bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive and clinical‐oriented evaluation criteria based on DVH information and gamma passing rates analysis for IMRT plan 3D verification
Authors: Yi Xin , Lu Wen‐li , Dang Jun , Huang Wei , Cui Hai‐xia , Wu Wan‐chun , Li Ying , Jiang Qing‐feng
Published: May 2020

Purpose

To accomplish the 3D dose verification to IMRT plan by incorporating DVH information and gamma passing rates (GPs) (DVH_GPs) so as to better correlate the patient‐specific quality assurance (QA) results with clinically relevant metrics.

Materials and methods

DVH_GPs analysis was performed to specific structures of 51 intensity‐modulated radiotherapy (IMRT) treatment plans (17 plans each for oropharyngeal neoplasm, esophageal neoplasm, and cervical neoplasm) with Delta4 3D dose verification system. Based on the DVH action levels of 5% and GPs action levels of 90% (3%/2 mm), the evaluation results of DVH_GPs analysis were categorized into four regions as follows: the true positive (TP) (%DE> 5%, GPs < 90%), the false positive (FP) (%DE ≤ 5%, GPs < 90%), the false negative (FN) (%DE> 5%, GPs ≥ 90%), and the true negative (TN) (%DE ≤ 5%, GPs ≥ 90%). Considering the actual situation, the final patient‐specific QA determination was made based on the DVH_GPs evaluation results. In order to exclude the impact of Delta4 phantom on the DVH_GPs evaluation results, 5 cm phantom shift verification was carried out to structures with abnormal results (femoral heads, lung, heart).

Results

In DVH_GPs evaluation, 58 cases with FN, 5 cases with FP, and 2 cases with TP were observed. After the phantom shift verification, the extremely abnormal FN of both lung (%DE = 21.52%±8.20%) and heart (%DE = 19.76%) in the oropharyngeal neoplasm plans and of the bilateral formal heads (%DE = 26.41%±13.45%) in cervical neoplasm plans disappeared dramatically. DVH_GPs analysis was performed to all evaluation results in combination with clinical treatment criteria. Finally, only one TP case from the oropharyngeal neoplasm plans and one FN case from the esophageal neoplasm plans did not meet the treatment requirements, so they needed to be replanned.

Conclusion

The proposed DVH_GPs evaluation method first make up the deficiency of conventional gamma analysis regarding intensity information and space information. Moreover, it improves the correlation between the patient‐specific QA results and clinically relevant metrics. Finally, it can distinguish the TP, TN, FP, and FN in the evaluation results. They are affected by many factors such as the action levels of DVH and GPs, the feature of the specific structure, the QA device, etc. Therefore, medical physicist should make final patient‐specific QA decision not only by taking into account the information of DVH and GPs, but also the practical situation.
Reversing 21 years of chronic paralysis via non‐invasive spinal cord neuromodulation: a case study
Authors: Alam Monzurul , Ling Yan To , Wong Arnold Y. L. , Zhong Hui , Edgerton Victor Reggie , Zheng Yong‐Ping
Published: May 2020

Objective

The objective of the current study was to investigate if a non‐invasive spinal cord neuromodulation modality could restore sensorimotor functions in a patient with chronic spinal cord injury (SCI).

Methods

In this study, transcutaneous electrical stimulation (tES) to the spinal cord was utilized to restore sensorimotor functions in a chronic SCI patient who sustained a traumatic C7 cervical cord injury 21 years ago. At baseline, the patient had very limited volitional movement in her right leg, and her left leg was completely paralyzed. tES parameters were optimized in eight stimulation sessions before the treatment. The therapeutic stimulation involved biphasic tES, applied to T11 and L1 spinal levels during a 1‐hour standing and walking training, 2–4 times per week for 16 weeks.

Results

Our pre‐treatment tests indicated that a shorter burst duration (100 µsec) was more effective than a longer burst duration of tES in improving functional movements. After 32 training sessions with tES, the patient regained significant left‐leg volitional movements (grade 0 to grade 10 according to the ISNCSCI scale). Right‐leg motor scores also increased from 17 to 21. The tES treatment also improved her pinprick sensation (from 73 to 79). Upon completion of the treatment (52 sessions), the patient’s standing ability noticeably improved. She could stabilize her knee to stand without any assistance. She could also squat while holding onto a walker.

Interpretation

These promising results demonstrate beneficial effects of non‐invasive tES in regaining volitional control of plegic lower limbs in patients with chronic paralysis.
Study on Cell Deformation of Low Porosity Aluminum Foams under Quasi‐Static Compression by X‐Ray Tomography
Authors: Wang Ningzhen , Chen Xiang , Maire Eric , Kamm Paul H. , Cheng Ying , Li Yanxiang , García-Moreno Francisco
Published: May 2020

