bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing national antimicrobial consumption in Latin America and the Caribbean: opportunities and lessons learned
Authors: Marin Gustavo Horacio , Giangreco Lucia , Lichtenberger Paola , Dorati Cristian , Mordujovich-Buschiazzo Perla , Rojas-Cortés Robin , Ramón-Pardo Pilar , Marín Danini , Castro José Luis
Published: January 2025

Surveillance of antimicrobial consumption (AMC) is essential to anticipate and inform policies and public health decisions to prevent and/or contain antimicrobial resistance (AMR). This manuscript shares the experience on AMC data collection in Latin American & Caribbean (LAC). The WHO GLASS-AMC methodology for AMC surveillance was used for data registration during the period 2019–2022. Focal points belonging to each country were contacted and trained for AMC source of information detection, managing registration tools, and data analysis. Thirteen countries were enrolled with significant heterogeneity in the AMC results (range 2.55–36.26 DID-AMC). This experience reflects the heterogeneity of realities in LAC countries; how each one of the nations selected the best sources to collect AMC data, which were the main problems in applying the WHO-AMC collection tool, and the approach that each country gave to the analysis of its data. Finally, some examples are provided on the use of AMC information in making the best decision-making related to AMR control policies at the national level.
Responses to Populism: Militant, Tolerant, and Social
Authors: Malkopoulou Anthoula , Moffitt Benjamin
Published: January 2025

What should we do about populism? In recent years, this question has become more urgent as populist leaders and parties have taken center stage in many countries across the globe. No longer a “minor” political phenomenon, populism has forced scholars to grapple with how to address its potential “threat” to “liberal democracy while also harnessing its “corrective” properties (Rovira Kaltwasser 2012). In this debate, the two questions of who “we” are—that is, who should respond—and how to do it often have taken different forms.
Populism and democracy: The road ahead
Authors: Rovira Kaltwasser Cristóbal , Taggart Paul
Published: January 2025

Pundits and academics alike are increasingly concerned about the health of democracy worldwide. Much of this concern is tied to the rise of populism, a global phenomenon presenting challenges to both long-established and relatively young democracies. Political science has been at the forefront of this debate, and thanks to a growing—but not universal—consensus on the ideational definition of populism, our understanding of the subject has deepened considerably. This symposium maps key debates on the complex and often ambivalent relationship between populism and democracy. In this concluding piece, we build on the arguments presented throughout the symposium and related academic discussions to outline two paths for future research on the populism and democracy nexus: a top-down and a bottom-up perspective.
Reactions to no-fault compensation schemes for occupational diseases in the Netherlands: the role of perceived procedural justice, outcome concerns and trust in authorities
Authors: Overheul Marlou , van den Bos Kees , Rijnhout Rianka
Published: January 2025

Financial redress for victims of occupational diseases can be offered through no-fault compensation schemes. No-fault compensation schemes have an explicit mission in promoting perceived fairness and justice. The objective is to offer a quick, fair and just procedure and outcome, while preventing civil court procedures and restoring trust. However, the question is whether applicants of these no-fault schemes indeed experience perceived fairness and justice. This paper discusses the result of an in-depth interview study with fifty-eight victims involved in no-fault schemes for occupational diseases in the Netherlands. We focus on the role of perceived procedural justice, outcome concerns and trust in the (former) employer.
Do the Vertical Movements of the Peak Height of F Region Truly Represent the Vertical E×B $\mathbf{E}\times \mathbf{B}$ Plasma Drift Velocity Over the Dip Equator?
Authors: Ashok Arya , Ambili K. M. , Choudhary R. K.
Published: January 2025

This study examines the reasons for the difference observed between the plasma drift and the drift calculated by tracing the movement of the ionospheric region peak, using a quasitwo‐dimensional theoretical ionospheric model. Analysis shows that vertical drift causes the electron density profiles in the region to steepen, where photochemistry dominates, and pushes the plasma to higher altitudes. Photochemical processes result in the lower peak , while the upper peak is attributed to vertical drift, which is difficult to trace due to diffusion effects. The close agreement between model‐derived and Scherliess‐Fejer (SF) vertical drifts confirms that the peak does not respond to vertical drift if it is below 300 km. Significant observational evidence of this phenomenon was recorded during the superstorm period of 10–11 May 2024 (Mother's Day solar storm). This superstorm period caused an increased vertical drift in the F region, leading the peak to rise above 300 km. The extreme conditions during this superstorm provided a rare opportunity to observe the dynamics of the ionosphere and validate our model. The observations during the superstorm period highlight the importance of understanding vertical drift dynamics and their impact on ionospheric behavior, especially during extreme space weather events.
Personalised estimation of exposure to ambient air pollution and application in a longitudinal cohort analysis of cognitive function in London-dwelling older adults
Authors: Wood Dylan , Evangelopoulos Dimitris , Kitwiroon Nutthida , Stewart Gregor , Vu Tuan , Smith James , Beevers Sean , Katsouyanni Klea
Published: January 2025

Background

Accurate estimates of personal exposure to ambient air pollution are difficult to obtain and epidemiological studies generally rely on residence-based estimates, averaged spatially and temporally, derived from monitoring networks or models. Few epidemiological studies have compared the associated health effects of personal exposure and residence-based estimates.

Objective

To evaluate the association between exposure to air pollution and cognitive function using exposure estimates taking mobility and location into account.

