bluuebunny/crossref_metadata_2025 huggingface dataset:
The Development of Fault Networks at the Termination of Continental Transform Faults When Their Connecting Plate Boundary Is “Misaligned”
Authors: Withers M. , Cruden A. R. , Quigley M. C.
Published: October 2023

We report the results of a series of scaled laboratory experiments that investigate the development of fault systems in plate boundary transition zones, where deformation is distributed between a continental transform fault (e.g., Alpine Fault, New Zealand; North Anatolian Fault (NAF), Turkey; San Andreas Fault (SAF), USA) and its connecting plate boundary. In these transition zones, continental transform faults are observed to branch into multiple subsidiary faults. Here we show that large‐scale transition zone fault networks comprise crustal‐scale Riedel shears that develop sequentially outwards and away from the parent transform fault. Such fault networks form within brittle upper crust that overlies a ductile lower crust that deforms by large‐scale distributed simple shear. We argue that large‐scale distributed deformation of the lower crust occurs when continental transform faults are “misaligned” relative to their connecting plate boundaries. This misalignment may occur: (a) where a transform fault does not directly connect with a convergent or divergent plate boundary, as in the northern termination of the Alpine Fault and the western termination of the NAF; and (b) where a significant bend in the transform fault occurs in the plate boundary transition zone, as in the southern termination of the SAF. The development of such plate boundary misalignments appears to occur when a plate boundary transition zone develops as a continental transform fault propagates toward a different type of “connecting” plate boundary.
Controls on Saturated Hydraulic Conductivity in a Degrading Permafrost Peatland Complex
Authors: Fewster Richard E. , Morris Paul J. , Swindles Graeme T. , Baird Andy J. , Turner T. Edward , Ivanovic Ruza F.
Published: October 2023

Permafrost peatlands are vulnerable to rapid structural changes under climatic warming, including vertical collapse. Peatland water budgets, and therefore peat hydraulic properties, are important determinants of vegetation and carbon fluxes. Measurements of hydraulic properties exist for only a limited number of permafrost peatland locations, primarily concentrated in North America. The impacts of thaw‐induced collapse upon properties such as horizontal saturated hydraulic conductivity (Kh), and thus lateral drainage, remain poorly understood. We made laboratory determinations of Kh from 82 peat samples from a degrading Swedish palsa mire. We fitted a linear mixed‐effects model (LMM) to establish the controls on Kh, which declined strongly with increasing depth, humification and dry bulk density. Depth exerted the strongest control on Kh in our LMM, which demonstrated strong predictive performance (r2 = 0.605). Humification and dry bulk density were influential predictors, but the high collinearity of these two variables meant only one could be included reliably in our LMM. Surprisingly, peat Kh did not differ significantly between desiccating and collapsed palsas. We compared our site‐specific LMM to an existing, multi‐site model, fitted primarily to boreal and temperate peatlands. The multi‐site model made less skillful predictions (r2 = 0.528) than our site‐specific model, possibly due to latitudinal differences in peat compaction, floristic composition and climate. Nonetheless, low bias means the multi‐site model may still be useful for estimating peat Kh at high latitudes. Permafrost peatlands remain underrepresented in multi‐site models of peat hydraulic properties, and measurements such as ours could be used to improve future iterations.
In-plane dipolar nano-antenna steers polariton waves at nanoscale
Authors: Chen Huanjun , Deng Shaozhi
Published: October 2023

Hyperbolic polaritons can be launched and guided into mirror-symmetric-broken trajectories using an in-plane dipolar nano-antenna, and this asymmetry can be configured by adjusting the polarization direction of the in-plane dipole moment.
Potential terahertz therapeutic strategy for the prevention or mitigation of Alzheimer’s disease pathology
Authors: Wang Xinke , Zhang Yan
Published: October 2023

With terahertz irradiation with a specific frequency, the fibrotic progression of β-amyloid oligomers is suppressed, which provides a potential therapeutic strategy for Alzheimer’s disease.
Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder
Authors: Huang Qiyun , Velthuis Hester , Pereira Andreia C. , Ahmad Jumana , Cooke Samuel F. , Ellis Claire L. , Ponteduro Francesca M. , Puts Nicolaas A. J. , Dimitrov Mihail , Batalle Dafnis , Wong Nichol M. L. , Kowalewski Lukasz , Ivin Glynis , Daly Eileen , Murphy Declan G. M. , McAlonan Gráinne M.
Published: October 2023