Understanding the correlation between cell deformation and initial cell structure during compression is important for improvement and development of effective applications of aluminum foams. Foams with porosities lower than 75% now get more attention because of more spherical cells and better mechanical performance. Herein, two low porosity aluminum foam samples are deformed by a compressive device allowing simultaneous X‐ray tomography. The foam cell structures in the initial undeformed state and in the state, where the first batch of cells deforms, are characterized and correlated. The absolute value of anisotropy change is selected as the most sensitive parameter to evaluate the cell deformation. A fitting formula between the cell deformation degree and the initial cell parameters is obtained, which can predict the cell deformation degree. It is found that a cell with small anisotropy, large angle between the longest axis of the cell and the loading direction, small sphericity, more neighbors, and large cell size is more prone to deform during compression. With the fitting formula, the weakest region where the first batch of deformed cells occurs can be predicted. The influence of cell morphology parameters in low porosity aluminum foams is significant and verified by experimental results.
Al(OTf)3‐Catalyzed Tandem Coupling Reaction between N,N‐Disubstituted Aminomalonitriles and Substituted Arenes: a Synthesis of 1‐Cyano‐bisindolylmethane Analogues≠
Authors: Lei Lin‐Sheng , Wang Bo‐Wen , Jin Da‐Ping , Gao Zhu‐Peng , Huan‐Liang  , Wang Shao‐Hua , Xu Xue‐Tao , Zhang Kun , Zhang Xiao‐Yun
Published: May 2020

A synthesis of 1‐cyano‐bisindolylmethane analogues via an Al(OTf)3‐catalyzed tandem coupling reaction between N,N‐disubstituted aminomalonitriles and substituted arenes has been developed. This method not only provides an alternative synthetic strategy for the synthesis of corresponding functional molecules, but also enriches the volume of bisarylmethanes library to facilitate related functional studies.

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Planting date, cultivar, seed treatment, and seeding rate effects on soybean growth and yield
Authors: Nleya Thandiwe , Schutte Matthew , Clay David , Reicks Graig , Mueller Nathan
Published: May 2020

Soybean [Glycine max (L.) Merr.] yield is a function of many factors including genetic attributes of the cultivar, environmental conditions, and management practices. Temporally variable weather patterns in North America, especially in the northern Great Plains, have resulted in the re‐examination of how spring production practices interact with the environmental conditions to influence yield. This study evaluated the impact of four plantings dates, four seeding rates, and two soybean maturity groups (MGs) using treated and untreated (control) seed on soybean growth, seed yield, and composition. The study was conducted at Volga, SD, in 2014, 2015, and 2016. The planting dates in the study ranged from early May to early July and the four seeding rates were 247,000; 333,500; 420,000; 506,500 seeds ha−1. Stand establishment decreased as seeding rate increased irrespective of planting date. The number of growing degree days (GDDs) to R1 decreased with delayed planting. Delayed planting also decreased the number of GDDs to R8, the length of the reproductive phase (R1−R8), and seed yield. Delayed planting decreased seed yield for both MGs but the rate of decrease was greater for MG 2.4 than MG 1.4. Seed treatment increased seed yield irrespective of planting date. Seed protein was variable among planting dates and between MGs while seed oil decreased with delayed planting. The research documents the impact of delayed planting on soybean yield and quality and highlights the importance of early planting in soybean irrespective of maturity group and growth habit.
Long‐term survival outcomes following laparoscopic surgery for clinical stage 0/I rectal carcinoma
Authors: Ito Masaaki , Yamamoto Seiichiro , Okuda Junji , Fujii Shoichi , Yamaguchi Shigeki , Otsuka Koki , Yoshimura Kenichi , Watanabe Masahiko ,   for the Japan Society of Laparoscopic Colorectal Surgery
Published: May 2020

Aim

To clarify and evaluate the long‐term outcomes of laparoscopic surgery for clinical stage 0/I rectal carcinoma patients.

Methods

This single‐arm phase II trial involved accredited surgeons from 43 Japanese institutions. Patients were registered preoperatively. The planned sample size was 490. The primary endpoint was overall survival, and long‐term outcomes were evaluated.

Results

A total of 495 patients were registered between February 2008 and August 2010. Eight patients (1.6%) required conversion to open surgery. Sphincter‐preserving procedures were performed in 477 (97%) patients. Positive radial resection margin was found in two (0.4%) patients. Of 490 patients, 22, 314, 38, 115, and one patient had final pathological stages (p‐stage) 0, I, II, III, and IV, respectively. Pathologically, 31.4% (154/490) of the patients did not have p‐stage 0/I. The 5‐year overall survival (OS) rates in p‐stages 0, I, II, and III were 100%, 98%, 97%, and 94%, respectively. The 5‐year OS of all patients at 96.6% (95% CI 94.6‐97.9) was significantly better than the expected 5‐year OS of 81.1% (P < .0001). The 5‐year relapse‐free survival in p‐stages 0, I, II, and III were 100%, 93%, 81%, and 79%, respectively. The 5‐year relapse‐free survival of all patients was 90.1%. Fifty patients (10.2%) had recurrence; lung recurrence was found in 22 patients, local recurrence in 14, liver in seven, distant lymph node in nine, and bone in three.

Conclusions

Laparoscopic surgery for clinical stage 0/I rectal carcinoma has feasible long‐term outcomes. (ClinicalTrials.gov No.NCT00635466.)
Real‐world effectiveness of eliglustat in treatment‐naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher Registry
Authors: Mistry Pramod K. , Balwani Manisha , Charrow Joel , Kishnani Priya , Niederau Claus , Underhill Lisa H. , McClain Monica R.
Published: May 2020

Eliglustat is a first‐line oral therapy for adults with Gaucher disease type 1 (GD1) with extensive, intermediate, or poor CYP2D6‐metabolizer phenotypes (90% of patients). We report real‐world outcomes after 2 years of eliglustat therapy in the International Collaborative Gaucher Group Gaucher Registry (NCT00358943). As of January 2019, baseline and 2‐year data (±1 year) were available for 231 eliglustat‐treated GD1 patients: 19 treatment‐naïve (zero splenectomized) and 212 ERT patients who switched to eliglustat (36 splenectomized). Most patients (89%) were from the United States, where eliglustat was first approved. In treatment‐naïve patients, mean hemoglobin increased from 12.4 to 13.4 g/dL (P = .004, n = 18), mean platelet count increased from 113 to 156 × 109/L (P < .001, n = 17); mean spleen volume decreased from 7.4 to 3.5 multiples of normal (MN) (P = .02, n = 7); mean liver volume remained normal (n = 7), and median spine Z‐score was unchanged (−1.3 to −1.2, n = 6). In non‐splenectomized switch patients, mean hemoglobin remained stable/non‐anemic (n = 167); mean platelet count remained stable/normal (n = 165); mean spleen volume decreased from 3.3 to 2.8 MN (P < .001, n = 64); mean liver volume remained normal (n = 63), and median lumbar spine Z‐score improved from −0.7 to −0.4 (P = .014, n = 68). In splenectomized switch patients, mean hemoglobin remained stable/non‐anemic (n = 31); mean platelet count increased from 297 to 324 × 109/L (non‐significant, n = 29); mean liver volume remained normal (n = 13); median spine Z‐score improved from −0.8 to −0.6 (non‐significant, n = 11). Median chitotriosidase decreased in all groups (P < .01 for all). These real‐world results are consistent with eliglustat clinical trial results demonstrating long‐term benefit in treatment‐naïve patients and stability in ERT switch patients.
Nissen fundoplication in Cornelia de Lange syndrome spectrum: Who are the potential candidates?
Authors: Parma Barbara , Cianci Paola , Mariani Milena , Cereda Anna , Panceri Roberto , Fossati Chiara , Maestri Luciano , Macchini Francesco , Onesimo Roberta , Zampino Giuseppe , Betalli Pietro , Cheli Maurizio , Selicorni Angelo
Published: May 2020

Cornelia de Lange spectrum (CdLSp) is a rare genetic condition characterized by intellectual disability, facial dysmorphisms, major malformations, growth impairment, and development delay. Approximately 80% of CdLSp patients have gastroesophageal reflux disease (GERD) with a varied clinical presentation. The aim of this study is to define potential clinical/genetic risk factors based on the clinical phenotype description of CdLSp patients with severe GERD who underwent surgical treatment. We retrospectively collected data from 23 CdLSp patients, 13 females and 10 males. Mean age of the patients undergoing surgical treatment was of 4 years. 21/23 (91%) had a molecular characterization, of which 21/21 (100%) had a NIPBL gene mutation, while 2/23 (9%) did not have a genetical characterization, only a clinical diagnosis. Most of our patients presented a moderate–severe severity score (21/23, 91%) with limb malformations evidenced in 10/23 (44%) of our patients and a moderate–severe intellectual disability in 20/23 (87%). Therefore, CdLSp patients harboring NIPBL variants, upper limb malformations and severe psychomotor delay are more likely to suffer from severe GERD, not responsive to proton pump inhibitors treatment. These features should be considered as clinical markers for potentially severe GERD that might require surgical treatment.
Protein and mRNA Delivery Enabled by Cholesteryl‐Based Biodegradable Lipidoid Nanoparticles
Authors: Li Yamin , Jarvis Rachel , Zhu Kuixin , Glass Zachary , Ogurlu Roza , Gao Peiyang , Li Peixuan , Chen Jinjin , Yu Yingjie , Yang Yongjie , Xu Qiaobing
Published: May 2020

Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long‐standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl‐based disulfide bond‐containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).
Biomolecular Densely Grafted Brush Polymers: Oligonucleotides, Oligosaccharides and Oligopeptides
Authors: Choi Wonmin , Sun Hao , Battistella Claudia , Berger Or , Vratsanos Maria A. , Wang Max M. , Gianneschi Nathan C.
Published: May 2020

In this Minireview, we describe synthetic polymers densely functionalized with sequence‐defined biomolecular sidechains. We focus on synthetic brush polymers of oligonucleotides, oligosaccharides, and oligopeptides, prepared via graft‐through polymerization from biomolecule functionalized monomers. The resulting structures are brush polymers wherein a biomolecular graft is positioned at each monomer backbone unit. We describe key synthetic milestones, identify synthetic opportunities, and highlight recent advances in the field, including biological applications.
Enantioselective Preparation of Arenes with β‐Stereogenic Centers: Confronting the 1,1‐Disubstituted Olefin Problem Using CuH/Pd Cooperative Catalysis
Authors: Lu Zhaohong , Buchwald Stephen L.
Published: May 2020

