bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceived patient burden and acceptability of MRI in comparison to PSA and ultrasound: results from the IP1-PROSTAGRAM study
Authors: Eldred-Evans David , Winkler Mathias , Klimowska-Nassar Natalia , Burak Paula , Connor Martin J. , Fiorentino Francesca , Day Emily , Price Derek , Gammon Martin , Tam Henry , Sokhi Heminder , Padhani Anwar R. , Ahmed Hashim U. 
Published: April 2023

Abstract
Background
The IP1-PROSTAGRAM study showed that a short, non-contrast MRI detected more significant cancers with similar rates of biopsy compared to PSA. Herein, we compare the expected and perceived burden of PSA, MRI and ultrasound as screening tests.

Methods
IP1-PROSTAGRAM was a prospective, population-based, paired screening study of 408 men conducted at seven UK primary care practices and two imaging centres. The screening tests were serum PSA, non-contrast MRI and ultrasound. If any test was screen-positive, a prostate biopsy was performed. Participants completed an Expected Burden Questionnaire (EBQ) and Perceived Burden Questionnaire (PBQ) before and after each screening test.

Results
The overall level of burden for MRI and PSA was minimal. Few men reported high levels of anxiety, burden, embarrassment or pain following either MRI or PSA. Participants indicated an overall preference for MRI after completing all screening tests. Of 408 participants, 194 (47.5%) had no preference, 106 (26.0%) preferred MRI and 79 (19.4%) preferred PSA. This indicates that prior to screening, participants preferred MRI compared to PSA (+6.6%, 95% CI 4.4–8.4, p = 0.02) and after completing screening, the preference for MRI was higher (+21.1%, 95% CI 14.9–27.1, p < 0.001). The proportion of participants who strongly agreed with repeating the test was 50.5% for ultrasound, 65% for MRI and 68% for PSA. A larger proportion of participants found ultrasound anxiety-inducing, burdensome, embarrassing and painful compared to both MRI and PSA.

Conclusions
Prostagram MRI and PSA are both acceptable as screening tests among men aged 50–69 years. Both tests were associated with minimal amounts of anxiety, burden, embarrassment and pain. The majority of participants preferred MRI over PSA and ultrasound.

Registration
This study was registered on clinicaltrials.gov at https://clinicaltrials.gov/ct2/show/NCT03702439.
Increased plasma DYRK1A with aging may protect against neurodegenerative diseases
Authors: Delabar Jean M. , Lagarde Julien , Fructuoso Marta , Mohammad Ammara , Bottlaender Michel , Doran Eric , Lott Ira , Rivals Isabelle , Schmitt Frederic A. , Head Elizabeth , Sarazin Marie , Potier Marie-Claude 
Published: April 2023

AbstractEarly markers are needed for more effective prevention of Alzheimer’s disease. We previously showed that individuals with Alzheimer’s disease have decreased plasma DYRK1A levels compared to controls. We assessed DYRK1A in the plasma of cognitively healthy elderly volunteers, individuals with either Alzheimer’s disease (AD), tauopathies or Down syndrome (DS), and in lymphoblastoids from individuals with DS. DYRK1A levels were inversely correlated with brain amyloid β burden in asymptomatic elderly individuals and AD patients. Low DYRK1A levels were also detected in patients with tauopathies. Individuals with DS had higher DYRK1A levels than controls, although levels were lower in individuals with DS and with dementia. These data suggest that plasma DYRK1A levels could be used for early detection of at risk individuals of AD and for early detection of AD. We hypothesize that lack of increase of DYRK1A at middle age (40–50 years) could be a warning before the cognitive decline, reflecting increased risk for AD.
Density and maturity of peritumoral tertiary lymphoid structures in oesophageal squamous cell carcinoma predicts patient survival and response to immune checkpoint inhibitors
Authors: Hayashi Yoshinori , Makino Tomoki , Sato Eiichi , Ohshima Kenji , Nogi Yuya , Kanemura Takashi , Honma Keiichiro , Yamashita Kotaro , Saito Takuro , Tanaka Koji , Yamamoto Kazuyoshi , Takahashi Tsuyoshi , Kurokawa Yukinori , Miyata Hiroshi , Nakajima Kiyokazu , Wada Hisashi , Morii Eiichi , Eguchi Hidetoshi , Doki Yuichiro 
Published: April 2023

Abstract
Background
Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates in non-lymphoid tissues, which are associated with improved prognosis in some cancer types. This study aimed to investigate the clinical significance of TLSs in oesophageal cancer (EC).

