bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing treatment plans for stomach cancer: three-dimensional conformal radiotherapy (3D-CRT), physical wedge-based conformal RT (WB-CRT) and intensity-modulated radiotherapy (IMRT)
Authors: Inan Gokcen , Gul Osman Vefa
Published: January 2021

Objective:

The aim of this study was to find the optimal radiotherapy (RT) method using three-dimensional (3D) conformal RT (CRT), physical wedge-based CRT (WB-CRT) and dynamic intensity-modulated RT (D-IMRT) techniques for stomach cancer.

Methods:

Ten patients with gastric cancer were selected for this study. For each patient, three different treatment plans were generated. 3D-CRT, WB-CRT and IMRT plans were evaluated in terms of dosimetry. Treatment plans were compared with respect to the planning target volume and organs at risk (OARs) volumes including right and left kidney doses (V13, V20 and V28), heart mean and maximum doses, spinal cord maximum doses, dose homogeneity index, conformity index (CI), delivery time and the monitor unit counts for the treatment. Statistical analysis was performed using the SPSS (Statistical Package for the Social Sciences) v25.1 software (IBM Inc., Chicago, IL, USA).

Results:

In stomach plans, IMRT showed a significantly lower dose for the left and right kidneys than that of WB-CRT or 3D-CRT (p < 0·05). Compared with WB-CRT or 3D-CRT, IMRT reduced the V28, V20, V13 and mean dose to bilateral kidneys (p < 0·05). IMRT plans indicated better dosimetry for at the Dmean of the liver and heart. Concerning the calculated CI, values for IMRT plans gave significant results than other plans (p < 0·05).

Conclusions:

IMRT plans provided better protection for the kidneys, liver, heart and spinal cord. For the treatment of stomach cancer, considering the dose to the OARs, IMRT appears to be the most superior technique.
Flattening filter free Stereotactic radiosurgery for brain metastases using dynamic conformal arcs: 6 MV or 10 MV?
Authors: Whitten Glenn , Daly Ursula , McCallum Candice D. , Harney Jackie , Conkey David , Flannery Tom , Irvine Denise M. , Skourou Christina , Hounsell Alan R. , McGarry Conor K.
Published: January 2021

Introduction:

Stereotactic radiosurgery (SRS) has proven itself as an effective tool in the treatment of intracranial lesions. Image-guided high dose single fraction treatments have the potential to deliver ablative doses to tumours; however, treatment times can be long. Flattening filter free (FFF) beams are available on most modern linacs and offer a higher dose rate compared to conventional flattened beams which should reduce treatment times. This study aimed to compare 6 MV FFF and 10 MV FFF to a 6 MV flattened beam for single fraction dynamic conformal arc SRS for a Varian Truebeam linac.

Materials and methods:

In total, 21 individual clinical treatment plans for 21 brain metastases treated with 6 MV were retrospectively replanned using both 6 MV FFF and 10 MV FFF. Plan quality and efficiency metrics were evaluated by analysing dose coverage, dose conformity, dose gradients, dose to normal brain, beam-on-time (BOT), treatment time and monitor units.

Results:

FFF resulted in a significant reduction in median BOT for both 6 MV FFF (57·9%; p < 0·001) and 10 MV FFF (76·3%; p < 0·001) which led to reductions in treatment times of 16·8 and 21·5% respectively. However, 6 MV FFF showed superior normal brain dose sparing (p < 0·001) and dose gradient (p < 0·001) compared to 10 MV FFF. No differences were observed for conformity.

Conclusion:

6 MV FFF offers a significant reduction in average treatment time compared to 6 MV (3·7 minutes; p = 0·002) while maintaining plan quality.
Preserving the ‘Essence’ of Fundamental Rights under Article 52(1) of the Charter: A Sisyphean Task?
Authors: Scarcello Orlando
Published: January 2021

Essence of fundamental rights – Article 52(1) of the Charter – Court of Justice of the EU – Methodology for determination of interference with essence – EU values – Proportionality – Balancing – Absolute and relative theory – Absolute rights – Interest theory of rights – Choice theory of rights – Hohfeld’s theory of rights – ‘Newtonian’ conception of rights – Case law on Article 52(1) of the Charter.
Present Heat Flow and Paleo‐Geothermal Anomalies in the Southern Golan Heights, Israel
Authors: Reznik Itay J. , Bartov Yuval
Published: January 2021

While present heat flow (HF) throughout Israel and the Dead Sea Transform (DST) area is considered low, a thermal anomaly exists near the Yarmuk valley at the southern tip of the Golan Heights. New temperature measurements in the southern Golan Heights show that the distribution of the thermal anomaly is significantly wider than previously thought. The new data conforms to either a local and shallow magmatic chamber, which is in thermal steady state with the surrounding rocks, or to a transient heat front associated with localized Pleistocene magmatic intrusions in the Yarmuk. An alternative mechanism suggests that the present HF intensity is higher than the HF value calculated based on the apparent borehole temperatures due to heat removal by deep aquifer flow. A paleothermal analysis was performed using high‐resolution organic matter maturation profiles on the Late Cretaceous source rocks, across the southern Golan basin. The maturation data show remarkably similar values throughout the basin, indicating that a single thermal event led to the source rock maturation. Constraints given by geological considerations have associated the paleothermal event with Pliocene volcanic eruptions, which has allowed the calculation of the basin paleo‐heat flows, and indicated on a basin wide heat source, such as a crustal heat source. The paleothermal event is sharply bounded by a DST branching fault. This observation is suggested to be related to either strike‐slip movement associated with the DST or to heat removal and modulation by a deep hydrological system.
Semi‐Monthly Lunar Tide Oscillation of foF2 in Equatorial Ionization Anomaly (EIA) Crests During 2014–2015 SSW
Authors: Tang Qiong , Zhou Chen , Li Zi‐Shen , Liu Yi , Chen Guan‐Yi
Published: January 2021

