bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare and Catholic Enlightenment in the Polish-Lithuanian Commonwealth
Authors: Witecki Stanisław
Published: June 2022

In the eighteenth century, the ideal of the priest in society was reformed by Polish and Lithuanian Catholic bishops. Instrumental in these reforms were Ignacy Massalski (1726–94), bishop of Vilnius (1762–94) and Michał Poniatowski (1736–94), bishop of Płock (1773–85), then archbishop of Gniezno (1785–94), and simultaneously administrator of the diocese of Kraków (1782–90). Their programmes included making clergy responsible for medical education and the organization of healthcare, and seeking to reform customs which were viewed as detrimental to health. The article draws on pastoral letters, popular educational books and administrative decrees to ascertain what ideas reformers imposed on the clergy. Episcopal visitation protocols, sermons and parish school textbooks are analysed to verify the effects of reforms and ascertain what was taught about health in the parishes. The examination of the relatively rare egodocuments of priests sheds light on how they experienced their afflictions. The article concludes that healthcare was an important topic for Catholic enlighteners in the Polish-Lithuanian Commonwealth, and that priests played a significant role in promoting it. Reforms were driven by humanitarian and physiocratic principles, and were facilitated by an optimistic belief in the benefits of medicine. Nonetheless, many enlightened programmes failed because priests were unwilling or unable to implement changes that interfered with lived religion.
Is vascular insulin resistance an early step in diet-induced whole-body insulin resistance?
Authors: Carmichael Lauren , Keske Michelle A. , Betik Andrew C. , Parker Lewan , Brayner Barbara , Roberts-Thomson Katherine M. , Wadley Glenn D. , Hamilton D. Lee , Kaur Gunveen
Published: June 2022

There is increasing evidence that skeletal muscle microvascular (capillary) blood flow plays an important role in glucose metabolism by increasing the delivery of glucose and insulin to the myocytes. This process is impaired in insulin-resistant individuals. Studies suggest that in diet-induced insulin-resistant rodents, insulin-mediated skeletal muscle microvascular blood flow is impaired post-short-term high fat feeding, and this occurs before the development of myocyte or whole-body insulin resistance. These data suggest that impaired skeletal muscle microvascular blood flow is an early vascular step before the onset of insulin resistance. However, evidence of this is still lacking in humans. In this review, we summarise what is known about short-term high-calorie and/or high-fat feeding in humans. We also explore selected animal studies to identify potential mechanisms. We discuss future directions aimed at better understanding the ‘early’ vascular mechanisms that lead to insulin resistance as this will provide the opportunity for much earlier screening and timing of intervention to assist in preventing type 2 diabetes.
Integrative PheWAS analysis in risk categorization of major depressive disorder and identifying their associations with genetic variants using a latent topic model approach
Authors: Meng Xiangfei , Wang Michelle , O’Donnell Kieran J. , Caron Jean , Meaney Michael J. , Li Yue
Published: June 2022

Major depressive disorder (MDD) is the most prevalent mental disorder that constitutes a major public health problem. A tool for predicting the risk of MDD could assist with the early identification of MDD patients and targeted interventions to reduce the risk. We aimed to derive a risk prediction tool that can categorize the risk of MDD as well as discover biologically meaningful genetic variants. Data analyzed were from the fourth and fifth data collections of a longitudinal community-based cohort from Southwest Montreal, Canada, between 2015 and 2018. To account for high dimensional features, we adopted a latent topic model approach to infer a set of topical distributions over those studied predictors that characterize the underlying meta-phenotypes of the MDD cohort. MDD probability derived from 30 MDD meta-phenotypes demonstrated superior prediction accuracy to differentiate MDD cases and controls. Six latent MDD meta-phenotypes we inferred via a latent topic model were highly interpretable. We then explored potential genetic variants that were statistically associated with these MDD meta-phenotypes. The genetic heritability of MDD meta-phenotypes was 0.126 (SE = 0.316), compared to 0.000001 (SE = 0.297) for MDD diagnosis defined by the structured interviews. We discovered a list of significant MDD - related genes and pathways that were missed by MDD diagnosis. Our risk prediction model confers not only accurate MDD risk categorization but also meaningful associations with genetic predispositions that are linked to MDD subtypes. Our findings shed light on future research focusing on these identified genes and pathways for MDD subtypes.
Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice
Authors: Lin Shaojian , Zhang Anke , Yuan Ling , Wang Yufan , Zhang Chuan , Jiang Junkun , Xu Houshi , Yuan Huiwen , Yao Hui , Zhang Qianying , Zhang Yong , Lou Meiqing , Wang Ping , Zhang Zhen-Ning , Luan Bing
Published: June 2022

Exercise benefits M2 macrophage polarization, energy homeostasis and protects against obesity partially through exercise-induced circulating factors. Here, by unbiased quantitative proteomics on serum samples from sedentary and exercised mice, we identify parvalbumin as a circulating factor suppressed by exercise. Parvalbumin functions as a non-competitive CSF1R antagonist to inhibit M2 macrophage activation and energy expenditure in adipose tissue. More importantly, serum concentrations of parvalbumin positively correlate with obesity in mouse and human, while treating mice with a recombinant parvalbumin blocker prevents its interaction with CSF1R and promotes M2 macrophage polarization and ameliorates diet-induced obesity. Thus, although further studies are required to assess the significance of parvalbumin in mediating the effects of exercise, our results implicate parvalbumin as a potential therapeutic strategy against obesity in mice.
Rapid, adaptable and sensitive Cas13-based COVID-19 diagnostics using ADESSO
Authors: Casati Beatrice , Verdi Joseph Peter , Hempelmann Alexander , Kittel Maximilian , Klaebisch Andrea Gutierrez , Meister Bianca , Welker Sybille , Asthana Sonal , Di Giorgio Salvatore , Boskovic Pavle , Man Ka Hou , Schopp Meike , Ginno Paul Adrian , Radlwimmer Bernhard , Stebbins Charles Erec , Miethke Thomas , Papavasiliou Fotini Nina , Pecori Riccardo
Published: June 2022

