bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical, nutritional, and sensory quality of rice‐based biscuits fortified with safou (Dacryodes edulis) fruit powder
Authors: Eyenga Eliane‐Flore , Tang Erasmus Nchuaji , Achu Mercy Bih Loh , Boulanger Renaud , Mbacham Wilfred F. , Ndindeng Sali Atanga
Published: May 2020

The reduction of postharvest losses in rice and safou is imperative to increase productivity in their respective value chains. In this study, fine broken rice grains were used to produce rice flour and subsequently rice‐based biscuits. The biscuits were further fortified with safou powder, and the physical, nutritional, and sensory quality and stability during storage of the different types of biscuits were analyzed using standard methods. Fine or nonsandy biscuits had peak particle size of 500 µm, while medium (slightly sandy) and large (sandy) biscuits had peak particle sizes of 1,000 µm and 1,400 µm, respectively. The hardness varied from 5.7 ± 2.3 N for biscuits with large particles to 16.1 ± 4.4 N for biscuits with fine particles. Fortification of biscuits with sour safou increased the protein and amino acid content of the biscuits. Tryptophan was absent in both safou and the biscuits produced. There was an increase in phosphorus, potassium, calcium, magnesium, copper, iron, manganese, and aluminum following fortification with safou. Nonsandy biscuits dissolved faster in the mouth (melt) during consumption than the other biscuits although most of the biscuits were perceived to be low in melting and buttery. Nonsandy biscuits were rated as “very good,” while slightly sandy and sandy were rated as “good.” Safou rice‐based biscuits were perceived as “very good,” while simple rice biscuits were perceived as “good.” Fortification of rice biscuits with safou increased the protein, essential amino acid, and mineral contents of the biscuits with very appreciable taste. These biscuits can be used to help fight protein, iron, and zinc malnutrition and in mitigating postharvest losses of underutilized broken rice and safou especially sour safou.
Sclerosing TSC1 mutated renal cell carcinoma: An unusual pattern mimicking MITF family translocation renal cell carcinoma
Authors: Williamson Sean R. , Cardili Leonardo , Whiteley Lisa J. , Sanchez Jessica , Kis Olena
Published: May 2020

The tuberous sclerosis genes and MTOR are increasingly being found to have important roles in novel subtypes of renal cancer, particularly emerging entities eosinophilic solid and cystic renal cell carcinoma (RCC) and high‐grade oncocytic renal tumor (HOT)/RCC with eosinophilic and vacuolated cytoplasm. We report a unique renal neoplasm in a 66‐year‐old woman that initially mimicked MITF family translocation RCC due to mixed clear and eosinophilic cells, extensive stromal hyalinization, and psammoma bodies, yet which was negative for TFE3 and TFEB fluorescence in situ hybridization and a next generation sequencing (NGS) gene fusion assay. Cytoplasmic stippling triggered consideration of TSC‐associated neoplasms, and a targeted NGS assay revealed a variant in exon 21 of TSC1 resulting in c.2626G>T p.(Glu876*) truncating mutation. This report adds to the morphologic spectrum of TSC‐related renal neoplasms, including prominent stromal hyalinization as a potentially deceptive pattern. Due to the overlap in cytoplasmic stippling between eosinophilic solid and cystic RCC and HOT/RCC with eosinophilic and vacuolated cytoplasm, it is debatable which category this example would best fit. Further understanding of these entities and other renal neoplasms with alterations in the TSC genes will elucidate whether they should be considered a family of tumors.
Inhibition of Sphingosine‐1‐Phosphate‐Induced Th17 Cells Ameliorates Alcohol‐Associated Steatohepatitis in Mice
Authors: Chu Shenghui , Sun Rui , Gu Xuemei , Chen Liang , Liu Min , Guo HaiXun , Ju Songwen , Vatsalya Vatsalya , Feng Wenke , McClain Craig J. , Deng Zhongbin
Published: May 2020

Background and Aims

Chronic alcohol consumption is accompanied by intestinal inflammation. However, little is known about how alterations to the intestinal immune system and sphingolipids contribute to the pathogenesis of alcohol‐associated liver disease (ALD).

Approach and Results

We used wild‐type mice, retinoid‐related orphan receptor gamma t (RORγt)‐deficient mice, sphingosine kinase–deficient mice, and local gut anti‐inflammatory, 5‐aminosalicyclic acid–treated mice in a chronic‐binge ethanol feeding model. Targeted lipidomics assessed the sphingolipids in gut and liver samples. Gut immune cell populations, the amounts of sphingolipids, and the level of liver injury were examined. Alcohol intake induces a pro‐inflammatory shift in immune cell populations in the gut, including an increase in Th17 cells. Using RORγt‐deficient mice, we found that Th17 cells are required for alcohol‐associated gut inflammation and the development of ALD. Treatment with 5‐aminosalicyclic acid decreases alcohol‐induced liver injury and reverses gut inflammation by the suppression of CD4+/RORγt+/interleukin‐17A+ cells. Increased Th17 cells were due to up‐regulation of sphingosine kinase 1 activity and RORγt activation. We found that S1P/S1PR1 signaling is required for the development of Th17 cell–mediated ALD. Importantly, in vivo intervention blocking of S1P/S1PR1 signaling markedly attenuated alcohol‐induced liver inflammation, steatosis, and damage.

