bluuebunny/crossref_metadata_2025 huggingface dataset:
Unstimulated apheresis for chimeric antigen receptor manufacturing in pediatric/adolescent acute lymphoblastic leukemia patients
Authors: Jarisch Andrea , Rettinger Eva , Sörensen Jan , Klingebiel Thomas , Schäfer Richard , Seifried Erhard , Bader Peter , Bonig Halvard
Published: September 2020

Autologous unstimulated leukapheresis product serves as starting material for a variety of innovative cell therapy products, including chimeric antigen receptor (CAR)‐modified T‐cells. Although it may be reasonable to assume feasibility and efficiency of apheresis for CAR‐T cell manufacture, several idiosyncrasies of these patients warrant their separate analysis: target cells (mononuclear cells [MNC] and T‐cells) are relatively few which may instruct the selection of apheresis technology, low body weight, and, hence, low total blood volume (TBV) can restrict process and product volume, and patients may be in compromised health. We here report outcome data from 46 consecutive leukaphereses in 33 unique pediatric patients performed for the purpose of CD19‐CAR‐T‐cell manufacturing. Apheresis targets of 2×109 MNC/1×109 T‐cells were defined by marketing authorization holder specification. Patient weight was 8 to 84 kg; TBV was 0.6 to 5.1 L. Spectra Optia apheresis technology was used. For 23 patients, a single apheresis sufficed to generate enough cells and manufacture CAR‐T‐cells, the remainder required two aphereses to meet target dose and/or two apheresis series because of production failure. Aphereses were technically feasible and clinically tolerable without serious adverse effects. The median collection efficiencies for MNC and T‐cells were 53% and 56%, respectively. In summary, CAR apheresis in pediatric patients, including the very young, is feasible, safe and efficient, but the specified cell dose targets can be challenging in smaller children. Continuous monitoring of apheresis outcomes is advocated in order to maintain quality.
Cytotoxic and chemotaxonomic study of isolated metabolites from Centaurea aegyptiaca
Authors: Mohamed Tarik A. , Elshamy Abdelsamed I. , Abd‐ElGawad Ahmed M. , Hussien Taha A. , El‐Toumy Sayed A. , Efferth Thomas , Hegazy Mohamed‐Elamir F.
Published: September 2020

The aerial parts of Centaureaa egyptiaca afforded 10 secondary metabolites including four sesquiterpene lactones; chlorohyssopifolin A (centaurepensin) (1), rediolpidetriol (2), linichlorinA (3), and sinaicin (4), one monoterpene; loliolid (5), one phenolic: tyrosol (6), three lignans; arctigenin (7), matairesinol (8), and pinoresinol (9), and one steroid; ergosta‐5,22‐dien‐3‐ol (10). The cluster analysis of 32 Centaurea species revealed that C. aegyptiaca is closely related to C. repens and C. solstitialise. The isolated compounds (1–10) were screened against CCRF‐CEM‐leukemia, MDA‐MB‐231‐pcDNA3 breast cancer, and HCT116 (p53+/+) colon carcinoma cell lines. Compounds1 and 2 were the most potent compounds against both leukemia and breast carcinoma cell lines.
A Differential Motivation Account for the Disparity between Willingness to Accept and Willingness to Pay
Authors: Kim Tom Joonhwan , Srivastava Joydeep
Published: September 2020

We take a motivated reasoning perspective to examine the robust finding that a seller's willingness to accept (WTA) to give up a good is typically higher than a buyer's willingness to pay (WTP) to obtain the good. We propose that the seller/buyer role and/or the WTA/WTP elicitation activate different motivations. Four studies, using different ways to test for motivational processes, demonstrate how motivational processes influence the WTA‐WTP disparity in a predictable and systematic way. Study 1 shows that the WTA/WTP elicitation activates distinct motivations and that altering the medium of exchange reverses the motivations. Study 2 shows that eliciting WTA/WTP using an auction mechanism activates multiple motivations, attenuating the WTA‐WTP disparity. Study 3 demonstrates that activating regulatory focus that is inconsistent (vs. consistent) with the motivation activated by the WTA/WTP elicitation attenuates the WTA‐WTP disparity. Study 4 demonstrates that WTA/WTP elicitation may bias perceptions of an ambiguous stimulus and that the WTA‐WTP disparity increases with delay. Together, our findings provide new insights into the valuation of sellers and buyers by highlighting the role of motivational processes underlying the WTA‐WTP disparity.
Fast skeletal muscle troponin activator CK‐2066260 mitigates skeletal muscle weakness independently of the underlying cause
Authors: Cheng Arthur J. , Ström Jennifer , Hwee Darren T. , Malik Fady I. , Westerblad Håkan
Published: September 2020

Background

Muscle weakness is a common symptom in numerous diseases and a regularly occurring problem associated with ageing. Prolonged low‐frequency force depression (PLFFD) is a form of exercise‐induced skeletal muscle weakness observed after exercise. Three different intramuscular mechanisms underlying PLFFD have been identified: decreased sarcoplasmic reticulum Ca2+ release, decreased myofibrillar Ca2+ sensitivity, and myofibrillar dysfunction. We here used these three forms of PLFFD as models to study the effectiveness of a fast skeletal muscle troponin activator, CK‐2066260, to mitigate muscle weakness.

Methods

Experiments were performed on intact single muscle fibres or fibre bundles from mouse flexor digitorum brevis, which were stimulated with electrical current pulses, while force and the free cytosolic [Ca2+] ([Ca2+]i) were measured. PLFFD was induced by three different stimulation protocols: (i) repeated isometric contractions at low intensity (350 ms tetani given every 5 s for 100 contractions); (ii) repeated isometric contractions at high intensity (250 ms tetani given every 0.5 s for 300 contractions); and (iii) repeated eccentric contractions (350 ms tetani with 20% length increase given every 20 s for 10 contractions). The extent and cause of PLFFD were assessed by comparing the force–[Ca2+]i relationship at low (30 Hz) and high (120 Hz) stimulation frequencies before (control) and 30 min after induction of PLFFD, and after an additional 5 min of rest in the presence of CK‐2066260 (10 μM).

Results

Prolonged low‐frequency force depression following low‐intensity and high‐intensity fatiguing contractions was predominantly due to decreased sarcoplasmic reticulum Ca2+ release and decreased myofibrillar Ca2+ sensitivity, respectively. CK‐2066260 exposure resulted in marked increases in 30 Hz force from 52 ± 16% to 151 ± 13% and from 6 ± 4% to 98 ± 40% of controls with low‐intensity and high‐intensity contractions, respectively. Following repeated eccentric contractions, PLFFD was mainly due to myofibrillar dysfunction, and it was not fully reversed by CK‐2066260 with 30 Hz force increasing from 48 ± 8% to 76 ± 6% of the control.

Conclusions

The fast skeletal muscle troponin activator CK‐2066260 effectively mitigates muscle weakness, especially when it is caused by impaired activation of the myofibrillar contractile machinery due to either decreased sarcoplasmic reticulum Ca2+ release or reduced myofibrillar Ca2+ sensitivity.
Electro‐oxidation of amoxicillin using titanium electrodes electrophoretically coated by iridium or ruthenium with tantalum oxides
Authors: León Itzel , Gomes Helena , Sepúlveda‐Guzmán Selene , Cárdenas Jesus , Rivera Fernando , Manríquez Juan , Bustos Erika
Published: September 2020

BACKGROUND

Amoxicillin (AMX) is one of the pharmaceutical compounds in waters being targeted in wastewater decontamination studies, and some of the technological alternatives to degrade it involve using modified surfaces with transition metal oxides, such as IrO2/Ta2O5|Ti and RuO2/Ta2O5|Ti, for in situ production of hydroxyl radical (•OH) to oxidize AMX in aqueous media.

RESULTS

The IrO2/Ta2O5|Ti 70:30 electrode was best suited for AMX electro‐oxidation, with 99.23% removal measured by HPLC‐UV–Vis, 81.13% by COD removal, and current efficiency of 41.1% in 0.1 mol L–1 Na2SO4 after applying 15 mA for 6 h. These results are due to a larger surface area (251.67 cm2) and a higher amount of •OH radicals being generated by cm2 in neutral pH (3.8 mol L–1 cm−2) compared to the other electrodes.

CONCLUSION

This paper shows the simulation of the experimental data regarding the complete degradation of AMX (100%) by HPLC, comparing the experimental results and simulation results for AMX degradation using the IrO2/Ta2O5|Ti 70:30. The modeling predicts and validates the disengagement of COD obtained experimentally, considering the mechanism proposed by Trovó and collaborators for the electro‐oxidation of AMX to product C6 (C16H22N3O7S) by generating •OH. © 2020 Society of Chemical Industry (SCI)
Sonography of pediatric gastrointestinal venous malformations
Authors: Zhang Min , Lin Hai , Qin Ling‐Ling
Published: September 2020

Gastrointestinal (GI) venous malformations are extremely rare. Such malformations present in the pediatric age group and can occur anywhere in the digestive tract (esophagus, stomach, small or large intestine, anus, and mesentery). We present the sonographic findings of three cases of pediatric GI venous malformation. Sonography is an important diagnostic method in pediatric GI venous malformations.
Early life exposure to hypercaloric diet impairs eating behavior during weaning: The role of BDNF signaling and astrocyte marks
Authors: Palazzo Roberta Passos , Torres Iraci L. S. , Grefenhagen Ágnis Iohana , da Silva Bruno Batista , de Meireles Louisiana Carolina Ferreira , de Vargas Kethleen Costa , Alves Zingara , Pereira Silva Lenir Orlandi , Siqueira Ionara Rodrigues
Published: September 2020

Literature shows that gestational and/or lactational exposure to hypercaloric diets induces long term effects on eating behavior and the involvement of neurochemical mechanisms. We hypothesized that the effects of hypercaloric diets in early development phases can precede an overweight or an obesity status. The aim of the present study was to evaluate the impact of gestational and lactational exposure to cafeteria diet on eating behavior and neurochemical parameters, BDNF signaling, epigenetic and astrocyte marks in the hippocampus and olfactory bulb during the weaning phase. Pregnant female rats were randomized between standard and cafeteria diet, the respective diet was maintained through the lactational period. The framework of feeding pattern, meal, and its microstructure, was observed in postnatal day 20. Exposure to cafeteria diet increased the number of meals, associated with a lower first inter‐meal interval and higher consumption in both genders, without any changes in body weight. Diet exposure also reduced the number of grooming, a behavior typically found at the end of meals. Hypercaloric diet exposure reduced BDNF levels in the olfactory bulb and hippocampus from rats of both sexes and increased the content of the TrkB receptor in hippocampi. It was observed an increase in HDAC5 levels, an epigenetic mark. Still, early exposure to the hypercaloric diet reduced hippocampal GFAP and PPARγ levels, without any effect on NeuN content, indicating that alterations in astrocytes can precede those neuronal outcomes. Our results showed that changes in interrelated neurochemical signaling, BDNF, and astrocyte marks, induced by hypercaloric diet in early stages of development may be related to impairment in the temporal distribution of eating pattern and consequent amounts of consumed food during the weaning phase.
Spatial association of SEMA3C with nerve endings/terminal Schwann cells in hair follicle isthmus region
Authors: Zhong Hong‐Bing , Chu Qing‐Song , Xiang Jan Jian , Zhang Arina Li , Chen Eve Qian , Shen Xing‐Ru , Liao Xin‐Hua
Published: September 2020

Nerve endings and terminal Schwann cells (TSCs) specifically and densely surround hair follicle at isthmus area, forming a neuromuscular‐junction‐like structure called lanceolate complex. The interplay between neuronal components and epidermis in this specialized structure enables hair to properly sense complex stimuli from environments. However, how nerves precisely attach to and innervate this specific region during development remains to be elucidated. Here, we demonstrate that SEMA3C, a secreted protein member of semaphorin family responsible for axonal guidance, is localized right below sebaceous gland and in close approximation with nerve endings and TSCs processes all through the entire hair cycle. SEMA3C protein is deposited outside of epithelial cells and its expression is independent on the presence of nerve endings/TSCs. SEMA3C is also found in portions of dermal papilla at growth phase. The tight spatial association of SEMA3C with lanceolate complex suggests that it might play roles in establishment and/or maintenance of the lanceolate complex in hair follicle.
Implication, visualization, and characterization through scanning electron microscopy as a tool to identify nonedible oil seeds
Authors: Cheema Saman Ilyas , Ahmad Mushtaq , Ullah Riaz , Mothana Ramzi A. , Noman Omar M. , Zafar Muhammad , Sultana Shazia , Hameed Ayesha , Naz Saeeda , Akhtar Maryam Tanveer
Published: September 2020

Second‐generation biofuels prove to be a distinctive and renewable source of sustainable energy and cleaner environment. The current study focuses on the exploration and identification of four nonedible sources, that is, Brassica oleracea L., Carthamus oxyacantha M.Bieb., Carthamus tinctorius L., and Beaumontia grandiflora Wall., utilizing light microscopy (LM) and scanning electron microscopy (SEM) for studying the detailed micromorphological features of these seeds. LM revealed that size ranges from 3 to 20 mm. furthermore, a great variety of color is observed from pitch black to greenish gray and yellowish white to off white. Seeds ultrastructure study with the help of SEM revealed a great variety in shape, size, color, sculpturing and periclinal wall shape, and so on. Followed by the production of fatty acid methyl esters from a novel source, that is, seeds oil of Brassica oleracea L. (seed oil content 42.20%, FFA content 0.329 mg KOH/g) using triple metal impregnated montmorillonite clay catalyst (Cu‐Mg‐Zn‐Mmt). Catalyst was characterized using SEM–EDX, FT‐IR. Maximum yield of Brassica oleracea L. biodiesel (87%) was obtained at the conditions; 1:9 of oil to methanol ratio, 0.5 g of catalyst, 5 hr reaction time, and 90°C of temperature. Synthesized biodiesel was characterized by FT‐IR, GC–MS, and NMR. Fuel properties of the Brassica oleracea L. FAMES were determined and found in accordance with ASTM standards.
Waveguide transmission line parameter analysis based on the FDTD method
Authors: Jiang Zhaoneng , Ji Fangzheng , Huang Shichun , Xuan Xiaofeng , Wang Zhixin
Published: September 2020

In order to quickly analyze discontinuity or periodic structure transmission characteristics, the combination of finite‐difference time‐domain method and singular value decomposition is applied. A double‐ridge waveguide (WRD) and its improvement are studied. According to the simulation results about propagation constant and eigen‐functions, the transmission performance of WRD can be improved by adding fillets and enlarging the radius of fillets or filling dielectric material. Guided wave and mode characteristics of substrate integrated waveguide (SIW) are also researched in detail. Simulation carried out for different periodic SIW structures shows that due to the periodic gap, electromagnetic energy leakage is present in the metallized via waveguide wall of the SIW. It is significant for the future improvement and application of SIW structure.
Deep proteomics and phosphoproteomics reveal novel biological pathways perturbed by morphine, morphine‐3‐glucuronide and morphine‐6‐glucuronide in human astrocytes
Authors: Dozio Vito , Daali Youssef , Desmeules Jules , Sanchez Jean‐Charles
Published: September 2020

Tolerance and hyperalgesia associated with chronic exposure to morphine are major limitations in the clinical management of chronic pain. At a cellular level, neuronal signaling can in part account for these undesired side effects, but unknown mechanisms mediated by central nervous system glial cells are likely also involved. Here we applied data‐independent acquisition mass spectrometry to perform a deep proteome and phosphoproteome analysis of how human astrocytes responds to opioid stimulation. We unveil time‐ and dose‐dependent effects induced by morphine and its major active metabolites morphine‐3‐glucuronide (M3G) and morphine‐6‐glucuronide that converging on activation of mitogen‐activated protein kinase and mammalian target of rapamycin signaling pathways. We also find that especially longer exposure to M3G leads to significant dysregulation of biological pathways linked to extracellular matrix organization, antigen presentation, cell adhesion, and glutamate homeostasis, which are crucial for neuron– and leukocyte–astrocyte interactions.
Noradrenaline protects neurons against H2O2‐induced death by increasing the supply of glutathione from astrocytes via β3‐adrenoceptor stimulation
Authors: Yoshioka Yasuhiro , Negoro Ryosuke , Kadoi Hisatsugu , Motegi Toshiki , Shibagaki Fumiya , Yamamuro Akiko , Ishimaru Yuki , Maeda Sadaaki
Published: September 2020

