bluuebunny/crossref_metadata_2025 huggingface dataset:
A theory of cortical map formation in the visual brain
Authors: Najafian Sohrab , Koch Erin , Teh Kai Lun , Jin Jianzhong , Rahimi-Nasrabadi Hamed , Zaidi Qasim , Kremkow Jens , Alonso Jose-Manuel
Published: April 2022

The cerebral cortex receives multiple afferents from the thalamus that segregate by stimulus modality forming cortical maps for each sense. In vision, the primary visual cortex maps the multiple dimensions of the visual stimulus in patterns that vary across species for reasons unknown. Here we introduce a general theory of cortical map formation, which proposes that map diversity emerges from species variations in the thalamic afferent density sampling sensory space. In the theory, increasing afferent sampling density enlarges the cortical domains representing the same visual point, allowing the segregation of afferents and cortical targets by multiple stimulus dimensions. We illustrate the theory with an afferent-density model that accurately replicates the maps of different species through afferent segregation followed by thalamocortical convergence pruned by visual experience. Because thalamocortical pathways use similar mechanisms for axon segregation and pruning, the theory may extend to other sensory areas of the mammalian brain.
Allogeneic TCRαβ deficient CAR T-cells targeting CD123 in acute myeloid leukemia
Authors: Sugita Mayumi , Galetto Roman , Zong Hongliang , Ewing-Crystal Nathan , Trujillo-Alonso Vicenta , Mencia-Trinchant Nuria , Yip Winnie , Filipe Stephanie , Lebuhotel Celine , Gouble Agnès , Hassane Duane C. , Smith Julianne , Roboz Gail J. , Guzman Monica L.
Published: April 2022

Acute myeloid leukemia (AML) is a disease with high incidence of relapse that is originated and maintained from leukemia stem cells (LSCs). Hematopoietic stem cells can be distinguished from LSCs by an array of cell surface antigens such as CD123, thus a candidate to eliminate LSCs using a variety of approaches, including CAR T cells. Here, we evaluate the potential of allogeneic gene-edited CAR T cells targeting CD123 to eliminate LSCs (UCART123). UCART123 cells are TCRαβneg T cells generated from healthy donors using TALEN® gene-editing technology, decreasing the likelihood of graft vs host disease. As safety feature, cells express RQR8 to allow elimination with Rituximab. UCART123 effectively eliminates AML cells in vitro and in vivo with significant benefits in overall survival of AML-patient derived xenograft mice. Furthermore, UCART123 preferentially target AML over normal cells with modest toxicity to normal hematopoietic stem/progenitor cells. Together these results suggest that UCART123 represents an off-the shelf therapeutic approach for AML.
Targeting CD123 in blastic plasmacytoid dendritic cell neoplasm using allogeneic anti-CD123 CAR T cells
Authors: Cai Tianyu , Gouble Agnès , Black Kathryn L. , Skwarska Anna , Naqvi Ammar S. , Taylor Deanne , Zhao Ming , Yuan Qi , Sugita Mayumi , Zhang Qi , Galetto Roman , Filipe Stéphanie , Cavazos Antonio , Han Lina , Kuruvilla Vinitha , Ma Helen , Weng Connie , Liu Chang-Gong , Liu Xiuping , Konoplev Sergej , Gu Jun , Tang Guilin , Su Xiaoping , Al-Atrash Gheath , Ciurea Stefan , Neelapu Sattva S. , Lane Andrew A. , Kantarjian Hagop , Guzman Monica L. , Pemmaraju Naveen , Smith Julianne , Thomas-Tikhonenko Andrei , Konopleva Marina
Published: April 2022

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcomes with conventional therapy. Nearly 100% of BPDCNs overexpress interleukin 3 receptor subunit alpha (CD123). Given that CD123 is differentially expressed on the surface of BPDCN cells, it has emerged as an attractive therapeutic target. UCART123 is an investigational product consisting of allogeneic T cells expressing an anti-CD123 chimeric antigen receptor (CAR), edited with TALEN® nucleases. In this study, we examine the antitumor activity of UCART123 in preclinical models of BPDCN. We report that UCART123 have selective antitumor activity against CD123-positive primary BPDCN samples (while sparing normal hematopoietic progenitor cells) in the in vitro cytotoxicity and T cell degranulation assays; supported by the increased secretion of IFNγ by UCART123 cells when cultured in the presence of BPDCN cells. UCART123 eradicate BPDCN and result in long-term disease-free survival in a subset of primary patient-derived BPDCN xenograft mouse models. One potential challenge of CD123 targeting therapies is the loss of CD123 antigen through diverse genetic mechanisms, an event observed in one of three BPDCN PDX studied. In summary, these results provide a preclinical proof-of-principle that allogeneic UCART123 cells have potent anti-BPDCN activity.
Vertically stacked, low-voltage organic ternary logic circuits including nonvolatile floating-gate memory transistors
Authors: Choi Junhwan , Lee Changhyeon , Lee Chungryeol , Park Hongkeun , Lee Seung Min , Kim Chang-Hyun , Yoo Hocheon , Im Sung Gap
Published: April 2022

