bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer
Authors: Fonseca Nicolette M. , Maurice-Dror Corinne , Herberts Cameron , Tu Wilson , Fan William , Murtha Andrew J. , Kollmannsberger Catarina , Kwan Edmond M. , Parekh Karan , Schönlau Elena , Bernales Cecily Q. , Donnellan Gráinne , Ng Sarah W. S. , Sumiyoshi Takayuki , Vergidis Joanna , Noonan Krista , Finch Daygen L. , Zulfiqar Muhammad , Miller Stacy , Parimi Sunil , Lavoie Jean-Michel , Hardy Edward , Soleimani Maryam , Nappi Lucia , Eigl Bernhard J. , Kollmannsberger Christian , Taavitsainen Sinja , Nykter Matti , Tolmeijer Sofie H. , Boerrigter Emmy , Mehra Niven , van Erp Nielka P. , De Laere Bram , Lindberg Johan , Grönberg Henrik , Khalaf Daniel J. , Annala Matti , Chi Kim N. , Wyatt Alexander W. 
Published: February 2024

AbstractNo consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.
A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling
Authors: Kang Sun Woo Sophie , Cunningham Rory P. , Miller Colin B. , Brown Lauryn A. , Cultraro Constance M. , Harned Adam , Narayan Kedar , Hernandez Jonathan , Jenkins Lisa M. , Lobanov Alexei , Cam Maggie , Porat-Shliom Natalie 
Published: February 2024

AbstractIn the liver, mitochondria are exposed to different concentrations of nutrients due to their spatial positioning across the periportal and pericentral axis. How the mitochondria sense and integrate these signals to respond and maintain homeostasis is not known. Here, we combine intravital microscopy, spatial proteomics, and functional assessment to investigate mitochondrial heterogeneity in the context of liver zonation. We find that periportal and pericentral mitochondria are morphologically and functionally distinct; beta-oxidation is elevated in periportal regions, while lipid synthesis is predominant in the pericentral mitochondria. In addition, comparative phosphoproteomics reveals spatially distinct patterns of mitochondrial composition and potential regulation via phosphorylation. Acute pharmacological modulation of nutrient sensing through AMPK and mTOR shifts mitochondrial phenotypes in the periportal and pericentral regions, linking nutrient gradients across the lobule and mitochondrial heterogeneity. This study highlights the role of protein phosphorylation in mitochondrial structure, function, and overall homeostasis in hepatic metabolic zonation. These findings have important implications for liver physiology and disease.
Structure of the p53 degradation complex from HPV16
Authors: Wang John C. K. , Baddock Hannah T. , Mafi Amirhossein , Foe Ian T. , Bratkowski Matthew , Lin Ting-Yu , Jensvold Zena D. , Preciado López Magdalena , Stokoe David , Eaton Dan , Hao Qi , Nile Aaron H. 
Published: February 2024

AbstractHuman papillomavirus (HPV) is a significant contributor to the global cancer burden, and its carcinogenic activity is facilitated in part by the HPV early protein 6 (E6), which interacts with the E3-ligase E6AP, also known as UBE3A, to promote degradation of the tumor suppressor, p53. In this study, we present a single-particle cryoEM structure of the full-length E6AP protein in complex with HPV16 E6 (16E6) and p53, determined at a resolution of ~3.3 Å. Our structure reveals extensive protein-protein interactions between 16E6 and E6AP, explaining their picomolar binding affinity. These findings shed light on the molecular basis of the ternary complex, which has been pursued as a potential therapeutic target for HPV-driven cervical, anal, and oropharyngeal cancers over the last two decades. Understanding the structural and mechanistic underpinnings of this complex is crucial for developing effective therapies to combat HPV-induced cancers. Our findings may help to explain why previous attempts to disrupt this complex have failed to generate therapeutic modalities and suggest that current strategies should be reevaluated.
Cryo-EM structure of cell-free synthesized human histamine 2 receptor/Gs complex in nanodisc environment
Authors: Köck Zoe , Schnelle Kilian , Persechino Margherita , Umbach Simon , Schihada Hannes , Januliene Dovile , Parey Kristian , Pockes Steffen , Kolb Peter , Dötsch Volker , Möller Arne , Hilger Daniel , Bernhard Frank 
Published: February 2024

