bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends and developments in oral health literacy: a scientometric research study (1991–2020)
Authors: Sun Yue , Li Chunying , Zhao Yan , Sun Jing
Published: March 2021

Objective

This study aimed to establish the current situation, intellectual base, hotspots, development trends, and frontiers of oral health literacy (OHL) from the literature.

Methods

We analyzed 1505 bibliographic records dated between January 1990 and December 2020 retrieved from the Web of Science Core Collection and the Scopus database. We used CiteSpace for word frequency analysis, co-occurrence analysis, co-citation analysis, clustering analysis, and burst analysis.

Results

The total number of publications increased year-on-year, with the majority of publications coming from the USA. Most studies focused on the relationship between (oral) health literacy and oral health, and the development of OHL instruments. The top 10 keywords by frequency were “health literacy”, “oral health”, “attitude to health”, “dental caries”, “adult”, “children”, “dental care”, “knowledge”, “questionnaire”, and “adolescent”. The keyword with the highest burst intensity was “dental health education”.

Conclusions

OHL research is a thriving field. The field is focused on the development of an OHL instrument and health promotion practice. Strategic cooperation among countries, institutions, authors, hospitals, and communities will be important to encourage further OHL research and address oral health problems.
Deubiquitinase USP39 and E3 ligase TRIM26 balance the level of ZEB1 ubiquitination and thereby determine the progression of hepatocellular carcinoma
Authors: Li Xiaomei , Yuan Jiahui , Song Conghua , Lei Yongbin , Xu Jiajia , Zhang Gongye , Wang Weiwei , Song Gang
Published: March 2021

Emerging evidence suggests that USP39 plays an important role in the development of hepatocellular carcinoma (HCC). However, the molecular mechanism by which USP39 promotes HCC progression has not been well defined, especially regarding its putative ubiquitination function. Zinc-finger E-box-binding homeobox 1 (ZEB1) is a crucial inducer of epithelial-to-mesenchymal transition (EMT) to promote tumor proliferation and metastasis, but the regulatory mechanism of ZEB1 stability in HCC remains enigmatic. Here, we reveal that USP39 is highly expressed in human HCC tissues and correlated with poor prognosis. Moreover, USP39 depletion inhibits HCC cell proliferation and metastasis by promoting ZEB1 degradation. Intriguingly, deubiquitinase USP39 has a direct interaction with the E3 ligase TRIM26 identified by co-immunoprecipitation assays and immunofluorescence staining assays. We further demonstrate that TRIM26 is lowly expressed in human HCC tissues and inhibits HCC cell proliferation and migration. TRIM26 promotes the degradation of ZEB1 protein by ubiquitination in HCC. Deubiquitinase USP39 and E3 ligase TRIM26 function in an antagonistic pattern, but not a competitive pattern, and play key roles in controlling ZEB1 stability to determine the HCC progression. In summary, our data reveal a previously unknown mechanism that USP39 and TRIM26 balance the level of ZEB1 ubiquitination and thereby determine HCC cell proliferation and migration. This novel mechanism may provide new approaches to target treatment for inhibiting HCC development by restoring TRIM26 or suppressing USP39 expression in HCC cases with high ZEB1 protein levels.
Mechanical stretch promotes hypertrophic scar formation through mechanically activated cation channel Piezo1
Authors: He Jiahao , Fang Bin , Shan Shengzhou , Xie Yun , Wang Chuandong , Zhang Yifan , Zhang Xiaoling , Li Qingfeng
Published: March 2021

Hypertrophic scar (HS) formation is a skin fibroproliferative disease that occurs following a cutaneous injury, leading to functional and cosmetic impairment. To date, few therapeutic treatments exhibit satisfactory outcomes. The mechanical force has been shown to be a key regulator of HS formation, but the underlying mechanism is not completely understood. The Piezo1 channel has been identified as a novel mechanically activated cation channel (MAC) and is reportedly capable of regulating force-mediated cellular biological behaviors. However, the mechanotransduction role of Piezo1 in HS formation has not been investigated. In this work, we found that Piezo1 was overexpressed in myofibroblasts of human and rat HS tissues. In vitro, cyclic mechanical stretch (CMS) increased Piezo1 expression and Piezo1-mediated calcium influx in human dermal fibroblasts (HDFs). In addition, Piezo1 activity promoted HDFs proliferation, motility, and differentiation in response to CMS. More importantly, intradermal injection of GsMTx4, a Piezo1-blocking peptide, protected rats from stretch-induced HS formation. Together, Piezo1 was shown to participate in HS formation and could be a novel target for the development of promising therapies for HS formation.
Neurog2 directly converts astrocytes into functional neurons in midbrain and spinal cord
Authors: Liu Fei , Zhang Yijie , Chen Fuliang , Yuan Jiacheng , Li Sanlan , Han Sue , Lu Dengyu , Geng Junlan , Rao Zhiping , Sun Li , Xu Jianhua , Shi Yuhan , Wang Xiaojing , Liu Yueguang
Published: March 2021