Altered reactivity and responses to auditory input are core to the diagnosis of autism spectrum disorder (ASD). Preclinical models implicate ϒ-aminobutyric acid (GABA) in this process. However, the link between GABA and auditory processing in humans (with or without ASD) is largely correlational. As part of a study of potential biosignatures of GABA function in ASD to inform future clinical trials, we evaluated the role of GABA in auditory repetition suppression in 66 adults (n = 28 with ASD). Neurophysiological responses (temporal and frequency domains) to repetitive standard tones and novel deviants presented in an oddball paradigm were compared after double-blind, randomized administration of placebo, 15 or 30 mg of arbaclofen (STX209), a GABA type B (GABAB) receptor agonist. We first established that temporal mismatch negativity was comparable between participants with ASD and those with typical development (TD). Next, we showed that temporal and spectral responses to repetitive standards were suppressed relative to responses to deviants in the two groups, but suppression was significantly weaker in individuals with ASD at baseline. Arbaclofen reversed weaker suppression of spectral responses in ASD but disrupted suppression in TD. A post hoc analysis showed that arbaclofen-elicited shift in suppression was correlated with autistic symptomatology measured using the Autism Quotient across the entire group, though not in the smaller sample of the ASD and TD group when examined separately. Thus, our results confirm: GABAergic dysfunction contributes to the neurophysiology of auditory sensory processing alterations in ASD, and can be modulated by targeting GABABactivity. These GABA-dependent sensory differences may be upstream of more complex autistic phenotypes.
Assessing the Cntnap2 knockout rat prepulse inhibition deficit through prepulse scaling of the baseline startle response curve
Authors: El-Cheikh Mohamad Alaa , Möhrle Dorit , Haddad Faraj L. , Rose Anton , Allman Brian L. , Schmid Susanne
Published: October 2023

Many neurodevelopmental disorders, including autism spectrum disorder (ASD), are associated with changes in sensory processing and sensorimotor gating. The acoustic startle response and prepulse inhibition (PPI) of startle are widely used translational measures for assessing sensory processing and sensorimotor gating, respectively. The Cntnap2 knockout (KO) rat has proven to be a valid model for ASD, displaying core symptoms, including sensory processing perturbations. Here, we used a novel method to assess startle and PPI in Cntnap2 KO rats that allows for the identification of separate scaling components: startle scaling, which is a change in startle amplitude to a given sound, and sound scaling, which reflects a change in sound processing. Cntnap2 KO rats show increased startle due to both an increased overall response (startle scaling) and a left shift of the sound/response curve (sound scaling). In the presence of a prepulse, wildtype rats show a reduction of startle due to both startle scaling and sound scaling, whereas Cntnap2 KO rats show normal startle scaling, but disrupted sound scaling, resulting in the reported PPI deficit. These results validate that startle and sound scaling by a prepulse are indeed two independent processes, with only the latter being impaired in Cntnap2 KO rats. As startle scaling is likely related to motor output and sound scaling to sound processing, this novel approach reveals additional information on the possible cause of PPI disruptions in preclinical models.
miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication
Authors: Fuertes Teresa , Álvarez-Corrales Emigdio , Gómez-Escolar Carmen , Ubieto-Capella Patricia , Serrano-Navarro Álvaro , de Molina Antonio , Méndez Juan , Ramiro Almudena R. , de Yébenes Virginia G.
Published: October 2023

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive B cell lymphoma and accounts for nearly 40% of cases of B cell non-Hodgkin lymphoma. DLBCL is generally treated with R-CHOP chemotherapy, but many patients do not respond or relapse after treatment. Here, we analyzed the therapeutic potential of the tumor suppressor microRNA-28 (miR-28) for DLBCL, alone and in combination with the Bruton’s tyrosine kinase inhibitor ibrutinib. Combination therapy with miR-28 plus ibrutinib potentiated the anti-tumor effects of monotherapy with either agent by inducing a specific transcriptional cell-cycle arrest program that impairs DNA replication. The molecular actions of miR-28 and ibrutinib synergistically impair DNA replication by simultaneous inhibition of origin activation and fork progression. Moreover, we found that downregulation of the miR-28-plus-ibrutinib gene signature correlates with better survival of ABC-DLBCL patients. These results provide evidence for the effectiveness of a new miRNA-based ibrutinib combination therapy for DLBCL and unveil the miR-28-plus-ibrutinib gene signature as a new predictor of outcome in ABC-DLBCL patients.
Conserved enhancers control notochord expression of vertebrate Brachyury
Authors: Kemmler Cassie L. , Smolikova Jana , Moran Hannah R. , Mannion Brandon J. , Knapp Dunja , Lim Fabian , Czarkwiani Anna , Hermosilla Aguayo Viviana , Rapp Vincent , Fitch Olivia E. , Bötschi Seraina , Selleri Licia , Farley Emma , Braasch Ingo , Yun Maximina , Visel Axel , Osterwalder Marco , Mosimann Christian , Kozmik Zbynek , Burger Alexa
Published: October 2023

The cell type-specific expression of key transcription factors is central to development and disease. Brachyury/T/TBXT is a major transcription factor for gastrulation, tailbud patterning, and notochord formation; however, how its expression is controlled in the mammalian notochord has remained elusive. Here, we identify the complement of notochord-specific enhancers in the mammalian Brachyury/T/TBXT gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three conserved Brachyury-controlling notochord enhancers, T3, C, and I, in human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers, in cis deletion of all three enhancers in mouse abolishes Brachyury/T/Tbxt expression selectively in the notochord, causing specific trunk and neural tube defects without gastrulation or tailbud defects. The three Brachyury-driving notochord enhancers are conserved beyond mammals in the brachyury/tbxtb loci of fishes, dating their origin to the last common ancestor of jawed vertebrates. Our data define the vertebrate enhancers for Brachyury/T/TBXTB notochord expression through an auto-regulatory mechanism that conveys robustness and adaptability as ancient basis for axis development.
Ubiquitin ligase CHFR mediated degradation of VE-cadherin through ubiquitylation disrupts endothelial adherens junctions
Authors: Tiruppathi Chinnaswamy , Wang Dong-Mei , Ansari Mohammad Owais , Bano Shabana , Tsukasaki Yoshikazu , Mukhopadhyay Amitabha , Joshi Jagdish C. , Loch Christian , Niessen Hans W. M. , Malik Asrar B.
Published: October 2023

