bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroprocessing of oleic acid for production of jet fuel range hydrocarbons over Sn(1)‐Fe(3)‐Cu(13)/SiO2‐Al2O3 catalyst: Process parameters optimization, kinetics, and thermodynamic study
Authors: Ayandiran Afees A. , Boahene Philip E. , Dalai Ajay K. , Hu Yongfeng
Published: February 2021

Hydroprocessing of vegetable oil to high‐quality jet fuel range hydrocarbons (HRJ) plays a significant role in the development of completely interchangeable substitute for conventional petroleum‐derived jet fuel and has drawn the attention of aviation experts due to its capacity to mitigate greenhouse gas emissions associated with the aviation industry. The limited performance of 1 wt. % Sn promoted Fe(3)‐Cu(13)/SiO2‐Al2O3 catalyst in our previous study has been attributed to the successive consideration of one variable at a time in its evaluation. Maximization of oleic acid conversion and selectivity of jet fuel range hydrocarbons from hydroprocessing of oleic acid over 1 wt. % Sn promoted Fe(3)‐Cu(13)/SiO2‐Al2O3 catalyst with the best combination of the process parameter involved via multivariate approach, and evaluation of kinetic and thermodynamic activation parameters is the focus of this study. Reduced cubic oleic acid conversion model and reduced quadratic jet fuel range hydrocarbons selectivity model of high significance levels, adequate precision, and high correlation coefficient were developed. Reaction temperature of 339.5°C, 1.6 MPa H2 pressure, 6.2 wt.% catalyst concentration, and 8.0 h reaction time were optimum process parameters that can maximize oleic acid conversion and selectivity of jet fuel range hydrocarbons at 98.2% and 82.2%, respectively. This process was found to be endothermic, irreversible, and nonspontaneous with 45.8 KJ/mol activation enthalpy of reaction, 0.25 KJ/mol entropy of reaction, and the reaction's Gibb's free energy of 198.8 KJ/mol at 340°C. The minimum energy required for the reaction to take place was evaluated as 50.7 KJ/mol.
Ancient high‐status burial of a woman at Tlailotlacan, a neighborhood in the city of Teotihuacan
Authors: Archer‐Velasco Jorge N. , Ortega Cabrera Verónica , Melgar Tísoc Emiliano , Perez‐Perez Julia
Published: February 2021

The discovery of an elite burial in Tlailotlacan, a neighborhood of Teotihuacan, gave us a unique opportunity not only to put together a group of multidisciplinary specialists, but to revive this remarkable woman who inhabited, ate, drank, and traveled through most of Mesoamerican. The different analysis carried out provided us with a unique opportunity to reconstruct part of the relations between inhabitants from different regions in ancient Mexico.
Individualized elective irradiation of the clinically node‐negative neck in definitive radiotherapy for head and neck squamous cell carcinoma
Authors: Kou Jia , Lin Li , Jiao Cheng‐Yang , Tian Meng‐Qiu , Zhou Guan‐Qun , Jiang Xue , Ma Jun , Qi Zhen‐Yu , Lu Yao , Sun Ying
Published: February 2021

Background

Oral cavity (OC), oropharyngeal (OP), hypopharyngeal (HP), and laryngeal (LA) squamous cell carcinoma (SCC) have a high incidence of regional lymph node metastasis (LNM). Elective irradiation for clinically node‐negative neck is routinely administered to treat lymph nodes harboring occult metastasis. However, the optimal elective irradiation schemes are still inconclusive. In this study, we aimed to establish individualized elective irradiation schemes for the ipsilateral and contralateral node‐negative neck of these four types of cancer.

Methods

From July 2005 to December 2018, 793 patients with OC‐SCC, 464 with OP‐SCC, 413 with HP‐SCC, and 645 with LA‐SCC were recruited retrospectively. Based on the actual incidence of LNM and the tumor characteristics, risk factors for contralateral LNM, as well as node level coverage schemes for elective irradiation, were determined using logistic regression analysis. Additionally, we developed a publicly available online tool to facilitate the widespread clinical use of these schemes.

Results

For the ipsilateral node‐negative neck, elective irradiation at levels I‐III for OC‐SCC and levels II‐IVa for OP‐, HP‐ and LA‐SCC are generally recommended. In addition, level VIIa should be included in patients with OP‐SCC. Multivariate analyses revealed that posterior hypopharyngeal wall and post‐cricoid region involvement were independently associated with level VIIa metastasis in HP‐SCC (all P < 0.05). For the contralateral node‐negative neck, multivariate analyses revealed that ipsilateral N2b2‐N3, tumors with body midline involvement, and degree of tumor invasion were the independent factors for contralateral LNM (all P < 0.05). In patients who require contralateral neck irradiation, levels I‐II are recommended for OC‐SCC, and additional level III is recommended for patients with ipsilateral N3 disease. Levels II‐III are recommended for OP‐, HP‐, and LA‐SCC, and additional level IVa is recommended for patients with advanced T or ipsilateral N classifications. Furthermore, additional level VIIa is recommended only for OP‐SCC with T4 and ipsilateral N3 disease.

