bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterization of the metabolites of moscatilin in mouse, rat, dog, monkey and human hepatocytes by LC–Orbitrap–MS/MS combined with diagnostic fragment ions and accurate mass measurements
Authors: Hu Aizhen , Liu Qingwang , Ouyang Jing
Published: December 2022

Moscatilin, a bibenzyl derivative from the stem of Dendrobium loddigesii, has been shown to have anticancer activity. The aim of this study was to identify and characterize the possible in vitro metabolites of moscatilin generated from hepatocytes. The metabolites generated in the hepatocytes of mouse, rat, dog, monkey and human were identified and characterized employing ultra‐high‐performance liquid chromatography coupled with quadrupole Orbitrap tandem mass spectrometry (LC–Orbitrap–MS/MS) based on diagnostic fragment ions and accurate mass measurements. A total of 18 metabolites were identified, among which seven were phase I and 11 were phase II metabolites. The plausible structures of the metabolites and the probable biotransformation pathways were proposed based on the diagnostic fragment ions, chemical formula and mass fragmentation pattern, as well as the accurate masses. The majority of phase I metabolites were generated by demethylation and hydroxylation, while phase II metabolites were mainly generated by glucuronidation, glutathione conjugation and sulfation. Our study first expounded the metabolites of moscatilin in mouse, rat, dog, monkey and human hepatocytes and provided a foundation for a further pharmacokinetic and toxicity study. More importantly, LC–Orbitrap–MS/MS combined with diagnostic fragment ions and accurate mass measurements has been proved to be an effective method for the rapid identification of bibenzyl derivatives and their metabolites.
Surgical repair of an obstructed mixed‐type total anomalous pulmonary venous connection
Authors: Shammout Reem , Alkhadraa Doaa , Alkadi Sidra , Al‐Dairy Alwaleed
Published: December 2022

Total anomalous pulmonary venous connection is a rare congenital anomaly and has four anatomical subtypes of which the mixed type represents diagnostic and therapeutic challenge. When associated with obstruction, however, urgent surgical repair is needed. Herein, we present a rare case of obstructed mixed type total anomalous pulmonary venous connection with successful surgical repair.
Managing soil acidity vs. soil Ca:Mg ratio: What is more important for crop productivity?
Authors: Leiva Soto Andrea , Culman Steve W , Herms Catherine , Sprunger Christine , Doohan Douglas
Published: December 2022

Soil balancing (SB), or base cation saturation ratio (BCSR), is a soil management approach that strives to maintain specific soil calcium (Ca) and magnesium (Mg) levels to improve soil health, decrease pest problems, have better crops, and increase crop yield. To achieve ideal levels of Ca to Mg, BCSR practitioners apply gypsum (calcium sulfate) and high‐calcium lime (Hi‐Cal lime) amendments, with the former increasing Ca base saturation and the later increasing both Ca base saturation and soil pH. We hypothesized that positive benefits ascribed by BCSR practitioners are due to increasing soil pH, rather than increasing Ca levels, both of which occur after lime application. Thus, we conducted successive applications of gypsum or epsom (magnesium sulfate) with and without Hi‐Cal or dolomitic lime, to either increase or lower soil Ca:Mg ratio and pH in an Ohio‐based experiment over 6 yr and evaluated soil and yield responses in a corn (Zea mays L.)–soybean (Glycine max L.)–small grain rotation. Repeated applications of gypsum with and without Hi‐Cal lime significantly increased soil Ca:Mg ratio and repeated applications of epsom with and without dolomitic lime significantly decreased the soil Ca:Mg ratio. Crop yield was not affected by soil Ca:Mg ratio for any crop in any year. However, over the 6 yr of the study, corn yields were positively related to increases in soil pH. We conclude that balancing soil Ca and Mg levels did not impact corn or soybean yields but managing soil acidity remains a fundamental tool to improve crop yields.
Cysteine‐Selective Modification of Peptides and Proteins via Desulfurative C−C Bond Formation
Authors: Griffiths Rhys C. , Smith Frances R. , Li Diyuan , Wyatt Jasmine , Rogers David M. , Long Jed E. , Cusin Lola M. L. , Tighe Patrick J. , Layfield Robert , Hirst Jonathan D. , Müller Manuel M. , Mitchell Nicholas J.
Published: December 2022

The site‐selective modification of peptides and proteins facilitates the preparation of targeted therapeutic agents and tools to interrogate biochemical pathways. Among the numerous bioconjugation techniques developed to install groups of interest, those that generate C(sp3)−C(sp3) bonds are significantly underrepresented despite affording proteolytically stable, biogenic linkages. Herein, a visible‐light‐mediated reaction is described that enables the site‐selective modification of peptides and proteins via desulfurative C(sp3)−C(sp3) bond formation. The reaction is rapid and high yielding in peptide systems, with comparable translation to proteins. Using this chemistry, a range of moieties is installed into model systems and an effective PTM‐mimic is successfully integrated into a recombinantly expressed histone.
Enantioselective Desymmetrization Triggered by Iminium‐Enamine Activation: Access to Complex Cyclohepta[b]indoles
Authors: Magham Lakshmi Revati , Thopate Satish B. , Samad Abdus , Chegondi Rambabu
Published: December 2022

