bluuebunny/crossref_metadata_2025 huggingface dataset:
Polar Substitutions on the Surface of a Lipase Substantially Improve Tolerance in Organic Solvents
Authors: Cui Haiyang , Vedder Markus , Zhang Lingling , Jaeger Karl‐Erich , Schwaneberg Ulrich , Davari Mehdi D.
Published: January 2022

Biocatalysis in organic solvents (OSs) enables more efficient routes to the synthesis of various valuable chemicals. However, OSs often reduce enzymatic activity, which limits the use of enzymes in OSs. Herein, we report a comprehensive understanding of interactions between surface polar substitutions and DMSO by integrating molecular dynamics (MD) simulations of 45 variants from Bacillus subtilis lipase A (BSLA) and substitution landscape into a “BSLA‐SSM” library. By systematically analyzing 39 structural‐, solvation‐, and interaction energy‐based observables, we discovered that hydration shell maintenance, DMSO reduction, and decreased local flexibility simultaneously govern the stability of polar variants in OS. Moreover, the fingerprints of 1631 polar‐related variants in three OSs demonstrated that substituting aromatic to polar amino acid(s) hold great potential to highly improve OSs resistance. Hence, surface polar engineering is a powerful strategy to generate OS‐tolerant lipases and other enzymes, thereby adapting the catalyst to the desired reaction and process with OSs.
Developmentally interdependent stretcher‐compressor relationship between the embryonic brain and the surrounding scalp in the preosteogenic head
Authors: Tsujikawa Koichiro , Saito Kanako , Nagasaka Arata , Miyata Takaki
Published: January 2022

Background

How developing brains mechanically interact with the surrounding embryonic scalp layers (ie, epidermal and mesenchymal) in the preosteogenic head remains unknown. Between embryonic day (E) 11 and E13 in mice, before ossification starts in the skull vault, the angle between the pons and the medulla decreases, raising the possibility that when the elastic scalp is directly pushed outward by the growing brain and thus stretched, it recoils inward in response, thereby confining and folding the brain.

Results

Stress‐release tests showed that the E11‐13 scalp recoiled and that the in vivo prestretch prerequisite for this recoil was physically dependent on the brain (pressurization at 77‐93 Pa) and on actomyosin and elastin within the scalp. In scalp‐removed heads, brainstem folding was reduced, and the spreading of ink from the lateral ventricle to the spinal cord that occurred in scalp‐intact embryos (with >5 μL injection) was lost, suggesting roles of the embryonic scalp in brain morphogenesis and cerebrospinal fluid homeostasis. Under nonstretched conditions, scalp cell proliferation declined, while the restretching of the shrunken scalp rescued scalp cell proliferation.

Conclusions

In the embryonic mouse head before ossification, a stretcher‐compressor relationship elastically develops between the brain and the scalp, underlying their mechanically interdependent development.
What accounts for the high mortality of anorexia nervosa?
Authors: Mehler Philip S. , Watters Ashlie , Joiner Thomas , Krantz Mori J.
Published: January 2022

The exact medical complications, leading to the well‐known high risk of death in patients with anorexia nervosa (AN), remain elusive. Such deaths are often abrupt with no satisfactory explanation. Suspected causes include cardiac QTc prolongation and, in turn, torsade de pointes (TdP). Psychotropic medications often prescribed to these patients are linked to QTc prolongation. AN is also presumed to cause heart failure due to malnutrition with increased susceptibility to QTc prolongation, and TdP, resulting in sudden cardiac death. Recent literature, however, is conflicting, and the likely cause of death may involve other cardiac abnormalities, such as low heart rate, abnormal heart rate variability, or increased QT dispersion. With an ongoing gap in research explaining the high mortality rate in AN, a compelling need to define the exact proximate causes of death in these patients remains. Because low serum potassium is the most common trigger for TdP, we postulate the early signal of sudden cardiac death, especially in patients with AN who purge, is hypokalemia. We also speculate that hypoglycemia could be a major factor in the sudden death of patients with AN as well as bradycardia or sinus arrest. A path forward to elucidate potential causes is offered.
Food insecurity is associated with eating disorders independent of depression and anxiety: Findings from the 2020–2021 Healthy Minds Study
Authors: Zickgraf Hana F. , Hazzard Vivienne M. , O'Connor Shannon M.
Published: January 2022

Objective

To examine the association between food insecurity and eating disorder (ED) risk independent of co‐occurring anxiety/depression.

Method

Data were provided by 121,627 undergraduate/graduate students who participated in the 2020–2021 Healthy Minds Study (HMS). Participants responded to questionnaire measures of food insecurity and risk for EDs, depression, and anxiety. Established cut‐offs were used to identify students with food insecurity and probable psychopathology. Separate modified Poisson regressions adjusted for age, gender, race/ethnicity, and socioeconomic background examined the association between food insecurity and each form of psychopathology. The association between food insecurity and probable ED was then examined in a regression further adjusted for probable depression and anxiety.

Results

Food insecurity was significantly associated with all three forms of psychopathology when examined separately (prevalence ratios ranged from 1.41 to 1.54, all p’s < .001). When accounting for probable depression/anxiety, food insecurity was significantly associated with 1.19 times greater prevalence of a probable ED (p < .001).