Conclusions

Gut inflammation is a functional alteration of immune cells in ALD. Reducing gut Th17 cells leads to reduced liver damage. S1P signaling was crucial in the pathogenesis of ALD in a Th17 cell–dependent manner. Furthermore, our findings suggest that compounds that reduce gut inflammation locally may represent a unique targeted approach in the treatment of ALD.
Effects of intrauterine exposure to 2,3′,4,4′,5‐pentachlorobiphenyl on the reproductive system and sperm epigenetic imprinting of male offspring
Authors: He Qi‐Long , Lyu Tian‐Qi , Zhang Yong‐Tao , Wang Hai‐Quan , Zhou Qian , Zhang Jian‐Mei , Liu Yuan‐Yuan , Li Jia‐Shuo , Jiang Li‐Gang , Cheng Dong , Ge Zhao‐Jia , Liu Shu‐Zhen
Published: May 2020

Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3′,4,4′,5‐pentachlorobiphenyl (PCB118) is one of the most important dioxin‐like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 μg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.
Hyperspectral imaging and characterization of allergic contact dermatitis in the short‐wave infrared
Authors: Du Tommy , Mishra Deependra K. , Shmuylovich Leonid , Yu Andy , Hurbon Helena , Wang Steven T. , Berezin Mikhail Y.
Published: May 2020

Short‐wave infrared hyperspectral imaging is applied to diagnose and monitor a case of allergic contact dermatitis (ACD) due to poison ivy exposure in one subject. This approach directly demonstrates increased tissue fluid content in ACD lesional skin with a spectral signature that matches the spectral signature of intradermally injected normal saline. The best contrast between the affected and unaffected skin is achieved through a selection of specific wavelengths at 1070, 1340 and 1605 nm and combining them in a pseudo‐red‐green‐blue color space. An image derived from these wavelengths normalized to unaffected skin defines a “tissue fluid index” that may aid in the quantitative diagnosis and monitoring of ACD. Further clinical testing of this promising approach towards disease detection and monitoring with tissue fluid content quantification is warranted.
Surface‐enhanced Raman scattering analysis of serum albumin via adsorption‐exfoliation on hydroxyapatite nanoparticles for noninvasive cancers screening
Authors: Gao Siqi , Zheng Mengmeng , Lin Yamin , Lin Kecan , Zeng Jinshu , Xie Shusen , Yu Yun , Lin Juqiang
Published: May 2020

Combining serum albumin via adsorption‐exfoliation on hydroxyapatite particles (HAp) with surface‐enhanced Raman scattering (SERS), we developed a novel quantitative analysis of albumin method from blood serum for cancers screening applications. The quantitatively analysis obtained by our HAp method had a good linear relationship from 1 to 10 g/dL, and the lower limit of detection was less than the albumin prognostic factor for disease (3.5 g/dL). Serum albumin was adsorbed and exfoliated by HAp from serum samples of liver cancer patients, breast cancer patients and healthy volunteers and mixed with silver colloids to perform SERS spectral analysis. Based on the PLS‐SVM algorithm, the diagnostic accuracies of liver cancer patients and breast cancer patients were 100% and 96.68%, respectively. Moreover, this algorithm successfully predicted the unidentified subjects with a diagnostic accuracy of 93.75%. This exploratory work demonstrated that HAp‐adsorbed‐exfoliated serum proteins combined with SERS spectroscopy has great potential for cancer screening.
Effects of different chemical groups on behaviors of bladder cancer cells
Authors: Cao Hui , Huang Denggao , Guo Lifang , Gao Yuanhui , Zheng Linlin , Xiao Jingchuan , Zhang Shufang , Yu Xiaolong
Published: May 2020

Chemical groups of microenvironment play an important role in the adhesion, proliferation, and apoptosis of tumor cells. The different chemical groups (CH3, OH, COOH) were grafted on the surfaces with the same density by self‐assembly monolayer (SAM) technique to introduce the influence of different microenvironments of the human bladder cancer (5637) cells. The results indicated that the 5637 cells on COOH surface exhibited the lowest proliferation rate and the highest apoptosis rate on the first and fifth day because of negative charge and polarity of the COOH group, which might help optimize biomedicine materials and find new methods to treat bladder cancer.
Gelatin hydrogel membrane containing carbonate hydroxyapatite for nerve regeneration scaffold
Authors: Ardhani Retno , Ana Ika Dewi , Tabata Yasuhiko
Published: May 2020

A scaffold that mimics physicochemical structure of nerve and supplies calcium ions in axonal environment is an attractive alternative for nerve regeneration, especially when applied in critical nerve defect. Various scaffold material, design, including their combination with several growth‐induced substances and cells application have been being investigated and used in the area of nerve tissue engineering. However, the development remains challenges today because they are still far from ideal concerning their stability, reproducibility, including complicated handling related to the poor mechanical strength. In view of the current basis, in this study, the introduction of carbonated hydroxyapatite (CHA) as promising candidate to increase mechanical properties of nerve scaffold is reported. The incorporation of CHA was not only expected to provide better mechanical properties of the scaffold. Under physiological condition, CHA is known to be the most stable phases of calcium phosphate compound. Therefore, CHA was expected to provide controlled release calcium for better axonal environment and promote fasten nerve regeneration. This study shows that CHA incorporated gelatin membrane has ideal microstructure to prevent fibrous tissue ingrowth into the injury site, while retaining its capability to survive nerve tissue by allowing adequate glucose and specific proteins diffusion. The provided Ca2+ release to the environment promoted neuronal growth, without suppressing acetylcholine esterase release activity. Neurite elongation was dramatically higher in the gelatin membrane incorporated with CHA. Introduction of CHA into gelatin membrane represents a new generation medical device for nerve reconstruction, with CHA was considered as a promising factor.
Self‐assembly of multiscale anisotropic hydrogels through interfacial polyionic complexation
Authors: Patel Akhil , Sant Vinayak , Velankar Sachin , Dutta Mayuri , Balasubramanian Vibishan , Sane Piyusha , Agrawal Vishi , Wilson Jamir , Rohan Lisa C. , Sant Shilpa
Published: May 2020

