bluuebunny/crossref_metadata_2025 huggingface dataset:
Paradoxical network excitation by glutamate release from VGluT3+ GABAergic interneurons
Authors: Pelkey Kenneth A , Calvigioni Daniela , Fang Calvin , Vargish Geoffrey , Ekins Tyler , Auville Kurt , Wester Jason C , Lai Mandy , Mackenzie-Gray Scott Connie , Yuan Xiaoqing , Hunt Steven , Abebe Daniel , Xu Qing , Dimidschstein Jordane , Fishell Gordon , Chittajallu Ramesh , McBain Chris J
Published: February 2020

In violation of Dale’s principle several neuronal subtypes utilize more than one classical neurotransmitter. Molecular identification of vesicular glutamate transporter three and cholecystokinin expressing cortical interneurons (CCK+VGluT3+INTs) has prompted speculation of GABA/glutamate corelease from these cells for almost two decades despite a lack of direct evidence. We unequivocally demonstrate CCK+VGluT3+INT-mediated GABA/glutamate cotransmission onto principal cells in adult mice using paired recording and optogenetic approaches. Although under normal conditions, GABAergic inhibition dominates CCK+VGluT3+INT signaling, glutamatergic signaling becomes predominant when glutamate decarboxylase (GAD) function is compromised. CCK+VGluT3+INTs exhibit surprising anatomical diversity comprising subsets of all known dendrite targeting CCK+ interneurons in addition to the expected basket cells, and their extensive circuit innervation profoundly dampens circuit excitability under normal conditions. However, in contexts where the glutamatergic phenotype of CCK+VGluT3+INTs is amplified, they promote paradoxical network hyperexcitability which may be relevant to disorders involving GAD dysfunction such as schizophrenia or vitamin B6 deficiency.
A large-scale resource for tissue-specific CRISPR mutagenesis in Drosophila
Authors: Port Fillip , Strein Claudia , Stricker Mona , Rauscher Benedikt , Heigwer Florian , Zhou Jun , Beyersdörffer Celine , Frei Jana , Hess Amy , Kern Katharina , Lange Laura , Langner Nora , Malamud Roberta , Pavlović Bojana , Rädecke Kristin , Schmitt Lukas , Voos Lukas , Valentini Erica , Boutros Michael
Published: February 2020

Genetic screens are powerful tools for the functional annotation of genomes. In the context of multicellular organisms, interrogation of gene function is greatly facilitated by methods that allow spatial and temporal control of gene abrogation. Here, we describe a large-scale transgenic short guide (sg) RNA library for efficient CRISPR-based disruption of specific target genes in a constitutive or conditional manner. The library consists currently of more than 2600 plasmids and 1700 fly lines with a focus on targeting kinases, phosphatases and transcription factors, each expressing two sgRNAs under control of the Gal4/UAS system. We show that conditional CRISPR mutagenesis is robust across many target genes and can be efficiently employed in various somatic tissues, as well as the germline. In order to prevent artefacts commonly associated with excessive amounts of Cas9 protein, we have developed a series of novel UAS-Cas9 transgenes, which allow fine tuning of Cas9 expression to achieve high gene editing activity without detectable toxicity. Functional assays, as well as direct sequencing of genomic sgRNA target sites, indicates that the vast majority of transgenic sgRNA lines mediate efficient gene disruption. Furthermore, we conducted the so far largest fully transgenic CRISPR screen in any metazoan organism, which further supported the high efficiency and accuracy of our library and revealed many so far uncharacterized genes essential for development.
The effects of single versus multiple training sessions on the motor learning of two Krav Maga strike techniques, in women
Authors: Di Bacco Vincenzo E. , Taherzadeh Mehran , Birot Olivier , Gage William H.
Published: February 2020

Background

Experts of the Krav Maga (KM) self-defense system propose that KM techniques are based on simple body movements which are suggested to be learned rapidly and retained. This study investigated the acquisition, retention, and further improvement with additional training of two KM strike techniques among novice female practitioners: straight punch and defensive kick.

Methods

Sixteen healthy females (age: 23 ± 3.7 years) without any previous martial arts/self-defense experience volunteered to participate. All participants received an initial 30-min instruction session (AQ), taught by a certified KM instructor, where each technique was deconstructed into three checkpoints (defined as a component of the entire movement) for learning. Participants were divided into two groups, one of which received additional training. Several kinematic and kinetic measures were recorded at four timepoints: immediately before AQ, immediately after AQ, 5 days after AQ, and 12 days after AQ.

Results

Results suggest that both techniques were learned rapidly, as checkpoint performance was significantly improved after AQ. Kick velocity and impact force also increased significantly after AQ; however, these measures did not change after AQ for the punch technique. Additional training did not improve either punch or kick performance beyond that learned during AQ.