We investigate the ionospheric responses to the 2014–2015 sudden stratospheric warming (SSW) event in winter and summer hemisphere by using ionosondes distributed in Equatorial Ionization Anomaly (EIA) crests. Daily mean value of foF2 at each station shows obvious semimonthly lunar tide (∼14.5‐day period) modulation from lower to higher latitude in both hemispheres during SSW period. Besides, lunar tide modulation in summer hemisphere is later than that in winter hemisphere, which can be explained by the planetary wave penetrating across the equator from winter to summer hemisphere. In addition, lunar semidiurnal tide extracted from foF2 presents evident enhancement after warming onset. Our results demonstrate the quasi 16‐day periodic oscillations in F region of EIA crests are caused by the enhanced lunar tide in dynamo wind of mesosphere and lower thermosphere region, which is due to the disturbances in the zonal mean wind distribution in connection with SSW.
New Insight Into the Onshore Intrusion of the Kuroshio Into the East China Sea
Authors: Cui Xuan , Yang Dezhou , Sun Chaojiao , Feng Xingru , Gao Guandong , Xu Lingjing , Yin Baoshu
Published: January 2021

The Kuroshio Current, a vigorous western boundary current in the Pacific, is responsible for bringing high temperature, high salinity, and phosphate‐rich open ocean water into the East China Sea (ECS) when it flows past Taiwan and generates a branch current, known as the Kuroshio Branch Current (KBC), which intrudes onto the continental shelf of the ECS. Based on observations and numerical modeling, a 1.5‐layer reduced‐gravity model is evaluated and modified to simulate the flow pattern of the Kuroshio intrusion (KI) northeast of Taiwan. We revised the analytical solution derived by Hsueh (1992), https://doi.org/10.1029/92JC01401 to conserve the horizontal momentum balance in the along‐shelf and cross‐shelf directions. The new analytical solution not only explains the KI angle but also addresses the KBC recirculation mechanism. To sustain the steady‐state momentum balance in the area adjacent to the shelf break northeast of Taiwan, there must be a recirculation that plays the same role in vorticity dynamics as the combination of the joint effect of baroclinicity and relief, bottom friction, and nonlinear advection. Unlike previous studies, our results agree well with the observations and could account for seasonal variations in the KI direction. Moreover, the new model predicts a reasonable velocity maximum (0.42 m s−1) over the shelf break. Satellite data and numerical results confirm that the new solution reflects a reasonable estimation for KI direction. This theory may potentially be applied to regions with trenches or valleys with completely different flow patterns by using similar analytical methods.
Validation of IASI Satellite Ammonia Observations at the Pixel Scale Using In Situ Vertical Profiles
Authors: Guo Xuehui , Wang Rui , Pan Da , Zondlo Mark A. , Clarisse Lieven , Van Damme Martin , Whitburn Simon , Coheur Pierre‐François , Clerbaux Cathy , Franco Bruno , Golston Levi M. , Wendt Lars , Sun Kang , Tao Lei , Miller David , Mikoviny Tomas , Müller Markus , Wisthaler Armin , Tevlin Alexandra G. , Murphy Jennifer G. , Nowak John B. , Roscioli Joseph R. , Volkamer Rainer , Kille Natalie , Neuman J. Andrew , Eilerman Scott J. , Crawford James H. , Yacovitch Tara I. , Barrick John D. , Scarino Amy Jo
Published: January 2021

Satellite ammonia (NH3) observations provide unprecedented insights into NH3 emissions, spatiotemporal variabilities and trends, but validation with in situ measurements remains lacking. Here, total columns from the Infrared Atmospheric Sounding Interferometer (IASI) were intercompared to boundary layer NH3 profiles derived from aircraft‐ and surface‐based measurements primarily in Colorado, USA, in the summer of 2014. IASI‐NH3 version 3 near real‐time data set compared well to in situ derived columns (windows ±15 km around centroid, ±1 h around overpass time) with a correlation of 0.58, a slope of 0.78 ± 0.14 and an intercept of 2.1 × 1015±1.5 × 1015 molecules cm−2. Agreement degrades at larger spatiotemporal windows, consistent with the short atmospheric lifetime of NH3. We also examined IASI version 3R data, which relies on temperature retrievals from the ERA Reanalysis, and a third product generated using aircraft‐measured temperature profiles. The overall agreement improves slightly for both cases, and neither is biased within their combined measurement errors. Thus, spatiotemporal averaging of IASI over large windows can be used to reduce retrieval noise. Nonetheless, sampling artifacts of airborne NH3 instruments result in significant uncertainties of the in situ‐derived columns. For example, large validation differences exist between ascent and descent profiles, and the assumptions of the free tropospheric NH3 profiles used above the aircraft ceiling significantly impact the validation. Because short‐lived species like NH3 largely reside within the boundary layer with complex vertical structures, more comprehensive validation is needed across a wide range of environments. More accurate and widespread in situ NH3 data sets are therefore required for improved validations of satellite products.
Observation‐Constrained Projection of Global Flood Magnitudes With Anthropogenic Warming
Authors: Liu Wenbin , Yang Tao , Sun Fubao , Wang Hong , Feng Yao , Du Muye
Published: January 2021