During the ongoing COVID-19 pandemic, PCR testing and antigen tests have proven critical for helping to stem the spread of its causative agent, SARS-CoV-2. However, these methods suffer from either general applicability and/or sensitivity. Moreover, the emergence of variant strains creates the need for flexibility to correctly and efficiently diagnose the presence of substrains. To address these needs we developed the diagnostic test ADESSO (Accurate Detection of Evolving SARS-CoV-2 through SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) Optimization) which employs Cas13 to diagnose patients in 1 h without sophisticated equipment. Using an extensive panel of clinical samples, we demonstrate that ADESSO correctly identifies infected individuals at a sensitivity and specificity comparable to RT-qPCR on extracted RNA and higher than antigen tests for unextracted samples. Altogether, ADESSO is a fast, sensitive and cheap method that can be applied in a point of care setting to diagnose COVID-19 and can be quickly adjusted to detect new variants.
Leukocyte cell-derived chemotaxin 2 is an antiviral regulator acting through the proto-oncogene MET
Authors: Shirasaki Takayoshi , Yamagoe Satoshi , Shimakami Tetsuro , Murai Kazuhisa , Imamura Ryu , Ishii Kiyo-Aki , Takayama Hiroaki , Matsumoto Yukako , Tajima-Shirasaki Natsumi , Nagata Naoto , Shimizu Ryogo , Yamanaka Souma , Abe Atsushi , Omura Hitoshi , Kawaguchi Kazunori , Okada Hikari , Yamashita Taro , Yoshikawa Tomoki , Takimoto Kazuhiro , Taharaguchi Motoko , Takatsuka Shogo , Miyazaki Yoshitsugu , Tamai Toshikatsu , Tanabe Yamato , Kurachi Makoto , Yamamoto Yasuhiko , Kaneko Shuichi , Matsumoto Kunio , Takamura Toshinari , Honda Masao
Published: June 2022

Retinoic acid-inducible gene (RIG)-I is an essential innate immune sensor that recognises pathogen RNAs and induces interferon (IFN) production. However, little is known about how host proteins regulate RIG-I activation. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine and ligand of the MET receptor tyrosine kinase is an antiviral regulator that promotes the RIG-I-mediated innate immune response. Upon binding to MET, LECT2 induces the recruitment of the phosphatase PTP4A1 to MET and facilitates the dissociation and dephosphorylation of phosphorylated SHP2 from MET, thereby protecting RIG-I from SHP2/c-Cbl-mediated degradation. In vivo, LECT2 overexpression enhances RIG-I-dependent IFN production and inhibits lymphocytic choriomeningitis virus (LCMV) replication in the liver, whereas these changes are reversed in LECT2 knockout mice. Forced suppression of MET abolishes IFN production and antiviral activity in vitro and in vivo. Interestingly, hepatocyte growth factor (HGF), an original MET ligand, inhibits LECT2-mediated anti-viral signalling; conversely, LECT2-MET signalling competes with HGF-MET signalling. Our findings reveal previously unrecognized crosstalk between MET-mediated proliferation and innate immunity and suggest that targeting LECT2 may have therapeutic value in infectious diseases and cancer.
Integration of multiple electronic components on a microfibre towards an emerging electronic textile platform
Authors: Hwang Sunbin , Kang Minji , Lee Aram , Bae Sukang , Lee Seoung-Ki , Lee Sang Hyun , Lee Takhee , Wang Gunuk , Kim Tae-Wook
Published: June 2022

Electronic fibres have been considered one of the desired device platforms due to their dimensional compatibility with fabrics by weaving with yarns. However, a precise connecting process between each electronic fibre is essential to configure the desired electronic circuits or systems. Here, we present an integrated electronic fibre platform by fabricating electronic devices onto a one-dimensional microfibre substrate. Electronic components such as transistors, inverters, ring oscillators, and thermocouples are integrated together onto the outer surface of a fibre substrate with precise semiconductor and electrode patterns. Our results show that electronic components can be integrated on a single fibre with reliable operation. We evaluate the electronic properties of the chip on the fibre as a multifunctional electronic textile platform by testing their switching and data processing, as well as sensing or transducing units for detecting optical/thermal signals. The demonstration of the electronic fibre suggests significant proof of concepts for the realization of high performance with wearable electronic textile systems.
Ligand recognition and biased agonism of the D1 dopamine receptor
Authors: Teng Xiao , Chen Sijia , Nie Yingying , Xiao Peng , Yu Xiao , Shao Zhenhua , Zheng Sanduo
Published: June 2022

Dopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological diseases. Here, we report three cryo-electron microscopy structures of the D1 dopamine receptor (D1R)-Gs complex bound to two agonists, fenoldopam and tavapadon, and a positive allosteric modulator LY3154207. The structure reveals unusual binding of two fenoldopam molecules, one to the orthosteric binding pocket (OBP) and the other to the extended binding pocket (EBP). In contrast, one elongated tavapadon molecule binds to D1R, extending from OBP to EBP. Moreover, LY3154207 stabilizes the second intracellular loop of D1R in an alpha helical conformation to efficiently engage the G protein. Through a combination of biochemical, biophysical and cellular assays, we further show that the broad conformation stabilized by two fenoldopam molecules and interaction between TM5 and the agonist are important for biased signaling of D1R.
Deep learning enables reference-free isotropic super-resolution for volumetric fluorescence microscopy
Authors: Park Hyoungjun , Na Myeongsu , Kim Bumju , Park Soohyun , Kim Ki Hean , Chang Sunghoe , Ye Jong Chul
Published: June 2022

Volumetric imaging by fluorescence microscopy is often limited by anisotropic spatial resolution, in which the axial resolution is inferior to the lateral resolution. To address this problem, we present a deep-learning-enabled unsupervised super-resolution technique that enhances anisotropic images in volumetric fluorescence microscopy. In contrast to the existing deep learning approaches that require matched high-resolution target images, our method greatly reduces the effort to be put into practice as the training of a network requires only a single 3D image stack, without a priori knowledge of the image formation process, registration of training data, or separate acquisition of target data. This is achieved based on the optimal transport-driven cycle-consistent generative adversarial network that learns from an unpaired matching between high-resolution 2D images in the lateral image plane and low-resolution 2D images in other planes. Using fluorescence confocal microscopy and light-sheet microscopy, we demonstrate that the trained network not only enhances axial resolution but also restores suppressed visual details between the imaging planes and removes imaging artifacts.
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant
Authors: Correia Lizelle , Magno Ramiro , Xavier Joana M. , de Almeida Bernardo P. , Duarte Isabel , Esteves Filipa , Ghezzo Marinella , Eldridge Matthew , Sun Chong , Bosma Astrid , Mittempergher Lorenza , Marreiros Ana , Bernards Rene , Caldas Carlos , Chin Suet-Feung , Maia Ana-Teresa
Published: June 2022

PIK3CA mutations are the most common in breast cancer, particularly in the estrogen receptor-positive cohort, but the benefit of PI3K inhibitors has had limited success compared with approaches targeting other less common mutations. We found a frequent allelic expression imbalance between the missense mutant and wild-type PIK3CA alleles in breast tumors from the METABRIC (70.2%) and the TCGA (60.1%) projects. When considering the mechanisms controlling allelic expression, 27.7% and 11.8% of tumors showed imbalance due to regulatory variants in cis, in the two studies respectively. Furthermore, preferential expression of the mutant allele due to cis-regulatory variation is associated with poor prognosis in the METABRIC tumors (P = 0.031). Interestingly, ER−, PR−, and HER2+ tumors showed significant preferential expression of the mutated allele in both datasets. Our work provides compelling evidence to support the clinical utility of PIK3CA allelic expression in breast cancer in identifying patients of poorer prognosis, and those with low expression of the mutated allele, who will unlikely benefit from PI3K inhibitors. Furthermore, our work proposes a model of differential regulation of a critical cancer-promoting gene in breast cancer.
Anisotropic Dzyaloshinskii-Moriya interaction protected by D2d crystal symmetry in two-dimensional ternary compounds
Authors: Ga Yonglong , Cui Qirui , Zhu Yingmei , Yu Dongxing , Wang Liming , Liang Jinghua , Yang Hongxin
Published: June 2022

Magnetic skyrmions, topologically protected chiral spin swirling quasiparticles, have attracted great attention in fundamental physics and applications. Recently, the discovery of two-dimensional (2D) van der Waals (vdW) magnets have aroused great interest due to their appealing physical properties. Moreover, both experimental and theoretical works have revealed that isotropic Dzyaloshinskii–Moriya interaction (DMI) can be achieved in 2D magnets or ferromagnet-based heterostructures. However, 2D magnets with anisotropic DMI haven’t been reported yet. Here, via using first-principles calculations, we unveil that anisotropic DMI protected by D2d crystal symmetry can exist in 2D ternary compounds MCuX2 (M: 3d transition metal (TM), X: group VIA). Interestingly, by using micromagnetic simulations, we demonstrate that ferromagnetic (FM) antiskyrmions, FM bimerons, antiferromagnetic (AFM) antiskyrmions, and AFM bimerons can be realized in the MCuX2 family. Our discovery opens up an avenue to creating antiskyrmions and bimerons with anisotropic DMI protected by D2d crystal symmetry in 2D magnets.
Enhancing the precision limits of interferometric satellite geodesy missions
Authors: Conlon Lorcán O. , Michel Thibault , Guccione Giovanni , McKenzie Kirk , Assad Syed M. , Lam Ping Koy
Published: June 2022

Satellite geodesy uses the measurement of the motion of one or more satellites to infer precise information about the Earth’s gravitational field. In this work, we consider the achievable precision limits on such measurements by examining approximate models for the three main noise sources in the measurement process of the current Gravitational Recovery and Climate Experiment (GRACE) Follow-On mission: laser phase noise, accelerometer noise and quantum noise. We show that, through time-delay interferometry, it is possible to remove the laser phase noise from the measurement, allowing for almost three orders of magnitude improvement in the signal-to-noise ratio. Several differential mass satellite formations are presented which can further enhance the signal-to-noise ratio through the removal of accelerometer noise. Finally, techniques from quantum optics have been studied, and found to have great promise for reducing quantum noise in other alternative mission configurations. We model the spectral noise performance using an intuitive 1D model and verify that our proposals have the potential to greatly enhance the performance of near-future satellite geodesy missions.
Solar flare accelerates nearly all electrons in a large coronal volume
Authors: Fleishman Gregory D. , Nita Gelu M. , Chen Bin , Yu Sijie , Gary Dale E.
Published: June 2022