Discussion

The association between food insecurity and EDs was replicated in a large, national sample of university students. To our knowledge, this is the first study to examine the independence of this relationship after adjusting for depression/anxiety. This finding supports the hypothesis that specific mechanisms, rather than general psychological distress, likely underlie the food insecurity–ED relationship.
Sensitized and Self‐Sensitized Photocatalytic Carbon Dioxide Reduction Under Visible Light with Ruthenium Catalysts Shows Enhancements with More Conjugated Pincer Ligands
Authors: Das Sanjit , Nugegoda Dinesh , Yao Wenzhi , Qu Fengrui , Figgins Matthew T. , Lamb Robert W. , Webster Charles Edwin , Delcamp Jared H. , Papish Elizabeth T.
Published: January 2022

A new method to synthesize complexes of the type [(CNC)RuII(NN)L]n+ has been introduced, where CNC is a tridentate pincer composed of two (benz)imidazole derived NHC rings and a pyridyl ring, NN is a bidentate aromatic diimine ligand, L=bromide or acetonitrile, and n=1 or 2. Following this new method a series of six new complexes has been synthesized and characterized by spectroscopic, analytic, crystallographic, and computational methods. Their electrochemical properties have been studied via cyclic voltammetry under both N2 and CO2 atmospheres. Photocatalytic reduction of CO2 to CO was performed using these complexes both in the presence (sensitized) and absence (self‐sensitized) of an external photosensitizer. This study evaluates the effect of different CNC, NN, and L ligands in sensitized and self‐sensitized photocatalysis. Catalysts bearing the benzimidazole derived CNC pincer show much better activity for both sensitized and self‐sensitized photocatalysis as compared to catalysts bearing the imidazole derived CNC pincer. Furthermore, self‐sensitized photocatalysis requires a diimine ligand for CO2 reduction with catalyst 2ACN being the most active catalyst in this series with TON=85 and TOF=22 h−1 with an electron donating 4,4′‐dimethyl‐2,2′‐bipyridyl (dmb) ligand and a benzimidazole derived CNC pincer.
A Facile Synthetic Strategy for Decavanadate and Transition Metal Based All‐Inorganic Coordination Polymers and Insights into Their Electrocatalytic OER Activity
Authors: Kar Aranya , Sharma Lalita , Kumar Akash , Halder Aditi , Pradeep Chullikkattil P.
Published: January 2022

This study reports a facile synthetic strategy for decavanadate ([V10O28]6−) cluster‐based all inorganic coordination polymers (CPs) containing earth‐abundant and redox‐active transition metals and their electrocatalytic oxygen evolution reaction (OER) activity. The first series of such isomorphous compounds containing the transition metals Mn, Co, and Ni, {(H2O)2K‐μ‐(H2O)3Mn(H2O)3}2n[V10O28]n (1), {(H2O)2K‐μ‐(H2O)3Co(H2O)3}2n[V10O28]n (2) and {(H2O)2K‐μ‐(H2O)3Ni(H2O)3}2n[V10O28]n (3), have been synthesized and structurally characterized. In these polymeric compounds, the [V10O28]6− clusters are interlaced and inter‐connected by {(H2O)2K‐μ‐(H2O)3‐M(H2O)3}+3 units leading to a linear chain‐like arrangement. Each of such chains is further interconnected to adjacent chains by bonding K+ ions with a [V10O28]6− cluster of the adjacent chain leading to a two‐dimensional (2D) sheet‐like arrangement. Hydrogen bonding interactions between the coordinated water molecules and the cluster oxygens further interconnect the adjacent sheets. All these compounds 1–3 are shown to catalyze the oxygen evolution reaction (OER) under alkaline (0.1 M KOH) conditions. Among the three, the Ni‐based catalyst 3 exhibited the best OER activity with a moderate overpotential of 270 mV at onset, a low Tafel slope of 89 mV dec−1, and a turnover frequency (TOF) of 7.5 s−1, which is comparable to similar Keggin POM‐based systems reported so far. The CPs were not highly stable under the OER conditions employed. The post‐catalytic analyses indicated the ‘precatalyst’ nature of these compounds in alkaline media forming V‐doped metal oxyhydroxides as the OER active species under the turnover conditions. Thus, this study provides a new and facile strategy for synthesizing [V10O28]6−cluster and transition metal‐based all‐inorganic CPs and insights into their OER electrocatalytic activities for the first time.
Versatile Activity of a Copper(II) Complex Bearing a N4‐Tetradentate Schiff Base Ligand with Reduced Oxygen Species
Authors: Richezzi Micaela , Ferreyra Joaquín , Puzzolo Juan , Milesi Lisandro , Palopoli Claudia M. , Moreno Diego M. , Hureau Christelle , Signorella Sandra R.
Published: January 2022

The reactivity of the Cu(II) complex of N,N’‐bis(pyridin‐2‐ylmethylene)propane‐1,3‐diamine (py2pn), [Cu(py2pn)(ClO4)2], toward O2.− and H2O2 has been examined. The complex reacts with O2.− with fast second order kinetics, kMcF=4.05×106 M−1 s−1, employing the Cu(II)/Cu(I) couple proved by spectroscopic detection of the reduced form at low temperature. At −40 °C in DMF, the reaction of the complex with H2O2/Et3N yields an stable end‐on Cu(II)‐hydroperoxide, with kOOH=0.31 min−1, the formation of which has been established by DFT calculations, electronic and EPR spectra. At room temperature, the end‐on Cu(II)‐hydroperoxide reacts with a second Cu(II) complex to evolve O2, with kCAT=83.2 M−2 s−1. The Cu(II)‐hydroperoxide can mediate phenol oxidation, probably through a trigonal bipyramidal ternary transition state based on DFT analysis, favored over catalase activity when low proportion of catalyst is used. In these reactions, structural constraints imposed by the ligand distort the coordination geometry of the metal and controls reactivity.
Inhibition of Cathepsin B by Ferrocenyl Indenes Highlights a new Pharmacological Facet of Ferrocifens
Authors: Sanz Garcia Juan , Gaschard Marie , Navizet Isabelle , Sahihi Mehdi , Top Siden , Wang Yong , Pigeon Pascal , Vessières Anne , Salmain Michèle , Jaouen Gérard
Published: January 2022