Polysaccharides are explored for various tissue engineering applications due to their inherent cytocompatibility and ability to form bulk hydrogels. However, bulk hydrogels offer poor control over their microarchitecture and multiscale hierarchy, parameters important to recreate extracellular matrix‐mimetic microenvironment. Here, we developed a versatile platform technology to self‐assemble oppositely charged polysaccharides into multiscale fibrous hydrogels with controlled anisotropic microarchitecture. We employed polyionic complexation through microfluidic flow of positively charged polysaccharide, chitosan, along with one of the three negatively charged polysaccharides: alginate, gellan gum, and kappa carrageenan. These hydrogels were composed of microscale fibers, which in turn were made of submicron fibrils confirming multiscale hierarchy. Fibrous hydrogels showed strong tensile mechanical properties, which were further modulated by encapsulation of shape‐specific antioxidant cerium oxide nanoparticles (CNPs). Specifically, hydrogels with chitosan and gellan gum showed more than eight times higher tensile strength compared to the other two pairs. Incorporation of sphere‐shaped cerium oxide nanoparticles in chitosan and gellan gum further reinforced fibrous hydrogels and increased their tensile strength by 40%. Altogether, our automated hydrogel fabrication platform allows fabrication of bioinspired biomaterials with scope for one‐step encapsulation of small molecules and nanoparticles without chemical modification or use of chemical crosslinkers.
Paclitaxel‐loaded polypeptide‐polyacrylamide nanomicelles overcome drug‐resistance by enhancing lysosomal membrane permeability and inducing apoptosis
Authors: Abbasi Sahar , Yousefi Gholamhossein , Tamaddon Ali‐mohammad , Firuzi Omidreza
Published: May 2020

The aim of the current project was to investigate the in vitro properties of Paclitaxel (PTX)‐loaded pHPMA5kD‐pHis5kD‐pLeu3kD nanomicelles (NMs) on multidrug resistance cell line. Circular dichroism analysis was done to investigate the effect of pH on the secondary structure of the copolymer. Cytotoxicity assay together with fluorescence imaging and flow cytometry were performed to get an insight about toxicity and cellular uptake mechanism of NMs. Acridine orange assay, rhodamine 123 (Rh123) accumulation assay, and apoptosis analysis were conducted for further investigation. It was found that the secondary structure of the copolymer changed in response to pH, PTX‐loaded NMs had higher cytotoxicity on both drug‐sensitive (MES‐SA and MCF‐7) and multidrug resistant cells (MES‐SA/DX5) compared to free PTX, and interestinly free copolymer inhibited the growth of MES‐SA/DX5 cells while it was nontoxic on drug‐sensitive cells. Moreover, the copolymer was able to induce lysosome membrane permeation and increase Rh123 accumulation inside cells indicating inhibition of the P‐gp efflux pumps. Finally, apoptosis was strongly induced in MES‐SA/DX5 cells upon treatment with PTX‐loaded NMs. It can be concluded that the designed hybrid copolymer is a good candidate for in vivo assay and developing a powerful system against multidrug resistance tumors.
Fabrication of self‐healing hydrogel from quaternized N‐[3(dimethylamino)propyl]methacrylamide copolymer for antimicrobial and drug release applications
Authors: An Heng , Yang Yan , Bo Yunyi , Ma Xiangbo , Wang Yong , Liu Longmei , Wang Haijun , He Yingna , Qin Jianglei
Published: May 2020

Self‐healing hydrogels have attracted great attention in recent years because of their wide application in bioscience and biotechnology. In this study, P(DMAPMA‐stat‐DAA) were synthesized by Reversible Addition‐Fragmentation Chain Transfer (RAFT) polymerization and quaternized to import antimicrobial properties. Then quaternized P(DMAPMA‐stat‐DAA) was used to prepare hydrogel containing acylhydrazone groups with Polyethylene oxide (PEO) diacylhydrazide as a cross‐linking agent. The acylhydrazone groups imparted a variety of properties, including group responsiveness and self‐healing properties to the hydrogel. At the same time, the quaternary ammonium endowed the hydrogel with the antimicrobial property. The mechanical property, self‐healing properties, and antimicrobial property of hydrogels were investigated intensively. Results showed hydrogels formed in neutral conditions, and the luminescent property was introduced with PEO23 dinaphthhydrazide (DNH) cross‐linking. The hydrogels showed a controlled pH‐sensitive DOX·HC l and Ovalbumin (OVA) release profile. In addition, the hydrogel showed the antimicrobial property and may have important applications in the biomedical field in the near future.
3Dprinting of high‐strength, porous, elastomeric structures to promote tissue integration of implants
Authors: Abar Bijan , Alonso‐Calleja Alejandro , Kelly Alexander , Kelly Cambre , Gall Ken , West Jennifer L.
Published: May 2020