Methods
In a series of 316 EC surgical specimens from two different institutes, we evaluated the density and maturity of peritumoral TLSs using haematoxylin/eosin, immunohistochemistry, and multiplex immunofluorescence staining. We analysed the association between TLSs and clinicopathological parameters. The clinical significance of TLSs was further evaluated in a different cohort of 34 patients with recurrent EC treated with anti-PD-1 antibody.

Results
Tumours with high TLS density predominantly consisted of matured TLSs. High TLS density was significantly associated with less advanced tumour stage, absence of lymphatic/vascular invasion, better serum nutrition parameters (neutrophils count, albumin, neutrophil-to-lymphocyte ratio, and prognostic nutritional index), and prolonged survival. This survival trend was more remarkable in cases with matured TLSs, which represented an increased population of CD138+ plasma cells. In the second EC cohort, TLS density predicted the clinical response to anti-PD-1 antibody and patient survival.

Conclusion
The density and maturity of peritumoral TLSs are useful parameters for predicting long-term survival and response to anti-PD-1 antibody treatment in EC patients.
Heating a dipolar quantum fluid into a solid
Authors: Sánchez-Baena J. , Politi C. , Maucher F. , Ferlaino F. , Pohl T. 
Published: April 2023

AbstractRaising the temperature of a material enhances the thermal motion of particles. Such an increase in thermal energy commonly leads to the melting of a solid into a fluid and eventually vaporises the liquid into a gaseous phase of matter. Here, we study the finite-temperature physics of dipolar quantum fluids and find surprising deviations from this general phenomenology. In particular, we describe how heating a dipolar superfluid from near-zero temperatures can induce a phase transition to a supersolid state with a broken translational symmetry. We discuss the observation of this effect in experiments on ultracold dysprosium atoms, which opens the door for exploring the unusual thermodynamics of dipolar quantum fluids.
Low-temperature and circadian signals are integrated by the sigma factor SIG5
Authors: Cano-Ramirez Dora L. , Panter Paige E. , Takemura Tokiaki , de Fraine Tara Saskia , de Barros Dantas Luíza Lane , Dekeya Richard , Barros-Galvão Thiago , Paajanen Pirita , Bellandi Annalisa , Batstone Tom , Manley Bethan F. , Tanaka Kan , Imamura Sousuke , Franklin Keara A. , Knight Heather , Dodd Antony N. 
Published: April 2023

AbstractChloroplasts are a common feature of plant cells and aspects of their metabolism, including photosynthesis, are influenced by low-temperature conditions. Chloroplasts contain a small circular genome that encodes essential components of the photosynthetic apparatus and chloroplast transcription/translation machinery. Here, we show that in Arabidopsis, a nuclear-encoded sigma factor that controls chloroplast transcription (SIGMA FACTOR5) contributes to adaptation to low-temperature conditions. This process involves the regulation of SIGMA FACTOR5 expression in response to cold by the bZIP transcription factors ELONGATED HYPOCOTYL5 and ELONGATED HYPOCOTYL5 HOMOLOG. The response of this pathway to cold is gated by the circadian clock, and it enhances photosynthetic efficiency during long-term cold and freezing exposure. We identify a process that integrates low-temperature and circadian signals, and modulates the response of chloroplasts to low-temperature conditions.
Condensation heat transfer in microgravity conditions
Authors: Berto Arianna , Azzolin Marco , Bortolin Stefano , Miscevic Marc , Lavieille Pascal , Del Col Davide 
Published: April 2023