Conversion of astrocytes into neurons in vivo offers an alternative therapeutic approach for neuronal loss after injury or disease. However, not only the efficiency of the conversion of astrocytes into functional neurons by single Neurog2, but also the conundrum that whether Neurog2-induced neuronal cells (Neurog2-iNs) are further functionally integrated into existing matured neural circuits remains unknown. Here, we adopted the AAV(2/8) delivery system to overexpress single factor Neurog2 into astrocytes and found that the majority of astrocytes were successfully converted into neuronal cells in multiple brain regions, including the midbrain and spinal cord. In the midbrain, Neurog2-induced neuronal cells (Neurog2-iNs) exhibit neuronal morphology, mature electrophysiological properties, glutamatergic identity (about 60%), and synapse-like configuration local circuits. In the spinal cord, astrocytes from both the intact and lesioned sources could be converted into functional neurons with ectopic expression of Neurog2 alone. Notably, further evidence from our study also proves that Neurog2-iNs in the intact spinal cord are capable of responding to diverse afferent inputs from dorsal root ganglion (DRG). Together, this study does not merely demonstrate the feasibility of Neurog2 for efficient in vivo reprogramming, it gives an indication for the Neurog2-iNs as a functional and potential factor in cell-replacement therapy.
Caspase-6-cleaved Tau fails to induce Tau hyperphosphorylation and aggregation, neurodegeneration, glial inflammation, and cognitive deficits
Authors: Noël Anastasia , Foveau Bénédicte , LeBlanc Andréa C.
Published: March 2021

Active Caspase-6 (Casp6) and Tau cleaved by Casp6 at amino acids 402 (Tau∆D402) and 421 (Tau∆D421) are present in early Alzheimer disease intraneuronal neurofibrillary tangles, which are made primarily of filamentous Tau aggregates. To assess whether Casp6 cleavage of Tau contributes to Tau pathology and Casp6-mediated age-dependent cognitive impairment, we generated transgenic knock-in mouse models that conditionally express full-length human Tau (hTau) 0N4R only (CTO) or together with human Casp6 (hCasp6) (CTC). Region-specific hippocampal and cortical hCasp6 and hTau expression were confirmed with western blot and immunohistochemistry in 2–25-month-old brains. Casp6 activity was confirmed with Tau∆D421 and Tubulin cleaved by Casp6 immunopositivity in 3–25-month-old CTC, but not in CTO, brains. Immunoprecipitated Tau∆D402 was detected in both CTC and CTO brains, but was more abundant in CTC brains. Intraneuronal hippocampal Tau hyperphosphorylation at S202/T205, S422, and T231, and Tau conformational change were absent in both CTC and CTO brains. A slight accumulation of Tau phosphorylated at S396/404 and S202 was observed in Cornu Ammonis 1 (CA1) hippocampal neuron soma of CTC compared to CTO brains. Eighteen-month-old CTC brains showed rare argentophilic deposits that increased by 25 months, whereas CTO brains only displayed them sparsely at 25 months. Tau microtubule binding was equivalent in CTC and CTO hippocampi. Episodic and spatial memory measured with novel object recognition and Barnes maze, respectively, remained normal in 3–25-month-old CTC and CTO mice, in contrast to previously observed impairments in ACL mice expressing equivalent levels of hCasp6 only. Consistently, the CTC and CTO hippocampal CA1 region displayed equivalent dendritic spine density and no glial inflammation. Together, these results reveal that active hCasp6 co-expression with hTau generates Tau cleavage and rare age-dependent argentophilic deposits but fails to induce cognitive deficits, neuroinflammation, and Tau pathology.
The genome of Magnolia biondii Pamp. provides insights into the evolution of Magnoliales and biosynthesis of terpenoids
Authors: Dong Shanshan , Liu Min , Liu Yang , Chen Fei , Yang Ting , Chen Lu , Zhang Xingtan , Guo Xing , Fang Dongming , Li Linzhou , Deng Tian , Yao Zhangxiu , Lang Xiaoan , Gong Yiqing , Wu Ernest , Wang Yaling , Shen Yamei , Gong Xun , Liu Huan , Zhang Shouzhou
Published: March 2021

Magnolia biondii Pamp. (Magnoliaceae, magnoliids) is a phylogenetically, economically, and medicinally important ornamental tree species widely grown and cultivated in the north-temperate regions of China. Determining the genome sequence of M. biondii would help resolve the phylogenetic uncertainty of magnoliids and improve the understanding of individual trait evolution within the Magnolia genus. We assembled a chromosome-level reference genome of M. biondii using ~67, ~175, and ~154 Gb of raw DNA sequences generated via Pacific Biosciences single-molecule real-time sequencing, 10X Genomics Chromium, and Hi-C scaffolding strategies, respectively. The final genome assembly was ~2.22 Gb, with a contig N50 value of 269.11 kb and a BUSCO complete gene percentage of 91.90%. Approximately 89.17% of the genome was organized into 19 chromosomes, resulting in a scaffold N50 of 92.86 Mb. The genome contained 47,547 protein-coding genes, accounting for 23.47% of the genome length, whereas 66.48% of the genome length consisted of repetitive elements. We confirmed a WGD event that occurred very close to the time of the split between the Magnoliales and Laurales. Functional enrichment of the Magnolia-specific and expanded gene families highlighted genes involved in the biosynthesis of secondary metabolites, plant–pathogen interactions, and responses to stimuli, which may improve the ecological fitness and biological adaptability of the lineage. Phylogenomic analyses revealed a sister relationship of magnoliids and Chloranthaceae, which are sister to a clade comprising monocots and eudicots. The genome sequence of M. biondii could lead to trait improvement, germplasm conservation, and evolutionary studies on the rapid radiation of early angiosperms.
Multiomics-based dissection of citrus flavonoid metabolism using a Citrus reticulata × Poncirus trifoliata population
Authors: Mou Jiaolin , Zhang Zhehui , Qiu Haiji , Lu Yang , Zhu Xiang , Fan Ziquan , Zhang Qinghua , Ye Junli , Fernie Alisdair R. , Cheng Yunjiang , Deng Xiuxin , Wen Weiwei
Published: March 2021

