bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging orbital ferromagnetism in a moiré Chern insulator
Authors: Tschirhart C. L. , Serlin M. , Polshyn H. , Shragai A. , Xia Z. , Zhu J. , Zhang Y. , Watanabe K. , Taniguchi T. , Huber M. E. , Young A. F.
Published: May 2021

Capturing exotic magnetism

Ferromagnetism is associated with the breaking of time-reversal symmetry, most frequently by the spin degree of freedom. Although the orbital motion of electrons can also contribute to ferromagnetism, in most materials, it is small relative to the spin contribution. Tschirhart
et al.
showed that the reverse is true in an unusual magnetic state hosted by twisted bilayer graphene. Their scanning magnetometry measurements were consistent with ferromagnetism of predominantly orbital origin.

Science
, abd3190, this issue p.
1323
3D genomics across the tree of life reveals condensin II as a determinant of architecture type
Authors: Hoencamp Claire , Dudchenko Olga , Elbatsh Ahmed M. O. , Brahmachari Sumitabha , Raaijmakers Jonne A. , van Schaik Tom , Sedeño Cacciatore Ángela , Contessoto Vinícius G. , van Heesbeen Roy G. H. P. , van den Broek Bram , Mhaskar Aditya N. , Teunissen Hans , St Hilaire Brian Glenn , Weisz David , Omer Arina D. , Pham Melanie , Colaric Zane , Yang Zhenzhen , Rao Suhas S. P. , Mitra Namita , Lui Christopher , Yao Weijie , Khan Ruqayya , Moroz Leonid L. , Kohn Andrea , St. Leger Judy , Mena Alexandria , Holcroft Karen , Gambetta Maria Cristina , Lim Fabian , