bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative in vitro to in vivo extrapolation for developmental toxicity potency of valproic acid analogues
Authors: Chang Xiaoqing , Palmer Jessica , Lumen Annie , Lee Un Jung , Ceger Patricia , Mansouri Kamel , Sprankle Catherine , Donley Elizabeth , Bell Shannon , Knudsen Thomas B. , Wambaugh John , Cook Bethany , Allen David , Kleinstreuer Nicole
Published: May 2022

Background

The developmental toxicity potential (dTP) concentration from the devTOX quickPredict (devTOXqP) assay, a metabolomics‐based human induced pluripotent stem cell assay, predicts a chemical's developmental toxicity potency. Here, in vitro to in vivo extrapolation (IVIVE) approaches were applied to address whether the devTOXqP assay could quantitatively predict in vivo developmental toxicity lowest effect levels (LELs) for the prototypical teratogen valproic acid (VPA) and a group of structural analogues.

Methods

VPA and a series of structural analogues were tested with the devTOXqP assay to determine dTP concentration and we estimated the equivalent administered doses (EADs) that would lead to plasma concentrations equivalent to the in vitro dTP concentrations. The EADs were compared to the LELs in rat developmental toxicity studies, human clinical doses, and EADs reported using other in vitro assays. To evaluate the impact of different pharmacokinetic (PK) models on IVIVE outcomes, we compared EADs predicted using various open‐source and commercially available PK and physiologically based PK (PBPK) models. To evaluate the effect of in vitro kinetics, an equilibrium distribution model was applied to translate dTP concentrations to free medium concentrations before subsequent IVIVE analyses.

Results

The EAD estimates for the VPA analogues based on different PK/PBPK models were quantitatively similar to in vivo data from both rats and humans, where available, and the derived rank order of the chemicals was consistent with observed in vivo developmental toxicity. Different models were identified that provided accurate predictions for rat prenatal LELs and conservative estimates of human safe exposure. The impact of in vitro kinetics on EAD estimates is chemical‐dependent. EADs from this study were within range of predicted doses from other in vitro and model organism data.

Conclusions

This study highlights the importance of pharmacokinetic considerations when using in vitro assays and demonstrates the utility of the devTOXqP human stem cell‐based platform to quantitatively assess a chemical's developmental toxicity potency.
Docosahexaenoic acid may inhibit immune evasion of colorectal cancer cells through targeting immune checkpoint and immunomodulator genes and their controlling microRNAs
Authors: Fadaee Manouchehr , Abbasi Hajar , Maralbashi Sepideh , Baradaran Behzad , Shanehbandi Dariush , Dinevari Masood Faghih , Kazemi Tohid
Published: May 2022

Colorectal cancer is one of the major concerns in both developed and developing societies. Because of the serious side effects of the current treatments, novel therapy agents have been developed that target immune checkpoint and immunomodulatory molecules in the tumor environment. Therefore, this study investigates the effect of docosahexaenoic acid (DHA) fatty acid on the expression of immune checkpoint molecule, PD‐L1, and immunomodulatory molecules, CD47 and CD39, and their controlling miRNAs in the colorectal cancer cell lines. Human colorectal cell lines HT‐29 and Caco‐2 were treated with 100 μM DHA and 50 μM LA for 24 h under the normoxic and hypoxic conditions. Total RNA was extracted and the qRT‐PCR was performed to analyze the expression of the studied genes and miRNAs. The western blotting technique was also used for validation. The qRT‐PCR results showed that DHA treatment decreased the expression of the PD‐L1, CD47, and CD39 genes, but decreases these genes controlling miRNAs, mir‐424, mir‐133a, and mir‐142, respectively. Western blotting analysis demonstrated that PD‐L1 protein expression decreased after DHA treatment. LA administration had no inhibitory effect on the studied genes. This study showed that DHA may have anti‐cancer properties by downregulation of proteins involved in the immune evasion of colorectal tumors. DHA could be used as a potential immune checkpoint inhibitor for the treatment of colorectal cancers.
Comparative histomorphological analysis of elbow ligaments and capsule
Authors: Lühmann Paul , Kremer Thomas , Siemers Frank , Rein Susanne
Published: May 2022

This study aimed to compare the histomorphology of the elbow capsule and its ligaments to gain a better understanding of the clinically relevant biomechanical stabilization. Eleven human elbows were dissected including the joint capsule with its anterior (AJC) and posterior (PJC) parts, the annular ligament (AL), the radial collateral ligament (RCL) and the ulnar collateral ligament with its anterior (AUCL), posterior (PUCL) and transverse (TUCL) parts. Hematoxylin–Eosin and Elastica van Gieson as conventional histology stainings were applied to determine collagenous and elastic fiber arrangements in transmission and polarization light microscopy. The radial collateral ligament and the anterior part of the ulnar collateral ligament showed significantly more densely packed parallel fiber arrangement than the anterior joint capsule, the posterior joint capsule, and the posterior part of the ulnar collateral ligament (p < 0.02, respectively). The PUCL had significantly more mixed tight and loose parallel arrangements than the PJC, the annular ligament, the RCL, the AUCL and the transverse part of the ulnar collateral ligamentp < 0.02, respectively), while the PJC showed significantly more interlaced mixed tight and loose fiber arrangement than the AL, the RCL and the AUCL (p < 0.003, respectively). The AJC had a significantly higher amount of elastic fibers as compared to the AL, the RCL, the AUCL and the TUCL in fascicular regions (p < 0.04, respectively), while the AUCL had significantly lesser elastic fibers than the AJC and the PJC (p < 0.004, respectively). The densely packed parallel fiber arrangement and few elastic fibers of the AUCL, RCL, and AL indicate a strong biomechanically stabilizing function. The fiber arrangement of the PUCL and the TUCL with few elastic fibers support the medial elbow stabilization. Crimping and elastic fibers provide the viscoelasticity of the joint capsule.
Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity
Authors: Maity Debabrata , Oh Yujeong , Gremer Lothar , Hoyer Wolfgang , Magzoub Mazin , Hamilton Andrew D.
Published: May 2022