Arenes with β‐stereogenic centers are important substructures in pharmaceuticals and natural products. We have developed an asymmetric anti‐Markovnikov hydroarylation of 1,1‐disubstituted olefins by dual palladium and copper hydride catalysis as a convenient and general approach to access these substructures. This efficient one‐step process addresses several limitations of the traditional stepwise approaches. The use of cesium benzoate as a base and a common phosphine ligand for both the Cu‐ and Pd‐catalyzed processes were important discoveries that allow these challenging olefin substrates to be efficiently transformed. A variety of aryl bromide coupling partners, including numerous heterocycles, were coupled with 1,1‐disubstituted alkenes to generate arenes with β‐stereogenic centers.
Synthesis, spectroscopic, electrochemical characterization, density functional theory (DFT), time dependent density functional theory (TD‐DFT), and antibacterial studies of some Co(II), Ni(II), and Cu(II) chelates of (E)‐4‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐1‐(3‐hydroxynaphthalen‐2‐yl)methylene) thiosemicarbazide Schiff base ligand
Authors: El‐Sawaf Ayman K. , Abdel‐Monem Yasser K. , Azzam Maged A.
Published: May 2020

In this study, mononuclear Co(II), Ni(II), and Cu(II) chelates of the potentially tridentate O, N, S donor ligand (E)‐4‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐1‐(3‐hydroxynaphthalen‐2‐yl)methylene) thiosemicarbazide (H2L) were synthesized and characterized by elemental analyses, conductivity measurements, Fourier transform infrared spectroscopy, UV–visible spectroscopy, magnetic susceptibility, electron spin resonance (ESR) spectral analysis, thermal thermogravimetric analyses, cyclic voltammetry, and theoretical density functional theory (DFT) and time dependent density functional theory (TD‐DFT) studies. The potential donors O (phenolic) and N (azomethine) are found in asynconfiguration due to a strong intramolecular hydrogen bond [O–H …. N(1)] as shown in the1H NMR spectrum of the free ligand. In addition, analytical results revealed the formation of the metal chelates in a ligand‐to‐metal molar ratio of 1:1. The organic ligand (H2L) coordinated to the metal center through azomethine nitrogen, phenolate oxygen, and thione/thiolate sulfur groups with the formation of a five‐ and six‐membered rings. The magnetic and spectral results supported the formation of tetrahedral geometry around the Co(II) and Ni(II) centers, while Cu(II) centers were assumed to have a square planar geometry. The time dependent density functional theory (TD‐DFT) calculation outputs were used to expect and explain the experimental bathochromic and hypsochromic shifts resulting from the ligand chelation. The antibacterial activity of the compounds under study was evaluatedin vitroagainstStaphylococcus aureusandEscherichia colidemonstrating Gram‐positive and Gram‐negative bacteria, respectively. It was found that among synthesized compounds, Cu(II) chelate5showed the most inhibitory activity against both Gram‐positive and Gram‐negative bacteria when compared to the organic ligand as well as to the other prepared chelates.
Comparative study on the photophysical properties between carbene‐based Fe (II) and Ru (II) complexes
Authors: Li Yuan , Fan Xue‐Wen , Wang Jian , Kong Chui‐Peng , Chen Jie , Wang Shi‐Ping , Li Hui‐Cong , Bai Fu‐Quan , Zhang Hong‐Xing
Published: May 2020

The comparative study on the photophysical properties between cheap metal Fe (II) complexes and noble metal Ru (II) complexes with identical ligand coordination is performed by the combination of density functional theory (DFT) and time‐dependent density functional theory (TDDFT) to evaluate the potential alternative applications of Fe (II) complexes. RuBIP (BIP = 2,6‐bis (imidazol‐2‐ ylidene)pyridine) is theoretically established that the radiative lifetime of the second lowest triplet state is more consistence with experimental value. However, FeBIP retains nonluminous because of low‐lying 3MC originated from weak d orbital splitting. FeBIPC (FeBIP with carboxylic acid groups) has twice longer lifetime than its parent complex FeBIP due to the great decrease of the energy gap between 3MLCT and 3MC. What's more, the lifetimes of Fe (II) complexes detected in the experiments are more accessible to nonradiative decay lifetimes of 3MC. The carboxylic acid groups are beneficial for the improvement of luminescent possibility and controllability of Fe (II) complexes, while there is still a huge challenge for effective material replacement comparing with Ru (II) complexes.
Message framing strategies for effective marine conservation communication
Authors: Kolandai‐Matchett Komathi , Armoudian Maria
Published: May 2020

Human activities are a major source of threat to marine ecosystems. Solutions thus require changes to or cessation of those activities in addition to multiple restorative and conservation efforts – all of which, in turn, require public support for success. However, scientific understanding of threats to marine ecosystems has not paralleled public understanding of those threats in many jurisdictions. Highly complex, interwoven, distant, vulnerable to multiple stressors, and hosting biota that are biologically unfamiliar to people, marine ecosystems present unique communication challenges.

The merits of effective communication capable of motivating behavioural change, policy action and support for marine conservation are often emphasized. To date, however, environmental communication, as a field, has largely focused on terrestrial ecosystems and more recently on climate change, leaving research‐informed marine conservation communication neglected.

