bluuebunny/crossref_metadata_2025 huggingface dataset:
Is home where the heat is? comparing residence-based with mobility-based measures of heat exposure in San Diego, California
Authors: Garber Michael D. , Teyton Anaïs , Jankowska Marta M. , Carrasco-Escobar Gabriel , Rojas-Rueda David , Barja-Ingaruca Antony , Benmarhnia Tarik
Published: September 2024

Background

Heat can vary spatially within an urban area. Individual-level heat exposure may thus depend on an individual’s day-to-day travel patterns (also called mobility patterns or activity space), yet heat exposure is commonly measured based on place of residence.

Objective

In this study, we compared measures assessing exposure to two heat indicators using place of residence with those defined considering participants’ day-to-day mobility patterns.

Methods

Participants (n = 599; aged 35-80 years old [mean =59 years]) from San Diego County, California wore a GPS device to measure their day-to-day travel over 14-day intervals between 2014-10-17 and 2017-10-06. We measured exposure to two heat indicators (land-surface temperature [LST] and air temperature) using an approach considering their mobility patterns and an approach considering only their place of residence. We compared participant mean and maximum exposure values from each method for each indicator.

Results

The overall mobility-based mean LST exposure (34.7 °C) was almost equivalent to the corresponding residence-based mean (34.8 °C; mean difference in means = −0.09 °C). Similarly, the mean difference between the overall mobility-based mean air temperature exposure (19.2 °C) and the corresponding residence-based mean (19.2 °C) was negligible (−0.02 °C). Meaningful differences emerged, however, when comparing maximums, particularly for LST. The mean mobility-based maximum LST was 40.3 °C compared with a mean residence-based maximum of 35.8 °C, a difference of 4.51 °C. The difference in maximums was considerably smaller for air temperature (mean = 0.40 °C; SD = 1.41 °C) but nevertheless greater than the corresponding difference in means.

Impact

As the climate warms, assessment of heat exposure both at and away from home is important for understanding its health impacts. We compared two approaches to estimate exposure to two heat measures (land surface temperature and air temperature). The first approach only considered exposure at home, and the second considered day-to-day travel. Considering the average exposure estimated by each approach, the results were almost identical. Considering the maximum exposure experienced (specific definition in text), the differences between the two approaches were more considerable, especially for land surface temperature.
Fractionated photoimmunotherapy stimulates an anti-tumour immune response: an integrated mathematical and in vitro study
Authors: Zahid Mohammad U. , Waguespack Matthew , Harman Rebecca C. , Kercher Eric M. , Nath Shubhankar , Hasan Tayyaba , Rizvi Imran , Spring Bryan Q. , Enderling Heiko
Published: September 2024

Background

Advanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery.

Methods

We use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction. The model outputs were used to calculate how photoimmunotherapy could be utilised for tumour control.

Results

In vitro measurements of PIT dose responses revealed that although low light doses (<10 J/cm2) lead to limited tumour cell killing they also increased proliferation of anti-tumour immune effector cells. Model simulations demonstrated that breaking up a larger light dose into multiple lower dose fractions (vis-à-vis fractionated radiotherapy) could be utilised to effect tumour control via stimulation of an anti-tumour immune response.

Conclusions

There is promise for applying fractionated PIT in the setting of EOC. However, recommending specific fractionated PIT dosimetry and timing will require appropriate model calibration on tumour-immune interaction data in human patients and subsequent validation of model predictions in prospective clinical trials.
Specific features of ß-catenin-mutated hepatocellular carcinomas
Authors: Dantzer Camille , Dif Lydia , Vaché Justine , Basbous Sara , Billottet Clotilde , Moreau Violaine
Published: September 2024

CTNNB1, encoding the ß-catenin protein, is a key oncogene contributing to liver carcinogenesis. Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer in adult, representing the third leading cause of cancer-related death. Aberrant activation of the Wnt/ß-catenin pathway, mainly due to mutations of the CTNNB1 gene, is observed in a significant subset of HCC. In this review, we first resume the major recent advances in HCC classification with a focus on CTNNB1-mutated HCC subclass. We present the regulatory mechanisms involved in β-catenin stabilisation, transcriptional activity and binding to partner proteins. We then describe specific phenotypic characteristics of CTNNB1-mutated HCC thanks to their unique gene expression patterns. CTNNB1-mutated HCC constitute a full-fledged subclass of HCC with distinct pathological features such as well-differentiated cells with low proliferation rate, association to cholestasis, metabolic alterations, immune exclusion and invasion. Finally, we discuss therapeutic approaches to target ß-catenin-mutated liver tumours and innovative perspectives for future drug developments.
Intracellular zinc protects tumours from T cell-mediated cytotoxicity
Authors: Lelliott Emily J. , Naddaf Jonathan , Ganio Katherine , Michie Jessica , Wang Shelly , Liu Lin , Silke Natasha , Ahn Antonio , Ramsbottom Kelly M. , Brennan Amelia J. , Freeman Andrew J. , Goel Shom , Vervoort Stephin J. , Kearney Conor J. , Beavis Paul A. , McDevitt Christopher A. , Silke John , Oliaro Jane
Published: September 2024