AbstractHere we describe the cryo-electron microscopy structure of the human histamine 2 receptor (H2R) in an active conformation with bound histamine and in complex with Gs heterotrimeric protein at an overall resolution of 3.4 Å. The complex was generated by cotranslational insertion of the receptor into preformed nanodisc membranes using cell-free synthesis in E. coli lysates. Structural comparison with the inactive conformation of H2R and the inactive and Gq-coupled active state of H1R together with structure-guided functional experiments reveal molecular insights into the specificity of ligand binding and G protein coupling for this receptor family. We demonstrate lipid-modulated folding of cell-free synthesized H2R, its agonist-dependent internalization and its interaction with endogenously synthesized H1R and H2R in HEK293 cells by applying a recently developed nanotransfer technique.
Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
Authors: Hvorecny Kelli L. , Sladewski Thomas E. , De La Cruz Enrique M. , Kollman Justin M. , Heaslip Aoife T. 
Published: February 2024

AbstractThe cytoskeletal protein actin plays a critical role in the pathogenicity of the intracellular parasite, Toxoplasma gondii, mediating invasion and egress, cargo transport, and organelle inheritance. Advances in live cell imaging have revealed extensive filamentous actin networks in the Apicomplexan parasite, but there are conflicting data regarding the biochemical and biophysical properties of Toxoplasma actin. Here, we imaged the in vitro assembly of individual Toxoplasma actin filaments in real time, showing that native, unstabilized filaments grow tens of microns in length. Unlike skeletal muscle actin, Toxoplasma filaments intrinsically undergo rapid treadmilling due to a high critical concentration, fast monomer dissociation, and rapid nucleotide exchange. Cryo-EM structures of jasplakinolide-stabilized and native (i.e. unstabilized) filaments show an architecture like skeletal actin, with differences in assembly contacts in the D-loop that explain the dynamic nature of the filament, likely a conserved feature of Apicomplexan actin. This work demonstrates that evolutionary changes at assembly interfaces can tune the dynamic properties of actin filaments without disrupting their conserved structure.
Epitaxy of wafer-scale single-crystal MoS2 monolayer via buffer layer control
Authors: Li Lu , Wang Qinqin , Wu Fanfan , Xu Qiaoling , Tian Jinpeng , Huang Zhiheng , Wang Qinghe , Zhao Xuan , Zhang Qinghua , Fan Qinkai , Li Xiuzhen , Peng Yalin , Zhang Yangkun , Ji Kunshan , Zhi Aomiao , Sun Huacong , Zhu Mingtong , Zhu Jundong , Lu Nianpeng , Lu Ying , Wang Shuopei , Bai Xuedong , Xu Yang , Yang Wei , Li Na , Shi Dongxia , Xian Lede , Liu Kaihui , Du Luojun , Zhang Guangyu 
Published: February 2024

AbstractMonolayer molybdenum disulfide (MoS2), an emergent two-dimensional (2D) semiconductor, holds great promise for transcending the fundamental limits of silicon electronics and continue the downscaling of field-effect transistors. To realize its full potential and high-end applications, controlled synthesis of wafer-scale monolayer MoS2 single crystals on general commercial substrates is highly desired yet challenging. Here, we demonstrate the successful epitaxial growth of 2-inch single-crystal MoS2 monolayers on industry-compatible substrates of c-plane sapphire by engineering the formation of a specific interfacial reconstructed layer through the S/MoO3 precursor ratio control. The unidirectional alignment and seamless stitching of MoS2 domains across the entire wafer are demonstrated through cross-dimensional characterizations ranging from atomic- to centimeter-scale. The epitaxial monolayer MoS2 single crystal shows good wafer-scale uniformity and state-of-the-art quality, as evidenced from the ~100% phonon circular dichroism, exciton valley polarization of ~70%, room-temperature mobility of ~140 cm2v−1s−1, and on/off ratio of ~109. Our work provides a simple strategy to produce wafer-scale single-crystal 2D semiconductors on commercial insulator substrates, paving the way towards the further extension of Moore’s law and industrial applications of 2D electronic circuits.
Continuous strain tuning of oxygen evolution catalysts with anisotropic thermal expansion
Authors: Du Yu , Xie Fakang , Lu Mengfei , Lv Rongxian , Liu Wangxi , Yan Yuandong , Yan Shicheng , Zou Zhigang 
Published: February 2024