Despite advances in biomaterials research, there is no ideal device for replacing weight‐bearing soft tissues like menisci or intervertebral discs due to poor integration with tissues and mechanical property mismatch. Designing an implant with a soft and porous tissue‐contacting structure using a material conducive to cell attachment and growth could potentially address these limitations. Polycarbonate urethane (PCU) is a soft and tough biocompatible material that can be 3D printed into porous structures with controlled pore sizes. Porous biomaterials of appropriate chemistries can support cell proliferation and tissue ingrowth, but their optimal design parameters remain unclear. To investigate this, porous PCU structures were 3D‐printed in a crosshatch pattern with a range of in‐plane pore sizes (0 to 800 μm) forming fully interconnected porous networks. Printed porous structures had ultimate tensile strengths ranging from 1.9 to 11.6 MPa, strains to failure ranging from 300 to 486%, Young's moduli ranging from 0.85 to 12.42 MPa, and porosity ranging from 13 to 71%. These porous networks can be loaded with hydrogels, such as collagen gels, to provide additional biological support for cells. Bare PCU structures and collagen‐hydrogel‐filled porous PCU support robust NIH/3T3 fibroblast cell line proliferation over 14 days for all pore sizes. Results highlight PCU's potential in the development of tissue‐integrating medical implants.
Study on the enhancement of colloidal stable poly(sodium 4‐styrene sulfonate) coated magnetite nanoparticles and regeneration capability for rapid magnetophoretic removal of organic dye
Authors: Chong Wai Hong , Ng Qi Hwa , Lim Jit Kang , Yeap Swee Pin , Low Siew Chun
Published: May 2020

BACKGROUND

A good colloidal stability of magnetite nanoparticles (MNPs) dispersion is of utmost importance for its environmentally related applications. In the present work, a water‐soluble anionic polyelectrolyte, poly(sodium 4‐styrene sulfonate) (PSS), was used to stabilize dispersions of MNPs in a pH‐dependent aqueous medium.

RESULTS

An excellent methylene blue (MB) dye removal efficiency at equilibrium of up to 94% has been observed by the colloidally stabilized nano‐magnetites. Dynamic light scattering and electrophoretic analysis showed that the PSS‐coated MNPs exhibited better colloidal stability, with an almost constant hydrodynamic diameter of ~150 nm and insignificant clustering behavior throughout the measuring time scale of 5 h. Transmission electron microscopy evidenced the success coating of PSS onto MNPs. In terms of its chemical resistance, the PSS‐coated MNPs were able to tolerate a wide pH range from 2 to 10. This work depicts a simple physiochemical coating method to stabilize dispersions of nano‐magnetites, which promoted a better MB adsorption capacity of PSS‐coated MNPs at 14.9 mg g–1 than the naked MNPs at 10.38 mg g–1. The adsorption process follows Langmuir isotherm and pseudo‐second‐order reaction kinetics with both correlations R2 > 0.99. PSS‐coated MNPs demonstrated outstanding regeneration capacity for four batch adsorption cycles with an almost consistent MB removal efficiency higher than 85%.

CONCLUSION

This in‐house developed nano‐sorbent has potential in economical applications with a less budgeted adsorbent replacement (at least 4 cycles of regeneration) for low‐cost separation of pollutants, such as MB from polluted water. © 2020 Society of Chemical Industry
Mass transfer efficiency inside the polyvinyl alcohol‐sodium alginate carriers: kinetic changes of immobilized anammox bacteria
Authors: Chen Wen‐Hsing , Lin Jih‐Gaw , Wei Yi‐Lin , Chen Shen‐Yi
Published: May 2020

BACKGROUND

Mass transfer inside the plain polyvinyl alcohol (PVA)‐sodium alginate (SA) carriers was determined to correlate with nitrogen removal by anaerobic ammonium‐oxidation (anammox) bacteria in this study. The anammox bacteria immobilized by the PVA‐SA material for nitrogen removal were inoculated into a sequencing batch reactor (SBR) operated at a hydraulic retention time of 4 days and a temperature of 35 ± 1 °C while another identical reactor inoculated with the un‐immobilized biomass was run for comparison.

RESULTS

Results show that the total nitrogen removals were 81 and 92% for the immobilized and un‐immobilized biomass, respectively, when the ammonium‐ and nitrite‐nitrogen, both at 200 mg N L−1, were fed into the SBRs. The poorer performance observed from the immobilized biomass was due to the lower mass transfer efficiency. The obtained diffusion coefficient of the ammonium‐nitrogen and specific surface area were 15.2 × 10−6 cm2 s−1 and 29.35 m2 g−1 gel beads, respectively. In addition, the mass transfer efficiency influenced the kinetics of the immobilized anammox bacteria. Results indicate that the ammonium‐nitrogen removal rate of the un‐immobilized biomass was 28 to 34% greater than that of the immobilized biomass, while the nitrite‐nitrogen removal rate was greater by 9 to 24% for the un‐immobilized biomass. This influence was more significant at high levels of ammonium‐ and nitrite‐nitrogen concentrations.