Deciphering the genetic basis of plant secondary metabolism will provide useful insights for genetic improvement and enhance our fundamental understanding of plant biological processes. Although citrus plants are among the most important fruit crops worldwide, the genetic basis of secondary metabolism in these plants is largely unknown. Here, we use a high-density linkage map to dissect large-scale flavonoid metabolic traits measured in different tissues (young leaf, old leaf, mature pericarp, and mature pulp) of an F1pseudo-testcross citrus population. We detected 80 flavonoids in this population and identified 138 quantitative trait loci (QTLs) for 57 flavonoids in these four tissues. Based on transcriptional profiling and functional annotation, twenty-one candidate genes were identified, and one gene encoding flavanone 3-hydroxylase (F3H)was functionally verified to result in naturally occurring variation in dihydrokaempferol content through genetic variations in its promoter and coding regions. The abundant data resources collected for diverse citrus germplasms here lay the foundation for complete characterization of the citrus flavonoid biosynthetic pathway and will thereby promote efficient utilization of metabolites in citrus quality improvement.
Reannotation of the cultivated strawberry genome and establishment of a strawberry genome database
Authors: Liu Tianjia , Li Muzi , Liu Zhongchi , Ai Xiaoyan , Li Yongping
Published: March 2021

Cultivated strawberry (Fragaria×ananassa) is an important fruit crop species whose fruits are enjoyed by many worldwide. An octoploid of hybrid origin, the complex genome of this species was recently sequenced, serving as a key reference genome for cultivated strawberry and related species of theRosaceaefamily. The current annotation of theF. ananassagenome mainly relies on ab initio predictions and, to a lesser extent, transcriptome data. Here, we present the structure and functional reannotation of theF. ananassagenome based on one PacBio full-length RNA library and ninety-two Illumina RNA-Seq libraries. This improved annotation of theF. ananassagenome, v1.0.a2, comprises a total of 108,447 gene models, with 97.85% complete BUSCOs. The models of 19,174 genes were modified, 360 new genes were identified, and 11,044 genes were found to have alternatively spliced isoforms. Additionally, we constructed a strawberry genome database (SGD) for strawberry gene homolog searching and annotation downloading. Finally, the transcriptome of the receptacles and achenes ofF. ananassaat four developmental stages were reanalyzed and qualified, and the expression profiles of all the genes in this annotation are also provided. Together, this study provides an updated annotation of theF. ananassagenome, which will facilitate genomic analyses across theRosaceaefamily and gene functional studies in cultivated strawberry.
Genome-wide association analysis identified molecular markers associated with important tea flavor-related metabolites
Authors: Fang Kaixing , Xia Zhiqiang , Li Hongjian , Jiang Xiaohui , Qin Dandan , Wang Qiushuang , Wang Qing , Pan Chendong , Li Bo , Wu Hualing
Published: March 2021

The characteristic secondary metabolites in tea (theanine, caffeine, and catechins) are important factors contributing to unique tea flavors. However, there has been relatively little research on molecular markers related to these metabolites. Thus, we conducted a genome-wide association analysis of the levels of these tea flavor-related metabolites in three seasons. The theanine, caffeine, and catechin levels in Population 1 comprising 191 tea plant germplasms were examined, which revealed that their heritability exceeded 0.5 in the analyzed seasons, with the following rank order (highest to lowest heritabilities): (+)-catechin > (−)-gallocatechin gallate > caffeine = (−)-epicatechin > (−)-epigallocatechin-3-gallate > theanine > (−)-epigallocatechin > (−)-epicatechin-3-gallate > catechin gallate > (+)-gallocatechin. The SNPs detected by amplified-fragment SNP and methylation sequencing divided Population 1 into three groups and seven subgroups. An association analysis yielded 307 SNP markers related to theanine, caffeine, and catechins that were common to all three seasons. Some of the markers were pleiotropic. The functional annotation of 180 key genes at the SNP loci revealed that FLS, UGT, MYB, and WD40 domain-containing proteins, as well as ATP-binding cassette transporters, may be important for catechin synthesis. KEGG and GO analyses indicated that these genes are associated with metabolic pathways and secondary metabolite biosynthesis. Moreover, in Population 2 (98 tea plant germplasm resources), 30 candidate SNPs were verified, including 17 SNPs that were significantly or extremely significantly associated with specific metabolite levels. These results will provide a foundation for future research on important flavor-related metabolites and may help accelerate the breeding of new tea varieties.
Identification of long noncoding RNAs involved in resistance to downy mildew in Chinese cabbage
Authors: Zhang Bin , Su Tongbing , Li Peirong , Xin Xiaoyun , Cao Yunyun , Wang Weihong , Zhao Xiuyun , Zhang Deshuang , Yu Yangjun , Li Dayong , Yu Shuancang , Zhang Fenglan
Published: March 2021