Two “hot segments” within an islet amyloid polypeptide are responsible for its self‐assembly, which in turn is linked to the decline of β‐cells in type 2 diabetes (T2D). A readily available water‐soluble, macrocyclic host, cucurbit[7]uril (CB[7]), effectively inhibits islet amyloid polypeptide (IAPP) aggregation through ion–dipole and hydrophobic interactions with different residues of the monomeric peptide in its random‐coil conformation. A HSQC NMR study shows that CB[7] likely modulates IAPP self‐assembly by interacting with and masking major residues present in the “hot segments” at the N terminus. CB[7] also prevents the formation of toxic oligomers and inhibits seed‐catalyzed fibril proliferation. Importantly, CB[7] recovers rat insulinoma cells (RIN‐m) from IAPP‐assembly associated cytotoxicity.
2‐O‐Acetyl‐3,4,5,6‐tetra‐O‐benzyl‐d‐myo‐inosityl diphenylphosphate: A new useful intermediate to inositol phosphate and phospholipids
Authors: Sangiorgio Sara , Cambò Mattia , Semproli Riccardo , Ubiali Daniela , Speranza Giovanna , Rabuffetti Marco
Published: May 2022

Inositol phosphates and inositol phospholipids are ubiquitous in biochemistry and play a central role in cell signaling and regulation events. For this reason, their synthesis has attracted widespread interest. This paper describes the preparation of a new optically active inositol phosphate derivative, 2‐O‐acetyl‐3,4,5,6‐tetra‐O‐benzyl‐d‐myo‐inosityl diphenylphosphate (6), and its characterization by spectroscopic methods. Compound (6) represents a useful intermediate for the preparation of inositol phosphate and phospholipids, in particular of glycerophosphoinositol (GPI), a natural anti‐inflammatory agent.
Comprehensive Theoretical View of the [Cu2O2] Side‐on‐Peroxo‐/Bis‐μ‐Oxo Equilibria
Authors: Stańczak Agnieszka , Chalupský Jakub , Rulíšek Lubomír , Straka Michal
Published: May 2022

Coupled binuclear copper (CBC) sites are employed by many metalloenzymes to catalyze a broad set of biochemical transformations. Typically, the CBC catalytic sites are activated by the O2molecule to form various [Cu2O2] reactive species. This has also inspired synthesis and development of various biomimetic inorganic complexes featuring the CBC core. From theoretical perspective, the [Cu2O2] reactivity often hinges on the side‐on‐peroxo‐dicopper(II) (P) vs. bis‐μ‐oxo‐dicopper(III) (O) isomerism ‐ an equilibrium that has become almost iconic in theoretical bioinorganic chemistry. Herein, we present a comprehensive calibration and evaluation of the performance of various composite computational protocols available in contemporary computational chemistry, involving coupled‐cluster and multireference (relativistic) wave function methods, popular density functionals and solvation models. Starting with the well‐studied reference [Cu2O2(NH3)6]2+system, we compared the performance of electronic structure methods and discussed the relativistic effects. This allowed us to select several ‘calibrated’ DFT functionals that can be conveniently employed to study ten experimentally well‐characterized [Cu2O2] inorganic systems. We mostly predicted the lowest‐energy structures (Pvs.O) of the studied systems correctly. In addition, we present calibration of the used electronic structure methods for prediction of the spectroscopic features of the [Cu2O2] core, mostly provided by the resonance Raman (rR) spectroscopy.
Next‐Generation Sequencing to Characterize Mitochondrial Genomic DNA Heteroplasmy
Authors: Yang Zeyu , Slone Jesse , Huang Taosheng
Published: May 2022

Mitochondria play a very important role in many crucial cellular functions. Each eukaryotic cell contains hundreds of mitochondria with hundreds of mitochondrial genomes. Mutant and wild‐type mitochondrial DNA (mtDNA) may co‐exist as heteroplasmy and cause human disease. The purpose of the protocols in this article is to simultaneously determine the mtDNA sequence and quantify the heteroplasmy level using parallel sequencing. The protocols include mitochondrial genomic DNA PCR amplification of two full‐length products using two distinct sets of PCR primers. The PCR products are mixed at an equimolar ratio, and the samples are then barcoded and sequenced with high‐throughput next‐generation sequencing technology. This technology is highly sensitive, specific, and accurate in determining mtDNA mutations and the degree/level of heteroplasmy. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: PCR amplification of mitochondrial DNA

Basic Protocol 2: Analysis of next‐generation sequencing of mitochondrial DNA

Basic Protocol 3: Mutect2 pipeline for automated sample processing and large‐scale data analysis
Extraction and Surfactant Properties of Glyoxylic Acid‐Functionalized Lignin
Authors: Bertella Stefania , Bernardes Figueirêdo Monique , De Angelis Gaia , Mourez Malcolm , Bourmaud Claire , Amstad Esther , Luterbacher Jeremy S.
Published: May 2022

