bluuebunny/crossref_metadata_2025 huggingface dataset:
Wild emmer chromosome arm substitution lines: Useful resources for wheat genetic study and breeding
Authors: Yu Jinsheng , Zhao Yanhao , Ding Mingquan , Yu Zitong , Jiang Yurong , Ma Wujun , Rong Junkang
Published: June 2020

As the progenitor of durum wheat (Triticum durum Desf.) and common wheat (T. aestivum L.), wild emmer wheat (T. turgidum L. subsp. dicoccoides, TTD) has many valuable alleles for enlarging the genetic pool of common wheat. Chromosome arm substitution lines (CASLs) are useful genetic resources producing genome‐wide variations in the background of certain cultivars, with each CASL containing a pair of an individual chromosome arms from the donor parent. Therefore, CASLs can be used to identify a broad range of phenotypes that are usually different from the parental lines, to map causal genes or quantitative trait loci and to broaden the genetic pools of existing cultivars as prebreeding materials. In this review we summarize recent progress in wheat genetic studies and breeding using two sets of CASLs of the wild emmer accession TTD140 in two common wheat backgrounds of ‘Chinese Spring’ and ‘Bethlehem’. We report the production of CASLs, confirmation of their chromosome structure using molecular markers, and their application in discovering and mapping agronomically important genes. We propose that, together with the release of high‐quality reference genomes of wild emmer and common wheat, wild emmer CASLs are useful resources for genetic study and breeding of wheat.
Analysis of FGF20‐regulated genes in organ of Corti progenitors by translating ribosome affinity purification
Authors: Yang Lu M. , Stout Lisa , Rauchman Michael , Ornitz David M.
Published: June 2020

Background

Understanding the mechanisms that regulate hair cell (HC) differentiation in the organ of Corti (OC) is essential to designing genetic therapies for hearing loss due to HC loss or damage. We have previously identified Fibroblast Growth Factor 20 (FGF20) as having a key role in HC and supporting cell differentiation in the mouse OC. To investigate the genetic landscape regulated by FGF20 signaling in OC progenitors, we employ Translating Ribosome Affinity Purification combined with Next Generation RNA Sequencing (TRAPseq) in the Fgf20 lineage.

Results

We show that TRAPseq targeting OC progenitors effectively enriched for RNA from this rare cell population. TRAPseq identified differentially expressed genes (DEGs) downstream of FGF20, including Etv4, Etv5, Etv1, Dusp6, Hey1, Hey2, Heyl, Tectb, Fat3, Cpxm2, Sall1, Sall3, and cell cycle regulators such as Cdc20. Analysis of Cdc20 conditional‐null mice identified decreased cochlea length, while analysis of Sall1‐null and Sall1‐ΔZn2‐10 mice, which harbor a mutation that causes Townes‐Brocks syndrome, identified a decrease in outer hair cell number.

Conclusions

We present two datasets: genes with enriched expression in OC progenitors, and DEGs downstream of FGF20 in the embryonic day 14.5 cochlea. We validate select DEGs via in situ hybridization and in vivo functional studies in mice.
A virtual issue highlighting animal studies of eating disorders as valuable tools for examining neurobiological underpinnings and treatment of eating disorders
Authors: Fowler Natasha , Klump Kelly L.
Published: June 2020

While studies in humans suggest a role for psychosocial factors as well as biological and genetic processes in the development of eating disorders, the specific etiologic mechanisms remain largely unknown. In this virtual issue, we present a collection of 14 archived articles from the International Journal of Eating Disorders to highlight the utility of animal studies of eating disorders to advance our understanding of eating disorder etiology. Selected articles establish animal studies as valid tools to study disordered eating behavior, offer insight into potential neurobiological mechanisms, and highlight novel targets for future pharmacological treatments. Clinical implications of each article's findings are included to demonstrate the translational value of animal studies for the eating disorders field. We hope that the exciting concepts and findings in this issue inspire future animal studies of eating disorders.
Unusual Outcome of Glycosylation: Hydrogen‐Bond Mediated Control of Stereoselectivity by N‐Trifluoroacetyl Group?
Authors: Abronina Polina I. , Zinin Alexander I. , Chizhov Alexander O. , Kononov Leonid O.
Published: June 2020

During the synthesis of protected tetrasaccharide fragment of the repeating unit of polysaccharide of Azospirillum brasilense sp7 we found that glycosylation with a mixture of protected N‐trifluoroacetyl (TFA)‐protected glucosamine N‐phenyltrifluoroacetimidate and the corresponding 2‐trifluoromethyl‐oxazoline led to 1,2‐cis‐linked glycoside along with the expected 1,2‐trans‐linked isomer. This fact looks quite unusual bearing in mind that both N‐TFA‐containing glycosyl donor and 2‐trifluoromethyl‐oxazoline are usually expected to favor the formation of 1,2‐trans‐glycosides. Formation of 1,2‐cis‐glycoside was explained by hydrogen‐bond mediated complexation of hydrogen atom of NHTFA at C‐2 of oxacarbenium ion derived from glycosyl donor and oxygen atom of hydroxy group of the incoming nucleophile. Conversely, glycosylations with N‐phthaloyl protected glycosyl donors resulted in exclusive formation of 1,2‐trans‐isomer presumably due to a significant steric effect and the absence of additional hydrogen‐bonding sites of N‐phthaloyl group.
Synthetic Studies of 2,2‐Difluorobicyclo[1.1.1]pentanes (BCP‐F2): The Scope and Limitation of Useful Building Blocks for Medicinal Chemists
Authors: Ma Xiaoshen , Pinto Wilfredo , Pham Luu N. , Sloman David L. , Han Yongxin
Published: June 2020