The family of ferrocifens initially built up from the anti‐oestrogen tamoxifen shows a broad antitumor activity bothin vitroandin vivo. Their mechanism of action relies on the presence of the redox motif [ferrocene‐ene‐phenol] that, under oxidative conditions, generates reactive oxygen species (ROS) and affords electrophilic quinone methides (QMs) having the ability to alkylate biological nucleophiles and in turn elicit a strong antiproliferative activity. In this context, the cysteine protease cathepsin B was initially presumed to be a target for ferrocenyl QMs.In vitroenzymatic assays ruled out this hypothesis but unexpectedly revealed that other ferrocifen metabolites, i. e. ferrocenyl indenes, acted as moderate inhibitors of cathepsin B. These experimental results were nicely confirmed by molecular docking calculations, that showed that the monophenol ferrocenyl indene and to a lower extent the diphenol interacted with the active site of cathepsin B, making it an unanticipated target of ferrocifens.
A Novel Nanoparticles‐based Electrochemical Sensing Platform for Sensitive Detection of Oral Anticoagulant; Edoxaban in Human Plasma
Authors: Ayish Nada S. , Marzouk Hoda M. , El‐Zeany Badr A. , Fayed Ahmed S.
Published: January 2022

During COVID‐19 pandemic, coagulopathy have been reported as a potential threat to most infected patients. Edoxaban (EDX) is a direct oral anticoagulant that is recently added to most COVID‐19 treatment protocols either as therapy or prophylaxis. Herein, a novel nanoparticles modified glassy carbon potentiometric sensor was developed for the selective quantitation of EDX in human plasma. The electrochemical performance of the proposed sensor was assessed and compared to nanoparticle free sensor. An enhancement in electrode performance including: detection limit (3.39×10−6 mol L−1), response time (8.0±2.0 s) and improved selectivity. The proposed sensor was able to determine EDX in pure form, pharmaceutical formulation and human plasma.
Home treatment as an add‐on to family‐based treatment in adolescents with anorexia nervosa: A pilot study
Authors: Pauli Dagmar , Flütsch Nicole , Hilti Nadine , Schräer Christiane , Soumana Mariama , Häberling Isabelle , Berger Gregor
Published: January 2022

Objective

This pilot study examines the feasibility and the effectiveness of add‐on home treatment (HT) to family‐based treatment (FBT) in adolescents with anorexia nervosa (AN). The HT intervention is delivered by specialised nurses and aims at supporting patients and parents to re‐establish family meals in the home environment.

Method

We performed a 3‐month study in AN patients with a waiting‐list control design comparing 45 (43 females, 2 males) adolescents receiving FBT augmented with HT compared to 22 (21 females, 1 male) participants receiving FBT alone on the waiting list for additional HT. Eating disorder diagnosis, psychopathology and severity of clinical symptoms were assessed using the Eating Disorder Examination (EDE) interview, the Eating Disorders Inventory (EDI‐2) and clinical parameters (BMI, menstrual status, level of over‐exercising) at baseline and after 3 months.

Results

After 3 months of treatment, both treatment groups showed a significant early weight gain, a reduction in the rate of AN diagnoses assessed with the EDE interview and a reduction in EDI‐2 total scores. The combined HT/FBT group showed a significantly greater increase in BMI than the FBT‐only group. In the combined HT/FBT group, none of the patients had to be admitted to hospital, while three (13.6%) of the FBT‐only group had to be referred to inpatient treatment.

Discussion

Our results suggest that HT augmented FBT might be useful compared to FBT alone in terms of early weight gain and might reduce the risk of hospital admission in adolescent AN.
Comparative Physicochemical, Microbiological, Antioxidant, and Sensory properties of pre‐ and post‐fermented yoghurt enriched with olive leaf and its extract
Authors: Pourghorban Samira , Yadegarian Linda , Jalili Maryam , Rashidi Ladan
Published: January 2022

This study investigated the comparative effect of yoghurt samples enriched with different concentrations of olive leaf powder (OLP) (0.1, 0.5, 1, and 1.5 mg/ml) and its extract (OLE) (0.5, 1, 3, and 5 mg/ml) on the microbiological, sensory, physicochemical, and antioxidant properties of pre‐ and post‐fermented samples during 21 days of storage. Sensory evaluation showed that concentrations lower than 1.5 and 5 mg/ml of OLP and OLE, respectively, were acceptable. Adding OLP or OLE did not have an influence on yoghurt starter culture bacteria (p > .05). All enriched samples significantly showed higher acidity and lower pH compared with control samples (p < .05). The most important polyphenols were oleuropein (from 0.132 to 0.224 and 0.373 to 0.413 mg/g for 0.5 and 3 mg/ml of OLE, from 0.194 to 0.321 mg/g and 0.413 to 1.280 mg/g for 0.5 and 1 mg/ml of OLP, respectively) and catechin (from 0.369 to 0.382 and 0.461 to 0.477 mg/g for 0.5 and 3 mg/ml of OLE, from 0.386 to 0.405 mg/g and 0.310 to 0.710 mg/g for 0.5 and 1 mg/ml of OLP, respectively) in enriched yoghurts. Adding OLP or OLE increased shelf life, antioxidant activity percentage (AA%), and total phenol content (TPC) of enriched samples (p < .05). During 21 days of storage of all samples, TPC, AA%, and pH decreased and TTA increased.
The expression and function of glutamate aspartate transporters in Bergmann glia are decreased in neuronal nitric oxide synthase‐knockout mice during postnatal development
Authors: Tellios Vasiliki , Maksoud Matthew J. E. , Lu Wei‐Yang
Published: January 2022

