bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiling Pro‐Inflammatory Proteases as Biomolecular Signatures of Material‐Induced Subcutaneous Host Response in Immuno‐Competent Mice
Authors: Tran Nam M.P. , Truong Anh T.H. , Nguyen Dang T. , Dang Tram T.
Published: December 2024

Proteases are important modulators of inflammation, but they remain understudied in material‐induced immune response, which is critical to clinical success of biomedical implants. Herein, molecular expression and proteolytic activity of three distinct proteases, namely neutrophil elastase, matrix metalloproteinases, cysteine cathepsins (cathepsin‐K and cathepsin‐B) are comprehensively profiled, in the subcutaneous host response of immuno‐competent mice against different biomaterial implants. Quantitative non‐invasive monitoring with activatable fluorescent probes reveals that different microparticulate materials induce distinct levels of protease activity with degradable poly(lactic‐co‐glycolic) acid inducing the strongest signal compared to nondegradable materials such as polystyrene and silica oxide. Furthermore, protein expression of selected proteases, attributable to both their inactive and active forms, notably deviates from their activities associated only with their active forms. Protease activity exhibits positive correlations with protein expression of pro‐inflammatory cytokines tumor necrosis factor α and interleukin 6 but negative correlation with pro‐fibrotic cytokine transforming growth factor β1. This study also demonstrates the predictive utility of protease activity as a non‐invasive, pro‐inflammatory parameter for evaluation of the anti‐inflammatory effects of model bioactive compounds on material‐induced host response. Overall, the findings provide new insights into protease presence in material‐induced immune responses, facilitating future biomaterial assessment to evoke appropriate host responses for implant applications.
Immune Dysregulation in a Child With SOD1‐Related Neurological Disease
Authors: Boutin Rozlyn Claire Thomas , Shobeirian Farzaneh , Adam Shelin , Lehman Anna , Salvarinova Ramona , Friedman Jan M
Published: December 2024

Spastic tetraplegia and axial hypotonia (STAHP) associated with biallelic SOD1 deficiency is a recently described neurological disorder affecting children. Five studies have described a total of nine cases thus far, all characterized by the onset of progressive spastic tetraplegia beginning before 2 years of age. All but two of these cases are associated with homozygosity for the same genetic variant (NM_000454.4:c.335dupG; NP_000445.1:p.Cys112Trpfs*11) that leads to a non‐functional enzyme product. More recently, a homozygous 3‐base pair in‐frame deletion (NM_000454.5: c.357_357+2delGGT) and a truncating frameshift variant (NM_000454.5: c.52_56del5ins154) in SOD1 have been described in similarly affected patients lacking SOD1 activity. Here we expand on the neurological and extra‐neuronal phenotypes of STAHP in a patient with a novel homozygous SOD1 variant predicted to result in disrupted calcium‐ and zinc‐binding activity of the encoded enzyme. We describe a 19‐year‐old male born to consanguineous parents who is homozygous for an NM_000454.4:c.369_371del SOD1 variant. The patient had progressive neuromuscular degeneration with onset before 1 year of age, consistent with a diagnosis of STAHP. Brain MRI at 7 years of age showed cerebellar atrophy, as has previously been described in this condition, as well as small optic nerves and a hypoplastic optic chiasm, which have not been reported previously. Our patient also exhibited clinical features of immune dysregulation with treatment‐refractory inflammatory bowel disease, asthma, recurrent infections, and dermatitis. Overall, the early‐onset progressive neurological disorder in our patient, found in association with homozygosity for an SOD1 variant that is predicted to result in impaired function of the transcribed protein, is consistent with a diagnosis of STAHP. Our patient also demonstrates optic atrophy and disrupted immune homeostasis, which have not been previously described as part of this condition. Taken together with previous case studies in children carrying loss‐of‐function variants of SOD1, this case highlights a possible role for antioxidant therapy in slowing disease progression in patients lacking SOD1 activity. These cases also draw attention to the need for careful consideration of possible harmful neuronal and extra‐neuronal complications of proposed SOD1 knockdown therapies against ALS.
Telehealth Is Effective in the Evaluation of Individuals With Undiagnosed Rare Disorders: An Undiagnosed Diseases Network Study
Authors: Tan Queenie K.‐G. , McConkie‐Rosell Allyn , Mahoney Rachel , Spillmann Rebecca C. , Schoch Kelly , Chanprasert Sirisak , Acosta Maria T. , Toro Camilo , Rosenfeld Jill A. , Orengo James P. , Scott Daryl A. , Granadillo Jorge L. , Sisco Kathleen , Wegner Daniel J. , Tekin Mustafa , Bivona Stephanie , Peart LéShon , Rodan Lance , Bonner Devon , Wheeler Matthew T. , Bernstein Jonathan A. , Ruzhnikov Maura ,   Undiagnosed Diseases Network, Adams David R. , Hisama Fuki M. , Shashi Vandana
Published: December 2024