Solar flares, driven by prompt release of free magnetic energy in the solar corona1,2, are known to accelerate a substantial portion (ten per cent or more)3,4 of available electrons to high energies. Hard X-rays, produced by high-energy electrons accelerated in the flare5, require a high ambient density for their detection. This restricts the observed volume to denser regions that do not necessarily sample the entire volume of accelerated electrons6. Here we report evolving spatially resolved distributions of thermal and non-thermal electrons in a solar flare derived from microwave observations that show the true extent of the acceleration region. These distributions show a volume filled with only (or almost only) non-thermal electrons while being depleted of the thermal plasma, implying that all electrons have experienced a prominent acceleration there. This volume is isolated from a surrounding, more typical flare plasma of mainly thermal particles with a smaller proportion of non-thermal electrons. This highly efficient acceleration happens in the same volume in which the free magnetic energy is being released2.
Mechanism of mitoribosomal small subunit biogenesis and preinitiation
Authors: Itoh Yuzuru , Khawaja Anas , Laptev Ivan , Cipullo Miriam , Atanassov Ilian , Sergiev Petr , Rorbach Joanna , Amunts Alexey
Published: June 2022

Mitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. 1) outcompetes RBFA to complete the assembly with the SSU–mS37–mtIF3 complex2 that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome.
PeSTK db a comprehensive data repository of Probiotic Serine Threonine kinases
Authors: Lokesh Dhanashree , PSN Suresh , Kammara Rajagopal
Published: June 2022

The signal transduction pathway of prokaryotes involves a peptidoglycan synthesis cluster (PG) to sense external stimuli. One of the major components of the PG synthesis cluster is protein kinases (pknA - G). The sequence data of probiotic eSTKs (Eukaryotic like Serine, Threonine kinases) are obscure, scarce and essentially required to understand the role of probiotic microbes in combating infectious diseases. The most essential need to understand and develop certain therapeutic drugs against pathogens is the eSTK sequence data. Hence, we developed a comprehensive user-friendly data repository of probiotic eSTK’s (PeSTK), which holds 830 STK sequences. Therefore, the data resource of PeSTK developed is unique, an open-access very summative containing various probiotic eSTK’s in a single locality. The sequence datasets of the eSTK developed with easy-to-operate browsing as well as searching. Therefore, eSTK data resources should be useful for sequence-based studies and drug development. The sequence datasets are available at Figshare Digital Object Identifier/DOI of the sequences is https://doi.org/10.6084/m9.figshare.146606.
Assessment of pavement deflection under vehicle loads using a 3D-DIC system in the field
Authors: Núñez-Temes Carlos , Bastos Guillermo , Arza-García Marcos , Castro Alberte , Lorenzana Fernández Jose Antonio , Ortiz-Sanz Juan , Portela María , Gil-Docampo Mariluz , Prego Francisco Javier
Published: June 2022

This study aims to introduce the use of 3D-digital image correlation (DIC) to the in situ testing of pavements and to support the development of techniques for a rapid evaluation of the conservation status of existing roads. Little research was found on this topic. The passage of a car wheel on an asphalt pavement was adopted as a case study. The DIC measurements were compared to those gathered by contact sensors. From a qualitative point of view, the DIC measurements captured the realistic shape of a deflection basin. From a quantitative point of view, the deflection values provided by the DIC system had a mean error of 0.015 mm and a standard deviation of 0.011 mm. At the moment of highest load, these errors had a mean value and standard deviation of − 0.016 mm and 0.021 mm, respectively. Thus, to improve the accuracy of the system, we propose modifying the camera support, speckle pattern, and control of natural light.
Substrate-dependent modulation of the leukotriene A4 hydrolase aminopeptidase activity and effect in a murine model of acute lung inflammation
Authors: Lee Kyung Hyeon , Ali Nadia Fazal , Lee Soo Hyeon , Zhang Zhimin , Burdick Marie , Beaulac Zachary J. , Petruncio Greg , Li Linxia , Xiang Jiangdong , Chung Ezra M. , Foreman Kenneth W. , Noble Schroeder M. , Shim Yun M. , Paige Mikell
Published: June 2022

The aminopeptidase activity (AP) of the leukotriene A4 hydrolase (LTA4H) enzyme has emerged as a therapeutic target to modulate host immunity. Initial reports focused on the benefits of augmenting the LTA4H AP activity and clearing its putative pro-inflammatory substrate Pro-Gly-Pro (PGP). However, recent reports have introduced substantial complexity disconnecting the LTA4H modulator 4-methoxydiphenylmethane (4MDM) from PGP as follows: (1) 4MDM inhibits PGP hydrolysis and subsequently inhibition of LTA4H AP activity, and (2) 4MDM activates the same enzyme target in the presence of alternative substrates. Differential modulation of LTA4H by 4MDM was probed in a murine model of acute lung inflammation, which showed that 4MDM modulates the host neutrophilic response independent of clearing PGP. X-ray crystallography showed that 4MDM and PGP bind at the zinc binding pocket and no allosteric binding was observed. We then determined that 4MDM modulation is not dependent on the allosteric binding of the ligand, but on the N-terminal side chain of the peptide. In conclusion, our study revealed that a peptidase therapeutic target can interact with its substrate and ligand in complex biochemical mechanisms. This raises an important consideration when ligands are designed to explain some of the unpredictable outcomes observed in therapeutic discovery targeting LTA4H.
A waste-to-wealth initiative exploiting the potential of Anabaena variabilis for designing an integrated biorefinery
Authors: Deb Dipanwita , Mallick Nirupama , Bhadoria P. B. S.
Published: June 2022

