bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting hyaluronan-mediated motility receptor (HMMR) enhances response to androgen receptor signalling inhibitors in prostate cancer
Authors: Hinneh Josephine A. , Gillis Joanna L. , Mah Chui Yan , Irani Swati , Shrestha Raj K. , Ryan Natalie K. , Atsushi Enomoto , Nassar Zeyad D. , Lynn David J. , Selth Luke A. , Kato Masashi , Centenera Margaret M. , Butler Lisa M. 
Published: September 2023

Abstract
Background
Resistance to androgen receptor signalling inhibitors (ARSIs) represents a major clinical challenge in prostate cancer. We previously demonstrated that the ARSI enzalutamide inhibits only a subset of all AR-regulated genes, and hypothesise that the unaffected gene networks represent potential targets for therapeutic intervention. This study identified the hyaluronan-mediated motility receptor (HMMR) as a survival factor in prostate cancer and investigated its potential as a co-target for overcoming resistance to ARSIs.

Methods
RNA-seq, RT-qPCR and Western Blot were used to evaluate the regulation of HMMR by AR and ARSIs. HMMR inhibition was achieved via siRNA knockdown or pharmacological inhibition using 4-methylumbelliferone (4-MU) in prostate cancer cell lines, a mouse xenograft model and patient-derived explants (PDEs).

Results
HMMR was an AR-regulated factor that was unaffected by ARSIs. Genetic (siRNA) or pharmacological (4-MU) inhibition of HMMR significantly suppressed growth and induced apoptosis in hormone-sensitive and enzalutamide-resistant models of prostate cancer. Mechanistically, 4-MU inhibited AR nuclear translocation, AR protein expression and subsequent downstream AR signalling. 4-MU enhanced the growth-suppressive effects of 3 different ARSIs in vitro and, in combination with enzalutamide, restricted proliferation of prostate cancer cells in vivo and in PDEs.

Conclusion
Co-targeting HMMR and AR represents an effective strategy for improving response to ARSIs.
Immune landscape and redox imbalance during neurological disorders in COVID-19
Authors: Thakur Abhimanyu , Sharma Vartika , Averbek Sera , Liang Lifan , Pandya Nirali , Kumar Gaurav , Cili Alma , Zhang Kui 
Published: September 2023

AbstractThe outbreak of Coronavirus Disease 2019 (COVID-19) has prompted the scientific community to explore potential treatments or vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the illness. While SARS-CoV-2 is mostly considered a respiratory pathogen, several neurological complications have been reported, raising questions about how it may enter the Central Nervous System (CNS). Receptors such as ACE2, CD147, TMPRSS2, and NRP1 have been identified in brain cells and may be involved in facilitating SARS-CoV-2 entry into the CNS. Moreover, proteins like P2X7 and Panx-1 may contribute to the pathogenesis of COVID-19. Additionally, the role of the immune system in the gravity of COVID-19 has been investigated with respect to both innate and adaptive immune responses caused by SARS-CoV-2 infection, which can lead to a cytokine storm, tissue damage, and neurological manifestations. A redox imbalance has also been linked to the pathogenesis of COVID-19, potentially causing mitochondrial dysfunction, and generating proinflammatory cytokines. This review summarizes different mechanisms of reactive oxygen species and neuro-inflammation that may contribute to the development of severe COVID-19, and recent progress in the study of immunological events and redox imbalance in neurological complications of COVID-19, and the role of bioinformatics in the study of neurological implications of COVID-19.
Levosulpiride for the treatment of diabetic macular oedema: a phase 2 randomized clinical trial
Authors: Núñez-Amaro Carlos D. , López Mariana , Adán-Castro Elva , Robles-Osorio Ma. Ludivina , García-Franco Renata , García-Roa Marlon , Villalpando-Gómez Yolanda , Ramírez-Neria Paulina , Pineiro Nayeli , Rubio-Mijangos Juan Fernando , Sánchez Jorge , Ramírez-Hernández Gabriela , Siqueiros-Márquez Lourdes , Díaz-Lezama Nundehui , López-Star Ellery , Bertsch Thomas , Marínez de la Escalera Gonzalo , Triebel Jakob , Clapp Carmen 
Published: September 2023