The amphiphilic chemical structure of native lignin, composed by a hydrophobic aromatic core and hydrophilic hydroxy groups, makes it a promising alternative for the development of bio‐based surface‐active compounds. However, the severe conditions traditionally needed during biomass fractionation make lignin prone to condensation and cause it to lose hydrophilic hydroxy groups in favour of the formation of C−C bonds, ultimately decreasing lignin's abilities to lower surface tension of water/oil mixtures. Therefore, it is often necessary to further functionalize lignin in additional synthetic steps in order to obtain a surfactant with suitable properties. In this work, multifunctional aldehyde‐assisted fractionation with glyoxylic acid (GA) was used to prevent lignin condensation and simultaneously introduce a controlled amount of carboxylic acid on the lignin backbone for its further use as surfactant. After fully characterizing the extracted GA‐lignin, its surface activity was measured in several water/oil systems at different pH values. Then, the stability of water/mineral oil emulsions was evaluated at different pH and over a course of 30 days by traditional photography and microscopy imaging. Further, the use of GA‐lignin as a surfactant was investigated in the formulation of a cosmetic hand cream composed of industrially relevant ingredients. Contrary to industrial lignins such as Kraft lignin, GA‐lignin did not alter the color or smell of the formulation. Finally, the surface activity of GA‐lignin was compared with other lignin‐based and fossil‐based surfactants, showing that GA‐lignin presented similar or better surface‐active properties compared to some of the most commonly used surfactants. The overall results showed that GA‐lignin, a biopolymer that can be made exclusively from renewable carbon, can successfully be extracted in one step from lignocellulosic biomass. This lignin can be used as an effective surfactant without further modification, and as such is a promising candidate for the development of new bio‐based surface‐active products.
Research about two‐step channel with lateral narrowing structures in the flow mass transfer of proton exchange membrane fuel cell
Authors: Li J.R. , Wang H.Y. , Lin P.J , Wang G.D. , Sun J.C. , Yang D.M.
Published: May 2022

Proton exchange membrane fuel cell (PEMFC) is a new energy device with wide application prospects. The design of its flow field is one of the effective methods to improve its performance. As key parameters of the PEMFC, mass transport is directly dependent on these channels in flow fields. To enhance the mass transport in the channel, some simple two‐step structures with forced convection are proposed in previous research. But the convections formed by these simple structures are only in one direction. Compared to the complex flow behaviors of the gas in PEMFC, these one‐direction convections are not enough. Then the more comprehensive dimensional convections are made by a new kind of two‐step structure with lateral narrowing. The mathematical model of the new‐designed PEMFC is simulated by the Fluent module in the computational fluid dynamics software ANSYS. Compared with the parallel‐straight‐flow channel, the current density of the new channel proposed in this paper can be increased by 12.5%.
Relationship between dementia, COVID‐19 risk, and adherence to COVID‐19 mitigation behaviors among older adults in the United States
Authors: Wong Roger , Lovier Margaret Anne
Published: May 2022

Objectives

To examine how dementia is associated with COVID‐19 risk and adherence to COVID‐19 mitigation behaviors, and whether mitigation behaviors mediate the relationship between dementia and COVID‐19 risk.

Methods/Design

We analyzed 2019 and 2020 data from the National Health and Aging Trends Study, a national prospective cohort study of United States older adults age 65+. Outcomes were COVID‐19 diagnosis and adherence to COVID‐19 mitigation behaviors (handwashing, mask‐wearing, and social distancing).

Results

Among the 3257 older adults in this study, 485 (14.9%) had dementia in 2019 and 98 (3.1%) were COVID‐19 positive in 2020. Dementia significantly increased the odds of COVID‐19 by 129% (odds ratio [OR] = 2.29, 95% confidence interval [CI] 1.32–3.97), and remained elevated after adjusting for sociodemographics and health (OR = 1.67, 95% CI 0.90–3.11). Dementia significantly decreased the odds of handwashing by 72% (OR = 0.28, 95% CI 0.17–0.44), which remained lower after adjusting for sociodemographics and health (OR = 0.53, 95% CI 0.23–1.21). Dementia was not significantly associated with mask‐wearing and social distancing. The relationship between dementia and COVID‐19 was primarily mediated by functional impairment, income, and residential setting.

Conclusions

Dementia was associated with an increased COVID‐19 risk and lower adherence to handwashing among U.S. older adults. Adherence to COVID‐19 mitigation behaviors did not mediate COVID‐19 risk by dementia status. For older adults with dementia, COVID‐19 risk could be decreased by prioritizing health interventions.
A data driven policy to minimise the tuberculosis testing cost among healthcare workers
Authors: Girishan Prabhu Vishnunarayan , Taaffe Kevin M. , Pirrallo Ronald G. , Shvorin Dotan
Published: May 2022

Introduction

The Centres for Disease Control and Prevention (CDC) mandates that healthcare employees at high‐risk exposure to Tuberculosis (TB) undergo annual testing. Currently, two methods of TB testing are used: a two‐step skin test (TST) or a whole‐blood test (IGRA). Healthcare leadership's test selection must account for not only direct costs such as procedure and resources but also indirect costs, including employee workplace absence.

Methods

A mathematical model based on Upstate South Carolina's largest health system affecting over 18,000 employees on six campuses was developed to investigate the value loss perspective of these testing methods and assist in decision‐making. A process flow map identified the varied direct and indirect costs for each test for four employee types, and 6 travel‐to‐testing‐site times were calculated.

Results

The switching point between testing procedures that minimised total system costs was most influenced by employee salary compared to travel distance. Switching from the current hospital policy to an integrated TST/IGRA testing could reduce TB compliance costs by 28%.