The current research work was an innovative approach providing dual advantages of waste bioremediation and an effective biorefinery. The study attempted to exploit wastewater like aqua discharge and solid wastes like poultry litter/cow dung for cyanobacterial cultivation. Aqua discharge appended with 7.5 g L−1 poultry litter turned out as the best combination generating 46% higher carbohydrate yield than BG-11 control. A. variabilis cultivation in this waste-utilized medium also revealed its excellent bioremediation ability. While 100% removal was observed for nitrite, nitrate, and orthophosphate, a respective 74% and 81% reduction was noted for ammonium and total organic carbon. Chemical and biological oxygen demands were also reduced by 90%. This work was also novel in developing a sequential design for the production of bioethanol and co-products like exopolysaccharides, sodium copper chlorophyllin, C-phycocyanin, and poly-β-hydroxybutyrate from the same cyanobacterial biomass. The developed biorefinery implementing the waste-utilized medium was one of its kind, enabling biomass valorization of 61%. Therefore, the present study would provide a leading-edge for tackling the high production costs that limit the practical viability of biorefinery projects. The recyclability of the bioremediated wastewater would not only curtail freshwater usage, the waste disposal concerns would also be mitigated to a great extent.
Reading speed in school-age children with intermittent exotropia
Authors: Fang Cheng , Wu Yidong , peng Tingting , Wang Chunxiao , Lou Jiangtao , Xu Meiping , Bao Jinhua , Chen Chonglin , Yu Xinping
Published: June 2022

Reading speed in intermittent exotropia (IXT) children has been minimally examined. This study assessed reading speed in school-age children with IXT and determined clinical characteristics of IXT that impacted their reading ability. We compared the reading speed of 63 school-age (10–14 years) children with IXT to 44 age-matched normal counterparts. In addition, the correlation between reading speed and clinical characteristics of IXT were evaluated. The reading speed in children with IXT was 231 ± 51 CPM, while reading speed in normal counterparts was 257 ± 33 CPM. Age, gender were found to be factors associated with reading speed in children with IXT. After adjusting for the age and gender, we found a significant correlation between the LogTNO and reading speed in IXT group based on a generalized linear model (p = 0.014). These data show that reading speed was slower in school-age children with IXT assessed with the International Reading Speed Texts. When age and gender were adjusted, poor stereo function at near was found to be related with a slower reading speed.
Association of human milk oligosaccharides and nutritional status of young infants among Bangladeshi mother–infant dyads
Authors: Nuzhat Sharika , Palit Parag , Mahfuz Mustafa , Islam Md. Ridwan , Hasan S. M. Tafsir , Islam M. Munirul , Sarker Shafiqul. A. , Kyle David J. , Flannery Robin L. , Vinjamuri Anita , Lebrilla Carlito B. , Ahmed Tahmeed
Published: June 2022

Human milk oligosaccharides (HMOs) support the development of a healthy gut microbiome and the growth of infants. We aimed to determine the association of different HMOs with severe acute malnutrition (SAM) among Bangladeshi young infants. This study was nested within a single-blind, randomized, pilot clinical trial (NCT0366657). A total of 45 breastmilk samples from mothers of < 6 months old infants who had SAM (n = 26) or were non-malnourished (n = 19) and were analyzed for constituent HMOs. Of the infants with SAM, 14 (53.85%) had secretor mothers, and 11 (57.89%) of the non-malnourished infants had secretor mothers. A one-unit increase in the relative abundance of sialylated HMOs was associated with higher odds of SAM in age and sex adjusted model (aOR = 2.00, 90% CI 1.30, 3.06), in age, sex, and secretor status adjusted model (aOR = 1.96, 90% CI 1.29, 2.98), and also in age and sex adjusted model among non-secretor mothers (aOR = 2.86, 90% CI 1.07, 7.62). In adjusted models, there was no evidence of a statistically significant association between SAM and fucosylated or undecorated HMOs. Our study demonstrates that a higher relative abundance of sialylated HMOs in mothers’ breastmilk may have a negative impact on young infants’ nutritional status.
Nondestructive cellular-level 3D observation of mouse kidney using laboratory-based X-ray microscopy with paraffin-mediated contrast enhancement
Authors: Kunishima Naoki , Hirose Raita , Takeda Yoshihiro , Ito Koichiro , Furuichi Kengo , Omote Kazuhiko
Published: June 2022

For three-dimensional observation of unstained bio-specimens using X-ray microscopy with computed tomography (CT), one main problem has been low contrast in X-ray absorption. Here we introduce paraffin-mediated contrast enhancement to visualize biopsy samples of mouse kidney using a laboratory-based X-tray microscope. Unlike conventional heavy-atom staining, paraffin-mediated contrast enhancement uses solid paraffin as a negative contrast medium to replace water in the sample. The medium replacement from water to paraffin effectively lowers the absorption of low-energy X-rays by the medium, which eventually enhances the absorption contrast between the medium and tissue. In this work, paraffin-mediated contrast enhancement with 8 keV laboratory X-rays was used to visualize cylindrical renal biopsies with diameters of about 0.5 mm. As a result, reconstructed CT images from 19.4 h of data collection achieved cellular-level resolutions in all directions, which provided 3D structures of renal corpuscles from a normal mouse and from a disease model mouse. These two structures with and without disease allowed a volumetric analysis showing substantial volume differences in glomerular subregions. Notably, this nondestructive method presents CT opacities reflecting elemental composition and density of unstained tissues, thereby allowing more unbiased interpretation on their biological structures.
Post-exposure persistence of nitric oxide upregulation in skin cells irradiated by UV-A
Authors: Hazell Gareth , Khazova Marina , Cohen Howard , Felton Sarah , Raj Ken
Published: June 2022