Patients with undiagnosed and/or rare disorders frequently manifest dysmorphic and neurological features. There is a lack of information on the effectiveness of telehealth in the evaluation of these disorders. We thus compared an unassisted virtual physical examination (PE) with an in‐person PE in undiagnosed individuals and also assessed participant telehealth satisfaction. Twenty‐six individuals enrolled in the Undiagnosed Diseases Network study underwent an in‐home synchronous virtual PE, and a subsequent in‐person PE, by the same clinician. The participants completed surveys on telehealth usability and provider empathy. On PE, general appearance and craniofacial features showed near perfect agreement (κ = 0.81–1.00) between the telehealth and in‐person evaluations. Specific components of the neurological examination demonstrated substantial agreement (speech, gait, coordination; κ > 0.61), whereas others had moderate agreement (muscle tone, strength; κ = 0.41–0.60), and a few had none to slight agreement (skin; κ < 0.20). Some systems could not be examined in the virtual PE. Importantly, features relevant to diagnosis or management were missed on the virtual PE in only 2/26 individuals. The participants were satisfied with the quality of the telehealth interaction, as well as empathy demonstrated by providers in the virtual interface. Telehealth is effective for PEs in undiagnosed diseases and is acceptable to affected individuals.
Bound States in the Continuum in Photonics and Metasurfaces: From Phenomena to Applications
Authors: Zhou Wenjie , Sun Guangcheng , Yuan Yueyi , Wang Yuxiang , Burokur Shah Nawaz , Wang Yue , Zhang Kuang
Published: December 2024

Bound states in the continuum (BICs) refer to nonradiative eigenmodes located within the radiation continuum, possessing infinitely high Q‐factor and enabling exceptionally strong light–matter interactions. BICs have found applications across various domains in photonics and metasurfaces, including nonlinear optical enhancement, vortex beam generation, sensor technology, microlasers, and other related areas. This work starts by classifying the phenomena of BICs and introducing the theoretical formation mechanisms and topological characteristics. Then, the current and advanced applications based on BIC‐devices are highlighted. Lastly, this work discusses the current challenges in studies related to BICs, such as structural precision, material selection, and measurement difficulties, and prospect the possible potentials in future developments. This review provides a theoretical background and application prospects of BIC‐engineered devices in optical and photonics fields, laying a solid foundation for future industrial applications.
A Molecular Engineering Approach to Conformationally Regulated Conductance Dualism in a Molecular Junction
Authors: Nau Moritz , Bro‐Jørgensen William , Linseis Michael , Bodensteiner Michael , Winter Rainer F. , Solomon Gemma C.
Published: December 2024

One key aspect for the development of functional molecular electronic devices is the ability to precisely tune and reversibly switch the conductance of individual molecules in electrode‐molecule‐electrode junctions in response to external stimuli. In this work, we present a new approach to access molecular switches by deliberately controlling the flexibility in the molecular backbone. We here describe two new conductance switches based on bis(triarylamines) that rely on the reversible toggling between two conformers, each associated with vastly different conductances. By molecular design, we were able to realize an on/off ratio Ghigh/Glow of ~103, which is one of the largest values reported to date. Flicker noise analysis and molecular transport calculations indicate that on/off switching relies on a change of the conduction pathway and vast differences in molecule‐electrode coupling. We thereby provide a new scaffold for further development of molecular conductance switches that are both efficient and easily refined.
A Conductive Cu‐Based Metal–Organic Framework Ribbon with High‐Density Redox‐Active Centers as Cathode for Stable High‐Capacity Lithium‐Ion Batteries
Authors: Yang Menghua , Wang Ying , Huang Yan‐Fang , Xiao Ji‐Miao , Zhu Guo‐Yu , Fang Ying , Zhou Xian‐Chao , Long Jian‐Hua , Xie Mo , Bin De‐Shan , Li Dan
Published: December 2024

Conductive Cu‐based metal–organic framework (Cu‐MOF) materials hold significant potential as cathodes for lithium‐ion batteries (LIBs) due to their flexible structural design, high electronic conductivity, and independence from costly resources. However, their practical application is often limited by their capacity and cyclability. In this study, we report a one‐dimensional Cu‐MOF (DDA−Cu, DDA=1, 5‐Diamino‐4, 8‐dihydroxy‐9, 10‐anthraceneedione) featuring extended π‐d conjugated coordination ribbon and high‐density redox‐active centers, making it a stable, high‐capacity cathode for LIBs. The π‐d conjugated Cu−O3N motifs embedded within the ribbon not only serve as redox‐active centers for enhanced lithium‐ion storage capacity but also contribute to structural robustness, enabling resistance against electrode solubility in organic electrolytes, thus ensuring superior cyclability. Furthermore, these π‐d conjugated Cu−O3N units promote efficient charge transfer, leading to high electronic conductivity at room temperature. These advantageous properties allow the Cu‐MOF cathode to deliver a remarkable capacity (353 mAh g−1 at 0.05 A g−1) and exceptional cyclability, achieving capacity retention of 78 % after 1000 cycles, surpassing state‐of‐the‐art MOF electrodes. Additionally, this DDA−Cu demonstrates considerable wettability with the electrolyte, achieving outstanding performance even when tested in a lean electrolyte environment (2 μL mg−1) with a high mass loading of the MOF (6.8 mg cm−2).
Industry‐Level Electrocatalytic CO2 to CO Enabled by 2D Mesoporous Ni Single Atom Catalysts
Authors: Ma Yao , Xiao Taishi , Zhu Kerun , Zhang Wei , Yin Ziqing , Dong Angang , Sun Zhengzong , Zhao Dongyuan , Li Wei
Published: December 2024