Conclusions

This study recommends an integrated approach as cost‐effective for large health systems with multiple campuses while considering the direct and indirect costs. When accounting for ‘inconvenience costs’ (stress, etc.) associated with visits, IGRAs are recommended irrespective of employee salary.
Physiologically Based Pharmacokinetic and Pharmacodynamic Modeling of Diazepam: Unbound Interstitial Brain Concentrations Correspond to Clinical End Points
Authors: Burkat P.M.
Published: May 2022

Benzodiazepines induce a series of clinical effects by modulating subtypes of γ‐aminobutyric acid type A receptors in the central nervous system. The brain concentration‐time profiles of diazepam that correspond to these effects are unknown, but can be estimated with physiologically based pharmacokinetic (PBPK) modeling. In this study, a PBPK model for the 1,4‐benzodiazepines diazepam and nordiazepam was developed from plasma concentration–time courses with PK‐Sim software to predict brain concentrations. The PBPK model simulations accurately parallel plasma concentrations from both an internal model training data set and an external data set for both intravenous and peroral diazepam administrations. It was determined that the unbound interstitial brain concentration–time profiles correlated with diazepam pharmacodynamic end points. With a 30‐mg intravenous diazepam dose, the peak unbound interstitial brain concentration from this model is 160 nM at 2 minutes and 28.9 nM at 120 minutes. Peak potentiation of recombinant γ‐aminobutyric acid type A receptors composed of α1β2γ2s, α2β2γ2s, and α5β2γ2s subunit combinations that are involved in diazepam clinical endpoints is 108%, 139%, and 186%, respectively, with this intravenous dose. With 10‐mg peroral administrations of diazepam delivered every 24 hours, steady‐state peak and trough unbound interstitial brain diazepam concentrations are 22.3 ± 7.5 and 9.3 ± 3.5 nM. Nordiazepam unbound interstitial brain concentration is 36.1 nM at equilibrium with this diazepam dosing schedule. Pharmacodynamic models coupled to the diazepam unbound interstitial brain concentrations from the PBPK analysis account for electroencephalographic drug effect, change in 13‐ to 30‐Hz electroencephalographic activity, amnesia incidence, and sedation score time courses from human subjects.
The Nocebo Response in Pharmacologic Treatments of Primary Headache: A Systematic Review and Meta‐Analysis
Authors: Zhang Yu , Xu Yingying , Liu Shuping , Liang Jingjing , Fan Shanghua , Ding Man , Wang Juan , Xiao Zheman
Published: May 2022

The nature and magnitude of nocebo responses in primary headache disorders are still unknown. To assess the distribution and possible predictors of nocebo responses in primary headache treatments, databases, including PubMed, EMBASE, and Cochrane Library were searched from 1988 to December 31, 2020, for parallel‐group, double‐blind, randomized placebo‐controlled trials of pharmacologic treatments of primary headaches. The nocebo responses were calculated using a random effects meta‐analysis model. Subgroup and metaregression analyses were performed to determine the associations of study design and demographic characteristics with nocebo responses. A total of 178 randomized controlled trials that satisfied the inclusion criteria were included. Prophylactic treatments elicited stronger nocebo responses than acute treatments. The majority of nocebo adverse events were mild to moderate in severity, with the nervous and digestive systems being the most commonly affected. There was a strong correlation between the active medication and control groups in terms of adverse events, both quantitatively and qualitatively. Long treatment duration, a high proportion of subjects receiving active medications, multicenter design, North America, high body mass index, women, previous treatment experiences, and a high proportion of patients with migraine headache with aura were all found to be significant positive predictors of nocebo responses, whereas the year of publication was found to be inversely related to them. Nocebo effects should be noticed for their contribution to discontinuation of or lack of adherence to active treatments. Clarifying these nocebo‐related risk factors can aid in their clinical prevention and management.
Biocompatible enhancement of poly(ethylene terephthalate) (PET) waste films by cold plasma aminolysis
Authors: Mora‐Cortes Luis F , Rivas‐Muñoz Areli N , Neira‐Velázquez María G , Contreras‐Esquivel Juan C , Roger Philippe , Mora‐Cura Yesica N , Soria‐Arguello Gustavo , Bolaina‐Lorenzo Ena D , Reyna‐Martínez Ricardo , Zugasti‐Cruz Alejandro , Narro‐Céspedes Rosa I
Published: May 2022

BACKGROUND

Poly(ethylene terephthalate) (PET) waste films were treated by cold plasma aminolysis to graft primary amino groups (‐NH2) and the surface biocompatibility of the polymer was improved. Aminated PET waste films were obtained by applying radiofrequency (RF) plasma treatment of either diethylenetriamine (DTA) or ethylenediamine (EDA). Aminolysis was applied during 5, 10 and 15 min at plasma power levels of 150, 175 and 200 W.

RESULTS

Water contact angle study revealed that the surface of PET waste films became more hydrophilic after plasma treatment, the contact angles decreased as exposure time or plasma power increased. Also, X‐ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) detected signals related to ‐NH2 functional groups at the surface of treated PET films. In relation to the biocompatibility properties of the aminated PET waste films, most of them, do not present hemolytic problems, but those treated with DTA at 150 W for 10 min (PET‐DTA/150 W‐10 min) showed the least hemolytic effect. On the other hand, it was proved that plasma treatment of PET waste films conferred a sterilization effect against Pseudomonas aeruginosa bacteria.