Brassica downy mildew, a severe disease caused by Hyaloperonospora brassicae, can cause enormous economic losses in Chinese cabbage (Brassica rapa L. ssp. pekinensis) production. Although some research has been reported recently concerning the underlying resistance to this disease, no studies have identified or characterized long noncoding RNAs involved in this defense response. In this study, using high-throughput RNA sequencing, we analyzed the disease-responding mRNAs and long noncoding RNAs in two resistant lines (T12–19 and 12–85) and one susceptible line (91–112). Clustering and Gene Ontology analysis of differentially expressed genes (DEGs) showed that more DEGs were involved in the defense response in the two resistant lines than in the susceptible line. Different expression patterns and proposed functions of differentially expressed long noncoding RNAs among T12–19, 12–85, and 91–112 indicated that each has a distinct disease response mechanism. There were significantly more cis- and trans-functional long noncoding RNAs in the resistant lines than in the susceptible line, and the genes regulated by these RNAs mostly participated in the disease defense response. Furthermore, we identified a candidate resistance-related long noncoding RNA, MSTRG.19915, which is a long noncoding natural antisense transcript of a MAPK gene, BrMAPK15. Via an agroinfiltration-mediated transient overexpression system and virus-induced gene silencing technology, BrMAPK15 was indicated to have a greater ability to defend against pathogens. MSTRG.19915-silenced seedlings showed enhanced resistance to downy mildew, probably because of the upregulated expression of BrMAPK15. This research identified and characterized long noncoding RNAs involved in resistance to downy mildew, laying a foundation for future in-depth studies of disease resistance mechanisms in Chinese cabbage.
Cavity-enhanced microwave readout of a solid-state spin sensor
Authors: Eisenach Erik R. , Barry John F. , O’Keeffe Michael F. , Schloss Jennifer M. , Steinecker Matthew H. , Englund Dirk R. , Braje Danielle A.
Published: March 2021

Overcoming poor readout is an increasingly urgent challenge for devices based on solid-state spin defects, particularly given their rapid adoption in quantum sensing, quantum information, and tests of fundamental physics. However, in spite of experimental progress in specific systems, solid-state spin sensors still lack a universal, high-fidelity readout technique. Here we demonstrate high-fidelity, room-temperature readout of an ensemble of nitrogen-vacancy centers via strong coupling to a dielectric microwave cavity, building on similar techniques commonly applied in cryogenic circuit cavity quantum electrodynamics. This strong collective interaction allows the spin ensemble’s microwave transition to be probed directly, thereby overcoming the optical photon shot noise limitations of conventional fluorescence readout. Applying this technique to magnetometry, we show magnetic sensitivity approaching the Johnson–Nyquist noise limit of the system. Our results pave a clear path to achieve unity readout fidelity of solid-state spin sensors through increased ensemble size, reduced spin-resonance linewidth, or improved cavity quality factor.
Degradable polymeric vehicles for postoperative pain management
Authors: Brigham Natasha C. , Ji Ru-Rong , Becker Matthew L.
Published: March 2021

Effective control of pain management has the potential to significantly decrease the need for prescription opioids following a surgical procedure. While extended release products for pain management are available commercially, the implementation of a device that safely and reliably provides extended analgesia and is sufficiently flexible to facilitate a diverse array of release profiles would serve to advance patient comfort, quality of care and compliance following surgical procedures. Herein, we review current polymeric systems that could be utilized in new, controlled post-operative pain management devices and highlight where opportunities for improvement exist.
Cells recognize osmotic stress through liquid–liquid phase separation lubricated with poly(ADP-ribose)
Authors: Watanabe Kengo , Morishita Kazuhiro , Zhou Xiangyu , Shiizaki Shigeru , Uchiyama Yasuo , Koike Masato , Naguro Isao , Ichijo Hidenori
Published: March 2021

Cells are under threat of osmotic perturbation; cell volume maintenance is critical in cerebral edema, inflammation and aging, in which prominent changes in intracellular or extracellular osmolality emerge. After osmotic stress-enforced cell swelling or shrinkage, the cells regulate intracellular osmolality to recover their volume. However, the mechanisms recognizing osmotic stress remain obscured. We previously clarified that apoptosis signal-regulating kinase 3 (ASK3) bidirectionally responds to osmotic stress and regulates cell volume recovery. Here, we show that macromolecular crowding induces liquid-demixing condensates of ASK3 under hyperosmotic stress, which transduce osmosensing signal into ASK3 inactivation. A genome-wide small interfering RNA (siRNA) screen identifies an ASK3 inactivation regulator, nicotinamide phosphoribosyltransferase (NAMPT), related to poly(ADP-ribose) signaling. Furthermore, we clarify that poly(ADP-ribose) keeps ASK3 condensates in the liquid phase and enables ASK3 to become inactivated under hyperosmotic stress. Our findings demonstrate that cells rationally incorporate physicochemical phase separation into their osmosensing systems.
Photocatalysis-mediated drug-free sustainable cancer therapy using nanocatalyst
Authors: Zhao Bin , Wang Yingshuai , Yao Xianxian , Chen Danyang , Fan Mingjian , Jin Zhaokui , He Qianjun
Published: March 2021