Oxidative stress has been implicated in a variety of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. Astrocytes play a significant role in maintaining survival of neurons by supplying antioxidants such as glutathione (GSH) to neurons. Recently, we found that noradrenaline increased the intracellular GSH concentration in astrocytes via β3‐adrenoceptor stimulation. These observations suggest that noradrenaline protects neurons from oxidative stress‐induced death by increasing the supply of GSH from astrocytes to neurons via the stimulation of β3‐adrenoceptor in astrocytes. In the present study, we examined the protective effect of noradrenaline against H2O2‐induced neurotoxicity using two different mixed cultures: the mixed culture of human astrocytoma U‐251 MG cells and human neuroblastoma SH‐SY5Y cells, and the mouse primary cerebrum mixed culture of neurons and astrocytes. H2O2‐induced neuronal cell death was significantly attenuated by pretreatment with noradrenaline in both mixed cultures but not in single culture of SH‐SY5Y cells or in mouse cerebrum neuron‐rich culture. The neuroprotective effect of noradrenaline was inhibited by SR59230A, a selective β3‐adrenoceptor antagonist, and CL316243, a selective β3‐adrenoceptor agonist, mimicked the neuroprotective effect of noradrenaline. DL‐buthionine‐[S,R]‐sulfoximine, a GSH synthesis inhibitor, negated the neuroprotective effect of noradrenaline in both mixed cultures. MK571, which inhibits the export of GSH from astrocytes mediated by multidrug resistance‐associated protein 1, also prevented the neuroprotective effect of noradrenaline. These results suggest that noradrenaline protects neurons against H2O2‐induced death by increasing the supply of GSH from astrocytes via β3‐adrenoceptor stimulation.
Value first, cost later: Total value contribution as a new approach to sourcing decisions
Authors: Gray John V. , Helper Susan , Osborn Beverly
Published: September 2020

Firms compete on value, not cost alone. However, sourcing decisions are often heavily weighted towards minimizing costs, even though these decisions also can affect revenue, risk, and other stakeholder values. To address this disconnect, we introduce a new approach to strategic sourcing, “total value contribution” (TVC). The TVC name by itself promotes attention to value. TVC's structured approach begins with the question: “what do our customers, current and future, value about our products?” The TVC approach builds on insights from the literature on individual and group decision‐making to offset human biases and organizational incentives that emphasize cost reduction. TVC builds on gains already achieved by “total cost of ownership” (TCO) sourcing methods, which broadened the list of factors considered in sourcing. We provide examples of TVC‐like thinking in real organizations and argue that such thinking would be more common with the dissemination of TVC. We also provide access to a version of this JOM Forum piece suitable to assign to students, and discuss a new teaching note which describes how to implement TVC in a popular strategic sourcing teaching case. We believe widespread implementation of TVC would improve both organizational and social outcomes.
Acute kidney injury risk with piperacillin‐tazobactam and vancomycin combination therapy: single centre retrospective study
Authors: McLaren Emma , Banakh Iouri , Cam Sok Leng , Loh Grace , Meanger Darshana , Wanniarachchi Lakmal
Published: September 2020

Aim

To evaluate the risk of acute kidney injury (AKI) in patients who receive vancomycin (VNC) and piperacillin‐tazobactam (PTZ) combination therapy.

Method

A single centre, retrospective audit of adult patients treated with VNC alone and in combination with PTZ between 2014–2015. Data was extracted from digital medical records and therapeutic drug monitoring sheets completed by clinical pharmacists. Rates of AKI and duration of combination therapy were analysed by chi‐square, with logistic regression analysis completed to control for nephrotoxins, intensive care unit admission, use of inotropes and pre‐existing chronic kidney disease.

Results

Out of 525 vancomycin courses, that met the inclusion criteria, 211 had PTZ co‐prescribed during the study period. Combination therapy was significantly both associated with an increased rate of AKI compared to VNC use alone (17.5% vs 10.5%, P = 0.02). The mean duration of combination therapy was 4 days (1–17 days). Increased duration of exposure to combination therapy was also associated with a higher incidence of AKI (3.8 days vs. 5.2 days, P = 0.014). VNC‐TPZ combination was identified to be an independent risk factor for AKI (OR 1.73, 95% CI 1.01–2.96, P = 0.046) after adjusting for other known risk factors for AKI, including vasopressor use and intensive care unit admission.

Conclusion

Combined use of VNC‐PTZ, as well as the duration of combination therapy are both associated with an increased risk of AKI compared with VNC alone. The results are similar to previous literature reports of AKI from the combination of antibiotics. Healthcare providers need to be vigilant and limit the exposure to this combination as clinically appropriate.
Dissemination of Information During Public Health Crises: Early COVID‐19 Data From The Laryngoscope
Authors: Chern Alexander , Selesnick Samuel H.
Published: September 2020

Objectives

During a public health crisis, it is important for medical journals to share information in a timely manner while maintaining a robust peer‐review process. This review reports and analyzes The Laryngoscope's publication trends and practices during the COVID‐19 pandemic, before the COVID‐19 pandemic, and during previous pandemics.