Adding to the small compilation of marine conservation communication literature, this integrative review provides a new understanding of how six message frames (emotional, problem/solution, outcome, value‐based, distance, and social norm) can interactively help enhance the effectuality of conservation messages. Insights from the framing‐related literature are merged with those from relevant fields including the theoretical literature, and the behavioural, social, and environmental sciences to define concepts, provide examples and explain the relevance of the six identified frames. The potential strength of these frames are discussed and suggestions on how they might be used to communicate different marine conservation issues are provided.
Impacts on product quality attributes of monoclonal antibodies produced in CHO cell bioreactor cultures during intentional mycoplasma contamination events
Authors: Fratz‐Berilla Erica J. , Angart Phillip , Graham Ryan J. , Powers David N. , Mohammad Adil , Kohnhorst Casey , Faison Talia , Velugula‐Yellela Sai Rashmika , Trunfio Nicholas , Agarabi Cyrus
Published: May 2020

A mycoplasma contamination event in a biomanufacturing facility can result in costly cleanups and potential drug shortages. Mycoplasma may survive in mammalian cell cultures with only subtle changes to the culture and penetrate the standard 0.2‐µm filters used in the clarification of harvested cell culture fluid. Previously, we reported a study regarding the ability ofMycoplasma argininito persist in a single‐use, perfusion rocking bioreactor system containing a Chinese hamster ovary (CHO) DG44 cell line expressing a model monoclonal immunoglobulin G 1 (IgG1) antibody. Our previous work showed thatM. argininiaffects CHO cell growth profile, viability, nutrient consumption, oxygen use, and waste production at varying timepoints afterM. argininiintroduction to the culture. Careful evaluation of certain identified process parameters over time may be used to indicate mycoplasma contamination in CHO cell cultures in a bioreactor before detection from a traditional method. In this report, we studied the changes in the IgG1 product quality produced by CHO cells considered to be induced by theM. argininicontamination events. We observed changes in critical quality attributes correlated with the duration of contamination, including increased acidic charge variants and high mannose species, which were further modeled using principal component analysis to explore the relationships amongM. argininicontamination, CHO cell growth and metabolites, and IgG1 product quality attributes. Finally, partial least square models using NIR spectral data were used to establish predictions of high levels (≥104colony‐forming unit [CFU/ml]) ofM. argininicontamination, but prediction of levels below 104CFU/ml were not reliable. Contamination of CHO cells withM. argininiresulted in significant reduction of antibody product quality, highlighting the importance of rapid microbiological testing and mycoplasma testing during particularly long upstream bioprocesses to ensure product safety and quality.
Overexpression of the mitochondrial pyruvate carrier reduces lactate production and increases recombinant protein productivity in CHO cells
Authors: Bulté Dubhe B. , Palomares Laura A. , Parra Carolina Gómez , Martínez Juan Andrés , Contreras Martha A. , Noriega Lilia G. , Ramírez Octavio T.
Published: May 2020

Chinese hamster ovary (CHO) cells are characterized by a low glucose catabolic efficiency, resulting in undesirable lactate production. Here, it is hypothesized that such low efficiency is determined by the transport of pyruvate into the mitochondria. The mitochondrial pyruvate carrier (MPC), responsible for introducing pyruvate into the mitochondria, is formed by two subunits, MPC1 and MPC2. Stable CHO cell lines, overexpressing the genes of both subunits, were constructed to facilitate the entry of pyruvate into the mitochondria and its incorporation into oxidative pathways. Significant overexpression of both genes, compared to the basal level of the control cells, was verified, and subcellular localization of both subunits in the mitochondria was confirmed. Kinetic evaluation of the best MPC overexpressing CHO cells showed a reduction of up to 50% in the overall yield of lactate production with respect to the control. An increase in specific growth rate and maximum viable cell concentration, as well as an increase of up to 40% on the maximum concentration of two recombinant model proteins transiently expressed (alkaline phosphatase or a monoclonal antibody), was also observed. Hybrid cybernetic modeling, that considered 89 reactions, 25 extracellular metabolites, and a network of 62 intracellular metabolites, explained that the best MPC overexpression case resulted in an increased metabolic flux across the mitochondrial membrane, activated a more balanced growth, and reduced the Warburg effect without compromising glucose consumption rate and maximum cell concentration. Overall, this study showed that transport of pyruvate into the mitochondria limits the efficiency of glucose oxidation, which can be overcome by a cell engineering approach.
Asymmetrical cortical vessel sign predicts prognosis after acute ischemic stroke
Authors: Liu Yong‐Lin , Xiao Wei‐Min , Lu Jie‐Kai , Wang Ya‐Zhi , Lu Zhi‐Hao , Zhong Huo‐Hua , Qu Jian‐Feng , Fang Xue‐Wen , Liang Man‐Qiu , Chen Yang‐Kun
Published: May 2020

Introduction

To assess whether the asymmetrical cortical vessel sign (ACVS) on susceptibility‐weighted imaging (SWI) could predict 90‐day poor outcomes in anterior circulation acute ischemic stroke (AIS) patients treated with recombinant tissue plasminogen activator (r‐tPA).

Methods

Clinical data of consecutive patients with anterior circulation AIS treated with r‐tPA were retrospectively analyzed. Clinical variables included age, sex, vascular risk factors, NIHSS score, onset to treatment time, and initial hematologic and neuroimaging findings. Follow‐up was performed 90 days after onset. Poor outcome was defined as a modified Rankin scale (mRS) ≥3 at 90 days.

Results

A total of 145 patients were included, 35 (24.1%) patients presented with ACVS (≥Grade 1) on SWI. Fifty‐three (36.6%) patients had a poor outcome at 90 days. ACVS (≥Grade 1) occurred in 21 (39.6%) patients with poor outcome compared with 14 (15.2%) patients with favorable outcome (p = .001). Univariate analysis indicated that age, NIHSS score on admission, previous stroke, hemorrhagic transformation, severe intracranial large artery stenosis or occlusion (SILASO), and ACVS were associated with 90‐day poor outcome (p < .05). Since SILASO and ACVS were highly correlated and ACVS had different grades, we used three logistic regression models. Results from the three models showed that ACVS was associated with 90‐day poor outcome.