Drug therapy unavoidably brings toxic side effects and drug content-limited therapeutic efficacy although many nanocarriers have been developed to improve them to a certain extent. In this work, a concept of drug-free therapeutics is proposed and defined as a therapeutic methodology without the use of traditional toxic drugs, without the consumption of therapeutic agents during treatment but with the inexhaustible therapeutic capability to maximize the benefit of treatment, and a Z-scheme SnS1.68-WO2.41 nanocatalyst is developed to achieve near infrared (NIR)-photocatalytic generation of oxidative holes and hydrogen molecules for realizing combined hole/hydrogen therapy by the drug-free therapeutic strategy. Without the need of any drug and other therapeutic agent assistance, the nanocatalyst oxidizes/consumes intratumoral over-expressed glutathione (GSH) by holes and simultaneously generates hydrogen molecules in a lasting and controllable way under NIR irradiation. Mechanistically, generated hydrogen molecules and GSH consumption inhibit cancer cell energy and destroy intratumoral redox balance, respectively, to synergistically damage DNA and induce tumor cell apoptosis. High efficacy and biosafety of combined hole/hydrogen therapy of tumors are achieved by the nanocatalyst. The proposed catalysis-based drug-free therapeutic strategy breaks a pathway to realize high efficacy and low toxicity of cancer treatment.
S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates
Authors: Liang Joshua G. , Su Danmei , Song Tian-Zhang , Zeng Yilan , Huang Weijin , Wu Jinhua , Xu Rong , Luo Peiwen , Yang Xiaofang , Zhang Xiaodong , Luo Shuangru , Liang Ying , Li Xinglin , Huang Jiaju , Wang Qiang , Huang Xueqin , Xu Qingsong , Luo Mei , Huang Anliang , Luo Dongxia , Zhao Chenyan , Yang Fan , Han Jian-Bao , Zheng Yong-Tang , Liang Peng
Published: March 2021

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.
Observation of magnetic adatom-induced Majorana vortex and its hybridization with field-induced Majorana vortex in an iron-based superconductor
Authors: Fan Peng , Yang Fazhi , Qian Guojian , Chen Hui , Zhang Yu-Yang , Li Geng , Huang Zihao , Xing Yuqing , Kong Lingyuan , Liu Wenyao , Jiang Kun , Shen Chengmin , Du Shixuan , Schneeloch John , Zhong Ruidan , Gu Genda , Wang Ziqiang , Ding Hong , Gao Hong-Jun
Published: March 2021

Braiding Majorana zero modes is essential for fault-tolerant topological quantum computing. Iron-based superconductors with nontrivial band topology have recently emerged as a surprisingly promising platform for creating distinct Majorana zero modes in magnetic vortices in a single material and at relatively high temperatures. The magnetic field-induced Abrikosov vortex lattice makes it difficult to braid a set of Majorana zero modes or to study the coupling of a Majorana doublet due to overlapping wave functions. Here we report the observation of the proposed quantum anomalous vortex with integer quantized vortex core states and the Majorana zero mode induced by magnetic Fe adatoms deposited on the surface. We observe its hybridization with a nearby field-induced Majorana vortex in iron-based superconductor FeTe0.55Se0.45. We also observe vortex-free Yu-Shiba-Rusinov bound states at the Fe adatoms with a weaker coupling to the substrate, and discover a reversible transition between Yu-Shiba-Rusinov states and Majorana zero mode by manipulating the exchange coupling strength. The dual origin of the Majorana zero modes, from magnetic adatoms and external magnetic field, provides a new single-material platform for studying their interactions and braiding in superconductors bearing topological band structures.
The TOPAZ study: a home-based trial of zoledronic acid to prevent fractures in neurodegenerative parkinsonism
Authors: Tanner Caroline M. , Cummings Steven R. , Schwarzschild Michael A. , Brown Ethan G. , Dorsey E. Ray , Espay Alberto J. , Galifianakis Nicholas B. , Goldman Samuel M. , Litvan Irene , Luthra Nijee , McFarland Nikolaus R. , Mitchell Kyle T. , Standaert David G. , Bauer Douglas C. , Greenspan Susan L. , Beck James C. , Lyles Kenneth W.
Published: March 2021

The Trial of Parkinson’s And Zoledronic acid (TOPAZ, https://clinicaltrials.gov/ct2/show/NCT03924414) is a unique collaboration between experts in movement disorders and osteoporosis to test the efficacy of zoledronic acid, an FDA-approved parenteral treatment for osteoporosis, for fracture prevention in people with neurodegenerative parkinsonism. Aiming to enroll 3,500 participants age 65 years or older, TOPAZ is one of the largest randomized, placebo-controlled clinical trials ever attempted in parkinsonism. The feasibility of TOPAZ is enhanced by its design as a U.S.- wide home-based trial without geographical limits. Participants receive information from multiple sources, including specialty practices, support groups and websites. Conducting TOPAZ in participants’ homes takes advantage of online consent technology, the capacity to confirm diagnosis using telemedicine and the availability of research nursing to provide screening and parenteral therapy in homes. Home-based clinical research may provide an efficient, convenient, less expensive method that opens participation in clinical trials to almost anyone with parkinsonism.
Reduced cortical gyrification in the posteromedial cortex in unaffected relatives of schizophrenia patients with high genetic loading
Authors: Park Inkyung , Kim Minah , Lee Tae Young , Hwang Wu Jeong , Bin Kwak Yoo , Oh Sanghoon , Lho Silvia Kyungjin , Moon Sun-Young , Kwon Jun Soo
Published: March 2021