Tumour immune evasion presents a significant challenge to the effectiveness of cancer immunotherapies. Recent advances in high-throughput screening techniques have uncovered that loss of antigen presentation and cytokine signalling pathways are central mechanisms by which tumours evade T cell immunity. To uncover additional vulnerabilities in tumour cells beyond the well-recognized antigen presentation pathway, we conducted a genome-wide CRISPR/Cas9 screen to identify genes that mediate resistance to chimeric-antigen receptor (CAR)-T cells, which function independently of classical antigen presentation. Our study revealed that loss of core-binding factor subunit beta (CBFβ) enhances tumour cell resistance to T cell killing, mediated through T cell-derived TNF. Mechanistically, RNA-sequencing and elemental analyses revealed that deletion of CBFβ disrupts numerous pathways including those involved in zinc homoeostasis. Moreover, we demonstrated that modulation of cellular zinc, achieved by supplementation or chelation, significantly altered tumour cell susceptibility to TNF by regulating the levels of inhibitor of apoptosis proteins. Consistent with this, treatment of tumour cells with a membrane-permeable zinc chelator had no impact on tumour cell viability alone, but significantly increased tumour cell lysis by CD8+ T cells in a TNF-dependent but perforin-independent manner. These results underscore the crucial role of intracellular zinc in regulating tumour cell susceptibility to T cell-mediated killing, revealing a novel vulnerability in tumour cells that might be exploited for the development of future cancer immunotherapeutics.
N6-methyladenosine (m6A) writer METTL5 represses the ferroptosis and antitumor immunity of gastric cancer
Authors: Li Xinli , Yang Guoqiang , Ma Lihong , Tang Bingxi , Tao Tao
Published: September 2024

Emerging evidence has shown that ferroptosis and antitumor immunity response of T lymphocytes play critical roles in multiple malignancies, including gastric cancer (GC). Here, the present research aims to reveal the function of novel N6-methyladenosine (m6A) methyltransferase METTL5 on GC immune microenvironment. Clinically, elevated METTL5 was negatively correlated to the prognosis of GC patients. METTL5 high-expression repressed the Fe2+ accumulation and ferroptosis to promote the GC immune evasion escaping from activated PBMCs’ killing effect. Mechanistically, upregulation of METTL5 promoted NRF2 mRNA stability, thereby inactivating the ferroptosis and repressing PBMCs’ cells antitumor immunity. One valuable finding is that ferroptosis inhibitor (Ferrostatin-1, Fer-1) could reduce the antitumor immunity of cocultured PBMCs. In other words, the increase of ferroptosis might contribute to the anti-tumor efficacy of immunotherapy. Further study revealed that m6A reader IGF2BP1 mediated the stability of NRF2 mRNA via METTL5/m6A/NRF2 axis. Collectively, these results demonstrate that METTL5 functions as an oncogene in GC immune microenvironment, and highlights a critical role in T lymphocytes’ antitumor immunity.
Sub-threshold neuronal activity and the dynamical regime of cerebral cortex
Authors: Amsalem Oren , Inagaki Hidehiko , Yu Jianing , Svoboda Karel , Darshan Ran
Published: September 2024

Cortical neurons exhibit temporally irregular spiking patterns and heterogeneous firing rates. These features arise in model circuits operating in a ‘fluctuation-driven regime’, in which fluctuations in membrane potentials emerge from the network dynamics. However, it is still debated whether the cortex operates in such a regime. We evaluated the fluctuation-driven hypothesis by analyzing spiking and sub-threshold membrane potentials of neurons in the frontal cortex of mice performing a decision-making task. We showed that while standard fluctuation-driven models successfully account for spiking statistics, they fall short in capturing the heterogeneity in sub-threshold activity. This limitation is an inevitable outcome of bombarding single-compartment neurons with a large number of pre-synaptic inputs, thereby clamping the voltage of all neurons to more or less the same average voltage. To address this, we effectively incorporated dendritic morphology into the standard models. Inclusion of dendritic morphology in the neuronal models increased neuronal selectivity and reduced error trials, suggesting a functional role for dendrites during decision-making. Our work suggests that, during decision-making, cortical neurons in high-order cortical areas operate in a fluctuation-driven regime.
Automated design of multi-target ligands by generative deep learning
Authors: Isigkeit Laura , Hörmann Tim , Schallmayer Espen , Scholz Katharina , Lillich Felix F. , Ehrler Johanna H. M. , Hufnagel Benedikt , Büchner Jasmin , Marschner Julian A. , Pabel Jörg , Proschak Ewgenij , Merk Daniel
Published: September 2024

Generative deep learning models enable data-driven de novo design of molecules with tailored features. Chemical language models (CLM) trained on string representations of molecules such as SMILES have been successfully employed to design new chemical entities with experimentally confirmed activity on intended targets. Here, we probe the application of CLM to generate multi-target ligands for designed polypharmacology. We capitalize on the ability of CLM to learn from small fine-tuning sets of molecules and successfully bias the model towards designing drug-like molecules with similarity to known ligands of target pairs of interest. Designs obtained from CLM after pooled fine-tuning are predicted active on both proteins of interest and comprise pharmacophore elements of ligands for both targets in one molecule. Synthesis and testing of twelve computationally favored CLM designs for six target pairs reveals modulation of at least one intended protein by all selected designs with up to double-digit nanomolar potency and confirms seven compounds as designed dual ligands. These results corroborate CLM for multi-target de novo design as source of innovation in drug discovery.
Factor XII signaling via uPAR-integrin β1 axis promotes tubular senescence in diabetic kidney disease
Authors: Elwakiel Ahmed , Gupta Dheerendra , Rana Rajiv , Manoharan Jayakumar , Al-Dabet Moh’d Mohanad , Ambreen Saira , Fatima Sameen , Zimmermann Silke , Mathew Akash , Li Zhiyang , Singh Kunal , Gupta Anubhuti , Pal Surinder , Sulaj Alba , Kopf Stefan , Schwab Constantin , Baber Ronny , Geffers Robert , Götze Tom , Alo Bekas , Lamers Christina , Kluge Paul , Kuenze Georg , Kohli Shrey , Renné Thomas , Shahzad Khurrum , Isermann Berend
Published: September 2024

Coagulation factor XII (FXII) conveys various functions as an active protease that promotes thrombosis and inflammation, and as a zymogen via surface receptors like urokinase-type plasminogen activator receptor (uPAR). While plasma levels of FXII are increased in diabetes mellitus and diabetic kidney disease (DKD), a pathogenic role of FXII in DKD remains unknown. Here we show that FXII is locally expressed in kidney tubular cells and that urinary FXII correlates with kidney dysfunction in DKD patients. F12-deficient mice (F12-/-) are protected from hyperglycemia-induced kidney injury. Mechanistically, FXII interacts with uPAR on tubular cells promoting integrin β1-dependent signaling. This signaling axis induces oxidative stress, persistent DNA damage and senescence. Blocking uPAR or integrin β1 ameliorates FXII-induced tubular cell injury. Our findings demonstrate that FXII-uPAR-integrin β1 signaling on tubular cells drives senescence. These findings imply previously undescribed diagnostic and therapeutic approaches to detect or treat DKD and possibly other senescence-associated diseases.
Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets
Authors: Su Tsu-Yi , Hauenstein Julia , Somuncular Ece , Dumral Özge , Leonard Elory , Gustafsson Charlotte , Tzortzis Efthymios , Forlani Aurora , Johansson Anne-Sofie , Qian Hong , Månsson Robert , Luc Sidinh
Published: September 2024

Age is a risk factor for hematologic malignancies. Attributes of the aging hematopoietic system include increased myelopoiesis, impaired adaptive immunity, and a functional decline of the hematopoietic stem cells (HSCs) that maintain hematopoiesis. Changes in the composition of diverse HSC subsets have been suggested to be responsible for age-related alterations, however, the underlying regulatory mechanisms are incompletely understood in the context of HSC heterogeneity. In this study, we investigated how distinct HSC subsets, separated by CD49b, functionally and molecularly change their behavior with age. We demonstrate that the lineage differentiation of both lymphoid-biased and myeloid-biased HSC subsets progressively shifts to a higher myeloid cellular output during aging. In parallel, we show that HSCs selectively undergo age-dependent gene expression and gene regulatory changes in a progressive manner, which is initiated already in the juvenile stage. Overall, our studies suggest that aging intrinsically alters both cellular and molecular properties of HSCs.
Observing the two-dimensional Bose glass in an optical quasicrystal
Authors: Yu Jr-Chiun , Bhave Shaurya , Reeve Lee , Song Bo , Schneider Ulrich
Published: September 2024

The presence of disorder substantially influences the behaviour of physical systems. It can give rise to slow or glassy dynamics, or to a complete suppression of transport as in Anderson insulators1, where normally extended wavefunctions such as light fields or electronic Bloch waves become exponentially localized. The combined effect of disorder and interactions is central to the richness of condensed-matter physics2. In bosonic systems, it can also lead to additional quantum states such as the Bose glass3,4—an insulating but compressible state without long-range phase coherence that emerges in disordered bosonic systems and is distinct from the well-known superfluid and Mott insulating ground states of interacting bosons. Here we report the experimental realization of the two-dimensional Bose glass using ultracold atoms in an eight-fold symmetric quasicrystalline optical lattice5. By probing the coherence properties of the system, we observe a Bose-glass-to-superfluid transition and map out the phase diagram in the weakly interacting regime. We furthermore demonstrate that it is not possible to adiabatically traverse the Bose glass on typical experimental timescales by examining the capability to restore coherence and discuss the connection to the expected non-ergodicity of the Bose glass. Our observations are in good agreement with recent quantum Monte Carlo predictions6 and pave the way for experimentally testing the connection between the Bose glass, many-body localization and glassy dynamics more generally7,8.
Ancient Rapanui genomes reveal resilience and pre-European contact with the Americas
Authors: Moreno-Mayar J. Víctor , Sousa da Mota Bárbara , Higham Tom , Klemm Signe , Gorman Edmunds Moana , Stenderup Jesper , Iraeta-Orbegozo Miren , Laborde Véronique , Heyer Evelyne , Torres Hochstetter Francisco , Friess Martin , Allentoft Morten E. , Schroeder Hannes , Delaneau Olivier , Malaspinas Anna-Sapfo
Published: September 2024

Rapa Nui (also known as Easter Island) is one of the most isolated inhabited places in the world. It has captured the imagination of many owing to its archaeological record, which includes iconic megalithic statues called moai1. Two prominent contentions have arisen from the extensive study of Rapa Nui. First, the history of the Rapanui has been presented as a warning tale of resource overexploitation that would have culminated in a major population collapse—the ‘ecocide’ theory2–4. Second, the possibility of trans-Pacific voyages to the Americas pre-dating European contact is still debated5–7. Here, to address these questions, we reconstructed the genomic history of the Rapanui on the basis of 15 ancient Rapanui individuals that we radiocarbon dated (1670–1950 ce) and whole-genome sequenced (0.4–25.6×). We find that these individuals are Polynesian in origin and most closely related to present-day Rapanui, a finding that will contribute to repatriation efforts. Through effective population size reconstructions and extensive population genetics simulations, we reject a scenario involving a severe population bottleneck during the 1600s, as proposed by the ecocide theory. Furthermore, the ancient and present-day Rapanui carry similar proportions of Native American admixture (about 10%). Using a Bayesian approach integrating genetic and radiocarbon dates, we estimate that this admixture event occurred about 1250–1430 ce.
Cooling positronium to ultralow velocities with a chirped laser pulse train
Authors: Shu K. , Tajima Y. , Uozumi R. , Miyamoto N. , Shiraishi S. , Kobayashi T. , Ishida A. , Yamada K. , Gladen R. W. , Namba T. , Asai S. , Wada K. , Mochizuki I. , Hyodo T. , Ito K. , Michishio K. , O’Rourke B. E. , Oshima N. , Yoshioka K.
Published: September 2024