Conclusions

In r‐tPA‐treated patients with anterior circulation AIS, ACVS might be a helpful neuroimaging predictor for poor outcome at 90 days.
BIX‐01294 enhanced chemotherapy effect in gastric cancer by inducing GSDME‐mediated pyroptosis
Authors: Deng Bei‐Bei , Jiao Bao‐Ping , Liu Yang‐Jun , Li Yan‐Rong , Wang Gui‐Jun
Published: May 2020

Adjuvant chemotherapy in combination with surgery is expected to be a curative strategy for gastric cancer. However, drug resistance remains an obstacle in effective chemotherapy. Therefore, understanding the potential mechanisms of chemotherapy induced gastric cancer cell death is of great importance. We demonstrated that BIX‐01294 (BIX) at low concentration could induce autophagic flux by converting LC3B‐I to LC3B‐II and directly activate autophagy associated cell death in gastric cancer cell lines at high concentration. BIX at low concentration could help obtain sensitivity of gastric cancer cells to chemotherapy with significantly reduced cell viability. Interestingly, BIX combined Cis (BIX + Cis) treated SGC‐7901 cells display pyroptosis related cell death with large bubbles blown around the membrane, significantly decreased cell viability, elevated lactate dehydrogenase release and increased percentage of propidium iodide and Annexin‐V double positive cells. Furthermore, the cleavage of gasdermin E (GSDME) and caspase‐3 but not GSDMD was detected by immunoblotting and the knockout of GSDME switched pyroptosis into apoptosis in the BIX + Cis combined treated group. Furthermore, the deficiency of Beclin‐1 to inhibit BIX induced autophagic flux completely blocked BIX + Cis combined treated induced cell pyroptosis related cell death. Additionally, BIX + Cis in vivo treatment could inhibit tumor growth, which could be reversed by the deficiency of Beclin‐1 and be delayed by the deficiency of GSDME. In conclusion, our data was the first to reveal that BIX enhanced the anticancer chemotherapy effect by induced GSDME‐mediated pyroptosis through the activation of autophagic flux in gastric cancer cells.
Anticarcinogenic effects of halofuginone on lung‐derived cancer cells
Authors: Demiroglu‐Zergeroglu Asuman , Turhal Gulseren , Topal Halime , Ceylan Hurmuz , Donbaloglu Fadime , Karadeniz Cerit Kivilcim , Odongo Ronald R.
Published: May 2020

Malignant mesothelioma is a rare but aggressive form of malignancy, which is difficult to diagnose and is resistant to current chemotherapeutic treatment options. Molecular techniques have been used to investigate the mechanisms of action and the beneficial therapeutic effects of halofuginone (HF) in several cancers but not malignant mesotheliomas. In this study, the antiproliferative and apoptotic effects of HF were investigated through its ability to deregulate EGFR downstream signalling cascade proteins in the pathologically aggressive malignant mesothelioma and non‐small‐cell lung cancer cells. We showed that administration of HF at nanomolar concentrations induced a dose‐dependent reduction in the viability of cancer cells, made cell cycle arrest, inhibited proliferation of cancer cells via STAT3 and ERK1/2 pathways and triggered the apoptotic cascade via p38MAPK. We demonstrated that the apoptotic cell death mechanism was mediated by enhanced activation of caspase‐3 and concomitant PARP cleavage, downregulation of Bcl‐2 and upregulation of Bax in both malignant mesothelioma and lung cancer cells. In particular, we demonstrated that cancer cells were more sensitive to HF treatment than normal mesothelial cells. Taken together, this study suggests that HF exerts its anticancer effects in lung‐derived cancers by targeting signal transduction pathways mainly through deregulation of ERK1/2, STAT3 and p38MAPK to reduce cancer cell viability, induce cell cycle arrest and apoptotic cell death. Thus, HF might be considered as a potential agent against malignant mesothelioma and/or lung cancer cells.
Bleeding from pancreatic arteriovenous malformation with duodenal ulcer penetration. Case report and literature review
Authors: Takayama Hiroshi , Shimodate Yuichi , Nomura Satoshi , Kitagawa Hirohisa , Akaike Yoko , Uchino Kaori , Watanabe Tetsuo , Mizuno Motowo
Published: May 2020

Dilated vessels at the ulcer floor of the second part of the duodenum can be signs of pancreatic arteriovenous malformation; contrast‐enhanced computed tomography should be performed, and surgical treatment should be considered.
Scalable approach to high coverages on oxides via iterative training of a machine‐learning algorithm
Authors: Liu Fuzhu , Yang Shengchun , Medford Andrew J.
Published: May 2020