Although abnormal cortical gyrification has been consistently reported in patients with schizophrenia, whether gyrification abnormalities reflect a genetic risk for the disorder remains unknown. This study investigated differences in cortical gyrification between unaffected relatives (URs) with high genetic loading for schizophrenia and healthy controls (HCs) to identify potential genetic vulnerability markers. A total of 50 URs of schizophrenia patients and 50 matched HCs underwent T1-weighted magnetic resonance imaging to compare whole-brain gyrification using the local gyrification index (lGI). Then, the lGI clusters showing significant differences were compared between the UR subgroups based on the number of first-degree relatives with schizophrenia to identify the effect of genetic loading on cortical gyrification changes. The URs exhibited significantly lower cortical gyrification than the HCs in clusters including medial parieto-occipital and cingulate regions comprising the bilateral precuneus, cuneus, pericalcarine, lingual, isthmus cingulate, and posterior cingulate gyri. Moreover, URs who had two or more first-degree relatives with schizophrenia showed greater gyrification reductions in these clusters than those who had at least one first-degree relative with schizophrenia. Our findings of reduced gyrification in URs, which are consistent with accumulated evidence of hypogyria observed in regions showing patient-control differences in previous studies, highlight that such hypogyria in posteromedial regions may serve as a genetic vulnerability marker and reflect early neurodevelopmental abnormalities resulting from a genetic risk for schizophrenia.
Pairing of white wine made with shade-grown grapes and Japanese cuisine
Authors: Takahashi Takuji , Nakano Kumiko , Yamashita Machiko , Yamazaki Hanae , Fushiki Tohru
Published: March 2021

This study investigated the effect of pairing of wine vinified from shade-grown grapes before onset of ripening on the palatability of sashimi, a typical Japanese cuisine. GC-MS analyses of volatile chemicals revealed that shading reduced phenolic compounds and terpenoids, and added fatty acid ethyl esters which are also known to contribute to the flavor of Japanese sake. When the pairing of sashimi with wine was evaluated by individuals who regularly drink Japanese sake during meals, shade wine was more highly rated than wine made from normally-grown grapes.
Hierarchical deep learning models using transfer learning for disease detection and classification based on small number of medical images
Authors: An Guangzhou , Akiba Masahiro , Omodaka Kazuko , Nakazawa Toru , Yokota Hideo
Published: March 2021

Deep learning is being employed in disease detection and classification based on medical images for clinical decision making. It typically requires large amounts of labelled data; however, the sample size of such medical image datasets is generally small. This study proposes a novel training framework for building deep learning models of disease detection and classification with small datasets. Our approach is based on a hierarchical classification method where the healthy/disease information from the first model is effectively utilized to build subsequent models for classifying the disease into its sub-types via a transfer learning method. To improve accuracy, multiple input datasets were used, and a stacking ensembled method was employed for final classification. To demonstrate the method’s performance, a labelled dataset extracted from volumetric ophthalmic optical coherence tomography data for 156 healthy and 798 glaucoma eyes was used, in which glaucoma eyes were further labelled into four sub-types. The average weighted accuracy and Cohen’s kappa for three randomized test datasets were 0.839 and 0.809, respectively. Our approach outperformed the flat classification method by 9.7% using smaller training datasets. The results suggest that the framework can perform accurate classification with a small number of medical images.
Novel gene signatures for stage classification of the squamous cell carcinoma of the lung
Authors: Juarez-Flores Angel , Zamudio Gabriel S. , José Marco V.
Published: March 2021

The squamous cell carcinoma of the lung (SCLC) is one of the most common types of lung cancer. As GLOBOCAN reported in 2018, lung cancer was the first cause of death and new cases by cancer worldwide. Typically, diagnosis is made in the later stages of the disease with few treatment options available. The goal of this work was to find some key components underlying each stage of the disease, to help in the classification of tumor samples, and to increase the available options for experimental assays and molecular targets that could be used in treatment development. We employed two approaches. The first was based in the classic method of differential gene expression analysis, network analysis, and a novel concept known as network gatekeepers. The second approach was using machine learning algorithms. From our combined approach, we identified two sets of genes that could function as a signature to identify each stage of the cancer pathology. We also arrived at a network of 55 nodes, which according to their biological functions, they can be regarded as drivers in this cancer. Although biological experiments are necessary for their validation, we proposed that all these genes could be used for cancer development treatments.
A fast-growing basal troodontid (Dinosauria: Theropoda) from the latest Cretaceous of Europe
Authors: Sellés Albert G. , Vila Bernat , Brusatte Stephen L. , Currie Philip J. , Galobart Àngel
Published: March 2021

A characteristic fauna of dinosaurs and other vertebrates inhabited the end-Cretaceous European archipelago, some of which were dwarves or had other unusual features likely related to their insular habitats. Little is known, however, about the contemporary theropod dinosaurs, as they are represented mostly by teeth or other fragmentary fossils. A new isolated theropod metatarsal II, from the latest Maastrichtian of Spain (within 200,000 years of the mass extinction) may represent a jinfengopterygine troodontid, the first reported from Europe. Comparisons with other theropods and phylogenetic analyses reveal an autapomorphic foramen that distinguishes it from all other troodontids, supporting its identification as a new genus and species,Tamarro insperatus. Bone histology shows that it was an actively growing subadult when it died but may have had a growth pattern in which it grew rapidly in early ontogeny and attained a subadult size quickly. We hypothesize that it could have migrated from Asia to reach the Ibero-Armorican island no later than Cenomanian or during the Maastrichtian dispersal events.
Ultrafast evolution of bulk, surface and surface resonance states in photoexcited $$\hbox {Bi}_{2}\hbox {Te}_{3}$$
Authors: Hedayat Hamoon , Bugini Davide , Yi Hemian , Chen Chaoyu , Zhou Xingjiang , Cerullo Giulio , Dallera Claudia , Carpene Ettore
Published: March 2021