Evidence suggests that exposure to UV-A radiation can liberate nitric oxide from skin cells eliciting vasodilation in-vivo. However, the duration of nitric oxide release in skin cells after UV exposure is not well studied, with emphasis on UV-B mediated iNOS upregulation. The current study demonstrated persistence of nitric oxide release in a dark reaction after moderate UV-A exposure, peaking around 48 h post exposure; this effect was shown in keratinocytes, fibroblasts and endothelial cells from neonatal donors and keratinocytes from aged donors and confirmed the hypothesis that UV-A exposure appeared to upregulate cNOS alongside iNOS. Release of nitric oxide in the skin cells induced by a moderate exposure to UV-A in sunlight may be especially beneficial for some demographic groups such as the elderly, hypertensive patients or those with impaired nitric oxide function, not only during exposure but many hours and days after that.
Development of a filter device for the prevention of aquatic bacterial disease using a single-chain variable fragment (scFv)-conjugated affinity silk
Authors: Prakash Harsha , Sato Mitsuru , Kojima Katsura , Sato Atsushi , Maruyama Shinpei , Nagasawa Takahiro , Nakao Miki , Somamoto Tomonori
Published: June 2022

Infectious disease is one of the most serious problems in the aquaculture industry for ornamental or edible fish. This study attempted to develop a new device for preventing an aquatic bacterial disease, ulcer disease, caused by Aeromonas salmonicida (As), using “affinity silk”. Affinity silk is a silk protein-containing fibroin L-chain (FibL) fused to the single-chain variable fragment (scFv). It can be easily processed into different formats such as fibers, gels, sponges, or films. A transgenic silkworm that could express a cDNA construct containing FibL fused to an scFv derived from a monoclonal antibody (MAb) against As was successfully generated. An enzyme-linked immunosorbent assay was used to detect As by employing 96-well plates coated with scFv-conjugated affinity silk. As could be captured efficiently by glass wool coated with affinity silk in the column. Furthermore, the air-lift water filter equipped with the affinity silk-coated wool could considerably reduce the concentration of As in water and was estimated to have sufficient ability to trap a lethal dose of As. These findings show that the “affinity silk filter” is a potential device for the prophylaxis of aquatic animal diseases.
Peripapillary RNFL/vessel density ratio in patients with type2 diabetes without clinical diabetic retinopathy
Authors: Lee Min-Woo , Lee Jong-Wook , Lee Kook-Hyung , Lee Young-Hoon , Kim Jung-Yeul
Published: June 2022

To identify how diabetic retinal neurodegeneration (DRN) and microvascular impairment are affected differently by various factors in type 2 diabetes (T2DM) patients without diabetic retinopathy via the ratio of RNFL thickness/vessel density (RNFL/VD) ratio. In this retrospective cross-sectional study, subjects were divided into two groups: controls (control group) and patients with T2DM (DM group). The RNFL thickness, VD, and RNDL/VD ratio were compared between two groups, and correlation analyses were performed to identify the relationship between the RNFL/VD ratio and various factors. A total of 411 eyes were enrolled: 195 eyes in the control group and 216 eyes in the DM group. The mean RNFL thickness was 95.9 ± 8.6 and 93.7 ± 8.7 μm (P = 0.016), the VD was 18.2 ± 0.7 and 17.6 ± 1.1 mm−1(P < 0.001), and the RNFL/VD ratio was 5.11 ± 0.47 and 5.22 ± 0.53 (P = 0.033) in the control group and DM group, respectively. In the DM group, age (coefficient = − 0.139, P = 0.041), axial length (coefficient = 0.163, P = 0.017), and T2DM duration (coefficient = − 0.180, P = 0.008) were significantly correlated with the RNFL/VD ratio. The RNFL/VD ratio of T2DM patients was higher than that of normal control, which would indicate that the impairment of microvasculature precedes DRN. Additionally, age and T2DM duration were negatively correlated with the RNFL/VD ratio, which suggests that inner retinal damage by DRN becomes more prominent over time than microvascular impairment in T2DM.
The neuropeptide Y receptor gene repository, phylogeny and comparative expression in allotetraploid common carp
Authors: Zou Xiaoqing , Chen Lin , Li Bijun , Xiao Junzhu , Xu Peng
Published: June 2022

