bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are disease-specific patient-reported outcomes measures (PROMs) used in cardiogenetics? A systematic review
Authors: van Pottelberghe Saar , Kupper Nina , Scheirlynck Esther , Amin Ahmad S. , Wilde Arthur A. M. , Hofman Nynke , Callus Edward , Biller Ruth , Nekkebroeck Julie , Van Dooren Sonia , Hes Frederik J. , van der Crabben Saskia N. 
Published: December 2023

AbstractPatient-reported outcome measures (PROMs) are used to facilitate patient-centered care (PCC). While studies in patients with cardiac conditions have revealed poorer health-related quality of life (HRQoL) and elevated emotional stress, studies in inherited cardiac conditions (ICC) seem rare. A systematic review evaluated which (specific domains of) PROMs are used in patients with ICC. From three databases (PubMed, PsychINFO, and Web of Science) quantitative studies investigating PROMs in patients with ICC were included. A Cochrane-based assessment tool was used to evaluate quality and potential risk of bias per subdomain. Data from 17 eligible articles were extracted. Among the included studies, risk of bias was predominantly high (35%) or unclear (30%). Most (n = 14) studies used a generic health status measure (SF-36, SF-12); 3 studies used a disease-specific PROM (KCCQ- cardiomyopathy and MLFHQ-heart failure). In addition to HRQoL measures, several studies used affective psychological measures (i.e., HADS, CAQ-18, IES-R, and IPQ). The mental health component of the PROMs showed lower scores overall in patients with ICC compared to population norms. Nine studies using HADS and GAD-7/PHQ-9 showed a prevalence of clinically significant anxiety (17–47%) and depression levels (8.3–28%) that were higher than the population norm (8.3% and 6.3%, respectively). HRQoL in patients with ICC is primarily assessed with generic PROMs. Results further confirmed high psychological morbidity in this population. Generic PROMS measures evaluate overall health status, but lack sensitivity to ICC-specific factors like heredity-related concerns. We propose developing a PROM specific for ICC to optimize PCC.
CA3 hippocampal synaptic plasticity supports ripple physiology during memory consolidation
Authors: El Oussini Hajer , Zhang Chun-Lei , François Urielle , Castelli Cecilia , Lampin-Saint-Amaux Aurélie , Lepleux Marilyn , Molle Pablo , Velez Legeolas , Dejean Cyril , Lanore Frederic , Herry Cyril , Choquet Daniel , Humeau Yann 
Published: December 2023

AbstractThe consolidation of recent memories depends on memory replays, also called ripples, generated within the hippocampus during slow-wave sleep, and whose inactivation leads to memory impairment. For now, the mobilisation, localisation and importance of synaptic plasticity events associated to ripples are largely unknown. To tackle this question, we used cell surface AMPAR immobilisation to block post-synaptic LTP within the hippocampal region of male mice during a spatial memory task, and show that: 1- hippocampal synaptic plasticity is engaged during consolidation, but is dispensable during encoding or retrieval. 2- Plasticity blockade during sleep results in apparent forgetting of the encoded rule. 3- In vivo ripple recordings show a strong effect of AMPAR immobilisation when a rule has been recently encoded. 4- In situ investigation suggests that plasticity at CA3-CA3 recurrent synapses supports ripple generation. We thus propose that post-synaptic AMPAR mobility at CA3 recurrent synapses is necessary for ripple-dependent rule consolidation.
Molecular sensitised probe for amino acid recognition within peptide sequences
Authors: Wu Xu , Borca Bogdana , Sen Suman , Koslowski Sebastian , Abb Sabine , Rosenblatt Daniel Pablo , Gallardo Aurelio , Mendieta-Moreno Jesús I. , Nachtigall Matyas , Jelinek Pavel , Rauschenbach Stephan , Kern Klaus , Schlickum Uta 
Published: December 2023

AbstractThe combination of low-temperature scanning tunnelling microscopy with a mass-selective electro-spray ion-beam deposition established the investigation of large biomolecules at nanometer and sub-nanometer scale. Due to complex architecture and conformational freedom, however, the chemical identification of building blocks of these biopolymers often relies on the presence of markers, extensive simulations, or is not possible at all. Here, we present a molecular probe-sensitisation approach addressing the identification of a specific amino acid within different peptides. A selective intermolecular interaction between the sensitiser attached at the tip-apex and the target amino acid on the surface induces an enhanced tunnelling conductance of one specific spectral feature, which can be mapped in spectroscopic imaging. Density functional theory calculations suggest a mechanism that relies on conformational changes of the sensitiser that are accompanied by local charge redistributions in the tunnelling junction, which, in turn, lower the tunnelling barrier at that specific part of the peptide.
Tracking exceptional points above the lasing threshold
Authors: Ji Kaiwen , Zhong Qi , Ge Li , Beaudoin Gregoire , Sagnes Isabelle , Raineri Fabrice , El-Ganainy Ramy , Yacomotti Alejandro M. 
Published: December 2023