We use circular dichroism (CD) in time- and angle-resolved photoemission spectroscopy (trARPES) to measure the femtosecond charge dynamics in the topological insulator (TI) $$\hbox {Bi}_{2}\hbox {Te}_{3}$$

Bi
2

Te
3

. We detect clear CD signatures from topological surface states (TSS) and surface resonance (SR) states. In time-resolved measurements, independently from the pump polarization or intensity, the CD shows a dynamics which provides access to the unexplored electronic evolution in unoccupied states of $$\hbox {Bi}_{2}\hbox {Te}_{3}$$

Bi
2

Te
3

. In particular, we are able to disentangle the unpolarized electron dynamics in the bulk states from the spin-textured TSS and SR states on the femtosecond timescale. Our study demonstrates that photoexcitation mainly involves the bulk states and is followed by sub-picosecond transport to the surface. This provides essential details on intra- and interband scattering in the relaxation process of TSS and SR states. Our results reveal the significant role of SRs in the subtle ultrafast interaction between bulk and surface states of TIs.
Pili and other surface proteins influence the structure and the nanomechanical properties of Lactococcus lactis biofilms
Authors: Drame Ibrahima , Lafforgue Christine , Formosa-Dague Cecile , Chapot-Chartier Marie-Pierre , Piard Jean-Christophe , Castelain Mickaël , Dague Etienne
Published: March 2021

Lactic acid bacteria, in particular Lactococcus lactis, are widely used in the food industry, for the control and/or the protection of the manufacturing processes of fermented food. While L. lactis has been reported to form compact and uniform biofilms it was recently shown that certain strains able to display pili at their surface form more complex biofilms exhibiting heterogeneous and aerial structures. As the impact of those biofilm structures on the biomechanical properties of the biofilms is poorly understood, these were investigated using AFM force spectroscopy and imaging. Three types of strains were used i.e., a control strain devoid of pili and surface mucus-binding protein, a strain displaying pili but no mucus-binding proteins and a strain displaying both pili and a mucus-binding protein. To identify potential correlations between the nanomechanical measurements and the biofilm architecture, 24-h old biofilms were characterized by confocal laser scanning microscopy. Globally the strains devoid of pili displayed smoother and stiffer biofilms (Young Modulus of 4–100 kPa) than those of piliated strains (Young Modulus around 0.04–0.1 kPa). Additional display of a mucus-binding protein did not affect the biofilm stiffness but made the biofilm smoother and more compact. Finally, we demonstrated the role of pili in the biofilm cohesiveness by monitoring the homotypic adhesion of bacteria to the biofilm surface. These results will help to understand the role of pili and mucus-binding proteins withstanding external forces.
A pilot study of cystic fibrosis exacerbation response phenotypes reveals contrasting serum and sputum iron trends
Authors: Gifford Alex H. , Polineni Deepika , He Jianghua , D’Amico Jessica L. , Dorman Dana B. , Williams Molly A. , Nymon Amanda B. , Balwan Akshu , Budden Theodore , Zuckerman Jonathan B.
Published: March 2021

The cystic fibrosis (CF) community seeks to explain heterogeneous outcomes of pulmonary exacerbation (PEX) treatment. Serum and sputum inflammatory mediators may identify people with CF (PwCF) at risk for suboptimal responses. However, lack of an established association between response phenotypes and these mediators limits clinical application. In this pilot study, we prospectively characterized treatment response phenotypes by assessing health-related quality-of-life (HRQoL) during PEX. We also measured lung function and iron-related biochemical parameters in serum and sputum. We classified subjects as sustained symptom-responders (SRs) or non-sustained symptom-responders (NSRs) based on the absence or presence, respectively, of worsened symptom scores after initial improvement. We used linear mixed models (LMMs) to determine whether trends in lung function, hematologic, serum, and sputum indices of inflammation differed between response cohorts. In 20 PwCF, we identified 10 SRs and 10 NSRs with no significant differences in lung function at PEX onset and treatment durations. SRs had better model-predicted trends in lung function than NSRs during PEX. Non-linear trends in serum and sputum iron levels significantly differed between SRs and NSRs. In adults with cystic fibrosis, PEX treatment response phenotypes may be correlated with distinctive trends in serum and sputum iron concentrations.
Oncologic immunomodulatory agents in patients with cancer and COVID-19
Authors: Jee Justin , Stonestrom Aaron J. , Devlin Sean , Nguyentran Teresa , Wills Beatriz , Narendra Varun , Foote Michael B. , Lumish Melissa , Vardhana Santosha A. , Pastores Stephen M. , Korde Neha , Patel Dhwani , Horwitz Steven , Scordo Michael , Daniyan Anthony F.
Published: March 2021