Multi-valued logic (MVL) circuits based on heterojunction transistor (HTR) have emerged as an effective strategy for high-density information processing without increasing the circuit complexity. Herein, an organic ternary logic inverter (T-inverter) is demonstrated, where a nonvolatile floating-gate flash memory is employed to control the channel conductance systematically, thus realizing the stabilized T-inverter operation. The 3-dimensional (3D) T-inverter is fabricated in a vertically stacked form based on all-dry processes, which enables the high-density integration with high device uniformity. In the flash memory, ultrathin polymer dielectrics are utilized to reduce the programming/erasing voltage as well as operating voltage. With the optimum programming state, the 3D T-inverter fulfills all the important requirements such as full-swing operation, optimum intermediate logic value (~VDD/2), high DC gain exceeding 20 V/V as well as low-voltage operation (< 5 V). The organic flash memory exhibits long retention characteristics (current change less than 10% after 104 s), leading to the long-term stability of the 3D T-inverter. We believe the 3D T-inverter employing flash memory developed in this study can provide a useful insight to achieve high-performance MVL circuits.
Stopping molecular rotation using coherent ultra-low-energy magnetic manipulations
Authors: Chadwick Helen , Somers Mark F. , Stewart Aisling C. , Alkoby Yosef , Carter Thomas J. D. , Butkovicova Dagmar , Alexandrowicz Gil
Published: April 2022

Rotational motion lies at the heart of intermolecular, molecule-surface chemistry and cold molecule science, motivating the development of methods to excite and de-excite rotations. Existing schemes involve perturbing the molecules with photons or electrons which supply or remove energy comparable to the rotational level spacing. Here, we study the possibility of de-exciting the molecular rotation of a D2 molecule, from J = 2 to the non-rotating J = 0 state, without using an energy-matched perturbation. We show that passing the beam through a 1 m long magnetic field, which splits the rotational projection states by only 10−12 eV, can change the probability that a molecule-surface collision will stop a molecule from rotating and lose rotational energy which is 9 orders larger than that of the magnetic manipulation. Calculations confirm that different rotational orientations have different de-excitation probabilities but underestimate rotational flips (∆mJ$$\ne$$
≠
0), highlighting the importance of the results as a sensitive benchmark for further developing theoretical models of molecule-surface interactions.
Deficiency in coatomer complex I causes aberrant activation of STING signalling
Authors: Steiner Annemarie , Hrovat-Schaale Katja , Prigione Ignazia , Yu Chien-Hsiung , Laohamonthonkul Pawat , Harapas Cassandra R. , Low Ronnie Ren Jie , De Nardo Dominic , Dagley Laura F. , Mlodzianoski Michael J. , Rogers Kelly L. , Zillinger Thomas , Hartmann Gunther , Gantier Michael P. , Gattorno Marco , Geyer Matthias , Volpi Stefano , Davidson Sophia , Masters Seth L.
Published: April 2022

Coatomer complex I (COPI) mediates retrograde vesicular trafficking from Golgi to the endoplasmic reticulum (ER) and within Golgi compartments. Deficiency in subunit alpha causes COPA syndrome and is associated with type I IFN signalling, although the upstream innate immune sensor involved was unknown. Using in vitro models we find aberrant activation of the STING pathway due to deficient retrograde but probably not intra-Golgi transport. Further we find the upstream cytosolic DNA sensor cGAS as essentially required to drive type I IFN signalling. Genetic deletion of COPI subunits COPG1 or COPD similarly induces type I IFN activation in vitro, which suggests that inflammatory diseases associated with mutations in other COPI subunit genes may exist. Finally, we demonstrate that inflammation in COPA syndrome patient peripheral blood mononuclear cells and COPI-deficient cell lines is ameliorated by treatment with the small molecule STING inhibitor H-151, suggesting targeted inhibition of the cGAS/STING pathway as a promising therapeutic approach.
Switchable bifunctional molecular recognition in water using a pH-responsive Endo-functionalized cavity
Authors: Wang Xiaoping , Quan Mao , Yao Huan , Pang Xin-Yu , Ke Hua , Jiang Wei
Published: April 2022

The construction of water-soluble synthetic hosts with a stimuli-responsive endo-functionalized cavity is challenging. These hosts feature a switchable cavity and may bring new properties to the fields of self-assembly, molecular machines, and biomedical sciences. Herein, we report a pair of water-soluble naphthotubes with a pH-responsive endo-functionalized cavity. The inward-directing secondary amine group of the hosts can be protonated and deprotonated. Thus, the hosts have different cavity features at the two states and show drastically different binding preference and selectivity in water. We reveal that the binding difference of the two host states is originated from the differences in charge repulsion, hydrogen bonding and the hydrophobic effects. Moreover, the guest binding can be easily switched in a ternary mixture with two guest molecules by adjusting the pH value of the solution. These pH-responsive hosts may be used for the construction of smart self-assembly systems and water-soluble molecular machines.
Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy
Authors: Kim Hong Joo , Mohassel Payam , Donkervoort Sandra , Guo Lin , O’Donovan Kevin , Coughlin Maura , Lornage Xaviere , Foulds Nicola , Hammans Simon R. , Foley A. Reghan , Fare Charlotte M. , Ford Alice F. , Ogasawara Masashi , Sato Aki , Iida Aritoshi , Munot Pinki , Ambegaonkar Gautam , Phadke Rahul , O’Donovan Dominic G. , Buchert Rebecca , Grimmel Mona , Töpf Ana , Zaharieva Irina T. , Brady Lauren , Hu Ying , Lloyd Thomas E. , Klein Andrea , Steinlin Maja , Kuster Alice , Mercier Sandra , Marcorelles Pascale , Péréon Yann , Fleurence Emmanuelle , Manzur Adnan , Ennis Sarah , Upstill-Goddard Rosanna , Bello Luca , Bertolin Cinzia , Pegoraro Elena , Salviati Leonardo , French Courtney E. , Shatillo Andriy , Raymond F. Lucy , Haack Tobias B. , Quijano-Roy Susana , Böhm Johann , Nelson Isabelle , Stojkovic Tanya , Evangelista Teresinha , Straub Volker , Romero Norma B. , Laporte Jocelyn , Muntoni Francesco , Nishino Ichizo , Tarnopolsky Mark A. , Shorter James , Bönnemann Carsten G. , Taylor J. Paul
Published: April 2022

Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with a severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD) but of much earlier onset, caused by heterozygous frameshift variants in the RBP hnRNPA2/B1. All disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and are translated to produce hnRNPA2/B1 protein with the same neomorphic C-terminal sequence. In contrast to previously reported disease-causing missense variants in HNRNPA2B1, these frameshift variants do not increase the propensity of hnRNPA2 protein to fibrillize. Rather, the frameshift variants have reduced affinity for the nuclear import receptor karyopherin β2, resulting in cytoplasmic accumulation of hnRNPA2 protein in cells and in animal models that recapitulate the human pathology. Thus, we expand the phenotypes associated with HNRNPA2B1 to include an early-onset form of OPMD caused by frameshift variants that alter its nucleocytoplasmic transport dynamics.
Efficient and stable noble-metal-free catalyst for acidic water oxidation
Authors: Pan Sanjiang , Li Hao , Liu Dan , Huang Rui , Pan Xuelei , Ren Dan , Li Jun , Shakouri Mohsen , Zhang Qixing , Wang Manjing , Wei Changchun , Mai Liqiang , Zhang Bo , Zhao Ying , Wang Zhenbin , Graetzel Michael , Zhang Xiaodan
Published: April 2022

Developing non-noble catalysts with superior activity and durability for oxygen evolution reaction (OER) in acidic media is paramount for hydrogen production from water. Still, challenges remain due to the inadequate activity and stability of the OER catalyst. Here, we report a cost-effective and stable manganese oxybromide (Mn7.5O10Br3) catalyst exhibiting an excellent OER activity in acidic electrolytes, with an overpotential of as low as 295 ± 5 mV at a current density of 10 mA cm−2. Mn7.5O10Br3 maintains good stability under operating conditions for at least 500 h. In situ Raman spectroscopy, X ray absorption near edge spectroscopy, and density functional theory calculations confirm that a self-oxidized surface with enhanced electronic transmission capacity forms on Mn7.5O10Br3 and is responsible for both the high catalytic activity and long-term stability during catalysis. The development of Mn7.5O10Br3 as an OER catalyst provides crucial insights into the design of non-noble metal electrocatalysts for water oxidation.
Quadrupolar magnetic excitations in an isotropic spin-1 antiferromagnet
Authors: Nag A. , Nocera A. , Agrestini S. , Garcia-Fernandez M. , Walters A. C. , Cheong Sang-Wook , Johnston S. , Zhou Ke-Jin
Published: April 2022

The microscopic origins of emergent behaviours in condensed matter systems are encoded in their excitations. In ordinary magnetic materials, single spin-flips give rise to collective dipolar magnetic excitations called magnons. Likewise, multiple spin-flips can give rise to multipolar magnetic excitations in magnetic materials with spin S ≥ 1. Unfortunately, since most experimental probes are governed by dipolar selection rules, collective multipolar excitations have generally remained elusive. For instance, only dipolar magnetic excitations have been observed in isotropic S = 1 Haldane spin systems. Here, we unveil a hidden quadrupolar constituent of the spin dynamics in antiferromagnetic S = 1 Haldane chain material Y2BaNiO5 using Ni L3-edge resonant inelastic x-ray scattering. Our results demonstrate that pure quadrupolar magnetic excitations can be probed without direct interactions with dipolar excitations or anisotropic perturbations. Originating from on-site double spin-flip processes, the quadrupolar magnetic excitations in Y2BaNiO5 show a remarkable dual nature of collective dispersion. While one component propagates as non-interacting entities, the other behaves as a bound quadrupolar magnetic wave. This result highlights the rich and largely unexplored physics of higher-order magnetic excitations.
Sucrose synthases are not involved in starch synthesis in Arabidopsis leaves
Authors: Fünfgeld Maximilian M. F. F. , Wang Wei , Ishihara Hirofumi , Arrivault Stéphanie , Feil Regina , Smith Alison M. , Stitt Mark , Lunn John E. , Niittylä Totte
Published: April 2022

Many plants accumulate transitory starch reserves in their leaves during the day to buffer their carbohydrate supply against fluctuating light conditions, and to provide carbon and energy for survival at night. It is universally accepted that transitory starch is synthesized from ADP-glucose (ADPG) in the chloroplasts. However, the consensus that ADPG is made in the chloroplasts by ADPG pyrophosphorylase has been challenged by a controversial proposal that ADPG is made primarily in the cytosol, probably by sucrose synthase (SUS), and then imported into the chloroplasts. To resolve this long-standing controversy, we critically re-examined the experimental evidence that appears to conflict with the consensus pathway. We show that when precautions are taken to avoid artefactual changes during leaf sampling, Arabidopsis thaliana mutants that lack SUS activity in mesophyll cells (quadruple sus1234) or have no SUS activity (sextuple sus123456) have wild-type levels of ADPG and starch, while ADPG is 20 times lower in the pgm and adg1 mutants that are blocked in the consensus chloroplastic pathway of starch synthesis. We conclude that the ADPG needed for starch synthesis in leaves is synthesized primarily by ADPG pyrophosphorylase in the chloroplasts.
A machine-learned interatomic potential for silica and its relation to empirical models
Authors: Erhard Linus C. , Rohrer Jochen , Albe Karsten , Deringer Volker L.
Published: April 2022