Methods

Residence-based dispersion model estimates of ambient NO2, PM10 and PM2.5 were assigned to 768 London-dwelling participants of the English Longitudinal Study of Ageing. The London Hybrid Exposure Model was implemented to adjust estimates per pollutant to reflect the estimated time-activity patterns of each participant based on age and residential location. Single pollutant linear mixed-effects models were fit for both exposure assessment methods to investigate the associations between assigned pollutant concentrations and cognitive function over a follow-up period of up to 15 years.

Results

Increased long-term exposures to residence-based ambient NO2 (IQR: 11.10 µg/m3), PM10 (2.35 µg/m3), and PM2.5 (2.50 µg/m3) were associated with decreases of −0.10 [95% CI: −0.20, 0.00], −0.07 [−0.11, −0.02] and −0.14 [−0.21, −0.06], respectively, in composite memory score. Similar decreases were observed for executive function scores (−0.38 [−0.58, −0.18], −0.11 [−0.20, −0.02] and −0.14 [−0.29, 0.01], respectively). When applying personalised exposure estimates, which were substantially lower, similar decreases were observed for composite memory score per IQR, but a consistent pattern of slightly more adverse effects with executive function score was evident.

Impact Statement

The present study constructed a framework through which time-activity information derived from a representative sample could be applied to estimates of ambient air pollution concentrations assigned to individuals in epidemiological cohort studies, with the intention of adjusting commonly used residence-based estimates to reflect population mobility and time spent in various microenvironments. Estimates of exposure were markedly lower when incorporating time-activity, likely because people in European populations spend a large proportion of their time indoors, where their exposure to ambient air pollution may be reduced through infiltration, which is not taken into account in residence-based ambient estimates. Further work into such methods could provide insights into the efficacy of personalising exposure estimates.
Nonlinear memristive computational spectrometer
Authors: Li Xin , Wang Jie , Yu Feilong , Chen Jin , Chen Xiaoshuang , Lu Wei , Li Guanhai
Published: January 2025

In the domain of spectroscopy, miniaturization efforts often face significant challenges, particularly in achieving high spectral resolution and precise construction. Here, we introduce a computational spectrometer powered by a nonlinear photonic memristor with a WSe2 homojunction. This approach overcomes traditional limitations, such as constrained Fermi level tunability, persistent dark current, and limited photoresponse dimensionality through dynamic energy band modulation driven by palladium (Pd) ion migration. The critical role of Pd ion migration is thoroughly supported by first-principles calculations, numerical simulations, and experimental verification, demonstrating its effectiveness in enhancing device performance. Additionally, we integrate this dynamic modulation with a specialized nonlinear neural network tailored to address the memristor’s inherent nonlinear photoresponse. This combination enables our spectrometer to achieve an exceptional peak wavelength accuracy of 0.18 nm and a spectral resolution of 2 nm within the 630–640 nm range. This development marks a significant advancement in the creation of compact, high-efficiency spectroscopic instruments and offers a versatile platform for applications across diverse material systems.
Neurophysiological correlates of ketamine-induced dissociative state in bipolar disorder: insights from real-world clinical settings
Authors: Agnorelli Claudio , Cinti Alessandra , Barillà Giovanni , Lomi Francesco , Scoccia Adriano , Benelli Alberto , Neri Francesco , Smeralda Carmelo Luca , Cuomo Alessandro , Santarnecchi Emiliano , Tatti Elisa , Godfrey Kate , Tarantino Francesca , Fagiolini Andrea , Rossi Simone
Published: January 2025

Ketamine, a dissociative compound, shows promise in treating mood disorders, including treatment-resistant depression (TRD) and bipolar disorder (BD). Despite its therapeutic potential, the neurophysiological mechanisms underlying ketamine’s effects are not fully understood. This study explored acute neurophysiological changes induced by subanesthetic doses of ketamine in BD patients with depression using electroencephalography (EEG) biomarkers. A cohort of 30 BD (F = 12) inpatients with TRD undergoing ketamine treatment was included in the study. EEG recordings were performed during one of the ketamine infusions with doses ranging from 0.5 to 1 mg/kg, and subjective effects were evaluated using the Clinician-Administered Dissociative States Scale (CADSS). Both rhythmic and arrhythmic features were extrapolated from the EEG signal. Patients who exhibited a clinical response to ketamine treatment within one week were classified as early responders (ER), whereas those who responded later were categorized as late responders (LR). Ketamine reduced low-frequency spectral power density while increasing gamma oscillatory power. Additionally, ketamine flattened the slope of the power spectra, indicating altered scale-free dynamics. Ketamine also increased brain signal entropy, particularly in high-frequency bands. Notably, LR exhibited greater EEG changes compared to ER, suggesting endophenotypic differences in treatment sensitivity. These findings provide valuable insights into the neurophysiological effects of ketamine in BD depression, highlighting the utility of EEG biomarkers for assessing ketamine’s therapeutic mechanisms in real-world clinical settings. Understanding the neural correlates of ketamine response may contribute to personalized treatment approaches and improved management of mood disorders.
Chimeric antigen receptor with novel intracellular modules improves antitumor performance of T cells
Authors: Wang Pengju , Wang Yiyi , Zhao Xiaojuan , Zheng Rui , Zhang Yiting , Meng Ruotong , Dong Hao , Liang Sixin , He Xinyi , Song Yang , Su Haichuan , Yan Bo , Yang An-Gang , Jia Lintao
Published: January 2025