Understanding the interaction of multiple types of adsorbate molecules on solid surfaces is crucial to establishing the stability of catalysts under various chemical environments. Computational studies on the high coverage and mixed coverages of reaction intermediates are still challenging, especially for transition‐metal compounds. In this work, we present a framework to predict differential adsorption energies and identify low‐energy structures under high‐ and mixed‐adsorbate coverages on oxide materials. The approach uses Gaussian process machine‐learning models with quantified uncertainty in conjunction with an iterative training algorithm to actively identify the training set. The framework is demonstrated for the mixed adsorption of CHx, NHx and OHx species on the oxygen vacancy and pristine rutile TiO2(110) surface sites. The results indicate that the proposed algorithm is highly efficient at identifying the most valuable training data, and is able to predict differential adsorption energies with a mean absolute error of ∼0.3 eV based on <25 % of the total DFT data. The algorithm is also used to identify 76 % of the low‐energy structures based on <30 % of the total DFT data, enabling construction of surface phase diagrams that account for high and mixed coverage as a function of the chemical potential of C, H, O, and N. Furthermore, the computational scaling indicates the algorithm scales nearly linearly (N1.12) as the number of adsorbates increases. This framework can be directly extended to metals, metal oxides, and other materials, providing a practical route toward the investigation of the behavior of catalysts under high‐coverage conditions.
Morphology and Composition Regulation of FeCoNi Prussian Blue Analogues to Advance in the Catalytic Performances of the Derivative Ternary Transition‐Metal Phosphides for OER
Authors: Du Yuanxin , Ding Xin , Han Meng , Zhu Manzhou
Published: May 2020

Prussian blue analogues (PBAs) are mostly binary metallic compounds with a cubic structure, which greatly limits the structure and component of derived transition‐metal phosphides (TMPs) and affects their catalytic activities. This work focuses on regulating the morphology and composition of the PBA at the front‐end to optimize the OER performance of the derived TMP. By temperature control surfactant desorption ability, we obtain a series of ternary FeCoNi (FCN‐PBAs). With the increase of temperature, their morphologies change from truncated octahedrons to cubic octahedrons and truncated cubes, in which the Fe content basically remains unchanged and the Co/Ni ratio gradually decreased. Due to the synergistic effect among ternary TMPs, all phosphidation products (FCN‐P) exhibit better OER activities than RuO2, among which FCN‐40‐P shows the best performance. As confirmed by XPS analyses, the appropriate chemical composition enhances the oxidizabilityof TM species, promotes the chemical adsorption of OH−, and accelerates OER kinetics.
Detection of LC3‐Associated Phagocytosis (LAP)
Authors: Martinez Jennifer
Published: May 2020

Phagocytes, notably macrophages, are critical sentinels of their environment, patrolling for and eradicating unwanted components. The ability of cells to process extracellular cargo in an appropriate manner is important for both clearance of the cargo and eventual return to homeostasis. Although the evolutionarily conserved pathway of autophagy involves the degradation and recycling of unnecessary or dysfunctional cellular components during starvation, we now appreciate that the reach of autophagy extends beyond nutrient deprivation, notably including cellular quality control (e.g., mitophagy) and host defense against internalized pathogens (i.e., xenophagy). Despite being seemingly disparate, autophagic functions are unified as conserved mechanisms for containment and immunosuppression, suggesting an original immune function for autophagy. A recently described pathway called LC3‐associated phagocytosis (LAP) marries the ancient concepts of phagocytosis and autophagy, revealing new ways in which the autophagy machinery, in a molecularly distinct pathway, contributes to the inflammatory response. In this article, protocols to detect LAP by electron microscopy, immunofluorescence, flow cytometry, and phagosome purification are described, allowing the user to detect multiple characteristics of LAP in both qualitative and quantitative manners. Published 2020. U.S. Government.

Basic Protocol 1: Detection of LAP by electron microscopy

Basic Protocol 2: Detection of LAP by confocal microscopy of LC3‐GFP‐expressing cells

Alternate Protocol 1: Detection of LAP by confocal microscopy using immunofluorescence

Basic Protocol 3: Detection of LAP using flow cytometry of LC3‐GFP‐expressing cells

Alternate Protocol 2: Detection of LAP using antibody staining and flow cytometry

Basic Protocol 4: Detection of LAP by western blot of purified LAPosomes
Mary, Hugo, and Hugo*: Learning to schedule distributed data‐parallel processing jobs on shared clusters
Authors: Thamsen Lauritz , Beilharz Jossekin , Tran Vinh Thuy , Nedelkoski Sasho , Kao Odej
Published: May 2020

Distributed data‐parallel processing systems like MapReduce, Spark, and Flink are popular for analyzing large datasets using cluster resources. Resource management systems like YARN or Mesos in turn allow multiple data‐parallel processing jobs to share cluster resources in temporary containers. Often, the containers do not isolate resource usage to achieve high degrees of overall resource utilization despite overprovisioning and the often fluctuating utilization of specific jobs. However, some combinations of jobs utilize resources better and interfere less with each other when running on the same shared nodes than others. This article presents an approach for improving the resource utilization and job throughput when scheduling recurring distributed data‐parallel processing jobs in shared clusters. The approach is based on reinforcement learning and a measure of co‐location goodness to have cluster schedulers learn over time which jobs are best executed together on shared resources. We evaluated this approach over the last years with three prototype schedulers that build on each other: Mary, Hugo, and Hugo*. For the evaluation we used exemplary Flink and Spark jobs from different application domains and clusters of commodity nodes managed by YARN. The results of these experiments show that our approach can increase resource utilization and job throughput significantly.
Whole‐Mount In Situ Hybridization in Post‐Implantation Staged Mouse Embryos
Authors: Barratt Kristen S. , Arkell Ruth M.
Published: May 2020