Conclusion

Based on our findings, we suggest that individualized and computer‐aided elective irradiation schemes could reduce irradiation volumes in OC‐, OP‐ and HP‐SCC patients, as compared to current guidelines, and could thus positively impact the patients' quality of life after radiotherapy.
Dynamic Modeling of a Sub‐zero, Fed‐Batch, Packed Distillation Column to Produce Tetrafluoroethylene
Authors: Espach Johannes I. , Sonnendecker Paul W. , Crouse Philippus L.
Published: February 2021

Equilibrium and rate‐based dynamic models are proposed for a laboratory‐scale, fed‐batch, packed distillation column that operates at sub‐zero temperatures. The purpose of the column is to separate tetrafluoroethylene from a ternary mixture that also contains hexafluoropropylene and octafluorocyclobutane. The simulation results for both models indicate second‐order type responses, with either increases or decreases from the expected steady‐state values. It is recommended to build a start‐up routine into the simulations. Experimental validation should also form part of future work.
Visible Light‐Promoted Sulfoxonium Ylides Synthesis from Aryl Diazoacetates and Sulfoxides
Authors: Lu Juan , Li Lei , He Xiang‐Kui , Xu Guo‐Yong , Xuan Jun
Published: February 2021

Main observation and conclusion

A visible light‐promoted reaction of donor/acceptor diazoalkanes with sulfoxides towards the synthesis of synthetically useful sulfoxonium ylides was reported. The reaction occurred under sole visible light irradiation without the need of any transition‐metals or additives, affording the corresponding sulfoxonium ylides in moderate to good yields. The success of late‐stage modification of natural isolates or drug candidates, scale‐up reaction and transformation of sulfoxonium ylides to other useful molecules further rendered the approach valuable.
Detection of tumor‐derived cell‐free DNA from colorectal cancer peritoneal metastases in plasma and peritoneal fluid
Authors: van't Erve Iris , Rovers Koen P , Constantinides Alexander , Bolhuis Karen , Wassenaar Emma CE , Lurvink Robin J , Huysentruyt Clément J , Snaebjornsson Petur , Boerma Djamila , van den Broek Daan , Buffart Tineke E , Lahaye Max J , Aalbers Arend GJ , Kok Niels FM , Meijer Gerrit A , Punt Cornelis JA , Kranenburg Onno , de Hingh Ignace HJT , Fijneman Remond JA
Published: February 2021

Tumor‐derived cell‐free DNA (cfDNA) is an emerging biomarker for guiding the personalized treatment of patients with metastatic colorectal cancer (CRC). While patients with CRC liver metastases (CRC‐LM) have relatively high levels of plasma cfDNA, little is known about patients with CRC peritoneal metastases (CRC‐PM). This study evaluated the presence of tumor‐derived cfDNA in plasma and peritoneal fluid (i.e. ascites or peritoneal washing) in 20 patients with isolated CRC‐PM and in the plasma of 100 patients with isolated CRC‐LM. Among tumor tissue KRAS/BRAF mutation carriers, tumor‐derived cfDNA was detected by droplet digital polymerase chain reaction (ddPCR) in plasma of 93% of CRC‐LM and 20% of CRC‐PM patients and in peritoneal fluid in all CRC‐PM patients. Mutant allele fraction (MAF) and mutant copies per ml (MTc/ml) were lower in CRC‐PM plasma than in CRC‐LM plasma (median MAF = 0.28 versus 18.9%, p < 0.0001; median MTc/ml = 21 versus 1,758, p < 0.0001). Within patients with CRC‐PM, higher cfDNA levels were observed in peritoneal fluid than in plasma (median MAF = 16.4 versus 0.28%, p = 0.0019; median MTc/ml = 305 versus 21, p = 0.0034). These data imply that tumor‐derived cfDNA in plasma is a poor biomarker to monitor CRC‐PM. Instead, cfDNA detection in peritoneal fluid may offer an alternative to guide CRC‐PM treatment decisions.
Comparison of different diagnostic approaches in the management of the clinically negative neck in early oral cancer patients
Authors: de Bree Remco , de Keizer Bart
Published: February 2021

In clinically node‐negative patients with early oral cavity cancer, [18F]fludeoxyglucose (FDG) positron emission tomography–computed tomography (PET‐CT) should be compared with sentinel node biopsy. Cost effectiveness is one of the important aspects for implementation of FDG/PET‐CT in clinical practice for this patient population.
Flow cytometry detection of CD138 expression continuum between monotypic B and plasma cells is associated with both high IgM peak levels and MYD88 mutation and contributes to diagnosis of Waldenström macroglobulinemia
Authors: Gayet Mylene , Leymarie Vincent , Derouault Paco , Guérin Estelle , Vaidié Julien , Pascal Virginie , Boulin Mélanie , Dmytruk Nataliya , Chauzeix Jasmine , Trimoreau Franck , Gachard Nathalie , Feuillard Jean , Rizzo David
Published: February 2021

Background

Differential diagnosis of Waldenström macroglobulinemia (WM) with other indolent B‐cell malignancies is still a challenge. Here, we propose an original and simple analysis of routine flow cytometry (FCM) unraveling the characteristic ongoing plasma cell (PC) differentiation of WM tumor B‐cells.

Methods

FCM analysis of both B‐cells and PC was performed on a series of 77 patients with IgM peak. MYD88 and CXCR4 mutations were studied using an allele‐specific PCR and by high throughput sequencing.

Results

Twenty seven (35%), 46 (58%) and 4 (5%) patients were classified as WM, IgM monoclonal gammopathy of undetermined significance (MGUS) or other B‐NHL respectively. MYD88 mutation was found in 25/27 WM (93%) and in 29/46 MGUS (63%). Using FCM, monotypic B‐cells were found in 27/27 WM (100%) and 34/46 MGUS (74%). Monotypic CD138pos/CD38pos PCs were detected in 23/27 WM (85%) and 25/46 MGUS (54%). Highlighting the ongoing PC differentiation of WM tumor B‐cells by FCM, we evidenced a CD138 expression continuum between monotypic B‐cells and PCs. This pattern remained absent in control samples and was significantly associated with higher IgM peaks (p = 6.10−5) and MYD88 mutations (p = 10−3) in both WM and MGUS cases.