Bergmann glia (BG) predominantly use glutamate/aspartate transporters (GLAST) for glutamate uptake in the cerebellum. Recently, nitric oxide (NO) treatment has been shown to upregulate GLAST function and increase glutamate uptake in vitro. We previously discovered that neuronal nitric oxide synthase knockout (nNOS−/−) mice displayed structural and functional neuronal abnormalities in the cerebellum during development, in addition to previously reported motor deficits. Although these developmental deficits have been identified in the nNOS−/− cerebellum, it is unknown whether BG morphology and GLAST expression are also affected in the absence of nNOS in vivo. This study is the first to characterize BG morphology and GLAST expression during development in nNOS−/− mice using immunohistochemistry and western blotting across postnatal development. Results showed that BG in nNOS−/− mice exhibited abnormal morphology and decreased GLAST expression compared with wildtype (WT) mice across postnatal development. Treating ex vivo WT cerebellar slices with the NOS inhibitor L‐NAME decreased GLAST expression while treating nNOS−/− slices with the slow‐release NO‐donor NOC‐18 increased GLAST expression when compared with their respective controls. In addition, treating primary BG isolated from WT mice with the selective nNOS inhibitor 7N decreased the membrane expression of GLAST and influx of Ca2+/Na+, while treating nNOS−/− BG with SNAP increased the membrane expression of GLAST and Ca2+/Na+ influx. Moreover, the effects of SNAP on GLAST expression and Ca2+/Na+ influx in nNOS−/− BG were significantly reduced by a PKG inhibitor. Together, these results reveal a novel role for nNOS/NO signaling in BG development, regulated by a PKG‐mediated mechanism.
Progressive loss of hepatocyte nuclear factor 4 alpha activity in chronic liver diseases in humans
Authors: Gunewardena Sumedha , Huck Ian , Walesky Chad , Robarts Dakota , Weinman Steven , Apte Udayan
Published: January 2022

Background and Aims

Hepatocyte nuclear factor 4 alpha (HNF4α) is indispensable for hepatocyte differentiation and critical for maintaining liver health. Here, we demonstrate that loss of HNF4α activity is a crucial step in the pathogenesis of chronic liver diseases (CLDs) that lead to development of HCC.

Approach and Results

We developed an HNF4α target gene signature, which can accurately determine HNF4α activity, and performed an exhaustive in silico analysis using hierarchical and K‐means clustering, survival, and rank‐order analysis of 30 independent data sets containing over 3500 individual samples. The association of changes in HNF4α activity to CLD progression of various etiologies, including HCV‐ and HBV‐induced liver cirrhosis (LC), NAFLD/NASH, and HCC, was determined. Results revealed a step‐wise reduction in HNF4α activity with each progressive stage of pathogenesis. Cluster analysis of LC gene expression data sets using the HNF4α signature showed that loss of HNF4α activity was associated with progression of Child‐Pugh class, faster decompensation, incidence of HCC, and lower survival with and without HCC. A moderate decrease in HNF4α activity was observed in NAFLD from normal liver, but a further significant decline was observed in patients from NAFLD to NASH. In HCC, loss of HNF4α activity was associated with advanced disease, increased inflammatory changes, portal vein thrombosis, and substantially lower survival.

Conclusions

In conclusion, these data indicate that loss of HNF4α function is a common event in the pathogenesis of CLDs leading to HCC and is important from both diagnostic and therapeutic standpoints.
The RSPO‐LGR4/5‐ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease
Authors: Annunziato Stefano , Sun Tianliang , Tchorz Jan S.
Published: January 2022

WNT/β‐catenin signaling plays pivotal roles during liver development, homeostasis, and regeneration. Likewise, its deregulation disturbs metabolic liver zonation and is responsible for the development of a large number of hepatic tumors. Liver fibrosis, which has become a major health burden for society and a hallmark of NASH, can also be promoted by WNT/β‐catenin signaling. Upstream regulatory mechanisms controlling hepatic WNT/β‐catenin activity may constitute targets for the development of novel therapies addressing these life‐threatening conditions. The R‐spondin (RSPO)–leucine‐rich repeat‐containing G protein‐coupled receptor (LGR) 4/5–zinc and ring finger (ZNRF) 3/ring finger 43 (RNF43) module is fine‐tuning WNT/β‐catenin signaling in several tissues and is essential for hepatic WNT/β‐catenin activity. In this review article, we recapitulate the role of the RSPO‐LGR4/5‐ZNRF3/RNF43 module during liver development, homeostasis, metabolic zonation, regeneration, and disease. We further discuss the controversy around LGR5 as a liver stem cell marker.
Modelling the performance of bunds and ditch dams in the hydrological restoration of tropical peatlands
Authors: Putra Santosa Sandy , Baird Andy J. , Holden Joseph
Published: January 2022

Many tropical peatlands are subjected to artificial drainage that leads to degradation. Hence, hydrological restoration has recently been prioritized. Nevertheless, as field monitoring data are limited, little is known about how restoration measures, such as ditch dams and bunds, can regulate tropical peatland water tables. We used a hydrodynamic model —DigiBog_Hydro— to simulate the effectiveness of ditch dams and bunds across three El Niño–Southern Oscillation (ENSO) scenarios, which are El Niño, La Niña and Neutral, in three typical sites. The sites were moderately degraded (Mod‐Dgr) and severely degraded (Sev‐Dgr) peatland plots (each 0.2 km2), representing typical peatland conditions in Sebangau National Park, Kalimantan, Indonesia. Our fine‐scale (1 m × 1 m spatial resolution) modelling revealed that in the dry season of any ENSO scenario, the significant effects of ditch‐dams alone on peatland water‐level were limited to lateral distances of 26 m (in Mod‐Dgr) and 12 m (in Sev‐Dgr) from the ditch. In the dry season of an El Niño year, the combination of ditch dams and bunds helped maintain water levels up to 72 cm (in Mod‐Dgr) and 69 cm (in Sev‐Dgr) higher than in the no‐restoration condition. During the extreme‐dry period of an El Niño year, the bunds reduced the number of days when the water table was deeper than 40 cm in Mod‐Dgr and in Sev‐Dgr by 50% and 73%, respectively. We suggest that bunds used in combination with ditch dams are a practical restoration measure for tropical peatlands, providing critical extra water storage and helping maintain water tables near the peatland surface in dry periods. We also demonstrate how fine‐scale hydrodynamic modelling is beneficial for planning and assessment of restoration measures in tropical peatlands.
Should infant psychology rely on the violation‐of‐expectation method? Not anymore
Authors: Paulus Markus
Published: January 2022