Conclusion

The findings from this study suggest that a single training session may be sufficient to learn and retain KM strike techniques relatively permanently; and the acquisition of the kick technique may lead to concomitant improvements in kick velocity and impact force.
Inhibition of Myc transcriptional activity by a mini‐protein based upon Mxd1
Authors: Demma Mark J. , Hohn Michael J. , Sun Angie , Mapelli Claudio , Hall Brian , Walji Abbas , O'Neil Jennifer
Published: February 2020

Myc, a transcription factor with oncogenic activity, is upregulated by amplification, translocation, and mutation of the cellular pathways that regulate its stability. Inhibition of the Myc oncogene by various modalities has had limited success. One Myc inhibitor, Omomyc, has limited cellular and in vivo activity. Here, we report a mini‐protein, referred to as Mad, which is derived from the cellular Myc antagonist Mxd1. Mad localizes to the nucleus in cells and is 10‐fold more potent than Omomyc in inhibiting Myc‐driven cell proliferation. Similar to Mxd1, Mad also interacts with Max, the binding partner of Myc, and with the nucleolar upstream binding factor. Mad binds to E‐Box DNA in the promoters of Myc target genes and represses Myc‐mediated transcription to a greater extent than Omomyc. Overall, Mad appears to be more potent than Omomyc both in vitro and in cells.
A dual PMMA/calcium sulfate carrier of vancomycin is more effective than PMMA‐vancomycin at inhibiting Staphylococcus aureus growth in vitro
Authors: Luo Shanchao , Jiang Tongmeng , Long Lina , Yang Yingnian , Yang Xiaoping , Luo Lan , Li Jinli , Chen Zhiyu , Zou Chongqi , Luo Shixing
Published: February 2020

Both antibiotic‐impregnated poly(methyl acrylate, methyl methacrylate) (PMMA) and antibiotic‐impregnated calcium sulfate have been successfully used as local antibiotic delivery vehicles for the management of chronic osteomyelitis. Here, we examined the antibiotic elution characteristics and antibacterial properties of a composite drug delivery system consisting of PMMA/calcium sulfate carrying vancomycin (dual carrier‐v) against Staphylococcus aureus, with PMMA loaded with vancomycin (PMMA‐v) as a control. Vancomycin gradually degraded from dual carrier‐v and PMMA‐v up to about 8 and 6 weeks, respectively. At different elution time points, the inhibition zones of the dual carrier‐v were larger than the inhibition zones of the PMMA‐v (P < 0.05). The colony inhibition rate of the dual carrier‐v was 95.57%, whereas it was 77.87% for PMMA‐v. Scanning electron microscopy was used to demonstrate biofilm formation on the surface of plates treated with vancomycin‐unloaded PMMA, whereas there was no biofilm formation on the surface of plates treated with dual carrier‐v or PMMA‐v. The dual carrier‐v was more effective at antibacterial adhesion at each time point after immersion in simulated body fluid as compared with PMMA‐v (P < 0.05). In conclusion, our results suggest that the dual carrier‐v can release higher concentrations of antibiotics and inhibit bacteria growth more effectively in vitro as compared with PMMA‐v. The dual carrier‐v thus may have potential as an alternative strategy for osteomyelitis management.
Iron overload inhibits self‐renewal of human pluripotent stem cells via DNA damage and generation of reactive oxygen species
Authors: Han Zhenbo , Xu Zihang , Chen Lei , Ye Danyu , Yu Yang , Zhang Ying , Cao Yang , Djibril Bamba , Guo Xiaofei , Gao Xinlu , Zhang Wenwen , Yu Meixi , Liu Shenzhen , Yan Gege , Jin Mengyu , Huang Qi , Wang Xiuxiu , Hua Bingjie , Feng Chao , Yang Fan , Ma Wenya , Liu Yu
Published: February 2020

Iron overload affects the cell cycle of various cell types, but the effect of iron overload on human pluripotent stem cells has not yet been reported. Here, we show that the proliferation capacities of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) were significantly inhibited by ferric ammonium citrate (FAC) in a concentration‐dependent manner. In addition, deferoxamine protected hESCs/hiPSCs against FAC‐induced cell‐cycle arrest. However, iron overload did not affect pluripotency in hESCs/hiPSCs. Further, treatment of hiPSCs with FAC resulted in excess reactive oxygen species production and DNA damage. Collectively, our findings provide new insights into the role of iron homeostasis in the maintenance of self‐renewal in human pluripotent stem cells.
Moderate‐intensity exercise increases renalase levels in the blood and skeletal muscle of rats
Authors: Tokinoya Katsuyuki , Yoshida Yasuko , Sugasawa Takehito , Takekoshi Kazuhiro
Published: February 2020

Renalase is predominantly expressed in the kidney, where it plays a role in catecholamine metabolism and blood pressure regulation. Moderate‐intensity exercise (MEX) has been shown to increase the concentration of renalase in the blood and to reduce renal function in humans. Moreover, such exercise was also reported to increase catecholamine levels. Here, we examined renalase concentration in the blood and renalase expression levels in different organs after MEX in rats. Twelve male Wistar rats were made to run on a treadmill (MEX group) for 60 min at 20 m·min−1, after resting for 15 min. The control group rats were euthanized after resting on the treadmill. Tissue and blood samples were analyzed using western blotting, real‐time RT‐PCR and ELISA. Overall, the concentrations of renalase in the blood were significantly higher in the MEX group than that in the control group. Renalase expression was decreased in the kidney after 60 min of exercise, whereas the expression of renalase mRNA and protein in the extensor digitorum longus and plantaris muscles, respectively, increased after exercise. However, the expression of renalase in the other tissues examined did not change after acute exercise. In conclusion, we report that MEX for 60 min increases both renalase concentration in the blood and its expression in skeletal muscle.
Insulin‐Sensitizing Activity of Sub‐Nanoscaled Polyalkoxyvanadate Clusters
Authors: Chen Kun , Jia Hongli , Liu Yuan , Yin Panchao , Wei Yongge
Published: February 2020

