bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism
Authors: Romitti Mírian , Tourneur Adrien , de Faria da Fonseca Barbara , Doumont Gilles , Gillotay Pierre , Liao Xiao-Hui , Eski Sema Elif , Van Simaeys Gaetan , Chomette Laura , Lasolle Helene , Monestier Olivier , Kasprzyk Dominika Figini , Detours Vincent , Singh Sumeet Pal , Goldman Serge , Refetoff Samuel , Costagliola Sabine
Published: November 2022

The thyroid gland captures iodide in order to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common disorder in humans and is not always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, functional human thyroid organoids could pave the way to explore new therapeutic approaches. Here we report the generation of transplantable thyroid organoids derived from human embryonic stem cells capable of restoring plasma thyroid hormone in athyreotic mice as a proof of concept for future therapeutic development.
Transposable elements maintain genome-wide heterozygosity in inbred populations
Authors: De Kort Hanne , Legrand Sylvain , Honnay Olivier , Buckley James
Published: November 2022

Elevated levels of inbreeding increase the risk of inbreeding depression and extinction, yet many inbred species are widespread, suggesting that inbreeding has little impact on evolutionary potential. Here, we explore the potential for transposable elements (TEs) to maintain genetic variation in functional genomic regions under extreme inbreeding. Capitalizing on the mixed mating system ofArabidopsis lyrata, we assess genome-wide heterozygosity and signatures of selection at single nucleotide polymorphisms near transposable elements across an inbreeding gradient. Under intense inbreeding, we find systematically elevated heterozygosity downstream of several TE superfamilies, associated with signatures of balancing selection. In addition, we demonstrate increased heterozygosity in stress-responsive genes that consistently occur downstream of TEs. We finally reveal that TE superfamilies are associated with specific signatures of selection that are reproducible across independent evolutionary lineages ofA. lyrata. Together, our study provides an important hypothesis for the success of self-fertilizing species.
TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks
Authors: Nore Alexandre , Juarez-Martinez Ariadna B. , Clément Julie , Brun Christine , Diagouraga Boubou , Laroussi Hamida , Grey Corinne , Bourbon Henri Marc , Kadlec Jan , Robert Thomas , de Massy Bernard
Published: November 2022

Meiosis requires the formation of programmed DNA double strand breaks (DSBs), essential for fertility and for generating genetic diversity. DSBs are induced by the catalytic activity of the TOPOVIL complex formed by SPO11 and TOPOVIBL. To ensure genomic integrity, DNA cleavage activity is tightly regulated, and several accessory factors (REC114, MEI4, IHO1, and MEI1) are needed for DSB formation in mice. How and when these proteins act is not understood. Here, we show that REC114 is a direct partner of TOPOVIBL, and identify their conserved interacting domains by structural analysis. We then analyse the role of this interaction by monitoring meiotic DSBs in female and male mice carrying point mutations in TOPOVIBL that decrease or disrupt its binding to REC114. In these mutants, DSB activity is strongly reduced genome-wide in oocytes, and only in sub-telomeric regions in spermatocytes. In addition, in mutant spermatocytes, DSB activity is delayed in autosomes. These results suggest that REC114 is a key member of the TOPOVIL catalytic complex, and that the REC114/TOPOVIBL interaction ensures the efficiency and timing of DSB activity.
N6-methyladenosine modification governs liver glycogenesis by stabilizing the glycogen synthase 2 mRNA
Authors: Zhang Xiang , Yin Huilong , Zhang Xiaofang , Jiang Xunliang , Liu Yongkang , Zhang Haolin , Peng Yingran , Li Da , Yu Yanping , Zhang Jinbao , Cheng Shuli , Yang Angang , Zhang Rui
Published: November 2022

Hepatic glycogen is the main source of blood glucose and controls the intervals between meals in mammals. Hepatic glycogen storage in mammalian pups is insufficient compared to their adult counterparts; however, the detailed molecular mechanism is poorly understood. Here, we show that, similar to glycogen storage pattern, N6-methyladenosine (m6A) modification in mRNAs gradually increases during the growth of mice in liver. Strikingly, in the hepatocyte-specific Mettl3 knockout mice, loss of m6A modification disrupts liver glycogen storage. On the mechanism, mRNA of Gys2, the liver-specific glycogen synthase, is a substrate of METTL3 and plays a critical role in m6A-mediated glycogenesis. Furthermore, IGF2BP2, a “reader” protein of m6A, stabilizes the mRNA of Gys2. More importantly, reconstitution of GYS2 almost rescues liver glycogenesis in Mettl3-cKO mice. Collectively, a METTL3-IGF2BP2-GYS2 axis, in which METTL3 and IGF2BP2 regulate glycogenesis as “writer” and “reader” proteins respectively, is essential on maintenance of liver glycogenesis in mammals.
Norepinephrine transporter defects lead to sympathetic hyperactivity in Familial Dysautonomia models
Authors: Wu Hsueh-Fu , Yu Wenxin , Saito-Diaz Kenyi , Huang Chia-Wei , Carey Joseph , Lefcort Frances , Hart Gerald W. , Liu Hong-Xiang , Zeltner Nadja
Published: November 2022

