bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comorbidity in patients with cancer treated at The Christie
Authors: Abravan Azadeh , Faivre-Finn Corinne , Gomes Fabio , van Herk Marcel , Price Gareth 
Published: September 2024

Abstract
Background
Comorbidities have been shown to impact the presentation and treatment of patients with cancers. This study investigates the prevalence and patterns of comorbidity in a pan-cancer cohort of patients treated at a large UK specialist cancer center over a 9-year period.

Methods
A retrospective review of 77,149 patients from 01/01/2014 to 15/12/2022 was conducted using the Adult Comorbidity Evaluation 27 score (ACE-27) to assess the burden of comorbidities across 12 organ systems and an overall comorbidity burden. Binary and multinomial logistic regressions were utilized to evaluate the relationships between comorbidity incidence and demographic and socio-economic factors.

Results
At the time of diagnosis, 59.7% of patients had at least one comorbidity, with the highest prevalence in lung cancer and the lowest in brain/CNS and endocrine gland cancers. Cardiovascular comorbidities were the most frequent. Comorbidity severity was higher in patients from more deprived areas. Age and performance status were associated with a higher incidence of all comorbidities examined. Patients with advanced stage had a lower risk of having a severe comorbidity burden.

Conclusion
Comorbidities are common across all cancers but are more prevalent in certain patient populations. Further research to understand the implications of comorbidities in cancer management is needed.
L3MBTL1, a polycomb protein, promotes Osimertinib acquired resistance through epigenetic regulation of DNA damage response in lung adenocarcinoma
Authors: Zhang Zihe , Li Yongwen , Shi Ruifeng , Jia Chaoyi , Xu Songlin , Zhu Guangsheng , Cao Peijun , Huang Hua , Li Xuanguang , Zhang Hongbing , Liu Minghui , Chen Chen , Liu Hongyu , Kang Chunsheng , Chen Jun 
Published: September 2024

AbstractOsimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI) approved for patients with EGFR T790M resistance mutations as first- or second-line treatment of EGFR-positive patients. Resistance to Osimertinib will inevitably develop, and the underlying mechanisms are largely unknown. In this study, we discovered that acquired resistance to Osimertinib is associated with abnormal DNA damage response (DDR) in lung adenocarcinoma cells. We discovered that the polycomb protein Lethal(3) Malignant Brain Tumor-Like Protein 1 (L3MBTL1) regulates chromatin structure, thereby contributing to DDR and Osimertinib resistance. EGFR oncogene inhibition reduced L3MBTL1 ubiquitination while stabilizing its expression in Osimertinib-resistant cells. L3MBTL1 reduction and treatment with Osimertinib significantly inhibited DDR and proliferation of Osimertinib-resistant lung cancer cells in vitro and in vivo. L3MBTL1 binds throughout the genome and plays an important role in EGFR-TKI resistance. It also competes with 53BP1 for H4K20Me2 and inhibits the development of drug resistance in Osimertinib-resistant lung cancer cells in vitro and in vivo. Our findings suggest that L3MBTL1 inhibition is a novel approach to overcoming EGFR-TKI-acquired resistance.
Renalase rs2296545 variant improve hypertension susceptibility by modifying binding affinity to catecholamines in obstructive sleep apnea
Authors: Shen Hangdong , Yang Jundong , Xue Wenjun , Wei Zhicheng , Li Lilin , Guan Jian , Li Xinyi , Wu Xiaolin 
Published: September 2024