Infant psychology has heavily drawn on the Violation‐of‐Expectation (VoE) method. In this piece, I analyse the assumptions that go into the VoE method by comparing it with other looking time measures. Reviewing key arguments in the literature, I argue that this method relies on too many questionable assumptions, that its conceptual foundations are thin, and that its findings are empirically not conclusive. Theoretical inferences based on VoE findings are thus too speculative to allow for solid progress in developmental psychology. Overall, while I appreciate that the VoE method has helped to make infant psychology a prominent field of research, I argue that it is time for infant psychology to move forward and to leave the VoE method behind.
Composite dietary antioxidant index and the risk of colorectal cancer: Findings from the Singapore Chinese Health Study
Authors: Yu Yi‐Chuan , Paragomi Pedram , Wang Renwei , Jin Aizhen , Schoen Robert E. , Sheng Li‐Ting , Pan An , Koh Woon‐Puay , Yuan Jian‐Min , Luu Hung N.
Published: January 2022

Colorectal cancer (CRC) is a major contributor to cancer death globally. Several studies showed some protections by certain individual dietary antioxidants against CRC development. Epidemiologic data on the composite dietary antioxidant index (CDAI) in relation to CRC risk are sparse. Using the Singapore Chinese Health Study, an ongoing prospective cohort consisting of 61 321 cancer‐free participants aged 45 to 74 years at baseline, a food‐based CDAI was calculated according to a previously established and validated method that included six food‐sourced antioxidants including vitamins A, C and E, manganese, selenium and zinc. Cox proportional hazard regression method was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for CRC associated with various levels of CDAI with adjustment for multiple potential confounders. After an average of 17.5 years of follow‐up, 2140 participants developed CRC. HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of CDAI were 0.94 (0.83‐1.07), 0.86 (0.75‐1.00) and 0.80 (0.66‐0.98), respectively, compared to the lowest quartile (Ptrend = .02). This inverse association between CDAI and CRC risk was more apparent in women or those without a history of diabetes, without family history of CRC, never smokers or overweight/obese individuals. However, none of the heterogeneity tests for the CDAI‐CRC risk association reached statistical significance. Our findings suggest that food‐based antioxidants may be beneficial for reducing the risk of CRC in the general population.
Skin lesion segmentation using an improved framework of encoder‐decoder based convolutional neural network
Authors: Kaur Ranpreet , GholamHosseini Hamid , Sinha Roopak
Published: January 2022

Automatic lesion segmentation is a key phase of skin lesion analysis that significantly increases the performance of subsequent classification steps. Segmentation is a highly complex task due to the varying nature of lesions, such as unique shapes, different colors, and structures. In this study, a two‐step system is proposed comprising preprocessing algorithm and lesion segmentation network. The hairlines removal algorithm is designed using morphological operators to eliminate noise artifacts. The resulting output images are fed to the convolutional neural network (CNN) to perform lesion segmentation. The proposed CNN network is a new framework designed from scratch based on encoder‐decoder architecture. The layers are stacked in a unique sequence to perform downsampling and upsampling, generating a high‐resolution segmentation map. Additionally, a Tversky loss function is implemented to reduce the error rate between predicted and target output. In this study, we focus on the challenges related to the extraction of accurate lesion regions and the presence of hairlines in lesion images that can occlude important information resulting in poor segmentation. The proposed model is evaluated on four publicly available datasets, namely ISIC 2016–2018. The mean intersection over union (IoU) obtained for ISIC 2016–2018 and is 87.1%, 77.8%, 85.2%, and 88.8%, respectively. The proposed model demonstrated higher performance as compared to other state‐of‐the‐art methods. The hair removal step aids in the improvement of the overall performance.
Solar‐powered chemistry: Engineering low‐dimensional carbon nitride‐based nanostructures for selective CO2 conversion to C1C2 products
Authors: Ng Sue‐Faye , Foo Joel Jie , Ong Wee‐Jun
Published: January 2022

CO2 capture and conversion has been prospected as an auspicious technology to simultaneously tackle the rise in global CO2 emission and produce value‐added fuels with the goal of accomplishing carbon neutrality. A sustainable route to achieve this is via the utilization of solar energy, thereby harnessing the abundant and nonexhaustive resource to shift our reliance away from rapidly depleting fossil fuels. Graphitic carbon nitride (g‐C3N4) and its allotrope have earned its rank as a fascinating metal‐free photocatalyst due to its superior stability, high surface‐area‐to‐volume ratio, and tunable surface engineering. By leveraging these properties, robust carbon nitride‐based nanostructures are engineered for photocatalytic CO2 conversion to energy‐rich C1C2 product, which is indispensable in the chemical industry. Thus, this review presents the latest panorama of experimental and computational research on tuning the local electronic, surface chemical coordination environment, charge dynamics and optical properties of low‐dimensional carbon nitride and its allotropes toward highly selective and efficient CO2 photoconversion. To name a few, structural engineering, point‐defect engineering, heterojunction construction, and cocatalyst loading. To advance this frontier, critical insights are elucidated to establish the structure‐performance relationship and unravel primary factors dictating the selectivity of C1C2 molecules from CO2 reduction. External‐field assisted photocatalysis such as with electric (photoelectro‐) and heat (photothermal) is discussed to uncover the synergistic contributions that drive the development in photochemistry. Last, future challenges and prospects are outlined for the potential application of solar‐driven CO2 conversion, along with the scale‐up strategy from the economic viewpoint toward the rational development of high‐efficiency carbon nitride catalysts.