The expeditious construction of complex molecules having multiple stereocentres is highly desirable in organic chemistry. In the present communication, we report the development of an organocatalytic asymmetric desymmetrization of prochiral enal‐tethered cyclohexadienones via the C3‐selective Friedel−Crafts alkylation of indoles triggered by LUMO‐lowering iminium activation/HOMO‐raising enamine activation. The reaction provides access to bicyclic enones, which further undergo acid‐mediated intramolecular annulation from C2‐position to afford highly strained cyclohepta[b]indoles with five contiguous stereocentres and three new C−C bonds in excellent enantioselectivity and diastereoselectivity.
Specific Signal Enhancement on an RNA‐Protein Interface by Dynamic Nuclear Polarization
Authors: Aladin Victoria , Sreemantula Arun K. , Biedenbänder Thomas , Marchanka Alexander , Corzilius Björn
Published: December 2022

Sensitivity and specificity are both crucial for the efficient solid‐state NMR structure determination of large biomolecules. We present an approach that features both advantages by site‐specific enhancement of NMR spectroscopic signals from the protein‐RNA binding site within a ribonucleoprotein (RNP) by dynamic nuclear polarization (DNP). This approach uses modern biochemical techniques for sparse isotope labeling and exploits the molecular dynamics of 13C‐labeled methyl groups exclusively present in the protein. These dynamics drive heteronuclear cross relaxation and thus allow specific hyperpolarization transfer across the biomolecular complex's interface. For the example of the L7Ae protein in complex with a 26mer guide RNA minimal construct from the box C/D complex in archaea, we demonstrate that a single methyl‐nucleotide contact is responsible for most of the polarization transfer to the RNA, and that this specific transfer can be used to boost both NMR spectral sensitivity and specificity by DNP.
Coordination and Stabilization of a Lithium Ion with a Silylene
Authors: Nazish Mohd , Legendre Christina M. , Graw Nico , Herbst‐Irmer Regine , Stalke Dietmar , Sankar Dutta Siddharth , Lourderaj Upakarasamy , Roesky Herbert W.
Published: December 2022

Herein, we report the stabilization of lithium‐ion as the source of lithium to use as a trans‐metalation reagent [{PhC(NtBu)2Si(tBu)Li}2I(tBuN)2CPh] (1). The reaction of 3 equivalents of the LSitBu (L=PhC(NtBu)2) and lithium iodide at low temperature leads to a silylene stabilized lithium‐ion with an additional coordination of amidinate ligand. Compound 1 shows two four membered and one six membered ring as confirmed by QTAIM calculations. Whereas the reaction of the LSiCl with 1.5 equivalents of carbodiimide (CyN)2C at room temperature affords compound [PhC(NtBu)2Si(Cl)(NCy)2NCy] (2) with the CN2SiN2C skeleton containing silicon as a central atom. Both the compounds were fully characterized by NMR, mass spectrometry, X‐ray crystallographic analysis, and quantum mechanical calculations.
4‐O‐Substituted Glucuronic Cyclophellitols are Selective Mechanism‐Based Heparanase Inhibitors
Authors: Borlandelli Valentina , Armstrong Zachary , Nin‐Hill Alba , Codée Jeroen D. C. , Raich Lluís , Artola Marta , Rovira Carme , Davies Gideon J. , Overkleeft Herman S.
Published: December 2022

Degradation of the extracellular matrix (ECM) supports tissue integrity and homeostasis, but is also a key factor in cancer metastasis. Heparanase (HPSE) is a mammalian ECM‐remodeling enzyme with β‐D‐endo‐glucuronidase activity overexpressed in several malignancies, and is thought to facilitate tumor growth and metastasis. By this virtue, HPSE is considered an attractive target for the development of cancer therapies, yet to date no HPSE inhibitors have progressed to the clinic. Here we report on the discovery of glucurono‐configured cyclitol derivatives featuring simple substituents at the 4‐O‐position as irreversible HPSE inhibitors. We show that these compounds, unlike glucurono‐cyclophellitol, are selective for HPSE over β‐D‐exo‐glucuronidase (GUSB), also in platelet lysate. The observed selectivity is induced by steric and electrostatic interactions of the substituents at the 4‐O‐position. Crystallographic analysis supports this rationale for HPSE selectivity, and computer simulations provide insights in the conformational preferences and binding poses of the inhibitors, which we believe are good starting points for the future development of HPSE‐targeting antimetastatic cancer drugs.
Reasons for refusal of the human papillomavirus vaccine among young cancer survivors
Authors: Cherven Brooke , Klosky James L. , Keith K. Elizabeth , Hudson Melissa M. , Bhatia Smita , Landier Wendy
Published: December 2022

Background

Cancer survivors are at risk for developing subsequent human papillomavirus (HPV)–related malignancies. HPV vaccination rates among survivors remain low, and the reasons for refusal of the vaccine are unclear in this population.

Methods

The authors conducted a secondary analysis of data from an open‐label clinical trial evaluating the immunogenicity and safety of the HPV vaccine among vaccine‐naive cancer survivors who were 9–26 years old and 1–5 years from the completion of their cancer treatment. Survivors/parents who declined trial participation were asked their reasons for declining. Refusal reasons were categorized, and multivariable logistic regression models were developed to identify associations between survivor characteristics and primary refusal reasons.

Results

Among the 301 survivors who refused participation in the clinical trial, 215 (71.4%) refused for reasons related to the HPV vaccine. Reasons for vaccine‐related refusal included safety concerns, vaccine hesitancy/disinterest, external influences, vaccine‐related information deficits, and health beliefs/family decisional processes. Compared with males, females were more likely to refuse for reasons related to health beliefs/family decisional processes (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.12–3.93; p = .022) and were less likely to do so because of external influences (OR, 0.43; 95% CI, 0.19–0.92; p = .035). Survivors approached about participation during the latter years of the trial were more likely to refuse because of safety concerns (OR, 3.33; 95% CI, 1.55–7.69; p = .003).

