bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remuneration of donors for cell and gene therapies: an update on the principles and perspective of the World Marrow Donor Association
Authors: Hamad Lina , Ahmed Salmah Mahmood , van Eerden Eefke , van Walraven Suzanna M. ,   World Marrow Donor Association Cellular Therapy Committee, Machin Laura 
Published: February 2024

AbstractThe cell and gene therapy (CGT) sector has witnessed significant advancement over the past decade, the inception of advanced therapy medicinal products (ATMPs) being one of the most transformational. ATMPs treat serious medical conditions, in some cases providing curative therapy for seriously ill patients. There is interest in pivoting the ATMP development from autologous based treatments to allogenic, to offer faster and greater patient access that should ultimately reduce treatment costs. Consequently, starting material from allogenic donors is required, igniting ethical issues associated with financial gains and donor remuneration within CGT. The World Marrow Donor Association (WMDA) established the Cellular Therapy Committee to identify the role WMDA can play in safeguarding donors and patients in the CGT field. Here we review key ethical principles in relation to donating cellular material for the CGT field. We present the updated statement from WMDA on donor remuneration, which supports non-remuneration as the best way to ensure the safety and well-being of donors and patients alike. This is in line with the fundamental objective of the WMDA to maintain the health and safety of volunteer donors while ensuring high-quality stem cell products are available for all patients. We acknowledge that the CGT field is evolving at a rapid pace and there will be a need to review this position as new practices and applications come to pass.
Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development
Authors: Brylka Laura J. , Alimy Assil-Ramin , Tschaffon-Müller Miriam E. A. , Jiang Shan , Ballhause Tobias Malte , Baranowsky Anke , von Kroge Simon , Delsmann Julian , Pawlus Eva , Eghbalian Kian , Püschel Klaus , Schoppa Astrid , Haffner-Luntzer Melanie , Beech David J. , Beil Frank Timo , Amling Michael , Keller Johannes , Ignatius Anita , Yorgan Timur A. , Rolvien Tim , Schinke Thorsten 
Published: February 2024

AbstractPiezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for bone-anabolic processes, there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage. Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis (OA) development. Mice with chondrocyte-specific inactivation of Piezo1 (Piezo1Col2a1Cre), but not of Piezo2, developed a near absence of trabecular bone below the chondrogenic growth plate postnatally. Moreover, all Piezo1Col2a1Cre animals displayed multiple fractures of rib bones at 7 days of age, which were located close to the growth plates. While skeletal growth was only mildly affected in these mice, OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age. Likewise, when OA was induced by anterior cruciate ligament transection, only the chondrocyte inactivation of Piezo1, not of Piezo2, resulted in attenuated articular cartilage degeneration. Importantly, osteophyte formation and maturation were also reduced in Piezo1Col2a1Cre mice. We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes. Finally, we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes. Collectively, our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes, but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.
Proliferative verrucous leukoplakia: a general dental practitioner-focused clinical review
Authors: Staines Konrad , Rogers Helen 
Published: February 2024

AbstractProliferative verrucous leukoplakia (PVL) is a distinct type of oral leukoplakia which has the potential to enlarge or develop into new areas of leukoplakia coupled with areas of a warty surface texture. PVL is usually diagnosed from the fifth decade onwards and is more common in female patients. The most frequent sites involved tend to be gingivae, followed by buccal mucosa and lateral border of tongue. It is one of the oral potentially malignant conditions with a high risk of malignant transformation. It is important for general dental practitioners (GDPs) to identify such lesions to facilitate referral for further investigation and diagnosis. Management is challenging with long-term monitoring and surgical excision when appropriate; however, PVL tends to recur following surgical excision. This article provides an up-to-date review tailored for GDPs on the present knowledge of PVL and illustrates the management challenges with clinical cases.
The management of pemphigus vulgaris and mucous membrane pemphigoid in a joint oral medicine and dermatology clinic: a five-year narrative review
Authors: Davis Gemma , Hathway Russell , Shipley Debbie , Staines Konrad 
Published: February 2024

AbstractPemphigus disease and mucous membrane pemphigoid are autoimmune blistering diseases (AIBDs) which may involve both oral and extra-oral tissues. The Bristol Joint Oral Medicine and Dermatology Combined Clinic was set up in 2014, with the primary aim of improving the standard of care for patients with AIBDs. This interdisciplinary approach aimed to address the medical management challenges due to the multisite nature of these AIBDs.We present a narrative report of the clinical work undertaken within this clinic, focused on the management of this patient cohort within a five-year span (2017-2022). This report outlines the multisite nature of AIBDs and the range of topical and systemic treatments that were employed to achieve adequate disease control and optimise outcomes for patients. We reflect on the experiential benefits of this multidisciplinary clinic extended beyond immediate patient benefits to areas such as specialist training, both from a dermatologist's and oral physician's perspective.
Modulation of cAMP/cGMP signaling as prevention of congenital heart defects in Pde2A deficient embryos: a matter of oxidative stress
Authors: Cardarelli Silvia , Biglietto Martina , Orsini Tiziana , Fustaino Valentina , Monaco Lucia , de Oliveira do Rêgo Ana Gabriela , Liccardo Francesca , Masciarelli Silvia , Fazi Francesco , Naro Fabio , De Angelis Luciana , Pellegrini Manuela 
Published: February 2024