Sub‐nanoscaled polyalkoxyvanadates (PAOVs) functionalized with various aliphatic acids are evaluated for their insulin‐sensitizing activity in lowering the blood glucose levels of diabetic mice in typical glucose tolerance tests. All the PAOVs can restore the blood glucose to normal levels after a single oral administration of PAOVs. Among them, the myristic acid‐modified PAOVs enable the response of insulin to the repeated glucose challenges, lasting for up to 13 h. The combined administration of PAOVs exerts better glucose control over insulin alone, while the capric acid‐ and myristic acid‐modified ones can enhance the responsiveness of insulin to glucose challenge and is comparable to a clinical‐used derivative of insulin. Interestingly, continuous glucose monitoring shows that myristic acid‐modified PAOV derivatives sensitize the responsiveness of insulin, almost matching with that of a healthy pancreas. These discoveries open up new opportunities for the application of PAOVs to promote glucose‐responsive and long‐lasting activity of insulin, which are expected to aid the accurate blood glucose control in insulin therapy while reducing the number of insulin administrations.
A Wirelessly Controlled Smart Bandage with 3D‐Printed Miniaturized Needle Arrays
Authors: Derakhshandeh Hossein , Aghabaglou Fariba , McCarthy Alec , Mostafavi Azadeh , Wiseman Chris , Bonick Zack , Ghanavati Ian , Harris Seth , Kreikemeier‐Bower Craig , Moosavi Basri Seyed Masoud , Rosenbohm Jordan , Yang Ruiguo , Mostafalu Pooria , Orgill Dennis , Tamayol Ali
Published: February 2020

Chronic wounds are one of the most devastating complications of diabetes and are the leading cause of nontraumatic limb amputation. Despite the progress in identifying factors and promising in vitro results for the treatment of chronic wounds, their clinical translation is limited. Given the range of disruptive processes necessary for wound healing, different pharmacological agents are needed at different stages of tissue regeneration. This requires the development of wearable devices that can deliver agents to critical layers of the wound bed in a minimally invasive fashion. Here, for the first time, a programmable platform is engineered that is capable of actively delivering a variety of drugs with independent temporal profiles through miniaturized needles into deeper layers of the wound bed. The delivery of vascular endothelial growth factor (VEGF) through the miniaturized needle arrays demonstrates that, in addition to the selection of suitable therapeutics, the delivery method and their spatial distribution within the wound bed is equally important. Administration of VEGF to chronic dermal wounds of diabetic mice using the programmable platform shows a significant increase in wound closure, re‐epithelialization, angiogenesis, and hair growth when compared to standard topical delivery of therapeutics.
Selenium‐Containing Nanoparticles Combine the NK Cells Mediated Immunotherapy with Radiotherapy and Chemotherapy
Authors: Gao Shiqian , Li Tianyu , Guo Ye , Sun Chenxing , Xianyu Banruo , Xu Huaping
Published: February 2020

Considering the limited clinical benefits of individual approaches against malignancy, natural killer (NK) cell‐mediated immunotherapy is increasingly utilized in combination with radiotherapy and target therapeutics. However, the interplay of targeted agents, immunotherapy, and radiotherapy is complex. An improved understanding of the effect of chemotherapy or radiotherapy on specific molecular pathways in immune cells would help to optimize the synergistic antitumor efficiency. In this study, the selenium‐containing nanoparticles (NPs) could deliver the chemotherapeutic drug doxorubicin (DOX) to tumor sites by systemic administration. Radiation stimuli facilitate DOX release and enhance chemotherapy efficiency. Moreover, radiation could oxidize diselenide‐containing NPs to seleninic acid, which have both synergistic antitumor effect and immunomodulatory activity through enhancing NK cells function. These results indicate that the selenium‐containing NPs would be a potential approach to achieve simultaneous treatments of immunotherapy, chemotherapy, and radiotherapy by a simple but effective method.
Solution‐Processed Centimeter‐Scale Highly Aligned Organic Crystalline Arrays for High‐Performance Organic Field‐Effect Transistors
Authors: Duan Shuming , Wang Tao , Geng Bowen , Gao Xiong , Li Chenguang , Zhang Jing , Xi Yue , Zhang Xiaotao , Ren Xiaochen , Hu Wenping
Published: February 2020

Solution‐printed organic single‐crystalline films hold great potential for achieving low‐cost manufacturing of large‐area and flexible electronics. For practical applications, organic field‐effect transistor arrays must exhibit high performance and small device‐to‐device variation. However, scalable fabrication of highly aligned organic crystalline arrays is rather difficult due to the lack of control over the crystallographic orientation, crystal uniformity, and thickness. Here, a facile solution‐printing method to fabricate centimeter‐sized highly aligned organic crystalline arrays with a thickness of a few molecular layers is reported. In this study, the solution shearing technique is used to produce large‐area, organic highly crystalline thin films. Water‐soluble ink is printed on the hydrophobic surface of organic crystalline films, to selectively protect it, followed by etching. It is shown that the addition of a surfactant dramatically changes the fluid drying dynamics and increases the contact line friction of the aqueous solution to the underlying nonwetting organic crystalline film. As a result, centimeter‐scale highly aligned organic crystalline arrays are successfully prepared on different substrates. The devices based on organic crystalline arrays show good performance and uniformity. This study demonstrates that solution printing is close to industrial application and also expands its applicability to various printed flexible electronics.
Water‐Stable Lithium Metal Anodes with Ultrahigh‐Rate Capability Enabled by a Hydrophobic Graphene Architecture
Authors: Dong Lei , Nie Lu , Liu Wei
Published: February 2020