Conclusions

Cancer survivors refused participation in an open‐label trial evaluating the immunogenicity and safety of the HPV vaccine primarily because of vaccine‐related concerns that were unrelated to the research study. Many of these concerns are potentially addressable by health care providers using evidence‐based messages tailored to the cancer survivor population.
Anti‐cancer effect of entacaponeon esophageal cancer cells via apoptosis induction and cell cycle modulation
Authors: Ramedani Fahimeh , Jafari Seyyed Mehdi , Saghaeian Jazi Marie , Mohammadi Zeinab , Asadi Jahanbakhsh
Published: December 2022

Background

Esophageal cancer (EC) is the sixth leading cause of cancer‐related death, despite many advances in treatment, the survival of patients still remains poor. In recent years, the N6‐methyladenosine (m6A) has been introduced as one of the most important modifications at the epitranscriptome level, with an important role in the mRNA regulation in various diseases, such as cancers. The m6A is regulated by different factors, including FTO as a demethylase. The m6A modification, especially through FTO overexpression has an oncogenic role in different cancer types such as EC. Recent studies showed that entacapone, a catechol‐o‐methyl transferase (COMT) inhibitor currently applied for Parkinson's disease, can inhibit FTO enzyme.

Aims

In this study, we aimed to investigate the effect of entacapone as an FTO inhibitor on the m6A level and also apoptosis and cell cycle response in KYSE‐30 and YM‐1 of esophageal squamous cancer cell (ESCC) lines.

Methods

Cell toxicity and IC50 of entacapone were evaluated using The MTT assay in YM‐1 and KYSE‐30 cells. Cells were treated into two groups: DMSO (control) and entacapone (mean IC50). Total RNA was extracted, and m6A levels were measured via the ELISA method. Subsequently, the apoptosis and cell cycle dys‐regulation were detected by annexin‐V‐FITC/PI staining and PI staining via flow cytometry.

Results

Entacapone has the cytotoxicity effect on both esophageal cancer cell lines compared to normal PBMC cells. As well, entacapone treatment (140 μM) can induce apoptosis (KYSE‐30: 50%. YM‐1:22.6%) and has a modulatory effect on cell cycle progression in both YM‐1 and KYSE‐30 cells (p‐value<.05). However, no significant difference in the m6A concentration was observed.

Conclusion

Our findings suggested that entacapone has the inhibitory effect on ESCC cell lines through induction of the apoptosis and modulation of the cell cycle without toxicity on the normal PBMC.
Human activity recognition based on integration of multilayer information of convolutional neural network architecture
Authors: Kushwaha Arati , Srivastava Prashant , Khare Ashish
Published: December 2022

Human activity recognition (HAR) has gained researcher's interest due to its increasing demand in automated monitoring applications. Development of efficient HAR algorithm is still an open research area due to the challenges like inter and intra‐class variations, diversity in lighting conditions, view point changes, and complex object motions. Convolutional neural network (CNN) based methods have achieved significant improvement in HAR. However, CNN implementations have drawback that it require a lot of computational resources due to the use of large number of learnable parameters. To overcome this drawback, we propose a simple and computationally efficient deep CNN architecture using multi‐layer information fusion for HAR. In this study, we explore the impact of information fusion at intermediate layers of the network, as each convolutional layer of the network hierarchically extracts information at different level of abstraction of the objects from the video frames. In this work, first we designed a simple and computationally efficient deep CNN architecture and then we introduce a feature fusion strategy to integrate the complementary information of intermediate layers to the layer of the proposed CNN architecture. The proposed architecture is fine‐tuned and trained from scratch with raw RGB data. Softmax classifier is used at the last layer of network for activity classification. Benefits of the proposed architecture over standard deep learning architectures is it's high computational efficiency and reduced requirement of computational resources. To prove the effectiveness of the proposed method, we performed several extensive experiments on publically available datasets. The experimental results of the proposed method have demonstrated its superiority over other existing state‐of‐the‐art methods.
Ultra‐Thin Layer Inside Separator Deposited by Spray Pyrolysis Using Methylaluminoxane Solution
Authors: Imai Masato , Kubota Tadahiko , Miyazawa Atsushi , Aoki Masahiro , Mori Haruna , Komaki Yuta , Yoshino Kenji
Published: December 2022

Depositions are conducted on monolayer porous membrane at 50 °C by spray pyrolysis using methylaluminoxanes diluted with N‐methylpyrrolidone. The solution penetrates the film during spraying and the ultra‐thin layers are deposited on the side wall of internal pores. It is suggested that these layers are fine polycrystalline of Al2O3. In the obtained film, most of the pores are exposed on the surface and there is no increase in film thickness. Further, the ionic conductivity is the same as that of the received film, and the thermal stability is improved. This method can be an effective technique for improving the function of the separator used in the lithium‐ion batteries.
Reduced early response to SARS‐CoV2 vaccination in people with type 1 and type 2 diabetes, a 6 months follow‐up study: The CoVaDiab study I
Authors: D’Onofrio Luca , Fogolari Marta , Amendolara Rocco , Siena Antonio , De Fata Riccardo , Davini Flavio , Coraggio Lucia , Mignogna Carmen , Moretti Chiara , Maddaloni Ernesto , Angeletti Silvia , Buzzetti Raffaella
Published: December 2022

Introduction

Diabetes mellitus worsens the prognosis of SARS‐CoV‐2 infection, and vaccination has been the major tool for reducing the risk of hospitalisation, and mortality.