When laser radiation is skilfully applied, atoms and molecules can be cooled1–3, allowing the precise measurements and control of quantum systems. This is essential for the fundamental studies of physics as well as practical applications such as precision spectroscopy4–7, ultracold gases with quantum statistical properties8–10 and quantum computing. In laser cooling, atoms are slowed to otherwise unattainable velocities through repeated cycles of laser photon absorption and spontaneous emission in random directions. Simple systems can serve as rigorous testing grounds for fundamental physics—one such case is the purely leptonic positronium11,12, an exotic atom comprising an electron and its antiparticle, the positron. Laser cooling of positronium, however, has hitherto remained unrealized. Here we demonstrate the one-dimensional laser cooling of positronium. An innovative laser system emitting a train of broadband pulses with successively increasing central frequencies was used to overcome major challenges posed by the short positronium lifetime and the effects of Doppler broadening and recoil. One-dimensional chirp cooling was used to cool a portion of the dilute positronium gas to a velocity distribution of approximately 1 K in 100 ns. A major advancement in the field of low-temperature fundamental physics of antimatter, this study on a purely leptonic system complements work on antihydrogen13, a hadron-containing exotic atom. The successful application of laser cooling to positronium affords unique opportunities to rigorously test bound-state quantum electrodynamics and to potentially realize Bose–Einstein condensation14–18 in this matter–antimatter system.
Axon-like active signal transmission
Authors: Brown Timothy D. , Zhang Alan , Nitta Frederick U. , Grant Elliot D. , Chong Jenny L. , Zhu Jacklyn , Radhakrishnan Sritharini , Islam Mahnaz , Fuller Elliot J. , Talin A. Alec , Shamberger Patrick J. , Pop Eric , Williams R. Stanley , Kumar Suhas
Published: September 2024

Any electrical signal propagating in a metallic conductor loses amplitude due to the natural resistance of the metal. Compensating for such losses presently requires repeatedly breaking the conductor and interposing amplifiers that consume and regenerate the signal. This century-old primitive severely constrains the design and performance of modern interconnect-dense chips1. Here we present a fundamentally different primitive based on semi-stable edge of chaos (EOC)2,3, a long-theorized but experimentally elusive regime that underlies active (self-amplifying) transmission in biological axons4,5. By electrically accessing the spin crossover in LaCoO3, we isolate semi-stable EOC, characterized by small-signal negative resistance and amplification of perturbations6,7. In a metallic line atop a medium biased at EOC, a signal input at one end exits the other end amplified, without passing through a separate amplifying component. While superficially resembling superconductivity, active transmission offers controllably amplified time-varying small-signal propagation at normal temperature and pressure, but requires an electrically energized EOC medium. Operando thermal mapping reveals the mechanism of amplification—bias energy of the EOC medium, instead of fully dissipating as heat, is partly used to amplify signals in the metallic line, thereby enabling spatially continuous active transmission, which could transform the design and performance of complex electronic chips.
Enriching productive mutational paths accelerates enzyme evolution
Authors: Patsch David , Schwander Thomas , Voss Moritz , Schaub Daniela , Hüppi Sean , Eichenberger Michael , Stockinger Peter , Schelbert Lisa , Giger Sandro , Peccati Francesca , Jiménez-Osés Gonzalo , Mutný Mojmír , Krause Andreas , Bornscheuer Uwe T. , Hilvert Donald , Buller Rebecca M.
Published: September 2024

Darwinian evolution has given rise to all the enzymes that enable life on Earth. Mimicking natural selection, scientists have learned to tailor these biocatalysts through recursive cycles of mutation, selection and amplification, often relying on screening large protein libraries to productively modulate the complex interplay between protein structure, dynamics and function. Here we show that by removing destabilizing mutations at the library design stage and taking advantage of recent advances in gene synthesis, we can accelerate the evolution of a computationally designed enzyme. In only five rounds of evolution, we generated a Kemp eliminase—an enzymatic model system for proton transfer from carbon—that accelerates the proton abstraction step >108-fold over the uncatalyzed reaction. Recombining the resulting variant with a previously evolved Kemp eliminase HG3.17, which exhibits similar activity but differs by 29 substitutions, allowed us to chart the topography of the designer enzyme’s fitness landscape, highlighting that a given protein scaffold can accommodate several, equally viable solutions to a specific catalytic problem.
FOS mapping reveals two complementary circuits for spatial navigation in mouse
Authors: Balcerek Edyta , Włodkowska Urszula , Czajkowski Rafał
Published: September 2024

Here, we show that during continuous navigation in a dynamic external environment, mice are capable of developing a foraging strategy based exclusively on changing distal (allothetic) information and that this process may involve two alternative components of the spatial memory circuit: the hippocampus and retrosplenial cortex. To this end, we designed a novel custom apparatus and implemented a behavioral protocol based on the figure-8-maze paradigm with two goal locations associated with distinct contexts. We assessed whether mice are able to learn to retrieve a sequence of rewards guided exclusively by the changing context. We found out that training mice in the apparatus leads to change in strategy from the internal tendency to alternate into navigation based exclusively on visual information. This effect could be achieved using two different training protocols: prolonged alternation training, or a flexible protocol with unpredictable turn succession. Based on the c-FOS mapping we also provide evidence of opposing levels of engagement of hippocampus and retrosplenial cortex after training of mice in these two different regimens. This supports the hypothesis of the existence of parallel circuits guiding spatial navigation, one based on the well-described hippocampal representation, and another, RSC-dependent.
Haplotype variability in mitochondrial rRNA predisposes to metabolic syndrome
Authors: Pecina Petr , Čunátová Kristýna , Kaplanová Vilma , Puertas-Frias Guillermo , Šilhavý Jan , Tauchmannová Kateřina , Vrbacký Marek , Čajka Tomáš , Gahura Ondřej , Hlaváčková Markéta , Stránecký Viktor , Kmoch Stanislav , Pravenec Michal , Houštěk Josef , Mráček Tomáš , Pecinová Alena
Published: September 2024

Metabolic syndrome is a growing concern in developed societies and due to its polygenic nature, the genetic component is only slowly being elucidated. Common mitochondrial DNA sequence variants have been associated with symptoms of metabolic syndrome and may, therefore, be relevant players in the genetics of metabolic syndrome. We investigate the effect of mitochondrial sequence variation on the metabolic phenotype in conplastic rat strains with identical nuclear but unique mitochondrial genomes, challenged by high-fat diet. We find that the variation in mitochondrial rRNA sequence represents risk factor in the insulin resistance development, which is associated with diacylglycerols accumulation, induced by tissue-specific reduction of the oxidative capacity. These metabolic perturbations stem from the 12S rRNA sequence variation affecting mitochondrial ribosome assembly and translation. Our work demonstrates that physiological variation in mitochondrial rRNA might represent a relevant underlying factor in the progression of metabolic syndrome.
High-performance single-crystalline In2O3 field effect transistor toward three-dimensional large-scale integration circuits
Authors: Yamazaki Shunpei , Isaka Fumito , Ohno Toshikazu , Egi Yuji , Tezuka Sachiaki , Kurata Motomu , Sawai Hiromi , Motoyoshi Ryosuke , Asano Etsuko , Saito Satoru , Onuki Tatsuya , Matsuzaki Takanori , Tajima Michio
Published: September 2024

Formation of a single crystalline oxide semiconductor on an insulating film as a channel material capable of three-dimensional (3D) stacking would enable 3D very-large-scale integration circuits. This study presents a technique for forming single-crystalline In2O3 having no grain boundaries in a channel formation region on an insulating film using the (001) plane of c-axis-aligned crystalline indium gallium zinc oxide as a seed. Vertical field-effect transistors using the single-crystalline In2O3 had an off-state current of 10−21 A μm−1 and electrical characteristics were improved compared with those using non-single-crystalline In2O3: the subthreshold slope was improved from 95.7 to 86.7 mV dec.−1, the threshold voltage showing normally-off characteristics (0.10 V) was obtained, the threshold voltage standard deviation was improved from 0.11 to 0.05 V, the on-state current was improved from 22.5 to 28.8 μA, and a 17-digit on/off ratio was obtained at 27 °C.
Indirect stratospheric moisture increase after a Pinatubo-magnitude eruption can be comparable to direct increase after 2022 Hunga
Authors: Kroll Clarissa A. , Schmidt Anja
Published: September 2024

The 2022 Hunga eruptions injected an observationally unprecedented amount of moisture directly into the stratosphere. However, stratospheric moisture can also be indirectly increased following a volcanic eruption, when heating from volcanic sulfate aerosol raises the tropical cold-point temperatures. In this work, we demonstrate that a 1 K increase in tropical cold-point temperatures can lead to indirect moisture increases in the stratosphere of comparable or even larger magnitude than observed for the direct injections during the Hunga eruptions. We base our reasoning on first-principle thermodynamic arguments combined with climate model and reanalysis output as well as observational data. We argue that following the next large-magnitude explosive eruption in the tropics, the strength of indirect increases in stratospheric moisture should be quantified using current measurement techniques.
Prospective multicenter study using artificial intelligence to improve dermoscopic melanoma diagnosis in patient care
Authors: Heinlein Lukas , Maron Roman C. , Hekler Achim , Haggenmüller Sarah , Wies Christoph , Utikal Jochen S. , Meier Friedegund , Hobelsberger Sarah , Gellrich Frank F. , Sergon Mildred , Hauschild Axel , French Lars E. , Heinzerling Lucie , Schlager Justin G. , Ghoreschi Kamran , Schlaak Max , Hilke Franz J. , Poch Gabriela , Korsing Sören , Berking Carola , Heppt Markus V. , Erdmann Michael , Haferkamp Sebastian , Drexler Konstantin , Schadendorf Dirk , Sondermann Wiebke , Goebeler Matthias , Schilling Bastian , Krieghoff-Henning Eva , Brinker Titus J.
Published: September 2024

Background

Early detection of melanoma, a potentially lethal type of skin cancer with high prevalence worldwide, improves patient prognosis. In retrospective studies, artificial intelligence (AI) has proven to be helpful for enhancing melanoma detection. However, there are few prospective studies confirming these promising results. Existing studies are limited by low sample sizes, too homogenous datasets, or lack of inclusion of rare melanoma subtypes, preventing a fair and thorough evaluation of AI and its generalizability, a crucial aspect for its application in the clinical setting.

Methods

Therefore, we assessed “All Data are Ext” (ADAE), an established open-source ensemble algorithm for detecting melanomas, by comparing its diagnostic accuracy to that of dermatologists on a prospectively collected, external, heterogeneous test set comprising eight distinct hospitals, four different camera setups, rare melanoma subtypes, and special anatomical sites. We advanced the algorithm with real test-time augmentation (R-TTA, i.e., providing real photographs of lesions taken from multiple angles and averaging the predictions), and evaluated its generalization capabilities.

Results

Overall, the AI shows higher balanced accuracy than dermatologists (0.798, 95% confidence interval (CI) 0.779–0.814 vs. 0.781, 95% CI 0.760–0.802; p = 4.0e−145), obtaining a higher sensitivity (0.921, 95% CI 0.900–0.942 vs. 0.734, 95% CI 0.701–0.770; p = 3.3e−165) at the cost of a lower specificity (0.673, 95% CI 0.641–0.702 vs. 0.828, 95% CI 0.804–0.852; p = 3.3e−165).