AbstractIn the present paper, a thorough review of the experimental and numerical studies dealing with filmwise and dropwise condensation under microgravity is reported, covering mechanisms both inside tubes and on plain or enhanced surfaces. The gravity effect on the condensation heat transfer is examined considering the results of studies conducted both in terrestrial environment and in the absence of gravity. From the literature, it can be inferred that the influence of gravity on the condensation heat transfer inside tubes can be limited by increasing the mass flux of the operating fluid and, at equal mass flux, by decreasing the channel diameter. There are flow conditions at which gravity does exert a negligible effect during in-tube condensation: predictive tools for identifying such conditions and for the evaluation of the condensation heat transfer coefficient are also discussed. With regard to dropwise condensation, if liquid removal depends on gravity, this prevents its application in low gravity space systems. Alternatively, droplets can be removed by the high vapor velocity or by passive techniques based on the use of condensing surfaces with wettability gradients or micrometric/nanometric structuration: these represent an interesting solution for exploiting the benefits of dropwise condensation in terms of heat transfer enhancement and equipment compactness in microgravitational environments. The experimental investigation of the condensation heat transfer for long durations in steady-state zero-gravity conditions, such as inside the International Space Station, may compensate the substantial lack of repeatable experimental data and allow the development of reliable design tools for space applications.
Experimental simulation of loop quantum gravity on a photonic chip
Authors: van der Meer Reinier , Huang Zichang , Anguita Malaquias Correa , Qu Dongxue , Hooijschuur Peter , Liu Hongguang , Han Muxin , Renema Jelmer J. , Cohen Lior 
Published: April 2023

AbstractThe unification of general relativity and quantum theory is one of the fascinating problems of modern physics. One leading solution is Loop Quantum Gravity (LQG). Simulating LQG may be important for providing predictions which can then be tested experimentally. However, such complex quantum simulations cannot run efficiently on classical computers, and quantum computers or simulators are needed. Here, we experimentally demonstrate quantum simulations of spinfoam amplitudes of LQG on an integrated photonics quantum processor. We simulate a basic transition of LQG and show that the derived spinfoam vertex amplitude falls within 4% error with respect to the theoretical prediction, despite experimental imperfections. We also discuss how to generalize the simulation for more complex transitions, in realistic experimental conditions, which will eventually lead to a quantum advantage demonstration as well as expand the toolbox to investigate LQG.
Extreme flooding controlled by stream network organization and flow regime
Authors: Basso Stefano , Merz Ralf , Tarasova Larisa , Miniussi Arianna 
Published: April 2023

AbstractRiver floods are among the most common natural disasters worldwide, with substantial economic and humanitarian costs. Despite enormous efforts, gauging the risk of extreme floods with unprecedented magnitude is an outstanding challenge. Limited observational data from very high-magnitude flood events hinders prediction efforts and the identification of discharge thresholds marking the rise of progressively larger floods, termed flood divides. Combining long hydroclimatic records and a process-based model for flood hazard assessment, here we demonstrate that the spatial organization of stream networks and the river flow regime control the appearance of flood divides and extreme floods. In contrast with their ubiquitous attribution to extreme rainfall and anomalous antecedent conditions, we show that the propensity to generate extreme floods is well predicted by intrinsic properties of river basins. Most importantly, it can be assessed prior to the occurrence of catastrophes through measurable metrics of these properties derived from commonly available discharge data, namely the hydrograph recession exponent and the coefficient of variation of daily flows. These results highlight the propensity of certain rivers for generating extreme floods and demonstrate the importance of using hazard mapping tools that, rather than solely relying on past flood records, identify regions susceptible to the occurrence of extreme floods from ordinary discharge dynamics.
Chiral antiferromagnetic Josephson junctions as spin-triplet supercurrent spin valves and d.c. SQUIDs
Authors: Jeon Kun-Rok , Hazra Binoy Krishna , Kim Jae-Keun , Jeon Jae-Chun , Han Hyeon , Meyerheim Holger L. , Kontos Takis , Cottet Audrey , Parkin Stuart S. P. 
Published: April 2023