AbstractRecent studies on exceptional points (EPs) in non-Hermitian optical systems have revealed unique traits, including unidirectional invisibility, chiral mode switching and laser self-termination. In systems featuring gain/loss components, EPs are commonly accessed below the lasing threshold, i.e., in the linear regime. In this work, we experimentally demonstrate that EP singularities in coupled semiconductor nanolasers can be accessed above the lasing threshold, where they become branch points of a nonlinear dynamical system. Contrary to the common belief that unavoidable cavity detuning impedes the formation of EPs, here we demonstrate that such detuning is necessary for compensating the carrier-induced frequency shift, hence restoring the EP. Furthermore, we find that the pump imbalance at lasing EPs varies with the total pump power, enabling their continuous tracking. This work uncovers the unstable nature of EPs above laser threshold in coupled semiconductor lasers, offering promising opportunities for the realization of self-pulsing nanolaser devices and frequency combs.
On-chip phonon-magnon reservoir for neuromorphic computing
Authors: Yaremkevich Dmytro D. , Scherbakov Alexey V. , De Clerk Luke , Kukhtaruk Serhii M. , Nadzeyka Achim , Campion Richard , Rushforth Andrew W. , Savel’ev Sergey , Balanov Alexander G. , Bayer Manfred 
Published: December 2023

AbstractReservoir computing is a concept involving mapping signals onto a high-dimensional phase space of a dynamical system called “reservoir” for subsequent recognition by an artificial neural network. We implement this concept in a nanodevice consisting of a sandwich of a semiconductor phonon waveguide and a patterned ferromagnetic layer. A pulsed write-laser encodes input signals into propagating phonon wavepackets, interacting with ferromagnetic magnons. The second laser reads the output signal reflecting a phase-sensitive mix of phonon and magnon modes, whose content is highly sensitive to the write- and read-laser positions. The reservoir efficiently separates the visual shapes drawn by the write-laser beam on the nanodevice surface in an area with a size comparable to a single pixel of a modern digital camera. Our finding suggests the phonon-magnon interaction as a promising hardware basis for realizing on-chip reservoir computing in future neuromorphic architectures.
Maternal antibiotic exposure enhances ILC2 activation in neonates via downregulation of IFN1 signaling
Authors: Xu Haixu , Yi Xianfu , Cui Zhaohai , Li Hui , Zhu Lin , Zhang Lijuan , Chen JiaLe , Fan Xutong , Zhou Pan , Li Mulin Jun , Yu Ying , Liu Qiang , Huang Dandan , Yao Zhi , Zhou Jie 
Published: December 2023

AbstractMicrobiota have an important function in shaping and priming neonatal immunity, although the cellular and molecular mechanisms underlying these effects remain obscure. Here we report that prenatal antibiotic exposure causes significant elevation of group 2 innate lymphoid cells (ILC2s) in neonatal lungs, in both cell numbers and functionality. Downregulation of type 1 interferon signaling in ILC2s due to diminished production of microbiota-derived butyrate represents the underlying mechanism. Mice lacking butyrate receptor GPR41 (Gpr41-/-) or type 1 interferon receptor IFNAR1 (Ifnar1-/-) recapitulate the phenotype of neonatal ILC2s upon maternal antibiotic exposure. Furthermore, prenatal antibiotic exposure induces epigenetic changes in ILC2s and has a long-lasting deteriorative effect on allergic airway inflammation in adult offspring. Prenatal supplementation of butyrate ameliorates airway inflammation in adult mice born to antibiotic-exposed dams. These observations demonstrate an essential role for the microbiota in the control of type 2 innate immunity at the neonatal stage, which suggests a therapeutic window for treating asthma in early life.
C5 methylation confers accessibility, stability and selectivity to picrotoxinin
Authors: Tong Guanghu , Griffin Samantha , Sader Avery , Crowell Anna B. , Beavers Ken , Watson Jerry , Buchan Zachary , Chen Shuming , Shenvi Ryan A. 
Published: December 2023