The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T (CAR-T) cell therapy in diverse tumors. Conventional CARs employ an intracellular domain (ICD) from the ζ subunit of CD3 as a signaling module, and it is largely unknown how alternative CD3 chains potentially contribute to CAR design. Here, we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs. While these reconstituted CARs conferred sufficient antigen-specific cytolytic activity on equipped T cells, they elicited low tonic signal, ameliorated the exhaustion and promoted memory differentiation of these cells. Intriguingly, the CD3ε-derived ICD outperformed others in generation of CAR-T cells that produced minimized cytokines. Mechanistically, CD3ε-based CARs displayed a restrained cytomembrane expression on engineered T cells, which was ascribed to endoplasmic reticulum retention mediated by the carboxyl terminal basic residues. The present study demonstrated the applicability of CAR reconstitution using signaling modules from different CD3 subunits, and depicted a novel pattern of CAR expression that reduces cytokine release, thus paving a way for preparation of CAR-T cells displaying improved safety and persistence against diverse tumor antigens.
Safety and efficacy of the ROCK-2-inhibitor Belumosudil in cGvHD treatment - a retrospective, German-Swiss multicenter real-world data analysis
Authors: Heidenreich Silke , Egger-Heidrich Katharina , Halter Jörg P. , Jost Lasse , Stölzel Friedrich , Perl Markus , Denk Alexander , Edinger Matthias , Herr Wolfgang , Kröger Nicolaus , Wolff Daniel , Ayuk Francis , Fante Matthias A.
Published: January 2025

Belumosudil is a first in class ROCK2-inhibitor approved by the FDA for the 3rd line treatment of chronic graft-versus-host disease (cGvHD). In this retrospective real-world analysis, we report safety and efficacy data of belumosudil treatment from 5 German/Swiss transplant centers. A total of 33 adult patients (median age 59 years) with moderate (n = 2) or severe (n = 31) cGvHD were treated on individual request due to lack of EMA approval. The patient cohort had a long history of cGvHD (median 44 months) and was heavily pretreated (median 4 prior lines). The overall response rate was 42% (95%CI, 25–60%) including organ responses in all organs except the liver (n = 2). The median time to response was 3 months (range, 1–9 months) and 8 of 14 patients (57%) had a durable response at last follow-up. One-third of patients had at least a 50% reduction in concomitant corticosteroid dosage. Median failure-free survival and median overall survival were 16.5 and 23.1 months, respectively. Adverse events ≥CTCAE grade 3 were reported in 27% of patients, with a predominance of infectious events, including one fatal course. The results are consistent with previous prospective trials including a favorable safety profile, while acknowledging the challenges of a heavily pretreated patient cohort.
The TRPV1-PKM2-SREBP1 axis maintains microglial lipid homeostasis in Alzheimer’s disease
Authors: Sha Xudong , Lin Jiayuan , Wu Kexin , Lu Jia , Yu Zhihua
Published: January 2025

Microglia are progressively activated by inflammation and exhibit phagocytic dysfunction in the pathogenesis of neurodegenerative diseases. Lipid-droplet-accumulating microglia were identified in the aging mouse and human brain; however, little is known about the formation and role of lipid droplets in microglial neuroinflammation of Alzheimer’s disease (AD). Here, we report a striking buildup of lipid droplets accumulation in microglia in the 3xTg mouse brain. Moreover, we observed significant upregulation of PKM2 and sterol regulatory element binding protein 1 (SREBP1) levels, which were predominantly localized in microglia of 3xTg mice. PKM2 dimerization was necessary for SREBP1 activation and lipogenesis of lipid droplet-accumulating microglia. RNA sequencing analysis of microglia isolated from 3xTg mice exhibited transcriptomic changes in lipid metabolism, innate inflammation, and phagocytosis dysfunction; these changes were improved with capsaicin-mediated pharmacological activation of TRPV1 via inhibition of PKM2 dimerization and reduction of SREBP1 activation. Lipid droplet-accumulating microglia exhibited increased mitochondrial injury accompanied by impaired mitophagy, which was abrogated upon of TRPV1 activation. Capsaicin also rescued neuronal loss, tau pathology, and memory impairment in 3xTg mice. Our study suggests that TRPV1-PKM2-SREBP1 axis regulation of microglia lipid metabolism could be a therapeutic approach to alleviate the consequences of AD.
Orphan nuclear receptor NR2E3 is a new molecular vulnerability in solid tumors by activating p53
Authors: Wang Yidan , Kroll Todd G. , Hao Linhui , Wen Zhi
Published: January 2025

The orphan nuclear receptor NR2E3 has emerged as a potential tumor suppressor, yet its precise mechanisms in tumorigenesis require further investigation. Here, we demonstrate that the full-length protein isoform of NR2E3 instead of its short isoform activates wild-type p53 and is capable of rescuing certain p53 mutations in various cancer cell lines. Importantly, we observe a higher frequency of NR2E3 mutations in three solid tumors compared to the reference population, highlighting its potential significance in tumorigenesis. Specifically, we identify a cancer-associated NR2E3R97H mutation, which not only fails to activate p53 but also impedes NR2E3WT-mediated p53 acetylation. Moreover, we show that the small-molecule agonist of NR2E3, 11a, penetrates tumor mass of uterine cancer patients and increases p53 activation. Additionally, both NR2E3 and 11a exhibit similar multifaceted anti-cancer properties, underscoring NR2E3 as a novel molecular vulnerability in cancer cells. We further explore drug repurposing screens of FDA-approved anti-cancer drugs to develop NR2E3-targeted combinatorial treatments, such as the 11a-Romidepsin combination in HeLa cells. The underlying molecular mechanisms of these drug synergies include the activation of p53 pathway and inhibition of oncogenic pathway like MYC. Overall, our findings suggest that NR2E3 holds promise as a therapeutic target for cancer treatment, offering new avenues for effective anti-cancer strategies.
Gap junction intercellular communications regulates activation of SARM1 and protects against axonal degeneration
Authors: Zhu Wen Jie , Liu Jun , Li Wan Hua , Zhao Zhi Ying , Huang Chongquan , Yang Jian Yuan , Lee Hon Cheung , Zhao Yong Juan
Published: January 2025