The primary aim of this study was to evaluate the response to the SARS‐CoV‐2 vaccine in subjects with diabetes and controls. Differences between type 1 (T1D) and type 2 (T2D) diabetes and clinical determinants of vaccination response were also evaluated.

Methods

128 subjects with diabetes (60 with T1D and 62 with T2D) and 202 subjects acting as controls who completed a full vaccination cycle with two doses of mRNA vaccine were enroled. People with previous SARS‐CoV‐2 infection were excluded. Antibodies (Ab) directed against the spike protein of the SARS‐CoV‐2 were evaluated at one and 6 months after vaccination.

Results

In the whole cohort, the Ab level was higher among women than in men (p = 0.011) and negatively correlated with age (rho = −0.155, p = 0.005). Subjects with diabetes showed decreased levels of Ab after one month compared to controls (1217[747–1887]BAU/mL vs. 1477[942–2556]BAU/mL, p = 0.002), even after correction for age and gender (p = 0.002). No difference was found between subjects with T1D and T2D. After 6 months, antibody levels significantly decreased in people with and without diabetes, with no differences between groups, although some subjects were lost at follow‐up. In subjects with diabetes, only a significant correlation was found between Ab level and renal function (rho 0.190, p = 0.042).

Conclusions

Both T1D and T2D are associated with a reduced early response to vaccination. The serum concentration of Ab significantly reduced over time in both groups, highlighting the relevance of vaccination boosters independently of the presence of diabetes.
Base41: A proposal for printable encoding of bit strings
Authors: Botta Marco , Cavagnino Davide
Published: December 2022

This article presents the proposal of a novel encoding method for representing binary data in printable format. The encoding procedure reversibly transforms binary strings into printable letter sequences using a mapping from bit strings to an alphabet of 41 symbols taken from a subset of the English uppercase and lowercase letters. The decoding process reversibly recovers an original bit string from the encoded printable string. The encoding and decoding algorithms along with the properties of this coding are examined and discussed. In particular, the use of only URL‐safe and clearly visually distinguishable characters is emphasized.
Safety and tolerability of short‐term infusions of intravenous lacosamide in pediatric patients with epilepsy: An open‐label, phase 2/3 trial
Authors: Farkas Mark Kristof , Beller Cynthia , Bozorg Ali , McClung Carrie , Roebling Robert , Yates Tanisia , Yuen Nancy , Makedonska Iryna
Published: December 2022

Objective

The objective of this study is to evaluate the safety and tolerability of intravenous (IV) lacosamide infusion in patients aged ≥1 month to <17 years with epilepsy.

Methods

This Phase 2/3 open‐label trial (EP0060; NCT02710890) enrolled patients in two age cohorts (cohort 1: ≥8 to <17 years; cohort 2: ≥1 month to <8 years). Eligible patients were receiving oral lacosamide as adjunctive treatment or monotherapy (in an open‐label long‐term trial or by prescription) or were not receiving lacosamide before enrolment. Patients initiated IV lacosamide (2‐12 mg/kg/day or 100‐600 mg/day; 15‐60 minutes infusion) as a replacement for oral lacosamide or as adjunctive treatment. The primary outcomes were treatment‐emergent adverse events (TEAEs) and discontinuations due to TEAEs.

Results

In total, 103 patients were enrolled and completed the trial; 55 patients were included in cohort 1 (≥8 to <17 years), 48 in cohort 2 (≥1 month to <8 years). During the 4 weeks before screening, 74 (71.8%) patients had focal seizures, 12 (11.7%) had generalized seizures, and two (1.9%) had unclassified seizures. Most patients (74 [71.8%]) initiated lacosamide as adjunctive IV treatment. The mean overall duration of exposure to IV lacosamide was 1.18 days. Seventy‐nine (76.7%) patients had one IV lacosamide infusion, 20 (19.4%) had two, one (1.0%) had three, and three (2.9%) had 10 infusions. Overall, five (4.9%) patients had a total of seven TEAEs. The only TEAEs reported in two or more patients were increased blood triglycerides (two [1.9%]). No serious or severe TEAEs were reported, and no patients discontinued due to TEAEs. No TEAEs were considered drug‐related by the investigator. No consistent or clinically relevant treatment‐related changes from baseline were observed for hematology, clinical chemistry parameters, vital signs, or 12‐lead electrocardiograms.

Significance

IV lacosamide was generally well tolerated in pediatric patients (≥1 month to <17 years) with epilepsy, and no new safety concerns were identified.
Is time‐restricted eating (8/16) beneficial for body weight and metabolism of obese and overweight adults? A systematic review and meta‐analysis of randomized controlled trials
Authors: Huang Lu , Chen Yan , Wen Shu , Lu Danhua , Shen Xiaoyang , Deng Hongxia , Xu Liangzhi
Published: December 2022