Bicyclo[1.1.1]pentanes (BCP's) have been applied in medicinal chemistry as bioisosteres for phenyl groups. In pursuit of novel BCP analogs, we reported the first synthesis of 2,2‐difluorobicyclo[1.1.1]pentanes (BCP–F2) in 2019. Herein, we detail the extension of our effort in the synthesis of BCP‐F2 analogs.
Antimony‐based nanomaterials for high‐performance potassium‐ion batteries
Authors: Gao Hong , Guo Xin , Wang Shijian , Zhang Fan , Liu Hao , Wang Guoxiu
Published: June 2020

Potassium‐ion batteries (PIBs) present great potential for large‐scale energy storage applications owing to their high energy density and the abundance of potassium reserve. However, the large radius of K+ and super‐reactive metallic nature of potassium make it difficult to realize electrochemically reversible storage with most conventional electrode materials. Currently, it remains a great challenge to develop appropriate anode materials with high specific capacities, long cycle life, and low cost for PIBs. Antimony‐based materials are recognized as a promising anode candidate because of their high theoretical capacities, appropriate potassiation potential, and relatively low cost. Herein, we review the recent progress of antimony‐based anode materials for PIBs, including metallic antimony, antimony‐based alloys, antimony chalcogenides, and composite combinations. Meanwhile, this review also focuses on the electrochemical reaction mechanisms, strategies for design and synthesis of electrode materials, and the advances of electrolyte modulation and electrode formulation. Finally, we present the critical challenges to be addressed and perspectives for ways forward to promote the development of PIBs.

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Nanobiopesticides: Silica nanoparticles with spiky surfaces enable dual adhesion and enhanced performance
Authors: Zhang Jun , Brown Geoff , Fu Jianye , James Peter , Mukandiwa Lillian , Huang Xiaodan , Yu Chengzhong
Published: June 2020

Biopesticides, such as spinosad, are a new‐generation of ecofriendly pesticides in livestock industry. However, spinosad suffers from short duration of effectiveness and low potency in field conditions. Herein we report the development of a new nanospinosad design with dual adhesion and protection functions. Silica nanoparticles with spiky nanotopography loaded with spinosad possess rough surfaces. When applied topically, this nanospinosad formulation exhibited enhanced adhesion to both cattle hair and pest surface. The dual adhesion property led to significantly higher pest mortality toward tick (Rhipicephalus microplus, an ectoparasite) than a nanospinosad formulation using nanoparticles with smooth surface and a benchmark commercial product. The adhesion performance was further quantitatively measured using rainfastness test. Moreover, solar radiation test revealed that the nanospinosad exhibited >10 times higher photostability over the commercial product. This work paves the way toward the development of high performance nanobiopesticides for sustainable agricultural applications.

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Characteristics of imbibition in tight oil reservoirs from the perspective of physical experiments and theory
Authors: Cao Renyi , Wu Zhiyu , Liang Xiaowei , Cheng Linsong , Xu Zhongyi , Guan Yun , Guo Zhuoliang , Jia Zhihao
Published: June 2020

Imbibition is an important recovery mechanism for tight oil reservoirs, which occurs during hydraulic fracturing and development. Due to the massive distribution of micro‐nano scale pore throats and the existence of a boundary layer in tight formation, agreement consensus has not been reached on the imbibition mechanism. Based on the effect of the boundary layer, experiments were conducted to study the imbibition in tight sandstone, and NMR was used to determine the efficiency of imbibition. The results reveal that the imbibition rate is related to the connection area of the matrix‐fracture, throat connection, and radius. Then, the effective capillary pressure was modified by describing the thickness of the boundary layer in the micro‐nano pore throats. The calculation results show that the existence of boundary layer in micro‐nano throats makes the capillary pressure much larger than those of reservoirs without boundary layer. And the boundary layer reduces the effective flow radius, which dramatically decreases the imbibition quantity. The final result of existence of a boundary layer dramatically weakens the imbibition ability of a tight oil reservoir, and thus, the existence of a boundary layer cannot be ignored. Finally, the effective throat radius limit was analyzed during imbibition in a water‐oil‐rock system of a tight oil reservoir. Without a boundary layer, the effective radius of the pore throats in the water‐oil‐rock system during imbibition is greater than 200 nm, which is due to the advantages of the large capillary force and pore throats that are not too small. With a boundary layer, the main radius of the pore throats used for the water‐oil‐rock imbibition is approximately 400 nm. Thus, the imbibition occurs in the pore throats larger than 200 nm in the water‐oil‐rock system, and a surfactant could reduce the limit of the throat radius during imbibition in tight oil reservoirs.
Preservation of Permian–Triassic boundary section in the Jurassic accretionary complex of the Lake Hamana, Central Japan
Authors: Ding Wang , Ujiie Kohtaro , Sashida Katsuo
Published: June 2020