AbstractPhosphodiesterase 2A (Pde2A) is a dual-specific PDE that breaks down both cAMP and cGMP cyclic nucleotides. We recently highlighted a direct relationship between Pde2A impairment, a consequent increase of cAMP, and the appearance of mouse congenital heart defects (CHDs). Here we aimed to characterize the pathways involved in the development of CHDs and in their prevention by pharmacological approaches targeting cAMP and cGMP signaling. Transcriptome analysis revealed a modulation of more than 500 genes affecting biological processes involved in the immune system, cardiomyocyte development and contractility, angiogenesis, transcription, and oxidative stress in hearts from Pde2A−/− embryos. Metoprolol and H89 pharmacological administration prevented heart dilatation and hypertabeculation in Pde2A−/− embryos. Metoprolol was also able to partially impede heart septum defect and oxidative stress at tissue and molecular levels. Amelioration of cardiac defects was also observed by using the antioxidant NAC, indicating oxidative stress as one of the molecular mechanisms underpinning the CHDs. In addition, Sildenafil treatment recovered cardiac defects suggesting the requirement of cAMP/cGMP nucleotides balance for the correct heart development.
Mechanistic exploration of polytetrafluoroethylene thermal plasma gasification through multiscale simulation coupled with experimental validation
Authors: Chu Chu , Ma Long Long , Alawi Hyder , Ma Wenchao , Zhu YiFei , Sun Junhao , Lu Yao , Xue Yixian , Chen Guanyi 
Published: February 2024

AbstractThe ever-growing quantities of persistent Polytetrafluoroethylene (PTFE) wastes, along with consequential ecological and human health concerns, stimulate the need for alternative PTFE disposal method. The central research challenge lies in elucidating the decomposition mechanism of PTFE during high-temperature waste treatment. Here, we propose the PTFE microscopic thermal decomposition pathways by integrating plasma gasification experiments with multi-scale simulations strategies. Molecular dynamic simulations reveal a pyrolysis—oxidation & chain-shortening—deep defluorination (POCD) degradation pathway in an oxygen atmosphere, and an F abstraction—hydrolysis—deep defluorination (FHD) pathway in a steam atmosphere. Density functional theory computations demonstrate the vital roles of 1O2 and ·H radicals in the scission of PTFE carbon skeleton, validating the proposed pathways. Experimental results confirm the simulation results and show that up to 80.12% of gaseous fluorine can be recovered through plasma gasification within 5 min, under the optimized operating conditions determined through response surface methodology.
Predator selection on phenotypic variability of cryptic and aposematic moths
Authors: Nokelainen Ossi , Silvasti Sanni A. , Strauss Sharon Y. , Wahlberg Niklas , Mappes Johanna 
Published: February 2024

AbstractNatural selection generally favours phenotypic variability in camouflaged organisms, whereas aposematic organisms are expected to evolve a more uniform warning coloration. However, no comprehensive analysis of the phenotypic consequences of predator selection in aposematic and cryptic species exists. Using state-of-the-art image analysis, we examine 2800 wing images of 82 moth species accessed via three online museum databases. We test whether anti-predator strategy (i.e., camouflage or aposematism) explains intraspecific variation in wing colour and pattern across northern hemisphere moths. In addition, we test two mutually non-exclusive, ecological hypotheses to explain variation in colour pattern: diel-activity or dietary-niche. In this work, taking into account phylogenetic relationships, moth phenotypic variability is best explained by anti-predator strategy with camouflaged moths being more variable in wing patterning than aposematic species.
Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
Authors: Standing Joseph F. , Buggiotti Laura , Guerra-Assuncao Jose Afonso , Woodall Maximillian , Ellis Samuel , Agyeman Akosua A. , Miller Charles , Okechukwu Mercy , Kirkpatrick Emily , Jacobs Amy I. , Williams Charlotte A. , Roy Sunando , Martin-Bernal Luz M. , Williams Rachel , Smith Claire M. , Sanderson Theo , Ashford Fiona B. , Emmanuel Beena , Afzal Zaheer M. , Shields Adrian , Richter Alex G. , Dorward Jienchi , Gbinigie Oghenekome , Van Hecke Oliver , Lown Mark , Francis Nick , Jani Bhautesh , Richards Duncan B. , Rahman Najib M. , Yu Ly-Mee , Thomas Nicholas P. B. , Hart Nigel D. , Evans Philip , Andersson Monique , Hayward Gail , Hood Kerenza , Nguyen-Van-Tam Jonathan S. , Little Paul , Hobbs F. D. Richard , Khoo Saye , Butler Christopher , Lowe David M. , Breuer Judith ,   PANORAMIC Virology Group, Allen Julie , Bayzid Nadua , Brown Julianne , Burns Doug , Hadley Elizabeth , Hatcher Jim , McHugh Tim , Thalasselis Chris , Tomlinson Mia , Yongblah Francis 
Published: February 2024