CONCLUSIONS

The biocompatible properties of PET were improved while the material was sterilized due to the ultraviolet radiation and free electrons generated during plasma treatment. These results suggest that aminated PET waste films have the potential to be used in biological or biomedical applications by taking advantage of ecofriendly technology such as cold plasma and the reuse of waste polymers such as PET from purified water bottles. © 2022 Society of Chemical Industry (SCI).
The association of acute COVID‐19 infection with Patient Safety Indicator‐12 events in a multisite healthcare system
Authors: Bhakta Shivang , Pollock Benjamin D. , Erben Young M. , Edwards Michael A. , Noe Katherine H. , Dowdy Sean C. , Moreno Franco Pablo , Cowart Jennifer B.
Published: May 2022

Background

Patient Safety Indicator (PSI)‐12, a hospital quality measure designed by Agency for Healthcare Research and Quality (AHRQ) to capture potentially preventable adverse events, captures perioperative venous thromboembolism (VTE). It is unclear how COVID‐19 has affected PSI‐12 performance.

Objective

We sought to compare the cumulative incidence of PSI‐12 in patients with and without acute COVID‐19 infection.

Design, Setting, and Participants

This was a retrospective cohort study including PSI‐12‐eligible events at three Mayo Clinic medical centers (4/1/2020‐10/5/2021).

Exposure, Main Outcomes, and Measures

We compared the unadjusted rate and adjusted risk ratio (aRR) for PSI‐12 events among patients with and without COVID‐19 infection using Fisher's exact χ2 test and the AHRQ risk‐adjustment software, respectively. We summarized the clinical outcomes of COVID‐19 patients with a PSI‐12 event.

Results

Our cohort included 50,400 consecutive hospitalizations. Rates of PSI‐12 events were significantly higher among patients with acute COVID‐19 infection (8/257 [3.11%; 95% confidence interval {CI}, 1.35%–6.04%]) compared to patients without COVID‐19 (210/50,143 [0.42%; 95% CI, 0.36%–0.48%]) with a PSI‐12 event during the encounter (p < .001). The risk‐adjusted rate of PSI‐12 was significantly higher in patients with acute COVID‐19 infection (1.50% vs. 0.38%; aRR, 3.90; 95% CI, 2.12–7.17; p < .001). All COVID‐19 patients with PSI‐12 events had severe disease and 4 died. The most common procedure was tracheostomy (75%); the mean (SD) days from surgical procedure to VTE were 0.12 (7.32) days.

Conclusion

Patients with acute COVID‐19 infection are at higher risk for PSI‐12. The present definition of PSI‐12 does not account for COVID‐19. This may impact hospitals' quality performance if COVID‐19 infection is not accounted for by exclusion or risk adjustment.
妊娠中に併発した縦隔原発B細胞性リンパ腫による気道狭窄症のために緊急帝王切開術を行い，ECMOを導入して救命した1例(A case report of fatal airway obstruction due to primary mediastinal B–cell lymphoma during pregnancy requiring cesarian section and ECMO)
Authors: (Kazuaki Shigemitsu) 重光 胤明 , (Aisa Matoi) 的井 愛紗 , (Yosuke Nakaya) 中舎 洋輔 , (Tomoya Yamashita) 山下 智也 , (Ayumu Tsuruoka) 鶴岡 歩 , (Yoshiki Hayashi) 林 良樹 , (Hiroshi Rinka) 林下 浩士
Published: May 2022

妊娠33週の30歳女性。6週間前から咳嗽が出現し数日前から臥位になれず近医を受診したところ，胸部CTで前縦隔腫瘍が気管と右主気管支とを圧排していたため同日転院となった。搬送時，起坐呼吸で頻脈があった。顔面の浮腫と頸静脈怒張があり，縦隔腫瘍による気道狭窄症と上大静脈症候群と診断した。呼吸苦は急速に進行しており気管挿管と陽圧換気が必要であった。妊娠継続は母体にとってリスクが高いと判断し緊急帝王切開術の方針としたが，術中に換気不全に陥る危険性があったためextra–corporeal membrane oxygenation（ECMO）を待機して手術を開始した。麻酔の導入から児の娩出までは問題なかったが，閉腹の際に換気量を保てず，veno–venous ECMOを導入した。第2病日に生検を行い，迅速病理検査で悪性リンパ腫と診断し化学療法を開始した。第6病日には胸部X線写真で肺野の透過性が改善して従圧式補助調節換気での一回換気量も増加したため，第8病日にECMOを離脱した。その後も化学療法を継続し，第35病日に人工呼吸器を離脱，第85病日に独歩退院となった。初診から3年8か月が経過した現在，再発はない。妊婦が縦隔腫瘍により重篤な呼吸不全を来すことは稀である。救命のためには，緊急帝王切開術の迅速な決断，必要なタイミングでECMOを導入したこと，迅速な病理診断と早期の治療開始が重要であった。
救急外来におけるサーフィン外傷の特徴(Characteristics of surfing injuries at the emergency department)
Authors: (Yusuke Tokida) 時田 裕介 , (Hiroshi Yamagami) 山上 浩 , (Ichiro Sekine) 関根 一朗 , (Kiyomitsu Fukaguchi) 鱶口 清満 , (Hiroyuki Fukui) 福井 浩之
Published: May 2022