Electrocatalytic CO2 reduction reaction (eCO2RR) has captivated widespread attentions, yet achieving the requisite efficiency, selectivity and stability for industrial applications poses a persistent challenge. Here, we report the synthesis of 2D mesoporous Ni single atom catalysts in N‐doped carbon framework via a bottom‐up interfacial assembly strategy. The 2D mesoporous Ni−N−C catalyst showcases an ultrathin thickness (~6.7 nm) with well‐distributed 5 to 40 nm‐width mesopores in plane and a high surface area. As a result, the Ni single atom sites with a high density (~6.0 wt %) are almost completely exposed and can be accessible, and the mass transfer can be greatly promoted even at high current densities. Thus, a high current density of 446 mA cm−2 with >95 % CO selectivity in a flow cell can be obtained. Concurrently, the catalyst demonstrates an impressive stability, maintaining a 50‐hours continuous electrolysis in the membrane electrode assembly test and achieving an energy efficiency of 42 %. Finite element analysis reveals that the 2D mesoporous design enhances CO2 diffusion, ensuring efficient adsorption and swift CO desorption at high current densities. Our study paves a way for the fabrication of 2D mesoporous single atom catalysts with nearly 100 % accessibility and expedited mass transport.
Metal–Organic Coordination Enhanced Metallopolymer Electrolytes for Wide‐Temperature Solid‐State Lithium Metal Batteries
Authors: Zhao Pei‐Chen , Wang Yaoda , Huang Qi‐Sheng , Jin Zhong , Li Cheng‐Hui
Published: December 2024

The practical application of polymer electrolytes is seriously hindered by the inferior Li+ ionic conductivity, low Li+ transference number (tLi+), and poor interfacial stability. Herein, a structurally novel metallopolymer is designed and synthesized by exploiting a molybdenum (Mo) paddle‐wheel complex as a tetratopic linker to bridge organic and inorganic moieties at molecular level. The prepared metallopolymer possesses combined merits of outstanding mechanical and thermal stability, as well as a low glass transition temperature (Tg <−50 °C). Based on this metallopolymer, an advanced metal–organic coordination enhanced metallopolymer electrolyte (MPE) is developed for constructing high‐performance solid‐state lithium metal batteries (LMBs). Due to the unsaturated coordination of Mo atoms, the uniformly distributed Mo‐polyoxometalates (Mo‐POMs) in metallopolymer skeleton can effectively immobilize anions (bis(fluorosulfonyl)imide anions, FSI−) and promote the dissociation of Li salts. Moreover, dynamic metal–organic coordination bonds endow the MPE with re‐processability and self‐healing, enabling it to accommodate electrode volume changes and maintain good interfacial contact. Consequently, the MPE achieves a competitive ionic conductivity of 0.712 mS cm−1 (25 °C), a high tLi+ (0.625), and a wide electrochemical stability window (>5.0 V). This study presents a unique MPE design based on metal–organic coordination enhanced strategy, providing a promising solution for developing wide‐temperature solid‐state LMBs.
Novel Findings on the SNP18 Sequence and Its Functional Analysis in Hygienic Behavior of Apis mellifera
Authors: Kibar Mustafa , Negiş İnci Şahin , Aytekin İbrahim
Published: December 2024

Hygienic behavior (HB) is a crucial biological mechanism in honeybees that is associated with disease resistance. This study aimed to investigate the effect of the SNP18 sequence and environmental factors on the HB of honey bees, using a total of 14 colonies and 148 bee samples from seven different bee breeds. Association analysis revealed that colonies with Italian hybrids (IH) or young queens statistically (p < 0.01) exhibited high hygienic behavior (HHB). HB increased by 71.6% when the number of frames in the colony, representing colony power (CP), increased by one (p < 0.05). In restriction fragment length polymorphism (RFLP) analysis, novel mutations in the MlyI polymorphism of the SNP18 sequence were firstly found in Apis mellifera. In addition, the restriction fragments of the novel variants of the SNP18 HHB and SNP18 low hygienic behavior (LHB) lines were determined by sequencing. In this study, several important findings emerged: Due to one‐base differences in the restriction fragment, this sequence could not be genotyped by RFLP. Honeybees could be homozygous (HHB or LHB) or heterozygous (HHB and LHB) for the SNP18. SNP18 sequence could be located in different regions of the chromosome and could only be determined by genome sequencing. Finally, since genotypes cannot be clearly determined, no specific allele or genotype can be recommended for HB selection in beekeeping. Therefore, additional research is required to assess discovered novel variants for genetic selection of HHB for ecological beekeeping, healthy products and sustainability.
3D Electrical Resistivity Tomography Using a Radial Array and Detailed Topography for Tumuli Prospection
Authors: Karaoulis Marios , Tsokas Grigorios N. , Tsourlos Panagiotis , Bogiatzis Petros , Vargemezis George
Published: December 2024