Conclusion

As the algorithm exhibits a significant performance advantage on our heterogeneous dataset exclusively comprising melanoma-suspicious lesions, AI may offer the potential to support dermatologists, particularly in diagnosing challenging cases.
Adverse cardiovascular and kidney outcomes in people with SARS-CoV-2 treated with SGLT2 inhibitors
Authors: Choi Taeyoung , Xie Yan , Al-Aly Ziyad
Published: September 2024

Background

Whether use of SGLT2 inhibitors reduces the risk of cardiovascular and kidney events in people who contracted SARS-CoV-2 infection is not clear.

Methods

We used the healthcare databases of the United States Department of Veterans Affairs to build a cohort of 107,776 participants on antihyperglycemic therapy and had SARS-CoV-2 infection between March 01, 2020 and June 10, 2023. Within them, 11,588 used SGLT2 inhibitors and 96,188 used other antihyperglycemics. We examined the risks of major adverse cardiovascular events (MACE)—a composite of death, myocardial infarction and stroke, and major adverse kidney events (MAKE)—a composite of death, eGFR decline > 50%, and end stage kidney disease after balancing baseline characteristics between groups through inverse probability weighting. Survival analyses were conducted to generate hazard ratio (HR) and absolute risk reduction per 100 person-years (ARR).

Results

Over a median follow up of 1.57 (IQR: 1.05–2.49) years, compared to the control group, SGLT2 inhibitors use is associated with reduced risk of MACE (HR 0.82 (0.77, 0.88), ARR 1.73 (1.21, 2.25)) and reduced risk of MAKE (HR 0.75 (0.71, 0.80), ARR 2.62 (2.13, 3.11)). Compared to the control group, SGLT2 inhibitors use is associated with reduced risk of the secondary outcomes of hospitalization (HR 0.94 (0.90, 0.98), ARR 1.06 (1.36, 1.76)), anemia (HR 0.71 (0.65, 0.76), ARR 2.43 (1.95, 2.90)), and acute kidney injury (HR 0.84 (0.79, 0.89), ARR 1.86 (1.29, 2.42)).

Conclusions

Among people with SARS-CoV-2 infection on antihyperglycemic therapy, compared to those on other antihyperglycemics, those on SGLT2 inhibitors have less risk of adverse cardiovascular and kidney outcomes.
Niche-dependent forest and savanna fragmentation in Tropical South America during the Last Glacial Maximum
Authors: Kelley Douglas I. , Sato Hiromitsu , Ecker Michaela , Burton Chantelle A. , Capurucho João M. G. , Bates John
Published: September 2024

The refugia hypothesis, often used to explain Amazonia’s high biodiversity, initially received ample support but has garnered increasing criticism over time. Palynological, phylogenetic, and vegetation model reconstruction studies have been invoked to support the opposing arguments of extensive fragmentation versus a stable Amazonian Forest during Pleistocene glacial maxima. Here, we test the past existence of forest fragments and savanna connectivity by bias-correcting vegetation distributions from a Dynamic Vegetation Model (DVM) driven by paleoclimate simulations for South America during the Last Glacial Maximum (LGM). We find evidence for fragmented forests akin to refugia with extensive tropical humid forests to the west and forest islands in central/southern Amazonia. Drier ecosystems of Northern Llanos, Caatinga and Cerrado may have merged into continuous savanna/grasslands that dominated the continent. However, our reconstructions suggest taller, dense woodland/tropical savanna vegetation and areas of similar bioclimate connected disparate forest fragments across Amazonia. This ecotonal biome may have acted as a corridor for generalist forest and savanna species, creating connectivity that allows for range expansion during glacial periods. Simultaneously, it could have served as a barrier for specialists, inducing diversification through the formation of ‘semi-refugia’.
Room temperature C–O bond cleavage of vinyl cyclic synthons via a metallaphotoredox approach
Authors: Keshri Santosh Kumar , Kapur Manmohan
Published: September 2024

Herein, we report visible-light induced C–O bond cleavage of vinyl-appended cyclic synthons via a Co(ii)-photoredox dual catalytic approach operating at room temperature.
Recent advances in sugar-based AIE luminogens and their applications in sensing and imaging
Authors: Liu Guang-jian , Zhang Jing-dong , Zhou Wei , Feng Gai-li , Xing Guo-wen
Published: September 2024

This feature article summarizes the recent development of sugar-based aggregation-induced emission luminogens as excellent chemosensors and bioprobes based on the specific interaction or reaction with analytes.
Metal-free small molecule-based piezoelectric energy harvesters
Authors: Sahoo Supriya , Deka Nilotpal , Panday Rishukumar , Boomishankar Ramamoorthy
Published: September 2024

The recent progress in the design of metal-free small-molecule derived piezoelectric materials and their utilization as all-organic piezoelectric energy harvesters has been discussed in this feature article.
Spectrometric monitoring of CO2 electrolysis on a molecularly modified copper surface
Authors: Kuzume Akiyoshi , Kume Shoko
Published: September 2024

Recent works on in situ monitoring of organically modified copper with vibrational spectroscopy have revealed a wide scale of effect modifiers can cause on CO2 electrolysis performance, which can also help design active organic/copper interface.
Oscillations in delayed positive feedback systems
Authors: Ryzowicz Christopher J. , Bertram Richard , Karamched Bhargav R.
Published: September 2024

Delayed positive feedback can generate oscillations in biochemical systems that may outlast the lifespan of the species in which they occur. This finding challenges the current norm of attributing oscillatory behavior to delayed negative feedback.
Nuclear quantum effects on the intramolecular hydrogen bonds in biuret and biguanide
Authors: Nishikawa Kotomi , Tanaka Hikaru , Kuwahata Kazuaki , Tachikawa Masanori , Udagawa Taro
Published: September 2024