Corticosteroids, anti-CD20 agents, immunotherapies, and cytotoxic chemotherapy are commonly used in the treatment of patients with cancer. It is unclear how these agents affect patients with cancer who are infected with SARS-CoV-2. We retrospectively investigated associations between SARS-CoV-2-associated respiratory failure or death with receipt of the aforementioned medications and with pre-COVID-19 neutropenia. The study included all cancer patients diagnosed with SARS-CoV-2 at Memorial Sloan Kettering Cancer Center until June 2, 2020 (N = 820). We controlled for cancer-related characteristics known to predispose to worse COVID-19 as well as level of respiratory support during corticosteroid administration. Corticosteroid administration was associated with worse outcomes prior to use of supplemental oxygen; no statistically significant difference was observed in sicker cohorts. In patients with metastatic thoracic cancer, 9 of 25 (36%) and 10 of 31 (32%) had respiratory failure or death among those who did and did not receive immunotherapy, respectively. Seven of 23 (30%) and 52 of 187 (28%) patients with hematologic cancer had respiratory failure or death among those who did and did not receive anti-CD20 therapy, respectively. Chemotherapy itself was not associated with worse outcomes, but pre-COVID-19 neutropenia was associated with worse COVID-19 course. Relative prevalence of chemotherapy-associated neutropenia in previous studies may account for different conclusions regarding the risks of chemotherapy in patients with COVID-19. In the absence of prospective studies and evidence-based guidelines, our data may aid providers looking to assess the risks and benefits of these agents in caring for cancer patients in the COVID-19 era.
Insight into the dynamics of second grade hybrid radiative nanofluid flow within the boundary layer subject to Lorentz force
Authors: Jawad Muhammad , Saeed Anwar , Tassaddiq Asifa , Khan Arshad , Gul Taza , Kumam Poom , Shah Zahir
Published: March 2021

The magnetohydrodynamic hybrid second-grade nanofluid flow towards a stretching/shrinking sheet with thermal radiation is inspected in current work. Main concern of current investigation is to consider hybrid $$Al_{2} O_{3} - Cu$$

A

l
2

O
3

-
C
u

nanofluid which is perceived by hanging two dissimilar kinds of nanoparticles known as alumina and copper within the base fluid. The fluid motion is produced by non-linear stretching/shrinking sheet. The modeled equations which comprise of energy, motion and continuity equations are changed into dimensionless form using group of similar variables. To determine the solution of transformed problem, the Homotopy Analysis technique is used. The findings of this work revealed that the magnetic parameter improves the heat transfer rate. This work also ensures that there are non-unique solutions of modeled problem for shrinking case and a unique solution for stretching case. Higher values of $${\text{Re}}_{x}$$

Re
x

results in declining of flow field. Rise in $$M$$
M
agrees to a decline in velocity distributions. Higher values of second order fluid parameter reduces the viscosity of fluid and accordingly velocity increases. Velocity profile is also a decreasing function of volume friction.
Delay to surgical treatment in lung cancer patients and its impact on survival in a video-assisted thoracoscopic lobectomy cohort
Authors: Ponholzer Florian , Kroepfl Veronika , Ng Caecilia , Maier Herbert , Kocher Florian , Lucciarini Paolo , Öfner Dietmar , Augustin Florian
Published: March 2021

Patient pathways from first suspicious imaging until final surgical treatment vary and in some instances cause considerable delay. This study aims to investigate the impact of this delay on survival of lung cancer patients. The institutional database was queried to identify patients with primary lung cancer who were treated with primary surgery. Time intervals were defined as date of first suspicious medical images until date of surgical treatment. All patients received PET-CT staging and tissue confirmation prior to treatment planning in a multidisciplinary tumor board. Patients with unknown date of first contact, follow-up CT-scans of pulmonary nodules, or neoadjuvant therapy were excluded. In total, 287 patients treated between 2009 and 2017 were included for further analysis. Median time between first suspicious medical imaging and surgical therapy was 62 (range 23–120) days and did not differ between male and female patients. Patients were then classified into two groups according to the duration of the medical work-up: group A up to 60 days, and group B from 61 to 120 days. Clinical T and N stages were comparable between the groups. There was no difference in overall survival between the two groups. In the subgroup of cT2 tumors (87 patients), there was a significant survival benefit for patients in group A (p = 0.043), while nodal stages, stage migration, lymphatic vessel invasion, grading and other potentially survival-influencing clinical parameters were comparable between the groups. Delay between diagnosis and treatment of lung cancer may result in dismal outcome. Efforts need to focus on improving and streamlining patient pathways to shorten the delay until surgical treatment to a minimum. Process improvement might be achieved by stringent interdisciplinary work-up and a patient-centered approach.
Identification of type III effectors modulating the symbiotic properties of Bradyrhizobium vignae strain ORS3257 with various Vigna species
Authors: Songwattana Pongpan , Chaintreuil Clémence , Wongdee Jenjira , Teulet Albin , Mbaye Mamadou , Piromyou Pongdet , Gully Djamel , Fardoux Joel , Zoumman Alexandre Mahougnon Aurel , Camuel Alicia , Tittabutr Panlada , Teaumroong Neung , Giraud Eric
Published: March 2021

The Bradyrhizobium vignae strain ORS3257 is an elite strain recommended for cowpea inoculation in Senegal. This strain was recently shown to establish symbioses on some Aeschynomene species using a cocktail of Type III effectors (T3Es) secreted by the T3SS machinery. In this study, using a collection of mutants in different T3Es genes, we sought to identify the effectors that modulate the symbiotic properties of ORS3257 in three Vigna species (V. unguiculata, V. radiata and V. mungo). While the T3SS had a positive impact on the symbiotic efficiency of the strain in V. unguiculata and V. mungo, it blocked symbiosis with V. radiata. The combination of effectors promoting nodulation in V. unguiculata and V. mungo differed, in both cases, NopT and NopAB were involved, suggesting they are key determinants for nodulation, and to a lesser extent, NopM1 and NopP1, which are additionally required for optimal symbiosis with V. mungo. In contrast, only one effector, NopP2, was identified as the cause of the incompatibility between ORS3257 and V. radiata. The identification of key effectors which promote symbiotic efficiency or render the interaction incompatible is important for the development of inoculation strategies to improve the growth of Vigna species cultivated in Africa and Asia.