Understanding RNA expression in space and time is a key initial step in dissecting gene function. The ability to visualize gene expression in whole‐tissue or whole‐specimen preparations, called in situ hybridization (ISH), was first developed 50 years ago. Two decades later, these protocols were adapted to establish robust methods for whole‐mount ISH to murine embryos. The precise protocols vary somewhat between early‐gestation and mid‐gestation mouse embryos; the protocol presented here is optimal for use with post‐implantation stage mouse embryos (stages 5.5–9.5 dpc). Routine uses of whole‐mount ISH include documenting the wild‐type expression pattern of individual genes and comparison of the expression pattern of signature genes (i.e., those that identify particular cells and tissues within an embryo) between wild‐type and mutant embryos as part of a phenotyping experiment. This technique remains a mainstay of developmental biology studies and complements the massively parallel assessment of gene expression from dissociated tissues and cells via RNA‐sequencing techniques. © 2020 by John Wiley & Sons, Inc.

Basic Protocol 1: Dissection of post‐implantation (5.5‐9.5 dpc) murine embryos

Basic Protocol 2: Whole‐mount in situ hybridization in post‐implantation embryos

Basic Protocol 3: Visualization of post‐WMISH embryos

Support Protocol 1: Creation of siliconized glass pipettes

Support Protocol 2: Creation of embryo powder
Management of Osteoarthritis During the COVID‐19 Pandemic
Authors: Ragni Enrico , Mangiavini Laura , Viganò Marco , Brini Anna Teresa , Peretti Giuseppe Michele , Banfi Giuseppe , de Girolamo Laura
Published: May 2020

The pandemic spread of the new coronavirus disease 2019 (COVID‐19) infection in China first, and all over the world at present, has become a global health emergency due to the rapidly increasing number of affected patients. Currently, a clear relationship between COVID‐19 infection incidence and/or complications due to chronic or occasional treatments for other pathologies is still not clear, albeit the COVID‐19 pandemic may condition the treatment strategy of complex disorders, such as osteoarthritis (OA). Importantly, OA is the most common age‐related joint disease, affecting more than 80% of people older than the age of 55, an age burden also shared with the highest severity in COVID‐19 patients. OA patients often show a large array of concomitant pathologies, such as diabetes, inflammation, and cardiovascular diseases that are again shared with COVID‐19 patients and may therefore increase complications. Moreover, different OA treatments, such as NSAIDs, paracetamol, corticosteroids, opioids, or other molecules have a wide array of iatrogenic effects, potentially increasing COVID‐19 secondary infection incidence or complications. In this review we critically analyze the evidence on either negative or positive effects of drugs commonly used to manage OA in this particular scenario. This would provide orthopedic surgeons in particular, and physicians, pharmacologists, and clinicians in general, a comprehensive description about the safety of the current pharmacological approaches and a decision‐making tool to treat their OA patients as the coronavirus pandemic continues.
Break Up to Make Up: Utilization of Photocleavable Groups in Biolabeling of Hydrogel Scaffolds
Authors: Truong Vinh X.
Published: May 2020

Understanding cell behavior within the extracellular matrix is essential for the implementation of biomaterials in medical applications. Conjugation of bioactive molecules to hydrogel scaffolds imparts the materials with biological cues necessary for controlling cell behavior such as adhesion, growth and migration. Photo‐induced ligation is a powerful tool to precisely control when and where such bioactivity can be initiated. Over the past decade, advances in light‐regulated technology have emerged to address the stringent demands for photochemical ligation in biological environments, including high sensitivity, fast reaction kinetics, longer wavelength absorption and site‐selectivity. Here, the utilization of contemporary photolabile groups for light‐mediated bioconjugation of hydrogels are highlighted. In this approach, reactive groups such as thiol, amine and aldehyde are masked with photolabile moieties, which can be photo‐released to participate in click reactions, such as Michael addition and oxime ligation. New chromophores with long wavelength visible light absorption are also examined for potential employment in light‐induced bioconjugation.
Generating Bacterial Foods in Toxicology Studies with Caenorhabditis elegans
Authors: Ke Tao , Santamaría Abel , Tinkov Alexey A. , Bornhorst Julia , Aschner Michael
Published: May 2020

Caenorhabditis elegans is a free‐living animal that is used as a powerful experimental model in biological sciences. The natural habitat of the animal are areas rich in material from rotting plants or fruits being decomposed by a growing number of microorganisms. The ecology of the natural habitat of C. elegans is a complex interactive network involving many species, including numerous types of bacteria, viruses, fungi, slugs, snails, and isopods, among which bacteria play multifaceted roles in the natural history of C. elegans. Under laboratory conditions, C. elegans is routinely cultured in a petri dish filled with solidified agar and seeded with Escherichia coli strain OP50, the latter offering an alternative model to study the interaction between bacteria and host. Because of the clear advantages of generating specific bacterial foods for mechanistic studies in C. elegans, it is important to develop a robust protocol to generate high‐quality bacterial foods commensurate with experimental requirements. Based on previous work by us and others, herein we present a protocol on how to generate these optimal bacterial food–based research tools. © 2020 by John Wiley & Sons, Inc.

Basic Protocol 1: Preparing concentrated E. coli OP50

Basic Protocol 2: Titrating bacteria concentration

Basic Protocol 3: Generating dead bacterial food by heating

Basic Protocol 4: Generating dead bacterial food by antibiotics

Basic Protocol 5: Feeding C. elegans with bacterial foods in liquid