River flooding is among the costliest natural disasters with severe economic, societal, and environmental consequences. However, substantial uncertainties remain in global and regional projections of future flood conditions simulated by global climate models (GCMs) and/or global hydrological models (GHMs). Using physical models coupled with machine learning (ML), for the first time, we project changes in flood magnitudes of 2062 global river basins by constraining physical‐based streamflow simulations with observations under 1.5°C and 2°C warming scenarios identified for the Representative Concentration Pathway 8.5. We found that, during the validation period, the GHMs‐simulated flood magnitudes would improve with reduced uncertainty over the selected river basins after ML with a Long Short‐Term Memory network. Our estimation suggested that flood magnitudes would increase in many Northern Hemisphere mid‐ and high‐latitude rivers (e.g., Lena River, Amur River and Volga River) but decrease in some river basins in southern Finland and Eastern Europe in future periods (i.e., 1.5°C and 2°C warming levels). In 1.5°C and 2°C warmer worlds, the decreasing flood magnitudes in most South American rivers are associated with decreased soil moisture and increased evapotranspiration induced by warmer temperatures. Although the geographical pattern of changes in flood magnitudes for the +2°C experiment is close to that of the +1.5°C experiment, a 1.5°C warming target is more likely to reduce flood magnitudes of many river basins worldwide (e.g., in central and eastern Siberia, Alaska/Northwest Canada and South America).
Hepatocyte nuclear factor 4α and cancer-related cell signaling pathways: a promising insight into cancer treatment
Authors: Lv Duo-Duo , Zhou Ling-Yun , Tang Hong
Published: January 2021

Hepatocyte nuclear factor 4α (HNF4α), a member of the nuclear receptor superfamily, is described as a protein that binds to the promoters of specific genes. It controls the expression of functional genes and is also involved in the regulation of numerous cellular processes. A large number of studies have demonstrated that HNF4α is involved in many human malignancies. Abnormal expression of HNF4α is emerging as a critical factor in cancer cell proliferation, apoptosis, invasion, dedifferentiation, and metastasis. In this review, we present emerging insights into the roles of HNF4α in the occurrence, progression, and treatment of cancer; reveal various mechanisms of HNF4α in cancer (e.g., the Wnt/β-catenin, nuclear factor-κB, signal transducer and activator of transcription 3, and transforming growth factor β signaling pathways); and highlight potential clinical uses of HNF4α as a biomarker and therapeutic target for cancer.
Investigating cytosolic 5′-nucleotidase II family genes as candidates for neuropsychiatric disorders in Drosophila (114/150 chr)
Authors: Singgih Euginia L. , van der Voet Monique , Schimmel-Naber Marlies , Brinkmann Emma L. , Schenck Annette , Franke Barbara
Published: January 2021

Cytosolic 5′-nucleotidases II (cNT5-II) are an evolutionary conserved family of 5′-nucleotidases that catalyze the intracellular hydrolysis of nucleotides. In humans, the family is encoded by five genes, namely NT5C2, NT5DC1, NT5DC2, NT5DC3, and NT5DC4. While very little is known about the role of these genes in the nervous system, several of them have been associated with neuropsychiatric disorders. Here, we tested whether manipulating neuronal expression of cNT5-II orthologues affects neuropsychiatric disorders-related phenotypes in the model organism Drosophila melanogaster. We investigated the brain expression of Drosophila orthologues of cNT5-II family (dNT5A-CG2277, dNT5B-CG32549, and dNT5C-CG1814) using quantitative real-time polymerase chain reaction (qRT-PCR). Using the UAS/Gal4 system, we also manipulated the expression of these genes specifically in neurons. The knockdown was subjected to neuropsychiatric disorder-relevant behavioral assays, namely light-off jump reflex habituation and locomotor activity, and sleep was measured. In addition, neuromuscular junction synaptic morphology was assessed. We found that dNT5A, dNT5B, and dNT5C were all expressed in the brain. dNT5C was particularly enriched in the brain, especially at pharate and adult stages. Pan-neuronal knockdown of dNT5A and dNT5C showed impaired habituation learning. Knockdown of each of the genes also consistently led to mildly reduced activity and/or increased sleep. None of the knockdown models displayed significant alterations in synaptic morphology. In conclusion, in addition to genetic associations with psychiatric disorders in humans, altered expression of cNT5-II genes in the Drosophila nervous system plays a role in disease-relevant behaviors.
Hsa_circ_0007456 regulates the natural killer cell-mediated cytotoxicity toward hepatocellular carcinoma via the miR-6852-3p/ICAM-1 axis
Authors: Shi Min , Li Zhao-Yun , Zhang Li-Ming , Wu Xiao-Yu , Xiang Shi-Hao , Wang Yu-Gang , Zhang Ya-Qiong
Published: January 2021