Familial dysautonomia (FD), a rare neurodevelopmental and neurodegenerative disorder affects the sympathetic and sensory nervous system. Although almost all patients harbor a mutation in ELP1, it remains unresolved exactly how function of sympathetic neurons (symNs) is affected; knowledge critical for understanding debilitating disease hallmarks, including cardiovascular instability or dysautonomic crises, that result from dysregulated sympathetic activity. Here, we employ the human pluripotent stem cell (hPSC) system to understand symN disease mechanisms and test candidate drugs. FD symNs are intrinsically hyperactive in vitro, in cardiomyocyte co-cultures, and in animal models. We report reduced norepinephrine transporter expression, decreased intracellular norepinephrine (NE), decreased NE re-uptake, and excessive extracellular NE in FD symNs. SymN hyperactivity is not a direct ELP1 mutation result, but may connect to NET via RAB proteins. We found that candidate drugs lowered hyperactivity independent of ELP1 modulation. Our findings may have implications for other symN disorders and may allow future drug testing and discovery.
A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer
Authors: Niu Nan , Qiu Fang , Xu Qianshi , He Guijin , Gu Xi , Guo Wenbin , Zhang Dianlong , Li Zhigao , Zhao Yi , Li Yong , Li Ke , Zhang Hao , Zhang Peili , Huang Yuanxi , Zhang Gangling , Han Hongbin , Cai Zhengang , Li Pengfei , Xu Hong , Chen Guanglei , Xue Jinqi , Jiang Xiaofan , Jahromi Alireza Hamidian , Li Jinshi , Zhao Yu , de Faria Castro Fleury Eduardo , Huo Shiwen , Li Huajun , Jerusalem Guy , Tripodi Domenico , Liu Tong , Zheng Xinyu , Liu Caigang
Published: November 2022

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II–III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)−0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3–41.3). RCB-0/I is 55.7% (95% CI, 44.7–66.1). ORR is 87.4%, (95% CI, 78.1–93.2) and bpCR is 35.4% (95% CI, 25.8–46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.
Asymmetric construction of allylicstereogenic carbon center featuring atrifluoromethyl group via enantioselective reductive fluoroalkylation
Authors: Jin Ruo-Xing , Wu Bing-Bing , Bian Kang-Jie , Yu Jian-Liang , Dai Jing-Cheng , Zuo Ya-Wen , Zhang Yi-Fan , Wang Xi-Sheng
Published: November 2022

Emerging as a powerful tool for lead optimization in pharmaceutical research and development, to develop the facile, general protocols that allows the incorporation of fluorine-containing motif in drug candidates has accumulated enormous research interest in recent years. Among these important motifs, the incorporation of strategic motif CF3on aliphatic chain especially with the concomitant construction of trifluoromethylated alkanes bearing a CF3-substituted stereogenic carbon, is of paramount importance. Herein, we disclose an asymmetric nickel-catalyzed reductive trifluoroalkylation of alkenyl halides for enantioselective syntheses of diverseα-trifluoromethylated allylic alkanes, offering a general protocol to access the trifluoromethyl analogue to chiralα-methylated allylic alkanes, one of the most prevalent key components among natural products and pharmaceuticals. Utilities of the method including the application of the asymmetric trifluoroalkylation on multiple biologically active complex molecules, derivatization of transformable alkenyl functionality were demonstrated, providing a facile method in the diversity-oriented syntheses of CF3-containing chiral drugs and bioactive-molecules.
Identification of purine biosynthesis as an NADH-sensing pathway to mediate energy stress
Authors: Yang Ronghui , Yang Chuanzhen , Ma Lingdi , Zhao Yiliang , Guo Zihao , Niu Jing , Chu Qiaoyun , Ma Yingmin , Li Binghui
Published: November 2022

An enhanced NADH/NAD+ ratio, termed reductive stress, is associated with many diseases. However, whether a downstream sensing pathway exists to mediate pathogenic outcomes remains unclear. Here, we generate a soluble pyridine nucleotide transhydrogenase from Escherichia coli (EcSTH), which can elevate the NADH/NAD+ ratio and meantime reduce the NADPH/NADP+ ratio. Additionally, we fuse EcSTH with previously described LbNOX (a water-forming NADH oxidase from Lactobacillus brevis) to resume the NADH/NAD+ ratio. With these tools and by using genome-wide CRISPR/Cas9 library screens and metabolic profiling in mammalian cells, we find that accumulated NADH deregulates PRPS2 (Ribose-phosphate pyrophosphokinase 2)-mediated downstream purine biosynthesis to provoke massive energy consumption, and therefore, the induction of energy stress. Blocking purine biosynthesis prevents NADH accumulation-associated cell death in vitro and tissue injury in vivo. These results underscore the pathophysiological role of deregulated purine biosynthesis in NADH accumulation-associated disorders and demonstrate the utility of EcSTH in manipulating NADH/NAD+ and NADPH/NADP+.
H2A.Z deposition by SWR1C involves multiple ATP-dependent steps
Authors: Fan Jiayi , Moreno Andrew T. , Baier Alexander S. , Loparo Joseph J. , Peterson Craig L.
Published: November 2022

