bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Bleeding Episodes With Efanesoctocog Alfa in Previously Treated Patients With Severe Hemophilia A in the Phase 3 XTEND‐1 Study
Authors: Weyand Angela C. , Meunier Sandrine , Suzuki Nobuaki , Bystrická Linda , Neill Graham , Abad‐Franch Lydia , Willemze Annemieke , Tosetto Alberto 
Published: February 2025

ABSTRACTDespite therapeutic advances, people with hemophilia experience bleeds. These may be life‐threatening, result in permanent joint damage, chronic pain, difficulties with mobility/daily activities, and impact quality of life. In the XTEND‐1 study (NCT04161495), once‐weekly efanesoctocog alfa (50 IU/kg) prophylaxis provided highly effective bleed prevention and high‐sustained factor levels for most of the week and was well‐tolerated. We report post hoc analysis of bleeding episodes and their treatment in previously treated patients (≥ 12 years old). Participants received 50 IU/kg efanesoctocog alfa either as once‐weekly prophylaxis (Arm A) or on‐demand followed by once‐weekly prophylaxis (Arm B) in XTEND‐1. Endpoints included treatment of bleeding episodes and response to treatment. During XTEND‐1, 422 bleeding episodes were reported among 159 participants; 362 were treated. Most treated bleeding episodes (74%; n = 268) occurred during the Arm B on‐demand period, of which 197 (74%) were spontaneous. Seventy‐five participants had no bleeding episodes in Arm A; all in Arm B had ≥ 1 bleeding episode while on‐demand. Most participants (n = 107, 81%) had zero treated spontaneous bleeding episodes and rates of treated bleeding episodes in Arm A (prophylaxis) were low (median [interquartile range] overall ABR: 0.00 [0.00–1.04]). A single injection was sufficient to resolve 97% (350/362) of treated bleeding episodes, no bleeding episodes required > 3 injections, and responses to 95% of evaluable injections were rated excellent/good. Median total dose was 50.9 IU/kg per bleeding episode. Results of this analysis further demonstrated that once‐weekly efanesoctocog alfa provides highly effective bleed protection and treatment of bleeding episodes in participants with severe hemophilia A.Trial Registration: NCT04161495
Mitochondrial DNA or Genomic DNA Variant(s): Utility of Exhaustive Sequencing in Leigh Syndrome
Authors: Gaignard Pauline , Becker Pierre‐Hadrien , Dessein Anne‐Frederique , Lebigot Elise , Slama Abdelhamid , Mention Karine , Ghoumid Jamal 
Published: February 2025

ABSTRACTPathogenic variants in the nuclear gene NDUFAF8 are a rare cause of mitochondrial complex I deficiency with only three cases described to date. We report here a new case of NDUFAF8 deficiency confirming the phenotype of NDUFAF8‐induced complex I biochemical defect, Leigh syndrome and premature death. As a mitochondrial DNA variant in a gene encoding a complex I subunit was also identified in this patient, we discuss the molecular heterogeneity of Leigh syndrome and the need to explore the mitochondrial and nuclear genome to ensure a reliable diagnosis.
Burosumab Treatment in a Girl With Cutaneous Skeletal Hypophosphatemia Syndrome: 2‐Year Follow‐Up
Authors: del Pino Mariana , Viterbo Gisela , Valentini María Agustina , Salvatierra Roberto , Belleri Florencia , La Forgia Pablo , Abbate Silvina , Chinton Josefina , Lazzati Juan Manuel , Maderna Osmar , Cervini Andrea Bettina , Fano Virginia 
Published: February 2025