Circular RNAs (circRNAs) is one type of important non-coding RNAs that participate in tumorigenesis and cancer progression. In our previous study, we performed a microarray analysis of circRNAs between the tumor tissues and the adjacent normal tissues of hepatocellular carcinoma (HCC) patients, and found that the circRNA hsa_circ_0007456 is significantly downregulated in the tumor tissues and correlated with the prognosis of HCC. We further investigated the relationship between the expression levels of hsa_circ_0007456 in HCC and the susceptibility of NK cells, and found that the expression levels of hsa_circ_0007456 in HCC cell lines significantly influenced their susceptibility to NK cells. Through a series of screening and validation, we found that hsa_circ_0007456 mainly functioned through sponging miR-6852-3p and regulating the expression of intercellular adhesion molecule-1 (ICAM-1) in HCC. The miR-6852-3p/ICAM-1 axis is essential for the NK cytotoxicity toward HCC mediated by hsa_circ_0007456. In conclusion, we identify here hsa_circ_0007456 as a promising biomarker of HCC, and highlight hsa_circ_0007456/miR-6852-3p/ICAM-1 axis as an important signaling pathway in the process of tumor immune evasion and the tumorigenesis of HCC.
Proteomics analysis of human intestinal organoids during hypoxia and reoxygenation as a model to study ischemia-reperfusion injury
Authors: Kip Anna M. , Soons Zita , Mohren Ronny , Duivenvoorden Annet A. M. , Röth Anjali A. J. , Cillero-Pastor Berta , Neumann Ulf P. , Dejong Cornelis H. C. , Heeren Ron M. A. , Olde Damink Steven W. M. , Lenaerts Kaatje
Published: January 2021

Intestinal ischemia-reperfusion (IR) injury is associated with high mortality rates, which have not improved in the past decades despite advanced insight in its pathophysiology using in vivo animal and human models. The inability to translate previous findings to effective therapies emphasizes the need for a physiologically relevant in vitro model to thoroughly investigate mechanisms of IR-induced epithelial injury and test potential therapies. In this study, we demonstrate the use of human small intestinal organoids to model IR injury by exposing organoids to hypoxia and reoxygenation (HR). A mass-spectrometry-based proteomics approach was applied to characterize organoid differentiation and decipher protein dynamics and molecular mechanisms of IR injury in crypt-like and villus-like human intestinal organoids. We showed successful separation of organoids exhibiting a crypt-like proliferative phenotype, and organoids exhibiting a villus-like phenotype, enriched for enterocytes and goblet cells. Functional enrichment analysis of significantly changing proteins during HR revealed that processes related to mitochondrial metabolism and organization, other metabolic processes, and the immune response were altered in both organoid phenotypes. Changes in protein metabolism, as well as mitophagy pathway and protection against oxidative stress were more pronounced in crypt-like organoids, whereas cellular stress and cell death associated protein changes were more pronounced in villus-like organoids. Profile analysis highlighted several interesting proteins showing a consistent temporal profile during HR in organoids from different origin, such as NDRG1, SDF4 or DMBT1. This study demonstrates that the HR response in human intestinal organoids recapitulates properties of the in vivo IR response. Our findings provide a framework for further investigations to elucidate underlying mechanisms of IR injury in crypt and/or villus separately, and a model to test therapeutics to prevent IR injury.
Correction to: ASH2L drives proliferation and sensitivity to bleomycin and other genotoxins in Hodgkin’s lymphoma and testicular cancer cells
Authors: Constantin Daniel , Widmann Christian
Published: January 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03386-4
Translation machinery reprogramming in programmed cell death in Saccharomyces cerevisiae
Authors: Monticolo Francesco , Palomba Emanuela , Chiusano Maria Luisa
Published: January 2021

Programmed cell death involves complex molecular pathways in both eukaryotes and prokaryotes. In Escherichia coli, the toxin–antitoxin system (TA-system) has been described as a programmed cell death pathway in which mRNA and ribosome organizations are modified, favoring the production of specific death-related proteins, but also of a minor portion of survival proteins, determining the destiny of the cell population. In the eukaryote Saccharomyces cerevisiae, the ribosome was shown to change its stoichiometry in terms of ribosomal protein content during stress response, affecting the relative proportion between ohnologs, i.e., the couple of paralogs derived by a whole genome duplication event. Here, we confirm the differential expression of ribosomal proteins in yeast also during programmed cell death induced by acetic acid, and we highlight that also in this case pairs of ohnologs are involved. We also show that there are different trends in cytosolic and mitochondrial ribosomal proteins gene expression during the process. Moreover, we show that the exposure to acetic acid induces the differential expression of further genes coding for products related to translation processes and to rRNA post-transcriptional maturation, involving mRNA decapping, affecting translation accuracy, and snoRNA synthesis. Our results suggest that the reprogramming of the overall translation apparatus, including the cytosolic ribosome reorganization, are relevant events in yeast programmed cell death induced by acetic acid.
Quantifying neurotransmitter secretion at single-vesicle resolution using high-density complementary metal–oxide–semiconductor electrode array
Authors: White Kevin A. , Kim Brian N.
Published: January 2021