Sterile alpha and Toll/interleukin-1 receptor motif containing 1 (SARM1), a nicotinamide adenine dinucleotide (NAD)-utilizing enzyme, mediates axon degeneration (AxD) in various neurodegenerative diseases. It is activated by nicotinamide mononucleotide (NMN) to produce a calcium messenger, cyclic ADP-ribose (cADPR). This activity is blocked by elevated NAD level. Here, we verified this metabolic regulation in somatic HEK-293T cells by overexpressing NMN-adenyltransferase to elevate cellular NAD, which resulted not only in inhibition of their own SARM1 from producing cADPR but, surprisingly, also in the 5–10 neighboring wildtype cells in mixed cultures via connexin (Cx)-43. Direct visualization of gap junction intercellular communication (GJIC) was achieved by incubating cells with a permeant probe, PC11, which is converted by SARM1 into PAD11, a fluorescent NAD analog capable of traversing GJs. Extending the findings to dorsal root ganglion neurons, we further showed that CZ-48, a permeant NMN analog, or axotomy, activated SARM1 and the produced PAD11 was transferred to contacting axons via GJIC. The gap junction involved was identified as Cx36 instead. This neuronal GJIC was demonstrated to be functional, enabling healthy neurons to protect adjacent axotomized axons from degeneration. Inhibition of GJIC in mice by AAV-PHP.eB-mediated knockdown of Cx36 in brain induced neuroinflammation, which in turn activated SARM1 and resulted in axon degeneration as well as behavioral deficits. Our results demonstrate a novel intercellular regulation mechanism of SARM1 and reveal a protective role of healthy tissue against AxD induced by injury or neuroinflammation.
A patient with TPCN2-related hypopigmentation and ocular phenotype
Authors: Courdier Cécile , Michaud Vincent , Diallo Modibo , Plaisant Claudio , Lasseaux Eulalie , Helot Isabelle , Philippe Elodie , Vrielynck Els , Willems Marjolaine , Arveiler Benoit
Published: January 2025

Pigmentation is orchestrated by hundreds of genes involved in cellular functions going from early developmental fate of pigment cells to melanin synthesis. The Two Pore Channel 2 (TPC2) a Ca2+ and Na+ channel acidifies melanosomal pH and thus inhibits pigmentation. A young patient was recently reported with generalized hypopigmentation but uneventful ocular examination, caused by the de novo heterozygous TPCN2 variant c.628C>T;p.Arg210Cys that constitutively activates TPC2. Here we report a young patient with the same de novo variant presenting with generalized hypopigmentation, and ophthalmologic features including low grade retinal hypopigmentation and foveal hypoplasia, photophobia, mild hypermetropia, and astigmatism, which are features of albinism. Skin fragility and episodes of fever with diarrhea and fatigue were also observed. This extends the phenotype of patients with TPCN2 variants, warranting further investigations in patients with alterations of this gene, and raises the question whether TPCN2 might be considered as an albinism gene.
Clade 2.3.4.4b but not historical clade 1 HA replicating RNA vaccine protects against bovine H5N1 challenge in mice
Authors: Hawman David W. , Tipih Thomas , Hodge Eddie , Stone E. Taylor , Warner Nikole , McCarthy Natalie , Granger Brian , Meade-White Kimberly , Leventhal Shanna , Hatzakis Kiara , Park Stephanie , Gaffney Karen , Rosenke Kyle , Erasmus Jesse H. , Feldmann Heinz
Published: January 2025

The ongoing circulation of influenza A H5N1 in the United States has raised concerns of a pandemic caused by highly pathogenic avian influenza. Although the United States has stockpiled and is prepared to produce millions of vaccine doses to address an H5N1 pandemic, currently circulating H5N1 viruses contain multiple mutations within the immunodominant head domain of hemagglutinin (HA) compared to the antigens used in stockpiled vaccines. It is unclear if these stockpiled vaccines will need to be updated to match the contemporary H5N1 strains. Here we show that a replicating RNA vaccine expressing the HA of an H5N1 isolated from a US dairy cow confers complete protection against homologous lethal challenge in mice. A repRNA encoding the HA of a clade 1 H5 from 2004 (A/Vietnam/1203/2004) as utilized by some stockpiled vaccines, confers only partial protection. Our data highlight the utility of nucleic acid vaccines to be rapidly updated to match emergent viruses of concern while demonstrating that contemporary bovine H5N1 viruses can evade immunity elicited by historical HA antigens.
Intelligent in-cell electrophysiology: Reconstructing intracellular action potentials using a physics-informed deep learning model trained on nanoelectrode array recordings
Authors: Rahmani Keivan , Yang Yang , Foster Ethan Paul , Tsai Ching-Ting , Meganathan Dhivya Pushpa , Alvarez Diego D. , Gupta Aayush , Cui Bianxiao , Santoro Francesca , Bloodgood Brenda L. , Yu Rose , Forro Csaba , Jahed Zeinab
Published: January 2025

Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells’ electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput. However, accessing intracellular potentials with NEAs remains challenging. This study presents an AI-supported technique that leverages thousands of synchronous eAP and iAP pairs from stem-cell-derived cardiomyocytes on NEAs. Our analysis revealed strong correlations between specific eAP and iAP features, such as amplitude and spiking velocity, indicating that extracellular signals could be reliable indicators of intracellular activity. We developed a physics-informed deep learning model to reconstruct iAP waveforms from extracellular recordings recorded from NEAs and Microelectrode arrays (MEAs), demonstrating its potential for non-invasive, long-term, high-throughput drug cardiotoxicity assessments. This AI-based model paves the way for future electrophysiology research across various cell types and drug interactions.
Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling
Authors: Kentistou Katherine A. , Lim Brandon E. M. , Kaisinger Lena R. , Steinthorsdottir Valgerdur , Sharp Luke N. , Patel Kashyap A. , Tragante Vinicius , Hawkes Gareth , Gardner Eugene J. , Olafsdottir Thorhildur , Wood Andrew R. , Zhao Yajie , Thorleifsson Gudmar , Day Felix R. , Ozanne Susan E. , Hattersley Andrew T. , O’Rahilly Stephen , Stefansson Kari , Ong Ken K. , Beaumont Robin N. , Perry John R. B. , Freathy Rachel M.
Published: January 2025

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests. We identify 9 genes; 5 with fetal-only effects on birth weight, 1 with maternal-only effects, 3 with both, and observe directionally concordant associations in an independent sample. Four of the genes were previously implicated by GWAS of birth weight. IGF1R and PAPPA2 (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling. PPARG, INHBE and ACVR1C (fetal-acting) are involved in adipose tissue regulation, and the latter two also show associations with favourable adiposity patterns in adults. We highlight the dual role of PPARG (fetal-acting) in adipocyte differentiation and placental angiogenesis. NOS3 (fetal and maternal-acting), NRK (fetal), and ADAMTS8 (maternal-acting) have been implicated in placental function and hypertension. To conclude, our analysis of rare coding variants identifies regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, and further evidence for the role of insulin-like growth factors.
Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa
Authors: Hirt Nell , Manchon Enzo , Chen Qian , Delaroque Clara , Corneau Aurelien , Hemon Patrice , Saker-Delye Safaa , Bataille Pauline , Bouaziz Jean-David , Bourrat Emmanuelle , Hovnanian Alain , Le Buanec Helene , Aoudjit Fawzi , El Costa Hicham , Jabrane-Ferrat Nabila , Al-Daccak Reem
Published: January 2025

Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood. To fill this gap, we apply systems immunology approaches using single-cell high-dimensional techniques to capture the signature of peripheral immune cells and the diversity of metabolic profiles in RDEB adults, sampled outside of any opportunistic infection and active cancer. Our study, demonstrates the particular inflammation and immunity characteristics of RDEB adults, with activated / effector T and dysfunctional natural killer cell signatures, concomitant with an overall pro-inflammatory lipid signature. Artificial intelligence prediction models and principal component analysis stress that RDEB is not solely confined to cutaneous issues but has complex systemic endotypes marked by immune dysregulation and hyperinflammation. By characterising the phenotype-endotype association in RDEB adults, our study lays the groundwork for translational interventions that could by lessening inflammation, alleviate the everlasting suffering of RDEB patients, while awaiting curative genetic therapies.
Vialess heterogeneous skin patch for multimodal monitoring and stimulation
Authors: Lee Hyeokjun , Song Soojeong , Yea Junwoo , Ha Jeongdae , Oh Saehyuck , Jekal Janghwan , Hong Myung Seok , Won Chihyeong , Jung Han Hee , Keum Hohyun , Han Sangyoon , Cho Jeong Ho , Lee Taeyoon , Jang Kyung-In
Published: January 2025

System-level wearable electronics require to be flexible to ensure conformal contact with the skin, but they also need to integrate rigid and bulky functional components to achieve system-level functionality. As one of integration methods, folding integration offers simplified processing and enhanced functionality through rigid-soft region separation, but so far, it has mainly been applied to modality of electrical sensing and stimulation. This paper introduces a vialess heterogeneous skin patch with multi modalities that separates the soft region and strain-robust region through folded structure. Our system includes electrical and optical modalities for hemodynamic and cardiovascular monitoring, and a force-electrically driven micropump for drug delivery. Each modality is demonstrated through on-demand drug delivery, flexible waveguide-based PPG monitoring, and ECG and body movement monitoring. Wireless data transmission and real-time measurement validate the feedback operation for multi-modalities. This engineered closed-loop platform offers the possibility for broad applications, including cardiovascular monitoring and chronic disease management.
White light-emitting electrochemical cells based on metal-free TADF emitters
Authors: Tang Shi , Tsuchiya Youichi , Wang Jia , Adachi Chihaya , Edman Ludvig
Published: January 2025