We examined the lithostratigraphy and deformation structures of the accreted pelagic rocks in Lake Hamana area, Central Japan, based on a detailed field mapping and the radiolarian ages. The constructed lithostratigraphy is composed of Lopingian (Upper Permian) grey chert, black chert, black claystone with a high carbon content of 4.85–6.78 wt%, siliceous claystone, black chert, and Anisian (Middle Triassic) grey chert, in the ascending order. The symmetry in the lithostratigraphy and the change in the radiolarian ages with respect to black carbonaceous claystone are presumed to represent a deep‐sea anoxic event that occurred across the Permian–Triassic (P–Tr) boundary. The P–Tr boundary black carbonaceous claystone suffered from an intense shear, resulting in blocks of siliceous claystone in the scaly black claystone matrix. In places, the sheared terrigenous rocks composed of sandstone blocks in the mudstone matrix are intercalated into the pelagic rocks, possibly representing complex mélange forming processes during the development of the Jurassic accretionary complex.
Social exclusion modulates dual mechanisms of cognitive control: Evidence from ERPs
Authors: Xu Mengsi , Li Zhiai , Qi Senqing , Fan Lingxia , Zhou Xiaolin , Yang Dong
Published: June 2020

Many studies have investigated how social exclusion influences cognitive control but reported inconsistent findings. Based on the dual mechanisms of control framework, this study investigated how social exclusion influences proactive and reactive modes of control (Experiment 1) and the underlying mechanisms (Experiment 2). The Cyberball game was used to manipulate social exclusion. Eighty‐six female participants (about 40 for each experiment) performed cognitive control tasks while event‐related potentials were recorded. In Experiment 1, an AX Continuous Performance Task (AX‐CPT) was adopted to differentiate between proactive and reactive control. Results showed that social exclusion weakened proactive control but enhanced reactive control, as reflected by the weaker proactive control indicators (i.e., P3b and CNV), but strengthened reactive control indicators (accuracy and N2) in excluded individuals. More importantly, in Experiment 2, through varying in whether task cues were available before or after target onset in a cued‐flanker task, we further manipulated the possibility of engaging proactive control, and found the weakened proactive control could be attributed to both impaired cognitive ability and lowered motivation to engage proactive control in excluded individuals. Together, these results provide insight on how social exclusion influences cognitive control and suggest promising implications for designing effective interventions to relieve the negative impact of social exclusion.
Negative illness perceptions are related to poorer health‐related quality of life among thyroid cancer survivors: Results from the PROFILES registry
Authors: Schoormans Dounya , Wijnberg Laura , Haak Harm , Husson Olga , Mols Floortje
Published: June 2020

Background

Differentiated thyroid cancer (DTC) reports a poorer health‐related quality of life (HRQoL) than a norm population. Patients' illness perceptions are modifiable and known associates of HRQoL in other cancers. The aim was to examine the relationship between illness perceptions and HRQoL among DTC survivors.

Methods

DTC survivors registered in the Netherlands Cancer Registry diagnosed between 1990 and 2008, received a survey on illness perceptions (Brief‐Illness Perception Questionnaire; B‐IPQ) and HRQoL (European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire‐Core 30; EORTC QLQ‐C30). Multiple regression analyses were conducted investigating the relation between illness perceptions and HRQoL, while controlling for sociodemographic and clinical characteristics.

Results

Two hundred and eighty‐four DTC survivors were included. DTC survivors who believed their illness had many negative consequences; who perceived their illness as controllable by treatment; who had strong beliefs symptoms could be attributed to their illness; and who had strong beliefs their illness causes negative emotions, reported a poorer HRQoL.

Conclusions

Stronger negative illness perceptions are related to a poorer HRQoL among DTC survivors.
Identifying an Optimal Liver Frailty Index Cutoff to Predict Waitlist Mortality in Liver Transplant Candidates
Authors: Kardashian Ani , Ge Jin , McCulloch Charles E. , Kappus Matthew R. , Dunn Michael A. , Duarte‐Rojo Andres , Volk Michael L. , Rahimi Robert S. , Verna Elizabeth C. , Ganger Daniel R. , Ladner Daniela , Dodge Jennifer L. , Boyarsky Brian , McAdams‐DeMarco Mara , Segev Dorry L. , Lai Jennifer C.
Published: June 2020

Background and Aims

Frailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality.

Approach and Results

Adults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo‐log‐likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease‐sodium (MELDNa) versus MELDNa alone in 3‐month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7‐5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0‐4.8) for 3‐month mortality, 4.2 (95% CI, 4.1‐4.4) for 6‐month mortality, and 4.2 (95% CI, 4.1‐4.4) for 12‐month mortality. The AUC for prediction of 3‐month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79.

Conclusions

LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.
Insouciance and inexperience: A deadly combination when dealing with COVID‐19
Authors: Paton Calum
Published: June 2020

This article gives key reasons for the UK's tardy and confused attempts to react to the COVID‐19 pandemic. It explains very poor outcomes in the UK (in terms of the spread of the virus and high mortality, already striking at the time of writing), in terms of an initial lack of political will to prioritise public health, itself a product of a strong Prime Minister who made the “wrong call”. It also highlights a failure to “follow the science”, except in so far as the “science” had already accepted some dubious political judgements and the lack of capacity to test as the starting‐point.
Immune phenotype of tumor microenvironment predicts response to bevacizumab in neoadjuvant treatment of ER‐positive breast cancer
Authors: von der Lippe Gythfeldt Hedda , Lien Tonje , Tekpli Xavier , Silwal‐Pandit Laxmi , Borgen Elin , Garred Øystein , Skjerven Helle , Schlichting Ellen , Lundgren Steinar , Wist Erik , Naume Bjørn , Kristensen Vessela , Børresen‐Dale Anne‐Lise , Lingjærde Ole Christian , Engebraaten Olav
Published: June 2020