Neuronal exocytosis facilitates the propagation of information through the nervous system pertaining to bodily function, memory, and emotions. Using amperometry, the sub-millisecond dynamics of exocytosis can be monitored and the modulation of exocytosis due to drug treatment or neurodegenerative diseases can be studied. Traditional single-cell amperometry is a powerful technique for studying the molecular mechanisms of exocytosis, but it is both costly and labor-intensive to accumulate statistically significant data. To surmount these limitations, we have developed a silicon-based electrode array with 1024 on-chip electrodes that measures oxidative signal in 0.1 millisecond intervals. Using the developed device, we are able to capture the modulation of exocytosis due to Parkinson’s disease treatment (L-Dopa), with statistical significance, within 30 total minutes of recording. The validation study proves our device’s capability to accelerate the study of many pharmaceutical treatments for various neurodegenerative disorders that affect neurotransmitter secretion to a matter of minutes.
Soliton microcomb based spectral domain optical coherence tomography
Authors: Marchand Paul J. , Riemensberger Johann , Skehan J. Connor , Ho Jia-Jung , Pfeiffer Martin H. P. , Liu Junqiu , Hauger Christoph , Lasser Theo , Kippenberg Tobias J.
Published: January 2021

Spectral domain optical coherence tomography (OCT) is a widely employed, minimally invasive bio-medical imaging technique, which requires a broadband light source, typically implemented by super-luminescent diodes. Recent advances in soliton based photonic integrated frequency combs (soliton microcombs) have enabled the development of low-noise, broadband chipscale frequency comb sources, whose potential for OCT imaging has not yet been unexplored. Here, we explore the use of dissipative Kerr soliton microcombs in spectral domain OCT and show that, by using photonic chipscale Si3N4 resonators in conjunction with 1300 nm pump lasers, spectral bandwidths exceeding those of commercial OCT sources are possible. We characterized the exceptional noise properties of our source (in comparison to conventional OCT sources) and demonstrate that the soliton states in microresonators exhibit a residual intensity noise floor at high offset frequencies that is ca. 3 dB lower than a traditional OCT source at identical power, and can exhibit significantly lower noise performance for powers at the milli-Watt level. Moreover, we demonstrate that classical amplitude noise of all soliton comb teeth are correlated, i.e., common mode, in contrast to superluminescent diodes or incoherent microcomb states, which opens a new avenue to improve imaging speed and performance beyond the thermal noise limit.
Ionic shape-morphing microrobotic end-effectors for environmentally adaptive targeting, releasing, and sampling
Authors: Zheng Zhiqiang , Wang Huaping , Dong Lixin , Shi Qing , Li Jianing , Sun Tao , Huang Qiang , Fukuda Toshio
Published: January 2021

Shape-morphing uses a single actuation source for complex-task-oriented multiple patterns generation, showing a more promising way than reconfiguration, especially for microrobots, where multiple actuators are typically hardly available. Environmental stimuli can induce additional causes of shape transformation to compensate the insufficient space for actuators and sensors, which enriches the shape-morphing and thereby enhances the function and intelligence as well. Here, making use of the ionic sensitivity of alginate hydrogel microstructures, we present a shape-morphing strategy for microrobotic end-effectors made from them to adapt to different physiochemical environments. Pre-programmed hydrogel crosslinks were embedded in different patterns within the alginate microstructures in an electric field using different electrode configurations. These microstructures were designed for accomplishing tasks such as targeting, releasing and sampling under the control of a magnetic field and environmental ionic stimuli. In addition to structural flexibility and environmental ion sensitivity, these end-effectors are also characterized by their complete biodegradability and versatile actuation modes. The latter includes global locomotion of the whole end-effector by self-trapping magnetic microspheres as a hitch-hiker and the local opening and closing of the jaws using encapsulated nanoparticles based on local ionic density or pH values. The versatility was demonstrated experimentally in both in vitro environments and ex vivo in a gastrointestinal tract. Global locomotion was programmable and the local opening and closing was achieved by changing the ionic density or pH values. This ‘structural intelligence’ will enable strategies for shape-morphing and functionalization, which have attracted growing interest for applications in minimally invasive medicine, soft robotics, and smart materials.
2,2-difluorovinyl benzoates for diverse synthesis of gem-difluoroenol ethers by Ni-catalyzed cross-coupling reactions
Authors: Du Bingnan , Chan Chun-Ming , Lee Pui-Yiu , Cheung Leong-Hung , Xu Xin , Lin Zhenyang , Yu Wing-Yiu
Published: January 2021

gem-Difluoroalkene is a bioisostere of carbonyl group for improving bioavailability of drug candidates. Herein we develop structurally diverse 2,2-difluorovinyl benzoates (BzO-DFs) as versatile building blocks for modular synthesis ofgem-difluoroenol ethers (44 examples) andgem-difluoroalkenes (2 examples) by Ni-catalyzed cross coupling reactions. Diverse BzO-DFs derivatives bearing sensitive functional groups (e.g., C = C, TMS, strained carbocycles) are readily prepared from their bromodifluoroacetates and bromodifluoroketones precursors using metallic zinc as reductant. With Ni(COD)2and dppf [1,1’-bis(diphenylphosphino)ferrocene] as catalyst, reactions of BzO-DFs with arylboronic acids and arylmagnesium/alkylzinc reagents afforded the desiredgem-difluoroenol ethersand gem-difluoroalkenes in good yields. The Ni-catalyzed coupling reactions features highly regioselective C(vinyl)–O(benzoate) bond activation of the BzO-DFs. Results from control experiments and DFT calculations are consistent with a mechanism involving initial oxidative addition of the BzO-DFs by the Ni(0) complex. By virtue of diversity of the BzO-DFs and excellent functional group tolerance, this method is amenable to late-stage functionalization of multifunctionalized bioactive molecules.
Author Correction: Time reversed optical waves by arbitrary vector spatiotemporal field generation
Authors: Mounaix Mickael , Fontaine Nicolas K. , Neilson David T. , Ryf Roland , Chen Haoshuo , Alvarado-Zacarias Juan Carlos , Carpenter Joel
Published: January 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-20944-8.
Pallidal stimulation as treatment for camptocormia in Parkinson’s disease
Authors: Lai Yijie , Song Yunhai , Su Daoqing , Wang Linbin , Zhang Chencheng , Sun Bomin , Nonnekes Jorik , Bloem Bastiaan R. , Li Dianyou
Published: January 2021