Abstract
Background/Objective
The prokinetic levosulpiride elevates vasoinhibin levels in the vitreous of patients with proliferative diabetic retinopathy (PDR) suggesting clinical benefits due to the anti-vasopermeability and anti-angiogenic properties of vasoinhibin. We investigated the biological activity of levosulpiride in centre-involving diabetic macular oedema (DME).

Patients/Methods
Prospective, randomized, double-blinded, dual-centre, phase 2 trial in patients with centre-involving DME orally treated with placebo (n = 17) or levosulpiride (n = 17) for 8 weeks or in patients with PDR undergoing elective pars plana vitrectomy and receiving placebo (n = 18) or levosulpiride (n = 18) orally for the 1 week before vitrectomy.

Results
Levosulpiride improved changes from baseline in best-corrected visual acuity (p ≤ 0.037), central foveal thickness (CFT, p ≤ 0.013), and mean macular volume (MMV, p ≤ 0.002) at weeks 4, 6, and 8 compared to placebo. At 8 weeks, the proportion of eyes gaining ≥5 ETDRS letters at 4 m (41% vs. 28%), losing ≥21 μm in CFT (55% vs. 28%), and dropping ≥0.06 mm3 in MMV (65% vs. 29%) was higher after levosulpiride than placebo. The overall grading of visual and structural parameters improved with levosulpiride (p = 0.029). Levosulpiride reduced VEGF (p = 0.025) and PlGF (p = 0.008) levels in the vitreous of PDR patients. No significant adverse side-effects were detected.

Conclusions
Oral levosulpiride for 8 weeks improved visual and structural outcomes in patients with centre-involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted.
Triplet maintenance therapy of olaparib, pembrolizumab and bevacizumab in women with BRCA wild-type, platinum-sensitive recurrent ovarian cancer: the multicenter, single-arm phase II study OPEB-01/APGOT-OV4
Authors: Kim Yoo-Na , Park Boram , Kim Jae Weon , Kim Byoung Gie , Kim Sang Wun , Kim Hee Seung , Choi Chel Hun , Lim Myong Cheol , YL Ngoi Natalie , SP Tan David , Lee Jung-Yun 
Published: September 2023

AbstractIn this multicenter, open-label, single-arm, Phase II study with Simon two-stage optimum design (NCT04361370), we investigate the efficacy and safety of triplet maintenance (olaparib, pembrolizumab, bevacizumab) in patients with platinum-sensitive recurrent ovarian cancer who are wild-type for BRCA 1/2. A total of 44 patients were enrolled, and the median follow-up duration was 22.9 months (interquartile range: 17.4–24.7). The primary outcome was 6-months progression-free survival (PFS), which was 88.6% (95% confidence interval [CI] 75.4–96.2), meeting the pre-specified primary endpoint. The secondary outcomes reported here include median PFS, 12-months PFS, and overall survival and safety. The median PFS was 22.4 months (20.4–∞), with a 12-months PFS rate of 84.0% (95% CI 69.3–92.0). The median overall survival was 28.6 months (27.3–∞). The combination demonstrated tolerable toxicity with manageable side effects. Other secondary outcomes include time-to-progression, time to subsequent treatment, time to second treatment and PFS2; however, this data is not reported, as treatment is still ongoing in a majority of patients. Exploratory analysis shows that patients who were homologous recombination deficiency-positive or had a programmed death-ligand 1 combined positive score ≥1 showed a favorable response (P = 0.043 and P < 0.001, respectively). Thus, triplet maintenance shows durable efficacy with tolerable safety in patients with platinum-sensitive recurrence.
Haldane topological spin-1 chains in a planar metal-organic framework
Authors: Tin Pagnareach , Jenkins Michael J. , Xing Jie , Caci Nils , Gai Zheng , Jin Rongyin , Wessel Stefan , Krzystek J. , Li Cheng , Daemen Luke L. , Cheng Yongqiang , Xue Zi-Ling 
Published: September 2023

AbstractHaldane topological materials contain unique antiferromagnetic chains with symmetry-protected energy gaps. Such materials have potential applications in spintronics and future quantum computers. Haldane topological solids typically consist of spin-1 chains embedded in extended three-dimensional (3D) crystal structures. Here, we demonstrate that [Ni(μ−4,4′-bipyridine)(μ-oxalate)]n (NiBO) instead adopts a two-dimensional (2D) metal-organic framework (MOF) structure of Ni2+ spin-1 chains weakly linked by 4,4′-bipyridine. NiBO exhibits Haldane topological properties with a gap between the singlet ground state and the triplet excited state. The latter is split by weak axial and rhombic anisotropies. Several experimental probes, including single-crystal X-ray diffraction, variable-temperature powder neutron diffraction (VT-PND), VT inelastic neutron scattering (VT-INS), DC susceptibility and specific heat measurements, high-field electron spin resonance, and unbiased quantum Monte Carlo simulations, provide a detailed, comprehensive characterization of NiBO. Vibrational (also known as phonon) properties of NiBO have been probed by INS and density-functional theory (DFT) calculations, indicating the absence of phonons near magnetic excitations in NiBO, suppressing spin-phonon coupling. The work here demonstrates that NiBO is indeed a rare 2D-MOF Haldane topological material.
Effect of SARS-CoV-2 prior infection and mRNA vaccination on contagiousness and susceptibility to infection
Authors: Mongin Denis , Bürgisser Nils , Laurie Gustavo , Schimmel Guillaume , Vu Diem-Lan , Cullati Stephane ,   Covid-SMC Study Group, Da Silva Mora Lucienne , Després Lena , Dudouit Rachel , Hirsch Béatrice , Müller Barbara , Roux Charlotte , Duc Géraldine , Zahnd Caroline , Caparros Adriana Uribe , Falcone Jean-Luc , Silva Nuno M. , Goeury Thomas , Charpilloz Christophe , Adamou Silas , Brindel Pauline , Petrucci Roberta , Allgöwer Andrea , Kadjangaba Abdel , Loha Christopher Abo , Macher Emilie , Vassant Marc , Donnat Nadia , Pittet Philippe , Joubert Dominique , Carballido Samia , Germain Ariane , Bontemps Sophie , Delaporte Elisabeth , Genecand Camille , Metsini Aliki , Creac’h Valérie , Calatraba Virginie , Flüeli Laura , Piccard Hippolyte , Lebowitz Dan , Tardin Aglaé , Regard Simon , Courvoisier Delphine Sophie 
Published: September 2023

AbstractThe immunity conferred by SARS-CoV-2 vaccines and infections reduces the transmission of the virus. To answer how the effect of immunity is shared between a reduction of infectiousness and an increased protection against infection, we examined >50,000 positive cases and >110,000 contacts from Geneva, Switzerland (June 2020 to March 2022). We assessed the association between secondary attack rate (i.e. proportion of new cases among contacts) and immunity from natural infection and/or vaccination, stratifying per four SARS-CoV-2 variants and adjusting for index cases and contacts’ socio-demographic characteristics and the propensity of the contacts to be tested. Here we show that immunity protected contacts from infection, rather than reducing infectiousness of index cases. Natural infection conferred the strongest immunity. Hybrid immunity did not surpass recent infection. Although of smaller amplitude, the reduction in infectiousness due to vaccination was less affected by time and by the emergence of new SARS-CoV-2 variants than the susceptibility to infection. These findings support the role of vaccine in reducing infectiousness and underscore the complementary role of interventions reducing SARS-CoV-2 propagation, such as mask use or indoor ventilation.
Synchronization of spin-driven limit cycle oscillators optically levitated in vacuum
Authors: Brzobohatý Oto , Duchaň Martin , Jákl Petr , Ježek Jan , Šiler Martin , Zemánek Pavel , Simpson Stephen H. 
Published: September 2023