The attainment of white emission from a light-emitting electrochemical cell (LEC) is important, since it enables illumination and facile color conversion from devices that can be cost-efficient and sustainable. However, a drawback with current white LECs is that they either employ non-sustainable metals as an emitter constituent or are intrinsically efficiency limited by that the emitter only converts singlet excitons to photons. Organic compounds that emit by thermally activated delayed fluorescence (TADF) can address these issues since they can harvest all excitons for light emission while being metal free. Here, we report on the first white LEC based on solely metal-free TADF emitters, as accomplished through careful tuning of the energy-transfer processes and the electrochemically formed doping structure in the single-layer active material. The designed TADF-LEC emits angle-invariant white light (color rendering index = 88) with an external quantum efficiency of 2.1 % at a luminance of 350 cd/m2.
Expression of some circulating microRNAs as predictive biomarkers for prognosis and treatment response in glioblastoma
Authors: Ali Elham , Ahmed Marwa Adel , Shawki May A. , El Arab Lobna R. Ezz , Khalifa Mohamed K. , Swellam Menha
Published: January 2025

Glioblastoma multiforme (GBM) is the most prevalent, treatment-resistant, and fatal form of brain malignancy. It is characterized by genetic heterogeneity, and an infiltrative nature, and GBM treatment is highly challenging. Despite multimodal therapies, clinicians lack efficient prognostic and predictive markers. Therefore, new insights into GBM management are urgently needed to increase the chance of therapeutic success. Circulating miRNAs (miRs) are important regulators of cancer progression and are potentially useful for GBM diagnosis and treatment. This study investigated how miR-29a, miR-106a, and miR-200a affect the prognosis of GBM patients. This study was conducted on 25 GBM patients and 20 healthy volunteers as a control group. The expression levels of target miRs were analyzed pre- and post-treatment using qRT-PCR and evaluated in relation to both clinical GBM criteria and the patient’s survival modes. The diagnostic efficacy of target miRs was assessed using the receiver operating characteristic (ROC) curve. MiRs levels showed significant differences among the enrolled participants. All investigated miRs were significantly elevated in GBM patients with non-frontal lesions. Only miR-200a showed a significant difference in GBM patients older than 60 years with a tumor size ≥ 5 mm. Regarding miR-106a, a significant difference was detected based on the surgical strategy and use of an Eastern Cooperative Oncology Group (ECOG) performance status equal to 2. For miR-29a, a significant upregulation was detected according to the surgical strategy. All post-treatment miRs levels in GBM patients were significantly downregulated. In conclusion, circulating miRs revealed a significant role in predicting GBM patient treatment outcomes providing valuable insights for personalized therapeutic strategies.
Liquid flows induced in a rotating drum with different fill ratios
Authors: Lee Daeun , Lee Jaebeen , Choi Seok Min , Lee Sangtak , Park Hyungmin
Published: January 2025

In the present study, we experimentally investigate the liquid flow induced in a rotating drum (cylindrical tank with a short aspect ratio) aligned horizontally, focusing on the variation in the time-averaged and fluctuating flow structures with different fill ratios. For each fill ratio, controlled by varying the water height, we measure the velocity fields at different cross-sectional planes with particle image velocimetry while varying the rotational speed of the drum. Compared to the condition of a fill ratio of 1.0, in which the liquid inside the drum rotates forming a large-scale (solid-body rotation) organized flow structure, a substantial asymmetric flow structure shows up in partially-filled conditions driven by the imbalance between (i) the momentum diffusion along the radial direction and the centrifugal acceleration, and (ii) the downward (gravitational) flux of the induced flow. In addition to the mean flow structure, we examine the fluctuating velocity fields together with the dynamics of the free surface, and we also briefly discuss the difference between the liquid flow and granular (particle) flow in a partially-filled drum. We think that the present results provide valuable insights on the partially-filled liquid drum toward various engineering applications.
Tomato ripeness and stem recognition based on improved YOLOX
Authors: Li Yanwen , Li Juxia , Luo Lei , Wang Lingqi , Zhi Qingyu
Published: January 2025

To address the challenges of unbalanced class labels with varying maturity levels of tomato fruits and low recognition accuracy for both fruits and stems in intelligent harvesting, we propose the YOLOX-SE-GIoU model for identifying tomato fruit maturity and stems. The SE focus module was incorporated into YOLOX to improve the identification accuracy, addressing the imbalance in the number of tomato fruits and stems. Additionally, we optimized the loss function to GIoU loss to minimize discrepancies across different scales of fruits and stems. The mean average precision (mAP) of the improved YOLOX-SE-GIoU model reaches 92.17%. Compared to YOLOv4, YOLOv5, YOLOv7, and YOLOX models, the improved model shows an improvement of 1.17–22.21%. The average precision (AP) for unbalanced semi-ripe tomatoes increased by 1.68–26.66%, while the AP for stems increased by 3.78–45.03%. Experimental results demonstrate that the YOLOX-SE-GIoU model exhibits superior overall recognition performance for unbalanced and scale-variant samples compared to the original model and other models in the same series. It effectively reduces false and missed detections during tomato harvesting, improving the identification accuracy of tomato fruits and stems. The findings of this work provide a technical foundation for developing advanced fruit harvesting techniques.
Fig abscission as a defense mechanism of Ficus trees against parasitism by non-pollinating fig wasps
Authors: Lin Shang-Yang , Di Giusto Bruno , Bain Anthony
Published: January 2025