Conclusions

FCM exploration of both B‐cells and PC led to identify a CD138 expression continuum as an objective marker of ongoing PC differentiation of WM tumor cells and was strongly associated with increased IgM peak levels and MYD88 mutations. This approach could contribute to place FCM at the forefront of WM diagnosis.
Strong impact of management regimes on rhizome biomass across Central European temperate grasslands
Authors: Ottaviani Gianluigi , Lubbe Frederick Curtis , Lepš Jan , Lisner Aleš , Martínková Jana , Mudrák Ondřej , Klimešová Jitka
Published: February 2021

Grassland ecosystems account for approximately 40% of terrestrial biomes globally. These communities are characterized by a large allocation to belowground biomass, often exceeding its aboveground counterpart. However, this biomass investment cannot be entirely attributed to the acquisitive function of roots. Grassland plants also allocate to non‐acquisitive, stem‐derived, belowground organs, such as rhizomes. These organs are responsible for the key plant functions of space occupancy, resprouting after damage, and seasonal rest. However, biomass investment to rhizomes has rarely been studied. Here we gathered community‐level aboveground and rhizome biomass data for 52 temperate grasslands in Czech Republic (Central Europe), differing in management intensity. We found that rhizome biomass scaled linearly with aboveground biomass, and more intensive management disproportionally (negatively) affected rhizome biomass. This finding may have important implications for the persistence of temperate grassland plants and their provision of ecosystem services (e.g., soil carbon sequestration, soil stabilization) in relation to changing environments.
The eggshell structure in apteryx; form, function, and adaptation
Authors: Vieco‐Galvez David , Castro Isabel , Morel Patrick C. H. , Chua Wei Hang , Loh Michael
Published: February 2021

Apteryx is a genus of flightless birds endemic to New Zealand known to lay very large eggs in proportion to body weight. The eggshell of Apteryx is unusually thin and less porous than allometrically expected possibly as a compensation for a very long incubation period. Past studies have been carried out on Apteryx australis, a species which once comprised all kiwi with brown plumage, now separated into three distinct species. These species use different habitats and live at different latitudes and altitudes, therefore generating a need to revise our knowledge of the attributes of their eggshells. In this study, we measured the physical characteristics and water conductance on eggshell fragments of these three species and Great‐spotted Kiwi and relate them to the environmental conditions of their respective environments; we also measured the water vapor conductance of Brown Kiwi eggs of late stages of incubation. We found that several trade‐offs exist between incubation behavior, environmental conditions, and eggshell structure. We found differences between species in eggshell water vapor conductance seemingly related to altitude; Brown Kiwi and Rowi generally inhabiting lower altitudes had the highest conductance and Tokoeka, generally living in montane environments, the lowest. This is achieved by an increased eggshell thickness rather than a pore area reduction. Finally, the water vapor conductance late in incubation was 58% higher than infertile unincubated eggs, suggesting a drastic increase in conductance throughout the long incubation period. Using the values previously reported, we calculated the embryonic eggshell thinning to be 32.5% at the equatorial region of the eggshell. We describe several new features, such as triangular mineral particles in the cuticle, reported for the extinct Trigonoolithus amoei, and confirmed the existence of plugged pores. We suggest that these structures provide microbial protection needed by a burrow nesting species with a long incubation period.
Stroke and systemic embolism in patients with atrial fibrillation and heart failure according to heart failure type
Authors: Uhm Jae‐Sun , Kim Jun , Yu Hee Tae , Kim Tae‐Hoon , Lee So‐Ryoung , Cha Myung‐Jin , Choi Eue‐Keun , Lee Jung Myung , Kim Jin‐Bae , Park Junbeom , Park Jin‐Kyu , Kang Ki‐Woon , Shim Jaemin , Park Hyung Wook , Lee Young Soo , Kim Chang‐Soo , Mun Ji Eun , Son Nak‐Hoon , Joung Boyoung
Published: February 2021

Aims

This study aimed to elucidate the risk for stroke and systemic embolism (SE) in patients with atrial fibrillation and heart failure (HF) according to HF type.

Methods and results

A total of 10 780 patients with atrial fibrillation were enrolled in a multicentre prospective registry and divided according to HF type: no‐HF, HF with preserved ejection fraction (EF) (HFpEF), HF with mid‐range EF (HFmrEF), and HF with reduced EF (HFrEF). Each group included 237 age‐matched and sex‐matched patients (age, 69.0 ± 10.3 years; men, 69.6%). The baseline characteristics, cumulative incidence, and hazard ratios for stroke/SE and major bleeding were compared across the groups. Patients with HF accounted for 10.3% of the total population; HFpEF, HFmrEF, and HFrEF represented 43.7%, 23.6%, and 32.7% of the patients with HF, respectively. The CHA2DS2‐VASc score was significantly higher in the HFpEF, HFmrEF, and HFrEF groups than in the no‐HF group. The annual stroke/SE incidence rates were 2.8%, 0.7%, 1.1%, and 0.9% in the HFpEF, HFmrEF, HFrEF, and no‐HF groups, respectively. The cumulative incidence of stroke/SE was significantly highest in the HFpEF group at 22.8 ± 10.0 months (P = 0.020). The stroke/SE risk was higher in the HFpEF group than in the HFmrEF and HFrEF groups (hazard ratio, 3.192; 95% confidence interval, 1.039–9.810; P = 0.043). E/e' value was an independent risk factor for stroke/SE. There were no significant differences in the incidence of major bleeding across the groups.