Silica (SiO2) is an abundant material with a wide range of applications. Despite much progress, the atomistic modelling of the different forms of silica has remained a challenge. Here we show that by combining density-functional theory at the SCAN functional level with machine-learning-based interatomic potential fitting, a range of condensed phases of silica can be accurately described. We present a Gaussian approximation potential model that achieves high accuracy for the thermodynamic properties of the crystalline phases, and we compare its performance (and performance–cost trade-off) with that of multiple empirically fitted interatomic potentials for silica. We also include amorphous phases, assessing the ability of the potentials to describe structures of melt-quenched glassy silica, their energetic stability, and the high-pressure structural transition to a mainly sixfold-coordinated phase. We suggest that rather than standing on their own, machine-learned potentials for silica may be used in conjunction with suitable empirical models, each having a distinct role and complementing the other, by combining the advantages of the long simulation times afforded by empirical potentials and the near-quantum-mechanical accuracy of machine-learned potentials. This way, our work is expected to advance atomistic simulations of this key material and to benefit further computational studies in the field.
Composition design of high-entropy alloys with deep sets learning
Authors: Zhang Jie , Cai Chen , Kim George , Wang Yusu , Chen Wei
Published: April 2022

High entropy alloys (HEAs) are an important material class in the development of next-generation structural materials, but the astronomically large composition space cannot be efficiently explored by experiments or first-principles calculations. Machine learning (ML) methods might address this challenge, but ML of HEAs has been hindered by the scarcity of HEA property data. In this work, the EMTO-CPA method was used to generate a large HEA dataset (spanning a composition space of 14 elements) containing 7086 cubic HEA structures with structural properties, 1911 of which have the complete elastic tensor calculated. The elastic property dataset was used to train a ML model with the Deep Sets architecture. The Deep Sets model has better predictive performance and generalizability compared to other ML models. Association rule mining was applied to the model predictions to describe the compositional dependence of HEA elastic properties and to demonstrate the potential for data-driven alloy design.
Insights into the influence of oxide inclusions on corrosion performance of additive manufactured magnesium alloys
Authors: Kuah Kai Xiang , Salehi Mojtaba , Ong Wee Kit , Seet Hang Li , Nai Mui Ling Sharon , Wijesinghe Sudesh , Blackwood Daniel J.
Published: April 2022

The corrosion performance of binder jet additive samples is compared with cast samples through potentiodynamic polarization in Na2SO4 solution. Higher zinc levels in the magnesium matrix and the presence of MgO within the microstructure of the binder jet printed alloy contribute to increases in the anodic and cathodic kinetics, respectively. It is proposed that electron inhomogeneity at the Mg/MgO interface in the binder jet printed alloy is the source of the catalytic activity of the hydrogen evolution reaction. The removal of MgO inclusions suppressed the cathodic reaction relative to the large increase in kinetics seen in similarly treated cast samples.
Gait abnormalities and non-motor symptoms predict abnormal dopaminergic imaging in presumed drug-induced Parkinsonism
Authors: Aamodt Whitley W. , Dubroff Jacob G. , Cheng Gang , Taylor Betty , Wood Stephanie , Duda John E. , Morley James F.
Published: April 2022

Drug-induced parkinsonism (DIP) can be clinically indistinguishable from degenerative parkinsonism, and bedside assessments are needed to differentiate between these conditions. We examined 34 U.S. Veterans with DIP using 123I-FP-CIT (DAT-SPECT) to identify underlying nigrostriatal degeneration. Participants were 94% male with mean age of 64.5 ± 7.1 years. DAT-SPECT was abnormal in 12/34 (35%). Comparing normal and abnormal imaging groups, there were no differences in age, sex, race/ethnicity, psychiatric diagnosis, motor severity, or RBD Screening Questionnaire scores. Those with underlying neurodegeneration reported significantly more non-motor symptoms (NMS), worse olfactory function on the University of Pennsylvania Smell Identification Test, and greater turning duration/steps on the instrumented Timed Up and Go. Area under the curve (AUC) combining poor olfaction and total NMS burden was 0.84 (CI 0.71–0.97), while AUC for turn steps was 0.91 (CI 0.81–1.00). Gait impairment, hyposmia, and NMS may be useful alone and in combination to identify DIP patients with underlying dopaminergic degeneration.
Forest degradation drives widespread avian habitat and population declines
Authors: Betts Matthew G. , Yang Zhiqiang , Hadley Adam S. , Smith Adam C. , Rousseau Josée S. , Northrup Joseph M. , Nocera Joseph J. , Gorelick Noel , Gerber Brian D.
Published: April 2022

In many regions of the world, forest management has reduced old forest and simplified forest structure and composition. We hypothesized that such forest degradation has resulted in long-term habitat loss for forest-associated bird species of eastern Canada (130,017 km2) which, in turn, has caused bird-population declines. Despite little change in overall forest cover, we found substantial reductions in old forest as a result of frequent clear-cutting and a broad-scale transformation to intensified forestry. Back-cast species distribution models revealed that breeding habitat loss occurred for 66% of the 54 most common species from 1985 to 2020 and was strongly associated with reduction in old age classes. Using a long-term, independent dataset, we found that habitat amount predicted population size for 94% of species, and habitat loss was associated with population declines for old-forest species. Forest degradation may therefore be a primary cause of biodiversity decline in managed forest landscapes.
Life tables of annual life expectancy and mortality for companion dogs in the United Kingdom
Authors: Teng Kendy Tzu-yun , Brodbelt Dave C. , Pegram Camilla , Church David B. , O’Neill Dan G.
Published: April 2022