Antiangiogenic drugs are potentially a useful supplement to neoadjuvant chemotherapy for a subgroup of patients with human epidermal growth factor receptor 2 (HER2) negative breast cancer, but reliable biomarkers for improved response are lacking. Here, we report on a randomized phase II clinical trial to study the added effect of bevacizumab in neoadjuvant chemotherapy with FEC100 (5‐fluorouracil, epirubicin and cyclophosphamide) and taxanes (n = 132 patients). Gene expression from the tumors was obtained before neoadjuvant treatment, and treatment response was evaluated by residual cancer burden (RCB) at time of surgery. Bevacizumab increased the proportion of complete responders (RCB class 0) from 5% to 20% among patients with estrogen receptor (ER) positive tumors (P = .02). Treatment with bevacizumab was associated with improved 8‐year disease‐free survival (P = .03) among the good responders (RCB class 0 or I). Patients treated with paclitaxel (n = 45) responded better than those treated with docetaxel (n = 21; P = .03). Improved treatment response was associated with higher proliferation rate and an immune phenotype characterized by high presence of classically activated M1 macrophages, activated NK cells and memory activated CD4 T cells. Treatment with bevacizumab increased the number of adverse events, including hemorrhage, hypertension, infection and febrile neutropenia, but despite this, the ECOG status was not affected.
Harnessing nerve–muscle cell interactions for biomaterials‐based skeletal muscle regeneration
Authors: Narayanan Naagarajan , Lengemann Paul , Kim Kun Ho , Kuang Liangju , Sobreira Tiago , Hedrick Victoria , Aryal Uma K. , Kuang Shihuan , Deng Meng
Published: June 2020

Nerve cells secrete neurotrophic factors that play a critical role in neuronal survival, proliferation, and regeneration. However, their role in regulating myoblast behavior and skeletal muscle repair remains largely unexplored. In the present study, we investigated the effects of PC12 secreted signaling factors in modulating C2C12 myoblast behavior under physiologically relevant conditions. We showed that PC12 conditioned media modulated myoblast proliferation and differentiation in both 2D culture and 3D aligned electrospun fiber scaffold system in a dose‐dependent manner. We further developed a biomimetic, tunable hydrogel consisting of hyaluronic acid, chondroitin sulfate, and polyethylene glycol as a 3D matrix encapsulating PC12 cells. The hydrogel‐encapsulated PC12 cells promoted survival and proliferation of myoblasts in co‐culture. Further proteomics analysis identified a total of 2,088 proteins from the secretome of the encapsulated PC12 cells and revealed the biological role and overlapping functions of nerve‐secreted proteins for skeletal muscle regeneration, potentially through regulating myoblast behavior, nerve function, and angiogenesis. These experiments provide insights into the nerve–muscle interactions and pave the way for developing advanced biomaterials strategies incorporating nerve cell secretome for accelerated skeletal muscle regeneration.
Increased yield of gelatin coated therapeutic cells through cholesterol insertion
Authors: Davis Kara A. , Peng Hsuan , Chelvarajan Lakshman , Abdel‐Latif Ahmed , Berron Brad J.
Published: June 2020

Gelatin coatings are effective in increasing the retention of MSCs injected into the heart and minimizing the damage from acute myocardial infarction (AMI), but early studies suffered from low fractions of the MSCs coated with gelatin. Biotinylation of the MSC surface is a critical first step in the gelatin coating process, and in this study, we evaluated the use of biotinylated cholesterol “lipid insertion” anchors as a substitute for the covalent NHS‐biotin anchors to the cell surface. Streptavidin‐eosin molecules, where eosin is our photoinitiator, can then be bound to the cell surface through biotin‐streptavidin affinity. The use of cholesterol anchors increased streptavidin density on the surface of MSCs further driving polymerization and allowing for an increased fraction of MSCs coated with gelatin (83%) when compared to NHS‐biotin (52%). Additionally, the cholesterol anchors increased the uniformity of the coating on the MSC surface and supported greater numbers of coated MSCs even when the streptavidin density was slightly lower than that of an NHS‐biotin anchoring strategy. Critically, this improvement in gelatin coating efficiency did not impact cytokine secretion and other critical MSC functions. Proper selection of the cholesterol anchor and the biotinylation conditions supports cellular function and densities of streptavidin on the MSC surface of up to ~105 streptavidin molecules/μm2. In all, these cholesterol anchors offer an effective path towards the formation of conformal coatings on the majority of MSCs to improve the retention of MSCs in the heart following AMI.
In vitro estimation of reduction in strength and wear resistance of UHMWPE for joint prostheses due to lipid‐induced degradation
Authors: Sakoda Hideyuki , Okamoto Yoshihiro , Haishima Yuji
Published: June 2020

