zu Putlitz Benedicta , Petersheim Daniel , Li Yue , Chen Pin-Hsuan , Kalauz Martina , Conca Raffaele , Sterr Michael , Geuder Johanna , Mizoguchi Yoko , Megens Remco T. A. , Linder Monika I. , Kotlarz Daniel , Rudelius Martina , Penninger Josef M. , Marr Carsten , Klein Christoph 
Published: February 2024

AbstractThe human bone marrow (BM) niche sustains hematopoiesis throughout life. We present a method for generating complex BM-like organoids (BMOs) from human induced pluripotent stem cells (iPSCs). BMOs consist of key cell types that self-organize into spatially defined three-dimensional structures mimicking cellular, structural and molecular characteristics of the hematopoietic microenvironment. Functional properties of BMOs include the presence of an in vivo-like vascular network, the presence of multipotent mesenchymal stem/progenitor cells, the support of neutrophil differentiation and responsiveness to inflammatory stimuli. Single-cell RNA sequencing revealed a heterocellular composition including the presence of a hematopoietic stem/progenitor (HSPC) cluster expressing genes of fetal HSCs. BMO-derived HSPCs also exhibited lymphoid potential and a subset demonstrated transient engraftment potential upon xenotransplantation in mice. We show that the BMOs could enable the modeling of hematopoietic developmental aspects and inborn errors of hematopoiesis, as shown for human VPS45 deficiency. Thus, iPSC-derived BMOs serve as a physiologically relevant in vitro model of the human BM microenvironment to study hematopoietic development and BM diseases.
Deadenylation kinetics of mixed poly(A) tails at single-nucleotide resolution
Authors: Lee Young-suk , Levdansky Yevgen , Jung Yoonseok , Kim V. Narry , Valkov Eugene 
Published: February 2024

AbstractShortening of messenger RNA poly(A) tails, or deadenylation, is a rate-limiting step in mRNA decay and is highly regulated during gene expression. The incorporation of non-adenosines in poly(A) tails, or ‘mixed tailing’, has been observed in vertebrates and viruses. Here, to quantitate the effect of mixed tails, we mathematically modeled deadenylation reactions at single-nucleotide resolution using an in vitro deadenylation system reconstituted with the complete human CCR4–NOT complex. Applying this model, we assessed the disrupting impact of single guanosine, uridine or cytosine to be equivalent to approximately 6, 8 or 11 adenosines, respectively. CCR4–NOT stalls at the 0, −1 and −2 positions relative to the non-adenosine residue. CAF1 and CCR4 enzyme subunits commonly prefer adenosine but exhibit distinct sequence selectivities and stalling positions. Our study provides an analytical framework to monitor deadenylation and reveals the molecular basis of tail sequence-dependent regulation of mRNA stability.
Whole Genome Sequence Dataset of Mycobacterium tuberculosis Strains from Patients of Campania Region
Authors: Folliero Veronica , Ferravante Carlo , Iovane Valentina , Salvati Annamaria , Crescenzo Laura , Perna Rossella , Corvino Giusy , Della Rocca Maria T. , Panetta Vittorio , Tranfa Alessandro , Greco Giuseppe , Baldoni Teresa , Pagnini Ugo , Finamore Emiliana , Giurato Giorgio , Nassa Giovanni , Coppola Mariagrazia , Atripaldi Luigi , Greco Rita , D’Argenio Annamaria , Foti Maria Grazia , Abate Rosamaria , Del Giudice Annalisa , Sarnelli Bruno , Weisz Alessandro , Iovane Giuseppe , Pinto Renato , Franci Gianluigi , Galdiero Massimiliano 
Published: February 2024

AbstractTuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018–2021, obtained from the analysis of whole genome sequence. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB, 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB. This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of this disease.
A raster-based spatial clustering method with robustness to spatial outliers
Authors: Wang Haoyu , Song Changqing , Wang Jinfeng , Gao Peichao 
Published: February 2024

AbstractSpatial clustering is an essential method for the comprehensive understanding of a region. Spatial clustering divides all spatial units into different clusters. The attributes of each cluster of the spatial units are similar, and simultaneously, they are as continuous as spatially possible. In spatial clustering, the handling of spatial outliers is important. It is necessary to improve spatial integration so that each cluster is connected as much as possible, while protecting spatial outliers can help avoid the excessive masking of attribute differences This paper proposes a new spatial clustering method for raster data robust to spatial outliers. The method employs a sliding window to scan the entire region to determine spatial outliers. Additionally, a mechanism based on the range and standard deviation of the spatial units in each window is designed to judge whether the spatial integration should be further improved or the spatial outliers should be protected. To demonstrate the usefulness of the proposed method, we applied it in two case study areas, namely, Changping District and Pinggu District in Beijing. The results show that the proposed method can retain the spatial outliers while ensuring that the clusters are roughly contiguous. This method can be used as a simple but powerful and easy-to-interpret alternative to existing geographical spatial clustering methods.
Examining the gray cube effect on naïve viewers’ appreciation of street-based art in Hong Kong and Poland
Authors: Szubielska Magdalena , Ho Robbie , Witeska-Młynarczyk Anna , Kopiś-Posiej Natalia 
Published: February 2024

AbstractThe present research investigates the appreciation of sanctioned street-based art among naïve viewers. It examines the role of viewing context in art appreciation, by experimentally testing agray cube effect, which posits that street-based artworks are more likely to be identified as art (H1), liked more (H2), and understood more (H3) when viewed on the street. Identical procedures were carried out in Hong Kong (Experiment 1) and Lublin, Poland (Experiment 2), separately, sampling local artworks and local viewers. Experiment 1 tested 14 murals with 100 Hong Kongers; Experiment 2 tested 7 sculptures and 7 murals with 88 Poles. Participants were randomly assigned to either viewing street-based artworks on the street (gray cube) or viewing digital images of street-based artworks in a laboratory. The participants assessed each artwork in terms of art identification, liking, and understanding. These “twin” experiments yielded identical results, i.e., street-based artworks were liked more (H2) and understood more (H3) but not more likely to be identified as art (H1) on the street than in the laboratory. Overall, the present findings support the gray cube effect with ecologically valid data, and the effect seems robust across Western and Eastern cultural contexts and across genres of sculpture and mural.