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Well‐balanced quadruple systems
Authors: Liu Ruijing , Zhou Junling
Published: January 2022

A set system with uniform block size is ‐balanced if any ‐subset of is contained in or blocks of for some nonnegative integer . is well‐balanced if it is ‐balanced for any positive integer . In this paper, we establish the necessary conditions for the existence of a ‐balanced set system, which is closely related with packing numbers and covering numbers . Then we concentrate on well‐balanced quadruple systems (with block size ). For , define the well‐balanced packing number to be the maximum number of blocks in any well‐balanced ‐ packing. Similarly, the well‐balanced covering number denotes the minimum number of blocks in any well‐balanced ‐ covering. The exact values of and are completely determined in this paper and the determinations of and are reduced to where .
Clinical application of low erythrocyte sedimentation rate/high C‐reactive protein to antineutrophil cytoplasmic antibody‐associated vasculitis
Authors: Park Pil Gyu , Song Jason Jungsik , Park Yong‐Beom , Lee Sang‐Won
Published: January 2022

Background

This study investigated whether the discordance between erythrocyte sedimentation rate (ESR) and C‐reactive protein at diagnosis could estimate the simultaneous clinical and laboratory variables and predict the poor outcomes during follow‐up in patients with antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV).

Methods

The medical records of 254 AAV patients were reviewed. Clinical and laboratory and AAV‐specific indices at diagnosis and all‐cause mortality, relapse and end‐stage renal disease during follow‐up were obtained. ESR and CRP levels were categorised as high and low based on the median values. Accordingly, the patients were divided into the following four groups: high ESR/low CRP; low ESR/high CRP; low ESR/low CRP; and high ESR/high CRP.

Results

Of the 254 AAV patients, 51 patients exhibited discordance between ESR and CRP. Among the 51 AAV patients, the median age was 59.0 years, and 20 patients were men (29 MPA, 13 GPA and 9 EGPA). Cardiovascular and nervous systemic manifestations were observed more frequently in AAV patients with low ESR/high CRP than in those with high ESR/low CRP. Six patients from the low ESR/high CRP group died. AAV patients with low ESR/high CRP exhibited significantly lower cumulative patients' survival rates than both those with high ESR/low CRP and those with low ESR/low CRP. Also, AAV patients with low ESR/high CRP exhibited significantly higher simultaneous BVAS than those with low ESR/low CRP.

Conclusions

Low ESR/high CRP at diagnosis could not only estimate the simultaneous high BVAS but also predict all‐cause mortality during follow‐up in AAV patients.
Assessment of frictional resistance and surface roughness in orthodontic wires coated with two different nanoparticles
Authors: da Silveira Ramiro Estacia , Elias Carlos Nelson , do Amaral Flávia Lucisano Botelho
Published: January 2022

Several mechanical and biological factors may change the orthodontic wire frictional resistance (FR). Titanium dioxide (TiO2) and silica dioxide (SiO2) nanoparticle (NP) coatings may be used to improve the characteristics of materials, reducing FR between archwire and bracket. This in vitro study aimed to evaluate the FR of orthodontic wires with and without coating in both dry and wet environments and measure the surface roughness (SR). One hundred and eighty segments of rectangular Cr–Ni orthodontic wires (Morelli Co, Brazil) were divided into three groups according to the NP coating applied: TiO2 group; SiO2 group; and control group. The SR parameters were measured in an optical profilometer, the surface morphology was analyzed with scanning electron microscopy (SEM), and FR was performed in a universal testing machine in dry and wet environments (n = 30). The statistical analysis was performed using the Generalized Estimated Equations model with a Bonferroni post‐test (α = 0.05). It was observed that SiO2 NP coating decreased FR significantly when compared to the TiO2 and control groups, in both environments (p < .001). The SiO2 and TiO2 groups presented statistically lower SR than the control group and were similar to each other (p < .001). The SiO2 group presented the lower depth of Valley parameter than the TiO2 group (p < .001). The SEM showed that the TiO2 coating had the most heterogeneous surface morphology than the SiO2 and control groups. The orthodontic wires with NP coating modified the FR and morphology. The SiO2 coating reduced FR in both dry and wet environments and decreased SR.

Titanium dioxide (TiO2) and silica dioxide (SiO2) nanoparticles coatings may be used to reduce frictional resistance (FR) between archwire and bracket as well as to improve surface morphology.

The SiO2 coating reduced FR in both dry and wet environments and decreased the SR of Cr–Ni orthodontic wire.