A life table is a tabulated expression of life expectancy and mortality-related information at specified ages in a given population. This study utilised VetCompass data to develop life tables for the UK companion dog population and broken down by sex, Kennel Club breed group, and common breeds. Among 30,563 dogs that died between 1st January 2016 and 31st July 2020, life expectancy at age 0 was 11.23 [95% confidence interval (CI): 11.19–11.27] years. Female dogs (11.41 years; 95% CI: 11.35–11.47) had a greater life expectancy than males (11.07 years; 95% CI: 11.01–11.13) at age 0. Life tables varied widely between breeds. Jack Russell Terrier (12.72 years; 95% CI: 12.53–12.90) and French Bulldog (4.53 years; 95% CI: 4.14–5.01) had the longest and shortest life expectancy at age 0, respectively. Life tables generated by the current study allow a deeper understanding of the varied life trajectory across many types of dogs and offer novel insights and applications to improve canine health and welfare. The current study helps promote further understanding of life expectancy, which will benefit pet owners and the veterinary profession, along with many other sectors.
Identification and validation of prognosis-associated DNA repair gene signatures in colorectal cancer
Authors: Song Dingli , Zhang Dai , Chen Sisi , Wu Jie , Hao Qian , Zhao Lili , Ren Hong , Du Ning
Published: April 2022

Colorectal cancer (CRC) is the third most common malignant tumor. DNA damage plays a crucial role in tumorigenesis, and abnormal DNA repair pathways affect the occurrence and progression of CRC. In the current study, we aimed to construct a DNA repair-related gene (DRG) signature to predict the overall survival (OS) of patients with CRC patients. The differentially expressed DRGs (DE-DRGs) were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The prognostic gene signature was identified by univariate Cox regression and least absolute shrinkage and selection operator (LASSO)-penalized Cox proportional hazards regression analysis. The predictive ability of the model was evaluated using the Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves. The gene set enrichment analysis (GSEA) was performed to explore the underlying biological processes and signaling pathways. ESTIMATE and CIBERSORT were implemented to estimate the tumor immune score and immune cell infiltration status between the different risk group. The half-maximal inhibitory concentration (IC50) was evaluated to representing the drug response of this signature. Nine DE-DRGs (ESCO2, AXIN2, PLK1, CDC25C, IGF1, TREX2, ALKBH2, ESR1 and MC1R) signatures was constructed to classify patients into high- and low-risk groups. The risk score was an independent prognostic indicator of OS (hazard ratio > 1, P < 0.001). The genetic alteration analysis indicated that the nine DE-DRGs in the signature were changed in 63 required samples (100%), and the major alteration was missense mutation. Function enrichment analysis revealed that the immune response and mtotic sister chromatid segregation were the main biological processes. The high-risk group had higher immune score than the low-risk group. What’s more, low-risk patients were more sensitive to selumetinib and dasatinib. The nine DE-DRGs signature was significantly associated with OS and provided a new insight for the diagnosis and treatment of CRC.
Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer
Authors: Miura Kouki , Kawakita Daisuke , Oze Isao , Suzuki Motoyuki , Sugasawa Masashi , Endo Kazuhira , Sakashita Tomohiro , Ohba Shinichi , Suzuki Mikio , Shiotani Akihiro , Kohno Naoyuki , Maruo Takashi , Suzuki Chiaki , Iki Takehiro , Hiwatashi Nao , Matsumoto Fumihiko , Kobayashi Kenya , Toyoda Minoru , Hanyu Kenji , Koide Yusuke , Murakami Yoshiko , Hasegawa Yasuhisa
Published: April 2022

Prophylactic elective neck dissection (ND) with navigation surgery using radioisotope-based sentinel lymph node biopsy (SLNB) is non-inferior to elective ND in terms of survival but has an advantage in postoperative functional disability. We conducted a subgroup analysis to identify predictive factors for false-negative (FN)-SLNB in patients with early oral cavity cancer. This study is a supplementary analysis using the dataset of a previously reported randomized clinical trial on SLN navigation surgery for oral cancers. This study investigated the association of clinical and SLN-related factors with false-negative cases in the SLNB group. From 2011 to 2016, 275 patients were enrolled and randomly assigned to the ND and SLNB study groups, with 134 patients assigned to the SLNB group. In the SLNB group, seven cases with negative SLNs and neck recurrences were judged as FN-SLNBs according to the general definition. The number of detected SLNs with and without adjusting for the propensity score was significantly associated with FNs in the logistic analysis. FN-SLNB was associated with the number of identified SLNs, suggesting the need for careful postoperative monitoring for neck recurrence in patients with one or two identified SLNs after acquiring sufficient experience in the identification technique.
Optimal cutoff values for physical function tests in elderly patients with heart failure
Authors: Aida Keita , Kamiya Kentaro , Hamazaki Nobuaki , Nozaki Kohei , Ichikawa Takafumi , Nakamura Takeshi , Yamashita Masashi , Uchida Shota , Maekawa Emi , Reed Jennifer L. , Yamaoka-Tojo Minako , Matsunaga Atsuhiko , Ako Junya
Published: April 2022