Methods

Comprehensive review of two databases (PubMed and The Laryngoscope) was performed. COVID‐19 manuscripts (published in The Laryngoscope during the first 4 months of the pandemic) were identified and compared to manuscripts pertaining to historic pandemics (published in The Laryngoscope during the first 2 years of each outbreak). Keywords included “Laryngoscope”, “flu”, “pandemic”, “influenza”, “SARS”, “severe acute respiratory syndrome”, “coronavirus”, “COVID‐19”, and “SARS‐CoV‐2”. Data were obtained from The Laryngoscope to characterize publication trends during and before the COVID‐19 pandemic.

Results

From March 1, 2020 to June 30, 2020, The Laryngoscope had 203 COVID‐19 submissions. As of July 8, 2020, 20 (9.9%) were accepted, 117 (57.6%) under review, and 66 (32.5%) rejected. During the first 4 months of the pandemic, 18 COVID‐19 manuscripts were published. The mean number of days from submission to online publication was 45, compared to 170 in 2018 and 196 in 2019. A total of 4 manuscripts concerning previous pandemics were published during the initial 2 years of each outbreak.

Conclusions

The Laryngoscope rapidly disseminated quality publications during the COVID‐19 pandemic by upholding a robust peer‐review process while expediting editorial steps, highlighting relevant articles online, and providing open access to make COVID‐19‐related publications available as quickly as possible. Laryngoscope, 130:2508–2515, 2020
Characterization of CRB1 splicing in retinal organoids derived from a patient with adult‐onset rod‐cone dystrophy caused by the c.1892A>G and c.2548G>A variants
Authors: Zhang Xiao , Thompson Jennifer A. , Zhang Dan , Charng Jason , Arunachalam Sukanya , McLaren Terri L. , Lamey Tina M. , De Roach John N. , Jennings Luke , McLenachan Samuel , Chen Fred K.
Published: September 2020

Background

Mutations in the human crumbs homologue 1 (CRB1) gene are associated with a spectrum of inherited retinal diseases. However, functional studies demonstrating the impact of individual CRB1 mutations on gene expression are lacking for most variants. Here, we investigated the effect of two CRB1 variants on pre‐mRNA splicing using neural retinal organoids (NRO) derived from a patient with recessive rod‐cone dystrophy caused by compound heterozygous mutations in CRB1 (c.1892A>G and c.2548G>A).

Methods

The patient received ophthalmological examinations including multimodal imaging. NRO were differentiated from induced pluripotent stem cells (iPSCs) derived from the patient and a control subject. CRB1 transcripts were characterized by RT‐PCR and Sanger sequencing.

Results

The Patient displayed retinal thickening with disorganization of retinal layers and preservation of para‐arteriolar retinal pigment epithelium. Both patient and control iPSC produced NRO containing photoreceptor progenitor cells expressing CRB1 mRNA. Patient NRO expressed a novel CRB1 transcript displaying skipping of exon 6. CRB1 transcripts containing the c.2548G>A substitution in exon 7 were expressed in patient NRO.

Conclusions

Together, these results confirm the pathogenicity of the c.1892A>G and c.2548G>A CRB1 variants in a family with recessive adult‐onset rod‐cone dystrophy and further demonstrate the effects of these variants on pre‐mRNA splicing. This data provide important insights into the pathogenic mechanisms associated with these variants.
Simultaneous maxillary and mandibular reconstruction with a single Osteocutaneous fibula free flap: A description of three cases
Authors: Krane Natalie A. , Fagin Adam , Ghanem Tamer A. , Cannady Steven B. , Petrisor Daniel , Wax Mark K.
Published: September 2020

Large defects that comprise both the maxilla and mandible prove to be difficult reconstructive endeavors and commonly require two free tissue transfers. Three cases are presented to discuss an option for simultaneous reconstruction of maxillary and mandibular defects using a single osteocutaneous fibula free flap. The first case describes a 16‐year‐old male with a history of extensive facial trauma sustained in a boat propeller accident resulting in a class IId maxillary and 5 cm mandibular defect status post three failed reconstructive surgeries; the second, a 33‐year‐old male with recurrent rhabdomyosarcoma of the muscles of mastication with resultant hemi‐mandibulectomy and class IId maxillary defects; and lastly, a 48‐year‐old male presenting after a failed scapular free flap to reconstruct defects resulting from a self‐inflicted gunshot wound, which included a 5 cm defect of the right mandibular body and 4.5 cm defect of the inferior maxillary bone. In all cases, a single osteocutaneous fibula free flap was used in two bone segments; one to obturate the maxillary defect and restore alveolar bone and the other to reconstruct the mandibular defect. The most recent patient was able to undergo implantable dental rehabilitation. Postoperatively, the free flaps were viable and masticatory function was restored in all patients during a follow‐up range of 2–4 years.
Fermentation Kinetics of Selected Dietary Fibers by Human Small Intestinal Microbiota Depend on the Type of Fiber and Subject
Authors: van Trijp Mara P. H. , Rösch Christiane , An Ran , Keshtkar Shohreh , Logtenberg Madelon J. , Hermes Gerben D. A. , Zoetendal Erwin G. , Schols Henk A. , Hooiveld Guido J. E. J.
Published: September 2020

Scope

An underexplored topic is the investigation of health effects of dietary fibers via modulation of human small intestine (SI) microbiota. A few previous studies hint at fermentation of some dietary fibers in the distal SI of humans and pigs. Here the potential of human SI microbiota to degrade dietary fibers and produce metabolites in vitro is investigated.