Ultra‐high molecular weight polyethylene (UHMWPE) is used as a bearing surface of joint prostheses and has been reported to absorb lipids such as squalene (SQ) and cholesterol esters in vivo. These lipids have been suggested by in vitro studies using SQ as a model lipid to have the potential to induce polymer degradation. However, the impact of lipid‐induced degradation on the strength and wear resistance of UHMWPE is unknown. In this study, lipid‐induced degradation was simulated by SQ absorption and subsequent accelerated aging, and its influence on the strength and wear resistance of UHMWPE was investigated using wear, fatigue crack growth, and delamination testing. Lipid‐induced degradation was found to have little impact on fatigue crack growth rates and delamination resistance. These results were consistent with previous reports that lipid‐induced degradation is localized near the surface. However, we also found that lipid‐induced degradation increased the wear rate of both non‐crosslinked and crosslinked UHMWPE by a factor of 2.5 and 14, respectively. These results indicate that lipid‐induced degradation may affect the durability and long‐term clinical outcome of joint replacements due to increased wear of UHMWPE.
Combined approaches for evaluation of xenoestrogen neural toxicity and thyroid dysfunction: Screening of oxido‐nitrosative markers, DNA fragmentation, and biogenic amine degradation
Authors: Taha Mohamed , Marie Abeer M. , Ahmed‐Farid Omar A.
Published: June 2020

Anthropogenic chemicals such as parabens and triclosan are used in personal care products. Due to their ability to decrease or prevent bacterial contamination and act as preservatives, these chemicals are used in cosmetic manufacturing processes to increase the shelf life of products. In this study, we assessed the side effects of environmental estrogens (such as the xenoestrogen butylparaben and the antimicrobial agent and preservative triclosan) on thyroid function, brain monoamine levels, and DNA aberration. Forty‐two male albino rats were divided into seven groups with six members each: the first group served as control; the second and the third groups were treated with butylparaben 10 and 50 mg/kg body weight, respectively; the fourth and fifth groups were treated with triclosan 10 and 50 mg/kg body weight, respectively; and the sixth and seventh groups were treated with butylparaben plus triclosan 10 and 50 mg/kg body weight, respectively. After 60 days, blood samples were collected and brain specimens were divided into striatum, midbrain, cortex, and thalamus. Thyroid function and levels of monoamines and monoamine metabolites were determined for each brain area. Comet assay was used for brain tissue analysis. The results showed that butylparaben and triclosan and their combinations induced hypothyroidism and disrupted monoamine levels, leading to a decrease in catecholamine and serotonin levels, and accelerated production of 5‐hydroxyindoleacetic acid. The obtained data indicate that anthropogenic chemicals such as butylparaben and triclosan have harmful effects on thyroid and brain function and accelerate cell destruction and mutation, as evidenced by single‐stranded DNA breaks in the comet assay.
PRKAA1 rs13361707 C/T polymorphism confers decreased susceptibility to esophageal cancer: A case‐control study
Authors: Li Cheng‐Lin , Zhao Jian‐Qiang , Zang Bao
Published: June 2020

Background

Several studies probed into the connection between esophageal cancer (EC) risk and PRKAA1 rs13361707 C/T

polymorphism, but obtained insignificant findings.

Methods

In this study, 814 EC cases and 961

controls from Eastern China were recruited to validate the relationship between this polymorphism and EC susceptibility.

Results

Data suggested rs13361707 C/T

polymorphism in PRKAA1 gene was significantly related with a lower risk for EC. Such significant connection was also uncovered in subgroups of males, smokers, drinkers and individuals with age ≥ 60 years. In addition, this polymorphism

was linked with the pathological grading, distant metastasis, and histology of EC.

Conclusion

In summary, PRKAA1 rs13361707 C/T

polymorphism is related to the risk and clinical properties of EC patients in East China.
Concomitant blockade of A2AR and CTLA‐4 by siRNA‐loaded polyethylene glycol‐chitosan‐alginate nanoparticles synergistically enhances antitumor T‐cell responses
Authors: Ghasemi‐Chaleshtari Mitra , Kiaie Seyed Hossein , Irandoust Mahzad , Karami Hadis , Nabi Afjadi Mohsen , Ghani Sepideh , Aghaei Vanda Nasimeh , Ghaderi Sede Mohammad Javad , Ahmadi Armin , Masjedi Ali , Hassannia Hadi , Atyabi Fatemeh , Hojjat‐Farsangi Mohammad , Namdar Afshin , Ghalamfarsa Ghasem , Jadidi‐Niaragh Farhad
Published: June 2020

Inhibitory immune checkpoint (ICP) molecules are important immunosuppressive factors in a tumor microenvironment (TME). They can robustly suppress T‐cell‐mediated antitumor immune responses leading to cancer progression. Among the checkpoint molecules, cytotoxic T‐lymphocyte‐associated protein‐4 (CTLA‐4) is one of the critical inhibitors of anticancer T‐cell responses. Besides, the expression of adenosine receptor (A2AR) on tumor‐infiltrating T cells potently reduces their function. We hypothesized that concomitant silencing of these molecules in T cells might lead to enhanced antitumor responses. To examine this assumption, we purified T cells from the tumor, spleen, and local lymph nodes of CT26 colon cancer‐bearing mice and suppressed the expression of A2AR and CTLA‐4 using the small interfering RNA (siRNA)‐loaded polyethylene glycol‐chitosan‐alginate (PCA) nanoparticles. The appropriate physicochemical properties of the produced nanoparticles (NPs; size of 72 nm, polydispersive index [PDI] < 0.2, and zeta potential of 11 mV) resulted in their high efficiency in transfection and suppression of target gene expression. Following the silencing of checkpoint molecules, various T‐cell functions, including proliferation, apoptosis, cytokine secretion, differentiation, and cytotoxicity were analyzed, ex vivo. The results showed that the generated nanoparticles had optimal physicochemical characteristics and significantly suppressed the expression of target molecules in T cells. Moreover, a concomitant blockade of A2AR and CTLA‐4 in T cells could synergistically enhance antitumor responses through the downregulation of PKA, SHP2, and PP2Aα signaling pathways. Therefore, this combination therapy can be considered as a novel promising anticancer therapeutic strategy, which should be further investigated in subsequent studies.
Selenium deficiency induced necroptosis, Th1/Th2 imbalance, and inflammatory responses in swine ileum
Authors: Zhang Yuan , Zhang Jiuli , Bao Jun , Tang Chaohua , Zhang Ziwei
Published: June 2020