AbstractObstructive sleep apnea (OSA), a condition often linked with hypertension, has an undefined relationship with renalase, a protein known for regulating blood pressure. This study aimed to investigate the relationship between serum renalase levels as well as renalase functional single nucleotide polymorphism (SNP) rs2296545 variant and hypertension in a Han Chinese OSA population. 126 subjects underwent serum renalase detection, with linear regression being performed to evaluate the relationship between serum renalase levels and OSA-related traits. Additional 4275 subjects were obtained rs2296545 genotype information by SNP microarray. And binary logistic regression was used to assess the effect of rs2296545 on hypertension risk. Molecular dynamics simulation and molecular docking were utilized to access the protein structures and the interplay between protein and catecholamines of wild-type and rs2296545 mutant renalase. The results showed that serum renalase levels were significantly higher in the severe OSA group. Further analysis showed renalase levels were positively correlated with blood pressure in the non-OSA group and negatively correlated in the severe OSA group. For rs2296545 polymorphism analysis, the hypertension risk significantly increased for the recessive model CC/GG + CG (OR = 1.211, 95% CI: 1.025–1.431) and the additive model CC/CG (OR = 1.223, 95% CI: 1.025–1.458) in the severe OSA. The rs2296545 polymorphism affected protein structure, and led to increase binding free energy, weakening interactions between renalase and catecholamines. In conclusion, serum renalase levels had independent association with blood pressure. And rs2296545 polymorphism may influence on susceptibility to hypertension by altering protein ability to bind to catecholamines, which might contribute to the intervention of hypertension in the OSA population.
Photochemical conversion of CO to C1 and C2 products mediated by porphyrin rhodium(II) metallo-radical complexes
Authors: Li Hongsen , Han Boao , Wang Rongyi , Li Wentao , Zhang Wentao , Fu Xuefeng , Fang Huayi , Ma Fuqiu , Wang Zikuan , Zhang Jiajing 
Published: September 2024

AbstractUnimolecular reduction and bimolecular reductive coupling of carbon monoxide (CO) represent important ways to synthesize organic feedstocks. Reductive activation of CO through open-shell pathways, though rare, can help overcome the barriers of many traditional organometallic elementary reactions that are hard to achieve. Herein we successfully achieve the unimolecular reduction of CO to (TPP)RhCH2OSiR1R2R3 (TPP = 5,10,15,20-tetraphenylporphyrin), and the release of products CH3OSiR1R2R3, TEMPO-CH2OSiR1R2R3 and BrCH2OSiR1R2R3 in near-quantitative yield under visible light (420–780 nm), which involves radical formation from Rh-C bond homolysis. Bimolecular CO reductive coupling products, (TPP)RhCOCH2OSiR1R2R3, are then obtained via a radical mechanism. Subsequent treatment with n-propylamine, BrCCl3 or TEMPO under thermal or photochemical conditions afford small-molecule bimolecular reductive coupling products. To the best of our knowledge, homogeneous systems which reductively couple CO under photochemical conditions have not been reported before. Here, the use of an open-shell transition metal complex, that delivers more than one kind of small-molecule CO reductive coupling products bearing different functional groups, provides opportunities for useful CO reductive transformations.
12.1 terabit/second data center interconnects using O-band coherent transmission with QD-MLL frequency combs
Authors: Bernal Santiago , Dumont Mario , Berikaa Essam , St-Arnault Charles , Hu Yixiang , Castrejon Ramon Gutierrez , Li Weijia , Wei Zixian , Krueger Benjamin , Pittalà Fabio , Bowers John , Plant David V. 
Published: September 2024

AbstractMost current Data Center Interconnects (DCI) use intensity modulation direct detection (IMDD) configurations due to their low complexity and cost. However, significant scaling challenges allow coherent solutions to become contenders in these short reach applications. We present an O-band coherent optical fiber transmission system based on Quantum Dot—Mode Locked Lasers (QD-MLLs) using two independent free-running comb lasers, one each for the carrier and the Local Oscillator (LO). Using a comb-to-comb configuration, we demonstrate a 10 km single mode fiber, O-band, coherent, heterodyne, 12.1 Tbps system operating at 0.47 Tbps/λ using 26 λs. We used fewer comb lines (26 λs), faster symbol rate (56 GBaud) and higher constellation cardinality (32 QAM) relative to the highest capacity C-band systems reported to date. Through design, analysis, and experimentation, we quantify the optimum comb line spacing for this use case. We compare potential configurations for increasing data center interconnect capacities whilst reducing power consumption, complexity, and cost.
Base excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain
Authors: Polyzos Aris A. , Cheong Ana , Yoo Jung Hyun , Blagec Lana , Toprani Sneh M. , Nagel Zachary D. , McMurray Cynthia T. 
Published: September 2024