CONCLUSION

Increasing the mass transfer efficiency inside the plain PVA‐SA carriers was needed before using the PVA‐SA carriers to immobilize anammox bacteria. © 2020 Society of Chemical Industry
Outcome of patients treated with molecular adsorbent recirculating system albumin dialysis: A national multicenter study
Authors: Camus Christophe , Locher Clara , Saliba Faouzi , Goubaux Bernard , Bonadona Agnès , Lavayssiere Laurence , Paugam Catherine , Quinart Alice , Barbot Olivier , Dharancy Sébastien , Delafosse Bertrand , Pichon Nicolas , Barraud Hélène , Galbois Arnaud , Veber Benoit , Cayot Sophie , Souche Bruno
Published: May 2020

Background and Aim

The molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real‐life use are lacking.

Methods

This was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives.

Results

A total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 μmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury–hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44–54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1‐year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P < 0.001). Among nonbiliary cirrhotic patients, hospital mortality was associated with the severity of liver disease (HE and severe cholestasis) and not being listed for transplant. In ALF, paracetamol etiology and ≥3 MARS sessions were associated with better transplant‐free survival.

Conclusion

Our study suggests that MARS should be mainly used as a bridge to liver transplantation. Survival was correlated with being listed for most etiologies and with the intensity of treatment in ALF.
Novel defect in phosphatidylinositol 4‐kinase type 2‐alpha (PI4K2A) at the membrane‐enzyme interface is associated with metabolic cutis laxa
Authors: Mohamed Miski , Gardeitchik Thatjana , Balasubramaniam Shanti , Guerrero‐Castillo Sergio , Dalloyaux Daisy , van Kraaij Sanne , Venselaar Hanka , Hoischen Alexander , Urban Zsolt , Brandt Ulrich , Al‐Shawi Raya , Simons J. Paul , Frison Michele , Ngu Lock‐Hock , Callewaert Bert , Spelbrink Hans , Kallemeijn Wouter W. , Aerts Johannes M. F. G. , Waugh Mark G. , Morava Eva , Wevers Ron A.
Published: May 2020

Inherited cutis laxa, or inelastic, sagging skin is a genetic condition of premature and generalised connective tissue ageing, affecting various elastic components of the extracellular matrix. Several cutis laxa syndromes are inborn errors of metabolism and lead to severe neurological symptoms. In a patient with cutis laxa, a choreoathetoid movement disorder, dysmorphic features and intellectual disability we performed exome sequencing to elucidate the underlying genetic defect. We identified the amino acid substitution R275W in phosphatidylinositol 4‐kinase type IIα, caused by a homozygous missense mutation in the PI4K2A gene. We used lipidomics, complexome profiling and functional studies to measure phosphatidylinositol 4‐phosphate synthesis in the patient and evaluated PI4K2A deficient mice to define a novel metabolic disorder. The R275W residue, located on the surface of the protein, is involved in forming electrostatic interactions with the membrane. The catalytic activity of PI4K2A in patient fibroblasts was severely reduced and lipid mass spectrometry showed that particular acyl‐chain pools of PI4P and PI(4,5)P2 were decreased. Phosphoinositide lipids play a major role in intracellular signalling and trafficking and regulate the balance between proliferation and apoptosis. Phosphatidylinositol 4‐kinases such as PI4K2A mediate the first step in the main metabolic pathway that generates PI4P, PI(4,5)P2 and PI(3,4,5)P3. Although neurologic involvement is common, cutis laxa has not been reported previously in metabolic defects affecting signalling. Here we describe a patient with a complex neurological phenotype, premature ageing and a mutation in PI4K2A, illustrating the importance of this enzyme in the generation of inositol lipids with particular acylation characteristics.
A novel anti‐NS2BNS3pro antibody‐based indirect ELISA test for the diagnosis of dengue virus infections
Authors: Gandikota Chaitanya , Gandhi Lekha , Maisnam Deepti , Kesavulu Muppuru Muni , Billoria Arcy , Prasad Vankayalapati Sri Venkateswara , Venkataramana Musturi
Published: May 2020

Dengue virus reportedly circulates as four genetically distinct serotypes for which there is no widely accepted vaccine or drug at present. Morbidity and mortality caused by this virus are alarming for the possible increased threat to human health. A suitable diagnostic test is the prerequisite for designing and developing control measures. But, the tests being employed at present possess one or the other drawback for this disease diagnosis. During the dengue virus infections, NS2B is essential for the stability and catalytic activity of the NS3 protease. N‐terminal 185 amino acids of NS3 protease domain along with hydrophilic portion of NS2B (NS2BNS3pro) is being used to screen dengue inhibitors but not for diagnosis until now. In the present study, we have used purified NS2BNS3pro as an antigen to trap anti‐NS2BNS3pro antibodies of the clinical samples. Antibodies were detected successfully in both Western blot analysis and enzyme‐linked immunosorbent assay (ELISA) tests. In ELISA, antibodies were detected in both primary and secondary infections of all serotypes. Interestingly, 17 samples declared as other febrile infections by NS1 and IgM/IgG tests were found to be positive in present test, which were further confirmed by reverse‐transcription polymerase chain reaction. In silico studies suggested the absence of conserved epitopes between NS2BNS3pro and the counterpart in JEV, Zika, and CHIKV, indicating less possibility of crossreaction, which was in turn confirmed by using synthetic peptides representing the above epitopes. Statistical analysis with 76% specificity, 87% sensitivity, and 95% concordance also supported the present test as a suitable test for large scale diagnosis of dengue virus infections.
Nutrition Support Team Reconsultation During Nutrition Therapy in Korea
Authors: Seol Eun‐Mi , Suh Yun‐Suhk , Ju Dal Lae , Bae Hye Jung , Kim Eunjung , Lee Hyuk‐Joon
Published: May 2020