NPY-family receptors belong to G protein-coupled receptors (GPCR), which lays a physiological foundation for the transmembrane transport of an endogenous appetite-stimulating factor neuropeptide Y and related peptides. In this study, we investigated the npyr genes in ten representative species, and twelve npyr genes were identified from allotetraploid C. carpio, the npyr gene number of C. carpio was twice the number of its subgenome B progenitor-like diploid Poropuntius huangchuchieni. Phylogenetic analysis showed that all npyr genes were divided into three subgroups, and they underwent strong purifying selection according to selection pressure analysis. Subsequently, synteny analysis showed that most npyr genes were evenly distributed on the homologous chromosomes of two subgenomes in allotetraploid C. carpio, in which npy1r and npy2r were tandem duplicated, respectively. In addition, the global expression of npyr genes during embryonic development in allotetraploid C. carpio suggested the potential function of npyr genes in immunity and reproduction. In adult tissues, npyr genes were mainly distributed in the brain, gonad, and skin, which displayed a similar expression pattern between the C. carpio B subgenome and P. huangchuchieni. In general, our research could provide reference information for future exploration of the NPY receptors and neuroendocrine system of allotetraploid C. carpio and vertebrates.
Analysis of the vulnerability estimation and neighbor value prediction in autonomous systems
Authors: Rahmatov Nematullo , Saeed Faisal , Paul Anand
Published: June 2022

The security within autonomous systems (AS)s is one of the important measures to keep network users safe and stable from the various type of Distributed Denial of Service (DDoS) attacks. Similar to the other existing attack types Internet control message protocol (ICMP) based attacks are remained open challenge on the Internet environment. In this study, we have proposed a method to estimate the vulnerability of 600 AS provider edge (PE) routers by sending ICMP packets and predicted AS neighbor values using least square regression (LSR) approach. The results of our study show that 265 AS PE routers are vulnerable due to ICMP flood attack from the 600 ASs which were analyzed. Additionally, we have predicted that about 60% of total AS neighbors will be reduced in the next 3 years. Our results indicate that some ASs still did not deploy the firewall system in the boundary of their networks. Similarly, we also observed that the majority of ASs which expected to have less neighbor values in the next 3 years is due to change their routing paths to find adjacent paths.
Seasonal and sex-dependent gene expression in emu (Dromaius novaehollandiae) fat tissues
Authors: Wright Kristina , Nip Ka Ming , Kim Ji Eun , Cheng Kimberly M. , Birol Inanc
Published: June 2022

Emu (Dromaius novaehollandiae) farming has been gaining wide interest for fat production. Oil rendered from this large flightless bird’s fat is valued for its anti-inflammatory and antioxidant properties for uses in therapeutics and cosmetics. We analyzed the seasonal and sex-dependent differentially expressed (DE) genes involved in fat metabolism in emus. Samples were taken from back and abdominal fat tissues of a single set of four male and four female emus in April, June, and November for RNA-sequencing. We found 100 DE genes (47 seasonally in males; 34 seasonally in females; 19 between sexes). Seasonally DE genes with significant difference between the sexes in gene ontology terms suggested integrin beta chain-2 (ITGB2) influences fat changes, in concordance with earlier studies. Six seasonally DE genes functioned in more than two enriched pathways (two female: angiopoietin-like 4 (ANGPTL4) and lipoprotein lipase (LPL); four male: lumican (LUM), osteoglycin (OGN), aldolase B (ALDOB), and solute carrier family 37 member 2 (SLC37A2)). Two sexually DE genes, follicle stimulating hormone receptor (FSHR) and perilipin 2 (PLIN2), had functional investigations supporting their influence on fat gain and loss. The results suggested these nine genes influence fat metabolism and deposition in emus.
Optimization of echo-enabled harmonic generation toward coherent EUV and soft X-ray free-electron laser at NSLS-II
Authors: Yang X. , Penn G. , Yu L. H. , Smaluk V. , Shaftan T.
Published: June 2022

Prebunching via echo-enabled harmonic generation (EEHG) is an efficient way to reduce the radiator length and improve the longitudinal coherence as well as output stability in storage-ring-based free-electron lasers. We propose a conceptual design, which uses two straight sections to seed coherent extreme-ultraviolet (EUV) and soft X-ray emission with nearly MHz repetition rate. To take the large energy spread (10−3) of a storage ring into account and utilize the existing bending magnets between the two straight sections as the first chicane, we implement a special modeling tool, named EEHG optimizer. This tool has been successfully applied to maximize the prebunching with a reasonably low energy modulation, thereby generating intense coherent X-ray pulses within a short undulator length (a few meters) limited by the available space of a storage ring. Numerical simulations confirm that the optimized EEHG parameters can be directly applied to generate a 10 MW scale peak power with fully coherent ultrafast EUV to soft X-ray pulses based on the NSLS-II parameters. This method can be easily extended to other types of diffraction-limited storage rings.
Anti-dermatophytic activity of cold atmospheric plasma against Trichophyton rubrum via affecting fungal growth, morphology, drug susceptibility and HSP90 gene expression
Authors: Safi-Samghabadi Asal , Atyabi Seyed-Mohammad , Razzaghi-Abyaneh Mehdi
Published: June 2022

Trichophyton rubrum, a major human pathogenic dermatophyte, is responsible for the most recurrent dermatophytoses as globally important superficial fungal infections. Typical chemotherapy is used to handle such infections; however, emerging drug resistance and side effects necessitate the new remedial method development. Cold atmospheric plasma (CAP) is an emerging technology, consisted of neutral and charged particles and photons newly developed as a potent and safe antimicrobial technique to combat drug-resistant microbial pathogens. In the present study, the vast effects of CAP irradiation containing oxygen (2%) and helium (98%) on T. rubrum growth and pathogenicity were explored. After exposure of T. rubrum to CAP jet for 90, 120, 150, 180, and 210 s in 96-well microtiter plates, cell morphology and viability, ergosterol content of fungal hyphae, HSP90 gene expression, and the pattern of drug susceptibility were studied by using electron microscopy, RT-qPCR, spectrophotometry, disk diffusion and CLSI microbroth dilution methods. CAP irradiation significantly inhibited the fungal growth by 25.83 to 89.10%, reduced fungal cell viability by 11.68 to 87.71%, disrupted cellular membranous organelles and structures of the fungal hyphae, and suppressed efficiently the expression of HSP90 gene by 2 folds in 210 s exposure. Taken together, our results demonstrated that CAP is an efficient tool with potential in-vivo therapeutic applications against chronic dermatophytosis caused by T. rubrum due to its effectiveness, harmless, and ease of access.
Highlighting uncertainty in clinical risk prediction using a model of emergency laparotomy mortality risk
Authors: Mathiszig-Lee Jakob F. , Catling Finneas J. R. , Moonesinghe S. Ramani , Brett Stephen J.
Published: June 2022