Implementing the utilization of lithium metal in actual processing and application conditions is essential for next‐generation high‐energy batteries at a practical level. However, the air/water instability of the high‐reactive Li metal remains unsolved. Here, a water‐stable Li metal anode with ultrahigh‐rate capability enabled by a rationally designed architecture is reported. A hydrophobic graphene framework, consists of an array of vertically aligned sheets and a roof of sloping‐aligned sheets, is utilized to fully host lithium metal. As a result, it is first demonstrated that the composite Li metal anode can run stably even after it directly contacts with water. In addition, both the arrays and the roof in the framework are directional graphene microsheets that can provide fast charge transport kinetics in the anode without tortuosity. Therefore, the anode can operate at an extremely high current density of 50 mA cm−2 with long‐term cycling stability. Importantly, the composite Li anodes in Li||LiFePO4 and Li||NCM‐811 cells also show much improved performances than Li metal foil under crucial conditions of lean electrolyte and low negative/positive capacity ratio. This design provides a significant stride in the safety toward the practicability of low air/water tolerance materials.
Influence of Nanoconfinement on the pKa of Polyelectrolyte Functionalized Silica Mesopores
Authors: Brilmayer Robert , Kübelbeck Sonja , Khalil Adnan , Brodrecht Martin , Kunz Ulrike , Kleebe Hans‐Joachim , Buntkowsky Gerd , Baier Grit , Andrieu‐Brunsen Annette
Published: February 2020

Functionalized ordered mesoporous materials are relevant in technologies, such as drug release, sensing, and separation. To design functionality, the silica framework can be functionalized with responsive molecules or polymers. Often, the pH value in those hybrid materials determines performance. Even though pH/pKa differences between polymers in bulk solutions and nanoscale confinement have been observed, the influence of confinement on pH‐ and pore filling dependent polyelectrolyte oligomer chain charge has yet not been investigated systematically. Here, mesoporous silica films are functionalized with (2‐dimethylamino)ethyl methacrylate) (DMAEMA) and 2‐(methacryloyloxy)ethyl phosphate (MEP) oligomers using photoiniferter initiated polymerization. This approach allows a controlled and environmentally friendly mesopore functionalization in water. The obtained oligomer functionalized pores are tunable with respect to pore filling. For both, poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(2‐(methacryloxy)ethyl phosphate) (PMEP), the charge generation inside mesopore confinement is significantly delayed toward harsher pH conditions resulting in pKa shifts of 1–2 pH units. Polymer amount and ionic strength show to further influence the pKa of PDMAEMA in mesopores. The technological importance of the pH value in confinement and its effect on enzyme stabilization is demonstrated. Lipase from Aspergillus oryzae loses its activity upon encapsulation in silica nanoparticles at pH values where the enzyme is stable in bulk solution.
Mercury Sorbents Made By Inverse Vulcanization of Sustainable Triglycerides: The Plant Oil Structure Influences the Rate of Mercury Removal from Water
Authors: Tikoalu Alfrets D. , Lundquist Nicholas A. , Chalker Justin M.
Published: February 2020

High sulfur content polymers are prepared through the copolymerization of sustainable triglycerides and sulfur. These products of “inverse vulcanization” contain 50% sulfur by mass and are evaluated in the removal of mercury from water. The structurally distinct triglycerides found in canola oil, castor oil, and rice bran oil are examined as co‐monomers to determine how each influences the rate and capacity of mercury uptake. An important discovery is that the high percentage of hydroxylated ricinoleic acid in castor oil improves both wetting and the rate of uptake of mercury(II) chloride into the polymer, in comparison with the polymers made from canola oil and rice bran oil. Detailed kinetic and isotherm modeling is carried out for all polymers for both inorganic and organic mercury sorption. All of the polymers are superior to elemental sulfur in their mercury capture ability. In terms of sustainability, this work advances the use of renewable monomers such as triglycerides sourced from plants and inexpensive industrial byproducts such as sulfur to make affordable mercury‐binding materials.
High‐Performance Thermoelectric SnSe: Aqueous Synthesis, Innovations, and Challenges
Authors: Shi Xiao‐Lei , Tao Xinyong , Zou Jin , Chen Zhi‐Gang
Published: February 2020

Tin selenide (SnSe) is one of the most promising candidates to realize environmentally friendly, cost‐effective, and high‐performance thermoelectrics, derived from its outstanding electrical transport properties by appropriate bandgaps and intrinsic low lattice thermal conductivity from its anharmonic layered structure. Advanced aqueous synthesis possesses various unique advantages including convenient morphology control, exceptional high doping solubility, and distinctive vacancy engineering. Considering that there is an urgent demand for a comprehensive survey on the aqueous synthesis technique applied to thermoelectric SnSe, herein, a thorough overview of aqueous synthesis, characterization, and thermoelectric performance in SnSe is provided. New insights into the aqueous synthesis‐based strategies for improving the performance are provided, including vacancy synergy, crystallization design, solubility breakthrough, and local lattice imperfection engineering, and an attempt to build the inherent links between the aqueous synthesis‐induced structural characteristics and the excellent thermoelectric performance is presented. Furthermore, the significant advantages and potentials of an aqueous synthesis route for fabricating SnSe‐based 2D thermoelectric generators, including nanorods, nanobelts, and nanosheets, are also discussed. Finally, the controversy, strategy, and outlook toward future enhancement of SnSe‐based thermoelectric materials are also provided. This Review guides the design of thermoelectric SnSe with high performance and provides new perspectives as a reference for other thermoelectric systems.
Switching from Fatty Acid Oxidation to Glycolysis Improves the Outcome of Acute‐On‐Chronic Liver Failure
Authors: Yu Zujiang , Li Jingjing , Ren Zhigang , Sun Ranran , Zhou Yang , Zhang Qi , Wang Qiongye , Cui Guangying , Li Juan , Li Ang , Duan Zhenfeng , Xu Yuming , Wang Zhichao , Yin Peiyuan , Piao Hailong , Lv Jun , Liu Xiaorui , Wang Yanfang , Fang Ming , Zhuang Zhengping , Xu Guowang , Kan Quancheng
Published: February 2020