Camptocormia is a common and often debilitating postural deformity in Parkinson’s disease (PD). Few treatments are currently effective. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) shows potential in treating camptocormia, but evidence remains limited to case reports. We herein investigate the effect of GPi-DBS for treating camptocormia in a retrospective PD cohort. Thirty-six consecutive PD patients who underwent GPi-DBS were reviewed. The total and upper camptocormia angles (TCC and UCC angles) derived from video recordings of patients who received GPi-DBS were used to compare camptocormia alterations. Correlation analysis was performed to identify factors associated with the postoperative improvements. DBS lead placement and the impact of stimulation were analyzed using Lead-DBS software. Eleven patients manifested pre-surgical camptocormia: seven had lower camptocormia (TCC angles ≥ 30°; TCC-camptocormia), three had upper camptocormia (UCC angles ≥ 45°; UCC-camptocormia), and one had both. Mean follow-up time was 7.3 ± 3.3 months. GPi-DBS improved TCC-camptocormia by 40.4% (angles from 39.1° ± 10.1° to 23.3° ± 8.1°,p = 0.017) and UCC-camptocormia by 22.8% (angles from 50.5° ± 2.6° to 39.0° ± 6.7°,p = 0.012). Improvement in TCC angle was positively associated with pre-surgical TCC angles, levodopa responsiveness of the TCC angle, and structural connectivity from volume of tissue activated to somatosensory cortex. Greater improvement in UCC angles was seen in patients with larger pre-surgical UCC angles. Our study demonstrates potential effectiveness of GPi-DBS for treating camptocormia in PD patients. Future controlled studies with larger numbers of patients with PD-related camptocormia should extend our findings.
Estimation of waste outflows for multiple product types in China from 2010–2050
Authors: Zeng Xianlai , Ali Saleem H. , Li Jinhui
Published: January 2021

Material flow has been accelerated from underground natural minerals and is accumulating as aboveground waste stock. China is not only the largest producer and consumer of material-driven products, but also the largest generator of product waste. No official annual product waste data are released for China, which creates challenges especially in light of China’s emerging waste management policies. Previous studies have presented only estimations of waste streams for single products. In this study, we considered three product types and 33 technological products and collected all the available data. A Kuznets curve and Bass diffusion model were employed to forecast their future consumption. Based on urban consumption metabolism, we created one systematic estimation model of product waste generation related to material flow and social regulation. Typical technological product waste outflows were estimated from 2010 to 2050, which can assist further material flow and environmental impact research, as well as waste management policy-making and technology development. The created model can be potentially extended to other types of product waste estimation.
Optical motion capture dataset of selected techniques in beginner and advanced Kyokushin karate athletes
Authors: Szczęsna Agnieszka , Błaszczyszyn Monika , Pawlyta Magdalena
Published: January 2021

Human motion capture is commonly used in various fields, including sport, to analyze, understand, and synthesize kinematic and kinetic data. Specialized computer vision and marker-based optical motion capture techniques constitute the gold-standard for accurate and robust human motion capture. The dataset presented consists of recordings of 37 Kyokushin karate athletes of different ages (children, young people, and adults) and skill levels (from 4th dan to 9th kyu) executing the following techniques: reverse lunge punch (Gyaku-Zuki), front kick (Mae-Geri), roundhouse kick (Mawashi-Geri), and spinning back kick (Ushiro-Mawashi-Geri). Each technique was performed approximately three times per recording (i.e., to create a single data file), and under three conditions where participants kicked or punched (i) in the air, (ii) a training shield, or (iii) an opponent. Each participant undertook a minimum of two trials per condition. The data presented was captured using a Vicon optical motion capture system with Plug-In Gait software. Three dimensional trajectories of 39 reflective markers were recorded. The resultant dataset contains a total of 1,411 recordings, with 3,229 single kicks and punches. The recordings are available in C3D file format. The dataset provides the opportunity for kinematic analysis of different combat sport techniques in attacking and defensive situations.
Incorporation and antimicrobial activity of nisin Z within carrageenan/chitosan multilayers
Authors: Webber Jessie L. , Namivandi-Zangeneh Rashin , Drozdek Sławomir , Wilk Kazimiera A. , Boyer Cyrille , Wong Edgar H. H. , Bradshaw-Hajek Bronwyn H. , Krasowska Marta , Beattie David A.
Published: January 2021