Path integral molecular dynamics simulations were used to investigate intramolecular hydrogen bonds in biuret and biguanide. Results indicate that π-electrons in the framework are delocalized, regardless of the ease of intramolecular proton transfer.
Deformation-induced phase separation of active vesicles
Authors: Jin Yi-yang , Jin Yan , Shi Zi-xuan , Tian Wen-de , Zhang Tian-hui , Chen Kang
Published: September 2024

Transition from a homogeneous gas state to a state of gas–liquid or gas–solid coexistence as the active vesicles become harder.
Salt-bridge mediated conformational dynamics in the figure-of-eight knotted ketol acid reductoisomerase (KARI)
Authors: Thakuria Sanjib , Paul Sandip
Published: September 2024

Denaturation of the figure-of-eight knotted monomeric KARI and conformational analyses of the knotted topology provide evidence that salt bridges play a crucial role in maintaining the stability and integrity of the knot.
Optimisation of dynamic nuclear polarisation using “off-the-shelf” Gd(iii)-based polarising agents
Authors: Cheney Daniel J. , Cerreia Vioglio Paolo , Brookfield Adam , Blanc Frédéric
Published: September 2024

A range of simple gadolinium salts has been demonstrated to be suitable for use as polarising agents for dynamic nuclear polarisation. The gadolinium concentrations providing the optimum signal enhancements were also identified.
Supramolecular gels: a versatile crystallization toolbox
Authors: Contreras-Montoya Rafael , Álvarez de Cienfuegos Luis , Gavira José A. , Steed Jonathan W.
Published: September 2024

Supramolecular gels are unique materials formed through the self-assembly of low molecular weight gelators (LMWGs). Their versatility has allowed the expansion of gel crystallization processes, giving a new impetus to this field.
Sulfonic acid-modified MOFs as heterogeneous bifunctional catalysts for ethylene oligomerization at room temperature without cocatalysts
Authors: Ning Yao , Yang Yuqi , Shan Dongming , Mei Shuxing , Yan Yibai , Ding Linjie , Zhang Ying
Published: September 2024

Ethylene oligomerization plays an important role in industrial production.
High temperature reductive treatment promotes thermal stability of Pt/hexaaluminate catalysts for CO and C3H8 oxidation
Authors: Xu Yumeng , Chen Rongzhou , Tang Hailian , Yan Lu , Huang Fei , Tian Ming , Wu Kaibao , Zhou Yanliang , Lin Jian , Zheng Ying , Wang Xiaodong
Published: September 2024

Pre-reduced Pt/hexaaluminate catalysts showed excellent stability under high temperature and redox atmosphere.
Selective CO production from CO2 over a metal catalyst supported on perovskite oxide in the presence of excess hydrogen
Authors: Tashiro Keigo , Sekizawa Shinnosuke , Doi Wataru , Konno Hikaru , Izutani Kensuke , Furukawa Takayuki , Yanagita Akihide , Satokawa Shigeo
Published: September 2024

Supporting platinum on perovskite-type oxides (BZY10) increased catalytic activity while maintaining in the reverse water–gas shift reaction, which reduces carbon dioxide to carbon monoxide.
Selective catalytic NOx reduction by H2 in excess O2 over Pt/zirconium phosphate nanosheets
Authors: Awaya Keisuke , Sato Yuka , Miyazaki Aoi , Furukubo Mana , Nishiyama Koshi , Tsushida Masayuki , Ida Shintaro , Ohyama Junya , Machida Masato
Published: September 2024

We demonstrated the selective catalytic NO reduction with H2 (H2-SCR) over Pt nanoparticles supported on a monolayer zirconium phosphate (ZrP) nanosheet derived from α-Zr(HPO4)2·H2O.
Enhancement mechanism of novel heterojunction Z-scheme-type composite BiOBr/ZnIn2S4 to degrade Congo red
Authors: Huang Junchao , Li Borui , Yu Jiaxing , Shu Zhan , Li Ming
Published: September 2024

The Z-scheme three-dimensional flower-like shape BiOBr/ZnIn2S4 showed excellent efficiency to degrade Congo red.
Observation of Haldane magnetism in organically templated vanadium phosphate (enH2)0.5VPO4OH
Authors: Samarin A. Sh. , Fedotov S. S. , Koo H.-J. , Whangbo M.-H. , Gippius A. A. , Zhurenko S. V. , Tkachev A. V. , Shvanskaya L. V. , Vasiliev A. N.
Published: September 2024

The Haldane-type behavior was observed in the first V-based organically templated magnet (enH2)0.5VPO4OH in magnetic susceptibility and nuclear magnetic resonance measurements.
A Dawson-type {P4W24} modified using phenylphosphonic acid with excellent proton conductivity
Authors: Liu Jiayu , Lei Wenjing , Zhang Shihao , Li Huafeng , Liu Siyu , Ma Pengtao , Wang Jingping , Niu Jingyang
Published: September 2024

The compound K4Na4H11[KCo2(H2O)10P4W24O92{(PhPO)2}]·48H2O (1) contains Dawson-type structural in the organophosphonate-functionalized POT field. The proton conductivity of 1 reaches 1.59 × 10−2 S cm−1 at 318 K and 95% RH.
Investigation of the effect of Al2O3/water nanofluid on the performance of a thermoelectric cooler to harvest water from humid air
Authors: Nazari Emad , Vakili Mohammad Hassan , Reiszadeh Mahdi
Published: September 2024

One of the sources of fresh water, especially in desert and water-scarce areas is atmospheric air.
Green energy driven methane conversion under mild conditions
Authors: You Jiakang , Bao Yifan , Zhang Yanzhao , Konarova Muxina , Wang Zhiliang , Wang Lianzhou
Published: September 2024