Vascular endothelial cadherin (VE-cadherin) expressed at endothelial adherens junctions (AJs) is vital for vascular integrity and endothelial homeostasis. Here we identify the requirement of the ubiquitin E3-ligase CHFR as a key mechanism of ubiquitylation-dependent degradation of VE-cadherin. CHFR was essential for disrupting the endothelium through control of the VE-cadherin protein expression at AJs. We observe augmented expression of VE-cadherin in endothelial cell (EC)-restricted Chfr knockout (ChfrΔEC) mice. We also observe abrogation of LPS-induced degradation of VE-cadherin in ChfrΔEC mice, suggesting the pathophysiological relevance of CHFR in regulating the endothelial junctional barrier in inflammation. Lung endothelial barrier breakdown, inflammatory neutrophil extravasation, and mortality induced by LPS were all suppressed in ChfrΔEC mice. We find that the transcription factor FoxO1 is a key upstream regulator of CHFR expression. These findings demonstrate the requisite role of the endothelial cell-expressed E3-ligase CHFR in regulating the expression of VE-cadherin, and thereby endothelial junctional barrier integrity.
Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry
Authors: Ristow Laura C. , Jezewski Andrew J. , Chadwick Benjamin J. , Stamnes Mark A. , Lin Xiaorong , Krysan Damian J.
Published: October 2023

Cryptococcusspp. are environmental fungi that first must adapt to the host environment before they can cause life-threatening meningitis in immunocompromised patients. Host CO2concentrations are 100-fold higher than the external environment and strains unable to grow at host CO2concentrations are not pathogenic. Using a genetic screening and transcriptional profiling approach, we report that the TOR pathway is critical forC. neoformansadaptation to host CO2partly through Ypk1-dependent remodeling of phosphatidylserine asymmetry at the plasma membrane. We also describe aC. neoformansABC/PDR transporter (PDR9) that is highly expressed in CO2-sensitive environmental strains, suppresses CO2-induced phosphatidylserine/phospholipid remodeling, and increases susceptibility to host concentrations of CO2. Interestingly, regulation of plasma membrane lipid asymmetry by the TOR-Ypk1 axis is distinct inC. neoformanscompared toS. cerevisiae. Finally, host CO2concentrations suppress theC. neoformanspathways that respond to host temperature (Mpk1) and pH (Rim101), indicating that host adaptation requires a stringent balance among distinct stress responses.
Light-oriented 3D printing of liquid crystal/photocurable resins and in-situ enhancement of mechanical performance
Authors: Sun Xiaolu , Chen Shaoyun , Qu Bo , Wang Rui , Zheng Yanyu , Liu Xiaoying , Li Wenjie , Gao Jianhong , Chen Qinhui , Zhuo Dongxian
Published: October 2023

Additive manufacturing technology has significantly impacted contemporary industries due to its ability to generate intricate computer-designed geometries. However, 3D-printed polymer parts often possess limited application potential, primarily because of their weak mechanical attributes. To overcome this drawback, this study formulates liquid crystal/photocurable resins suitable for the stereolithography technique by integrating 4’-pentyl-4-cyanobiphenyl with a photosensitive acrylic resin. This study demonstrates that stereolithography facilitates the precise modulation of the existing liquid crystal morphology within the resin. Furthermore, the orientation of the liquid crystal governs the oriented polymerization of monomers or prepolymers bearing acrylate groups. The products of this 3D printing approach manifest anisotropic behavior. Remarkably, when utilizing liquid crystal/photocurable resins, the resulting 3D-printed objects are approximately twice as robust as those created using commercial resins in terms of their tensile, flexural, and impact properties. This pioneering approach holds promise for realizing autonomously designed structures that remain elusive with present additive manufacturing techniques.
In situ X-ray spectroscopies beyond conventional X-ray absorption spectroscopy on deciphering dynamic configuration of electrocatalysts
Authors: Wang Jiali , Hsu Chia-Shuo , Wu Tai-Sing , Chan Ting-Shan , Suen Nian-Tzu , Lee Jyh-Fu , Chen Hao Ming
Published: October 2023

Realizing viable electrocatalytic processes for energy conversion/storage strongly relies on an atomic-level understanding of dynamic configurations on catalyst-electrolyte interface. X-ray absorption spectroscopy (XAS) has become an indispensable tool to in situ investigate dynamic natures of electrocatalysts but still suffers from limited energy resolution, leading to significant electronic transitions poorly resolved. Herein, we highlight advanced X-ray spectroscopies beyond conventional XAS, with emphasis on their unprecedented capabilities of deciphering key configurations of electrocatalysts. The profound complementarities of X-ray spectroscopies from various aspects are established in a probing energy-dependent “in situ spectroscopy map” for comprehensively understanding the solid-liquid interface. This perspective establishes an indispensable in situ research model for future studies and offers exciting research prospects for scientists and spectroscopists.
mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy
Authors: Riedmayr Lisa Maria , Hinrichsmeyer Klara Sonnie , Thalhammer Stefan Bernhard , Mittas David Manuel , Karguth Nina , Otify Dina Yehia , Böhm Sybille , Weber Valentin Johannes , Bartoschek Michael David , Splith Victoria , Brümmer Manuela , Ferreira Raphael , Boon Nanda , Wögenstein Gabriele Maria , Grimm Christian , Wijnholds Jan , Mehlfeld Verena , Michalakis Stylianos , Fenske Stefanie , Biel Martin , Becirovic Elvir
Published: October 2023