Acute‐on‐chronic liver failure (ACLF) has a high mortality rate. Metabolic reprogramming is an important mechanism for cell survival. Herein, the metabolic patterns of ACLF patients are analyzed. An in vitro model of ACLF is established using Chang liver cells under hyperammonemia and hypoxia. A randomized clinical trial (ChiCTR‐OPC‐15006839) is performed with patients receiving L‐ornithine and L‐aspartate (LOLA) daily intravenously (LOLA group) and trimetazidine (TMZ) tid orally (TMZ group) based on conventional treatment (control group). The primary end point is 90‐day overall survival, and overall survival is the secondary end point. By analyzing metabolic profiles in liver tissue samples from hepatitis B virus (HBV)‐related ACLF patients and the controls, the metabolic characteristics of HBV‐related ACLF patients are identified: inhibited glycolysis, tricarboxylic acid cycle and urea cycle, and enhanced fatty acid oxidation (FAO) and glutamine anaplerosis. These effects are mainly attributed to hyperammonemia and hypoxia. Further in vitro study reveals that switching from FAO to glycolysis could improve hepatocyte survival in the hyperammonemic and hypoxic microenvironment. Importantly, this randomized clinical trial confirms that inhibiting FAO using TMZ improves the prognosis of patients with HBV‐related ACLF. In conclusion, this study provides a practical strategy for targeting metabolic reprogramming using TMZ to improve the survival of patients with HBV‐related ACLF.
Lifestyle Factors and Other Influences on Medical Students Choosing a Career in Emergency Medicine
Authors: Keith Kevin C. , Smith Elizabeth , Reddy Shalini , Bourne Christina L.
Published: February 2020

Objective

The purpose of this study was to determine which lifestyle factors influence medical students who choose a career in emergency medicine (EM).

Methods

Final‐year medical students from 10 medical schools were surveyed after the National Residency Match Program match but prior to graduation regarding preferred medical specialty and lifestyle preferences. Responses from students pursuing EM regarding importance of lifestyle factors were compared to students interested in other specialties.

Results

A total of 453 of 1,575 invited medical students completed an electronic survey. EM was the third most preferred specialty. Students selecting EM were less likely to endorse “having control of work schedule” as being important (p < 0.005), but more likely to endorse “having time off work” as important (p < 0.05). When students were asked what specific factors were important in choosing a specialty, EM students differed from other students in the importance of flexible work schedule, time outside of work, and balance between work and personal life (p < 0.001). Fewer EM students endorsed that having a “low‐stress work day” was an important consideration in their specialty choice (p < 0.001).

Conclusions

In this study representing 10 medical schools, graduating medical students who prefer EM as opposed to other specialties exhibit differences in lifestyle factors deemed important when choosing a specialty as a physician. Further investigation regarding any potential link to these factors and career longevity is warranted.
Genetic considerations for adults with congenital heart disease
Authors: Ito Seiji , Chapman Kimberly A. , Kisling Monisha , John Anitha S.
Published: February 2020

Congenital heart disease (CHD) remains the most common birth defect, with an estimated incidence of approximately 1% of all births. The population of adults with CHD is growing rapidly with advances in medical care. Overall survival to adulthood in the current era estimated to exceed 90%. Genetic causes of CHD can be classified into several broad categories: (a) chromosomal aneuploidy, (b) large chromosomal deletion or duplication, (c) single gene mutation, and (d) copy number variation. However, only 20–30% of CHD cases have an established etiology characterized by either genetic abnormalities or environmental factors. The role of genetics in the field of adult CHD is only increasing. More adult patients with CHD are seeking genetic counseling to understand the etiology of their underlying CHD and the risks to future offspring. A multidisciplinary approach is essential to provide appropriate counseling to patients regarding indications for genetic testing and interpretations of results. Novel advances with precision medicine may soon enable clinicians to individualize therapies for a comprehensive approach to the care of adult patients with CHD.
Chronic rhinosinusitis after radiotherapy in patients with head and neck cancer: a population‐based cohort study in Taiwan
Authors: Lu Yen‐Ting , Lu Ying‐Chou , Cheng Hui‐Chen , Hsin Chung‐Han , Yang Shun‐Fa , Wang Po‐Hui , Yeh Huan‐Jui
Published: February 2020

Background

Chronic rhinosinusitis (CRS) is a common post‐radiotherapy (RT) side effect in patients with nasopharyngeal cancer (NPC). However, whether RT is a risk factor for CRS in patients with other types of head and neck cancer remains unclear. This study investigated the association, if any, between CRS and RT in patients with head and neck cancer.

Methods

This retrospective cohort study included the data of patients newly diagnosed as having head and neck cancer between January 1, 2005, and December 31, 2008, from the 2005 Longitudinal Health Insurance Database. Patients were categorized into the following groups according to the treatment regimens received: RT alone (RT‐alone), RT combined with other treatments (any‐RT), and treatments without RT (no‐RT). The outcome was the occurrence of CRS after treatment.