Six-minute walk distance (6MWD) of 300 and 400 m are important targets of functional capacity. The present study was performed to determine cutoff values of physical function associated with 6MWD < 300 m and < 400 m in elderly patients with heart failure (HF). 6MWD, handgrip strength, quadriceps isometric strength (QIS), one-leg standing time (OLST), and 5-times sit-to-stand (5STS) before hospital discharge were evaluated in 1001 patients > 65 years (median age, 75: interquartile range, 71–80, 607 men) with HF. 6MWD < 300 and < 400 m were seen in 323 patients (32.3%) and 658 patients (65.7%), respectively. Handgrip strength, QIS, OLST, and 5STS were associated with 6MWD < 300 and < 400 m, respectively (P < 0.001). The cutoff values of handgrip strength, QIS, OLST, and 5STS were 18.9 kg, 35.0% body mass (BM), 9.1 s, and 9.5 s for 6MWD < 300 m, and 21.9 kg, 40.0% BM, 12.0 s, and 8.8 s for < 400 m, respectively. The cutoff values of physical function could be used to set cardiac rehabilitation goals and limiting determinants of reduced functional capacity in a clinical setting in elderly patients with HF.
A novel soluble epoxide hydrolase vaccine protects murine cardiac muscle against myocardial infarction
Authors: Kitsuka Takahiro , Shiraki Aya , Oyama Jun-ichi , Nakagami Hironori , Tanaka Atsushi , Node Koichi
Published: April 2022

Myocardial infarction is still a life-threatening disease, even though its prognosis has been improved through the development of percutaneous coronary intervention and pharmacotherapy. In addition, heart failure due to remodeling after myocardial infarction requires lifelong management. The aim of this study was to develop a novel treatment suppressing the myocardial damage done by myocardial infarction. We focused on inhibition of soluble epoxide hydrolase to prolong the activation of epoxyeicosatrienoic acids, which have vasodilatory and anti-inflammatory properties. We successfully made a new vaccine to inactivate soluble epoxide hydrolase, and we have evaluated the effect of the vaccine in a rat myocardial infarction model. In the vaccinated group, the ischemic area was significantly reduced, and cardiac function was significantly preserved. Vaccine treatment clearly increased microvessels in the border area and suppressed fibrosis secondary to myocardial infarction. This soluble epoxide hydrolase vaccine is a novel treatment for improving cardiac function following myocardial infarction.
Responses of butter leaf lettuce to mixed red and blue light with extended light/dark cycle period
Authors: Chen Xiao-li , Li You-li , Wang Li-chun , Yang Qi-chang , Guo Wen-zhong
Published: April 2022

To investigate the effects of extended light/dark (L/D) cycle period (relative to the diurnal L/D cycle) on lettuce and explore potential advantages of abnormal L/D cycles, butter leaf lettuce were grown in a plant factory with artificial light (PFAL) and exposed to mixed red (R) and blue (B) LED light with different L/D cycles that were respectively 16 h light/8 h dark (L16/D8, as control), L24/D12, L48/D24, L96/D48 and L120/D60. The results showed that, all the abnormal L/D cycles increased shoot dry weight (DW) of lettuce (by 34–83%) compared with the control, and lettuce DW increased with the L/D cycle period prolonged. The contents of soluble sugar and crude fiber in lettuce showed an overall upward trend with the length of L/D cycle extended, and the highest vitamin C content as well as low nitrate content were both detected in lettuce treated with L120/D60. The light use efficiency (LUE) and electric use efficiency (EUE) of lettuce reached the maximum (respectively 5.37% and 1.76%) under L120/D60 treatment and so were DW, Assimilation rate (A), RC/CS, ABS/CS, TRo/CS and DIo/CS, indicating that longer L/D cycle period was beneficial for the assimilation efficiency and dry matter accumulation in lettuce leaves. The highest shoot fresh weight (FW) and nitrate content detected in lettuce subjected to L24/D12 may be related to the vigorous growth of root, specific L/D cycle seemed to strengthen root growth and water absorption of lettuce. The openness level of RC in PSII (Ψo), ETo/CS, and PIabs were all the highest in lettuce treated with L24/D12, implying that slightly extending the L/D cycle period might promote the energy flowing to the final electron transfer chain. In general, irradiation modes with extended L/D cycle period had the potential to improve energy use efficiency and biomass of lettuce in PFAL. No obvious stress or injury was detected in lettuce subjected to prolonged L/D cycles in terms of plant growth and production. From the perspective of shoot FW, the optimal treatment in this study was L24/D12, while L120/D60 was the recommended treatment as regards of the energy use efficiency and nutritional quality.
Direct observation of DNA alterations induced by a DNA disruptor
Authors: Ohshiro Takahito , Asai Ayumu , Konno Masamitsu , Ohkawa Mayuka , Komoto Yuki , Ofusa Ken , Ishii Hideshi , Taniguchi Masateru
Published: April 2022

DNA alterations, such as base modifications and mutations, are closely related to the activity of transcription factors and the corresponding cell functions; therefore, detection of DNA alterations is important for understanding their relationships. Particularly, DNA alterations caused by exposure to exogenous molecules, such as nucleic acid analogues for cancer therapy and the corresponding changes in cell functions, are of interest in medicine for drug development and diagnosis purposes. However, detection of comprehensive direct evidence for the relationship of DNA modifications/mutations in genes, their effect on transcription factors, and the corresponding cell functions have been limited. In this study, we utilized a single-molecule electrical detection method for the direct observation of DNA alterations on transcription factor binding motifs upon exposure to a nucleic acid analogue, trifluridine (FTD), and evaluated the effects of the DNA alteration on transcriptional activity in cancer cell line cells. We found ~ 10% FTD incorporation at the transcription factor p53 binding regions in cancer cells exposed to FTD for 5 months. Additionally, through single-molecule analysis of p53-enriched DNA, we found that the FTD incorporation at the p53 DNA binding regions led to less binding, likely due to weaken the binding of p53. This work suggests that single-molecule detection of DNA sequence alterations is a useful methodology for understanding DNA sequence alterations.
Alterations in intestinal microbiota in ultramarathon runners
Authors: Sato Mika , Suzuki Yoshio
Published: April 2022

To date, only one study has reported changes in the gut microbiome of an ultramarathon runner before and after competing in the race. Herein we aimed to investigate changes in intestinal microbiota in nine ultramarathon runners. Eight of the nine participants ran 96.102 km (up 8062 m, down 6983 km) and one ran 99.12 km (up 8448 m, down 7369 m) within 38–44 h. Intestinal microbiota alterations were examined at three timepoints: before (Pre), after (Post), and 10 days after (Recovery) the race. The α- and β-diversity of intestinal microbiota were unaffected by the race. Six of the nine participants showed the B-type enterotype, while the remaining three showed the P-type enterotype; however, significant difference between enterotypes was not observed in the influence of the ultramarathon on intestinal microbiota. The abundance of mean Faecalibacterium prausnitzii, was significantly decreased from 2.9% (Pre) to 1.6% (Post), as well as other three butyrate producing bacteria. One participant with the largest decrease in F. prausnitzii abundance (− 85.7%) reported sluggishness and shallow sleep from Post to Recovery. Our findings revealed that the abundance of butyrate-producing bacteria is decreased in ultramarathon runners, which consequently decreases butyrate levels in the intestine and affects host immune function.
Protein and antigen profiles of third-stage larvae of Gnathostoma spinigerum assessed with next-generation sequencing transcriptomic information
Authors: Nogrado Kathyleen , Thiangtrongjit Tipparat , Adisakwattana Poom , Dekumyoy Paron , Muangnoicharoen Sant , Thawornkuno Charin , Reamtong Onrapak
Published: April 2022

Gnathostomiasis is a food-borne zoonotic disease that can affect humans who eat improperly cooked meat containg infective third-stage larvae. Definitive diagnosis is through larval recovery. However, this is an invasive technique and is impractical if the larvae have encysted in inaccessible areas of the body. Antigen or antibody detection might be more interesting techniques for diagnosis. Proteomic could elucidate diagnostic markers and improve our understanding of parasite biology. However, proteomic studies on Gnathostoma spinigerum are hampered by the lack of a comprehensive database for protein identification. This study aimed to explore the protein and antigen profiles of advanced third-stage G. spinigerum larvae (aL3Gs) using interrogation of mass spectrometry data and an in-house transcriptomic database for protein identification. Immunoproteomic analysis found 74 proteins in 24-kDa SDS-PAGE bands, which is size-specific for the immunodiagnosis of gnathostomiasis. Moreover, 13 proteins were found in 2-DE 24-kDa bands. The data suggest that collagenase 3, cathepsin B, glutathione S-transferase 1, cuticle collagen 14, major antigen, zinc metalloproteinase nas-4, major egg antigen, peroxiredoxin, and superoxide dismutase [Cu–Zn] may be good candidates for novel human gnathostomiasis diagnostic assays. These findings improve our understanding of the parasite’s biology and provide additional potential targets for novel therapeutics, diagnostics, and vaccines.
Development of biodegradable films using sunflower protein isolates and bacterial nanocellulose as innovative food packaging materials for fresh fruit preservation
Authors: Efthymiou Maria-Nefeli , Tsouko Erminta , Papagiannopoulos Aristeidis , Athanasoulia Ioanna-Georgia , Georgiadou Maria , Pispas Stergios , Briassoulis Demetres , Tsironi Theofania , Koutinas Apostolis
Published: April 2022

This study presents the valorization of side streams from the sunflower-based biodiesel industry for the production of bio-based and biodegradable food packaging following circular economy principles. Bacterial cellulose (BC) was produced via fermentation in 6 L static tray bioreactors using nutrient-rich supplements derived from the enzymatic hydrolysis of sunflower meal (SFM) combined with crude glycerol as carbon source. Novel biofilms were produced using either matrices of protein isolates extracted from sunflower meal (SFMPI) alone or SFMPI matrices reinforced with nanocellulose biofillers of commercial or bacterial origin. Acid hydrolysis was employed for ex-situ modification of BC to nanostructures (56 nm). The biofilms reinforced with bacterial nanocellulose structures (SFMPI-BNC) showed 64.5% higher tensile strength, 75.5% higher Young’s modulus, 131.5% higher elongation at break, 32.5% lower water solubility and 14.1% lower water vapor permeability than the biofilms produced only with SFMPI. The biofilms were evaluated on fresh strawberries packaging showing that the SFMPI-BNC-based films lead to effective preservation at 10 °C considering microbial growth and physicochemical profile (weight loss, chemical characterization, color, firmness and respiration activity). The SFMPI-BNC-based films could be applied in fresh fruit packaging applications.
Increased emergency cardiovascular events among under-40 population in Israel during vaccine rollout and third COVID-19 wave
Authors: Sun Christopher L. F. , Jaffe Eli , Levi Retsef
Published: April 2022