ABSTRACTCutaneous skeletal hypophosphatemia syndrome (CSHS) is a mosaic RASopathy caused by postzygotic, activating pathogenic variants in HRAS, NRAS, or KRAS. It is characterized by congenital epidermal, melanocytic, or sebaceous nevi, elevated FGF23 levels that cause renal phosphate wasting and rickets, and focal bone lesions. We report a 13‐year‐old girl with CSHS from Argentina. At 15 days old, she was presented with an extensive epidermal nevus (pigmento‐keratotic phacomatosis). She developed valgus deformity of the right lower limb at the age of 2 years. X‐rays showed extended skeletal involvement, poorly defined corticomedullary junctions, and lytic lesions located in the affected skin area. All the metaphyses showed rickets. Lab tests showed persistently low phosphatemia 2.1 mg/dL (NV: 3.8–6.2), with hyperphosphaturia and elevated alkaline phosphatase (ALP) 661 IU/L (NV < 300). The patient received treatment with oral phosphate salts and calcitriol, resulting in a favorable metabolic control until she was 6 years old. At that time, she developed central precocious puberty and presented severe clinical compromise, with asthenia, chronic pain, weakness, reduced functional capacity, and loss of independent walking. Sanger sequencing test of the main hotspots of HRAS, NRAS, and KRAS was performed. A previously reported somatic variant, c.37G>C (p.Gly13Arg) in HRAS, was detected in the DNA isolated from the affected skin tissue. Due to clinical, radiological, and biochemical worsening, with a decrease in phosphatemia (1.4 mg/dL) and an increase in ALP (2117 IU/L), the patient was initiated on burosumab at the age of 11 years. After 3 months, she reported improvement in her physical abilities. The x‐ray findings showed progressive healing of rickets in the long bones: ulna, radius, femur, tibia, and fibula. Phosphatemia and tubular reabsorption of phosphate increased gradually with the up‐titration of burosumab dose to 2 mg/kg. However, the patient developed hypercalciuria 6–12 mg/kg/day (NV ≤ 4), with calcemia 9.6–10.8 mg/dL (NV 8.9–10.5) and normal parathormone (PTH) 26–53 pg/mL (NV: 12–95), and the dose of burosumab had to be reduced to 1.6 mg/kg every 2 weeks. We report a girl with CSHS confirmed by somatic HRAS pathogenic variant. Conventional treatment was replaced by burosumab, with healing of bone rickets, and a clear improvement in mineral homeostasis and physical functioning after 2 years of treatment.
A Macaque Model for the Effects of Hybridization on Body Size
Authors: Buck Laura T. , Katz David C. , Ackermann Rebecca Rogers , Hlusko Leslea J. , Kanthaswamy Sree , Weaver Timothy D. 
Published: February 2025

ABSTRACTObjectivesGenomics research has uncovered recurrent hybridization between hominin species, yet its morphological impact remains understudied. Non‐human primate research has suggested a morphological signature of hybrid ancestry, which could be used to identify hybrids in the hominin fossil record. This pattern may include extreme size, heightened variation, and markers of developmental instability, but factors affecting these characteristics are poorly understood. Studies of non‐mammalian taxa suggest that extreme morphology is more likely in early‐generation hybrids and with a greater parental distance. To understand hybridization in hominins, therefore, we must use appropriate proxy taxa.Materials and MethodsHere, we use Chinese × Indian Macaca mulatta hybrids with a comparable divergence time in generations to Homo sapiens/Neanderthals and wide variation in admixture. Measuring limb lengths, body length, and weight, we investigate the relationship between admixture and size/variation.ResultsCompared to previous work with more phylogenetically distant primate taxa and a focus on early generation hybrids, we found no evidence of a relationship between admixture and extreme large size, nor with increased size variation. Hybrids in our sample are relatively small but within the range of variation of the smaller parental taxon.ConclusionsOur results suggest that hybridization between closely related taxa, such as Neanderthals and H. sapiens, may lead to more subtle morphological patterns than previously anticipated. It will be necessary, however, to better understand the factors governing primate hybrid morphology before we can produce robust inferences on how hybridization has affected hominin evolution.
The Ontogeny of the Human Calcaneus: Insights From Morphological and Trabecular Changes During Postnatal Growth
Authors: Figus Carla , Carlson Kristian J. , Bortolini Eugenio , Saers Jaap , Seghi Francesca , Sorrentino Rita , Bernardini Federico , Vazzana Antonino , Erjavec Igor , Novak Mario , Tuniz Claudio , Belcastro Maria Giovanna , Stock Jay , Ryan Timothy M. , Benazzi Stefano 
Published: February 2025