Histone variant H2A.Z is a conserved feature of nucleosomes flanking protein-coding genes. Deposition of H2A.Z requires ATP-dependent replacement of nucleosomal H2A by a chromatin remodeler related to the multi-subunit enzyme, yeast SWR1C. How these enzymes use ATP to promote this nucleosome editing reaction remains unclear. Here we use single-molecule and ensemble methodologies to identify three ATP-dependent phases in the H2A.Z deposition reaction. Real-time analysis of single nucleosome remodeling events reveals an initial priming step that occurs after ATP addition that involves a combination of both transient DNA unwrapping from the nucleosome and histone octamer deformations. Priming is followed by rapid loss of histone H2A, which is subsequently released from the H2A.Z nucleosomal product. Surprisingly, rates of both priming and the release of the H2A/H2B dimer are sensitive to ATP concentration. This complex reaction pathway provides multiple opportunities to regulate timely and accurate deposition of H2A.Z at key genomic locations.
Molecular magneto-ionic proton sensor in solid-state proton battery
Authors: Hu Yong , Guo Zipeng , Chen Yingjie , Zhou Chi , Li Yuguang C. , Ren Shenqiang
Published: November 2022

High proton conductivity originated from its small size and the diffusion-free Grotthuss mechanism offers immense promise for proton-based magneto-ionic control of magnetic materials. Despite such promise, the realization of proton magneto-ionics is hampered by the lack of proton-responsive magnets as well as the solid-state sensing method. Here, we report the proton-based magneto-ionics in molecule-based magnet which serves as both solid-state proton battery electrode and radiofrequency sensing medium. The three-dimensional hydrogen-bonding network in such a molecule-based magnet yields a high proton conductivity of 1.6 × 10−3 S cm−1. The three-dimensional printed vascular hydrogel provides the on-demand proton stimulus to enable magneto-ionics, where the Raman spectroscopy shows the redox behavior responsible for the magnetism control. The radiofrequency proton sensor shows high sensitivity in a wide proton concentration range from 10−6 to 1 molar under a low working radiofrequency and magnetic field of 1 GHz and 405 Oe, respectively. The findings shown here demonstrate the promising sensing application of proton-based magneto-ionics.
CRY2 interacts with CIS1 to regulate thermosensory flowering via FLM alternative splicing
Authors: Zhao Zhiwei , Dent Craig , Liang Huafeng , Lv Junqing , Shang Guandong , Liu Yawen , Feng Fan , Wang Fei , Pang Junhong , Li Xu , Ma Libang , Li Bing , Sureshkumar Sridevi , Wang Jia-Wei , Balasubramanian Sureshkumar , Liu Hongtao
Published: November 2022

Cryptochromes (CRYs) are evolutionarily conserved photolyase-like photoreceptors found in almost all species, including mammals. CRYs regulate transcription by modulating the activity of several transcription factors, but whether and how they affect pre-mRNA processing are unknown. Photoperiod and temperature are closely associated seasonal cues that influence reproductive timing in plants. CRYs mediate photoperiod-responsive floral initiation, but it is largely unknown whether and how they are also involved in thermosensory flowering. We establish here that blue light and CRY2 play critical roles in thermosensory flowering in Arabidopsis thaliana by regulating RNA alternative splicing (AS) to affect protein expression and development. CRY2 INTERACTING SPLICING FACTOR 1 (CIS1) interacts with CRY2 in a blue light–dependent manner and promotes CRY2–mediated thermosensory flowering. Blue light, CRYs, and CISs affect transcriptome-wide AS profiles, including those of FLOWERING LOCUS M (FLM), which is critical for temperature modulation of flowering. Moreover, CIS1 binds to the FLM pre-mRNA to regulate its AS, while CRY2 regulates the RNA-binding activity of CIS1. Thus, blue light regulates thermosensory flowering via a CRY2–CIS1–FLM signaling pathway that links flowering responses to both light and ambient temperature.
A computational framework for guiding the MOCVD-growth of wafer-scale 2D materials
Authors: Momeni Kasra , Ji Yanzhou , Nayir Nadire , Sakib Nuruzzaman , Zhu Haoyue , Paul Shiddartha , Choudhury Tanushree H. , Neshani Sara , van Duin Adri C. T. , Redwing Joan M. , Chen Long-Qing
Published: November 2022

Reproducible wafer-scale growth of two-dimensional (2D) materials using the Chemical Vapor Deposition (CVD) process with precise control over their properties is challenging due to a lack of understanding of the growth mechanisms spanning over several length scales and sensitivity of the synthesis to subtle changes in growth conditions. A multiscale computational framework coupling Computational Fluid Dynamics (CFD), Phase-Field (PF), and reactive Molecular Dynamics (MD) was developed – called the CPM model – and experimentally verified. Correlation between theoretical predictions and thorough experimental measurements for a Metal-Organic CVD (MOCVD)-grown WSe2 model material revealed the full power of this computational approach. Large-area uniform 2D materials are synthesized via MOCVD, guided by computational analyses. The developed computational framework provides the foundation for guiding the synthesis of wafer-scale 2D materials with precise control over the coverage, morphology, and properties, a critical capability for fabricating electronic, optoelectronic, and quantum computing devices.
Dynamics of superconducting qubit relaxation times
Authors: Carroll M. , Rosenblatt S. , Jurcevic P. , Lauer I. , Kandala A.
Published: November 2022