Background

The aim of this study was to investigate the nutrition support team (NST) reconsultation practice and to evaluate reasons and describe risk factors for NST reconsultation during nutrition therapy (NT) in hospitalized patients.

Methods

This study included 2505 patients aged >18 years who received NT through NST consultation between January 2016 and December 2016 at Seoul National University Hospital. NST reconsultation refers to consulting the NST more than twice during a single hospitalization period. Risk factors affecting NST reconsultation were included only when NST reconsultation occurred for specific reasons other than routine evaluations.

Results

The NST reconsultation rate was 36.4% (913/2505) with 926 reasons, including ‘changes in the nutrition provision method’ (n = 474, 51.2%), ‘NT‐related complications’ (n = 284, 30.7%), ‘routine evaluations’ (n = 137, 14.8%), and ‘discharge planing including home NT’ (n = 31, 3.3%). The reconsultation rate of enteral nutrition (EN) was 40.8% (n = 378) and that of parenteral nutrition (PN) was 59.2% (n = 548). Among the NT‐related complications, diarrhea (n = 65, 49.2%) was the most common with EN, whereas electrolyte abnormality (n = 52, 34.2%) was the most common with PN. Performance of surgery (odds ratio [OR], 2.061; P < .001), low serum albumin levels (<3 mg/dL; OR, 1.672; P < .001), presence of comorbidities (OR, 1.556; P < .001), and low body mass index (kg/m2) (<18.5; OR, 1.508; P < .001) were predictive risk factors for NST reconsultation.

Conclusions

Frequent evaluation of nutrition status through a multidisciplinary NST is important in patients with these risk factors.
Biologically informed stratification of periodontal disease holds the key to achieving precision oral health
Authors: Divaris Kimon , Moss Kevin , Beck James D.
Published: May 2020

Medicine and dentistry need to treat the individual not the “average patient.” This personalized or precision approach to health care involves correctly diagnosing and properly classifying people to effectively customize prevention, diagnosis, and treatment. This is not a trivial undertaking. Achieving precision health requires making sense of big data, both at the population level and at the molecular level. The latter can include genetic, epigenetic, transcriptomic, proteomic, metabolomic data, and microbiome data. This biological information can augment established clinical measurements and supplement data on socioeconomic status, lifestyle, behaviors, and environmental conditions. Here, the central thesis is that, with sufficient data and appropriate methods, it is possible to segregate symptom‐based and phenotypically based categories of patients into clinically and biologically similar groups. These groups are likely to have different clinical trajectories and benefit from different treatments. Additionally, such groups are optimal for investigations seeking to unveil the genomic basis of periodontal disease susceptibility. Analysis of these complex data to produce actionable and replicable health and disease categories requires appropriately sophisticated bioinformatics approaches and thorough validation in diverse patient samples and populations. Successful research programs will need to consider both population‐level and well‐controlled deep phenotyping approaches. Biologically informed stratification of periodontal disease is both feasible and desirable. Ultimately, this approach can accelerate the development of precision health through improvements in research and clinical applications.
Late Quaternary vegetation and climate dynamics in central‐eastern Brazil: insights from a ~35k cal a bp peat record in the Cerrado biome
Authors: Horák‐Terra Ingrid , Cortizas Antonio Martínez , Da Luz Cynthia Fernandes Pinto , Silva Alexandre Christófaro , Mighall Tim , De Camargo Plínio Barbosa , Mendonça‐Filho Carlos Victor , De Oliveira Paulo Eduardo , Cruz Francisco Willian , Vidal‐Torrado Pablo
Published: May 2020

The late Quaternary evolution of central‐eastern Brazil has been under‐researched. Questions remain as to the origin of the Cerrado, a highly endangered biome, and other types of vegetation, such as the Capões – small vegetation islands of semi‐deciduous and mountain forests. We investigated the factors that influenced the expansion and contraction of the Cerrado and Capões during the late Quaternary (last ~35 ka), using a multi‐proxy approach: stable isotopes (δ13C, δ15N), geochemistry, pollen and multivariate statistics derived from a peat core (Pinheiro mire, Serra do Espinhaço Meridional). Five major shifts in precipitation, temperature, vegetation and landscape stability occurred at different timescales. Our study revealed that changes in the South Atlantic Convergence Zone (SACZ) seem to have been coeval with these shifts: from the Late Glacial Maximum to mid‐Holocene the SACZ remained near (~29.6 to ~16.5k cal a bp) and over (~16.5 to ~6.1 k cal a bp) the study area, providing humidity to the region. This challenges previous research which suggested that climate was drier for this time period. At present, the Capões are likely to be a remnant of a more humid climate; meanwhile, the Cerrado biome seems to have stablished in the late Holocene, after ~3.1 k cal a bp.
Dermatofibrosarcoma protuberans in children and adolescents: Primary and Relapsed disease—Experience of the Cooperative Weichteilsarkomstudiengruppe (CWS)
Authors: Krewer Julia , Rolle Udo , Koscielniak Ewa , Vokuhl Christian , Mentzel Thomas , Seitz Guido , Feuchtgruber Simone , von Kalle Thekla , Scheer Monika , Münter Marc , Bielack Stefan S. , Fuchs Joerg , Niggli Felix , Hettmer Simone , Klingebiel Thomas , Sparber‐Sauer Monika ,   CWS Study Group
Published: May 2020