Tumuli, ancient burial mounds, stand as intriguing archaeological features, offering valuable insights into past cultures and burial practices. This paper explores the significance of tumuli inspection and utilizes electrical resistivity tomography (ERT) as a noninvasive and powerful tool for inspecting these enigmatic structures, using a nonconventional array. Tumuli, spanning various shapes and sizes, serve as repositories of cultural and funerary traditions, and understanding their internal composition is crucial for unravelling historical narratives. ERT has emerged as a promising geophysical method for investigating subsurface structures, including tumuli. By imaging the electrical resistivity of the ground, ERT enables archaeologists to map variations in soil composition and identify buried features without excavation. This paper reviews the principles of ERT and its application in tumulus studies, showcasing a case study where ERT has successfully revealed internal structures, burial chambers and associated artefacts. The use of 2D ERT is common in tumuli inspection, ignoring accurate 3D effects from the topography. Here we highlight the benefits of the 3D inversion, while we provide a different way to measure which is cost efficient and provides increased spatial resolution to the area of interest. The integration of 3D ERT into archaeological investigations not only enhances our understanding of tumuli construction but also preserves these cultural heritage sites by minimizing the need for invasive excavation. This research contributes to the evolving methodologies in archaeology, emphasizing the synergy between modern technology and traditional archaeological inquiry to uncover the secrets held within tumuli.
Outcomes following intradetrusor onabotulinumtoxinA in a national cohort of nursing home residents
Authors: Dreyfuss Leo D. , Nik‐Ahd Farnoosh , Wang Lufan , Shatkin‐Margolis Abigail , Covinsky Kenneth , Boscardin W. John , Suskind Anne M.
Published: December 2024

Objectives

To determine predictors of treatment success and complications following intradetrusor onabotulinumtoxinA injections among a large cohort of nursing home (NH) residents, representing one of the most frail and vulnerable populations in the United States.

Materials and methods

This is a retrospective cohort study of long‐stay NH residents who underwent onabotulinumtoxinA injections between 2014 and 2016. Residents were identified using the Minimum Data Set (MDS) linked to Medicare claims. Frailty was measured using the Claims‐based Frailty Index and socioeconomic status using the Area Deprivation Index (ADI; higher ADI = increasing social deprivation). The primary outcome was treatment success, defined as repeat onabotulinumtoxinA injection within 1 year of index injection. Secondary outcomes included 30‐day complications and urinary retention, defined as new indwelling urinary catheters identified on the MDS at 3 months.

Results

OnabotulinumtoxinA injections were performed in 1683 NH residents. Mean age was 78.2 years, 74% were female and 22.8% had an indwelling urinary catheter at baseline. A total of 38.4% of residents had ≥1 30‐day complication and 14.6% had a new catheter at 3 months. Repeat injections were performed in 34.3% of residents within 1 year. Repeat injections were more likely among residents who were female [adjusted relative risk (aRR) 1.29; 95% CI 1.08–1.54] and who had a baseline catheter (aRR 1.30; 95% CI 1.11–1.52). Residents who were ≥85 years (aRR 0.78; 95% CI 0.64–0.96) and those in the lowest quartile ADI (aRR 0.75; 95% CI 0.61–0.93) were less likely to undergo repeat injections.

Conclusion

Among this population of NH residents, who are by definition frail and comorbid, rates of repeat onabotulinumtoxinA injections are comparable to retrospective analyses of younger adults and independent of frailty and comorbidity. Based on these findings, surgeons should consider the entire clinical picture when evaluating patients for onabotulinumtoxinA injections and should not necessarily exclude those who are frail or comorbid from this potentially quality‐of‐life‐improving therapy.
Board Remuneration, Remuneration Committee, and Earnings Management in a Two‐Tier System for Company Sustainable Development
Authors: Putra Ferdy , Setiawan Doddy , Hartoko Sri , Arifin Taufiq
Published: December 2024

This study aims to analyze the effect of directors' and board of commissioners' remuneration on earnings management using the remuneration committee as a moderating variable. Using a sample of Indonesian non‐financial companies from 2014 to 2023 and using multiple regression analysis and moderated regression analysis, we found that directors' remuneration has a positive effect, while the board of commissioners' remuneration has a negative effect on earnings management. The remuneration committee negatively moderates the effect of directors' remuneration and positively moderates the effect of the board of commissioners' remuneration on earnings management. These results also remain consistent when using alternative measurements and the endogeneity test. We found many companies do not yet have a remuneration committee, so corporate governance can still be improved. This study has practical and theoretical contributions to increasing knowledge about agency theory, earnings management, and factors that can align the interests of directors, boards of commissioners, and shareholders so that the company's sustainable development can continue to be improved.
Environmental and Social Performance, Firm Value, and the Role of Sustainability Committee
Authors: Rini Rima Kusuma
Published: December 2024

The presence of a specific role, such as a sustainability committee, is crucial for enhancing environmental and social performance and increasing market value. This study aims to examine the direct relationship between sustainability committee to environmental and social performance, as well as between environmental and social performance and firm value to provide additional evidence among mixed findings from previous result. The moderating relationship of the sustainability committee given the significant outcomes in the direct relationship between environmental and social performance and firm value. Using 11 years data in Indonesia, the sustainability committee has positive significant to environmental and social performance. Social performance has positive significant to firm value while environmental does not. Additionally, sustainability committee strengthens the relationship between environmental performance and firm value while social performance is not. These findings portray the importance of sustainability committee to both leverage the environmental and social performance, as well as firm value. The Difference‐in‐Difference (DiD) analysis reveals that, following POJK No. 51/2017, sustainability committee significantly impacts environmental and social performance and firm value, though with negative way. This distinction result provides additional insight since in short‐term the sustainability role still perceived in negative ways. This study contributes to the literature by presence of the role sustainability committee, which no previous studies documented in developing country and difference governance mechanisms such as Indonesia. The limitation of data sustainability committee recommends the future study should consider the role sustainability responsibilities in other committees, identify the characteristics and performance of sustainability committee.
Chemoselective Anaerobic Dehydrogenation of Alcohols by Using Visible Light and a Positively Charged Deazaflavin Catalyst Regenerated by Acetonitrile Solvent
Authors: Obertík Róbert , Ludvíková Lucie , Chudoba Josef , Cibulka Radek
Published: December 2024