Large genes including several CRISPR-Cas modules like gene activators (CRISPRa) require dual adeno-associated viral (AAV) vectors for an efficient in vivo delivery and expression. Current dual AAV vector approaches have important limitations, e.g., low reconstitution efficiency, production of alien proteins, or low flexibility in split site selection. Here, we present a dual AAV vector technology based on reconstitution via mRNA trans-splicing (REVeRT). REVeRT is flexible in split site selection and can efficiently reconstitute different split genes in numerous in vitro models, in human organoids, and in vivo. Furthermore, REVeRT can functionally reconstitute a CRISPRa module targeting genes in various mouse tissues and organs in single or multiplexed approaches upon different routes of administration. Finally, REVeRT enabled the reconstitution of full-length ABCA4 after intravitreal injection in a mouse model of Stargardt disease. Due to its flexibility and efficiency REVeRT harbors great potential for basic research and clinical applications.
Lipid complexation reduces rice starch digestibility and boosts short-chain fatty acid production via gut microbiota
Authors: Shen Yi , An Zengxu , Huyan Zongyao , Shu Xiaoli , Wu Dianxing , Zhang Ning , Pellegrini Nicoletta , Rubert Josep
Published: October 2023

In this study, two rice varieties (RS4 and GZ93) with different amylose and lipid contents were studied, and their starch was used to prepare starch-palmitic acid complexes. The RS4 samples showed a significantly higher lipid content in their flour, starch, and complex samples compared to GZ93. The static in vitro digestion highlighted that RS4 samples had significantly lower digestibility than the GZ93 samples. The C∞ of the starch-lipid complex samples was found to be 17.7% and 18.5% lower than that of the starch samples in GZ93 and RS4, respectively. The INFOGEST undigested fractions were subsequently used for in vitro colonic fermentation. Short-chain fatty acids (SCFAs) concentrations, mainly acetate, and propionate were significantly higher in starch-lipid complexes compared to native flour or starch samples. Starch-lipid complexes produced a distinctive microbial composition, which resulted in different gene functions, mainly related to pyruvate, fructose, and mannose metabolism. Using Model-based Integration of Metabolite Observations and Species Abundances 2 (MIMOSA2), SCFA production was predicted and associated with the gut microbiota. These results indicated that incorporating lipids into rice starch promotes SCFA production by modulating the gut microbiota selectively.
Overshooting the critical threshold for the Greenland ice sheet
Authors: Bochow Nils , Poltronieri Anna , Robinson Alexander , Montoya Marisa , Rypdal Martin , Boers Niklas
Published: October 2023

Melting of the Greenland ice sheet (GrIS) in response to anthropogenic global warming poses a severe threat in terms of global sea-level rise (SLR)1. Modelling and palaeoclimate evidence suggest that rapidly increasing temperatures in the Arctic can trigger positive feedback mechanisms for the GrIS, leading to self-sustained melting2–4, and the GrIS has been shown to permit several stable states5. Critical transitions are expected when the global mean temperature (GMT) crosses specific thresholds, with substantial hysteresis between the stable states6. Here we use two independent ice-sheet models to investigate the impact of different overshoot scenarios with varying peak and convergence temperatures for a broad range of warming and subsequent cooling rates. Our results show that the maximum GMT and the time span of overshooting given GMT targets are critical in determining GrIS stability. We find a threshold GMT between 1.7 °C and 2.3 °C above preindustrial levels for an abrupt ice-sheet loss. GrIS loss can be substantially mitigated, even for maximum GMTs of 6 °C or more above preindustrial levels, if the GMT is subsequently reduced to less than 1.5 °C above preindustrial levels within a few centuries. However, our results also show that even temporarily overshooting the temperature threshold, without a transition to a new ice-sheet state, still leads to a peak in SLR of up to several metres.
Antiviral type III CRISPR signalling via conjugation of ATP and SAM
Authors: Chi Haotian , Hoikkala Ville , Grüschow Sabine , Graham Shirley , Shirran Sally , White Malcolm F.
Published: October 2023