AbstractSpin-triplet supercurrent spin valves are of practical importance for the realization of superconducting spintronic logic circuits. In ferromagnetic Josephson junctions, the magnetic-field-controlled non-collinearity between the spin-mixer and spin-rotator magnetizations switches the spin-polarized triplet supercurrents on and off. Here we report an antiferromagnetic equivalent of such spin-triplet supercurrent spin valves in chiral antiferromagnetic Josephson junctions as well as a direct-current superconducting quantum interference device. We employ the topological chiral antiferromagnet Mn3Ge, in which the Berry curvature of the band structure produces fictitious magnetic fields, and the non-collinear atomic-scale spin arrangement accommodates triplet Cooper pairing over long distances (>150 nm). We theoretically verify the observed supercurrent spin-valve behaviours under a small magnetic field of <2 mT for current-biased junctions and the direct-current superconducting quantum interference device functionality. Our calculations reproduce the observed hysteretic field interference of the Josephson critical current and link these to the magnetic-field-modulated antiferromagnetic texture that alters the Berry curvature. Our work employs band topology to control the pairing amplitude of spin-triplet Cooper pairs in a single chiral antiferromagnet.
G-CSF drives autoinflammation in APLAID
Authors: Mulazzani Elisabeth , Kong Klara , Aróstegui Juan I. , Ng Ashley P. , Ranathunga Nishika , Abeysekera Waruni , Garnham Alexandra L. , Ng Sze-Ling , Baker Paul J. , Jackson Jacob T. , Lich John D. , Hibbs Margaret L. , Wicks Ian P. , Louis Cynthia , Masters Seth L. 
Published: April 2023

AbstractMissense mutations in PLCG2 can cause autoinflammation with phospholipase C gamma 2-associated antibody deficiency and immune dysregulation (APLAID). Here, we generated a mouse model carrying an APLAID mutation (p.Ser707Tyr) and found that inflammatory infiltrates in the skin and lungs were only partially ameliorated by removing inflammasome function via the deletion of caspase-1. Also, deleting interleukin-6 or tumor necrosis factor did not fully prevent APLAID mutant mice from autoinflammation. Overall, these findings are in accordance with the poor response individuals with APLAID have to treatments that block interleukin-1, JAK1/2 or tumor necrosis factor. Cytokine analysis revealed increased granulocyte colony-stimulating factor (G-CSF) levels as the most distinct feature in mice and individuals with APLAID. Remarkably, treatment with a G-CSF antibody completely reversed established disease in APLAID mice. Furthermore, excessive myelopoiesis was normalized and lymphocyte numbers rebounded. APLAID mice were also fully rescued by bone marrow transplantation from healthy donors, associated with reduced G-CSF production, predominantly from non-hematopoietic cells. In summary, we identify APLAID as a G-CSF-driven autoinflammatory disease, for which targeted therapy is feasible.
Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results
Authors: Glitza Oliva Isabella C. , Ferguson Sherise D. , Bassett Roland , Foster Alexandra P. , John Ida , Hennegan Tarin D. , Rohlfs Michelle , Richard Jessie , Iqbal Masood , Dett Tina , Lacey Carol , Jackson Natalie , Rodgers Theresa , Phillips Suzanne , Duncan Sheila , Haydu Lauren , Lin Ruitao , Amaria Rodabe N. , Wong Michael K. , Diab Adi , Yee Cassian , Patel Sapna P. , McQuade Jennifer L. , Fischer Grant M. , McCutcheon Ian E. , O’Brien Barbara J. , Tummala Sudhakar , Debnam Matthew , Guha-Thakurta Nandita , Wargo Jennifer A. , Carapeto Fernando C. L. , Hudgens Courtney W. , Huse Jason T. , Tetzlaff Michael T. , Burton Elizabeth M. , Tawbi Hussein A. , Davies Michael A. 
Published: April 2023

AbstractThere is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50 mg (with IV nivolumab 240 mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256.
Norepinephrine links astrocytic activity to regulation of cortical state
Authors: Reitman Michael E. , Tse Vincent , Mi Xuelong , Willoughby Drew D. , Peinado Alba , Aivazidis Alexander , Myagmar Bat-Erdene , Simpson Paul C. , Bayraktar Omer A. , Yu Guoqiang , Poskanzer Kira E. 
Published: April 2023