Cardiovascular adverse conditions are caused by coronavirus disease 2019 (COVID-19) infections and reported as side-effects of the COVID-19 vaccines. Enriching current vaccine safety surveillance systems with additional data sources may improve the understanding of COVID-19 vaccine safety. Using a unique dataset from Israel National Emergency Medical Services (EMS) from 2019 to 2021, the study aims to evaluate the association between the volume of cardiac arrest and acute coronary syndrome EMS calls in the 16–39-year-old population with potential factors including COVID-19 infection and vaccination rates. An increase of 25% was detected in both call types during January–May 2021, compared with the years 2019–2020. Using Negative Binomial regression models, the weekly emergency call counts were significantly associated with the rates of 1st and 2nd vaccine doses administered to this age group but were not with COVID-19 infection rates. While not establishing causal relationships, the findings raise concerns regarding vaccine-induced undetected severe cardiovascular side-effects and underscore the already established causal relationship between vaccines and myocarditis, a frequent cause of unexpected cardiac arrest in young individuals. Surveillance of potential vaccine side-effects and COVID-19 outcomes should incorporate EMS and other health data to identify public health trends (e.g., increased in EMS calls), and promptly investigate potential underlying causes.
Speed management across road environments of varying complexities and self-regulation behaviors in drivers with cataract
Authors: Ortiz-Peregrina Sonia , Ortiz Carolina , Martino Francesco , Casares-López Miriam , Castro-Torres José J. , Anera Rosario G.
Published: April 2022

Evidence suggests that drivers with cataract self-regulate their driving, but there is a lack of objective information. This study compared speed behavior in older drivers with and without cataract and how the parameter is influenced by road traffic complexity and driver characteristics. The study included 15 drivers with cataract and a control group of 20 drivers. Visual status was assessed using visual acuity, contrast sensitivity, and intraocular straylight. Speed management was studied using a driving simulator. Driving difficulty and self-regulation patterns were evaluated by means of the Driver Habits Questionnaire (DHQ). The cataract group showed a significant decrease in visual function in all the parameters evaluated (p < 0.05). These drivers tended to drive at lower speeds than the control group. Road characteristics, gender, and intraocular straylight in the better eye were identified as significant predictors of speed management. Drivers with cataract experience greater driving difficulty, particularly when driving at night (p < 0.05). Drivers with cataract reduce their driving speed more than older drivers without visual impairment. The straylight parameter may be a good indicator of each driver’s subjective perception of their own visual ability to drive. This work helps shed light on the mechanisms through which age-related visual impairment influences driving behavior.
Nutritional value and bioaccumulation of heavy metals in nine commercial fish species from Dachen Fishing Ground, East China Sea
Authors: Huang Hong , Li Yingdong , Zheng Xinyun , Wang Zuanyi , Wang Zhenhua , Cheng Xiaopeng
Published: April 2022

The study evaluated the nutritional quality in muscle tissues of nine commercially important marine fish species. And the concentrations of trace metals (i.e. As, Hg, Cu, Pb, Cr, Cd and Zn) in the muscles (edible part) and tissues (gill and liver) of fishes caught from Dachen fishing ground, the coast of Zhejiang Province, East China Sea, were determined, and the values of target hazard quotient (THQ) and the carcinogenic risk (TR) were calculated for assessing human health risk. Significant differences(P < 0.05) were observed in the proximate chemical composition of fish muscles in these species. The muscle protein content of fish species ranged from 12.36 to 23.41%. The muscle lipid content of fishes ranged from 0.48 to 2.54%. The accumulation capacity of heavy metals (except Cr) in livers and gills was higher than that in muscles. In addition, the accumulation ability of most fishes is related to the water layer they live, the fishes living in the demersal layer showed more accumulation of heavy metals than the middle-upper layer(except Cu). Estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI) and the carcinogenic risk (TR) assessed for potential human health risk implications suggest that the values were within the acceptable threshold for human. However, the carcinogenic risk(TR) of As and Cr was close to the critical limit (10–4). Therefore, in order to ensure the health and safety of human consumption, the continuous monitoring of heavy metals in Dachen fishing ground area is suggested.
Impact of temperature on dengue and chikungunya transmission by the mosquito Aedes albopictus
Authors: Mercier Aurélien , Obadia Thomas , Carraretto Davide , Velo Enkelejda , Gabiane Gaelle , Bino Silvia , Vazeille Marie , Gasperi Giuliano , Dauga Catherine , Malacrida Anna R. , Reiter Paul , Failloux Anna-Bella
Published: April 2022

The mosquito Aedes albopictus is an invasive species first detected in Europe in Albania in 1979, and now established in 28 European countries. Temperature is a limiting factor in mosquito activities and in the transmission of associated arboviruses namely chikungunya (CHIKV) and dengue (DENV). Since 2007, local transmissions of CHIKV and DENV have been reported in mainland Europe, mainly in South Europe. Thus, the critical question is how far north transmission could occur. In this context, the Albanian infestation by Ae. albopictus is of interest because the species is present up to 1200 m of altitude; this allows using altitude as a proxy for latitude. Here we show that Ae. albopictus can transmit CHIKV at 28 °C as well as 20 °C, however, the transmission of DENV is only observed at 28 °C. We conclude that if temperature is the key environmental factor limiting transmission, then transmission of CHIKV, but not DENV is feasible in much of Europe.