AbstractMinor changes to complex structures can exert major influences on synthesis strategy and functional properties. Here we explore two parallel series of picrotoxinin (PXN, 1) analogs and identify leads with selectivity between mammalian and insect ion channels. These are the first SAR studies of PXN despite its >100-year history and are made possible by advances in total synthesis. We observe a remarkable stabilizing effect of a C5 methyl, which completely blocks C15 alcoholysis via destabilization of an intermediate twist-boat conformer; suppression of this secondary hydrolysis pathway increases half-life in plasma. C5 methylation also decreases potency against vertebrate ion channels (γ-Aminobutyric acid type A (GABAA) receptors) but maintains or increases antagonism of homologous invertebrate GABA-gated chloride channels (resistance to dieldrin (RDL) receptors). Optimal 5MePXN analogs appear to change the PXN binding pose within GABAARs by disruption of a hydrogen bond network. These discoveries were made possible by the lower synthetic burden of 5MePXN (2) and were illuminated by the parallel analog series, which allowed characterization of the role of the synthetically simplifying C5 methyl in channel selectivity. These are the first SAR studies to identify changes to PXN that increase the GABAA-RDL selectivity index.
Revealing the room temperature superplasticity in bulk recrystallized molybdenum
Authors: Chen Wenshuai , Li Xiyao , Jin Shenbao , Yang Lunwei , Li Yan , He Xueliang , Zhang Wanting , Wu Yinxing , Hui Zhilin , Yang Zhimin , Yang Jian , Xiao Wei , Sha Gang , Wang Jiangwei , Zhou Zenglin 
Published: December 2023

AbstractBody-centered cubic refractory metallic materials exhibit excellent high-temperature strength, but often suffer from brittle intergranular fracture due to the recrystallization-induced enrichment of trace elements at grain boundaries (GBs). Here, we report a fully-recrystallized pure molybdenum (Mo) material with room temperature (RT) superplasticity, fabricated by a facile method of powder metallurgy, Y-type hot rolling and annealing. By engineering the ultralow concentration of O at GBs, the inherent GB brittleness of Mo can be largely eliminated, which, in conjunction with high fractions of soft texture and low angle GBs, enables a significant development of ordered dislocation networks and the effective dislocation transmission across low angle GBs. Synergy of these factors greatly suppress the brittle intergranular fracture of Mo, contributing to an enhanced deformability of 108.7% at RT. These findings should have general implication for fabricating a broad class of refractory metals and alloys toward harsh applications.
A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity
Authors: Ji Linong , Jiang Hongwei , Cheng Zhifeng , Qiu Wei , Liao Lin , Zhang Yawei , Li Xiaoli , Pang Shuguang , Zhang Lihui , Chen Liming , Yang Tao , Li Yan , Qu Shen , Wen Jie , Gu Jieyu , Deng Huan , Wang Yanqi , Li Li , Han-Zhang Han , Ma Qingyang , Qian Lei 
Published: December 2023

AbstractMazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m2) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m2) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg (n = 62), 4.5 mg (n = 63), 6 mg (n = 61) or placebo (n = 62). The mean percentage changes from baseline to week 24 in body weight were −6.7% (SE 0.7) with mazdutide 3 mg, −10.4% (0.7) with 4.5 mg, −11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from −7.7% to −12.3% (all p < 0.0001). All mazdutide doses were well tolerated and the most common adverse events included diarrhoea, nausea and upper respiratory tract infection. In summary, in Chinese overweight adults or adults with obesity, 24-week treatment with mazdutide up to 6 mg was safe and led to robust and clinically meaningful body weight reduction.
Molecular basis for proofreading by the unique exonuclease domain of Family-D DNA polymerases
Authors: Betancurt-Anzola Leonardo , Martínez-Carranza Markel , Delarue Marc , Zatopek Kelly M. , Gardner Andrew F. , Sauguet Ludovic 
Published: December 2023