【目的】サーフィン外傷についての報告は諸外国からあるも限られており，傷害予防を実践するに至っていない。また国による海洋条件の違いが，受傷機転や外傷形態に違いがあると予測されるが，我が国での報告は少なく明らかではない。そこで，多くのサーフィン外傷の受診がある当院で受傷機転・部位，傷害形態などの特徴を明らかにし，傷害予防策を検討することとした。【方法】2018年から2019年の2年間にサーフィン中に受傷し当院救急外来を受診した患者の診療録と電話聞き取りから調査を行った。【結果】対象患者は119人，受傷機転はサーフボード接触型88人，非接触型28人，不明3人であった。接触型では鋭利なフィンやノーズが，露出部位である頭部・顔面，四肢へ接触した皮膚損傷が最も多く約6割を占め，過去の諸外国の報告と同様な受傷機転・受傷部位・外傷形態であった。非接触型では着地時の下肢骨折が多く，手術・入院を要する傾向にあった。傷害予防策として，露出部位を最小限としたウェットスーツやヘッドギアの装着，安全性の高いサーフボードの製品導入が望まれる。【結語】鋭利なフィンやノーズが露出部位である頭部・顔面，四肢へ接触した皮膚損傷が最も多く，これまでの報告と同様な受傷機転/部位・外傷形態であった。傷害予防策や軽減化のためのサーフィン関連製品の導入が望まれる。
Form and function in the avian pelvis
Authors: Frank Tanner M. , Dodson Peter , Hedrick Brandon P.
Published: May 2022

The avian pelvis plays a critical role in the hindlimb function of birds, connecting the hindlimb and axial skeleton and serving as the major attachment site for proximal hindlimb musculature. To assess how diversification of locomotor modes in birds has impacted the evolution of avian pelvic morphology, we conducted a two‐dimensional geometric morphometric analysis of bird pelves in dorsal and lateral views from 163 species (n = 261) across Aves. We investigated the relationships among pelvic shape and ecology, phylogeny, and allometry, and conducted disparity analyses to understand how pelvic morphospace has been explored through the diversification of Aves. We found that while phylogeny was correlated with shape, locomotor categories were significantly discriminated in morphospace in phylogenetically corrected analyses, as was pelvic size. Major shape trends across Aves distinguishing locomotor categories included the relative area of the preacetabular versus postacetabular ilium, how squat or narrow the pelvis is, and the extent of the caudal pelvic border. Birds adapted for hind limb‐propelled swimming had particularly distinctive pelves, with narrow, elongated ilia likely useful for holding the hindlimbs close to the body midline and reducing drag. However, ecology and allometry only account for a small proportion of morphological variation, and in general locomotor groups overlapped substantially in morphospace. These results, alongside disparity through time analyses showing widespread convergence in pelvic morphology throughout the Cenozoic, suggest that avian lineages and ecotypes have extensively explored pelvic morphospace, perhaps aided by a loosening of evolutionary constraints following the evolution of forelimb‐powered flight.
Neural network based heuristic fractional order adaptive PID‐controller for eliminating communication time delay in multi‐area LFC
Authors: Saka Mustafa , Gozde Haluk , Eke Ibrahim , Taplamacioglu M. Cengiz
Published: May 2022

Communication of interconnected power system components with each other and with control centers is provided by using various communication links. However, these links can cause significant time delays (TD) depending on the types, distance and conditions of the communication channel. In addition to temporary time delays caused by the time constants of the components due to system failures, this article draws attention to the negative effects that may be caused by permanent communication time delays in particular, as different from the literature. The communication time delays can disrupt the stable operation of power systems and even cause the whole system to breakdown by making it unstable, when combining with other delays. In the study, the fiber‐optic (F/O) links are assumed to commonly use in supervisory control and data acquisition (SCADA) systems and the communication time delays are calculated based on this scenario. However, it is no doubt that less used radio frequency (RF)‐links will create more time delays. Moreover, to eliminate the negative effects of these types of time delays, a novel neural network based‐heuristic fractional order hybrid adaptive proportional‐integral‐derivative (ML‐H‐PIλDμ) controller for multi area load frequency control (LFC) scheme is developed and analyzed.
Organic materials with high P and low C:P ratio improve P availability for lowland rice in highly weathered soils: Pot and incubation experiments
Authors: Rinasoa Seheno , Nishigaki Tomohiro , Rabeharisoa Lilia , Tsujimoto Yasuhiro , Rakotoson Tovohery
Published: May 2022

Background

Phosphorus (P) deficiency remains a serious problem for lowland rice cultivation in Sub‐Saharan Africa. Locally available organic materials (OM) are potential amendment resources, but they vary widely in nutrient composition. How different OM affect P availability and rice production under different soil types remains poorly understood.

Aims

We aimed to determine soil responses to OM application varying in carbon (C) and P contents on P uptake, rice production, and P availability.

Methods

A pot experiment with eight different soils from lowland rice fields amended with four different farmer‐produced OM at an equal dose of 7.5 g kg–1 soil; and an incubation experiment with six soils amended with cellulose and two OM applied at the same C dose were conducted.

Results

An OM associated with high P and low C:P ratio increased shoot biomass and P uptake of rice in all soils by two‐ and threefold, respectively, compared to the control treatment. Low P saturation in soils (low P:Fe in oxalate extract) produced greater OM effects. Shoot biomass and P uptake decreased significantly in one soil with a high P saturation following application of the other three OM. Although increased soil P solubilization was observed with the addition of fresh C, OM effects on P availability were mostly attributed to their direct P supply.

Conclusion

OM with high P and low C:P ratio is effective in improving P availability for rice in P‐deficient lowland rice soils.
Use of traditional knowledge in weather prediction and averting climate risks: A case study in livestock‐based smallholder farming systems in Sri Lanka
Authors: Siriwardana Amila Nuwan , Samarakone Thusith Semini , Silva Gamameda Liyanage Lalanie Pradeepa , Dematawewa Chandrarathne Mahinda Bandara , Punyawardena Batugedara Vidanalage Ranjith , Marambe Buddhi , Nidumolu Uday , Howden Mark
Published: May 2022

Background

Integration of traditional knowledge (TK) to decision making in agriculture is a continued practice of the smallholder farmers in the tropics. There is a knowledge gap in the use of TK in weather or climate prediction by farmers to minimize climate risks. Hence, a field survey was conducted using a pre‐tested questionnaire coupled with key informant discussions. The study focused on the farmers practicing livestock‐based farming systems in Thabbowa village of the north‐western province of Sri Lanka.