Selenium (Se) deficiency has a significant impact on the swine breeding industry by inducing digestive system damage and diarrhea. However, the molecular mechanism remains unclear. Our objectives were to investigate if different amounts of necroptosis, inflammatory responses, and T helper cell 1/T helper cell 2 (Th1/Th2) imbalances were induced by Se deficiency in intestinal porcine jejunal epithelial cells (IPEC‐J2) and swine ileum tissue. Therefore, Se‐deficient models were successfully established both in vitro and in vivo. In the current study, the cell morphological observation results showed that Se deficiency seriously affected the growth and differentiation of IPEC‐J2 cells. Moreover, the necroptosis staining and histomorphology observation results showed that the number of necroptotic cells increased significantly, and the ileal tissue exhibited abnormal structures, including necroptotic features and inflammatory cell infiltration, in the Se‐deficient group. Furthermore, Se deficiency resulted in accelerated cell necroptosis by increasing (p < .05) the expression of genes related to the tumor necrosis factor‐α pathway at both the protein and messenger RNA (mRNA) levels compared to the control group. Moreover, the relative mRNA and protein expression of the inflammatory genes and their responses to dietary Se deficiency were consistent with the resultant Th1/Th2 imbalances in vitro and in vivo. Taken together, the results suggested that Se deficiency caused necroptosis, inflammatory responses, and abnormal expression of cytokines in swine ileum tissue. These findings might help us to explain the damage induced by Se deficiency to the digestive system of swine.
Base promoted regioselective aromatization for the preparation of substituted 3‐hydroxybenzene dicarboxylate
Authors: Guo Weihang , Wang Xianheng , Zhao Changkuo , Wang Yuhe
Published: June 2020

A new convenient base promoted aromatization process has been developed to prepare substituted 3‐hydroxybenzene dicarboxylate using commercially available materials. In particular, regioselectivity will occur for substrates with mono‐substitution at 5‐ or 6‐position. This new process provides less reaction steps and moderate yields, and can be used extensively in the synthesis of other substrates to functionalize phenol esters.
Microcredit and Economic Welfare: Experience of Poor Rural Households from Pakistan
Authors: Latif Waqas Umar , Ullah Sana , Ahmed Wasim , Sultan Muhammad Umar , Jafar Rana Muhammad Sohail , Tariq Muhammad , Linping Wang
Published: June 2020

This research article effort to empirically assess the effect of microcredit on household economic welfare consequences, for example income and consumption in rural Pakistan. The valuation is based on the difference‐in‐difference method that is a progressively popular technique of tackling the selection bias issue in measuring the influences of microcredit. This paper uses a 2‐year panel data set, together with both primary and secondary data gained through a household survey in rural Pakistan. Our empirical outcomes favour the full belief in the literature that participates in microcredit programme helps expand households' economic welfare, for example income and consumption. Despite the positive results on how microcredit has improved the rural households' living status, our outcomes display that the huge majority of the program applicants are non‐poor, which casts roughly uncertainties on the social potential (for example poverty alleviation) of Pakistan's microcredit programs. © 2020 John Wiley & Sons, Ltd.
Quantifying lymphocyte vacuolization serves as a measure of CLN3 disease severity
Authors: Kuper Willemijn F. E. , Oostendorp Marlies , van den Broek Brigitte T. A. , van Veghel Karin , Nonkes Lourens J. P. , Nieuwenhuis Edward E. S. , Fuchs Sabine A. , Veenendaal Tineke , Klumperman Judith , Huisman Albert , Nierkens Stefan , van Hasselt Peter M.
Published: June 2020

Background

The CLN3 disease spectrum ranges from a childhood‐onset neurodegenerative disorder to a retina‐only disease. Given the lack of metabolic disease severity markers, it may be difficult to provide adequate counseling, particularly when novel genetic variants are identified. In this study, we assessed whether lymphocyte vacuolization, a well‐known yet poorly explored characteristic of CLN3 disease, could serve as a measure of disease severity.

Methods

Peripheral blood obtained from healthy controls and CLN3 disease patients was used to assess lymphocyte vacuolization by (a) calculating the degree of vacuolization using light microscopy and (b) quantifying expression of lysosomal‐associated membrane protein 1 (LAMP‐1), using flow cytometry in lymphocyte subsets as well as a qualitative analysis using electron microscopy and ImageStream analysis.

Results

Quantifying lymphocyte vacuolization allowed to differentiate between CLN3 disease phenotypes (P = .0001). On immunofluorescence, classical CLN3 disease lymphocytes exhibited abundant vacuole‐shaped LAMP‐1 expression, suggesting the use of LAMP‐1 as a proxy for lymphocyte vacuolization. Using flow cytometry in lymphocyte subsets, quantifying intracellular LAMP‐1 expression additionally allowed to differentiate between infection and storage and to differentiate between CLN3 phenotypes even more in‐depth revealing that intracellular LAMP‐1 expression was most pronounced in T‐cells of classical‐protracted CLN3 disease while it was most pronounced in B‐cells of “retina‐only” CLN3 disease.