AbstractWe explore, experimentally and theoretically, the emergence of coherent coupled oscillations and synchronization between a pair of non-Hermitian, stochastic, opto-mechanical oscillators, levitated in vacuum. Each oscillator consists of a polystyrene microsphere trapped in a circularly polarized, counter-propagating Gaussian laser beam. Non-conservative, azimuthal forces, deriving from inhomogeneous optical spin, push the micro-particles out of thermodynamic equilibrium. For modest optical powers each particle shows a tendency towards orbital circulation. Initially, their stochastic motion is weakly correlated. As the power is increased, the tendency towards orbital circulation strengthens and the motion of the particles becomes highly correlated. Eventually, centripetal forces overcome optical gradient forces and the oscillators undergo a collective Hopf bifurcation. For laser powers exceeding this threshold, a pair of limit cycles appear, which synchronize due to weak optical and hydrodynamic interactions. In principle, arrays of such Non-Hermitian elements can be arranged, paving the way for opto-mechanical topological materials or, possibly, classical time crystals. In addition, the preparation of synchronized states in levitated optomechanics could lead to new and robust sensors or alternative routes to the entanglement of macroscopic objects.
Visualizing the membrane disruption action of antimicrobial peptides by cryo-electron tomography
Authors: Chen Eric H.-L. , Wang Chun-Hsiung , Liao Yi-Ting , Chan Feng-Yueh , Kanaoka Yui , Uchihashi Takayuki , Kato Koichi , Lai Longsheng , Chang Yi-Wei , Ho Meng-Chiao , Chen Rita P.-Y. 
Published: September 2023

AbstractThe abuse of antibiotics has led to the emergence of multidrug-resistant microbial pathogens, presenting a pressing challenge in global healthcare. Membrane-disrupting antimicrobial peptides (AMPs) combat so-called superbugs via mechanisms different than conventional antibiotics and have good application prospects in medicine, agriculture, and the food industry. However, the mechanism-of-action of AMPs has not been fully characterized at the cellular level due to a lack of high-resolution imaging technologies that can capture cellular-membrane disruption events in the hydrated state. Previously, we reported PepD2M, a de novo-designed AMP with potent and wide-spectrum bactericidal and fungicidal activity. In this study, we use cryo-electron tomography (cryo-ET) and high-speed atomic force microscopy (HS-AFM) to directly visualize the pepD2M-induced disruption of the outer and inner membranes of the Gram-negative bacterium Escherichia coli, and compared with a well-known pore-forming peptide, melittin. Our high-resolution cryo-ET images reveal how pepD2M disrupts the E. coli membrane using a carpet/detergent-like mechanism. Our studies reveal the direct membrane-disrupting consequence of AMPs on the bacterial membrane by cryo-ET, and this information provides critical insights into the mechanisms of this class of antimicrobial agents.
Field-free spin-orbit switching of perpendicular magnetization enabled by dislocation-induced in-plane symmetry breaking
Authors: Liang Yuhan , Yi Di , Nan Tianxiang , Liu Shengsheng , Zhao Le , Zhang Yujun , Chen Hetian , Xu Teng , Dai Minyi , Hu Jia-Mian , Xu Ben , Shi Ji , Jiang Wanjun , Yu Rong , Lin Yuan-Hua 
Published: September 2023

AbstractCurrent induced spin-orbit torque (SOT) holds great promise for next generation magnetic-memory technology. Field-free SOT switching of perpendicular magnetization requires the breaking of in-plane symmetry, which can be artificially introduced by external magnetic field, exchange coupling or device asymmetry. Recently it has been shown that the exploitation of inherent crystal symmetry offers a simple and potentially efficient route towards field-free switching. However, applying this approach to the benchmark SOT materials such as ferromagnets and heavy metals is challenging. Here, we present a strategy to break the in-plane symmetry of Pt/Co heterostructures by designing the orientation of Burgers vectors of dislocations. We show that the lattice of Pt/Co is tilted by about 1.2° when the Burgers vector has an out-of-plane component. Consequently, a tilted magnetic easy axis is induced and can be tuned from nearly in-plane to out-of-plane, enabling the field-free SOT switching of perpendicular magnetization components at room temperature with a relatively low current density (~1011 A/m2) and excellent stability (> 104 cycles). This strategy is expected to be applicable to engineer a wide range of symmetry-related functionalities for future electronic and magnetic devices.
Ancient Clostridium DNA and variants of tetanus neurotoxins associated with human archaeological remains
Authors: Hodgins Harold P. , Chen Pengsheng , Lobb Briallen , Wei Xin , Tremblay Benjamin J. M. , Mansfield Michael J. , Lee Victoria C. Y. , Lee Pyung-Gang , Coffin Jeffrey , Duggan Ana T. , Dolphin Alexis E. , Renaud Gabriel , Dong Min , Doxey Andrew C. 
Published: September 2023

AbstractThe analysis of microbial genomes from human archaeological samples offers a historic snapshot of ancient pathogens and provides insights into the origins of modern infectious diseases. Here, we analyze metagenomic datasets from 38 human archaeological samples and identify bacterial genomic sequences related to modern-day Clostridium tetani, which produces the tetanus neurotoxin (TeNT) and causes the disease tetanus. These genomic assemblies had varying levels of completeness, and a subset of them displayed hallmarks of ancient DNA damage. Phylogenetic analyses revealed known C. tetani clades as well as potentially new Clostridium lineages closely related to C. tetani. The genomic assemblies encode 13 TeNT variants with unique substitution profiles, including a subgroup of TeNT variants found exclusively in ancient samples from South America. We experimentally tested a TeNT variant selected from an ancient Chilean mummy sample and found that it induced tetanus muscle paralysis in mice, with potency comparable to modern TeNT. Thus, our ancient DNA analysis identifies DNA from neurotoxigenic C. tetani in archaeological human samples, and a novel variant of TeNT that can cause disease in mammals.
An electronic origin of charge order in infinite-layer nickelates
Authors: Chen Hanghui , Yang Yi-feng , Zhang Guang-Ming , Liu Hongquan 
Published: September 2023

AbstractA charge order (CO) with a wavevector $${{{{{{{\bf{q}}}}}}}}\simeq \left(\frac{1}{3},\, 0,\, 0\right)$$
q
≃

1

3

,

0
,

0

is observed in infinite-layer nickelates. Here we use first-principles calculations to demonstrate a charge-transfer-driven CO mechanism in infinite-layer nickelates, which leads to a characteristic Ni1+-Ni2+-Ni1+ stripe state. For every three Ni atoms, due to the presence of near-Fermi-level conduction bands, Hubbard interaction on Ni-d orbitals transfers electrons on one Ni atom to conduction bands and leaves electrons on the other two Ni atoms to become more localized. We further derive a low-energy effective model to elucidate that the CO state arises from a delicate competition between Hubbard interaction on Ni-d orbitals and charge transfer energy between Ni-d orbitals and conduction bands. With physically reasonable parameters, $${{{{{{{\bf{q}}}}}}}}=\left(\frac{1}{3},\, 0,\, 0\right)$$
q
=

1

3

,

0
,

0

CO state is more stable than uniform paramagnetic state and usual checkerboard antiferromagnetic state. Our work highlights the multi-band nature of infinite-layer nickelates, which leads to some distinctive correlated properties that are not found in cuprates.
A cytotoxic T cell inspired oncolytic nanosystem promotes lytic cell death by lipid peroxidation and elicits antitumor immune responses
Authors: Zuo Zhigui , Yin Hao , Zhang Yu , Xie Congying , Wang Qinyang 
Published: September 2023