Time‐restricted eating (TRE) is a new therapeutic strategy for the management of weight loss and dysmetabolic diseases. At present, TRE (8/16, 8 h eating:16 h fasting) is the most common form of TRE. Therefore, this meta‐analysis included randomized controlled trials (RCTs) on TRE (8/16) in overweight and obese adults to determine its impact on body weight and metabolism. Articles reviewed from PubMed, Ovid MEDLINE, Embase, and Cochrane Central Register for the relevant RCTs that compared TRE (8/16) to non‐TRE in overweight and obese adults. Eight RCTs were included in this meta‐analysis. Participants following TRE (8/16) showed significant body weight reduction (mean difference [MD]: −1.48 kg, 95% confidence interval [CI]: −2.53 to −0.44) and fat mass reduction (MD: −1.09 kg, 95% CI: −1.55 to −0.63). There was no significant difference in lean mass change with TRE intervention (MD: −0.48 kg, 95% CI: −1.02 to 0.05, p = .08, I2 = 41%). The energy restriction and early TRE (eTRE) subgroups resulted in greater weight loss. TRE (8/16) showed beneficial effects on the homeostatic model assessment of insulin resistance (HOMA‐IR, MD: −0.32, 95% CI: −0.59 to −0.06), but had no significant effect on other parameters of glucose metabolism and lipid profiles. In conclusion, TRE (8/16), especially eTRE, or in combination with caloric intake restriction, is a potential therapeutic strategy for weight control in overweight and obese adults. TRE (8/16) also reduced HOMA‐IR; therefore, it may have a positive effect on glucose metabolism.
Investigation of the influence of Pt/C percentage and humidity on the voltage decay rate of proton exchange membrane fuel cell
Authors: Mathan C. , Karthikeyan P. , Dineshkumar P. , Thanarajan K.
Published: December 2022

Voltage degradation is the main parameter that determines the effective usable life of a fuel cell, here the influence of Pt/C% and relative humidity (RH%) on the voltage decay rate of a fuel cell is experimentally evaluated and reported. This study implements a stress test with frequent interrupts of purging for determining the durability of the fuel cells. In the course of the 1456 h stress test for each membrane electrode assembly (MEA), the polarization curve and electrochemical impedance spectroscopy (EIS) were measured. The experimental results make it evident that the lowest voltage degradation was 6 µV/h for MEA with 40% Pt/C tested under 70% RH while the highest was 183 µV/h recorded for MEA with 20% Pt/C tested under 90% RH. From EIS results, the ohmic resistance increased for all the tested MEAs, which is also reflected in the performance degradation. Field emission scanning electron microscopy images also indicate the delamination of MEA layers which in turn increases the electron transfer resistance. So, the decisive factors for the fuel cell performance degradation were flooding, catalyst surface contamination, and delamination of MEA layers due to repeated mechanical and chemical stresses.
Feasibility of ipsilateral elective neck irradiation of levels Ib and II without level III in patients with node‐negative sinonasal squamous cell carcinoma
Authors: Liu Qian , Lun Lixin , Sun Meng , Wang Zekun , Huang Xiaodong , Chen Xuesong , Wang Jingbo , Zhang Jianghu , Qu Yuan , Wang Kai , Wu Runye , Zhang Ye , Xiao Jianping , Yi Junlin , Luo Jingwei
Published: December 2022

Background

The necessity of level III irradiation in patients with node‐negative advanced sinonasal squamous cell carcinoma (SNSCC) is unclear.

Methods

Seventy‐eight patients with advanced SNSCC were included. Survival rates were estimated and compared between treatment groups.

Results

Twenty‐five patients received ipsilateral levels Ib and II irradiation (group 1) and 53 patients received ipsilateral levels Ib and II plus level III irradiation (group 2). The median follow‐up time was 75.56 months. Five‐year survival rates (regional relapse‐free survival, overall survival, local relapse‐free survival, and distant metastasis‐free survival) were similar between groups 1 and 2 (all p > 0.05). Irradiation doses to the thyroid and larynx were significantly lower in group 1 than in group 2.

Conclusions

Ipsilateral irradiation of levels Ib and II neck provides similar regional control and results as irradiation of these levels plus level III, with lower irradiation doses to normal neck tissue, in patients with node‐negative advanced SNSCC.
Long telomeres at baseline and male sex are main determinants of telomere loss following chemotherapy exposure in lymphoma patients
Authors: Derenzini Enrico , Gueli Angela , Risso Alessandra , Bruna Riccardo , Gottardi Daniela , Cignetti Alessandro , Pileri Stefano , Avvedimento Enrico V. , Tarella Corrado
Published: December 2022

Although chemotherapy (CHT) exposure is an established cause of telomere attrition, determinants of telomere length (TL) dynamics after chemotherapy are poorly defined. In this study, we analyzed granulocyte telomere dynamics in 34 adult lymphoma patients undergoing first‐line CHT. TL was measured by southern blot at each CHT cycle and after 1 year from CHT completion. Median age was 59 yrs (range 22–77). Median number of CHT cycles was 6 (range 3–6). The majority of patients (79%, n = 27) experienced TL shortening following CHT exposure. Mean telomere loss was 673 base pairs (bp) by cycle 6. Telomere shortening was an early event as 87% of the total telomere loss (mean 586 bp) occurred by the end of cycle 3, with no significant recovery after 1 year. A significant correlation was observed between baseline TL and total or fractional telomere loss (p < 0.001), with telomere shortening by cycle 3 observed predominantly in male patients with long telomeres at pre‐treatment evaluation. Stratifying the analysis by gender and age only young women (<51 years of age) did not show significant telomere shortening following chemotherapy exposure. These findings indicate that gender and baseline TL are major determinants of TL dynamics following chemotherapy exposure in lymphoma patients.
Effect of low thermal conductivity wick on the performance of compact loop heat pipe
Authors: Veeramachaneni Sireesha , Pisipaty Srinivas K. , Brusly Solomon Arulanantham , Vadisa Venkata C. , Vedula Dharma R. , Srinivasa Rao Devisetty
Published: December 2022

The existing work deals with the evaluation of compact loop heat pipe by means of a low thermal conductivity sintered chrysotile wick to avoid large heat leaks as of the evaporator to the compensation chamber. Accordingly, a wick with low thermal conductivity (0.068–0.098 W/mK) chrysotile powder of a mean particle diameter of 3.4 μm is fabricated through sintering. Nine chrysotile wicks are sintered with different compositions of binders (bentonite and dextrin) and pore‐forming agent NaCl at sintering temperatures of 500°C, 600°C, and 700°C with a sintering time of 30 min. The wick properties, for instance, porosity, permeability, wettability, and capillary rise are studied owing to sintering temperature. Consequently, it is observed that a pure chrysotile powdered wick at a sintering temperature of 600°C exhibits a high porosity of 61.8% with permeability 1.04 × 10−13 m2 and a capillary rise of 4.5 cm in 30 s and is considered optimal. This optimal wick is used for performance evaluation in compact loop heat pipe and a decrease of 36.1% in thermal resistance is found when compared with copper mesh wick in a loop heat pipe. The lowermost thermal resistance originates to be 0.147 K/W at 120 W with wall temperature 57.7°C. This indicates that loop heat pipe with sintered chrysotile wick can operate at lower heat loads efficiently when compared with copper mesh wick and as heat load increases a chance of dry out condition occurs. The highest evaporative heat transfer coefficient obtained is 65.7 kW/m2 K at a minimum heat load.
Exosomal miR‐205‐5p derived from periodontal ligament stem cells attenuates the inflammation of chronic periodontitis via targeting XBP1
Authors: Kang Lixun , Miao Yibin , Jin Ying , Shen Siyu , Lin Xiaoping
Published: December 2022

Introduction

Chronic periodontitis (CP) is an inflammatory periodontal disease with high incidence and complex pathology. This research is aimed to investigate the function of exosomal miR‐205‐5p (Exo‐miR‐205‐5p) in CP and the underlying molecular mechanisms.

Method

Exo‐miR‐205‐5p was isolated from miR‐205‐5p mimics‐transfected periodontal ligament stem cells (PDLSCs), and subsequently cocultured with lipopolysaccharide (LPS)‐induced cells or injected into LPS‐treated rats. The mRNA expression of inflammatory factors and Th17/Treg‐related factors were measured by quantitative real‐time PCR. The contents of inflammatory factors and the percentages of Th17/Treg cells were measured by enzyme‐linked immunosorbent assay and flow cytometry, respectively. Besides, the target relation between miR‐205‐5p and X‐box binding protein 1 (XBP1) was explored.

Results

MiR‐205‐5p was downregulated in LPS‐induced PDLSCs and corresponding exosomes. Exo‐miR‐205‐5p inhibited inflammatory cell infiltration, decreased the production of TNF‐α, IL‐1β, and IL‐6, and decreased the percentage of Th17 cells in LPS‐treated rats. In addition, XBP1 was a target of miR‐205‐5p. Overexpression of XBP1 weakened the effects of Exo‐miR‐205‐5p on inhibiting inflammation and regulating Treg/Th17 balance in LPS‐induced cells.

Conclusions

Exo‐miR‐205‐5p derived from PDLSCs relieves the inflammation and balances the Th17/Treg cells in CP through targeting XBP1.
Epitope identification for p53R273C mutant
Authors: Zhang Jian , Liu Minglu , Chen Yin , Zhou Zishan , Wang Ping , Yu Yang , Jiao Shunchang
Published: December 2022

Background

With the rise of immunotherapy based on cancer neoantigen, identification of neoepitopes has become an urgent problem to be solved. The TP53 R273C mutation is one of the hotspot mutations of TP53, however, the immunogenicity of this mutation is not yet clear. The aim of this study is to identify potential epitopes for p53R273C mutant.

Methods

In this study, bioinformatic methods, peptide exchange assay, and peptide‐immunized human leukocyte antigen (HLA) transgenic mouse model were used to explore the immunogenicity of this mutation.

Results

Peptides with higher affinity to common HLA‐A alleles (A*11:01, A*02:01) were discovered by computational prediction. All the 8–11 mer peptides contain the mutation site were synthesized and soluble peptides were used in the peptide exchange assay. However, the exchange efficiencies of these predicted peptides to HLAs were lower. Fortunately, other peptides with higher exchange efficiency were discovered. Then, the immunogenicity of these peptides was validated with the HLA‐A2 transgenic mice model.

Conclusion

We identified three potential neoepitopes of p53R273C for HLA‐A*02:01, one potential neoepitope for HLA‐A*11:01 and no neoepitope for HLA‐A*24:02.
Shifting incidence and survival of epithelial ovarian cancer (1995‐2014): A SurvMark‐2 study
Authors: Cabasag Citadel J. , Arnold Melina , Rutherford Mark , Ferlay Jacques , Bardot Aude , Morgan Eileen , Butler John , O'Connell Dianne L. , Nelson Gregg , Høgdall Claus , Schnack Tine , Gavin Anna , Elwood Mark , Hanna Louise , Gourley Charlie , De Prithwish , Saint‐Jacques Nathalie , Mørch Lina Steinrud , Woods Ryan R , Altman Alon D. , Sykes Peter , Cohen Paul A. , McNally Orla , Møller Bjørn , Walsh Paul , Morrison David S. , Bray Freddie , Soerjomataram Isabelle
Published: December 2022

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom). Data on invasive EOC diagnosed in women aged 15 to 99 years during 1995 to 2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15‐64 and 65‐99 years). Net survival (NS) was estimated by subtype, age group and 5‐year period using Pohar‐Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995 and 2014 among women aged 65 to 99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma “not otherwise specified” with estimates ranging between 4.4% and 7.4% in women aged 15 to 64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20‐year study period in all countries with 5‐year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival.
Twelve Months of Denosumab and/or Alendronate Is Associated With Improved Bone Fatigue Life, Microarchitecture, and Density in Ovariectomized Cynomolgus Monkeys
Authors: Haider Ifaz T. , Loundagin Lindsay L. , Sawatsky Andrew , Kostenuik Paul J. , Boyd Steven K. , Edwards W. Brent
Published: December 2022

Prolonged use of antiresorptives such as the bisphosphonate alendronate (ALN) and the RANKL inhibitor denosumab (DMAb) are associated with rare cases of atypical femoral fracture (AFF). The etiology of AFF is unclear, but it has been hypothesized that potent osteoclast inhibitors may reduce bone fatigue resistance. The purpose of this study was to quantify the relationship between antiresorptive treatment and fatigue life (cycles to failure) in bone from ovariectomized cynomolgus monkeys. We analyzed humeral bone from 30 animals across five treatment groups. Animals were treated for 12 months with subcutaneous (sc) vehicle (VEH), sc DMAb (25 mg/kg/month), or intravenous (iv) ALN (50 μg/kg/month). Another group received 6 months VEH followed by 6 months DMAb (VEH‐DMAb), and the final group received 6 months ALN followed by 6 months DMAb (ALN‐DMAb). A total of 240 cortical beam samples were cyclically tested in four‐point bending at 80, 100, 120, or 140 MPa peak stress. High‐resolution imaging and density measurements were performed to evaluate bone microstructure and composition. Samples from the ALN (p = 0.014), ALN‐DMAb (p = 0.008), and DMAb (p < 0.001) groups illustrated higher fatigue‐life measurements than VEH. For example, at 140 MPa the VEH group demonstrated a median ± interquartile range (IQR) fatigue life of 1987 ± 10593 cycles, while animals in the ALN, ALN‐DMAb, and DMAb groups survived 9850 ± 13648 (+395% versus VEH), 10493 ± 16796 (+428%), and 14495 ± 49299 (+629%) cycles, respectively. All antiresorptive treatment groups demonstrated lower porosity, smaller pore size, greater pore spacing, and lower number of canals versus VEH (p < 0.001). Antiresorptive treatment was also associated with greater apparent density, dry density, and ash density (p ≤ 0.03). We did not detect detrimental changes following antiresorptive treatments that would explain their association with AFF. In contrast, 12 months of treatment may have a protective effect against fatigue fractures. © 2022 American Society for Bone and Mineral Research (ASBMR).
Effect of gluten on the digestive tract and fat body of Telodeinopus aoutii (Diplopoda)
Authors: Błaszczyk Florentyna , Sosinka Agnieszka , Wilczek Grażyna , Student Sebastian , Rost‐Roszkowska Magdalena
Published: December 2022

Adult specimens or larvae of invertebrates used as food for vertebrates are often maintained close to gluten so they might become vectors for cereal proteins. However, the tissues and internal organs can respond differently in animals with different feeding habits. The midgut epithelium might be a first and sufficient barrier preventing uptake and effects of gluten on the whole body, while the fat body is the main organ that accumulates different xenobiotics. Good models for such research are animals that do not feed on gluten‐rich products in their natural environment. The project's goal was to investigate alterations in the midgut epithelium and fat body of the herbivorous millipede Telodeinopus aoutii (Diplopoda) and analyze cell death processes activated by gluten. It enabled us to determine whether changes were intensified or reversed by adaptive mechanisms. Adult specimens were divided into control and experimental animals fed with mushrooms supplemented with gluten and analyzed using transmission electron microscopy, flow cytometry, and confocal microscopy. Two organs were isolated for the qualitative and quantitative analysis: the midgut and the fat body. Our study of the herbivorous T. aoutii which does not naturally feed on gluten containing diet showed that continuous and prolonged gluten feeding activates repair processes that inhibit the processes of cell death (apoptosis and necrosis) and induce an increase in cell viability.
Use of probiotic yeasts with biocontrol activity for fermentation of ewe's milk
Authors: Fernández‐Pacheco Pilar , Ramos Monge Inés María , Poveda Justa María , Díaz‐Maroto M. Consuelo , Arévalo‐Villena María
Published: December 2022

BACKGROUND

There are sufficient scienctific studies that support the benefit that fermented dairy products produce in those who consume them. Traditionally, cow's milk has been the most commonly used milk but there is a growing interest in the development of new dairy products, substituting cow's milk with milk from other sources, as well as in the use of microorganisms in fermentation to replace artificial preservatives or treatments that may affect the chemical and organoleptic characteristics of the product. For these reasons, the aim of the present work was to understand the behavior of five potential probiotic yeasts during the fermentation of ewe's milk and to consider their potential use as biocontrol agents.

RESULTS

Saccharomyces cerevisiae 3 and Hanseniaspora osmophila 1056 provided the most promising kinetic parameters in the different salt, temperature and pH conditions tested in their technological characterization. The profiles of organic acids and volatile compounds after the fermentation period was noteworthy for contributing to the final aroma of the dairy product. Sensory analysis revealed the sour taste of all samples, and S. cerevisiae 3, Lachancea thermotolerans 1039, and H. osmophila 1056 stood out for an accentuated cheese flavor. In addition, all strains showed biocontrol activity; they reduced the mycelium of the mycotoxigenic molds.