CRISPR systems are widespread in the prokaryotic world, providing adaptive immunity against mobile genetic elements1,2. Type III CRISPR systems, with the signature gene cas10, use CRISPR RNA to detect non-self RNA, activating the enzymatic Cas10 subunit to defend the cell against mobile genetic elements either directly, via the integral histidine–aspartate (HD) nuclease domain3–5 or indirectly, via synthesis of cyclic oligoadenylate second messengers to activate diverse ancillary effectors6–9. A subset of type III CRISPR systems encode an uncharacterized CorA-family membrane protein and an associated NrN family phosphodiesterase that are predicted to function in antiviral defence. Here we demonstrate that the CorA-associated type III-B (Cmr) CRISPR system from Bacteroides fragilis provides immunity against mobile genetic elements when expressed in Escherichia coli. However, B. fragilis Cmr does not synthesize cyclic oligoadenylate species on activation, instead generating S-adenosyl methionine (SAM)-AMP (SAM is also known as AdoMet) by conjugating ATP to SAM via a phosphodiester bond. Once synthesized, SAM-AMP binds to the CorA effector, presumably leading to cell dormancy or death by disruption of the membrane integrity. SAM-AMP is degraded by CRISPR-associated phosphodiesterases or a SAM-AMP lyase, potentially providing an ‘off switch’ analogous to cyclic oligoadenylate-specific ring nucleases10. SAM-AMP thus represents a new class of second messenger for antiviral signalling, which may function in different roles in diverse cellular contexts.
Clinical trial links oncolytic immunoactivation to survival in glioblastoma
Authors: Ling Alexander L. , Solomon Isaac H. , Landivar Ana Montalvo , Nakashima Hiroshi , Woods Jared K. , Santos Andres , Masud Nafisa , Fell Geoffrey , Mo Xiaokui , Yilmaz Ayse S. , Grant James , Zhang Abigail , Bernstock Joshua D. , Torio Erickson , Ito Hirotaka , Liu Junfeng , Shono Naoyuki , Nowicki Michal O. , Triggs Daniel , Halloran Patrick , Piranlioglu Raziye , Soni Himanshu , Stopa Brittany , Bi Wenya Linda , Peruzzi Pierpaolo , Chen Ethan , Malinowski Seth W. , Prabhu Michael C. , Zeng Yu , Carlisle Anne , Rodig Scott J. , Wen Patrick Y. , Lee Eudocia Quant , Nayak Lakshmi , Chukwueke Ugonma , Gonzalez Castro L. Nicolas , Dumont Sydney D. , Batchelor Tracy , Kittelberger Kara , Tikhonova Ekaterina , Miheecheva Natalia , Tabakov Dmitry , Shin Nara , Gorbacheva Alisa , Shumskiy Artemy , Frenkel Felix , Aguilar-Cordova Estuardo , Aguilar Laura K. , Krisky David , Wechuck James , Manzanera Andrea , Matheny Chris , Tak Paul P. , Barone Francesca , Kovarsky Daniel , Tirosh Itay , Suvà Mario L. , Wucherpfennig Kai W. , Ligon Keith , Reardon David A. , Chiocca E. Antonio
Published: October 2023

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110—an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318).
High-resolution maps show that rubber causes substantial deforestation
Authors: Wang Yunxia , Hollingsworth Peter M. , Zhai Deli , West Christopher D. , Green Jonathan M. H. , Chen Huafang , Hurni Kaspar , Su Yufang , Warren-Thomas Eleanor , Xu Jianchu , Ahrends Antje
Published: October 2023

Understanding the effects of cash crop expansion on natural forest is of fundamental importance. However, for most crops there are no remotely sensed global maps1, and global deforestation impacts are estimated using models and extrapolations. Natural rubber is an example of a principal commodity for which deforestation impacts have been highly uncertain, with estimates differing more than fivefold1–4. Here we harnessed Earth observation satellite data and cloud computing5 to produce high-resolution maps of rubber (10 m pixel size) and associated deforestation (30 m pixel size) for Southeast Asia. Our maps indicate that rubber-related forest loss has been substantially underestimated in policy, by the public and in recent reports6–8. Our direct remotely sensed observations show that deforestation for rubber is at least twofold to threefold higher than suggested by figures now widely used for setting policy4. With more than 4 million hectares of forest loss for rubber since 1993 (at least 2 million hectares since 2000) and more than 1 million hectares of rubber plantations established in Key Biodiversity Areas, the effects of rubber on biodiversity and ecosystem services in Southeast Asia could be extensive. Thus, rubber deserves more attention in domestic policy, within trade agreements and in incoming due-diligence legislation.
Hydrological model-based streamflow reconstruction for Indian sub-continental river basins, 1951–2021
Authors: Chuphal Dipesh Singh , Mishra Vimal
Published: October 2023

Streamflow is a vital component of the global water cycle. Long-term streamflow observations are required for water resources planning and management, hydroclimatic extremes analysis, and ecological assessment. However, long-term streamflow observations for the Indian-Subcontinental (ISC) river basins are lacking. Using meteorological observations, state-of-the-art hydrological model, and river routing model, we developed hydrological model-simulated monthly streamflow from 1951–2021 for the ISC river basins. We used high-resolution vector-based routing model (mizuRoute) to generate streamflow at 9579 stream reaches in the sub-continental river basins. The model-simulated streamflow showed good performance against the observed flow with coefficient of determination (R2) and Nash-Sutcliffe efficiency (NSE) above 0.70 for more than 60% of the gauge stations. The dataset was used to examine the variability in low, average, and high flow across the streams. Long-term changes in streamflow showed a significant decline in flow in the Ganga basin while an increase in the semi-arid western India and Indus basin. Long-term streamflow can be used for planning water management and climate change adaptation in the Indian sub-continent.
A dataset of skin lesion images collected in Argentina for the evaluation of AI tools in this population
Authors: Ricci Lara María Agustina , Rodríguez Kowalczuk María Victoria , Lisa Eliceche Maite , Ferraresso María Guillermina , Luna Daniel Roberto , Benitez Sonia Elizabeth , Mazzuoccolo Luis Daniel
Published: October 2023

In recent years, numerous dermatological image databases have been published to make possible the development and validation of artificial intelligence-based technologies to support healthcare professionals in the diagnosis of skin diseases. However, the generation of these datasets confined to certain countries as well as the lack of demographic information accompanying the images, prevents having a real knowledge of in which populations these models could be used. Consequently, this hinders the translation of the models to the clinical setting. This has led the scientific community to encourage the detailed and transparent reporting of the databases used for artificial intelligence developments, as well as to promote the formation of genuinely international databases that can be representative of the world population. Through this work, we seek to provide details of the processing stages of the first public database of dermoscopy and clinical images created in a hospital in Argentina. The dataset comprises 1,616 images corresponding to 1,246 unique lesions collected from 623 patients.
Infection prediction in swine populations with machine learning
Authors: Halev Avishai , Martínez-López Beatriz , Clavijo Maria , Gonzalez-Crespo Carlos , Kim Jeonghoon , Huang Chao , Krantz Seth , Robbins Rebecca , Liu Xin
Published: October 2023

The pork industry is an essential part of the global food system, providing a significant source of protein for people around the world. A major factor restraining productivity and compromising animal wellbeing in the pork industry is disease outbreaks in pigs throughout the production process: widespread outbreaks can lead to losses as high as 10% of the U.S. pig population in extreme years. In this study, we present a machine learning model to predict the emergence of infection in swine production systems throughout the production process on a daily basis, a potential precursor to outbreaks whose detection is vital for disease prevention and mitigation. We determine features that provide the most value in predicting infection, which include nearby farm density, historical test rates, piglet inventory, feed consumption during the gestation period, and wind speed and direction. We utilize these features to produce a generalizable machine learning model, evaluate the model’s ability to predict outbreaks both seven and 30 days in advance, allowing for early warning of disease infection, and evaluate our model on two swine production systems and analyze the effects of data availability and data granularity in the context of our two swine systems with different volumes of data. Our results demonstrate good ability to predict infection in both systems with a balanced accuracy of $$85.3\%$$

85.3
%

on any disease in the first system and balanced accuracies (average prediction accuracy on positive and negative samples) of $$58.5\%$$

58.5
%

, $$58.7\%$$

58.7
%

, $$72.8\%$$

72.8
%

and $$74.8\%$$

74.8
%

on porcine reproductive and respiratory syndrome, porcine epidemic diarrhea virus, influenza A virus, and Mycoplasma hyopneumoniae in the second system, respectively, using the six most important predictors in all cases. These models provide daily infection probabilities that can be used by veterinarians and other stakeholders as a benchmark to more timely support preventive and control strategies on farms.
Untargeted lipidomics reveal association of elevated plasma C18 ceramide levels with reduced survival in metastatic castration-resistant prostate cancer patients
Authors: Cattrini Carlo , Manfredi Marcello , Barboro Paola , Ghirimoldi Marco , Mennitto Alessia , Martini Veronica , Battioni Alessio , Le Van Marco , Gobbato Simone , Branni Carmen , Ayed Rahma Ben , Pinato David James , Catalano Fabio , Zanardi Elisa , Boccardo Francesco , Gennari Alessandra
Published: October 2023

Emerging evidence highlights the potential prognostic relevance of circulating lipids in metastatic castration-resistant prostate cancer (mCRPC), with a proposed 3-lipid signature. This study aims to analyze the lipidomic profiles of individuals with mCRPC to identify lipid species that could serve as predictive indicators of prognosis and therapeutic response. Plasma samples were collected from mCRPC patients initiating first-line treatment (1 L) (n = 29) and those previously treated with at least two lines of therapy (> 2 L) (n = 19), including an androgen-receptor signaling inhibitor and a taxane. Employing an untargeted lipidomic approach, lipids were extracted from the plasma samples and subjected to analysis. A comprehensive identification and quantification of 789 plasma lipids was achieved. Notably, 75 species displayed significant dysregulation in > 2 L patients in comparison to the 1 L group. Among these, 63 species exhibited elevated levels, while 12 were reduced. Patients included in > 2 L cohort showed elevated levels of acylcarnitines (CAR), diacylglycerols (DG), phosphatidylethanolamines (PE), triacylglycerols (TG), and ceramides (Cer). Notably, some upregulated lipids, including CAR 14:0, CAR 24:1, Cer d18:1/16:0, Cer d18:1/18:0 (C18 Cer), Cer d18:2/18:0, Cer d18:1/24:1, and Cer d20:1/24:1, showed significant associations with overall survival (OS) in univariate models. Specifically, increased levels of C18 Cer remained significantly associated with poorer OS in the multivariate model, even after adjusting for treatment line and PSA levels (Hazard Ratio: 3.59 [95% Confidence Interval 1.51–8.52], p = 0.004). Employing quantitative mass spectrometry, our findings underscore the independent prognostic significance of C18 Cer in individuals with mCRPC. This discovery opens avenues for further studies within this field.
Improving the quality of image generation in art with top-k training and cyclic generative methods
Authors: Vela Laura , Fuentes-Hurtado Félix , Colomer Adrián
Published: October 2023