Clinical prediction models typically make point estimates of risk. However, values of key variables are often missing during model development or at prediction time, meaning that the point estimates mask significant uncertainty and can lead to over-confident decision making. We present a model of mortality risk in emergency laparotomy which instead presents a distribution of predicted risks, highlighting the uncertainty over the risk of death with an intuitive visualisation. We developed and validated our model using data from 127134 emergency laparotomies from patients in England and Wales during 2013–2019. We captured the uncertainty arising from missing data using multiple imputation, allowing prospective, patient-specific imputation for variables that were frequently missing. Prospective imputation allows early prognostication in patients where these variables are not yet measured, accounting for the additional uncertainty this induces. Our model showed good discrimination and calibration (95% confidence intervals: Brier score 0.071–0.078, C statistic 0.859–0.873, calibration error 0.031–0.059) on unseen data from 37 hospitals, consistently improving upon the current gold-standard model. The dispersion of the predicted risks varied significantly between patients and increased where prospective imputation occurred. We present a case study that illustrates the potential impact of uncertainty quantification on clinical decision making. Our model improves mortality risk prediction in emergency laparotomy and has the potential to inform decision-makers and assist discussions with patients and their families. Our analysis code was robustly developed and is publicly available for easy replication of our study and adaptation to predicting other outcomes.
Predicting biochemical recurrence of prostate cancer with artificial intelligence
Authors: Pinckaers Hans , van Ipenburg Jolique , Melamed Jonathan , De Marzo Angelo , Platz Elizabeth A. , van Ginneken Bram , van der Laak Jeroen , Litjens Geert
Published: June 2022

Background

The first sign of metastatic prostate cancer after radical prostatectomy is rising PSA levels in the blood, termed biochemical recurrence. The prediction of recurrence relies mainly on the morphological assessment of prostate cancer using the Gleason grading system. However, in this system, within-grade morphological patterns and subtle histopathological features are currently omitted, leaving a significant amount of prognostic potential unexplored.

Methods

To discover additional prognostic information using artificial intelligence, we trained a deep learning system to predict biochemical recurrence from tissue in H&E-stained microarray cores directly. We developed a morphological biomarker using convolutional neural networks leveraging a nested case-control study of 685 patients and validated on an independent cohort of 204 patients. We use concept-based explainability methods to interpret the learned tissue patterns.

Results

The biomarker provides a strong correlation with biochemical recurrence in two sets (n = 182 and n = 204) from separate institutions. Concept-based explanations provided tissue patterns interpretable by pathologists.

Conclusions

These results show that the model finds predictive power in the tissue beyond the morphological ISUP grading.
Multipole-moment effects in ion–molecule reactions at low temperatures: part III – the He+ + CH4 and He+ + CD4 reactions at low collision energies and the effect of the charge-octupole interaction
Authors: Zhelyazkova Valentina , Martins Fernanda B. V. , Merkt Frédéric
Published: June 2022

We present measurements and calculations of the collision-energy dependence of the ion–molecule reactions He+ + CH4 and He+ + CD4 at collision energies in the range between 0 and kB·10 K.
Photoactivation of triosmium dodecacarbonyl at 400 nm probed with time-resolved X-ray liquidography
Authors: Ki Hosung , Kim Tae Wu , Moon Jiwon , Kim Jungmin , Lee Yunbeom , Heo Jun , Kim Kyung Hwan , Kong Qingyu , Khakhulin Dmitry , Newby Gemma , Kim Joonghan , Kim Jeongho , Wulff Michael , Ihee Hyotcherl
Published: June 2022

Photoactivation mechanism of triosmium dodecacarbonyl is elucidated via time-resolved X-ray liquidography, identifying two pathways, vibrational relaxation and ligand dissociation.
Tuning the conformational flexibility of quinoxaline cavitands for complexation at the gas–solid interface
Authors: Rozzi Andrea , Pedrini Alessandro , Pinalli Roberta , Massera Chiara , Elmi Ivan , Zampolli Stefano , Dalcanale Enrico
Published: June 2022

Molecular recognition meets preconcentration in aromatic VOC complexation at the gas–solid interface.
Extensive characterization of choline chloride and its solid–liquid equilibrium with water
Authors: Lobo Ferreira Ana I. M. C. , Vilas-Boas Sérgio M. , Silva Rodrigo M. A. , Martins Mónia A. R. , Abranches Dinis. O. , Soares-Santos Paula C. R. , Almeida Paz Filipe A. , Ferreira Olga , Pinho Simão P. , Santos Luís M. N. B. F. , Coutinho João A. P.
Published: June 2022

A comprehensive evaluation of the thermal behavior and heat capacities of ChCl and ChCl + H2O and the SLE of ChCl + H2O is performed. A new structural model that includes small amounts of water in the ChCl crystal structure is proposed.