ABSTRACTObjectivesTo investigate the developmental changes in the human calcaneal internal and external morphology linked to the acquisition of mature bipedal locomotion.MethodsSeventy seven micro‐CT scans of modern juvenile calcanei (from perinates to 15 years old) are employed. The chronological period spans from the Middle/Late Neolithic (4800–4500 BCE) to the 20th century. Through a comprehensive approach that comprises geometric morphometric methods and whole‐bone trabecular analysis, the calcaneal growing morphology has been explored.ResultsMorphological changes reflect the development of bipedal locomotion, showing its potential when tracking the major locomotor milestones. The calcaneal shape is immature and almost featureless during the first year of life. The internal architecture is dense and isotropic with numerous thin trabeculae closely packed together. The internal architecture changes to better adapt to variations in load stimulated by a more mature gait by increasing bone mass and alignment, with fewer and thicker struts. The external morphology shows its plasticity by increasing the surface area where greater strain is expected and changing the orientation of the articular facets.ConclusionsAnalysis of morphological changes in the growing calcaneus highlights the importance of an integrative methodology when exploring developmental bone plasticity. The changes in calcaneal internal and external morphologies reflect the different loading patterns experienced during growth, gradually shifting from a more generalized morphology to a more adult‐like one, reflecting major locomotor achievement. Our research shows that although initially genetically driven, calcaneal plasticity may display mechanical influences and provide precious information on tracking the main locomotor milestones.
Effects of Qingyangshen glycosides on neuroplasticity in a mouse model of social defeat
Authors: Wang Jingru , Chen Weishi , Zhu Qiang , Liu Yao , Kang Zheng , Liu Dingding , Zeng Guirong 
Published: February 2025

AbstractBackgroundQingyangshen (Cynanchum otophyllum C.K. Schneid) is a folk drug for treating depression and other mental disorders induced by social defeat stress. Neuroplasticity in the hippocampus is essential for the modulation of cognition and emotion, and its impairment may contribute to the development and progression of depression. Our previous studies have found that Qingyangshen glycosides (QYS) can improve depression‐like behavior in social failure mouse models, mainly through PGC‐1α/FNDC5/BDNF signaling pathways activation, but its effects and mechanisms on hippocampal neuroplasticity remain unknown.MethodsChronic social defeat stress (CSDS) was used to induce social defeat in mice. Morphological changes in the hippocampus were observed by H&E staining and Golgi staining. Immunofluorescence double staining was used to detect the expression of synaptophysin (SYN) and postsynaptic density protein‐95 (PSD‐95), while western blot was employed to evaluate PSD‐95, SYN, and doublecortin (DCX) proteins. The pathological processing of social defeat and the therapeutic effects of QYS on it was confirmed through behavioral assessment associated with morphologic observation.ResultsDuring the whole study, the sucrose preference indices and OFT activity time of CSDS mice were significantly decreased (p ≤ 0.05), and the tail suspension immobility time was significantly increased (p ≤ 0.05), suggesting that the mice had significant depressive symptoms. Treatment with QYS (25, 50, and 100 mg/kg) significantly alleviated depressive symptoms in CSDS mice, which was demonstrated by significantly (p ≤ 0.05 or p ≤ 0.01) reducing the duration of tail‐hanging immobility and increasing the tendency of sucrose preference indices and OFT activity time. QYS treatment also significantly increased the expression of DCX, PSD‐95, and SYN proteins, which play a crucial role in depression.ConclusionsQYS alleviated these symptoms by enhancing hippocampal neuroplasticity through upregulating the expression of synapse‐associated proteins (SAPs). The therapeutic mechanism of QYS may involve modulating the neuroplasticity of hippocampus neurons by altering the expression of SAPs.
Binding‐site purification of actives (B‐SPA) enables efficient large‐scale progression of fragment hits by combining multi‐step array synthesis with HT crystallography
Authors: Grosjean Harold , Aimon Anthony , Hassell-Hart Storm , Thompson Warren , Koekemoer Lizbé , Bennett James , Bradley Anthony , Anderson Cameron , Wild Conor , Bradshaw William J , FitzGerald Edward A. , Krojer Tobias , Fedorov Oleg , Biggin Philip C. , Spencer John , von Delft Frank 
Published: February 2025