The creation of artistic images through the use of Artificial Intelligence is an area that has been gaining interest in recent years. In particular, the ability of Neural Networks to separate and subsequently recombine the style of different images, generating a new artistic image with the desired style, has been a source of study and attraction for the academic and industrial community. This work addresses the challenge of generating artistic images that are framed in the style of pictorial Impressionism and, specifically, that imitate the style of one of its greatest exponents, the painter Claude Monet. After having analysed several theoretical approaches, the Cycle Generative Adversarial Networks are chosen as base model. From this point, a new training methodology which has not been applied to cyclical systems so far, the top-kapproach, is implemented. The proposed system is characterised by using in each iteration of the training thosekimages that, in the previous iteration, have been able to better imitate the artist’s style. To evaluate the performance of the proposed methods, the results obtained with both methodologies, basic and top-k, have been analysed from both a quantitative and qualitative perspective. Both evaluation methods demonstrate that the proposed top-kapproach recreates the author’s style in a more successful manner and, at the same time, also demonstrate the ability of Artificial Intelligence to generate something as creative as impressionist paintings.
Assessment of key parameters of normal uterus in women of reproductive age
Authors: Chen Fang , Gong Yingxin , Xie Yu , Zhu Lei , Chen Limei , Xiao Jingjing , Jiang Ninghong , Sun Li , Sui Long
Published: October 2023

Currently, the precise and detailed anatomical data of the normal uterus, especially the myometrium thickness in various parts of the uterus, are lacking. This study aims to provide normal references for uterine size in healthy reproductive-aged Chinese women to facilitate the application of hysteroscopic surgery. A total of 298 women of reproductive age with normal uterine were included. Parity was significantly correlated with uterine measurements (P < 0.05), and age impacted several measurements (P < 0.05). At each uterine site examined, the myometrium was thinner in nulliparous women than in parous or primiparous women (P < 0.001). Similarly, the extrauterine measurements for parous or primiparous women were larger than those for nulliparous women. Weight affected some external measurements but not myometrial thicknesses, while height did not affect uterine measurements (P > 0.05). There was a positive correlation between body mass index (BMI) and extrauterine measurements as well as myometrial thickness (P < 0.05). The mathematical model of the uterine size for women of reproductive age was constructed stratified by parity. The study is the first to provide a detailed statistical description of the accurate anatomical parameters of the uterus in Chinese reproductive-aged women and has great significance for improving the safety and effectiveness of hysteroscopic surgery for patients.
Depression and anxiety mediate the relationship between the retrospectively measured symptoms of premenstrual disorders and negative but not positive psychotic-like experiences
Authors: Antosz-Rekucka Rachela , Prochwicz Katarzyna
Published: October 2023

The aim of this study was to examine the relationship between retrospectively measured premenstrual symptoms and subclinical forms of positive and negative psychotic symptoms (psychotic-like experiences; PLEs). It was hypothesised that subjective intensity of the symptoms of premenstrual disorders predicts PLEs frequency and that this relationship is mediated by anxiety and depression. The study sample comprised 108 non-clinical subjects. Study variables were assessed with self-report questionnaires: the Premenstrual Symptoms Screening Tool (PSST); the Beck Depression Inventory Second Edition (BDI-II); the State-Trait Anxiety Inventory (STAI; trait sub-scale); the Community Assessment of Psychic Experiences (CAPE). Regression and mediation analyses were performed. The PSST scores were significantly and positively associated with psychotic-like experiences frequency. The relation was stronger for positive PLEs. Anxiety and depression partially mediated the relationship between premenstrual symptoms and negative PLEs, but not between premenstrual symptoms and positive PLEs. Although the design of the study does not allow to infer causality, it demonstrates strong, positive relationship between the symptoms of premenstrual disorders and psychotic-like experiences. The relationship between premenstrual disorders and negative PLEs seems to be partially based on a general psychopathological factor. Further longitudinal studies are needed to test whether premenstrual disturbances increase risk of psychotic symptoms.
Cuproptosis-related gene SLC31A1: prognosis values and potential biological functions in cancer
Authors: Qi Yue , Yao Qingqing , Li Xuanyan , Li Xinyu , Zhang Wenwen , Qu Pengpeng
Published: October 2023