Results

Of the 701 patients, 7% experienced CRS within 5 years after initial treatment. Patients were divided into subgroups according to different treatment policies, and the RT‐alone group, any‐RT group, and no‐RT group had 5‐year incidence of CRS of 12%, 9.3%, and 4.5%, respectively. Patients in the RT‐alone and any‐RT groups exhibited an increased risk of CRS compared with patients in the no‐RT group (hazard ratio: 6.76 and 2.91; 95% confidence interval: 2.60 to 17.5 and 1.60 to 5.31, respectively).

Conclusion

This is the first nationwide population‐based cohort study to evaluate the risk of posttreatment CRS in patients with head and neck cancer. Our findings indicate that RT is a major risk factor for CRS. Thus, physicians should consider this potential risk in patients with head and neck cancer after RT.
N‐Methyl‐D‐Aspartate Receptor Antibodies in Autoimmune Encephalopathy Alter Oligodendrocyte Function
Authors: Matute Carlos , Palma Ana , Serrano‐Regal María Paz , Maudes Estibaliz , Barman Sumanta , Sánchez‐Gómez María Victoria , Domercq María , Goebels Norbert , Dalmau Josep
Published: February 2020

Objective

Antibodies against neuronal N‐methyl‐D‐aspartate receptors (NMDARs) in patients with anti‐NMDAR encephalitis alter neuronal synaptic function and plasticity, but the effects on other cells of the nervous system are unknown.

Methods

Cerebrospinal fluid (CSF) of patients with anti‐NMDAR encephalitis (preabsorbed or not with GluN1) and a human NMDAR‐specific monoclonal antibody (SSM5) derived from plasma cells of a patient, along the corresponding controls, were used in the studies. To evaluate the activity of oligodendrocyte NMDARs and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors in vitro after exposure to patients' CSF antibodies or SSM5, we used a functional assay based on cytosolic Ca2+ imaging. Expression of the glucose transporter (GLUT1) in oligodendrocytes was assessed by immunocytochemistry.

Results

NMDAR agonist responses were robustly reduced after preincubation of oligodendrocytes with patients' CSF or SSM5 but remained largely unaltered with the corresponding controls. These effects were NMDAR specific, as patients' CSF did not alter responses to AMPA receptor agonists and was abrogated by preabsorption of CSF with HEK cells expressing GluN1 subunit. Patients' CSF also reduced oligodendrocyte expression of glucose transporter GLUT1 induced by NMDAR activity.

Interpretation

Antibodies from patients with anti‐NMDAR encephalitis specifically alter the function of NMDARs in oligodendrocytes, causing a decrease of expression of GLUT1. Considering that normal GLUT1 expression in oligodendrocytes and myelin is needed to metabolically support axonal function, the findings suggest a link between antibody‐mediated dysfunction of NMDARs in oligodendrocytes and the white matter alterations reported in patients with this disorder. ANN NEUROL 2020;87:670–676
Gravitational Lensing in a Model of Nonlinear Electrodynamics: The Case for Electrically and Magnetically Charged Compact Objects
Authors: Gurtug Ozay , Mangut Mert
Published: February 2020

The astrophysical applicability of the electrically and magnetically charged black hole solutions obtained in a model of nonlinear electrodynamics proposed by Kruglov is investigated. Theoretical calculations of the bending angles and gravitational redshifts from the theory of general relativity are studied numerically by using the stellar data of charged compact objects and a hypothetical quark star model. Calculations have revealed that although the theoretical outcomes differ from the linear Maxwell case, the plotted bending angles coincide with the linear case and it becomes hard to identify the effect of nonlinearity. However, the calculation of the redshift has shown that while the increase in the electric field leads to a decrease in the gravitational redshift,the presence of the strong magnetic field contributes to the gravitational redshift in an increasing manner.
Molecular Photochemistry: Recent Developments in Theory
Authors: Mai Sebastian , González Leticia
Published: February 2020

Photochemistry is a fascinating branch of chemistry that is concerned with molecules and light. However, the importance of simulating light‐induced processes is reflected also in fields as diverse as biology, material science, and medicine. This Minireview highlights recent progress achieved in theoretical chemistry to calculate electronically excited states of molecules and simulate their photoinduced dynamics, with the aim of reaching experimental accuracy. We focus on emergent methods and give selected examples that illustrate the progress in recent years towards predicting complex electronic structures with strong correlation, calculations on large molecules, describing multichromophoric systems, and simulating non‐adiabatic molecular dynamics over long time scales, for molecules in the gas phase or in complex biological environments.
MDM2‐Associated Clusterization‐Triggered Emission and Apoptosis Induction Effectuated by a Theranostic Spiropolymer
Authors: Liu Pai , Fu Weiqiang , Verwilst Peter , Won Miae , Shin Jinwoo , Cai Zhengxu , Tong Bin , Shi Jianbing , Dong Yuping , Kim Jong Seung
Published: February 2020

Heteroatom‐containing spiropolymers were constructed in a facile manner by a catalyst‐free multicomponent spiropolymerization route. P1a2b as the most potent of these spiropolymers, demonstrates cluster‐triggered emission resulting from strong interactions with the MDM2 protein. By preventing the anti‐apoptotic p53/MDM2 interaction, P1a2b triggers apoptosis in cancerous cells, while demonstrating a good biocompatibility and non‐toxicity in non‐cancerous cells. The combined results from solution and cell‐based cluster‐triggered emission studies, docking, protein expression experiments and cytotoxicity data strongly support the MDM2‐binding hypothesis and indicate a potential application as a fluorescent cancer marker as well as therapeutic for this spiropolymer.
Preparation of polyacrylamide–montmorillonite nanocomposite and its application in Cr(III) adsorption
Authors: Qiu Jinghong , Du Xiaosheng , Komarneni Sridhar , Wang Haibo , Cheng Xu , Du Zongliang
Published: February 2020