AbstractReplicative DNA polymerases duplicate entire genomes at high fidelity. This feature is shared among the three domains of life and is facilitated by their dual polymerase and exonuclease activities. Family D replicative DNA polymerases (PolD), found exclusively in Archaea, contain an unusual RNA polymerase-like catalytic core, and a unique Mre11-like proofreading active site. Here, we present cryo-EM structures of PolD trapped in a proofreading mode, revealing an unanticipated correction mechanism that extends the repertoire of protein domains known to be involved in DNA proofreading. Based on our experimental structures, mutants of PolD were designed and their contribution to mismatch bypass and exonuclease kinetics was determined. This study sheds light on the convergent evolution of structurally distinct families of DNA polymerases, and the domain acquisition and exchange mechanism that occurred during the evolution of the replisome in the three domains of life.
Automating General Movements Assessment with quantitative deep learning to facilitate early screening of cerebral palsy
Authors: Gao Qiang , Yao Siqiong , Tian Yuan , Zhang Chuncao , Zhao Tingting , Wu Dan , Yu Guangjun , Lu Hui 
Published: December 2023

AbstractThe Prechtl General Movements Assessment (GMA) is increasingly recognized for its role in evaluating the integrity of the developing nervous system and predicting motor dysfunctions, particularly in conditions such as cerebral palsy (CP). However, the necessity for highly trained professionals has hindered the adoption of GMA as an early screening tool in some countries. In this study, we propose a deep learning-based motor assessment model (MAM) that combines infant videos and basic characteristics, with the aim of automating GMA at the fidgety movements (FMs) stage. MAM demonstrates strong performance, achieving an Area Under the Curve (AUC) of 0.967 during external validation. Importantly, it adheres closely to the principles of GMA and exhibits robust interpretability, as it can accurately identify FMs within videos, showing substantial agreement with expert assessments. Leveraging the predicted FMs frequency, a quantitative GMA method is introduced, which achieves an AUC of 0.956 and enhances the diagnostic accuracy of GMA beginners by 11.0%. The development of MAM holds the potential to significantly streamline early CP screening and revolutionize the field of video-based quantitative medical diagnostics.
Csu pili dependent biofilm formation and virulence of Acinetobacter baumannii
Authors: Ahmad Irfan , Nadeem Aftab , Mushtaq Fizza , Zlatkov Nikola , Shahzad Muhammad , Zavialov Anton V. , Wai Sun Nyunt , Uhlin Bernt Eric 
Published: December 2023

AbstractAcinetobacter baumannii has emerged as one of the most common extensive drug-resistant nosocomial bacterial pathogens. Not only can the bacteria survive in hospital settings for long periods, but they are also able to resist adverse conditions. However, underlying regulatory mechanisms that allow A. baumannii to cope with these conditions and mediate its virulence are poorly understood. Here, we show that bi-stable expression of the Csu pili, along with the production of poly-N-acetyl glucosamine, regulates the formation of Mountain-like biofilm-patches on glass surfaces to protect bacteria from the bactericidal effect of colistin. Csu pilus assembly is found to be an essential component of mature biofilms formed on glass surfaces and of pellicles. By using several microscopic techniques, we show that clinical isolates of A. baumannii carrying abundant Csu pili mediate adherence to epithelial cells. In addition, Csu pili suppressed surface-associated motility but enhanced colonization of bacteria into the lungs, spleen, and liver in a mouse model of systemic infection. The screening of c-di-GMP metabolizing protein mutants of A. baumannii 17978 for the capability to adhere to epithelial cells led us to identify GGDEF/EAL protein AIS_2337, here denoted PdeB, as a major regulator of Csu pili-mediated virulence and biofilm formation. Moreover, PdeB was found to be involved in the type IV pili-regulated robustness of surface-associated motility. Our findings suggest that the Csu pilus is not only a functional component of mature A. baumannii biofilms but also a major virulence factor promoting the initiation of disease progression by mediating bacterial adherence to epithelial cells.
Optimal adjuvant therapy in older (≥70 years of age) women with low-risk early-stage breast cancer
Authors: Chadha M. , White J. , Swain S. M. , Rakovitch E. , Jagsi R. , Whelan T. , Sparano J. A. 
Published: December 2023

AbstractOlder women are under-represented in breast cancer (BC) clinical trials, and treatment guidelines are primarily based on BC studies in younger women. Studies uniformly report an increased incidence of local relapse with omission of breast radiation therapy. Review of the available literature suggests very low rates of distant relapse in women ≥70 years of age. The incremental benefit of endocrine therapy in decreasing rate of distant relapse and improving disease-free survival in older patients with low-risk BC remains unclear. Integration of molecular genomic assays in diagnosis and treatment of estrogen receptor positive BC presents an opportunity for optimizing risk-tailored adjuvant therapies in ways that may permit treatment de-escalation among older women with early-stage BC. The prevailing knowledge gap and lack of risk-specific adjuvant therapy guidelines suggests a compelling need for prospective trials to inform selection of optimal adjuvant therapy, including omission of adjuvant endocrine therapy in older women with low risk BC.
Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s disease
Authors: Chen Szu-Ju , Wu Yu-Jun , Chen Chieh-Chang , Wu Yu-Wei , Liou Jyh-Ming , Wu Ming-Shiang , Kuo Ching-Hua , Lin Chin-Hsien 
Published: December 2023