Superconducting qubits are a leading candidate for quantum computing but display temporal fluctuations in their energy relaxation times T1. This introduces instabilities in multi-qubit device performance. Furthermore, autocorrelation in these time fluctuations introduces challenges for obtaining representative measures of T1 for process optimization and device screening. These T1 fluctuations are often attributed to time varying coupling of the qubit to defects, putative two level systems (TLSs). In this work, we develop a technique to probe the spectral and temporal dynamics of T1 in single junction transmons by repeated T1 measurements in the frequency vicinity of the bare qubit transition, via the AC-Stark effect. Across 10 qubits, we observe strong correlations between the mean T1 averaged over approximately nine months and a snapshot of an equally weighted T1 average over the Stark shifted frequency range. These observations are suggestive of an ergodic-like spectral diffusion of TLSs dominating T1, and offer a promising path to more rapid T1 characterization for device screening and process optimization.
An expert curated global legume checklist improves the accuracy of occurrence, biodiversity and taxonomic data
Authors: le Roux M. Marianne , Miller Joseph T. , Waller John , Döring Markus , Bruneau Anne
Published: November 2022

The Legume Phylogeny Working Group’s Taxonomy Working Group was tasked to create a community endorsed global legume checklist that will serve as a primary source of taxa for biodiversity data platforms and legume-related research. The checklist was published in June 2021, recognising 772 genera and 22,360 species. It is disseminated through the new Legume Data Portal as part of the Global Biodiversity Information Facility (GBIF) hosted portal initiative. The process that was followed to publish and disseminate the checklist and its content is described here. The impact of the work by the Taxonomy Working Group are quantified by comparing the published checklist with the GBIF taxonomic backbone. A total of 44,157 names overlapped with the GBIF taxonomic backbone while 30,456 names were added, which enabled more accurate name matching of 61,235 legume occurrences. Continuous improvement to the World Checklist of Vascular Plants (WCVP): Fabaceae checklist will allow the GBIF taxonomic backbone and other checklist managers to converge to a consistent and comprehensive list of legume taxa globally over time.
Predicting survival of glioblastoma from automatic whole-brain and tumor segmentation of MR images
Authors: Pálsson Sveinn , Cerri Stefano , Poulsen Hans Skovgaard , Urup Thomas , Law Ian , Van Leemput Koen
Published: November 2022

Survival prediction models can potentially be used to guide treatment of glioblastoma patients. However, currently available MR imaging biomarkers holding prognostic information are often challenging to interpret, have difficulties generalizing across data acquisitions, or are only applicable to pre-operative MR data. In this paper we aim to address these issues by introducing novel imaging features that can be automatically computed from MR images and fed into machine learning models to predict patient survival. The features we propose have a direct anatomical–functional interpretation: They measure the deformation caused by the tumor on the surrounding brain structures, comparing the shape of various structures in the patient’s brain to their expected shape in healthy individuals. To obtain the required segmentations, we use an automatic method that is contrast-adaptive and robust to missing modalities, making the features generalizable across scanners and imaging protocols. Since the features we propose do not depend on characteristics of the tumor region itself, they are also applicable to post-operative images, which have been much less studied in the context of survival prediction. Using experiments involving both pre- and post-operative data, we show that the proposed features carry prognostic value in terms of overall- and progression-free survival, over and above that of conventional non-imaging features.
The first complete genome of the simian malaria parasite Plasmodium brasilianum
Authors: Bajic Marko , Ravishankar Shashidhar , Sheth Mili , Rowe Lori A. , Pacheco M. Andreina , Patel Dhruviben S. , Batra Dhwani , Loparev Vladimir , Olsen Christian , Escalante Ananias A. , Vannberg Fredrik , Udhayakumar Venkatachalam , Barnwell John W. , Talundzic Eldin
Published: November 2022

Naturally occurring human infections by zoonotic Plasmodium species have been documented for P. knowlesi, P. cynomolgi, P. simium, P. simiovale, P. inui, P. inui-like, P. coatneyi, and P. brasilianum. Accurate detection of each species is complicated by their morphological similarities with other Plasmodium species. PCR-based assays offer a solution but require prior knowledge of adequate genomic targets that can distinguish the species. While whole genomes have been published for P. knowlesi, P. cynomolgi, P. simium, and P. inui, no complete genome for P. brasilianum has been available. Previously, we reported a draft genome for P. brasilianum, and here we report the completed genome for P. brasilianum. The genome is 31.4 Mb in size and comprises 14 chromosomes, the mitochondrial genome, the apicoplast genome, and 29 unplaced contigs. The chromosomes consist of 98.4% nucleotide sites that are identical to the P. malariae genome, the closest evolutionarily related species hypothesized to be the same species as P. brasilianum, with 41,125 non-synonymous SNPs (0.0722% of genome) identified between the two genomes. Furthermore, P. brasilianum had 4864 (82.1%) genes that share 80% or higher sequence similarity with 4970 (75.5%) P. malariae genes. This was demonstrated by the nearly identical genomic organization and multiple sequence alignments for the merozoite surface proteins msp3 and msp7. We observed a distinction in the repeat lengths of the circumsporozoite protein (CSP) gene sequences between P. brasilianum and P. malariae. Our results demonstrate a 97.3% pairwise identity between the P. brasilianum and the P. malariae genomes. These findings highlight the phylogenetic proximity of these two species, suggesting that P. malariae and P. brasilianum are strains of the same species, but this could not be fully evaluated with only a single genomic sequence for each species.
Super-resolved time–frequency measurements of coupled phonon dynamics in a 2D quantum material
Authors: Gentry Christian , Liao Chen-Ting , You Wenjing , Ryan Sinéad A. , Varner Baldwin Akin , Shi Xun , Guan Meng-Xue , Gray Thomas , Temple Doyle , Meng Sheng , Raschke Markus , Rossnagel Kai , Kapteyn Henry C. , Murnane Margaret M. , Cating-Subramanian Emma
Published: November 2022