Fragment approaches are long‐established in target‐based ligand discovery yet their full transformative potential lies dormant, because progressing hits to potency remains underserved by methodological work. The only credible progression paradigm is multiple cycles of costly conventional design‐make‐test‐analyse (DMTA) medicinal chemistry, necessitating picking winners early and discarding others. It is effective to cheaply parallelize large numbers of non‐uniform multi‐step reactions, because, even without compound purification, a high‐quality readout of binding is available, viz. crystallography. This can detect low‐level binding of slightly active compounds, which the targeted binding site extracts directly from crude reaction mixtures (CRMs). In this proof‐of‐concept study, we expand a fragment hit from a crystal‐based screen of the bromodomain PHIP2, using array synthesis on low‐cost robotics to implement 6 independent multi‐step reaction routes of up to 5 steps, attempting the synthesis of 1876 diverse expansions, designs entirely driven by synthetic tractability. The expected product was present in 1108 (59%) CRMs, detected by automated mass spectrometry, 22 individual products were resolved in crystal structures of CRMs added to crystals, providing an initial SAR map, pose stability in 19 and instability in 3 products and resolved stereochemical preference. One compound showed biochemical potency (IC50=34 μM) and affinity (Kd=50 μM) after resynthesis.
Oxygen‐Coordinated Cr Single‐Atom Catalyst for Oxygen Reduction Reaction in Proton Exchange Membrane Fuel Cells
Authors: Luo Junming , Zhang Yating , Lu Zhe , Liu Chao , Xu Yueshan , Chen Hui , Wang Qi , Wu Daoxiong , Dang Dai , Deng Yijie , Rao Peng , Deng Peilin , Li Jing , Miao Zhengpei , Tian Xinlong 
Published: February 2025

AbstractCarbon‐supported metal single‐atom catalysts (M‐SACs) are promising oxygen reduction reaction (ORR) catalysts. Their ORR activity and selectivity are significantly affected by the heteroatoms that coordinate the central metal atoms. Previous reports found that oxygen‐coordinated M‐SACs promoted a 2e− ORR rather than the 4e− ORR that is more desirable for fuel cells. Herein, we report for the first time that oxygen‐coordinated M‐SACs are capable of promoting the 4e− ORR in acid media. We prepared a Cr(acac)‐NC catalyst with the central Cr atom coordinated by two O atoms. The Cr(acac)‐NC catalyst not only exhibits excellent ORR activity and stability in acid media, but also delivers high proton exchange membrane fuel cell (PEMFC) performance comparable to N‐coordinated M‐SACs. Density functional theory (DFT) calculations reveal that Cr−O2 moieties located on the zigzag edge of the carbon support are the ORR‐active sites.
A Mechanochromic Rotaxane that Releases Azetidine‐Trityl‐Maleimide, a Versatile Fluorescent Probe
Authors: Wu Mengjiao , De Bo Guillaume 
Published: February 2025