AbstractCompressive strain, downshifting the d-band center of transition metal oxides, is an effective way to accelerate the sluggish kinetics of oxygen evolution reaction (OER) for water electrolysis. Here, we find that anisotropic thermal expansion can produce compressive strains of the IrO6 octahedron in Sr2IrO4 catalyst, thus downshifting its d-band center. Different from the previous strategies to create constant strains in the crystals, the thermal-triggered compressive strains can be real-timely tuned by varying temperature. As a result of the thermal strain accelerating OER kinetics, the Sr2IrO4 exhibits the nonlinear lnjo - T−1 (jo, exchange current density; T, absolute temperature) Arrhenius relationship, resulting from the thermally induced low-barrier electron transfer in the presence of thermal compressive strains. Our results verify that the thermal field can be utilized to manipulate the electronic states of Sr2IrO4 via thermal compressive strains downshifting the d-band center, significantly accelerating the OER kinetics, beyond the traditional thermal diffusion effects.
Low pressure reversibly driving colossal barocaloric effect in two-dimensional vdW alkylammonium halides
Authors: Gao Yi-Hong , Wang Dong-Hui , Hu Feng-Xia , Huang Qing-Zhen , Song You-Ting , Yuan Shuai-Kang , Tian Zheng-Ying , Wang Bing-Jie , Yu Zi-Bing , Zhou Hou-Bo , Kan Yue , Lin Yuan , Wang Jing , Li Yun-liang , Liu Ying , Chen Yun-Zhong , Sun Ji-Rong , Zhao Tong-Yun , Shen Bao-Gen 
Published: February 2024

AbstractPlastic crystals as barocaloric materials exhibit the large entropy change rivalling freon, however, the limited pressure-sensitivity and large hysteresis of phase transition hinder the colossal barocaloric effect accomplished reversibly at low pressure. Here we report reversible colossal barocaloric effect at low pressure in two-dimensional van-der-Waals alkylammonium halides. Via introducing long carbon chains in ammonium halide plastic crystals, two-dimensional structure forms in (CH3–(CH2)n-1)2NH2X (X: halogen element) with weak interlayer van-der-Waals force, which dictates interlayer expansion as large as 13% and consequently volume change as much as 12% during phase transition. Such anisotropic expansion provides sufficient space for carbon chains to undergo dramatic conformation disordering, which induces colossal entropy change with large pressure-sensitivity and small hysteresis. The record reversible colossal barocaloric effect with entropy change ΔSr ~ 400 J kg−1 K−1 at 0.08 GPa and adiabatic temperature change ΔTr ~ 11 K at 0.1 GPa highlights the design of novel barocaloric materials by engineering the dimensionality of plastic crystals.
Wide-field mid-infrared hyperspectral imaging beyond video rate
Authors: Fang Jianan , Huang Kun , Qin Ruiyang , Liang Yan , Wu E , Yan Ming , Zeng Heping 
Published: February 2024

AbstractMid-infrared hyperspectral imaging has become an indispensable tool to spatially resolve chemical information in a wide variety of samples. However, acquiring three-dimensional data cubes is typically time-consuming due to the limited speed of raster scanning or wavelength tuning, which impedes real-time visualization with high spatial definition across broad spectral bands. Here, we devise and implement a high-speed, wide-field mid-infrared hyperspectral imaging system relying on broadband parametric upconversion of high-brightness supercontinuum illumination at the Fourier plane. The upconverted replica is spectrally decomposed by a rapid acousto-optic tunable filter, which records high-definition monochromatic images at a frame rate of 10 kHz based on a megapixel silicon camera. Consequently, the hyperspectral imager allows us to acquire 100 spectral bands over 2600-4085 cm−1 in 10 ms, corresponding to a refreshing rate of 100 Hz. Moreover, the angular dependence of phase matching in the image upconversion is leveraged to realize snapshot operation with spatial multiplexing for multiple spectral channels, which may further boost the spectral imaging rate. The high acquisition rate, wide-field operation, and broadband spectral coverage could open new possibilities for high-throughput characterization of transient processes in material and life sciences.
A perspective on the evidence for glymphatic obstruction in spaceflight associated neuro-ocular syndrome and fatigue
Authors: Bateman Grant Alexander , Bateman Alexander Robert 
Published: February 2024

AbstractSpaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. Previously, the current authors have discussed the similarities and differences between SANS and idiopathic intracranial hypertension to try to elucidate a possible pathophysiology. Recently, a theory has been advanced that SANS may occur secondary to failure of the glymphatic system caused by venous dilatation within the brain and optic nerves. There is recent evidence to suggest glymphatic obstruction occurs in childhood hydrocephalus, multiple sclerosis and syringomyelia due to venous outflow dilatation similar to that proposed in SANS. The purpose of the current paper is to discuss the similarities and differences between the known CSF and venous pathophysiology in SANS with these other terrestrial diseases, to see if they can shed any further light on the underlying cause of this microgravity-induced disease.
Supramolecular polymers form tactoids through liquid–liquid phase separation
Authors: Fu Hailin , Huang Jingyi , van der Tol Joost J. B. , Su Lu , Wang Yuyang , Dey Swayandipta , Zijlstra Peter , Fytas George , Vantomme Ghislaine , Dankers Patricia Y. W. , Meijer E. W. 
Published: February 2024

AbstractLiquid–liquid phase separation (LLPS) of biopolymers has recently been shown to play a central role in the formation of membraneless organelles with a multitude of biological functions1–3. The interplay between LLPS and macromolecular condensation is part of continuing studies4,5. Synthetic supramolecular polymers are the non-covalent equivalent of macromolecules but they are not reported to undergo LLPS yet. Here we show that continuously growing fibrils, obtained from supramolecular polymerizations of synthetic components, are responsible for phase separation into highly anisotropic aqueous liquid droplets (tactoids) by means of an entropy-driven pathway. The crowding environment, regulated by dextran concentration, affects not only the kinetics of supramolecular polymerizations but also the properties of LLPS, including phase-separation kinetics, morphology, internal order, fluidity and mechanical properties of the final tactoids. In addition, substrate–liquid and liquid–liquid interfaces proved capable of accelerating LLPS of supramolecular polymers, allowing the generation of a myriad of three-dimensional-ordered structures, including highly ordered arrays of micrometre-long tactoids at surfaces. The generality and many possibilities of supramolecular polymerizations to control emerging morphologies are demonstrated with several supramolecular polymers, opening up a new field of matter ranging from highly structured aqueous solutions by means of stabilized LLPS to nanoscopic soft matter.
Feasibility of online managing cancer and living meaningfully (CALM) in Chinese patients with metastatic breast cancer: a pilot randomized control trial
Authors: Zhang Yening , Pang Ying , He Yi , You Miaoning , Tang Lili 
Published: February 2024

AbstractMetastatic breast cancer could cause various psychological symptoms. Managing Cancer and Living Meaningfully (CALM) is a brief, manualized psychotherapy that has been validated for advanced cancer patients. We conducted a pilot randomized control trial (RCT) to verify the feasibility and preliminary efficacy of CALM therapy in this population. Patients who met the inclusion criteria were randomly assigned into CALM or Wait-list Control (WLC) groups. Patients in the CALM group received CALM therapy and usual care; patients in WLC group first received usual care and then underwent CALM therapy after completing all assessments. All patients were asked to complete three assessments: T0(baseline), T1(3 months), and T2(6 months). The primary outcomes was death anxiety; other outcomes were depression, distress, suicide ideation, attachment security, spiritual well-being and quality of life at the end of life. Analysis of Covariance (ANCOVA) and t-test were used for statistics analysis. Thirty-six patients were randomly assigned to either of the two groups, with 34 patients completing the three assessments. At six months, we found significant between group differences in suicide ideation, distress, and life completion between the CALM and WLC groups. At T2, patients in CALM group reported lower levels of depression (F = 5.016, p = 0.033, partial η2 = 0.143), distress (F = 7.969, p = 0.010, partial η2 = 0.257), attachment avoidance (F = 4.407, p = 0.044, partial η2 = 0.128), and better sense of life completion (F = 5.493, p = 0.026, partial η2 = 0.155) than patients in the WLC group. Compared with results of the T0 assessments, we found significant differences in socres for depression (T2&T0, t = − 2.689, p = 0.011, Cohen’s d = 0.940) and distress (T2&T0, t = − 2.453, p = 0.022, Cohen’s d = 0.965) between the two groups. CALM therapy was well received by the study population, and CALM therapy can reduce depression, distress, attachment avoidance while improving quality of life in Chinese metastatic breast cancer patients. A Phase III RCT was recommended to verify the impact of CALM therapy on psychological burden and survival in this population.Trial registration: This study is part of the “Preliminary application study for Managing Cancer and Living Meaningfully (CALM) therapy in Chinese advanced cancer patients” clinical trial, with the Trial Registration Number of ChiCTR1900023129 (13/05/2019) in the Chinese Clinical Trial Registry (ChiCTR) website. (https://www.chictr.org.cn/index.html).
Establishing forward mixing model to mass transfer overview in multi-impeller agitated column for rare Earth extraction process
Authors: Torkaman Rezvan , Rovais Mohammad Reza Aboudzadeh , Asadollahzadeh Mehdi , Torab-Mostaedi Meisam , Saremi Mojtaba 
Published: February 2024