Three series of novel deazaflavinum salts differing in their substitutions at positions 5 (R = H, phenyl, or mesityl), 7, and 8 (R = OMe, Me, H, or Cl) were synthesized as potential catalysts of a novel chemoselective visible light‐mediated anaerobic oxidation of primary and secondary alcohols to carbonyl compounds. This mild procedure uses acetonitrile as a solvent, which acts simultaneously as a sacrificial electron acceptor (in place of the oxygen usually used in photooxidation reactions), and therefore the reaction does not need any additives. Structure and properties‐versus‐catalytic activity studies identified 5‐mesityl‐7,8‐dimethoxy‐3‐methyldeazaflavinium chloride (3a‐Cl) as the most potent catalyst. 3a‐Cl was effective in non‐deuterated acetonitrile (CH3CN), unlike its original 5‐phenyl analogue 2a‐Cl, which is efficient only in deuterated solvent (CD3CN). This difference arises because the regeneration of the 2a‐Cl catalyst is slower in CH3CN than in CD3CN. Our method using the optimized 3a‐Cl photocatalyst and CH3CN as a sacrificial oxidant and solvent in one is a useful addition to synthetic organic chemistry. Anaerobic conditions prevent side oxygenation reactions and overoxidations that usually occur in air or oxygen. This property makes this method suitable for dehydrogenations of alcohols that possess additional group(s) sensitive to oxygenation.
Carbon Monoxide and Alkoxycarbonyl Radical Enabled Migration Strategy for the Carbonylative Functionalization of Unactivated Alkenes
Authors: Hou Ming , Wang Yuanrui , Yang Hefei , Zhang Jiajun , Wu Xiao‐Feng
Published: December 2024

Herein we report a “carbonylative migration” strategy for the acylation‐esterification type double functionalization of unactivated alkenes using alkyloxalkyl chlorides and CO as the reagents. The transformation is proceeded by the alkoxycarbonyl radical addition to unactivated alkenes, followed by the insertion of carbon monoxide to induce intramolecular migration of heteroaryl groups, which is different from the traditional reaction modes. The reaction conditions were mild and well tolerated with varieties of functional groups. A variety of 1,4‐dicarbonyl compounds with different ester groups were produced easily which has high potential applications in biology, medicine, and other fields.
Riesige Elementarzelle mitten in Brüssel
Authors: Saal Frederike , Wunsch Jonas Florian
Published: December 2024

Die hier vorgestellte Aufgabe soll eine Einführung in grundlegende Berechnungen zu Elementarzellen und Kernspaltungsprozessen geben. Inspiration dazu stiftet die Architektur und Bedeutungsebene des Atomiums.
Evaluating Red Blood Cells' Membrane Fluidity in Diabetes: Insights, Mechanisms, and Future Aspects
Authors: Pitocco Dario , Hatem Duaa , Riente Alessia , Giulio Michele Maria De , Rizzi Alessandro , Abeltino Alessio , Serantoni Cassandra , Tartaglione Linda , Rizzo Emanuele , Paoli Lorenzo Lucacchini , Spirito Marco De , Maulucci Giuseppe
Published: December 2024

Aims

This review evaluates the mechanisms underlying red blood cell (RBC) membrane fluidity changes in diabetes mellitus (DM) and explores strategies to assess and address these alterations. Emphasis is placed on developing a comprehensive index for membrane fluidity to improve monitoring and management in diabetic patients.

Materials and Methods

We reviewed current literature on RBC membrane fluidity, focussing on lipid composition, glycation, oxidative stress, and lipid transport alterations in diabetic patients. Key methodologies include lipidomics, multi‐scale probe assessment, and machine learning integration for standardized fluidity measurement.

Results

Diabetic RBCs exhibit increased membrane fluidity, primarily due to oxidative stress, increased glycation, and dysregulated lipid composition. These alterations contribute to vascular complications and impair RBC functionality. Assessing membrane composition as a nutritional marker provides insights into the metabolic impacts of glycaemic management.

Conclusions

There is a critical need for a unified and comprehensive membrane fluidity index in DM, which could support personalised interventions through dietary, medicinal, and lifestyle modifications. Future research should prioritise standardising measurement techniques and integrating lipidomic data with machine learning for predictive modelling, aiming to enhance clinical outcomes for diabetic patients.
Children's Books as a Tool for Raising Young Readers' Awareness of Dyslexia
Authors: Lise Lemoine , Emmanuelle Bonjour , Benoît Schneider , Nathalie Marec‐Breton
Published: December 2024

French law requires children with disabilities to receive schooling, wherever possible in ordinary schools. To achieve this goal, schools must create a truly inclusive environment that meets every child's specific needs. Ensuring other students accept peers with disabilities is an essential part of providing an inclusive environment. We postulated that reading children's books featuring characters with disabilities can foster this acceptance by enabling students to understand and empathise with peers with disabilities. Indeed, readers' tendency to attribute emotions, beliefs, intentions and perceptions to characters helps them better appreciate characters' feelings, mental states and experiences. The present study analysed the impact that reading a children's book about a young boy with dyslexia had on children without dyslexia. We read Les mots d'Enzo to 25 fourth‐ and fifth‐grade students (13 girls and 12 boys) and then conducted semi‐structured interviews with each student. Reading Les mots d'Enzo taught participants a lot about dyslexia, the difficulties it causes, its consequences for children with dyslexia and the help these children need. In addition to gaining a relatively accurate understanding of dyslexia, participants grasped the story's moral, attributed emotions, beliefs and intentions to the character with dyslexia, appreciated how he felt, and showed empathy towards him. They were also capable of generalising these aspects to real students with dyslexia or other disorders.
Parafoveal Processing and Transposed‐Letter Effects in Developmental Dyslexic Reading
Authors: Kirkby Julie A. , Barrington Rhiannon S. , Drieghe Denis , Liversedge Simon P.
Published: December 2024

During reading, adults and children independently parafoveally encode letter identity and letter position information using a flexible letter position encoding mechanism. The current study examined parafoveal encoding of letter position and letter identity for dyslexic children. Eye movements were recorded during a boundary‐change paradigm. Parafoveal previews were either an identity preview (e.g., nearly), a transposed‐letter preview (e.g., enarly) or a substituted‐letter preview (e.g., acarly). Dyslexic readers showed a preview benefit for identity previews, indicating that orthographic information was encoded parafoveally. Furthermore, dyslexic readers benefitted from transposed‐letter previews more than substituted‐letters previews, demonstrating that letter identity was encoded independently to letter position during parafoveal processing. Although a transposed‐letter effect was found for dyslexic readers, they demonstrated a reduced sensitivity to detect transposed‐letters in later measures of reading, that is, go‐past times, relative to that found for typically developing readers. We conclude that dyslexic readers, with less rich and fully specified lexical representations, have a reduced sensitivity to transpositions of the first two letters of the upcoming word in preview. These findings are compatible with the view that orthographic representations of dyslexic children are not sufficiently specified.
Implicit Statistical Learning of Brazilian Children With Developmental Dyslexia
Authors: Ardiles Roseline , Custódio Eda Marconi , dos Santos Suelen Nascimento , de Oliveria Matheus Assis
Published: December 2024

Implicit statistical learning (ISL) is non‐conscious learning where participants identify patterns in their environment after repeated exposures. This study verified whether Brazilian children with DD present disturbances in the ISL mechanism and if these disturbances may be related to the difficulties associated with DD through artificial grammar learning (AGL) and reaction time in serial tasks (SRT Task). It also intended to verify which of the paradigms proves to be the most sensitive to assess ISL and which is most associated with participants' learning to read and write. Two groups of children with and without DD from the end of the first cycle and the beginning of the second cycle of the elementary school participated in this study, paired according to socioeconomic level, education network, schooling, gender and age. Children with DD showed no disturbances in the ISL process; the AGL paradigm exhibited the most significant association with performance on reading/writing tasks. When compared to the SRT Task, the AGL paradigm proved to be more sensitive in assessing implicit processes and effectively distinguishing between the groups with and without DD. The results of the SRT Task emphasise the importance of task practice and structure for implicit learning in children with developmental dyslexia. These findings have important implications for understanding ISL and its relevance to reading and writing skills in children with developmental dyslexia.
E‐52862—A selective sigma‐1 receptor antagonist, in peripheral neuropathic pain: Two randomized, double‐blind, phase 2 studies in patients with chronic postsurgical pain and painful diabetic neuropathy
Authors: Gálvez Rafael , Mayoral Victor , Cebrecos Jesús , Medel Francisco J. , Morte Adelaida , Sust Mariano , Vaqué Anna , Montes‐Pérez Antonio , Neira‐Reina Fernando , Cánovas Luz , Margarit César , Bouhassira Didier
Published: December 2024

Background

We report the efficacy and safety of E‐52862—a selective, sigma‐1 receptor antagonist—from phase 2, randomized, proof‐of‐concept studies in patients with moderate‐to‐severe, neuropathic, chronic postsurgical pain (CPSP) and painful diabetic neuropathy (PDN).

Methods

Adult patients (CPSP [N = 116]; PDN [N = 163]) were randomized at a 1:1 ratio to 4 weeks of treatment with E‐52862 (CPSP [n = 55]; PDN [n = 85]) or placebo (CPSP [n = 61]; PDN [n = 78]) orally once daily. Pain intensity scores were measured using a numerical pain rating scale from 0 (no pain) to 10 (worst pain imaginable). The primary analysis population comprised patients who received study drug with ≥1 baseline and on‐treatment observation (full analysis set).