An antimicrobial peptide, nisin Z, was embedded within polyelectrolyte multilayers (PEMs) composed of natural polysaccharides in order to explore the potential of forming a multilayer with antimicrobial properties. Using attenuated total reflection Fourier transform infrared spectroscopy (ATR FTIR), the formation of carrageenan/chitosan multilayers and the inclusion of nisin Z in two different configurations was investigated. Approximately 0.89 µg cm−2 nisin Z was contained within a 4.5 bilayer film. The antimicrobial properties of these films were also investigated. The peptide containing films were able to kill over 90% and 99% of planktonic and biofilm cells, respectively, against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) strains compared to control films. Additionally, surface topography and wettability studies using atomic force microscopy (AFM) and the captive bubble technique revealed that surface roughness and hydrophobicity was similar for both nisin containing multilayers. This suggests that the antimicrobial efficacy of the peptide is unaffected by its location within the multilayer. Overall, these results demonstrate the potential to embed and protect natural antimicrobials within a multilayer to create functionalised coatings that may be desired by industry, such as in the food, biomaterials, and pharmaceutical industry sectors.
Identifying protein subcellular localisation in scientific literature using bidirectional deep recurrent neural network
Authors: David Rakesh , Menezes Rhys-Joshua D. , De Klerk Jan , Castleden Ian R. , Hooper Cornelia M. , Carneiro Gustavo , Gilliham Matthew
Published: January 2021

The increased diversity and scale of published biological data has to led to a growing appreciation for the applications of machine learning and statistical methodologies to gain new insights. Key to achieving this aim is solving the Relationship Extraction problem which specifies the semantic interaction between two or more biological entities in a published study. Here, we employed two deep neural network natural language processing (NLP) methods, namely: the continuous bag of words (CBOW), and the bi-directional long short-term memory (bi-LSTM). These methods were employed to predict relations between entities that describe protein subcellular localisation in plants. We applied our system to 1700 published Arabidopsis protein subcellular studies from the SUBA manually curated dataset. The system combines pre-processing of full-text articles in a machine-readable format with relevant sentence extraction for downstream NLP analysis. Using the SUBA corpus, the neural network classifier predicted interactions between protein name, subcellular localisation and experimental methodology with an average precision, recall rate, accuracy and F1 scores of 95.1%, 82.8%, 89.3% and 88.4% respectively (n = 30). Comparable scoring metrics were obtained using the CropPAL database as an independent testing dataset that stores protein subcellular localisation in crop species, demonstrating wide applicability of prediction model. We provide a framework for extracting protein functional features from unstructured text in the literature with high accuracy, improving data dissemination and unlocking the potential of big data text analytics for generating new hypotheses.
Magnetic field promoted irreversible process of water based nanocomposites with heat and mass transfer flow
Authors: Khan Noor Saeed , Kumam Poom , Thounthong Phatiphat
Published: January 2021

Analytical analysis of two-dimensional, magnetohydrodynamic, heat and mass transfer flow of hybrid nanofluid incorporating Hall and ion-slip effects and viscous dissipation in the presence of homogeneous-heterogeneous chemical reactions and entropy generation is performed. The governing equations are modified with the help of similarity variables. The reduced resulting nonlinear coupled ordinary differential equations are solved with the help of homotopy analysis method. The effects of all the physical parameters are demonstrated graphically through a detailed analysis. The main outcome of the study is the use of applied strong magnetic field which generates the cross flow of hybrid nanofluid along the z-axis. The numerical comparison to the existing published literature is also provided.
Effect of Berberis vulgaris L. root extract on ifosfamide-induced in vivo toxicity and in vitro cytotoxicity
Authors: Ilyas Shazia , Tabasum Raheela , Iftikhar Ali , Nazir Mamoona , Hussain Amina , Hussain Aroosha , Ali Muhammad Sajjad , Saleem Farooq , Saleem Uzma , Froeyen Matheus , Abdullah Iskandar , Mirza Muhammad Usman , Ahmad Sarfraz
Published: January 2021

Ifosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors. However, nephro, hepato, neuro cardio, and hematological toxicities associated with ifosfamide render its use limited. These side effects could range from organ failure to life-threatening situations. The present study aimed to evaluate the attenuating efficiency of Berberis vulgaris root extract (BvRE), a potent nephroprotective, hepatoprotective, and lipid-lowering agent, against ifosfamide-induced toxicities. The study design comprised eight groups of Swiss albino rats to assess different dose regimes of BvRE and ifosfamide. Biochemical analysis of serum (serum albumin, blood urea nitrogen, creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, and triglycerides) along with complete blood count was performed. Kidney, liver, brain, and heart tissue homogenates were used to find malondialdehyde, catalase, and glutathione S-transferase levels in addition to the acetylcholinesterase of brain tissue. The results were further validated with the help of the histopathology of the selected organs. HeLa cells were used to assess the effect of BvRE on ifosfamide cytotoxicity in MTT assay. The results revealed that pre- and post-treatment regimens of BvRE, as well as the combination therapy exhibited marked protective effects against ifosfamide-induced nephro, hepato, neuro, and cardiotoxicity. Moreover, ifosfamide depicted a synergistic in vitro cytotoxic effect on HeLa cells in the presence of BvRE. These results corroborate that the combination therapy of ifosfamide with BvRE in cancer treatment can potentiate the anticancer effects of ifosfamide along with the amelioration of its conspicuous side effects.
Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome
Authors: Coelho-Silva Juan L. , Silveira Douglas R. A. , Pereira-Martins Diego A. , Rojas Cesar A. O. , Lucena-Araujo Antonio R. , Rego Eduardo M. , Machado-Neto João A. , Bendit Israel , Rocha Vanderson , Traina Fabiola
Published: January 2021