Conclusions

The stroke/SE risk was the highest in the HFpEF group and comparable between the HFmrEF and HFrEF groups.
Atroposelective Synthesis, Structure and Properties of a Novel Class of Axially Chiral N‐Aryl Quinolinium Salt
Authors: Sweet Jamie S. , Rajkumar Sundaram , Dingwall Paul , Knipe Peter C.
Published: February 2021

Inspired by naturally occurring molecules containing atropisomeric N+‐C axes, we have developed a novel synthetic approach to generate a library of axially chiral N‐aryl quinolinium salts. Enantiopurities up to 93 % ee were obtained via a four‐step route from commercially available precursors. Axial stereochemistry was controlled through an enantioselective ring‐closing Buchwald–Hartwig coupling reaction. The structure and properties of the salts were examined by X‐ray crystallography, DFT, UV‐Vis, and fluorescence spectroscopy, revealing high rotational barriers and solvatochromic behaviour.
Magnetic resonance spectroscopy with transcranial direct current stimulation to explore the underlying biochemical and physiological mechanism of the human brain: A systematic review
Authors: Choi Chang‐Hoon , Iordanishvili Elene , Shah N. Jon , Binkofski Ferdinand
Published: February 2021

A large body of molecular and neurophysiological evidence connects synaptic plasticity to specific functions and energy metabolism in particular areas of the brain. Furthermore, altered plasticity and energy regulation has been associated with a number of neuropsychiatric disorders. A favourable approach enabling the modulation of neuronal excitability and energy in humans is to stimulate the brain using transcranial direct current stimulation (tDCS) and then to observe the effect on neurometabolites using magnetic resonance spectroscopy (MRS). In this way, a well‐defined modulation of brain energy and excitability can be achieved using a dedicated tDCS protocol to a predetermined brain region. This systematic review was guided by the preferred reporting items for systematic reviews and meta‐analysis and summarises recent literature studying the effect of tDCS on neurometabolites in the human brain as measured by proton or phosphorus MRS. Limitations and recommendations are discussed for future research. The findings of this review provide clear evidence for the potential of using tDCS and MRS to examine and understand the effect of neurometabolites in the in vivo human brain.
Health insurance, risk attitudes, and household financial behavior
Authors: Li Zhongda , Liu Lu , Shi Jiayu , Sui Yubing
Published: February 2021

Medical expenditure risk is widely believed to reduce households' willingness to bear other risks and in turn alter their behavior. In this paper, we investigate the role of health insurance in household financial decision. To this end, we consider a double‐multinomial discrete‐factor model of insurance choice and portfolio allocation. Using data from a Chinese household survey, we find that enrolling in a health insurance scheme with better policies is associated with a higher probability of owning risky assets. This positive effect is stronger for households with lower risk aversion. Our findings suggest that risk attitudes could indirectly influence portfolio outcomes through affecting households' responsiveness to changes in medical expenditure risk.
Coagulopathy, Bleeding Events, and Outcome According to Rotational Thromboelastometry in Patients With Acute Liver Injury/Failure
Authors: Stravitz R. Todd , Fontana Robert J. , Meinzer Caitlyn , Durkalski‐Mauldin Valerie , Hanje A. James , Olson Jody , Koch David , Hamid Bilal , Schilsky Michael L. , McGuire Brendan , Ganger Daniel , Liou Iris , Karvellas Constantine J. , Rule Jody A. , Lisman Ton , Clasen Kristin , Reuben Adrian , Cripps Michael , Lee William M. ,   ALF Study Group
Published: February 2021

Background and Aims

Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival.

Approach and Results

A total of 200 patients were recruited from sites of the ALF Study Group. Blood collected daily for up to 5 days was analyzed using ROTEM delta devices. Consistent with standard laboratory evidence of hypocoagulability (median international normalized ratio = 2.9 and platelet count = 144 × 109/L), patients frequently exhibited ROTEM parameters outside the normal range (73% and 62% had abnormalities in clot formation from extrinsic and intrinsic clotting cascades, respectively); however, measures of clot stability were generally normal. Eighteen patients (9%) experienced bleeding events, in whom clot initiation, assembly, and firmness were more severely deranged than patients without bleeding. Abnormal ROTEM parameters were more frequently observed in patients with non‐acetaminophen ALI/ALF than those with acetaminophen ALI/ALF (clot initiation [P < 0.001], assembly [P = 0.02], firmness at 10 minutes [P = 0.05], and maximal firmness [P = 0.06]). Patients with more severe systemic complications (high‐grade hepatic encephalopathy and need for renal replacement therapy) also had a higher incidence of abnormal ROTEM parameters. Finally, more hypocoagulable ROTEM parameters (clot initiation (P = 0.005), stiffness at 10 minutes (P = 0.05), and maximal stiffness by fibrin assembly (P = 0.004)) were observed in patients who died or underwent liver transplantation than those who survived with their native liver.