How does the fig tree Ficus benguetensis protect its investment in the production of figs and pollinating fig wasps against parasitism from non-pollinating fig wasps? This study documents a previously overlooked defense mechanism: fig abscission—the natural shedding of the fig fruit as a defense mechanism. Our bagging experiments showed that both the absence of pollination and high parasitism levels lead to the abortion of F. benguetensis figs, with positive correlations between parasitism levels, increased abscission rates, and decreased pollinator production. Moreover, we found that high parasitism corresponds to shortened fig development periods until abscission, while medium parasitism levels result in fewer pollinators. Our findings suggest that abscission may function as a resource conservation strategy, as most of the tree’s investment in the figs occurs post-pollination. This study uncovers for the first time the use of fig abscission as a unique defense against non-pollinating fig wasp parasites, broadening our understanding of plant defense mechanisms within mutualistic interactions.
Understanding tinnitus symptom dynamics and clinical improvement through intensive longitudinal data
Authors: Engelke Milena , Simões Jorge Piano , Basso Laura , Wunder Nina , Langguth Berthold , Probst Thomas , Pryss Rüdiger , Schlee Winfried
Published: January 2025

Intensive longitudinal sampling enhances subjective data collection by capturing real-time, dynamic inputs in natural settings, complementing traditional methods. This study evaluates the feasibility of using daily self-reported app data to assess clinical improvement among tinnitus patients undergoing treatment. App data from a multi-center randomized clinical trial were analysed using time-series feature extraction and nested cross-validated ordinal regression with elastic net regulation to predict clinical improvement based on the Clinical Global Impression—Improvement scale (CGI-I). With 50% app compliance (N = 129, 8480 entries), the model demonstrated good fit to the test data (McFadden R2 = 0.82) suggesting its generalizability. Clinical improvement was associated with linear declines in tinnitus-related thoughts, jaw tension, tinnitus loudness, increases in happiness, and variability changes in tinnitus loudness and distress. These findings suggest that daily self-reported data on tinnitus symptoms is sensitive to treatment response and provides insights into specific symptom changes that occur during treatment.
Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA
Authors: Megrian Daniela , Martinez Mariano , Alzari Pedro M. , Wehenkel Anne Marie
Published: January 2025

MoeA, also known as gephyrin in higher eukaryotes, is an enzyme essential for molybdenum cofactor (Moco) biosynthesis and involved in GABA and GlyR receptor clustering at the synapse in animals. We recently discovered that Actinobacteria have a repurposed version of MoeA (Glp) linked to bacterial cell division. Since MoeA exists in all domains of life, our study explores how it gained multifunctionality over time. We use phylogenetic inference and protein structure analyses to study its diversity and evolutionary history. Glp-expressing Bacteria have at least two copies of the gene, and analysis of their putative active sites suggests that Glp lost its enzymatic role. In Archaea, we find an ancestral duplication, with one paralog that may bind tungsten instead of molybdenum. Early eukaryotes acquired MoeA from Bacteria, MogA fused with MoeA in the opisthokont ancestors, and it finally gained roles in anchoring inhibitory neurotransmitters. Our findings highlight MoeA’s functional versatility and repurposing.
Stable centromere association of the yeast histone variant Cse4 requires its essential N-terminal domain
Authors: Popchock Andrew R , Hedouin Sabrine , Mao Yizi , Asbury Charles L , Stergachis Andrew B , Biggins Sue
Published: January 2025

Chromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formation in vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomes in vivo. The extended Cse4 N-terminal tail binds to the chaperone Scm3, and a short essential region called END within the N-terminal tail binds the inner kinetochore complex Okp1/Ame1. To address the roles of these interactions, we utilized single-molecule fluorescence assays to monitor Cse4 during kinetochore assembly. We found that Okp1/Ame1 and Scm3 independently stabilize Cse4 at centromeres via their END interaction. Scm3 and Cse4 stability at the centromere are enhanced by Ipl1/Aurora B phosphorylation of the Cse4 END, identifying a previously unknown role for Ipl1 in ensuring Cse4 stability. Strikingly, a phosphomimetic mutation in the Cse4 END restores Cse4 recruitment in mutants defective in Okp1/Ame1 binding. Together, these data suggest that a key function of the essential Cse4 N-terminus is to ensure Cse4 localization at centromeres.
Nanoparticle-aptamer based cytosensing for the detection of human non-small cell lung cancer cells
Authors: Chen Lianju , Yang Rong , Li Wenwei , Wen Xu , Li Yue , Tang Jiaming , Hu Jing , Kou Qiming
Published: January 2025

This study reports a simple and rapid aptamer-based sensor platform designed for the sensitive and selective detection of human non-small cell lung cancer (NSCLC) cells.
Uncovering the substrate of olefin synthase loading domains in cyanobacteria Picosynechococcus sp. strain PCC 7002
Authors: Yñigez-Gutierrez Audrey E. , Conley Erin , Thomas Michael G. , Pfleger Brian F.
Published: January 2025

We report the heterologous expression of two olefin synthases in PCC 7002 to generate shorter chain α-olefins. Genetic deletions show that membrane-liberated fatty acids are substrates for the chain-length specific loading domain of olefin synthase.
CTF stabilizes truncated octahedral Cu2O nanocrystals and SnO2 nanoparticle assisted photocatalytic CO2 reduction in hybrid ternary Cu2O/SnO2/CTF nanostructures
Authors: Mandal Pranay Chandra , Sherpa Ningma Dorzi , Sarkar Shashanka , Roy Chayan Krishna , Ali Osman , Roy Nitish
Published: January 2025