Deregulated cellular energetics is formally incorporated as an emerging hallmark of cancer, however little is known about its processes in myelodysplastic syndromes (MDS). Using transcriptomic data of CD34+ cells from 159 MDS patients and 17 healthy donors, we selected 37 genes involved in cellular energetics and interrogated about its clinical and prognostic functions. Based on the low expression of ACLY, ANPEP, and PANK1, as well as high expression of PKM and SLC25A5, we constructed our Molecular-Based Score (MBS), that efficiently discriminated patients at three risks groups: favourable risk (n = 28; 3-year overall survival (OS): 100%); intermediate (n = 60; 76% [62–93%]) and adverse (n = 71; 35% [17–61%]). Adverse MBS risk was independently associated with inferior OS (HR = 10.1 [95% CI 1.26–81]; P = 0.029) in multivariable analysis using age, gender and the revised international prognostic score system as confounders. Transcriptional signature revealed that Favourable- and intermediate-risk patients presented enriched molecular programs related to mature myeloid progenitors, cell cycle progression, and oxidative phosphorylation, indicating that this cells differs in their origin, metabolic state, and cell cycle regulation, in comparison to the adverse-risk. Our study provides the first evidence that cellular energetics is transcriptionally deregulated in MDS CD34+ cells and establishes a new useful prognostic score based on the expression of five genes.
An objective structural and functional reference standard in glaucoma
Authors: Mariottoni Eduardo B. , Jammal Alessandro A. , Berchuck Samuel I. , Shigueoka Leonardo S. , Tavares Ivan M. , Medeiros Felipe A.
Published: January 2021

The current lack of consensus for diagnosing glaucoma makes it difficult to develop diagnostic tests derived from deep learning (DL) algorithms. In the present study, we propose an objective definition of glaucomatous optic neuropathy (GON) using clearly defined parameters from optical coherence tomography and standard automated perimetry. We then use the proposed objective definition as reference standard to develop a DL algorithm to detect GON on fundus photos. A DL algorithm was trained to detect GON on fundus photos, using the proposed objective definition as reference standard. The performance was evaluated on an independent test sample with sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and likelihood ratios (LR). The test sample had 2118 fundus photos from 585 eyes of 405 individuals. The AUC to discriminate between GON and normal was 0.92 with sensitivity of 77% at 95% specificity. LRs indicated that the DL algorithm provided large changes in the post-test probability of disease for the majority of eyes. A DL algorithm to evaluate fundus photos had high performance to discriminate GON from normal. The newly proposed objective definition of GON used as reference standard may increase the comparability of diagnostic studies of glaucoma across devices and populations.
Effect of calcination temperature on the properties and applications of bio extract mediated titania nano particles
Authors: Saikumari N. , Dev S. Monish , Dev S. Avinaash
Published: January 2021

In order to deal with the arising environmental issues across the globe at present nano particles with unique properties laid a benchmark in the name of nano catalysis. In this work the significance of calcination temperature on the thermal, electronic, structural and surface properties of a nano catalyst produced by sol–gel method using ultrasonic radiation against the disposal of toxic textile pollutants is studied in detail. The extract of tea leaves has been used as a bio-template during the synthesis to revise the crystallite size, surface area, optical absorption potential, and rate of agglomeration of nano sized grains by regulating their physico-chemical and surface properties. The influence of calcination in the transformation of single phased anatase titania to mixed phase anatase–rutile titania and the corresponding outcome in its photocatalytic activity employed in water treatment applications have been verified. The nano catalyst obtained is characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Transition electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), Thermo gravimetric analysis (TGA), Brunaueur Emmett Teller (BET) analysis, UV–Vis diffused reflectance spectroscopy (DRS-UV–Vis) etc. The mesoporosity of the particle was examined using Barrett Joyner Halenda (BJH) model. The enhanced photo catalytic efficiency (about 97.7%) of templated nano titania due to calcination is verified against Congo red, a textile dye under optimized conditions. The nano catalyst produced can be easily separated, recycled to support its economic feasibility.
Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation
Authors: Giunti Debora , Marini Chiara , Parodi Benedetta , Usai Cesare , Milanese Marco , Bonanno Giambattista , Kerlero de Rosbo Nicole , Uccelli Antonio
Published: January 2021

Mesenchymal stromal/stem cells (MSCs) are characterized by neuroprotective, immunomodulatory, and neuroregenerative properties, which support their therapeutic potential for inflammatory/neurodegenerative diseases, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). One mode of action through which MSCs exert their immunomodulatory effects is release of extracellular vesicles that carry proteins, mRNAs, and microRNAs (miRNAs), which, once transferred, modify the function of target cells. We identified nine miRNAs significantly dysregulated in IFN-γ-primed MSCs, but present at different levels in their derived small extracellular vesicles (s-EV). We show that miR-467f and miR-466q modulate the pro-inflammatory phenotype of activated N9 microglia cells and of primary microglia acutely isolated from late symptomatic SOD1G93A mice, a murine ALS model, by downregulating Tnf and Il1b expression. Further analysis of the mode of action of miR-467f and miR-466q indicated that they dampen the pro-inflammatory phenotype of microglia by modulating p38 MAPK signaling pathway via inhibition of expression of their target genes, Map3k8 and Mk2. Finally, we demonstrated that in vivo administration of s-EV leads to decreased expression of neuroinflammation markers in the spinal cord of EAE-affected mice, albeit without affecting disease course. Overall, our data suggest that MSC-derived exosomes could affect neuroinflammation possibly through specific immunomodulatory miRNAs acting on microglia.