Methods and Results

Fructans, galacto‐oligosaccharides, lemon pectins, and isomalto/malto‐polysaccharides are subjected to in vitro batch fermentations inoculated with ileostomy effluent from five subjects. Fiber degradation products, formation of bacterial metabolites, and microbiota composition are determined over time. Galacto‐ and fructo‐oligosaccharides are rapidly utilized by the SI microbiota of all subjects. At 5h of fermentation, 31%–82% of galacto‐oligosaccharides and 29%–89% fructo‐oligosaccharides (degree of polymerization DP4‐8) are utilized. Breakdown of fructo‐oligosaccharides/inulin DP ≥ 10, lemon pectin, and iso‐malto/maltopolysaccharides only started after 7h incubation. Degradation of different fibers result in production of mainly acetate, and changed microbiota composition over time.

Conclusion

Human SI microbiota have hydrolytic potential for prebiotic galacto‐ and fructo‐oligosaccharides. In contrast, the higher molecular weight fibers inulin, lemon pectin, and iso‐malto/maltopolysaccharides show slow fermentation rate. Fiber degradation kinetics and microbiota responses are subject dependent, therefore personalized nutritional fiber based strategies are required.
Theoretical calculation of power densities in the near‐field region of phased array antenna
Authors: Kim Ilkyu , Lee Jeong‐Hae
Published: September 2020

While a phased array antenna offers new possibilities for cutting edge technologies, implementation of the array antenna raises an important motivation for computing the power densities in the proximity distance where its radiation becomes substantial. In this paper, the power densities of the antenna in the near‐field region is computed using the integral coupling formula based on the far‐field pattern easily attainable using a full‐wave simulation or a measurement. This feature enables to extend its applicability to the practical phased array antenna, which is different from the existing approaches that are restricted to the theoretically derived field distribution of the aperture antennas. Based on the far‐field pattern, the coupling program enables to provide the rapid computation (8.4‐9.7 seconds for a displacement) without a repetition of the lengthy theoretical derivation for each type of antennas. The calculated power densities for the array antenna has a deviation less than 0.7‐1.2 dB for the main beam and 3‐4 dB for the side lobe, which is comparable to the previous works.
Immunohistochemistry-Based Consensus Molecular Subtypes as a Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer
Authors: Li Yaqi , Yao Qianlan , Zhang Long , Mo Shaobo , Cai Sanjun , Huang Dan , Peng Junjie
Published: September 2020

Background

For stage II colorectal cancer (CRC), the efficacy of adjuvant chemotherapy remains controversial. Consensus molecular subtype (CMS) has been validated to be a prognostic tool for CRCs. In this study, CMS status was investigated as a prognostic biomarker for the efficacy of adjuvant chemotherapy for stage II colorectal cancer.

Materials and Methods

The tissue microarray was retrospectively constructed of 165 nonconsecutive, primary, and sporadic stage II CRCs. CMS status was determined by immunohistochemistry staining of CDX2, HTR2B, FRMD6, and ZEB1, combining with microsatellite instability testing. The prognostic for adjuvant chemotherapy efficacy of CMS status was calculated by Kaplan-Meier curves and Cox regression analysis. Subgroup analyses were conducted according to tumor location.

Results

Kaplan-Meier curves indicated that CMS was associated with overall survival (OS) and disease-free survival for stage II CRCs. Cox regression analysis showed that CMS was an independent risk factor for OS. Among high-risk clinicopathological factors, patients with CMS2/3 (hazard ratio [HR]: 0.445, 95% confidence interval [CI]: 0.227–0.875), left-sided tumors (HR: 0.488, 95% CI: 0.247–0.968), or fewer than 12 lymph nodes examined (HR: 0.307, 95% CI: 0.097–0.974) had survival benefit from adjuvant chemotherapy. Subgroup analysis showed that adjuvant chemotherapy only improved OS for patients with left-sided tumors of CMS2/3 subtype. Regardless of CMS, right-sided tumors had no benefit from adjuvant chemotherapy.

Conclusion

CMS is a better prognostic factor for adjuvant chemotherapy for stage II CRCs. Together with tumor location, CMS classification will aid in personalized treatment for stage II CRCs.

Implications for Practice

For stage II colorectal cancer (CRC), the efficacy of adjuvant chemotherapy remains controversial, in that its minimal benefit (no more than 5% on average) is considered not worth the toxic effects of the drugs. There are still no effective prognostic and predictive biomarkers. This study showed that consensus molecular subtype (CMS) status is a predictive marker for adjuvant chemotherapy efficacy. Patients with left-sided tumors of CMS2/3 subtype have survival benefit by receiving adjuvant chemotherapy, which will aid in personalized treatment for stage II CRCs. Moreover, this test of CMS based on immunohistochemistry is cheap, not time consuming, and easily conducted in the laboratories of most hospitals.
Phase II Study of Panitumumab Monotherapy in Chemotherapy-Naïve Frail or Elderly Patients with Unresectable RAS Wild-Type Colorectal Cancer: OGSG 1602
Authors: Terazawa Tetsuji , Kato Takeshi , Goto Masahiro , Ohta Katsuya , Noura Shingo , Satake Hironaga , Kagawa Yoshinori , Kawakami Hisato , Hasegawa Hiroko , Yanagihara Kazuhiro , Shingai Tatsushi , Nakata Ken , Kotaka Masahito , Hiraki Masayuki , Konishi Ken , Nakae Shiro , Sakai Daisuke , Kurokawa Yukinori , Shimokawa Toshio , Satoh Taroh
Published: September 2020

Lessons Learned

Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild-type unresectable colorectal cancer. It is especially effective for left-sided tumors; therefore, panitumumab as first-line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin-based or irinotecan-based combination regimens.