Background

Dermatofibrosarcoma protuberans (DFSP) is a rare low‐grade tumor. Little is known about best treatment of primary and relapsed disease (RD).

Methods

Treatment and outcome of 40 patients with DFSP prospectively registered within the CWS‐96 and ‐2002P trials and the registry SoTiSaR (1996‐2016) were analysed.

Results

Median age was 8 years (range, 0.64‐17.77). Fluorescence in situ hybridization analysis to detect COL1A1‐PDGFB fusion genes was positive in 86% (12/14) of evaluated patients. Primary resection was performed in all patients. Patients had IRS group I (n = 28), II (n = 9), and III (n = 2); not available (n = 1). To achieve complete remission (CR), a secondary resection was performed in 18 patients resulting in microscopically complete (R0, n = 34/40) and microscopically incomplete (R1, n = 5/40) resection. All patients achieved CR. The 5‐year event‐free survival (EFS) and overall survival was 86% (±12; CI, 95%) and 100% (±0; CI, 95%), respectively. R0 resection/IRS I was significantly favorable for the 5‐year EFS. Local relapse occurred after a median time of 1.1 years (range, 0.04‐5.1) in 15% (6/40) after CR. All patients with RD underwent resection and achieved CR. Three patients had fibrosarcomatous DFSP, two were alive after R0 resection.

Conclusion

Complete surgical resection is mandatory to prevent relapse of DFSP.
Validation and refinement of PROSASH model using the neutrophil‐to‐lymphocyte ratio in patients with HCC receiving sorafenib
Authors: Casadei‐Gardini Andrea , Cabibbo Giuseppe , Dadduzio Vincenzo , Orsi Giulia , Vukotic Ranka , Rizzato Mario Domenico , Rossi Margherita , Guarneri Valeria , Lonardi Sara , D'Agostino Dario , Celsa Ciro , Rovesti Giulia , Rimini Margherita , Andreone Pietro , Zagonel Vittorina , Scartozzi Mario , Johnson Philip , Cascinu Stefano , Cucchetti Alessandro
Published: May 2020

The recently developed PROSASH model is proving to be a useful tool in risk‐group discrimination in hepatocellular carcinoma (HCC) patients treated with sorafenib. Several studies highlighted that the neutrophil‐to‐lymphocyte ratio (NLR) is one of the most important predictors of survival in HCC patients treated with sorafenib. The aims of the present study were to validate the PROSASH model and determine whether the incorporation of inflammatory markers can improve risk stratification. This study included 438 patients. According to the four categories of the PROSASH model, median overall survival (OS) was 20.0, 14.9, 8.5 and 3.0 months respectively (P < .001). The Harrell's c for this categorized model was 0.621. NLR (cut‐off 3) stratified OS in each of the PROSASH categories. After reclassification, median OS was 21.0, 15.1, 8.2 and 4.1 months (P < .001). The Harrell's c increased from 0.621 to 0.673 (P = .001). Integrating NLR into the PROSASH model allowed a more accurate classification of the patients in the risk groups.
Classification and syzygies of smooth projective varieties with 2‐regular structure sheaf
Authors: Kwak Sijong , Park Jinhyung
Published: May 2020

The geometric and algebraic properties of smooth projective varieties with 1‐regular structure sheaf are well understood, and the complete classification of these varieties is a classical result. The aim of this paper is to study the next case: smooth projective varieties with 2‐regular structure sheaf. First, we give a classification of such varieties using adjunction mappings. Next, under suitable conditions, we study the syzygies of section rings of those varieties to understand the structure of the Betti tables, and show a sharp bound for Castelnuovo–Mumford regularity.
Machine learning techniques for biomedical image segmentation: An overview of technical aspects and introduction to state‐of‐art applications
Authors: Seo Hyunseok , Badiei Khuzani Masoud , Vasudevan Varun , Huang Charles , Ren Hongyi , Xiao Ruoxiu , Jia Xiao , Xing Lei
Published: May 2020

In recent years, significant progress has been made in developing more accurate and efficient machine learning algorithms for segmentation of medical and natural images. In this review article, we highlight the imperative role of machine learning algorithms in enabling efficient and accurate segmentation in the field of medical imaging. We specifically focus on several key studies pertaining to the application of machine learning methods to biomedical image segmentation. We review classical machine learning algorithms such as Markov random fields, k‐means clustering, random forest, etc. Although such classical learning models are often less accurate compared to the deep‐learning techniques, they are often more sample efficient and have a less complex structure. We also review different deep‐learning architectures, such as the artificial neural networks (ANNs), the convolutional neural networks (CNNs), and the recurrent neural networks (RNNs), and present the segmentation results attained by those learning models that were published in the past 3 yr. We highlight the successes and limitations of each machine learning paradigm. In addition, we discuss several challenges related to the training of different machine learning models, and we present some heuristics to address those challenges.
Machine and deep learning methods for radiomics
Authors: Avanzo Michele , Wei Lise , Stancanello Joseph , Vallières Martin , Rao Arvind , Morin Olivier , Mattonen Sarah A. , El Naqa Issam
Published: May 2020