AbstractLytic cell death triggers an antitumour immune response. However, cancer cells evade lytic cell death by several mechanisms. Moreover, a prolonged and uncontrolled immune response conversely leads to T-cell exhaustion. Therefore, an oncolytic system capable of eliciting an immune response by killing cancer cells in a controlled manner is needed. Here, we establish a micro-scale cytotoxic T-cell-inspired oncolytic system (TIOs) to precisely lyse cancer cells by NIR-light-controlled lipid peroxidation. Our TIOs present antigen-based cell recognition, tumour-targeting and catalytic cell-lysis ability; thus, the TIOs induce oncolysis in vivo. We apply TIOs to preclinical cancer models, showing anti-tumor activity with negligible side-effects. Tumour regression is correlated with a T-cell based anti-tumour immune response and TIOs also improve responses to anti-PD-1 therapy or STING activation. Our study provides insights to design oncolytic systems for antitumour immunity. Moreover, activation of STING can reverse T-cell exhaustion in oncolysis.
Accelerated epigenetic aging and decreased natural killer cells based on DNA methylation in patients with untreated major depressive disorder
Authors: Shindo Ryota , Tanifuji Takaki , Okazaki Satoshi , Otsuka Ikuo , Shirai Toshiyuki , Mouri Kentaro , Horai Tadasu , Hishimoto Akitoyo 
Published: September 2023

AbstractMajor depressive disorder (MDD) is known to cause significant disability. Genome-wide DNA methylation (DNAm) profiles can be used to estimate biological aging and as epigenetic clocks. However, information on epigenetic clocks reported in MDD patients is inconsistent. Since antidepressants are likely confounders, we evaluated biological aging using various DNAm-based predictors in patients with MDD who had never received depression medication. A publicly available dataset consisting of whole blood samples from untreated MDD patients (n = 40) and controls (n = 40) was used. We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAm-based telomere length (DNAmTL), and DNAm-based age-related plasma proteins (GrimAge components), as well as DNAm-based white blood cell composition. The results indicate that patients with untreated MDD were significantly associated with epigenetic aging acceleration in HannumAge and GrimAge. Furthermore, a decrease in natural killer cells, based on DNAm, was observed in patients with untreated MDD.
Spatial predictors of immunotherapy response in triple-negative breast cancer
Authors: Wang Xiao Qian , Danenberg Esther , Huang Chiun-Sheng , Egle Daniel , Callari Maurizio , Bermejo Begoña , Dugo Matteo , Zamagni Claudio , Thill Marc , Anton Anton , Zambelli Stefania , Russo Stefania , Ciruelos Eva Maria , Greil Richard , Győrffy Balázs , Semiglazov Vladimir , Colleoni Marco , Kelly Catherine M. , Mariani Gabriella , Del Mastro Lucia , Biasi Olivia , Seitz Robert S. , Valagussa Pinuccia , Viale Giuseppe , Gianni Luca , Bianchini Giampaolo , Ali H. Raza 
Published: September 2023

AbstractImmune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear1. Because ICB targets cell–cell interactions2, we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately linked, influence ICB effect and differ in sensitive versus resistant tumours early on-treatment. We used imaging mass cytometry3 to profile the in situ expression of 43 proteins in tumours from patients in a randomized trial of neoadjuvant ICB, sampled at three timepoints (baseline, n = 243; early on-treatment, n = 207; post-treatment, n = 210). Multivariate modelling showed that the fractions of proliferating CD8+TCF1+T cells and MHCII+ cancer cells were dominant predictors of response, followed by cancer–immune interactions with B cells and granzyme B+ T cells. On-treatment, responsive tumours contained abundant granzyme B+ T cells, whereas resistant tumours were characterized by CD15+ cancer cells. Response was best predicted by combining tissue features before and on-treatment, pointing to a role for early biopsies in guiding adaptive therapy. Our findings show that multicellular spatial organization is a major determinant of ICB effect and suggest that its systematic enumeration in situ could help realize precision immuno-oncology.