Background

First-line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy-naïve frail or elderly patients with unresectable RAS wild-type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first-line treatment.

Methods

We conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities.

Results

Thirty-six patients (median age: 81 [range, 67–88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty-three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty-eight patients (77.8%) had left-sided CRC, whereas eight (22.2%) had right-sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4–67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5–87.7). The RR of patients with left- and right-sided tumors was 65.4% (95% CI, 44.3–82.8) and 0.0% (95% CI, 0.0–36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%).

Conclusion

Panitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.
Crystal structure analysis of (E)‐N‐(3,5‐dimethylphenyl)‐2‐(substituted benzylidene)thiosemicarbazone: Experimental and theoretical studies
Authors: Wang Sifan , Zhang Xing , Qi Fan , Huang Jie , Wei Chenli , Guo Zeyu
Published: September 2020

Two novel thiosemicarbazone derivatives (E)‐N‐(3,5‐dimethylphenyl)‐2‐(3‐methylbenzylidene)thiosemicar‐bazone (1) and (E)‐N‐(3,5‐dimethylphenyl)‐2‐(3‐fluorobenzylidene)thiosemicarbazone (2) had been synthesized and characterized by FT‐IR, nuclear magnetic resonance, and elemental analysis. Single crystal X‐ray diffraction analysis showed that compound 1 belongs to triclinic system in P‐1 space group and compound 2 belongs to monoclinic system in C2/c space group. It could be seen from the determined crystal structure that the central skeleton NNHC(S)NH of both thiosemicarbazone compounds have good planarity. Density functional theory (DFT) calculations were done using B3LYP/6‐31+G(d, p) basis set and the calculated results are in good agreement with the experimental data. In addition, the UV‐visible absorption spectrum was estimated based on TD‐DFT quantum chemistry calculations. Likewise, the simulated absorption spectrum is very consistent with the experimental data. Combining Hirshfeld surface analysis and molecular structure, it was found that the intermolecular hydrogen bond NH···SC constitutes central symmetric dimer
. Through quantum chemical calculation, we investigated the reduced density gradient function and the independent gradient model, which provided a deeper insight into the intermolecular and intramolecular interaction force of the compounds. The frontier molecular orbital analysis and molecular electrostatic potential were also discussed by theoretical calculations.
Preparation of Nano‐Spherical Cu‐en and Its Catalytic Study on the Performance of Solid Propellant
Authors: Song Naimeng , Liu Jianchao , Yang Li , Liu Pingan
Published: September 2020

This paper mainly describes a nano‐spherical energetic catalyst Cu‐en. The result of particle size distribution shows that the D50 value of Cu‐en is 80.18 nm. The thermal decomposition process of RDX, AP, and NC is improved obviously after mixed with Cu‐en. Among them, the change of AP is the most significant, and its peaks of high‐temperature decomposition and low‐temperature decomposition degenerate into one decomposition peak. The thermal decomposition temperature of NC also decreased from 214.5 °C to 191.6 °C. In the range of 3–9 MPa, Cu‐en can significantly increase the burning rate of HTPB propellant and reduce the pressure exponent n from 0.684 to 0.459. According to the test data results of the CMDB propellant, the nano‐spherical Cu‐en prepared by the spray drying method has a stronger catalytic ability than the micro‐nano Cu‐en prepared by the high‐energy ball milling method.
Structure of the Plasmodium falciparum PfSERA5 pseudo‐zymogen
Authors: Smith Nicholas A. , Clarke Oliver B. , Lee Mihwa , Hodder Anthony N. , Smith Brian J.
Published: September 2020

PfSERA5, a significantly abundant protein present within the parasitophorous vacuole (PV) and essential for normal growth during the blood‐stage life cycle of the malaria parasite Plasmodium falciparum, displays structural similarity to many other cysteine proteases. However, PfSERA5 does not exhibit any detectable protease activity and therefore the role of the PfSERA5 papain‐like domain (PfSERA5E), thought to remain bound to its cognate prodomain, remains unknown. In this study, we present a revised structure of the central PfSERA5E domain at a resolution of 1.2 Å, and the first structure of the “zymogen” of this papain‐like domain including its cognate prodomain (PfSERA5PE) to 2.2 Å resolution. PfSERA5PE is somewhat structurally similar to that of other known proenzymes, retaining the conserved overall folding and orientation of the prodomain through, and occluding, the archetypal papain‐like catalytic triad “active‐site” cleft, in the same reverse direction as conventional prodomains. Our findings are congruent with previously identified structures of PfSERA5E and of similar “zymogens” and provide a foundation for further investigation into the function of PfSERA5.
Identification of key genes associated with overwintering in Anoplophora glabripennis larva using gene co‐expression network analysis
Authors: Xu Yabei , Li Yurong , Wang Qianqian , Zheng Chunchun , Zhao Dongfang , Shi Fengming , Liu Xinhai , Tao Jing , Zong Shixiang
Published: September 2020

BACKGROUND

Anoplophora glabripennis (Coleoptera: Cerambycidae) is a major quarantine pest in forestry. It is widely distributed throughout many regions such as Asia, Europe, and North America, and has enormous destructive potential for forests. The larvae of A. glabripennis overwinter in a dormant state with strong cold tolerance, and whether the larvae survive winter determines the population density in the following year. However, the molecular mechanisms of this process are not clear.