Methods to probe and understand the dynamic response of materials following impulsive excitation are important for many fields, from materials and energy sciences to chemical and neuroscience. To design more efficient nano, energy, and quantum devices, new methods are needed to uncover the dominant excitations and reaction pathways. In this work, we implement a newly-developed superlet transform—a super-resolution time-frequency analytical method—to analyze and extract phonon dynamics in a laser-excited two-dimensional (2D) quantum material. This quasi-2D system, 1T-TaSe2, supports both equilibrium and metastable light-induced charge density wave (CDW) phases mediated by strongly coupled phonons. We compare the effectiveness of the superlet transform to standard time-frequency techniques. We find that the superlet transform is superior in both time and frequency resolution, and use it to observe and validate novel physics. In particular, we show fluence-dependent changes in the coupled dynamics of three phonon modes that are similar in frequency, including the CDW amplitude mode, that clearly demonstrate a change in the dominant charge-phonon couplings. More interestingly, the frequencies of the three phonon modes, including the strongly-coupled CDW amplitude mode, remain time- and fluence-independent, which is unusual compared to previously investigated materials. Our study opens a new avenue for capturing the coherent evolution and couplings of strongly-coupled materials and quantum systems.
Classification of rice leaf blast severity using hyperspectral imaging
Authors: Zhang Guosheng , Xu Tongyu , Tian Youwen , Feng Shuai , Zhao Dongxue , Guo Zhonghui
Published: November 2022

Rice leaf blast is prevalent worldwide and a serious threat to rice yield and quality. Hyperspectral imaging is an emerging technology used in plant disease research. In this study, we calculated the standard deviation (STD) of the spectral reflectance of whole rice leaves and constructed support vector machine (SVM) and probabilistic neural network (PNN) models to classify the degree of rice leaf blast at different growth stages. Average accuracies at jointing, booting and heading stages under the full-spectrum-based SVM model were 88.89%, 85.26%, and 87.32%, respectively, versus 80%, 83.16%, and 83.41% under the PNN model. Average accuracies at jointing, booting and heading stages under the STD-based SVM model were 97.78%, 92.63%, and 92.20%, respectively, versus 88.89%, 91.58%, and 92.20% under the PNN model. The STD of the spectral reflectance of the whole leaf differed not only within samples with different disease grades, but also among those at the same disease level. Compared with raw spectral reflectance data, STDs performed better in assessing rice leaf blast severity.
Model-based exploration of hypokalemia in dairy cows
Authors: Plöntzke Julia , Berg Mascha , Ehrig Rainald , Leonhard-Marek Sabine , Müller Kerstin Elisabeth , Röblitz Susanna
Published: November 2022

Hypokalemia in dairy cows, which is characterized by too low serum potassium levels, is a severe mineral disorder that can be life threatening. In this paper, we explore different originating conditions of hypokalemia—reduced potassium intake, increased excretion, acid-base disturbances, and increased insulin—by using a dynamic mathematical model for potassium balance in non-lactating and lactating cows. The simulations confirm observations described in literature. They illustrate, for example, that changes in dietary intake or excretion highly effect intracellular potassium levels, whereas extracellular levels vary only slightly. Simulations also show that the higher the potassium content in the diet, the more potassium is excreted with urine. Application of the mathematical model assists in experimental planning and therefore contributes to the 3R strategy: reduction, refinement and replacement of animal experiments.
Formulation, characterization of glucosamine loaded transfersomes and in vivo evaluation using papain induced arthritis model
Authors: Rasheed Muhammad Shahzad , Ansari Sameen Fatima , Shahzadi Iram
Published: November 2022

The aim of current study was to develop the transdermal transfersomes of glucosamine for better drug delivery. Stretch ability and plasticity of transfersomes membranes mitigate the risk of vesicle rupture in the skin and allows the drug carrying transfersome to pass through the epidermis following the natural water gradient. Transdermal delivery of Glucosamine has an advantage over oral route, having greater local concentration and fewer systemic effects. Thin Film Rotary method was use to prepare transfersomes, and characterization was carried out physio-chemically using electron microscopic studies, zeta potential evaluation, entrapment efficiency studies. To add on in the stability, development of a secondary topical vehicle using Carbopol 940 was carried out to enhance the shelf life of transfersomes. Furthermore, in vivo studies on rabbits were also carried out using the papain induced arthritis model to support the effectiveness of treatment. The radiology studies of knee joint of rabbits proved the effectiveness of glucosamine loaded transfersomes in healing the osteoarthritis with the blood plasma analysis remain unaltered. In vitro characterization showed the successful development of nano-deformable entities with good entrapment efficiency but with little stability, therefore modified into a gel. In a nut shell this modified new dosage from can be best alternative to other conventional options that owe lot of demerits.
Effectiveness of ultrasound-guided fascia hydrorelease on the coracohumeral ligament in patients with global limitation of the shoulder range of motion: a pilot study
Authors: Kimura Hiroaki , Suda Masei , Kobayashi Tadashi , Suzuki Shigeki , Fukui Sho , Obata Hideaki
Published: November 2022