AbstractWe lack the fundamental information needed to understand how DNA damage in the brain is generated and how it is controlled over a lifetime in the absence of replication check points. To address these questions, here, we integrate cell-type and region-specific features of DNA repair activity in the normal brain. The brain has the same repair proteins as other tissues, but normal, canonical repair activity is unequal and is characterized by high base excision repair (BER) and low double strand break repair (DSBR). The natural imbalance creates conditions where single strand breaks (SSBs) can convert to double strand breaks (DSBs) and reversibly switch between states in response to oxidation both in vivo and in vitro. Our data suggest that, in a normal background of repair, SSBs and DSBs are in an equilibrium which is pushed or pulled by metabolic state. Interconversion of SSB to DSBs provides a physiological check point, which would allow the formation of unrepaired DSBs for productive functions, but would also restrict them from exceeding tolerable limits.
Spatial segregation of catalytic sites within Pd doped H-ZSM-5 for fatty acid hydrodeoxygenation to alkanes
Authors: Ding Shengzhe , Fernandez Ainaga Dario Luis , Hu Min , Qiu Boya , Khalid Ushna , D’Agostino Carmine , Ou Xiaoxia , Spencer Ben , Zhong Xiangli , Peng Yani , Hondow Nicole , Theodoropoulos Constantinos , Jiao Yilai , Parlett Christopher M. A. , Fan Xiaolei 
Published: September 2024

AbstractSpatial control over features within multifunctional catalysts can unlock efficient one-pot cascade reactions, which are themselves a pathway to aviation biofuels via hydrodeoxygenation. A synthesis strategy that encompasses spatial orthogonality, i.e., one in which different catalytic species are deposited exclusively within discrete locations of a support architecture, is one solution that permits control over potential interactions between different sites and the cascade process. Here, we report a Pd doped hierarchical zeolite, in which Pd nanoparticles are selectively deposited within the mesopores, while acidity is retained solely within the micropores of ZSM-5. This spatial segregation facilitates hydrodeoxygenation while suppressing undesirable decarboxylation and decarbonation, yielding significant enhancements in activity (30.6 vs 3.6 moldodecane molPd−1 h−1) and selectivity (C12:C11 5.2 vs 1.9) relative to a conventionally prepared counterpart (via wet impregnation). Herein, multifunctional material design can realise efficient fatty acid hydrodeoxygenation, thus advancing the field and inspiring future developments in rationalised catalyst design.
Inducible auto-phosphorylation regulates a widespread family of nucleotidyltransferase toxins
Authors: Arrowsmith Tom J. , Xu Xibing , Xu Shangze , Usher Ben , Stokes Peter , Guest Megan , Bronowska Agnieszka K. , Genevaux Pierre , Blower Tim R. 
Published: September 2024

AbstractNucleotidyltransferases (NTases) control diverse physiological processes, including RNA modification, DNA replication and repair, and antibiotic resistance. The Mycobacterium tuberculosis NTase toxin family, MenT, modifies tRNAs to block translation. MenT toxin activity can be stringently regulated by diverse MenA antitoxins. There has been no unifying mechanism linking antitoxicity across MenT homologues. Here we demonstrate through structural, biochemical, biophysical and computational studies that despite lacking kinase motifs, antitoxin MenA1 induces auto-phosphorylation of MenT1 by repositioning the MenT1 phosphoacceptor T39 active site residue towards bound nucleotide. Finally, we expand this predictive model to explain how unrelated antitoxin MenA3 is similarly able to induce auto-phosphorylation of cognate toxin MenT3. Our study reveals a conserved mechanism for the control of tuberculosis toxins, and demonstrates how active site auto-phosphorylation can regulate the activity of widespread NTases.
The V-ATPase complex component RNAseK is required for lysosomal hydrolase delivery and autophagosome degradation
Authors: Makar Agata N. , Boraman Alina , Mosen Peter , Simpson Joanne E. , Marques Jair , Michelberger Tim , Aitken Stuart , Wheeler Ann P. , Winter Dominic , von Kriegsheim Alex , Gammoh Noor 
Published: September 2024