RESULTS

RNA sequencing (RNA‐Seq) analysis of A. glabripennis larvae at five overwintering stages identified 6876 differentially expressed genes (DEGs). Among these, 46 functional genes that might respond to low temperature were identified. Weighted gene co‐expression network analysis revealed that the MEturquoise module was correlated with the overwintering process. The STPK, PP2A, DGAT, and HSF genes were identified as hub genes using visualization of gene network. In addition, four genes related to sugar transport, gluconeogenesis and glycosylation were screened, which may be involved in the metabolic regulation of overwintering larvae. The protein–protein interaction network indicated that ribosomal protein and ATP synthase may play an important role in connecting with other proteins. The expression levels of fifteen hub genes were further validated by quantitative RT‐PCR, and the results were consistent with RNA‐Seq.

CONCLUSION

This study demonstrates key genes that may reveal the molecular mechanism of overwintering in A. glabripennis larvae. The genes may be the potential targets to prevent larvae from surviving the cold winter by developing new biological agents using genetic engineering.
Sensor‐based outdoor monitoring of insects in arable crops for their precise control
Authors: Bieganowski Andrzej , Dammer Karl‐Heinz , Siedliska Anna , Bzowska‐Bakalarz Małgorzata , Bereś Paweł K , Dąbrowska‐Zielińska Katarzyna , Pflanz Michael , Schirrmann Michael , Garz Andreas
Published: September 2020

The implementation of precision farming technologies into agricultural practice requires, among other things, precise determination of the extent and intensity of insect infestation in the farmer' fields. Manual insect identification is time‐consuming and has low efficiency, especially for large fields. Therefore, scientists and practitioners devote much effort to the automatization of this process. There are two complementary approaches to insect identification: (i) direct, in which the insect (ultimately the species) is determined, and (ii) indirect, in which the damage caused by the insects is monitored and forms the basis on which to formulate the information about insect infestation. A mini‐review of both approaches is presented in this work. Additionally, the advantages and disadvantages of each are briefly described. Methods of insect identification are still characterized by relatively small selectivity and efficiency, therefore it is necessary to keep searching for new methods and improve the development of existing ones. The goal of such systems should be to work in real time and be inexpensive to run, enabling widespread use amongst farmers. A possible solution seems to be integrating various techniques (sensor fusion) into a single measurement system. © 2020 Society of Chemical Industry
Ginger (Zingiber officinaleRosc.) and its bioactive components are potential resources for health beneficial agents
Authors: Zhang Mengmeng , Zhao Rong , Wang Dan , Wang Li , Zhang Qing , Wei Shujun , Lu Feng , Peng Wei , Wu Chunjie
Published: September 2020

Zingiber officinaleRosc. (Zingiberacae), commonly known as ginger, is a perennial and herbaceous plant with long cultivation history. Ginger rhizome is one of the most popular food spices with unique pungent flavor and is prescribed as a well‐known traditional Chinese herbal medicine. To date, over 160 constituents, including volatile oil, gingerol analogues, diarylheptanoids, phenylalkanoids, sulfonates, steroids, and monoterpenoid glycosides compounds, have been isolated and identified from ginger. Increasing evidence has revealed that ginger possesses a broad range of biological activities, especially gastrointestinal‐protective, anti‐cancer, and obesity‐preventive effects. In addition, gingerol analogues such as 6‐gingerol and 6‐shogaol can be rapidly eliminated in the serum and detected as glucuronide and sulfate conjugates. Structural variation would be useful to improve the metabolic characteristics and bioactivities of lead compounds derived from ginger. Furthermore, some clinical trials have indicated that ginger can be consumed for attenuating nausea and vomiting during early pregnancy; however, there is not sufficient data available to rule out its potential toxicity, which should be monitored especially over longer periods. This review provides an up‐to‐date understanding of the scientific evidence on the development of ginger and its active compounds as health beneficial agents in future clinical trials.
Study of the impurity profile and characteristic fragmentation of Δ3‐isomers in cephapirin sodium using dual liquid chromatography coupled with ion trap/time‐of‐flight mass spectrometry
Authors: Ren Xiaojuan , Zhou Jinjin , Hu Feifeng , Wang Jian
Published: September 2020

Rationale

According to the requirements of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), the structures of impurities in pharmaceutical products present at over 0.1% need to be confirmed. Therefore, the aim of this study is to separate and identify the impurities in cephapirin sodium drug substances, so as to guide the industry to improve the production process and storage conditions and reduce the amount of impurities in the product.

Methods

In the first chromatography dimension, a Boston Green ODS (4.6 mm × 250 mm, 5 μm) column was used, with a mobile phase composed of 0.05 M sodium dihydrogen phosphate aqueous solution and acetonitrile. In the second dimension, the column was a Shimadzu Shim‐pack GISS C18 (50 mm × 2.1 mm, 1.9 μm), using 10 mM ammonium formate solution and methanol as the mobile phase.

Results

The fragmentation behavior of cephapirin and its impurities and isomers was studied and the structures of impurities were deduced based on the MSn data. For six unknown impurities tentative structures were proposed. The degradation behavior of cephapirin sodium was also studied. Impurities 1 to 11 were found in commercial cephapirin sodium samples, indicating that cephapirin sodium should be stored in closed containers.

Conclusions

The contradiction between the non‐volatile mobile phase and mass spectrometry was solved by means of multiple heart‐cutting approaches and an on‐line desalting technique. Twelve impurities and isomers were separated and characterized. These results could be used to improve the methods described in pharmacopoeias for the quality control of cephapirin sodium.