We conducted a prospective single-arm interventional study of the treatment efficacy of ultrasound-guided fascia hydrorelease (US-FHR) on the coracohumeral ligament (CHL) of patients with global limitation of shoulder range of motion (ROM) without local inflammation. The primary outcome was the change in passive ROM (pROM) of external rotation (ER) after first US-FHR. Secondary outcomes included the change in pROM of other directions from baseline, the pain visual analogue scale (pVAS) at the timepoints after each procedure (first, second US-FHR and rehabilitation) as well as the change in the Shoulder Pain and Disability Index (SPADI) from the first to the second visit. Eleven patients underwent US-FHR. The pROM of ER after the 1st US-FHR changed by a median of 7.1° (p < 0.01). There was a statistically significant improvement in the pROM of flexion, extension, abduction, external rotation, and internal rotation from baseline to each timepoints. The pVAS at rest showed no significant improvement, although the pVAS at maximal ER showed a trend towards improvement. The SPADI score decreased by a median of 13.4 (p < 0.01). No adverse events were observed. US-FHR on the CHL with or without rehabilitation might be an effective, less invasive treatment for patients with global limitation of shoulder ROM.
Fractal interwoven resonator based penta-band metamaterial absorbers for THz sensing and imaging
Authors: Ozpinar Hurrem , Aksimsek Sinan
Published: November 2022

This paper presents a unique penta-band metamaterial absorber platform for terahertz imaging systems.The proposed fractal metamaterial absorber (FMMA) consists of fractal triangle section metasurfaces. By combining fractal resonators posing different operation skills in the same unit cell, the absorber shows multiband spectral response. The proposed unit cell structure operates at five near perfect absorption modes corresponding to the frequency bands of 1.1 THz, 3.4 THz, 4.9 THz, 5.9 THz, and 7.8 THz, respectively. Based on the fractal metamaterial absorber array, we also propose a sensing pixel design for bimaterial cantilever array sensing systems. The single pixel assembles 4x6 fractal resonator array and $$SiO_2$$

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-Al bimaterial microcantilevers. The sensing region of the FMMA pixel can bend the bimaterial cantilevers effectively at multiple modes, enhancing the imaging capacity. The effective medium theory is executed to visualize the constitute parameters during the absorption and reveal the origin of the rising modes. The absorption mechanism is also discussed based on the surface current distributions and electric field profiles. The numerical outcomes prove that the proposed fractal metamaterial unit cell is a promising candidate as an absorbing platform for THz band sensing and imaging applications. The derived iterative formula used in the fractal design procedure is explained for further investigations of microelectromechanical systems (MEMS) compatible compact absorber arrays.
Uncertainty-aware mixed-variable machine learning for materials design
Authors: Zhang Hengrui , Chen Wei , Iyer Akshay , Apley Daniel W. , Chen Wei
Published: November 2022

Data-driven design shows the promise of accelerating materials discovery but is challenging due to the prohibitive cost of searching the vast design space of chemistry, structure, and synthesis methods. Bayesian optimization (BO) employs uncertainty-aware machine learning models to select promising designs to evaluate, hence reducing the cost. However, BO with mixed numerical and categorical variables, which is of particular interest in materials design, has not been well studied. In this work, we survey frequentist and Bayesian approaches to uncertainty quantification of machine learning with mixed variables. We then conduct a systematic comparative study of their performances in BO using a popular representative model from each group, the random forest-based Lolo model (frequentist) and the latent variable Gaussian process model (Bayesian). We examine the efficacy of the two models in the optimization of mathematical functions, as well as properties of structural and functional materials, where we observe performance differences as related to problem dimensionality and complexity. By investigating the machine learning models’ predictive and uncertainty estimation capabilities, we provide interpretations of the observed performance differences. Our results provide practical guidance on choosing between frequentist and Bayesian uncertainty-aware machine learning models for mixed-variable BO in materials design.
Sirt3 deficiency induced down regulation of insulin degrading enzyme in comorbid Alzheimer’s disease with metabolic syndrome
Authors: Tyagi Alpna , Musa Musa , Labeikovsky Wladimir , Pugazhenthi Subbiah
Published: November 2022

SIRT3 deacetylates mitochondrial proteins, thereby enhancing their function. We have previously demonstrated that Sirt3 gene deletion leads to brain mitochondrial dysfunction and neuroinflammation. We also reported that silencing of Sirt3 gene in APP/PS1 mice results in exacerbation of insulin resistance, neuroinflammation and β amyloid plaque deposition. To further understand how metabolic syndrome and amyloid pathology interact, we performed RNA-seq analysis of the brain samples of APP/PS1/Sirt3-/- mice. Gene expression patterns were modulated in metabolic and inflammatory pathways by Sirt3 gene deletion, amyloid pathology, and the combination. Following Sirt3 gene deletion, a key finding was the decreased expression of insulin-degrading enzyme (IDE), an enzyme that regulates the levels of insulin and Aβ peptides. Western diet feeding of Sirt3-/- and APP/PS1 mice resulted in decrease of IDE protein, parallel to Sirt3 downregulation. Conversely, activation of SIRT3 by nicotinamide riboside in vivo and in vitro resulted in IDE upregulation. SIRT3 activation in vivo also increased the levels of neprilysin, another Aβ degrading enzyme and decreased the levels of BACE1 which generates Aβ peptide suggesting SIRT3’s role in amyloid plaque reduction. Our findings provide a plausible mechanism linking metabolic syndrome and amyloid pathology. SIRT3 may be a potential therapeutic target to treat AD.
Soil weathering dynamics and erosion in a dry oceanic area of the southern hemisphere (Otago, New Zealand)
Authors: Raab Gerald , Egli Markus , Norton Kevin P. , Martin Adam P. , Ketterer Michael E. , Tikhomirov Dmitry , Wanner Rahel , Scarciglia Fabio
Published: November 2022

Landscape evolution is driven by tectonics, climate and surface denudation. In New Zealand, tectonics and steep climatic gradients cause a dynamic landscape with intense chemical weathering, rapid soil formation, and high soil losses. In this study, soil, and elemental redistribution along two adjacent hillslopes in East Otago, New Zealand, having different landscape settings (ridge versus valley) are compared to identify soil weathering and erosion dynamics. Fallout radionuclides (239+240Pu) show that over the last ~ 60 years, average soil erosion rates in the valley (~ 260 [t km−2 year−1]) are low compared to the ridge (~ 990 [t km−2 year−1]). The ridge yields up to 26% lower soil weathering intensity than the topographical-protected valley. The lowest soil weathering intensity is found at both hilltop positions, where tors (residual rocks) are present and partially disintegrate. The soil weathering intensity increases with distance from tors, suggesting that tors rejuvenate the chemical weathering signature at the hilltop positions with fresh material. The inversed and decreasing weathering degree with all soil depth indicates that the fresh mineral contribution must be higher at the soil surface than at the bedrock weathering front. Higher erosion rates at the exposed ridge may be partially attributed to wind, consistent with rock abrasion of tors, and low local river sediment yields (56 [t km−2 year−1]). Thus, the East Otago spatial patterns of soil chemistry and erosion are governed by tor degradation and topographic exposure.
Improving performance of deep learning models using 3.5D U-Net via majority voting for tooth segmentation on cone beam computed tomography
Authors: Hsu Kang , Yuh Da-Yo , Lin Shao-Chieh , Lyu Pin-Sian , Pan Guan-Xin , Zhuang Yi-Chun , Chang Chia-Ching , Peng Hsu-Hsia , Lee Tung-Yang , Juan Cheng-Hsuan , Juan Cheng-En , Liu Yi-Jui , Juan Chun-Jung
Published: November 2022

Deep learning allows automatic segmentation of teeth on cone beam computed tomography (CBCT). However, the segmentation performance of deep learning varies among different training strategies. Our aim was to propose a 3.5D U-Net to improve the performance of the U-Net in segmenting teeth on CBCT. This study retrospectively enrolled 24 patients who received CBCT. Five U-Nets, including 2Da U-Net, 2Dc U-Net, 2Ds U-Net, 2.5Da U-Net, 3D U-Net, were trained to segment the teeth. Four additional U-Nets, including 2.5Dv U-Net, 3.5Dv5 U-Net, 3.5Dv4 U-Net, and 3.5Dv3 U-Net, were obtained using majority voting. Mathematical morphology operations including erosion and dilation (E&D) were applied to remove diminutive noise speckles. Segmentation performance was evaluated by fourfold cross validation using Dice similarity coefficient (DSC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV). Kruskal–Wallis test with post hoc analysis using Bonferroni correction was used for group comparison. P < 0.05 was considered statistically significant. Performance of U-Nets significantly varies among different training strategies for teeth segmentation on CBCT (P < 0.05). The 3.5Dv5 U-Net and 2.5Dv U-Net showed DSC and PPV significantly higher than any of five originally trained U-Nets (all P < 0.05). E&D significantly improved the DSC, accuracy, specificity, and PPV (all P < 0.005). The 3.5Dv5 U-Net achieved highest DSC and accuracy among all U-Nets. The segmentation performance of the U-Net can be improved by majority voting and E&D. Overall speaking, the 3.5Dv5 U-Net achieved the best segmentation performance among all U-Nets.
The significance of right ear auditory processing to balance
Authors: Putter-Katz Hanna , Horev Niza , Yaakobi Erez , Been Ella
Published: November 2022