The TiO2 coating promoted the most heterogeneous surface morphology of Cr–Ni orthodontic wire.
Exploring the enzyme‐catalyzed synthesis of isotope labeled cyclopropanes
Authors: Sardana Malvika , Mühlfenzl Kim S. , Wenker Sylvia T. M. , Åkesson Christian , Hayes Martin A. , Elmore Charles S. , Pithani Subhash
Published: January 2022

Cyclopropanes are commonly employed structural moieties in drug design since their incorporation is often associated with increased target affinity, improved metabolic stability, and increased rigidity to access bioactive conformations. Robust chemical cyclopropanation procedures have been developed which proceed with high yield and broad substrate scope, and have been applied to labeled substrates. Recently, engineered enzymes have been shown to perform cyclopropanations with remarkable diastereoselectivity and enantioselectivity, but this biocatalytic approach has not been applied to labeled substrates to date. In this study, the use of enzyme catalysis for the synthesis of labeled cyclopropanes was investigated. Two readily available enzymes, a modified CYP450 enzyme and a modified Aeropyrum pernix protoglobin, were investigated for the cyclopropanation of a variety of substituted styrenes. For this biocatalytic transformation, the enzymes required the use of ethyl diazoacetate. Due to the highly energetic nature of this molecule, alternatives were investigated. The final optimized cyclopropanation was successfully demonstrated using n‐hexyl diazoacetate, resulting in moderate to high enantiomeric excess. The optimized procedure was used to generate labeled cyclopropanes from 13C‐glycine, forming all four labeled stereoisomers of phosphodiesterase type‐IV inhibitor, MK0952. These reactions provide a convenient and effective biocatalytic route to stereoselective 13C‐labeled cyclopropanes and serve as a proof‐of‐concept for generating stereoselective labeled cyclopropanes.
Aortic Pulse Wave Velocity Evaluated by 4D Flow MRI Across the Adult Lifespan
Authors: Jarvis Kelly , Scott Michael B. , Soulat Gilles , Elbaz Mohammed S. M. , Barker Alex J. , Carr James C. , Markl Michael , Ragin Ann
Published: January 2022

Background

Evaluation of aortic stiffness by pulse wave velocity (PWV) across the adult lifespan is needed to better understand normal aging in women and men.

Purpose

To characterize PWV in the thoracic aorta using 4D flow MRI in an age‐ and sex‐stratified cohort of healthy adults.

Study Type

Retrospective.

Population

Ninety nine healthy participants (age: 46 ± 15 [19–79] years, 50% female), divided into young adults (<45 years) (N = 48), midlife (45–65 years) (N = 37), and later life (>65 years) (N = 14) groups.

Field Strength/Sequence

1.5 T or 3 T, 2D cine bSSFP, 4D flow MRI.

Assessment

Cardiac functional parameters of end‐diastolic volume (EDV), end‐systolic volume (ESV), stroke volume (SV) and myocardial mass were assessed by 2D cine bSSFP. PWV and aortic blood flow velocity were assessed by 4D flow MRI. Reproducibility of PWV was evaluated in a subset of nine participants.

Statistical Tests

Analysis of variance, Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC). A P value < 0.05 was considered statistically significant.

Results

PWV increased significantly with age (young adults: 5.4 ± 0.9 m/sec, midlife: 7.2 ± 1.1 m/sec, and later life: 9.4 ± 1.8 m/sec) (r = 0.79, slope = 0.09 m/sec/year). PWV did not differ in women and men in entire sample (P = 0.40) or within age groups (young adults: P = 0.83, midlife: P = 0.17, and later life: P = 0.96). PWV was significantly correlated with EDV (r = −0.29), ESV (r = −0.23), SV (r = −0.28), myocardial mass (r = 0.21), and mean aortic blood flow velocity (r = −0.62). In the test–retest subgroup (N = 9), PWV was 6.7 ± 1.5 [4.4–9.3] m/sec and ICC = 0.75.

Data Conclusion

4D flow MRI quantified higher aortic PWV with age, by approximately 1 m/sec per decade, and significant differences between young adults, midlife and later life. Reproducibility analysis showed good test–retest agreement. Increased PWV was associated with decline in cardiac function and reduced aortic blood flow velocity. This study demonstrates the utility of 4D flow MRI‐derived aortic PWV for studying aging.

Evidence Level

2

Technical Efficacy

Stage 2
Magnetic Resonance Imaging Radiomics‐Based Nomogram From Primary Tumor for Pretreatment Prediction of Peripancreatic Lymph Node Metastasis in Pancreatic Ductal Adenocarcinoma: A Multicenter Study
Authors: Shi Zhenshan , Ma Chengle , Huang Xinming , Cao Dairong
Published: January 2022

Background

Determining the absence or presence of peripancreatic lymph nodal metastasis (PLNM) is important to the pathologic staging, prognostication, and guidance of treatment in pancreatic ductal adenocarcinoma (PDAC) patients. Computed tomography and MRI had a poor sensitivity and diagnostic accuracy in the assessment of PLNM.

Purposes

To develop and validate a 3 T MRI primary tumor radiomics‐based nomogram from multicenter datasets for pretreatment prediction of the PLNM in PDAC patients.

Study Type

Retrospective.

Subjects

A total of 251 patients (156 men and 95 women; mean age, 60.85 ± 8.23 years) with histologically confirmed pancreatic ductal adenocarcinoma from three hospitals.

Field Strength and Sequences

A 3.0 T and fat‐suppressed T1‐weighted imaging.

Assessment

Quantitative imaging features were extracted from fat‐suppressed T1‐weighted (FS T1WI) images at the arterial phase.

Statistical Tests

Normally distributed data were compared by using t‐tests, while the Mann–Whitney U test was used to evaluate non‐normally distributed data. The diagnostic performances of the preoperative and postoperative nomograms were assessed in the external validation cohort with the area under receiver operating characteristics curve (AUC), calibration curve, and decision curve analysis (DCA). AUCs were compared with the De Long test. A p value below 0.05 was considered to be statistically significant.

Results

The AUCs of magnetic resonance imaging (MRI) Rad‐score were 0.868 (95% confidence level [CI]: 0.613–0.852) and 0.772 (95% CI: 0.659–0.879) in the training and internal validation cohort, respectively. The preoperative and postoperative nomograms could accurately predict PLNM in the training cohort (AUC = 0.909 and 0.851) and were validated in both the internal and external cohorts (AUC = 0.835 and 0.805, 0.808 and 0.733, respectively). DCA indicated that the two novel nomograms are of similar clinical usefulness.