Force sensing at the molecular level has enabled the study of materials failure and it offers great promises for the investigation of mechanobiological processes. Traditional force probes rely on the reversible or irreversible activation of mechanochromic precursors to assess transient or permanent changes in the polymer networks. A promising approach involves force‐controlled release of sensing molecules, as the accumulation of chromic molecules at specific sites would enable the recording of deformation histories. However, many fluorescent probes are limited by environmental sensitivity, specific release conditions, or low release efficiency. Maleimide‐based dyes, especially amino maleimides, offer a robust alternative due to their small size, structural versatility, and tuneable fluorescence properties. Here, we present a mechanochromic rotaxane device that releases an azetidine‐trityl‐maleimide (ATM) fluorescent probe via a retro‐[4+2] cycloaddition reaction. ATM, is a rigidochromic, chemically stable, and environmentally insensitive probe, generated exclusively through rotaxane actuation, underscoring the unique mechanochemical properties of rotaxanes. This device holds potential for applications in material science and biology, such as the investigation of polymer networks and active tissues.
Antibacterial, Stretchable, and Self‐Adhesive Laponite‐TA Based Conductive Hydrogel Sensor for Human Motion Detection
Authors: Xu Hongyu , Zhang Jingjing , Lv Xue 
Published: February 2025

ABSTRACTDue to their biocompatibility and tissue‐like properties, hydrogels have garnered considerable interest in bioelectronics field. Nevertheless, their practical implementation is limited by factors such as inadequate mechanical strength, weak interface adhesion, and the lack of antimicrobial properties. To address these challenges, a novel conductive hydrogel was synthesized through free radical polymerization, incorporating laponite (LA), tannic acid (TA), polyacrylic acid (PAA), and polyacrylamide (pAAm). An innovative approach was employed to enhance LA's dispersion through ionic liquid (IL) in water through electrostatic interactions. The integration of TA, PAA, and PAAm with LA sheets via multiple hydrogen bonds resulted in excellent mechanical properties. The resulting P(AAm‐AA)/IL‐LA/TA hydrogel exhibits impressive characteristics, including a fracture stress of 0.44 MPa, a strain of 1800%. Notably, the hydrogel's TA component exhibits strong antibacterial activity against Staphylococcus aureus and Escherichia coli. This advanced hydrogel sensor effectively monitors human movements, displaying a gauge factor of 12.7. Furthermore, its versatile and conductive nature facilitates adhesion to a wide range of substrates, making it a promising candidate for applications in human activity monitoring, electronic devices, and medical health surveillance.
Rheological and Thermal Behavior of Xanthan Gum Nanofluids Based on Hexagonal Boron Nitride Under High‐Pressure and High‐Temperature Conditions
Authors: Soares Yago Chamoun F. , Fernandes Nathália Maria M. , Berghe Lara Schimith , Costa Lidiane Cristina , de Credo Fernanda Alice , Ribeiro Hélio , Naccache Mônica Feijó , Andrade Ricardo Jorge E. 
Published: February 2025

ABSTRACTXanthan gum (XG) is a biopolymer widely used in different industries, such as food, cosmetics, oil, among others, which requires modifications in its properties. The present study aims to study the thermal and rheological properties of XG nanofluids based on oxidized hexagonal boron nitride (hBN‐oxi) under high temperature and pressure conditions. The hBN‐oxi was obtained through liquid exfoliation and then dispersed in the XG at different concentrations. The thermal conductivity of the nanofluids was investigated at different temperatures, and the addition of 6.0 wt% of hBN‐oxi in the polymeric system increased thermal conductivity up to 12% at 70°C. The rheological behavior was obtained through steady‐state and oscillatory flow measurements to evaluate the effect of hBN‐oxi concentration under different temperatures and pressures. At higher concentrations, these nanostructures induced a yield stress in the fluid reaching a value of 12.8 Pa.s. Under high shear rates, the viscosity of the nanofluid decreased by only 16% at 80°C, indicating effective mitigation of temperature effect on viscosity. The pressure influence was also suppressed with the addition of these modified nanoparticles. This study highlights that well‐designed formulations can significantly improve performance under extreme conditions.
Hydrophilic Photothermal Polydopamine/Polyurethane Foam for Efficient Solar‐Driven Water Evaporation
Authors: Zong Jiale , Wang Daxin , Yang Heng , Lu Bo , Huang Dan , Wang Xiangdong , Li Shuhong , Zang Xiaoling 
Published: February 2025