AbstractThe current study develops comprehensive mass transfer models to optimize the rare earth extraction. A plug flow, axial dispersion, backflow, forward mixing-based mass transfer model was created and solved numerically using the fitting technique. The investigated process is a multi-impeller agitated column designed to provide proper contact between organic and aqueous phases to extract rare-earth ions. Taking Sm(III)–Gd(III) separation as an application case, extraction efficiency in the agitation speed of 200 rpm was obtained equal to 95.14%, 76.67% by this column for Gd(III), and Sm(III) ions, respectively. The model's findings were compared with experimental data, and a significant agreement was achieved with the forward mixing model. The results indicated that the high agitation speed is beneficial to increasing the interfacial area while reducing the mass-transfer coefficient. On the contrary, the circulation within the larger droplet improves the transfer of mass, albeit at the expense of reducing the interfacial area. The results showed that the drop size distribution is a crucial factor as the droplet sizes significantly affect the droplet mass transfer. The mathematical models’ values of Ec for mass transfer parameters showed that the operational variables significantly affect the mass transfer rate and can cause deviations from the ideal flow path. A reasonable and appropriate estimation of the organic-side volumetric overall mass transfer coefficient was provided, which can be applied to this contactor’s design and scale-up.
Instrumental activities of daily living in older patients with metastatic prostate cancer: results from the meet-URO network ADHERE prospective study
Authors: Fratino Lucia , Polesel Jerry , Giunta Emilio Francesco , Maruzzo Marco , Buti Sebastiano , Hassan Mona Ali , Basso Umberto , Rebuzzi Sara Elena , De Giorgi Ugo , Cinausero Marika , Lipari Helga , Gamba Teresa , Bimbatti Davide , Dri Arianna , Ermacora Paola , Vignani Francesca , Fornarini Giuseppe , Rescigno Pasquale , Banna Giuseppe Luigi 
Published: February 2024

AbstractInstrumental activities of daily living (IADL) are significant health indicators closely related to executive functions and able to detect mild cognitive impairment. A decline in IADL usually precedes ADL limitation, including taking medications, and may therefore predict a cognitive decline. We aimed to investigate the association of patients’ IADL score with other clinical factors, with a particular focus on the presence of a caregiver, and the impact on adherence to androgen receptor pathway inhibitors (ARPIs) and survival outcomes within the Meet-URO 5—ADHERE study. It was a large prospective multicentre observational cohort study monitoring adherence to ARPIs in 234 metastatic castrate-resistant PC (mCRPC) patients aged ≥ 70. We observed an association between impaired IADL and lower geriatric G8 scores (p < 0.01), and lower adherence to ARPIs whether assessed by pill counting (p = 0.01) or self-reported by the patient himself (p = 0.03). The combination of an IADL < 6 and the absence of a caregiver resulted in a significantly high risk of non-adherence to the ARPIs at the multivariable analysis (HR 9.23, 95% confidence interval 2.28–37.43, p = 0.01). IADL alongside the geriatric G8 scales represent essential tools to identify frail and less auto-sufficient patients who are extremely vulnerable particularly if not supported by a caregiver and have the highest risk of nonadherence to ARPIs.