Conclusion

Lymphocyte vacuolization serves as a proxy for CLN3 disease severity. Quantifying vacuolization may help interpretation of novel genetic variants and provide an individualized readout for upcoming therapies.
Successful management of a neonate with OTC deficiency presenting with hyperammonemia and severe cardiac dysfunction with extracorporeal membrane oxygenation support and continuous renal replacement therapy
Authors: Mattke Adrian C. , Shikata Fumiaki , McGill James , Justo Rob , Venugopal Prem
Published: June 2020

Ornithine transcarbamylase (OTC) deficiency is an X‐linked urea cycle disorder which—in severe form—results in rapid accumulation of ammonia and glutamine with subsequent irreversible brain injury. We present a case of severe left ventricular dysfunction with hyperammonemic crisis caused by OTC deficiency which was managed with veno‐arterial extracorporeal membrane oxygenation support combined with continuous renal replacement therapy. Aggressive treatment led to normalization of ammonia and full left ventricular recovery.
MRI‐Based Radiomics Signature: A Potential Biomarker for Identifying Glypican 3‐Positive Hepatocellular Carcinoma
Authors: Gu Dongsheng , Xie Yongsheng , Wei Jingwei , Li Wencui , Ye Zhaoxiang , Zhu Zhongyuan , Tian Jie , Li Xubin
Published: June 2020

Background

Glypican 3 (GPC3) expression has proved to be a critical risk factor related to prognosis in hepatocellular carcinoma (HCC) patients.

Purpose

To investigate the performance of MRI‐based radiomics signature in identifying GPC3‐positive HCC.

Study Type

Retrospective.

Population

An initial cohort of 293 patients with pathologically confirmed HCC was involved in this study, and patients were randomly divided into training (195) and validation (98) cohorts.

Field Strength/Sequences

Contrast‐enhanced T1‐weight MRI was performed with a 1.5T scanner.

Assessment

A total of 853 radiomic features were extracted from the volume imaging. Univariate analysis and Fisher scoring were utilized for feature reduction. Subsequently, forward stepwise feature selection and radiomics signature building were performed based on a support vector machine (SVM). Incorporating independent risk factors, a combined nomogram was developed by multivariable logistic regression modeling.

Statistical Tests

The predictive performance of the nomogram was calculated using the area under the receive operating characteristic curve (AUC). Decision curve analysis (DCA) was applied to estimate the clinical usefulness.

Results

The radiomics signature consisting of 10 selected features achieved good prediction efficacy (training cohort: AUC = 0.879, validation cohort: AUC = 0.871). Additionally, the combined nomogram integrating independent clinical risk factor α‐fetoprotein (AFP) and radiomics signature showed improved calibration and prominent predictive performance with AUCs of 0.926 and 0.914 in the training and validation cohorts, respectively.

Data Conclusion

The proposed MR‐based radiomics signature is strongly related to GPC3‐positive. The combined nomogram incorporating AFP and radiomics signature may provide an effective tool for noninvasive and individualized prediction of GPC3‐positive in patients with HCC. J. MAGN. RESON. IMAGING 2020;52:1679–1687.
Harmonization of Quantitative Parenchymal Enhancement in T1‐Weighted Breast MRI
Authors: van der Velden Bas H.M. , van Rijssel Michael J. , Lena Beatrice , Philippens Marielle E.P. , Loo Claudette E. , Ragusi Max A.A. , Elias Sjoerd G. , Sutton Elizabeth J. , Morris Elizabeth A. , Bartels Lambertus W. , Gilhuijs Kenneth G.A.
Published: June 2020

Background

Differences in imaging parameters influence computer‐extracted parenchymal enhancement measures from breast MRI.

Purpose

To investigate the effect of differences in dynamic contrast‐enhanced MRI acquisition parameter settings on quantitative parenchymal enhancement of the breast, and to evaluate harmonization of contrast‐enhancement values with respect to flip angle and repetition time.

Study Type

Retrospective.

Phantom/Populations

We modeled parenchymal enhancement using simulations, a phantom, and two cohorts (N = 398 and N = 302) from independent cancer centers.

Sequence Field/Strength

1.5T dynamic contrast‐enhanced T1‐weighted spoiled gradient echo MRI. Vendors: Philips, Siemens, General Electric Medical Systems.

Assessment

We assessed harmonization of parenchymal enhancement in simulations and phantom by varying the MR parameters that influence the amount of T1‐weighting: flip angle (8°–25°) and repetition time (4–12 msec). We calculated the median and interquartile range (IQR) of the enhancement values before and after harmonization. In vivo, we assessed overlap of quantitative parenchymal enhancement in the cohorts before and after harmonization using kernel density estimations. Cohort 1 was scanned with flip angle 20° and repetition time 8 msec; cohort 2 with flip angle 10° and repetition time 6 msec.

Statistical Tests

Paired Wilcoxon signed‐rank‐test of bootstrapped kernel density estimations.