Results

About 94% of farmers had access to national level weather forecasting (WF); however, 54% were not confident enough of the accuracy of the WF. Only elderly farmers had confidence in predicting the weather using TK. While using the outcome of the production, those elderly have passed the outcome of the TK‐based weather predictions (WP) to the rest of the farmers where 46% of the study sample used such information at some level of decision making in agriculture. However, it was evident that the farmers used TK‐based WP combined with the national level WF for deciding on agricultural operations. Plant phenology, animal behavior and astronomical evidence were the commonly used biotic and abiotic factors in TK for WP. The behavior of birds was the prominent TK‐based animal indicator for short to medium range and seasonal WP.

Conclusion

The smallholder farmers need to be strengthened to use national WF with the correct application of TK‐based WP to fulfill the gaps in deciding climate‐adaptation strategies in mixed‐farming systems.
Feasibility of machine‐delivered sequential massage for the management of lymphedema in the head and neck cancer survivor
Authors: Shires Courtney Brooke , Harris Patricia , Dewan Karuna
Published: May 2022

Background

Lymphedema after treatment for head and neck cancer negatively impacts the quality of life and can produce neck tissue stiffness, dysphagia, pain, and swelling. One form of treatment for lymphedema is machine‐delivered sequential lymphedema massage, which is home based and self administered. This study was undertaken to determine economic and system access to home‐based lymphedema therapy and to measure patient‐reported outcomes among those able to access therapy.

Methods

This study is a retrospective cohort study of 84 head and neck cancer patients who met the criteria for referral for home‐based lymphedema treatment. Patients who were able to access lymphedema therapy were surveyed prior to initiation of therapy and again after therapy.

Results

Thirty‐five out of 84 patients were approved for home‐based therapy and received the equipment. Medicare denial of coverage (21/84) was the most common cause of the inability to access therapy. Of the 35 patients who accessed therapy, presenting complaints included: stiffness (31), pain (29), dysphagia (20), and swelling (19). The average time from completion of cancer treatment to initiation of lymphedema therapy was 9 months. Thirty‐four (97%) reported compliance with prescribed therapy, 33 (94%) reported reduced fibrosis, and 30 (89%) reported improvement in activities of daily living. All reported symptoms improved with therapy in 30 (86%) patients. Thirty‐two (91%) reported overall satisfaction with home‐based lymphedema treatment.

Conclusions

Stiffness and pain were the most common complaints of our patients with head and neck lymphedema. Forty‐two percent of patients who were recommended home lymphedema machine use were able to obtain this with cost coverage by their insurance company or by donation from the company. We found a high compliance rate and a highly reported improvement in symptoms with the machine. The only identifiable factor for the patients with less improvement in symptoms was a greater time gap between treatment and initiation of use of home lymphedema machine.

Level of evidence

2 Retrospective cohort analysis.
Sex Differences for Clinical Correlates of Alzheimer's Pathology in People with Lewy Body Pathology
Authors: Bayram Ece , Coughlin David G. , Litvan Irene
Published: May 2022

Background

Lewy body (LB) dementias have limited clinical diagnostic accuracy because of frequent copathologies contributing to clinical heterogeneity. Although sex differences in clinical prevalence and frequency of pure LB pathology were shown, differences for clinicopathological correlations are less known.

Objective

The aim of this study was to determine sex differences for clinical associations of Alzheimer's disease (AD) copathology in those with LB pathology.

Methods

Data were from National Alzheimer's Coordinating Center for 223 women and 468 men with limbic or neocortical LB, separated into two groups as those with high likelihood and low/intermediate likelihood for LB clinical phenotype based on pathology. Clinical associations of sex and interaction of sex and pathology for the clinical phenotype were analyzed.

Results

More severe AD copathology was associated with worse cognitive decline and lower likelihood of LB disease clinical phenotype. Women with more severe AD copathology and tau had worse cognitive decline and higher likelihood of AD clinical phenotype than men. Men with more severe AD copathology had lower likelihood of LB clinical phenotype than women. Interaction of sex and pathology was more pronounced in those aged between 70 and 80 years.

Conclusions

AD copathology reduces the likelihood of LB clinical phenotype for both women and men; however, men may be at higher risk for LB disease underdiagnosis and women at higher risk for dementia. The use of both LB and AD biomarkers, even when LB or AD pathology is not clinically expected, is necessary for the accurate clinical diagnosis of both LB diseases and AD. © 2022 International Parkinson and Movement Disorder Society.
An x‐band coplanar magic‐T with high power handing
Authors: Guo Long , Shi Yiping , Wang Guangming , Tian Yin
Published: May 2022

An x‐band coplanar magic‐T with high power handing is proposed by combining an H‐plane power divider and an iris for matching in E‐plane. The proposed magic‐T has −15 dB impedance bandwidth in experiment, which is about 23% covering form 8.9 to 11.2 GHz. Furthermore, the isolation is better than 46.2 dB with the typical insertion loss of 0.15 dB in the whole bandwidth with the contribute of the symmetrical structure. Herein, the average power‐handling capability (APHC) could be estimated at 865 W by simulated analysis, since the structure is all‐metal. Excellent correspondence between the simulated and measured results is demonstrated.
Cancer‐associated fibroblasts in pancreatic cancer: new subtypes, new markers, new targets
Authors: Menezes Shinelle , Okail Mohamed Hazem , Jalil Siti Munira Abd , Kocher Hemant M , Cameron Angus J M
Published: May 2022