CONCLUSION

Saccharomyces cerevisiae 3 and H. osmophila 1056 could be inoculated along with bacterial starters to provide a functional fermented beverage with improved flavor. These strains also have an added value as they act as biocontrol agents. © 2022 Society of Chemical Industry.
Exploiting Desired Phosphor‐In‐Glass for All‐Inorganic Solid‐State White Illumination
Authors: Bao Shuyang , Liang Yueyuan , Zhao Cong , Wang Luhan , Liang Xiaojuan , Xiang Weidong
Published: December 2022

Solid‐state white lighting applications with high brightness, low power consumption and long operating life have gradually dominated the modern industrial illumination market. For applications in white light‐emitting diodes (WLEDs) and white‐lighting laser diodes (WLDs), Phosphor‐in‐Glass (PiG), owing to its facile process, high efficiency and excellent chromaticity tunability, stands out as an optimal choice among various types of color converters. Currently, research in yellow‐emitting Y3Al5O12:Ce3+ (YAG: Ce) phosphors combined with different glass system has reached a mature stage and the poor illumination is a major bottleneck. Moreover, to realize high‐quality white lighting, exploiting full‐color PiGs is of great importance for its commercialization. Herein, the multicolour PiGs their successfully obtained by deliberately matching different color‐emitting phosphors with the glass matrix. Glass composition selection rules for specific phosphors their proposed based on investigations of glass protection mechanism and the corrosion reaction between phosphors and glass matrix. In addition, an astonishing YAG: Ce PiG phenomenon (zero thermal quenching) is founded and discussed. As for practical applications, high‐quality 5‐W chip‐on‐board (COB) WLEDs their constructed by utilizing simple matches of colorful PiGs. Assembled WLDs modules also rendered a high‐efficiency and stable lighting source. These results dramatically inspire the development of high‐quality solid‐state white lighting applications.
Synergistic Effects of Surface Ligand Engineering and Double Matrices Protecting Enable Ultrastable and Highly Emissive Blue/Cyan Perovskite Nanocrystal Films for Multifunctional Applications
Authors: Hu Xiaobo , Xu Yanqiao , Wang Jiancheng , Ma Jiaxin , Wang Lianjun , Jiang Wan
Published: December 2022

Perovskite nanocrystals (NCs) have attracted considerable attention because of the extraordinary optoelectronic properties, making them promising candidates for lighting and display applications. However, the emissive efficiency and stability of blue/cyan‐emitting NCs lag far behind other color emissive perovskites, which greatly restrict their practical application. Herein, a feasible strategy is proposed for synthesizing highly luminescent and stable CsPbClxBr3−x NCs by the didodecyldimethylammonium bromide (DDAB) ligand‐assisted post‐treatment. The prepared DDAB‐CsPbCl0.8Br2.2 and DDAB‐CsPbCl2.0Br1.0 NCs exhibit bright cyan and blue emission, respectively, and their quantum yields are significantly enhanced from 12.2% and 7.5% to 83.1% and 75.3% owing to the obvious decrease of surface defects by the ligand‐exchange and halogen‐compensation mechanisms. The outstanding fluorescence properties are almost remained by grafting perovskite NCs onto the surface of SiO2 nanospheres. Notably, the ultrahigh water‐stability is realized after encapsulating the composite nanospheres into polystyrene‐polyisoprene‐polystyrene (SIS) film, which is benefit from the triple protection of DDA+ cations, SiO2 nanospheres and SIS copolymers. The fabricated SiO2@DDAB‐CsPbCl2.0Br1.0/SIS film is assembled into an white light emitting diode with high color rendering index of 83.4. Importantly, the blue/cyan‐emitting films display superb temperature‐sensitivity (30–160 °C) and favorable elasticity (1200% stretch rate), indicating their promising application prospect in flexible multifunctional photoelectric devices.
Emerging Trends of J‐Aggregate Formation within Polymeric Nanoassemblies
Authors: Hou Mingxuan , Liu Shiyong
Published: December 2022

J‐aggregation of dyes is a unique type of fluorescence aggregation phenomenon exhibiting bathochromic shift and higher absorption coefficient compared to the nonaggregated monomeric form. The incorporation of J‐aggregation dyes with polymeric nanoassemblies endows the former with enhanced microstructural stability and aqueous dispersity, as well as functional integration. Importantly, near‐infrared (NIR) polymeric J‐aggregates have been widely used for in vivo imaging and therapeutic functions. This perspective aims to discuss recent trends of J‐aggregate formation within polymeric nanoassemblies either covalently conjugating or physically encapsulating specific fluorescent dyes. Current challenges and future opportunities are also summarized for the subfield of polymeric J‐aggregates.
Automated detection of toxicophores and prediction of mutagenicity using PMCSFG algorithm
Authors: Schietgat Leander , Cuissart Bertrand , De Grave Kurt , Efthymiadis Kyriakos , Bureau Ronan , Crémilleux Bruno , Ramon Jan , Lepailleur Alban
Published: December 2022

Maximum common substructures (MCS) have received a lot of attention in the chemoinformatics community. They are typically used as a similarity measure between molecules, showing high predictive performance when used in classification tasks, while being easily explainable substructures. In the present work, we applied the Pairwise Maximum Common Subgraph Feature Generation (PMCSFG) algorithm to automatically detect toxicophores (structural alerts) and to compute fingerprints based on MCS. We present a comparison between our MCS‐based fingerprints and 12 well‐known chemical fingerprints when used as features in machine learning models. We provide an experimental evaluation and discuss the usefulness of the different methods on mutagenicity data. The features generated by the MCS method have a state‐of‐the‐art performance when predicting mutagenicity, while they are more interpretable than the traditional chemical fingerprints.