Conclusions

In patients with ALI/ALF, abnormal ROTEM parameters are frequent and proportional to disease severity. Whether the increased bleeding risk associated with abnormal ROTEM indicates hemostatic failure or is a proxy for disease severity requires additional study.
The effect of Joule heating and viscous dissipation on the boundary layer flow of a magnetohydrodynamics micropolar‐nanofluid over a stretching vertical Riga plate
Authors: Eldabe Nabil T. , Gabr Mahmoud E. , Zaher Abdullah Z. , Zaher Sameh A.
Published: February 2021

Joule heating and viscous dissipation effects on the behavior of the boundary layer flow of a micropolar nanofluid over a stretching vertical Riga plate (electro magnetize plate) are considered. The flow is disturbed by an external electric magnetic field. The problem is formulated mathematically by nonlinear system of partial differential equations (PDEs). By using suitable variables transformations, this system is transformed onto a system of nonlinear ordinary differential equations (ODEs). The Parametric NDsolve package of the commercial software Mathematica is used to solve the obtained ODEs as well as the considered numerical results for different physical parameters with appropriate boundary conditions. Novel results are obtained by studying the stream lines flow around the plate in two and three dimensions. Moreover, the effects of the pertinent parameters on the skin friction coefficient, couple stress, local Nusselt, and Sherwood number are discussed. Special cases of the obtained results show excellent agreements with previous works. The results showed that as the magnetic field parameter increases the velocity of the boundary layer adjacent to the stretching sheet decreases. Also, for a productive chemical reaction near the sheet surface, the angular velocity decreases but opposite trend is observed far from the sheet surface. The importance of this study comes from its significant applications in many scientific fields, such as nuclear reactors, industry, medicine, and geophysics.
ER−/PR+ breast cancer: A distinct entity, which is morphologically and molecularly close to triple‐negative breast cancer
Authors: Beltjens Françoise , Molly Damien , Bertaut Aurélie , Richard Corentin , Desmoulins Isabelle , Loustalot Catherine , Charon‐Barra Céline , Courcet Emilie , Bergeron Anthony , Ladoire Sylvain , Jankowski Clémentine , Boidot Romain , Arnould Laurent
Published: February 2021

Determining the status of steroid hormone receptors [oestrogen (ER) and progesterone receptors (PR)] is a crucial part of the breast cancer workup. Thereby, breast cancers can be classified into four subtypes. However, the existence of ER−/PR+ tumours, often reported to be ill‐classified due to technical errors, remains controversial. In order to address this controversy, we reviewed the hormone receptor status of 49 breast tumours previously classified as ER−/PR+ by immunohistochemistry, and compared clinical, pathological and molecular characteristics of confirmed ER−/PR+ tumours with those of ER+ and triple‐negative tumours. We unequivocally confirmed the ER−/PR+ status in 27 of 49 tumours (0.3% of all breast cancers diagnosed in our institution between 2000 and 2014). We found that ER−/PR+ were morphologically and histologically similar to triple‐negative tumours, but very distinct from ER+ tumours, with more aggressive phenotypes and more frequent basal marker expression than the latter. On the molecular level, RNA sequencing revealed different gene expression profiles between the three groups. Of particular interest, several genes controlled by the suppressor of zest 12 (SUZ12) were upregulated in ER−/PR+ tumours. Overall, our results confirm that ER−/PR+ breast cancers are an extremely rare but ‘real’ tumour subtype that requires careful diagnosis and has distinct features warranting different responsiveness to therapies and different clinical outcomes. Studies on larger cohorts are needed to further characterise these tumours. The likely involvement of SUZ12 in their biology is an interesting finding which may – in a long run – give rise to the development of new therapeutic alternatives.
Upregulation of lncRNA DARS‐AS1 accelerates tumor malignancy in cervical cancer by activating cGMP‐PKG pathway
Authors: Kong Xia , Wang Ji‐Shui , Yang Hua
Published: February 2021

This paper investigates the function of lncRNA DARS‐AS1 in cervical cancer (CC) as well as its in‐depth mechanism. The differential expression of DARS‐AS1 and ATP1B2 were analyzed based on The Cancer Genome Atlas and the Genotype‐Tissue Expression databases, and the survival rate was measured using Kaplan–Meier survival analysis. Biological function experiments were performed to detect cell proliferation, invasion, and migration. Quantitative real‐time polymerase chain reaction was carried out to detect the expression of DARS‐AS1 and ATP1B2. Western blot analysis was utilized to assess the protein levels of ATP1B2 and cGMP‐PKG pathway‐related proteins. DARS‐AS1 was expressed at high levels in CC tissues and cell lines, and high expression of DARS‐AS1 indicated a lower survival rate. CCK‐8 and colony formation assays revealed that the overexpression of DARS‐AS1 promoted the proliferation of CC cells. Furthermore, bioinformatics analysis suggested that the cGMP‐PKG pathway ranks as the first pathway enriched by the differential genes that correlated with DARS‐AS1 (|r| > 0.4). ATP1B2, as a cGMP‐PKG pathway‐related gene, was significantly correlated with the overall survival of CC patients. We further confirmed that ATP1B2 was lowly expressed in CC and negatively correlated with the DARS‐AS1 expression. Then, biological function experiments exhibited that the promotion of cell proliferation, invasion, and migration resulted due to the upregulation of DARS‐AS1 could be canceled by ATP1B2 overexpression. Finally, Western blot revealed that upregulation of DARS‐AS1 could activate the cGMP‐PKG pathway, while overexpression of ATP1B2 reversed this activation. Our study revealed that DARS‐AS1/ATP1B2 contributes to regulating the progression of CC at least partially by modulating the cGMP‐PKG pathway.
Efficient small toxic gaseous molecule scavengers in metal‐defective graphene: A density functional analysis
Authors: Deng Jin‐Pei , Chuang Wen‐Hua , Kao Hsien‐Chang , Wang Bo‐Cheng
Published: February 2021

The adsorption property of small toxic gaseous molecules (SO2, SO3, H2S, and N2O) with metal/hexa‐vacancy defective graphene (denoted as HDG‐M, M: Fe2+, Co2+, Ni2+, Cu2+, and Zn2+) was determined by density functional theory. The results of these calculations show that the Fe2+ ion has the best and Cu2+ the worst absorption ability to capture all of the above toxic gases with selected adsorption orientation. These results can provide useful information for the application of the designed HDG‐M adsorbents in food science and ecosystem monitoring.
Initiation of cell volume regulation and unique cell volume regulatory mechanisms in mammalian oocytes and embryos
Authors: Tscherner Allison K. , Macaulay Angus D. , Ortman Chyna S. , Baltz Jay M.
Published: February 2021

The period beginning with the signal for ovulation, when a fully‐grown oocyte progresses through meiosis to become a mature egg that is fertilized and develops as a preimplantation embryo, is crucial for healthy development. The early preimplantation embryo is unusually sensitive to cell volume perturbations, with even moderate decreases in volume or dysregulation of volume‐regulatory mechanisms resulting in developmental arrest. To prevent this, early embryos possess mechanisms of cell volume control that are apparently unique to them. These rely on the accumulation of glycine and betaine (N, N, N‐trimethylglycine) as organic osmolytes—compounds that can provide intracellular osmotic support without the deleterious effects of inorganic ions. Preimplantation embryos also have the same mechanisms as somatic cells that mediate rapid responses to deviations in cell volume, which rely on inorganic ion transport. Both the unique, embryo‐specific mechanisms that use glycine and betaine and the inorganic ion‐dependent mechanisms undergo major changes during meiotic maturation and preimplantation development. The most profound changes occur immediately after ovulation is triggered. Before this, oocytes cannot regulate their volume, since they are strongly attached to their rigid extracellular matrix shell, the zona pellucida. After ovulation is triggered, the oocyte detaches from the zona pellucida and first becomes capable of independent volume regulation. A complex set of developmental changes in each cell volume‐regulatory mechanism continues through egg maturation and preimplantation development. The unique cell volume‐regulatory mechanisms in eggs and preimplantation embryos and the developmental changes they undergo appear critical for normal healthy embryo development.
New insights into carnitine‐acylcarnitine translocase deficiency from 23 cases: Management challenges and potential therapeutic approaches
Authors: Ryder Bryony , Inbar‐Feigenberg Michal , Glamuzina Emma , Halligan Rebecca , Vara Roshni , Elliot Aoife , Coman David , Minto Tahlee , Lewis Katherine , Schiff Manuel , Vijay Suresh , Akroyd Rhonda , Thompson Sue , MacDonald Anita , Woodward Abigail J. M. , Gribben Joanne. E. L. , Grunewald Stephanie , Belaramani Kiran , Hall Madeleine , van der Haak Natalie , Devanapalli Beena , Tolun Adviye Ayper , Wilson Callum , Bhattacharya Kaustuv
Published: February 2021

Carnitine acyl‐carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of mitochondrial long‐chain fatty‐acid transport. Most patients present in the first 2 days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. Multi‐centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients. Twenty‐three patients from nine tertiary metabolic units were identified. Seven attenuated patients of Pakistani heritage, six of these homozygous c.82G>T, had later onset manifestations and long‐term survival without chronic hyperammonemia. Of the 16 classical cases, 15 had cardiac involvement at presentation comprising cardiac arrhythmias (9/15), cardiac arrest (7/15), and cardiac hypertrophy (9/15). Where recorded, ammonia levels were elevated in all but one severe case (13/14 measured) and 14/16 had hypoglycaemia. Nine classical patients survived longer‐term—most with feeding difficulties and cognitive delay. Hyperammonaemia appears refractory to ammonia scavenger treatment and carglumic acid, but responds well to high glucose delivery during acute metabolic crises. High‐energy intake seems necessary to prevent decompensation. Anaplerosis utilising therapeutic d,l‐3‐hydroxybutyrate, Triheptanoin and increased protein intake, appeared to improve chronic hyperammonemia and metabolic stability where trialled in individual cases. CACTD is a rare disorder of fatty acid oxidation with a preponderance to severe cardiac dysfunction. Long‐term survival is possible in classical early‐onset cases with long‐chain fat restriction, judicious use of glucose infusions, and medium chain triglyceride supplementation. Adjunctive therapies supporting anaplerosis may improve longer‐term outcomes.
Glycoproteins as diagnostic and prognostic biomarkers for neurodegenerative diseases: A glycoproteomic approach
Authors: Xu Ming‐ming , Zhou Mao‐tian , Li Shu‐wei , Zhen Xue‐chu , Yang Shuang
Published: February 2021

Neurodegenerative diseases (NDs) are incurable and can develop progressively debilitating disorders, including dementia and ataxias. Alzheimer's disease and Parkinson's disease are the most common NDs that mainly affect the elderly people. There is an urgent need to develop new diagnostic tools so that patients can be accurately stratified at an early stage. As a common post‐translational modification, protein glycosylation plays a key role in physiological and pathological processes. The abnormal changes in glycosylation are associated with the altered biological pathways in NDs. The pathogenesis‐related proteins, like amyloid‐β and microtubule‐associated protein tau, have altered glycosylation. Importantly, specific glycosylation changes in cerebrospinal fluid, blood and urine are valuable for revealing neurodegeneration in the early stages. This review describes the emerging biomarkers based on glycoproteomics in NDs, highlighting the potential applications of glycoprotein biomarkers in the early detection of diseases, monitoring of the disease progression, and measurement of the therapeutic responses. The mass spectrometry‐based strategies for characterizing glycoprotein biomarkers are also introduced.
Mechanisms of immunogenic cell death and immune checkpoint blockade therapy
Authors: Lin Richard A. , Lin Jessica K. , Lin Shiaw‐Yih
Published: February 2021