Results

Before harmonization, simulated enhancement values had a median (IQR) of 0.46 (0.34–0.49). After harmonization, the IQR was reduced: median (IQR): 0.44 (0.44–0.45). In the phantom, the IQR also decreased, median (IQR): 0.96 (0.59–1.22) before harmonization, 0.96 (0.91–1.02) after harmonization. Harmonization yielded significantly (P < 0.001) better overlap in parenchymal enhancement between the cohorts: median (IQR) was 0.46 (0.37–0.58) for cohort 1 vs. 0.37 (0.30–0.44) for cohort 2 before harmonization (57% overlap); and 0.35 (0.28–0.43) vs. .0.37 (0.30–0.44) after harmonization (85% overlap).

Data Conclusion

The proposed practical harmonization method enables an accurate comparison between patients scanned with differences in imaging parameters.

Level of Evidence

3

Technical Efficacy Stage

4
Evidence for mutations in SARS‐CoV‐2 Italian isolates potentially affecting virus transmission
Authors: Benvenuto Domenico , Demir Ayse Banu , Giovanetti Marta , Bianchi Martina , Angeletti Silvia , Pascarella Stefano , Cauda Roberto , Ciccozzi Massimo , Cassone Antonio
Published: June 2020

Italy is the first western country suffering heavy severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission and disease impact after coronavirus disease‐2019 pandemia started in China. Even though the presence of mutations on spike glycoprotein and nucleocapsid in Italian isolates has been reported, the potential impact of these mutations on viral transmission has not been evaluated. We have compared SARS‐CoV‐2 genome sequences from Italian patients with virus sequences from Chinese patients. We focussed upon three nonsynonymous mutations of genes coding for S(one) and N (two) viral proteins present in Italian isolates and absent in Chinese ones, using various bioinformatics tools. Amino acid analysis and changes in three‐dimensional protein structure suggests the mutations reduce protein stability and, particularly for S1 mutation, the enhanced torsional ability of the molecule could favor virus binding to cell receptor(s). This theoretical interpretation awaits experimental and clinical confirmation.
Potential neuroinvasive pathways of SARS‐CoV‐2: Deciphering the spectrum of neurological deficit seen in coronavirus disease‐2019 (COVID‐19)
Authors: Baig Abdul Mannan , Sanders Erin C.
Published: June 2020

Coronavirus disease‐2019 (COVID‐19) was declared a global pandemic on 11 March 2020. Scientists and clinicians must acknowledge that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has the potential to attack the human body in multiple ways simultaneously and exploit any weaknesses of its host. A multipronged attack could potentially explain the severity and extensive variety of signs and symptoms observed in patients with COVID‐19. Understanding the diverse tactics of this virus to infect the human body is both critical and incredibly complex. Although patients diagnosed with COVID‐19 have primarily presented with pulmonary involvement, viral invasion, and injury to diverse end organs is also prevalent and well documented in these patients, but has been largely unheeded. Human organs known for angiotensin‐converting enzyme 2 (ACE2) expression including the gastrointestinal tract, kidneys, heart, adrenals, brain, and testicles are examples of extra pulmonary tissues with confirmed invasion by SARS‐CoV‐2. Initial multiple organ involvement may present with vague signs and symptoms to alert health care professionals early in the course of COVID‐19. Another example of an ongoing, yet neglected element of the syndromic features of COVID‐19, are the reported findings of loss of smell, altered taste, ataxia, headache, dizziness, and loss of consciousness, which suggest a potential for neural involvement. In this review, we further deliberate on the neuroinvasive potential of SARS‐CoV‐2, the neurologic symptomology observed in COVID‐19, the host‐virus interaction, possible routes of SARS‐CoV‐2 to invade the central nervous system, other neurologic considerations for patients with COVID‐19, and a collective call to action.
Determining host factors contributing to disease severity in a family cluster of 29 hospitalized SARS‐CoV‐2 patients: Could genetic factors be relevant in the clinical course of COVID‐19?
Authors: Ikitimur Hande , Borku Uysal Betul , Cengiz Mahir , Ikitimur Barış , Uysal Harun , Ozcan Erkan , Islamoglu Mehmet Sami , Seyhan Serhat , Yavuzer Hakan , Yavuzer Serap
Published: June 2020

In this study, we report a large family cluster consisting of 29 genetically related patients hospitalized with coronavirus disease‐2019 (COVID‐19). We sought to determine the clinical characteristics relevant to the clinical course of COVID‐19 by comparing the family cluster to unrelated patients with SARS‐CoV‐2 infection so that the presence of potential determinants of disease severity, other than traditional risk factors previously reported, could be investigated. Twenty‐nine patient files were investigated in group 1 and group 2 was created with 52 consecutive patients with COVID‐19 having age and gender compatibility. The virus was detected for diagnosis. The clinical, laboratory and imaging features of all patients were retrospectively screened. Disease course was assessed using records regarding outcome from patient files retrospectively. Groups were compared with respect to baseline characteristics, disease severity on presentation, and disease course. There was no difference between the two groups in terms of comorbidity and smoking history. In terms of inhospital treatment, use differed not significantly between two groups. We found that all 29 patients in the group 1 had severe pneumonia, 18 patients had severe pneumonia. Hospitalization rates, length of hospital stay, and transferred to intensive care unit were found to be statistically significantly higher in the group 1. In the present study, COVID‐19 cases in the large family cluster were shown to have more severe disease and worse clinical course compared with consecutive patients with COVID‐19 presenting to the same time. We believe further studies into potential genetic mechanisms of host susceptibility to COVID‐19 should include such family clusters.