Schematic representation of covalent triazine framework deposited over Cu2O/SnO2 nanostructures for enhanced photocatalytic CO2 reduction to produce primarily CO and CH4.
Enhanced two-temperature model and its application in comprehensive analysis of femtosecond laser melting of gold, copper and their alloys
Authors: C. D. Aeaby , Ray Aditi
Published: January 2025

This study investigates the melting damage threshold (DT) of three intermetallic alloys of Au and Cu (Au3Cu, AuCu and AuCu3) subjected to single-pulse femtosecond laser irradiation, comparing them with their constituent metals.
Translational nanorobotics breaking through biological membranes
Authors: Ressnerova Alzbeta , Heger Zbynek , Pumera Martin
Published: January 2025

Within the landscape of the human body, biological membranes stand as critical barriers in the successful delivery of therapeutic cargo to the target site. Their crossing is a pivotal criterion for the clinical success of nanorobotics.
Hexagonal In2O3 short nanorods rich in O vacancy-defects toward promoting highly efficient photothermal CO2 reduction into C2H5OH
Authors: Zhao Kai , Han Qiutong , Lu Zhe , Zheng Yubin , Zhou Boye , Chi Haoqiang , Liu Dawei , Wang Lu , Zou Zhigang , Zhou Yong
Published: January 2025

The introduction of oxygen vacancies into hexagonal In2O3 nanorods via H2 treatment has significantly enhanced both the yield and selectivity of C2H5OH in the photothermal reduction of CO2.
Open frameworks in the NaxMny(P2O7)mFn fluoro-pyrophosphates system
Authors: Li Feifan , Li Yaping , Duffort Victor , Mentré Olivier , Minaud Claire , Huang Qingqing , Cheng Xiedong , Cui Rui , Lü Minfeng
Published: January 2025

The framework structure of Na9Mn3(P2O7)4F allowed Na+ ion mobility via a zig-zag chain along the b axis, with a total Na+ ion conductivity of ∼10−5 S cm−1 at 400 °C.
Paddlewheel-type and half-paddlewheel-type diruthenium(ii,ii) complexes with 1,8-naphthyridine-2-carboxylate
Authors: Kataoka Yusuke , Tada Nozomi , Masamori Naoki , Yano Natsumi , Moriyoshi Chikako , Handa Makoto
Published: January 2025

The synthesis, characterization, crystal structures, and electronic properties of 1,8-naphthyridine-2-carboxylate bridged diruthenium(ii,ii) complexes are presented.
A hindered-urea vitrimer: recyclable for circular use and upcyclable for rechargeable batteries
Authors: Wang Yanjun , Wang Yue , Duan Wenjing , Bai Xuang , Liu Pengyuan , Xu Chiwei , Wang Hongqin , Zeng Jinjue , Wang Qi , Zhou Fanyu , Meng Yuhang , Yang Lijun , Li Chenghui , Hu Zheng , Jiang Xiangfen , Jiang Liang , Lei Jingxin , Wang Xuebin
Published: January 2025

A comprehensive approach to the recycling and upcycling of a dynamic cross-linked thermoset commodity plastic, highlighting its contributions both as a recyclable material and as a resource for renewable energy.
The INGENIOUS project: towards understanding air pollution in homes
Authors: Carslaw Nicola , Aghaji Jennifer , Budisulistiorini Sri Hapsari , Carslaw David C. , Chatzidiakou Lia , Cheung Rachael W. , Dillon Terry J. , Edwards Pete , Genes Denisa , Giorio Chiara , Hamilton Jacqueline F. , Ikeda Erika , Jones Roderic L. , Lee James , Lewis Alastair C. , Kumar Ashish , McEachan Rosemary , McFiggans Gordon , Murrels Tim , Pleace Nicholas , Ruangkanit Athina , Shao Yunqi , O'Meara Simon P. , Shaw David R. , Shaw Marvin , Waiblinger Dagmar , Warburton Tom , West Sarah , Wood Chantelle , Yang Tiffany
Published: January 2025

This paper provides an overview of the INGENIOUS (UnderstandING the sourcEs, traNsformations and fates of IndOor air pollUtantS) project, aiming to better understand air pollution in homes.
The interplay of composition and mechanics in the thermodynamics of asymmetric ternary lipid membranes
Authors: Varma Malavika , Deserno Markus
Published: January 2025

Eukaryotic lipid membranes are both compositionally complex and strongly asymmetric. Preferential lipid interactions enable coexistence between two fluid phases and an associated critical point, while bilayer asymmetry leads to leaflet-specific...
Scaling up lignin-based polyols for PU coatings
Authors: Lorenzo Leire , Pitacco Walter , Mattar Nour , Faye Ibrahima , Maestro Belén , Ortiz Pablo
Published: January 2025

Lignin-derived polyols have been synthesized and scaled-up to industrially relevant settings (5L reactors). They have been used as partial replacement of polyols in polyurethane dispersions for wood coatings.
Semiconductor photocatalytic antibacterial materials and their application for bone infection treatment
Authors: He Ruizhong , Gu Yulong , Jia Jiye , Yang Feng , Wu Ping , Feng Pei , Shuai Cijun
Published: January 2025

This review discusses commonly used semiconductor photocatalytic antibacterial materials, methods for improving their photocatalysis performance and their application for bone infection treatment.