Cuproptosis is a unique type of cell death that may influence tumour formation by targeting lipoylated tricarboxylic acid cycle proteins. Solute carrier family 31 member 1 (SLC31A1), an important copper transporter, influences dietary copper absorption in the cell membrane. However, various SLC31A1 properties in pan-cancer profiles remain unknown. This study investigated the role of SLC31A1 in human malignancies and analysed its prognostic value. Raw data were obtained from The Cancer Genome Atlas database and processed using numerous internet databases, including UALCAN, GEPIA, cBioPortal, TIMER2.0, and Human Protein Atlas. SLC31A1 expression was found to be elevated in cervical, endometrial, and breast cancers compared to that in normal tissues, but reduced in clear cell renal cell carcinoma, liver hepatocellular carcinoma, and lung adenocarcinoma. Furthermore, SLC31A1 expression was strongly associated with overall survival and disease-free survival in several cancers. SLC31A1 gene mutations and methylations were identified in 33 cancers. SLC31A1 expression was positively correlated with immune cells in immune infiltration data. Single-cell sequencing revealed that SLC31A1 may play key roles in DNA repair, DNA damage, and proliferation. These findings may lead to better understanding of SLC31A1 in pan-cancer profiles and suggest that SLC31A1 could be a viable predictive biomarker, particularly in gynaecological cancers.
Results of Eustachian tube balloon dilation measured using the nine-step test
Authors: Bae Seong Hoon , Kwak Seungmin , Han Ji Hyuk , Jung Jinsei , Kim Sung Huhn , Choi Jae Young , Moon In Seok
Published: October 2023

Suggested several decades ago, the nine-step test is an intuitive test of Eustachian tube function. However, studies employing the nine-step test to assess the results of Eustachian tube balloon dilation (EBD) are limited. We aimed to objectively evaluate the efficacy of EBD in opening failure patients with decreased maximal peak pressure difference (MPD) using the nine-step test. Patients who had MPD values ≤ 13 daPa in the nine-step test were enrolled. The patients were categorized into two groups according to treatment decisions after discussion with a clinician: an EBD group (N = 26) and a medication group (N = 30). One month after treatment, the seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ7) and the nine-step test were administered to all participants and subgroups of symptomatic participants (ETDQ7 > 15). MPD improved (increased) in both the EBD group and the medication group. ETDQ7 values improved (decreased) in the EBD group, but not in the medication group. In subgroup analysis, MPD and ETDQ7 values improved only in the symptomatic EBD group. According to the nine-step test, EBD can normalize 53.8% of decreased MPD. Posttreatment MPD and ETDQ7 scores were significantly better in the EBD group than in the medication group. However, EBD in patients with abnormal nine-step test results seemed less efficacious when the treatment results of the medication group were considered.
Improving citrus bud grafting efficiency
Authors: Niedz Randall P. , Bowman Kim D.
Published: October 2023

Commercial citrus trees are composed of a scion grafted onto a rootstock. Because grafting is one of the most expensive methods of plant propagation, grafting efficiency is of large practical importance. The purpose of this study was to improve citrus bud-grafting efficiency. The effects of six factors that included BA, Tween-20, DMSO, type of solvent (water or EtOH), cardinal orientation of grafted bud, and type of supplemental light (LED, metal halide, none) on forty-four bud-grafting measures were determined using a multifactor design of experiment approach. Four measures useful for identifying treatments of practical value included the number of rootstock axial buds that formed shoots, the percentage of grafted buds that formed shoots, the length of the longest shoot formed from the grafted buds, and the total leaf area of the grafted bud shoots. The factors that most affected these responses were no supplemental light to minimize the number of shoots from rootstock axial buds, a south orientation and 5 mM BA to maximize the percentage of grafted buds that formed shoots, a north orientation and 5 mM BA to maximize the length of the longest grafted bud shoot, and 5 mM BA to maximize the leaf area of the grafted bud shoots.
Effect of remote ischemic preconditioning on lung function after surgery under general anesthesia: a systematic review and meta-analysis
Authors: Kashiwagi Shizuka , Mihara Takahiro , Yokoi Ayako , Yokoyama Chisaki , Nakajima Daisuke , Goto Takahisa
Published: October 2023

Remote ischemic preconditioning (RIPC) protects organs from ischemia–reperfusion injury. Recent trials showed that RIPC improved gas exchange in patients undergoing lung or cardiac surgery. We performed a systematic search to identify randomized controlled trials involving RIPC in surgery under general anesthesia. The primary outcome was the PaO2/FIO2 (P/F) ratio at 24 h after surgery. Secondary outcomes were A-a DO2, the respiratory index, duration of postoperative mechanical ventilation (MV), incidence of acute respiratory distress syndrome (ARDS), and serum cytokine levels. The analyses included 71 trials comprising 7854 patients. Patients with RIPC showed higher P/F ratio than controls (mean difference [MD] 36.6, 95% confidence interval (CI) 12.8 to 60.4, I2 = 69%). The cause of heterogeneity was not identified by the subgroup analysis. Similarly, A-a DO2 (MD 15.2, 95% CI − 29.7 to − 0.6, I2 = 87%) and respiratory index (MD − 0.17, 95% CI − 0.34 to − 0.01, I2 = 94%) were lower in the RIPC group. Additionally, the RIPC group was weaned from MV earlier (MD − 0.9 h, 95% CI − 1.4 to − 0.4, I2 = 78%). Furthermore, the incidence of ARDS was lower in the RIPC group (relative risk 0.73, 95% CI 0.60 to 0.89, I2 = 0%). Serum TNFα was lower in the RIPC group (SMD − 0.6, 95%CI − 1.0 to − 0.3 I2 = 87%). No significant difference was observed in interleukin-6, 8 and 10. Our meta-analysis suggested that RIPC improved oxygenation after surgery under general anesthesia.

Clinical trial number: This study protocol was registered in the University Hospital Medical Information Network (registration number: UMIN000030918), https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035305.