Although the association between balance and hearing thresholds at different frequencies in the right/left ear is crucial, it has received scant empirical attention. Balance is widely ignored when evaluating hearing in adults. This study examined the relative contribution of left versus right ear hearing at different frequencies to balance, and the mediating role of suprathreshold speech perception on age-balance associations. Pure tone hearing thresholds (500–4000 Hz), suprathreshold speech perception, balance, and risk of falling were evaluated in 295 adults. The results indicate that the right ear contributes more to balance than the left ear. This might imply dominance of the left hemisphere in processing hearing cues for balance. Frequencies within the speech range (500/1000/2000 Hz) were correlated with balance and mediated the interaction between age and balance. These results should be considered when tailoring hearing and balance rehabilitation programs.
Hot weather hazard analysis over India
Authors: Srivastava Akhil , Mohapatra M. , Kumar Naresh
Published: November 2022

Heat waves are often termed as the silent killer and have become even more important as recent studies suggest that the heat wave have become second most devastating extreme weather events in terms of human deaths and losses. It is also been largely realised by scientific community that it is not just the high temperatures which are responsible for the gruesome effect of heat waves but several other meteorological parameters play a vital role in aggravating the impact and causing much more damages. In view of the above the attention of scientific community, weather forecasters as well as disaster managers has shifted to also take into account the different meteorological parameters like maximum and minimum temperatures, relative humidity, wind speed, duration/spell of heat waves and its intensity which are aggravating the impact of heat stress. In this background, this study is undertaken as an attempt to quantify the effect of different meteorological parameters on heat wave on different regions of India for different summer months (March, April, May and June). In this study the impact of individual meteorological parameter as well their cumulative effect is studied based on data of 30 years (1981–2010) for 300 stations. The effect of different meteorological parameters is identified for different months for different regions of the country. Also the cumulative scores are calculated for different regions considering different meteorological parameters, as a first initiative to perform heat hazard analysis and zonation over the entire country. This could serve as initial step for planning mitigation and adaptation strategies throughout the country. These scores as thresholds for different regions may be also useful for operational forecaster’s for early impact based warning services as well as for the disaster managers, for taking effective and timely actions.
Factors underlying bird community assembly in anthropogenic habitats depend on the biome
Authors: Vaccaro Anahí S. , Filloy Julieta
Published: November 2022

Production activities drive the replacement of original habitats with artificial ones, leading to new bird assemblages. In this study, we assessed if anthropogenic habitats acted as environmental filters causing functional redundancy or as promoters of functional divergence, depending on the biome. We also investigated if functional patterns derived from phylogenetic convergence or clustering. For this purpose, we computed the standardized effect sizes (SES) for avian functional and phylogenetic diversity using null models and compared the SES values among tree plantations, urban settlements (US), cattle pastures (CP), crop fields (CF) and natural habitats from two biomes: grassland and forest. We used generalized least squares models to test if functional and phylogenetic SES indicated functional redundancy or divergence, and phylogenetic convergence or clustering. We found functional redundancy in grassland and functional divergence in forest associated with environmental filtering and competitive exclusion, respectively. In grassland, functional structure was not associated with a clear phylogenetic pattern, while in forest functional divergence was caused by evolutionary convergence in CF and CP and conservation in US. The prevalences of functional redundancy and functional divergence patterns and their associated predominant mechanism of community assembly were found to depend on the biome and the regional species pool.
Future behaviours decision-making regarding travel avoidance during COVID-19 outbreaks
Authors: Ito Koichi , Kanemitsu Shunsuke , Kimura Ryusuke , Omori Ryosuke
Published: November 2022

Human behavioural changes are poorly understood, and this limitation has been a serious obstacle to epidemic forecasting. It is generally understood that people change their respective behaviours to reduce the risk of infection in response to the status of an epidemic or government interventions. We must first identify the factors that lead to such decision-making to predict these changes. However, due to an absence of a method to observe decision-making for future behaviour, understanding the behavioural responses to disease is limited. Here, we show that accommodation reservation data could reveal the decision-making process that underpins behavioural changes, travel avoidance, for reducing the risk of COVID-19 infections. We found that the motivation to avoid travel with respect to only short-term future behaviours dynamically varied and was associated with the outbreak status and/or the interventions of the government. Our developed method can quantitatively measure and predict a large-scale population’s behaviour to determine the future risk of COVID-19 infections. These findings enable us to better understand behavioural changes in response to disease spread, and thus, contribute to the development of reliable long-term forecasting of disease spread.
Metacognitive deficits are associated with lower sensitivity to preference reversals in nicotine dependence
Authors: Soutschek Alexander , Bulley Adam , Wittekind Charlotte E.
Published: November 2022

Deficits in impulse control belong to the core profile of nicotine dependence. Smokers might thus benefit from voluntarily self-restricting their access to the immediate temptation of nicotine products (precommitment) in order to avoid impulse control failures. However, little is known about how smokers’ willingness to engage in voluntary self-restrictions is determined by metacognitive insight into their general preferences for immediate over delayed rewards. Here, with a series of monetary intertemporal choice tasks, we provide empirical evidence for reduced metacognitive accuracy in smokers relative to non-smokers and show that smokers overestimate the subjective value of delayed rewards relative to their revealed preferences. In line with the metacognitive deficits, smokers were also less sensitive to the risk of preference reversals when deciding whether or not to restrict their access to short-term financial rewards. Taken together, the current findings suggest that deficits not only in impulse control but also in metacognition may hamper smokers’ resistance to immediate rewards and capacity to pursue long-term goals.