AbstractGut microbial proteolytic metabolism has been reportedly altered in Parkinson’s disease (PD). However, the circulating aromatic amino acids (AAA) described in PD are inconsistent. Here we aimed to investigate plasma AAA profiles in a large cohort of PD patients, and examine their correlations with clinical severity and gut microbiota changes. We enrolled 500 participants including 250 PD patients and 250 neurologically normal controls. Plasma metabolites were measured using liquid chromatography mass spectrometry. Faecal samples were newly collected from 154 PD patients for microbiota shotgun metagenomic sequencing combined with data derived from 96 PD patients reported before. Data were collected regarding diet, medications, and motor and non-motor symptoms of PD. Compared to controls, PD patients had higher plasma AAA levels, including phenylacetylglutamine (PAGln), p-cresol sulfate (Pcs), p-cresol glucuronide (Pcg), and indoxyl sulfate (IS). Multivariable linear regression analyses, with adjustment for age, sex, and medications, revealed that the plasma levels of PAGln (coefficient 4.49, 95% CI 0.40–8.58, P = 0.032) and Pcg (coefficient 1.79, 95% CI 0.07–3.52, P = 0.042) positively correlated with motor symptom severity but not cognitive function. After correcting for abovementioned potential confounders, these AAA metabolites were also associated with the occurrence of constipation in PD patients (all P < 0.05). Furthermore, plasma levels of AAA metabolites were correlated with the abundance of specific gut microbiota species, including Bacteroides sp. CF01-10NS, Bacteroides vulgatus, and Clostridium sp. AF50-3. In conclusion, elevated plasma AAA metabolite levels correlated with disease characteristics in PD, suggesting that upregulated proteolytic metabolism may contribute to the pathophysiology of PD.
A Pvs25 mRNA vaccine induces complete and durable transmission-blocking immunity to Plasmodium vivax
Authors: Kunkeaw Nawapol , Nguitragool Wang , Takashima Eizo , Kangwanrangsan Niwat , Muramatsu Hiromi , Tachibana Mayumi , Ishino Tomoko , Lin Paulo J. C. , Tam Ying K. , Pichyangkul Sathit , Tsuboi Takafumi , Pardi Norbert , Sattabongkot Jetsumon 
Published: December 2023

AbstractPlasmodium vivax (P. vivax) is the major malaria parasite outside of Africa and no vaccine is available against it. A vaccine that interrupts parasite transmission (transmission-blocking vaccine, TBV) is considered highly desirable to reduce the spread of P. vivax and to accelerate its elimination. However, the development of a TBV against this pathogen has been hampered by the inability to culture the parasite as well as the low immunogenicity of the vaccines developed to date. Pvs25 is the most advanced TBV antigen candidate for P. vivax. However, in previous phase I clinical trials, TBV vaccines based on Pvs25 yielded low antibody responses or had unacceptable safety profiles. As the nucleoside-modified mRNA–lipid nanoparticle (mRNA–LNP) vaccine platform proved to be safe and effective in humans, we generated and tested mRNA–LNP vaccines encoding several versions of Pvs25 in mice. We found that in a prime-boost vaccination schedule, all Pvs25 mRNA–LNP vaccines elicited robust antigen-specific antibody responses. Furthermore, when compared with a Pvs25 recombinant protein vaccine formulated with Montanide ISA-51 adjuvant, the full-length Pvs25 mRNA–LNP vaccine induced a stronger and longer-lasting functional immunity. Seven months after the second vaccination, vaccine-induced antibodies retained the ability to fully block P. vivax transmission in direct membrane feeding assays, whereas the blocking activity induced by the protein/ISA-51 vaccine dropped significantly. Taken together, we report on mRNA vaccines targeting P. vivax and demonstrate that Pvs25 mRNA–LNP outperformed an adjuvanted Pvs25 protein vaccine suggesting that it is a promising candidate for further testing in non-human primates.