Data Conclusion

Pre−/postoperative nomograms and the constructed radiomics signature from primary tumor based on FS T1WI of arterial phase could serve as a potential tool to predict PLNM in patients with PDAC.

Evidence Level

3

Technical Efficacy

Stage 2
Comparison of COVID‐19 laboratory diagnosis by commercial kits: Effectivity of RT‐PCR to the RT‐LAMP
Authors: Artik Yakup , Coşğun Alp B. , Cesur Nevra P. , Hızel Nedret , Uyar Yavuz , Sur Haydar , Ayan Alp
Published: January 2022

Coronavirus disease 2019 or COVID‐19 caused by novel coronavirus/severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 or 2019‐nCoV) is an ongoing pandemic that has emerging global effects and requires rapid and reliable diagnostic testing. Quantitative reverse transcription‐polymerase chain reaction (q‐RT‐PCR) is the gold standard method for SARS‐CoV‐2 detections. On the other hand, new approaches remedy the diagnosis difficulties gradually. Reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) as one of these novel approaches may also contribute to faster and cheaper field‐based testing. The present study was designed to evaluate this rapid screening diagnostic test that can give results in 30–45 min and to compare the effectiveness of LAMP to the q‐RT‐PCR. The 30 randomly chosen patient samples were generated by nasopharyngeal swabs with a portion of the SARS‐CoV‐2 nucleic sequence. The sample of quantification cycle (Cq) values was tested using RT‐LAMP as well as by conventional q‐RT‐PCR. The patient samples were tested with four different kits (SENSObiz COVID‐19 [SARS‐CoV‐2] LAMP Assay, the QIAseq DIRECT SARS‐CoV‐2 kit, Biospeedy SARS‐CoV‐2 Variant Plus kit, and CoVirion‐CV19‐2 SARS‐CoV‐2 OneStep RT‐PCR kit) and two different PCR devices (GDS Rotor‐Gene Q Thermocycler and Inovia Technologies GenX series). Based on 30 patient samples, the positive/negative ratio (P/N) was 30/0 as Biospeedy and Covirion (positivity 100%), 28/2 as Qiagen kit (positivity 93.3%) for the samples studied on the Inovia device while the same samples on the Rotor‐Gene device were 30/0 as Biospeedy and Covirion (positivity 100%), 29/1 as Qiagen kit at the first day (96.7%). On the fifth day, the samples were studied in the Inovia device and the respective results were obtained: 27/3 as Biospeedy (positivity 90%), 16/14 as Qiagen (positivity 53.3%), 28/2 as Covirion kit (positivity 93.3%). When these samples were studied in the Rotor‐Gene device, it was 29/1 in Biospeedy and Covirion (positivity 96.7%), 19/11 in the Qiagen kit (positivity 63.3%). When these samples were compared with the LAMP method it was found to be 19/11 (positivity 63.3%) on the first day and 18/12 (positivity 60%) on the fifth day. SARS‐CoV‐2 test studies will contribute to a proactive approach to the development of rapid diagnosis systems. The LAMP approach presents promising results to monitor exposed individuals and also improves screening efforts in potential ports of entry.
Distinct mutations and lineages of SARS‐CoV‐2 virus in the early phase of COVID‐19 pandemic and subsequent 1‐year global expansion
Authors: Chen Yan , Li Shiyong , Wu Wei , Geng Shuaipeng , Mao Mao
Published: January 2022

A novel coronavirus, SARS‐CoV‐2, has caused over 274 million cases and over 5.3 million deaths worldwide since it occurred in December 2019 in Wuhan, China. Here we conceptualized the temporospatial evolutionary and expansion dynamics of SARS‐CoV‐2 by taking a series of the cross‐sectional view of viral genomes from early outbreak in January 2020 in Wuhan to the early phase of global ignition in early April, and finally to the subsequent global expansion by late December 2020. Based on the phylogenetic analysis of the early patients in Wuhan, Wuhan/WH04/2020 is supposed to be a more appropriate reference genome of SARS‐CoV‐2, instead of the first sequenced genome Wuhan‐Hu‐1. By scrutinizing the cases from the very early outbreak, we found a viral genotype from the Seafood Market in Wuhan featured with two concurrent mutations (i.e., M type) had become the overwhelmingly dominant genotype (95.3%) of the pandemic 1 year later. By analyzing 4013 SARS‐CoV‐2 genomes from different continents by early April, we were able to interrogate the viral genomic composition dynamics of the initial phase of global ignition over a time span of 14 weeks. Eleven major viral genotypes with unique geographic distributions were also identified. WE1 type, a descendant of M and predominantly witnessed in western Europe, consisted of half of all the cases (50.2%) at the time. The mutations of major genotypes at the same hierarchical level were mutually exclusive, which implies that various genotypes bearing the specific mutations were propagated during human‐to‐human transmission, not by accumulating hot‐spot mutations during the replication of individual viral genomes. As the pandemic was unfolding, we also used the same approach to analyze 261 323 SARS‐CoV‐2 genomes from the world since the outbreak in Wuhan (i.e., including all the publicly available viral genomes) to recapitulate our findings over 1‐year time span. By December 25, 2020, 95.3% of global cases were M type and 93.0% of M‐type cases were WE1. In fact, at present all the five variants of concern (VOC) are the descendants of WE1 type. This study demonstrates that viral genotypes can be utilized as molecular barcodes in combination with epidemiologic data to monitor the spreading routes of the pandemic and evaluate the effectiveness of control measures. Moreover, the dynamics of viral mutational spectrum in the study may help the early identification of new strains in patients to reduce further spread of infection, guide the development of molecular diagnosis and vaccines against COVID‐19, and help assess their accuracy and efficacy in real world at real time.