AbstractAutophagy is a finely orchestrated process required for the lysosomal degradation of cytosolic components. The final degradation step is essential for clearing autophagic cargo and recycling macromolecules. Using a CRISPR/Cas9-based screen, we identify RNAseK, a highly conserved transmembrane protein, as a regulator of autophagosome degradation. Analyses of RNAseK knockout cells reveal that, while autophagosome maturation is intact, cargo degradation is severely disrupted. Importantly, lysosomal protease activity and acidification remain intact in the absence of RNAseK suggesting a specificity to autolysosome degradation. Analyses of lysosome fractions show reduced levels of a subset of hydrolases in the absence of RNAseK. Of these, the knockdown of PLD3 leads to a defect in autophagosome clearance. Furthermore, the lysosomal fraction of RNAseK-depleted cells exhibits an accumulation of the ESCRT-III complex component, VPS4a, which is required for the lysosomal targeting of PLD3. Altogether, here we identify a lysosomal hydrolase delivery pathway required for efficient autolysosome degradation.
Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma
Authors: Liu Yang , Ye Shuang-Yan , He Shuai , Chi Dong-Mei , Wang Xiu-Zhi , Wen Yue-Feng , Ma Dong , Nie Run-Cong , Xiang Pu , Zhou You , Ruan Zhao-Hui , Peng Rou-Jun , Luo Chun-Ling , Wei Pan-Pan , Lin Guo-Wang , Zheng Jian , Cui Qian , Cai Mu-Yan , Yun Jing-Ping , Dong Junchao , Mai Hai-Qiang , Xia Xiaojun , Bei Jin-Xin 
Published: September 2024

AbstractTertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.
Kinetic ferromagnetism and topological magnons of the hole-doped Kitaev spin liquid
Authors: Jin Hui-Ke , Kadow Wilhelm , Knap Michael , Knolle Johannes 
Published: September 2024

AbstractWe study the effect of hole doping on the Kitaev spin liquid (KSL) and find that for ferromagnetic (FM) Kitaev exchange K the system is very susceptible to the formation of a FM spin polarization. Through density matrix renormalization group simulations on finite systems, we uncover that the introduction of a single hole, corresponding to ≈1% hole doping for the system size we consider, with a hopping strength of just t ~ 0.28K is enough to disrupt fractionalization and polarize the spins in the [001] direction due to an order-by-disorder mechanism. Taking into account a material relevant FM anisotropic exchange Γ drives the polarization towards the [111] direction via a transition into a topological FM state with chiral magnon excitations. We develop a parton mean-field theory incorporating fermionic holons and bosonic magnons, which accounts for the doping induced FM phases and topological magnon excitations. We discuss experimental implications for Kitaev candidate materials.
Broad protection and respiratory immunity of dual mRNA vaccination against SARS-CoV-2 variants
Authors: Hajnik Renee L. , Plante Jessica A. , Reddy Bonam Srinivasa , Rafael Grace H. , Liang Yuejin , Hazell Nicholas C. , Walker Jordyn , Reyna Rachel A. , Walker David H. , Alameh Mohamad-Gabriel , Weissman Drew , Weaver Scott C. , Plante Kenneth S. , Hu Haitao 
Published: September 2024