Results

In CPSP, mean baseline average pain was 6.2 for E‐52862 vs. 6.5 for placebo. Week 4 mean change from baseline (CFB) for average pain was −1.6 for E‐52862 vs. –0.9 for placebo (least squares mean difference [LSMD]: −0.9; p = 0.029). In PDN, mean baseline average pain was 5.3 for E‐52862 vs. 5.4 for placebo. Week 4 mean CFB for average pain was −2.2 for E‐52862 vs. –2.1 for placebo (LSMD: –0.1; p = 0.766). Treatment‐emergent adverse events (TEAEs) were reported in 90.9% of E‐52862‐treated patients vs. 76.7% of placebo‐treated patients in CPSP and 34.1% vs. 26.9% in PDN. Serious TEAEs occurred in CPSP only: E‐52862: 5.5%; placebo: 6.7%.

Conclusions

E‐52862 demonstrated superior relief of CPSP vs. placebo after 4 weeks. Reductions in pain intensity were seen in PDN with E‐52862; high placebo response rates may have prevented differentiation between treatments. E‐52862 had acceptable tolerability in both populations.

Significance Statement

These proof‐of‐concept studies validate the mode of action of E‐52862, a selective sigma‐1 receptor antagonist. In CPSP, E‐52862 resulted in clinically meaningful pain relief. In PDN, reductions in pain intensity were seen with E‐52862; high placebo response rates may have prevented differentiation between E‐52862 and placebo. These findings are clinically relevant given that neuropathic pain is highly incapacitating, lacking effective treatments and representing a significant unmet medical need, and support further development of sigma‐1 receptor antagonists for peripheral neuropathic pain.
A genome‐wide association study of European advanced cancer patients treated with opioids identifies regulatory variants on chromosome 20 associated with pain intensity
Authors: Minnai Francesca , Shkodra Morena , Noci Sara , Esposito Martina , Brunelli Cinzia , Pigni Alessandra , Zecca Ernesto , Skorpen Frank , Klepstad Pål , Kaasa Stein , Corli Oscar , Pallotti Maria C. , Maltoni Marco C. , Caraceni Augusto T. , Colombo Francesca
Published: December 2024

Background

Opioids in step III of the WHO analgesic ladder are the standard of care for treating cancer pain. However, a significant minority of patients do not benefit from therapy. Genetics might play a role in predisposing patients to a good or poor response to opioids. Here, we investigated this issue by conducting a genome‐wide association study (GWAS).

Methods

We genotyped 2057 European advanced cancer patients treated with morphine, buprenorphine, fentanyl and oxycodone. We carried out a whole‐genome regression model (using REGENIE software) between genotypes and the opioid response phenotype, defined as a numerical score measuring patient pain intensity.

Results

The GWAS identified five non‐coding variants on chromosome 20 with a p‐value <5.0 × 10−8. For all of them, the minor allele was associated with lower pain intensity. These variants were intronic to the PCMTD2 gene and were 200 kbp downstream of OPRL1, the opioid related nociceptin receptor 1. Notably according to the eQTLGen database, these variants act as expression quantitative trait loci, modulating the expression mainly of PCMTD2 but also of OPRL1. Variants in the same chromosomal region were recently reported to be significantly associated with pain intensity in a GWAS conducted in subjects with different chronic pain conditions.

Conclusions

Our results support the role of genetics in the opioid response in advanced cancer patients. Further functional analyses are needed to understand the biological mechanism underlying the observed association and lead to the development of individualized pain treatment plans, ultimately improving the quality of life for cancer patients.

Significance Statement

This genome‐wide association study on European advanced cancer patients treated with opioids identifies novel regulatory variants on chromosome 20 (near PCMTD2 and OPRL1 genes) associated with pain intensity. These findings enhance our understanding of the genetic basis of opioid response, suggesting new potential markers for opioid efficacy. The study is a significant advancement in pharmacogenomics, providing a robust dataset and new insights into the genetic factors influencing pain intensity, which could lead to personalized cancer pain management.
Evaluation of the standard battery of in vitro genotoxicity tests to predict in vivo genotoxicity through mathematical modeling: A report from the 8th International Workshop on Genotoxicity Testing
Authors: Luijten Mirjam , van Benthem Jan , Morita Takeshi , Corvi Raffaella , Escobar Patricia A. , Fujita Yurika , Hemmerich Jennifer , Honarvar Naveed , Kirkland David , Koyama Naoki , Lovell David P. , Mathea Miriam , Williams Andrew , Dertinger Stephen , Pfuhler Stefan , Pennings Jeroen L. A.
Published: December 2024