The polyacrylamide–montmorillonite “water in water” (PAM‐MMT W/W) emulsion was prepared by dispersion polymerization method in the presence of organo‐montmorillonite (OMMT). Based on the analysis of the polymerization process, the structure of material was investigated using thermogravimetry, Fourier transform infrared spectroscopy, X‐ray diffractometry, scanning electron microscopy, and transmission electron microscopy experiments. Here, the dispersion was determined to be a blend of PAM W/W emulsion and PAM network interspersed by MMT particles, this unique structure of the material was considered to provide better adsorption ability compared to PAM without MMT. Therefore, a PAM‐MMT adsorbent was made from the PAM‐MMT W/W emulsion, and its adsorption capacity toward Cr(III), one of the heavy metal pollutants from the tannery waste was investigated. The PAM‐MMT nanocomposite was demonstrated to have good Cr(III) removal performance, the maximum adsorption capacity of the nanocomposite was found to be 59.74 mg/g at a pH of 5.5 and temperature of 70°C. Results show that pseudo‐second‐order kinetic model and Langmuir isotherm were applicable for Cr(III) adsorption.
Lost but revived. Revisiting the medieval village of Nieuw‐Roeselare (Flanders) using large‐scale frequency‐domain multi‐receiver EMI and landscape archaeological prospection
Authors: Verbrugghe Gerben , Saey Timothy , De Clercq Wim
Published: February 2020

During the 10th to 13th centuries, the rural settlement landscapes of the County of Flanders underwent major changes. Complex interactions between urbanization, growing comital power, demographic changes and rural development formed the basis for intensified reclamations of the landscape. Based on historical research, the ab nihilo plantation of grouped rural settlements by the counts and other landlords played an important role in the organization and systematization of these reclamations. To date, however, archaeological attention for these grouped settlements is scarce, mainly due to Flanders' build‐up and urbanized character. This article describes the renewed cross‐disciplinary landscape archaeological research at the site of the lost village of Nieuw‐Roeselare (northern East Flanders), which was the first medieval village to be partly excavated in Flanders between 1967 and 1979. Believed to have been planted in 1241 and lost to floods in 1375, little is known historically about the site nor does the modern‐day polder landscape show any remnants of a former settlement. Now, a large‐scale cross‐disciplinary prospection comprising 35 ha of frequency‐domain multi‐receiver electromagnetic induction (EMI), oblique aerial photography, augering, pseudo‐two‐dimensional tomography and site specific artefact‐accurate field walking, allowed to define the settlement's full extent, clarify its geographical context and identify its morphology as a planted settlement in the context of the medieval landscape reclamations.
Fluorinated Phenanthrenes as Aryne Precursors: PAH Synthesis Based on Domino Ring Assembly Using 1,1‐Difluoroallenes
Authors: Fuchibe Kohei , Abe Masashi , Idate Hiroto , Ichikawa Junji
Published: February 2020

On treatment with the catalyst InBr3, 1,1‐difluoroallenes that bear a cyclopentene moiety and an aryl group underwent domino ring assembly in the presence or absence of N‐bromosuccinimide or N‐iodosuccinimide to afford aryne precursors such as three‐ringed ortho‐fluoro(halo)phenanthrenes, four‐ringed ortho‐fluoro(halo)tetraphenes, ortho‐fluoro(halo)chrysenes and fluoro[4]helicenes. Metalation of the aryne precursors followed by elimination of the fluoride resulted in the unprecedented systematic generation of arynes bearing π‐extended systems. Diels−Alder reactions of these arynes with isobenzofurans afforded the corresponding cycloadducts whose reductive aromatisation in an SnCl2/HBr system furnished fully aromatised benzotriphenylenes. In addition, oxidative aryl−aryl coupling (the Scholl reaction) of these benzotriphenylenes facilitated the synthesis of ‘half HBCs’ (hexabenzocoronenes).
Association between body mass index and folate insufficiency indicative of neural tube defects risk among nonpregnant women of childbearing age in the United States, NHANES, 2007–2010
Authors: Manandhar Meryna , Beydoun Hind , Kancherla Vijaya
Published: February 2020

Background

Maternal folate status and obesity are known risk factors for neural tube defects (NTD) in the offspring. We examined the association between body mass index (BMI) categories and blood folate concentrations, specifically, red blood cell (RBC) folate concentrations indicative of NTD risk among nonpregnant women of child‐bearing age (20–44 years) in the United States.

Methods

We used data from 2007 to 2010 US National Health and Nutrition Examination Survey (NHANES). Overweight, obesity, and strata within obesity were examined. Serum and RBC folate concentrations were examined as continuous and categorical variables. RBC folate concentrations were grouped indicating high (≤585 nmol/L) and elevated risk (586–747 nmol/L) for NTDs. Unadjusted and adjusted prevalence odds ratios (aPOR) and their 95% confidence intervals (CI) were estimated using logistic regression.

Results

Of the 30,878 participants, 25.6% were overweight, 32.7% obese, and 32.3% had RBC folate concentration indicating NTD risk (<748 nmol/L). Overweight was not associated with RBC folate level for NTD risk; however, a marginally significant negative association was noted for overall obesity and RBC folate concentrations indicative of elevated NTD risk (aPOR = 0.76; 95% CI = 0.45, 1.00). A significant protective association was noted between Class 3 obesity (BMI ≥40 kg/m2) and folate concentration indicative of high NTD risk (≤585 nmol/L; aPOR = 0.46; 95% CI = 0.24, 0.89).