Immunogenic cell death (ICD) refers to a form of regulated cell death that activates adaptive immunity, forming long‐term immunological memory. Using chemotherapeutic drugs to induce ICD in cancer cells can help create an inflamed, immunogenic tumor environment, key for optimal immune checkpoint blockade (ICB) therapy response. ICB targets immune checkpoints such as cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA4) and programmed death 1 (PD‐1). Durable responses and better quality of life in ICB patients compared with many other treatments has prompted additional investigation into its therapeutic potential and possible approaches, in an effort to further understand the functions of the costimulatory molecules and how new treatments may be designed. In this review, we will summarize ICD induction, including stress responses, damage‐associated molecular patterns, and various assays by which immunogenicity is evaluated in dying cells. In addition, the mechanisms and biomarkers underlying the CTLA4 and PD‐1 pathways of checkpoint blockade will be covered. Finally, we will review the synergistic effects of ICD induction combined with ICB therapy, as well as combination blockade therapies involving the use of multiple drugs.
The Impact of Dental Care in Head and Neck Cancer Outcomes: A Systematic Review and Meta‐Analysis
Authors: Haynes David Aaron , Vanison Christopher C. , Gillespie M. Boyd
Published: February 2021

Objective/Hypothesis

The objective of this study was to perform a systematic review and meta‐analysis to determine the impact of dental care on head and neck (H&N) cancer survival.

Methods

A comprehensive literature search was performed using PubMed, MEDLINE, and CINAHL to find all relevant studies from the date of inception to March 2020. Systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, and meta‐analysis was performed using the random effects logistic regression model. Primary outcomes of interest were 5‐year survival and hazard ratios comparing survival between dental care subgroups.

Results

H&N cancer survival rates strongly correlate with dental care adherence. Patients with good dental care had significantly better survival than patients with poor dental care (HR = 0.67, 95% CI: 0.55–0.83), with similar improved survival among patients with moderate versus poor dental care (HR = 0.67, 95% CI: 0.57–0.80). In addition, patients with good dental care had significantly decreased mortality than those with moderate dental care (HR = 0.81, 95% CI: 0.69–0.96), indicating an exposure‐response gradient.

Conclusions

For patients with H&N cancer, survival is significantly higher in those who receive recommended dental care compared with those who do not.

Level of Evidence

NA Laryngoscope, 132:45–52, 2022
Intraoperative nerve monitoring in thyroid surgery: Analysis of recurrent laryngeal nerve identification and operative time
Authors: Maneeprasopchoke Prachya , Chongkolwatana Cheerasook , Pongsapich Warut , Iwata Ayaka J. , Kamani Dipti , Randolph Gregory W.
Published: February 2021

Objective

To evaluate the clinical value of intraoperative nerve monitoring (IONM) by comparing the procedure times for thyroidectomies performed with and without IONM.

Methods

A prospective, randomized, controlled study was conducted on 32 patients (representing 41 nerves at risk) undergoing thyroidectomies carried out by two experienced head and neck surgeons (CC & WP). Sixteen thyroidectomies were performed without IONM (the “non‐IONM group”), while 16 thyroidectomies were performed with IONM (the “IONM group”). The measured datapoints were setup time, time to visual identification of the recurrent laryngeal nerve (RLN), time to confirm the RLN electrophysiologically, dissection time, and total operative time.

Results

With both surgeons, the IONM group had shorter visual times to RLN identification than the non‐IONM group (CC: 3.7 minutes vs 5.3 minutes; WP: 3.4 minutes vs 9.7 minutes). Additionally, the electrophysiological identification time for the IONM group was shorter than the visual identification time for the non‐IONM group. The setup times, dissection times, and total operative times of the 2 groups did not significantly differ (P > .05). No RLN injuries were observed.

Conclusions

IONM reduces the time needed for RLN identification in thyroidectomies. Functional RLN confirmation can reassure surgeons of the operative results. Moreover, use of IONM does not significantly impact setup and total operative times.

Level of evidence

2.
Geo‐integrated assessment of the landslide zone around Gadora along NH 58 of the Garhwal Himalayas, India
Authors: Falae Philips Omowumi , Dash Rajesh Kumar , Samanta Manojit , Kanungo D.P.
Published: February 2021

The Gadora village landslide zone situated along National Highway 58 has become very active in recent years. The landslide zone is causing a lot of damage to property along the highway and endangering the lives of people living uphill and downhill of the slopes. In the present study, a combined geological, geophysical and geotechnical investigation has been carried out to establish the subsurface layering system of the landslide. Undisturbed and disturbed samples were collected along the depth of the boreholes to determine the engineering properties of different layers. The subsurface layering and drainage patterns of the slope were inferred from electrical resistivity tomography conducted at different stretches of the slope. The present paper describes the layering system along with the engineering and physical properties obtained from the integrated geo‐investigation. The established near‐surface geometric, hydrological and material model enabled the stability study of the slope.
Ab initio dynamics of gas‐phase and aqueous‐phase hydrolysis of adenosine triphosphate
Authors: Saxena Raghav , Avanigadda V B K Sai Phani Kumar , Singh Raghvendra , Agarwal Vishal
Published: February 2021

In this study, we have modelled the non‐enzymatic hydrolysis of ATP in the gas‐phase and the aqueous‐phase by performing ab initio molecular dynamics simulations combined with an enhanced sampling technique. In the gas‐phase, we studied hydrolysis of fully protonated ATP molecule, and in the aqueous‐phase, we studied hydrolysis of ATP coordinated with: a) two H+ ions (H‐ATP), b) Mg2+ (Mg‐ATP), and c) Ca2+ (Ca‐ATP). We show that gas‐phase ATP hydrolysis follows a two‐step dissociative mechanism via a highly stable metaphosphate intermediate. The Adenine group of the ATP molecule plays a crucial role of a general base; temporarily accepting protons and thus helping in the elimination‐addition process. In the aqueous‐phase hydrolysis of ATP, we find that the cage of solvent molecules increases the stability of the terminal phospho‐anhydride bond through a well‐known cage‐effect. The nature of the ions has an important effect on the mechanism of the reaction. We find a two‐step dissociative‐type mechanism for H‐ATP, a single‐step dissociative‐type mechanism for Mg‐ATP, and an SN‐2 type concerted hydrolysis pathway for Ca‐ATP.
Hydrochar, digestate, and process water impacts on a soil's microbial community, processes, and metal bioavailability
Authors: Watson Conor , Schlösser Charlotte , Vögerl Jakob , Wichern Florian
Published: February 2021

Hydrothermal carbonization converts organic wastes into potentially soil‐improving solids. The nutrient‐rich process waters generated are prospective fertilizers. Two hydrochars were produced from maize (Zea mays L.) biogas digestate after 1 or 6 h of carbonization. Nutrient concentrations of the digestate, hydrochars, and process waters were determined. A 28‐d incubation, in which digestate, hydrochars, or process waters were added to a sandy loam soil, assessed their effects on microbial biomass, community composition, respiration, and nitrification. The hydrochars became enriched in Fe and Zn but featured lower macronutrient concentrations than the feedstock. The application of process waters as fertilizers could be hindered by their electrical conductivity and nitrite levels. All amendments stimulated nitrification and C mineralization. The C losses of the latter add to losses during hydrochar production. Growth of microbial biomass was induced particularly by digestate, due to its high bioavailable fractions of C and nutrients. Fungal biomass thrived in hydrochar‐amended soils, possibly due to a combination of their aromaticity and elevated micronutrient concentrations. A separate 56‐d incubation tested the amendments’ impact on metal bioavailability in an artificially contaminated substrate. In reducing concentrations of Cd, Zn and Cu, hydrochars were less effective than digestate, whose application likely led to increased complexation and sorption. However, application to the contaminated substrate of hydrochar permitted superior microbial biomass growth; its higher surface area and porosity may have provided an improved microbial habitat. Hydrochar application to soils may benefit the microbial biomass, but hydrothermal carbonization is not advantageous where the goal is C sequestration or increasing feedstock nutrient availability.
A Nanoplasmonic Assay of Oligonucleotide‐Cargo Delivery from Cationic Lipoplexes
Authors: Kho Kiang W. , Berselli Guilherme B. , Keyes Tia E.
Published: February 2021

A powerful new biophysical model is reported to assay nanocarrier lipid membrane permeability. The approach employs a nanophotonic biophysical membrane model as an assay to study oligonucleotide escape from delivery vector following fusion with endosomal membrane that relies on plasmonic hotspots within the receptor well, below the membrane to follow cargo arrival. Through the combined use of surface enhanced Raman spectroscopy and fluorescence lifetime correlation spectroscopy (FLCS), the model enables identification of a lipoplex‐mediated endosomal‐escape mechanism facilitated by DOTAP‐oligonucleotide interaction that dictates the rate of oligonucleotide release. This work reveals a hitherto unreported release mechanism as a complex multistep interplay between the oligonucleotide cargo and the target membrane, rather than a process based solely on lipid mixing at the fusing site as previously proposed. This substantiates the observations that lipid mixing is not necessarily followed by cargo release. The approach presents a new paradigm for assessment of vector delivery at model membranes that promises to have wide application within the drug delivery design application space. Overall, this plasmonic membrane model offers a potential solution to address persistent challenges in engineering the release mechanism of large therapeutic molecules from their nanocarrier, which is a major bottleneck in intracellular delivery.
Study of Thermal Expansion Coefficient of Graphene via Raman Micro‐Spectroscopy: Revisited
Authors: Feng Qianchi , Wei Dongshan , Su Yudan , Zhou Zhiguang , Wang Feng , Tian Chuanshan
Published: February 2021

The thermal expansion coefficient (TEC) of a 2D material is a fundamental parameter for both material property and applications. A joint study is hereby reported, using Raman microspectroscopy and molecular dynamics (MD) simulations, of the substrate effects on thermal properties of graphene. It is found that besides the lateral strain induced by the substrate, out‐of‐plane coupling strongly affects the temperature‐dependent vibrational modes and TEC of graphene. MD simulation shows significant reduction of the density of states for longer wavelength out‐of‐plane vibrations when the graphene is supported on an alkane substrate. The negative TEC of freestanding graphene becomes smaller when out‐of‐plane rippling is suppressed. In order to measure TEC of 2D materials with the out‐of‐plane coupling being taken into consideration, a Raman microspectroscopic scheme to separate the contributions of lateral strain and out‐of‐plane coupling to TEC is developed. The TEC of graphene on octadecyltrichlorosilane substrate is found to be (−0.6 ± 0.5) × 10−6 K−1 at room temperature, which is fundamentally smaller than that of freestanding graphene. These results shed light on the fundamental understanding of the interaction between 2D material and substrate, and offer a general recipe for studying separately in‐plane and out‐of‐plane couplings on supported materials.