Radiomics is an emerging area in quantitative image analysis that aims to relate large‐scale extracted imaging information to clinical and biological endpoints. The development of quantitative imaging methods along with machine learning has enabled the opportunity to move data science research towards translation for more personalized cancer treatments. Accumulating evidence has indeed demonstrated that noninvasive advanced imaging analytics, that is, radiomics, can reveal key components of tumor phenotype for multiple three‐dimensional lesions at multiple time points over and beyond the course of treatment. These developments in the use of CT, PET, US, and MR imaging could augment patient stratification and prognostication buttressing emerging targeted therapeutic approaches. In recent years, deep learning architectures have demonstrated their tremendous potential for image segmentation, reconstruction, recognition, and classification. Many powerful open‐source and commercial platforms are currently available to embark in new research areas of radiomics. Quantitative imaging research, however, is complex and key statistical principles should be followed to realize its full potential. The field of radiomics, in particular, requires a renewed focus on optimal study design/reporting practices and standardization of image acquisition, feature calculation, and rigorous statistical analysis for the field to move forward. In this article, the role of machine and deep learning as a major computational vehicle for advanced model building of radiomics‐based signatures or classifiers, and diverse clinical applications, working principles, research opportunities, and available computational platforms for radiomics will be reviewed with examples drawn primarily from oncology. We also address issues related to common applications in medical physics, such as standardization, feature extraction, model building, and validation.
Genomics models in radiotherapy: From mechanistic to machine learning
Authors: Kang John , Coates James T. , Strawderman Robert L. , Rosenstein Barry S. , Kerns Sarah L.
Published: May 2020

Machine learning (ML) provides a broad framework for addressing high‐dimensional prediction problems in classification and regression. While ML is often applied for imaging problems in medical physics, there are many efforts to apply these principles to biological data toward questions of radiation biology. Here, we provide a review of radiogenomics modeling frameworks and efforts toward genomically guided radiotherapy. We first discuss medical oncology efforts to develop precision biomarkers. We next discuss similar efforts to create clinical assays for normal tissue or tumor radiosensitivity. We then discuss modeling frameworks for radiosensitivity and the evolution of ML to create predictive models for radiogenomics.
Molecular characterization of different preproGnRHs in Astyanax altiparanae (Characiformes): Effects of GnRH on female reproduction
Authors: Chehade Chayrra , Amaral Fernanda G. , Branco Giovana S. , Cassel Mônica , De Jesus Lázaro W. O. , Costa Fabiano G. , Bordin Silvana A. , Moreira Renata G. , Borella Maria I.
Published: May 2020

Gonadotropin‐releasing hormone (GnRH) is a key molecule in the initiation of the hypothalamic–pituitary–gonadal axis. Thus, knowledge about GnRH may contribute to the effectiveness of species reproduction. Using a Neotropical tetra Astyanax altiparanae as a fish model species, the GnRH forms were characterized at the molecular level and the role of injected GnRHs in vivo was evaluated. The full‐length complementary DNA (cDNA) sequences of preproGnRH2 (612 bp) and preproGnRH3 (407 bp) of A. altiparanae were obtained, and the GnRH1 form was not detected. The cDNA sequences of preproGnRH2 and preproGnRH3 were found to be conserved, but a change in the amino acid at position 8 of the GnRH3 decapeptide of A. altiparanae was observed. All the injected GnRHs stimulated lhβ messenger RNA (mRNA) expression but not fshβ mRNA expression, and only GnRH2 was able to increase maturation‐inducing steroid (MIS) levels and possibly stimulate oocyte release. Furthermore, only GnRH2 was able to start the entire reproductive hormonal cascade and induce spawning.
Angiotensin‐converting enzyme 2 (ACE2), SARS‐CoV‐2 and the pathophysiology of coronavirus disease 2019 (COVID‐19)
Authors: Bourgonje Arno R , Abdulle Amaal E , Timens Wim , Hillebrands Jan‐Luuk , Navis Gerjan J , Gordijn Sanne J , Bolling Marieke C , Dijkstra Gerard , Voors Adriaan A , Osterhaus Albert DME , van der Voort Peter HJ , Mulder Douwe J , van Goor Harry
Published: May 2020

Angiotensin‐converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID‐19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter‐regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin–angiotensin–aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID‐19 severity and progression, including age, sex, ethnicity, medication, and several co‐morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2‐expressing organs do not equally participate in COVID‐19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID‐19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS‐CoV‐2 infection is crucially important as it has major implications for understanding COVID‐19 pathophysiology and the development of evidence‐based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers, and RAAS inhibitors. Ultimately, prevention is key to combat COVID‐19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID‐19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID‐19 severity. In addition, we discuss the relevant pathological changes resulting from SARS‐CoV‐2 infection. Finally, we highlight a selection of potential treatment modalities for COVID‐19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.