AbstractCortical state, defined by population-level neuronal activity patterns, determines sensory perception. While arousal-associated neuromodulators—including norepinephrine (NE)—reduce cortical synchrony, how the cortex resynchronizes remains unknown. Furthermore, general mechanisms regulating cortical synchrony in the wake state are poorly understood. Using in vivo imaging and electrophysiology in mouse visual cortex, we describe a critical role for cortical astrocytes in circuit resynchronization. We characterize astrocytes’ calcium responses to changes in behavioral arousal and NE, and show that astrocytes signal when arousal-driven neuronal activity is reduced and bi-hemispheric cortical synchrony is increased. Using in vivo pharmacology, we uncover a paradoxical, synchronizing response to Adra1a receptor stimulation. We reconcile these results by demonstrating that astrocyte-specific deletion of Adra1a enhances arousal-driven neuronal activity, while impairing arousal-related cortical synchrony. Our findings demonstrate that astrocytic NE signaling acts as a distinct neuromodulatory pathway, regulating cortical state and linking arousal-associated desynchrony to cortical circuit resynchronization.
Control of transcription elongation and DNA repair by alarmone ppGpp
Authors: Weaver Jacob W. , Proshkin Sergey , Duan Wenqian , Epshtein Vitaly , Gowder Manjunath , Bharati Binod K. , Afanaseva Elena , Mironov Alexander , Serganov Alexander , Nudler Evgeny 
Published: April 2023

AbstractSecond messenger (p)ppGpp (collectively guanosine tetraphosphate and guanosine pentaphosphate) mediates bacterial adaptation to nutritional stress by modulating transcription initiation. More recently, ppGpp has been implicated in coupling transcription and DNA repair; however, the mechanism of ppGpp engagement remained elusive. Here we present structural, biochemical and genetic evidence that ppGpp controls Escherichia coli RNA polymerase (RNAP) during elongation via a specific site that is nonfunctional during initiation. Structure-guided mutagenesis renders the elongation (but not initiation) complex unresponsive to ppGpp and increases bacterial sensitivity to genotoxic agents and ultraviolet radiation. Thus, ppGpp binds RNAP at sites with distinct functions in initiation and elongation, with the latter being important for promoting DNA repair. Our data provide insights on the molecular mechanism of ppGpp-mediated adaptation during stress, and further highlight the intricate relationships between genome stability, stress responses and transcription.
Expanded forehead flap in Asian nasal reconstruction
Authors: Wei Muqian , Bu Xi , Wang Guanhuier , Zhen Yonghuan , Yang Xin , Li Dong , An Yang 
Published: April 2023

AbstractThis article reviewed our experience of Chinese nasal reconstruction over 12 years and evaluated the effect of expanded forehead flap both aesthetically and functionally. The special skin type and other anatomic features of Chinese patients was understood thoroughly during the treatment. This article thus catered for the need of multiracial nasal reconstruction. We analyzed existing clinical data and demonstrated a typical case in detail. The postoperative result supported our strategy which advocated the extensive application of expanded forehead flap, together with flip scar flap as the internal lining. The features of Chinese patients also prompted the use of costal and auricular cartilage. Emerging technology like 3D-printing would benefit nasal reconstruction from more aspects.
Non-invasive authentication of mail packages using nuclear quadrupole resonance spectroscopy
Authors: Horace-Herron Kelsey , Masna Naren Vikram Raj , Dehghanzadeh Peyman , Mandal Soumyajit , Bhunia Swarup 
Published: April 2023

AbstractThe international postal network is one of the most widely used methods for correspondence throughout the world. Most postal traffic across the globe consists of legitimate interpersonal, business-consumer, and business-business communications. However, the global postal system is also utilized for criminal activity. In particular, it is often utilized to ship and distribute contraband, including illegal psychoactive drugs such as fentanyl and heroin, to consumers. Existing technological solutions are capable of identifying synthetic opioids and other illegal drugs within packages, but are accompanied by several disadvantages that make them unsuitable for large-scale authentication of international mail traffic. This paper presents a novel method for non-invasive authentication of mail packages that overcomes these challenges. The approach uses nuclear quadrupole resonance (NQR) spectroscopy to detect and quantify the presence of known active pharmaceutical ingredients (APIs) within the package. It has been experimentally demonstrated using a bench top prototype. Test results from a variety of package types demonstrate the effectiveness of the proposed authentication approach.