AbstractWhile first-generation, spike (S)-based COVID-19 vaccines were effective against early SARS-CoV-2 strains, the rapid evolution of novel Omicron subvariants have substantially reduced vaccine efficacy. As such, broadly protective vaccines against SARS-CoV-2 are needed to prevent future viral emergence. In addition, it remains less clear whether peripheral immunization, especially with mRNA vaccines, elicits effective respiratory immunity. Our group has developed a nucleoside-modified mRNA vaccine expressing the nucleocapsid (N) protein of the ancestral SARS-CoV-2 virus and has tested its use in combination with the S-based mRNA vaccine (mRNA-S). In this study, we examined efficacy of mRNA-N alone or in combination with mRNA-S (mRNA-S+N) against more immune evasive Omicron variants in hamsters. Our data show that mRNA-N alone induces a modest but significant protection against BA.5 and that dual mRNA-S+N vaccination confers complete protection against both BA.5 and BQ.1, preventing detection of virus in the hamster lungs. Analysis of respiratory immune response in mice shows that intramuscular mRNA-S+N immunization effectively induces respiratory S- and N-specific T cell responses in the lungs and in bronchoalveolar lavage (BAL), as well as antigen-specific binding IgG in BAL. Together, our data further support mRNA-S+N as a potential pan-COVID-19 vaccine for broad protection against current and emerging SARS-CoV-2 variants.
Trajectory of the stellar flyby that shaped the outer Solar System
Authors: Pfalzner Susanne , Govind Amith , Portegies Zwart Simon 
Published: September 2024

AbstractUnlike the Solar System planets, thousands of smaller bodies beyond Neptune orbit the Sun on eccentric (e > 0.1 and i > 3°) orbits. While migration of the giant planets during the early stages of Solar System evolution could have induced substantial scattering of trans-Neptunian objects (TNOs), this process cannot account for the small number of distant TNOs (rp > 60 au) outside the planets’ reach. The alternative scenario of the close flyby of another star can instead produce all these TNO features simultaneously, but the possible parameter space for such an encounter is vast. Here we compare observed TNO properties with thousands of flyby simulations to determine the specific properties of a flyby that reproduces all the different dynamical TNO populations, their locations and their relative abundances, and find that a $$0.{8}_{-0.1}^{+0.1}\,{M}_{\odot }$$

0
.

8

−
0.1

+
0.1

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⊙

star passing at a distance of rp = 110 ± 10 au, inclined by i = 70°$${\,}_{-10}^{+5}$$

+
5

−
10

, gives a near-perfect match. This flyby also replicates the retrograde TNO population, which has proved difficult to explain. Such a flyby is reasonably frequent; at least 140 million solar-type stars in the Milky Way are likely to have experienced a similar one. In light of these results, we predict that the upcoming Vera Rubin telescope will reveal that distant and retrograde TNOs are relatively common.
A local-to-global emissions inventory of macroplastic pollution
Authors: Cottom Joshua W. , Cook Ed , Velis Costas A. 
Published: September 2024

AbstractNegotiations for a global treaty on plastic pollution1 will shape future policies on plastics production, use and waste management. Its parties will benefit from a high-resolution baseline of waste flows and plastic emission sources to enable identification of pollution hotspots and their causes2. Nationally aggregated waste management data can be distributed to smaller scales to identify generalized points of plastic accumulation and source phenomena3–11. However, it is challenging to use this type of spatial allocation to assess the conditions under which emissions take place12,13. Here we develop a global macroplastic pollution emissions inventory by combining conceptual modelling of emission mechanisms with measurable activity data. We define emissions as materials that have moved from the managed or mismanaged system (controlled or contained state) to the unmanaged system (uncontrolled or uncontained state—the environment). Using machine learning and probabilistic material flow analysis, we identify emission hotspots across 50,702 municipalities worldwide from five land-based plastic waste emission sources. We estimate global plastic waste emissions at 52.1 [48.3–56.3] million metric tonnes (Mt) per year, with approximately 57% wt. and 43% wt. open burned and unburned debris, respectively. Littering is the largest emission source in the Global North, whereas uncollected waste is the dominant emissions source across the Global South. We suggest that our findings can help inform treaty negotiations and develop national and sub-national waste management action plans and source inventories.