In human health risk assessment of chemicals and pharmaceuticals, identification of genotoxicity hazard usually starts with a standard battery of in vitro genotoxicity tests, which is needed to cover all genotoxicity endpoints. The individual tests included in the battery are not designed to pick up all endpoints. This explains why resulting data can appear contradictory, thereby complicating accurate interpretation of the findings. Such interpretation could be improved through application of mathematical modeling. One of the advantages of mathematical modeling is that the strengths and weaknesses of each test are taken into account. Furthermore, the generated predictions are objective and convey the associated uncertainties. This approach was explored by the working group “Predictivity of In Vitro Genotoxicity Testing,” convened in the context of the 8th International Workshop on Genotoxicity Testing (IWGT). Specifically, we applied mathematical modeling to a database with publicly available in vitro and in vivo data for genotoxicity. The results indicate that a mammalian in vitro clastogenicity test and a mammalian cell gene mutation test together provide strong predictive weight‐of‐evidence for evaluating genotoxic hazard of a substance, although they are better in predicting absence of genotoxic potential than in predicting presence of genotoxic potential. Remarkably, the bacterial reverse mutation (Ames) test did not significantly change these predictions when used in combination with in vitro mutagenicity and clastogenicity tests using cells of mammalian origin. However, in case only data from a bacterial reverse mutation test are available for the assessment of genotoxic potential, these do bear weight of evidence and thus can be used. Genotoxicity assays are generally executed in tiers, in which the bacterial reverse mutation test often is the starting point. Thus, it is reasonable to suspect that early in development test results from the bacterial reverse mutation test have influenced the composition of the database studied here. We performed several tests on the robustness of the database used for the analyses presented here, and the forthcoming results do not indicate a strong bias. Further research comparing in vitro genotoxicity data with in vivo data for additional compounds will provide more insights whether it is indeed time to reconsider the composition of the standard in vitro genotoxicity battery.
Money Growth and Inflation—How to Account for the Differences in Empirical Results
Authors: Mandler Martin , Scharnagl Michael
Published: December 2024

Empirical analyses have presented different results on the long‐run relationship between money growth and inflation with some pointing to a stable relationship with a slope coefficient of close to one and others suggesting instability or a weakening of the relationship over time. Using the example case of the United States and nearly 150 years of data, we provide a systematic investigation into and comparison of the results from time series‐based empirical evidence on the relationship between money growth and inflation. We use the results from a wavelet analysis as a benchmark as it offers a flexible framework that provides information on the relationship both across different frequencies and different points in time. We relate these results to those in the literature obtained from other empirical approaches and investigate the underlying causes of differences in the results. We argue that it is possible to arrive at a consistent conclusion of a stable correlation between money growth and inflation in the United States at cycles of 30 to 60 years with a declining trend in the slope relationship even though the empirical results in the literature appear to be at odds. We show that in some analyses, the evidence on the “long‐run” relationship is distorted by unintentionally including higher frequencies or that results are dominated by outliers at very low frequencies for which the data do not contain much information. Furthermore, the way in which different analyses account for time variation also can influence the results.
Scenario‐based water balance analysis of estuary reservoir for multipurpose water supply
Authors: Bang Jehong , Choi Jin‐Yong , Lee Sang‐Hyun , Hwang Soonho , Kang Moon‐Seong
Published: December 2024

In the circumstance of increasing industrial and municipal water demand, estuary reservoirs are one of the critical water resources that can be a solution. Therefore, we simulated the water balance model of an estuary agricultural reservoir to evaluate the impact of additional industrial water release on its performance. We considered runoff and treated water as water inflow and irrigation requirement in paddy fields and water use in the hydrogen plant as water release. Runoff and irrigation water requirements were estimated using the Tank model and the FAO modified Penman method, respectively. Industrial water demand was surveyed at 32,000 m3 day−1 throughout the year. The results show that the reservoir's reliability increases as the water loss and irrigation area decrease with reusing the return flow, which is hardly affected by the industrial water supply. The trend of resiliency resembles reliability; however, the industrial release has the most significant impact when lower water loss is applied and the paddy area is decreased. Vulnerability gets worse when additional purpose water is released. In other words, the more water the reservoir releases, the more severe the drought gets. Therefore, the engineer and operator should consider the expected risks presented as reliability, resiliency and vulnerability in the design and management of the reservoir.
Skull Ossification in the Andean Toad Rhinella spinulosa (Bufonidae) and the Genetic Model Organism Xenopus tropicalis (Pipidae) Reveals Heterochrony Phenomena and Frontoparietal Suture Modifications
Authors: Mundaca Marco , Rojas Japhet , Cumilaf Lefney , Jara Federico , Muñoz David , Pastenes Luis , Méndez Marco , Tovar Lina M. , Torrejón Marcela , Montoya‐Sanhueza Germán , Marcellini Sylvain
Published: December 2024

Anurans are famous for having evolved a highly simplified skull through bone loss and fusion events. Nevertheless, their skeleton displays a rich morphological diversity associated with adaptations to diverse lifestyles and ecological niches. Here, we report larval skull ossification in the Andean toad Rhinella spinulosa (Bufonidae), and compare it to the phylogenetically distant genetic model organism Xenopus tropicalis (Pipidae). We find that the ossification timing of most skull bones is conserved between both species, except for the prootic and the angulosplenial that ossify at much later stages in R. spinulosa than X. tropicalis. We propose that a delayed lower jaw ossification in R. spinulosa is tightly related to the more extensive metamorphosis process observed in this species where the ventrally oriented mouth opening shifts anteriorly. We also report two conspicuous notches in the R. spinulosa frontoparietal bone mineralization front which are absent in X. tropicalis, and presumably represent evolutionary remnants of the coronal suture that separates the frontal and parietal bones in most vertebrates. As such notches have not been overtly reported in the literature, we examined the X. tropicalis sibling species Xenopus laevis, and were able to identify similar, albeit transient, indentations in the forming frontoparietal bone, suggesting that vestigial coronal sutures might exist in more frog species than anticipated. Taken together, we show that R. spinulosa represents an ideal organism to study heterochronic shifts and the mechanisms underlying cranial suture loss which drove anuran skull simplification.