This review provides a comprehensive overview of recent efforts and understanding in methane conversion to valuable products, including oxygenates and hydrocarbons, by taking advantage of electrocatalysis and photocatalysis.
Protein-bound AGEs derived from methylglyoxal induce pro-inflammatory response and barrier integrity damage in epithelial cells by disrupting the retinol metabolism
Authors: Yu Gang , He Jianxin , Gao Zhongshan , Fu Linglin , Zhang Qiaozhi
Published: September 2024

Protein-bound advanced glycation end-products (AGEs) induce pro-inflammatory response and barrier integrity damage in epithelial cells by disrupting the retinol metabolism.
Stabilization of hypoxia-inducible factor 1α and regulation of specific gut microbes by EGCG contribute to the alleviation of ileal barrier disorder and obesity
Authors: Ma Hui , Wang Yuanyifei , Wei Jiayu , Wang Xiaochi , Yang Hui , Wang Shuo
Published: September 2024

The stabilization of HIF1α and regulation of specific gut microbes by EGCG facilitated the restoration of the ileal barrier and the elevation of SCFA contents, ultimately contributing to the alleviation of obesity.
Effects and individual response of salt substitute intervention on blood pressure in a high-risk stroke population: findings from 4200 participants of the China Salt Substitute and Stroke Study
Authors: Ma Bing , Zhang Jing , Zhou Ying , Song Xinying , Li Xilei , Peng Yuyi , Wang Xin , Sun Hao , Zhou Bo
Published: September 2024

Low sodium has different antihypertensive effects in stroke high-risk groups with different characteristics (BMI, age, blood pressure).
Molecular structural engineering of donor–acceptor-based porous organic polymers for sulfide photooxidation in water: a sustainable approach
Authors: Saini Neha , Dhingra Kirti , Kumar Amit , Kailasam Kamalakannan
Published: September 2024

The present work foreshadows the use of molecular-engineered organic polymeric networks as a green and sustainable approach for the upgradation of chemicals via photocatalytic organic transformation reactions.
A nanoporous hydrogel-based model to study chemokine gradient-driven angiogenesis under luminal flow
Authors: Mote Nidhi , Kubik Sarah , Polacheck William J. , Baker Brendon M. , Trappmann Britta
Published: September 2024

We develop a biomimetic model to uncover the synergistic effects of luminal flow and chemokine gradients on angiogenic sprouting.
DC-derived whole cell cytokine nano-regulator for remodelling extracellular matrix and synergizing tumor immunotherapy
Authors: Lu Jingsong , Li Ying , Gao Xiaohan , Chen Sumei , Jin Zeping , Guo Xiaoxiao , Xie Wensheng , Guo Zhenhu , Wei Yen , Zhao Lingyun
Published: September 2024

A smart DC-derived whole cell cytokine nano-regulator of TCPs was developed. It was found that TCPs could remodel extracellular matrices and synergize tumor immunotherapy combined with radiotherapy.
Synergistic enhancement of thermomechanical properties and oxidation resistance in aligned Co-continuous carbon–ceramic hybrid fibers
Authors: Denk Jakob , Liao Xiaojian , Dulle Martin , Schafföner Stefan , Förster Stephan , Greiner Andreas , Motz Günter , Agarwal Seema
Published: September 2024

Continuous carbon–ceramic hybrid fibers with highly aligned co-continuous topological structures exhibit enhanced thermomechanical stability and oxidation resistance.
NIR-triggered photooxygenation of α-terpinene with upconversion nanohybrids
Authors: Francés-Soriano Laura , Bellezza Delia , Ferrera-González Juan , González-Béjar María , Pérez-Prieto Julia
Published: September 2024

Upconversion nanohybrids (NHs) containing different amounts of Rose Bengal (RB) can selectively photocatalyse terpinene oxidation upon NIR-irradiation. The amount and aggregation of RB in the NH clearly influence the reaction yield.
Integrating 2D graphitic carbon nitride with Gd2S3 nanoparticles towards development of multiutility water treatment nanomaterial: synergistic effects on electrochemical dopamine sensing and photocatalytic degradation of contaminants
Authors: Haq Zia ul , Ganaie Firdous Ahmad , Bhat Sajad Ahmad , Nazir Irfan , Qureashi Aaliya , Bashir Arshid , Rizvi Masood Ahmad
Published: September 2024

This study envisages the utilization of unique properties of Gd2S3 and 2D graphitic carbon nitride towards the development of novel multiutility nanomaterial with sensing and water treatment application.
Hydrophobic poly(ethylene-co-vinyl acetate) and nanoclay-based polymeric adsorbent for effective removal of oils and various organic solvents from contaminated wastewater
Authors: Dutta Riku , Baruah Kankana , Doley Simanta , Dolui S. K. , Ray B. C.
Published: September 2024

Poly(ethylene-co-vinyl acetate blended with organically modified montmorillonite (OMMT) nanoclay following a green pathway by melt blending in a Brabender plasticoder to develop novel nanoadsorbent.
An on–off–on chemiluminescence resonance energy transfer sensing platform based on Au/Pt@Cu2O/CuO nanozyme for the determination of ascorbic acid
Authors: Zhang Xiaoxu , Cai Xiangyu , Fei Yanqun , Jia Yuying , Shan Hongyan , Huan Yanfu
Published: September 2024

The mechanism of ascorbic acid detection by the Au/Pt@Cu2O/CuO NPs–luminol–H2O2–MnO2 NSs CRET system.
Refining Mn–Ni synergy for the design of efficient catalysts in electrochemical ethanol oxidation
Authors: Zhong Qitong , Tan Xing , Du Ruixing , Liao Longfei , Tang Zhenchen , Chen Shiming , Yan Dafeng , Zeng Feng
Published: September 2024

The Mn promoter tailors the electrochemically active surface area and intrinsic activity of Ni foam, enhancing the electrochemical oxidation of ethanol.