Cancer‐associated fibroblasts (CAFs) have conflicting roles in the suppression and promotion of cancer. Current research focuses on targeting the undesirable properties of CAFs, while attempting to maintain tumour‐suppressive roles. CAFs have been widely associated with primary or secondary therapeutic resistance, and strategies to modify CAF function have therefore largely focussed on their combination with existing therapies. Despite significant progress in preclinical studies, clinical translation of CAF targeted therapies has achieved limited success. Here we will review our emerging understanding of heterogeneous CAF populations in tumour biology and use examples from pancreatic ductal adenocarcinoma to explore why successful clinical targeting of protumourigenic CAF functions remains elusive. Single‐cell technologies have allowed the identification of CAF subtypes with a differential impact on prognosis and response to therapy, but currently without clear consensus. Identification and pharmacological targeting of CAF subtypes associated with immunotherapy response offers new hope to expand clinical options for pancreatic cancer. Various CAF subtype markers may represent biomarkers for patient stratification, to obtain enhanced response with existing and emerging combinatorial therapeutic strategies. Thus, CAF subtyping is the next frontier in understanding and exploiting the tumour microenvironment for therapeutic benefit. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Synchronously improved ozone aging resistance and tribological performance of self‐lubricating fabric composites via 2‐mercaptobenzimidazole
Authors: Li Peilong , Zhang Zhaozhu , Chen Zujun , Yang Mingming , Yuan Junya , Jiang Wei
Published: May 2022

Self‐lubricating fabric composite can be used as liner material in plain bearings of aeronautical aircraft. The concentration of ozone in the cruising altitude of aircraft is relatively high and the oxidation of ozone will reduce the tribological property and service life of the self‐lubricating fabric composites. In present work, 2‐mercaptobenzimidazole (MB) was chosen and filled into self‐lubricating fabric composites to improve their ozone aging resistance and wear resistance performance. Characterizations demonstrated that the optimum filling ratio of MB was 4 wt%. The glass transition temperature of resin and decomposition temperature of the composite filled with 4 wt% MB were 96.3 s and 475°C, which increased by 12.6% and 6.7% compared with that of resin and composites without filling MB, respectively. The tribological performance and ozone aging resistance performance of MB reinforced self‐lubricating fabric composites acquired obviously enhancement. The wear rate of MB reinforced self‐lubricating fabric composites after different ozone aging time decreased by 42.4%–61.8% compared with that of composites without filling MB owing to that the addition of MB improved the oxidation resistance and thermal stability of self‐lubricating composites.
An antibody‐free enrichment approach enabled by reductive glutaraldehydation for monomethyllysine proteome analysis
Authors: Li Zhouxian , Wang Qi , Wang Keyun , Zhang Weibing , Ye Mingliang
Published: May 2022

Protein lysine monomethylation is an important post‐translational modification participated in regulating many biological processes. There is growing interest in identifying these methylation events. However, the introduction of one methyl group on lysine residues has negligible effect on changing the physical and chemical properties of proteins or peptides, making enriching and identifying monomethylated lysine (Kme1) proteins or peptides extraordinarily challenging. In this study, we proposed an antibody‐free chemical proteomics approach to capture Kme1 peptides from complex protein digest. By exploiting reductive glutaraldehydation, 5‐aldehyde‐pentanyl modified Kme1 residues and piperidine modified primary amines were generated at the same time. The peptides with aldehyde modified Kme1 residues were then enriched by solid‐phase hydrazide chemistry. This chemical proteomics approach was validated by using several synthetic peptides. It was demonstrated that it can enrich and detect Kme1 peptide from peptide mixture containing 5000‐fold more bovine serum albumin tryptic digest. Besides, we extended our approach to profile Kme1 using heavy methyl stable isotope labeling by amino acids in cell culture (hmSILAC) labeled Jurkat T cells and Hela cells. Totally, 29 Kme1 sites on 25 proteins were identified with high confidence and 11 Kme1 sites were identified in both two types cells. This is the first antibody‐free chemical proteomics approach to enrich Kme1 peptides from complex protein digest, and it provides a potential avenue for the analysis of methylome.
Stabilization of a class of stochastic nonlinear systems using a bang‐bang controller
Authors: Barbata Asma , Zasadzinski Michel , Souley Ali Harouna
Published: May 2022

In this article, a bang‐bang control strategy is proposed to almost surely exponentially stabilize a class of nonlinear stochastic systems driven by multiplicative noises. Two cases are considered: first, a state feedback control if the whole state is measured and, second, an observer‐based feedback control if the state is partially measured.
Model-free data-driven simulation of inelastic materials using structured data sets, tangent space information and transition rules
Authors: Ciftci Kerem , Hackl Klaus
Published: May 2022

Model-free data-driven computational mechanics replaces phenomenological constitutive functions by numerical simulations based on data sets of representative samples in stress-strain space. The distance of strain and stress pairs from the data set is minimized, subject to equilibrium and compatibility constraints. Although this method operates well for non-linear elastic problems, there are challenges dealing with history-dependent materials, since one and the same point in stress-strain space might correspond to different material behaviour. In recent literature, this issue has been treated by including local histories into the data set. However, there is still the necessity to include models for the evolution of specific internal variables. Thus, a mixed formulation of classical and data-driven modeling is obtained. In the presented approach, the data set is augmented with directions in the tangent space of points in stress-strain space. Moreover, the data set is divided into subsets corresponding to different material behaviour. Based on this classification, transition rules map the modeling points to the various subsets. The approach will be applied to non-linear elasticity and elasto-plasticity with isotropic hardening.