AbstractViral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days of SARS-CoV-2 symptoms randomised to receive molnupiravir (n = 253) or Usual Care (n = 324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN30448031
Repeated blood–brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial
Authors: Carpentier Alexandre , Stupp Roger , Sonabend Adam M. , Dufour Henry , Chinot Olivier , Mathon Bertrand , Ducray François , Guyotat Jacques , Baize Nathalie , Menei Philippe , de Groot John , Weinberg Jeffrey S. , Liu Benjamin P. , Guemas Eric , Desseaux Carole , Schmitt Charlotte , Bouchoux Guillaume , Canney Michael , Idbaih Ahmed 
Published: February 2024

AbstractHere, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope (n = 3), fatigue (n = 1), wound infection (n = 2), and pain at time of device connection (n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery.
Real-time two-axis control of a spin qubit
Authors: Berritta Fabrizio , Rasmussen Torbjørn , Krzywda Jan A. , van der Heijden Joost , Fedele Federico , Fallahi Saeed , Gardner Geoffrey C. , Manfra Michael J. , van Nieuwenburg Evert , Danon Jeroen , Chatterjee Anasua , Kuemmeth Ferdinand 
Published: February 2024

AbstractOptimal control of qubits requires the ability to adapt continuously to their ever-changing environment. We demonstrate a real-time control protocol for a two-electron singlet-triplet qubit with two fluctuating Hamiltonian parameters. Our approach leverages single-shot readout classification and dynamic waveform generation, allowing full Hamiltonian estimation to dynamically stabilize and optimize the qubit performance. Powered by a field-programmable gate array (FPGA), the quantum control electronics estimates the Overhauser field gradient between the two electrons in real time, enabling controlled Overhauser-driven spin rotations and thus bypassing the need for micromagnets or nuclear polarization protocols. It also estimates the exchange interaction between the two electrons and adjusts their detuning, resulting in extended coherence of Hadamard rotations when correcting for fluctuations of both qubit axes. Our study highlights the role of feedback in enhancing the performance and stability of quantum devices affected by quasistatic noise.
Phonon promoted charge density wave in topological kagome metal ScV6Sn6
Authors: Hu Yong , Ma Junzhang , Li Yinxiang , Jiang Yuxiao , Gawryluk Dariusz Jakub , Hu Tianchen , Teyssier Jérémie , Multian Volodymyr , Yin Zhouyi , Xu Shuxiang , Shin Soohyeon , Plokhikh Igor , Han Xinloong , Plumb Nicholas C. , Liu Yang , Yin Jia-Xin , Guguchia Zurab , Zhao Yue , Schnyder Andreas P. , Wu Xianxin , Pomjakushina Ekaterina , Hasan M. Zahid , Wang Nanlin , Shi Ming 
Published: February 2024

AbstractCharge density wave (CDW) orders in vanadium-based kagome metals have recently received tremendous attention, yet their origin remains a topic of debate. The discovery of ScV6Sn6, a bilayer kagome metal featuring an intriguing $$\sqrt{3}\times\sqrt{3}\times3$$

3

×

3

×
3
CDW order, offers a novel platform to explore the underlying mechanism behind the unconventional CDW. Here, we combine high-resolution angle-resolved photoemission spectroscopy, Raman scattering and density functional theory to investigate the electronic structure and phonon modes of ScV6Sn6. We identify topologically nontrivial surface states and multiple van Hove singularities (VHSs) in the vicinity of the Fermi level, with one VHS aligning with the in-plane component of the CDW vector near the $$\bar{K}$$

K

¯

point. Additionally, Raman measurements indicate a strong electron-phonon coupling, as evidenced by a two-phonon mode and new emergent modes. Our findings highlight the fundamental role of lattice degrees of freedom in promoting the CDW in ScV6Sn6.
Broadband thermal imaging using meta-optics
Authors: Huang Luocheng , Han Zheyi , Wirth-Singh Anna , Saragadam Vishwanath , Mukherjee Saswata , Fröch Johannes E. , Tanguy Quentin A. A. , Rollag Joshua , Gibson Ricky , Hendrickson Joshua R. , Hon Philip W. C. , Kigner Orrin , Coppens Zachary , Böhringer Karl F. , Veeraraghavan Ashok , Majumdar Arka 
Published: February 2024