ABSTRACTSolar‐driven seawater desalination is considered an promising technology coping with water scarcity due to the sustainability of solar energy and its substitutability for fossil fuels. Nevertheless, the complex fabrication, high cost and low efficiency of solar‐driven evaporator limit its large‐scale application. Herein, the PDA/PU composite foam with porous three‐dimensional structure is developed to achieve low cost and high‐efficient solar‐driven water evaporation. Thereinto, hydrophilic PDA contributes to the real solar energy absorption, and provides an extremely high photothermal conversion efficiency. Meanwhile, the porous PU foam provides excellent capillary effect for sufficient water supply. The as‐fabricated PDA/PU foam can reach 77.8°C and 48.1°C under the laser and simulated solar irradiation (1 kW/m2), respectively. Further, the specific water evaporation rate is 1.93 kg/m2 h−1 under simulated solar irradiation. Therefore, the PDA/PU foam exhibits effective solar‐driven water evaporation rate which provides inspiration for the future development of high‐performance seawater desalination devices.
Structural, Optical, and Electrical Characteristics of Synthesized Novel and Flexible PCCCe Polymer Nanocomposites for EMI Shielding Applications
Authors: Sharma Neha , Aakansha  , Siddiqui M. G. , Dalela Saurabh , Kumar Shalendra , Hashmi S. Z. , Ahmad M. Ayaz , Quraishi A. M. , Alvi P. A. 
Published: February 2025

ABSTRACTThis article reports, for the first time, the electromagnetic interference (EMI) shielding performance of a flexible PCCCe polymer nanocomposite, which was manufactured using a mini twin‐screw extrusion process. In the manufacturing of PCCCe polymer nanocomposites, the binary polymer blends PVA (polyvinyl alcohol) and CS (chitosan) have been used as a host matrix, while CeO2 nanoparticles (synthesized via the sol–gel method) and CB (carbon black) have been used in the form of nanofillers. The incorporation of nanofillers in the matrix was verified through XRD analysis, causing the expansion in the crystallite size ranging from 18 to 28 nm along with the existing micro‐strain. The increased amount of nanofillers has shown an increase in the absorbance with blue shift and enhancement in the refractive index (from 2.09 to 2.16), with reduction in the optical band gap (from 4.79 to 4.03 eV) and lowering of the Urbach energy (from 1.36 to 0.33 eV). Blue emission has been observed and confirmed through the CIE plot studied in PL spectra. Thus, it demonstrates a unique combination of increased refractive index, reduced optical band gap, and lowered Urbach energy, along with blue‐shifted absorbance and blue emission confirmed via PL spectra, offering innovative control over optical properties for advanced multifunctional applications. Moreover, Raman spectroscopy reveals the presence of D, G, and D+G band peaks at 1361, 1560, and 2910 cm−1 due to the disordered crystal structure of carbon atoms. In addition to the structural and optical characterizations, the composites were also studied through the dielectric and shielding effect analysis in the X‐band frequency range that lies in the 5G spectrum. High dielectric constant and dielectric loss are claimed along with a high total shielding effectiveness parameter in the synthesized polymer nanocomposites. The flexible PCCCe polymer nanocomposites exhibit remarkable total shielding effectiveness elevated to 90 dB at 12 GHz, surpassing the performance of the other samples investigated in the study. This breakthrough in the PCCCe nanocomposite design highlights its potential as a next‐generation material for superior electromagnetic wave absorption and advanced EMI shielding applications.