Conclusions

The prevalence of RBC folate concentrations indicating elevated or high NTD risk varied by level of obesity among nonpregnant women of child‐bearing age. Further studies are needed to understand the folate pathway in overweight and obese women and subsequent NTD risk in their offspring.
How do corporate environmental policy and corporate reputation affect risk‐adjusted financial performance?
Authors: Gangi Francesco , Daniele Lucia Michela , Varrone Nicola
Published: February 2020

The current study aims to answer dual, related questions: Does corporate environmental policy affect corporate reputation, and does this link also influence risk‐adjusted profitability and company's risk? With a comprehensive framework involving analyses of each question, among a sample of firms traced by the Reputation Institute, this study reveals several notable results, after correcting for endogeneity biases. First, environmental engagement and green product innovation are both antecedents of corporate reputation. Second, corporate reputation has a positive impact on risk‐adjusted profitability and Z score indicator of financial distress risk. Thus, corporate environmental responsibility and green practices represent cospecialized assets that enhances an intangible asset, namely, corporate reputation. The latter influence constitutes a missing link between sustainable development and the firm's financial performance. Overall, environmental engagement and corporate reputation act as insurance‐like protections of firm competitiveness.
Impact of delayed treatment in women diagnosed with breast cancer: A population‐based study
Authors: Ho Peh Joo , Cook Alex R. , Binte Mohamed Ri Nur Khaliesah , Liu Jenny , Li Jingmei , Hartman Mikael
Published: February 2020

The impact of timely treatment on breast cancer‐specific survival may differ by tumor stage. We aim to study the impact of delayed first treatment on overall survival across different tumor stages. In addition, we studied the impact of delayed adjuvant treatments on survival in patients with invasive nonmetastatic breast cancer who had surgery ≤90 days postdiagnosis. This population‐based study includes 11 175 breast cancer patients, of whom, 2318 (20.7%) died (median overall survival = 7.9 years). To study the impact of delayed treatment on survival, hazard ratios and corresponding 95% confidence intervals were estimated using Cox proportional‐hazards models. The highest proportion of delayed first treatment (>30 days postdiagnosis) was in patients with noninvasive breast cancer (61%), followed by metastatic breast cancer (50%) and invasive nonmetastatic breast cancer (22%). Delayed first treatment (>90 vs ≤30 days postdiagnosis) was associated with worse overall survival in patients with invasive nonmetastatic (HR: 2.25, 95% CI 1.55‐3.28) and metastatic (HR: 2.09, 95% CI 1.66‐2.64) breast cancer. Delayed adjuvant treatment (>90 vs 31‐60 days postsurgery) was associated with worse survival in patients with invasive nonmetastatic (HR: 1.50, 95% CI 1.29‐1.74). Results for the Cox proportional‐hazards models were similar for breast cancer‐specific death. A longer time to first treatment (31‐90 days postdiagnosis) may be viable for more extensive diagnostic workup and patient‐doctor decision‐making process, without compromising survival. However, patients’ preference and anxiety status need to be considered.
RP11‐81H3.2 promotes gastric cancer progression through miR‐339‐HNRNPA1 interaction network
Authors: Chen Fen‐Rong , Sha Su‐Mei , Wang Shen‐Hao , Shi Hai‐Tao , Dong Lei , Liu Dong , Cheng Yan , An Miao , Wang Yan , Zhang Jun
Published: February 2020

Recent studies have demonstrated that various long non‐coding RNAs (lncRNAs) participate in the gastric cancer (GC) development and metastasis. Some lncRNAs exert their regulatory function by interacting with microRNAs. Here we identified a novel lncRNA RP11‐81H3.2 that was highly expressed in the GC tissue and cell lines. RP11‐81H3.2 knockdown significantly inhibited the proliferation, migration, and invasion of GC cells. Mechanistically, we demonstrated that RP11‐81H3.2 directly interacted with miR‐339 while miR‐339 regulated the HNRNPA1 expression by targeting HRRNPA1 3’‐UTR. RP11‐81H3.2‐miR‐339‐HNRNPA1 interaction network regulated the GC cell proliferation, migration, and invasion. Moreover, our results confirmed that RP11‐81H3.2 knockdown suppressed the tumor growth of GC in a xenograft model in vivo. In summary, the results suggest that RP11‐81H3.2 functions as an oncogene in GC and could be utilized as a promising diagnosis and therapeutic marker for GC treatment.
The facilitative interpersonal skills method: Difficult psychotherapy moments and appropriate therapist responsiveness
Authors: Anderson Timothy , Finkelstein Joshua D. , Horvath Sarah A.
Published: February 2020

The Facilitative Interpersonal Skills (FIS) task is a performance test of therapists’ use of common relational skills (e.g. empathy, building expectations). The FIS method includes (a) materials that simulate difficult client moments on video, which are used to collect therapists’ responses to these situations; and (b) independent ratings of these responses. Many of the FIS items are informed by psychotherapy processes that have been linked to outcome and facilitative conditions that have been reframed as individual therapist skills (e.g. alliance bond capacity). Overall, the FIS has predicted psychotherapy outcome. A single study is described in which FIS predicted the therapist effect using multilevel modelling of a large sample of clients who were nested within therapists. We also summarise two additional outcome studies that used experimental designs. One future direction is to better understand how therapists form responses to these difficult moments. We conclude that forming an optimal therapeutic response during challenging, emergent in‐session situations involves responsiveness (Stiles et al., 1998), or finding a response that fits the clients’ needs within any moment.