AbstractSubwavelength diffractive optics known as meta-optics have demonstrated the potential to significantly miniaturize imaging systems. However, despite impressive demonstrations, most meta-optical imaging systems suffer from strong chromatic aberrations, limiting their utilities. Here, we employ inverse-design to create broadband meta-optics operating in the long-wave infrared (LWIR) regime (8-12 μm). Via a deep-learning assisted multi-scale differentiable framework that links meta-atoms to the phase, we maximize the wavelength-averaged volume under the modulation transfer function (MTF) surface of the meta-optics. Our design framework merges local phase-engineering via meta-atoms and global engineering of the scatterer within a single pipeline. We corroborate our design by fabricating and experimentally characterizing all-silicon LWIR meta-optics. Our engineered meta-optic is complemented by a simple computational backend that dramatically improves the quality of the captured image. We experimentally demonstrate a six-fold improvement of the wavelength-averaged Strehl ratio over the traditional hyperboloid metalens for broadband imaging.
Japanese wolves are most closely related to dogs and share DNA with East Eurasian dogs
Authors: Gojobori Jun , Arakawa Nami , Xiaokaiti Xiayire , Matsumoto Yuki , Matsumura Shuichi , Hongo Hitomi , Ishiguro Naotaka , Terai Yohey 
Published: February 2024

AbstractAlthough the domestic dog’s origin is still unclear, this lineage is believed to have been domesticated from an extinct population of gray wolves, which is expected to be more closely related to dogs than to other populations of gray wolves. Here, we sequence the whole genomes of nine Japanese wolves (7.5–100x: Edo to Meiji periods) and 11 modern Japanese dogs and analyze them together with those from other populations of dogs and wolves. A phylogenomic tree shows that, among the gray wolves, Japanese wolves are closest to the dog, suggesting that the ancestor of dogs is closely related to the ancestor of the Japanese wolf. Based on phylogenetic and geographic relationships, the dog lineage has most likely originated in East Asia, where it diverged from a common ancestor with the Japanese wolf. Since East Eurasian dogs possess Japanese wolf ancestry, we estimate an introgression event from the ancestor of the Japanese wolf to the ancestor of the East Eurasian dog that occurred before the dog’s arrival in the Japanese archipelago.
Single cell-transcriptomic analysis informs the lncRNA landscape in metastatic castration resistant prostate cancer
Authors: Saha Debanjan , Dang Ha X. , Zhang Meng , Quigley David A. , Feng Felix Y. , Maher Christopher A. 
Published: February 2024

AbstractMetastatic castration-resistant prostate cancer (mCRPC) is a lethal form of prostate cancer. Although long-noncoding RNAs (lncRNAs) have been implicated in mCRPC, past studies have relied on bulk sequencing methods with low depth and lack of single-cell resolution. Hence, we performed a lncRNA-focused analysis of single-cell RNA-sequencing data (n = 14) from mCRPC biopsies followed by integration with bulk multi-omic datasets. This yielded 389 cell-enriched lncRNAs in prostate cancer cells and the tumor microenvironment (TME). These lncRNAs demonstrated enrichment with regulatory elements and exhibited alterations during prostate cancer progression. Prostate-lncRNAs were correlated with AR mutational status and response to treatment with enzalutamide, while TME-lncRNAs were associated with RB1 deletions and poor prognosis. Finally, lncRNAs identified between prostate adenocarcinomas and neuroendocrine tumors exhibited distinct expression and methylation profiles. Our findings demonstrate the ability of single-cell analysis to refine our understanding of lncRNAs in mCRPC and serve as a resource for future mechanistic studies.
Rockfall from an increasingly unstable mountain slope driven by climate warming
Authors: Stoffel Markus , Trappmann Daniel G. , Coullie Mattias I. , Ballesteros Cánovas Juan A. , Corona Christophe 
Published: February 2024

AbstractRockfall in high-mountain regions is thought to be changing due to accelerating climate warming and permafrost degradation, possibly resulting in enhanced activity and larger volumes involved in individual falls. Yet the systematic lack of long-term observations of rockfall largely hampers an in-depth assessment of how activity may have been altered by a warming climate. Here we compile a continuous time series from 1920 to 2020 of periglacial rockfall activity using growth-ring records from 375 trees damaged by past rockfall at Täschgufer (Swiss Alps). We show that the ongoing warming favours the release of rockfall and that changes in activity correlate significantly with summer air temperatures at interannual and decadal timescales. An initial increase in rockfall occurred in the late 1940s to early 1950s following early twentieth century warming. From the mid-1980s, activity reached new and hitherto unprecedented levels. This long-term record of rockfall activity can help to inform the design of vital mitigation and risk reduction measures in inhabited mountain environments.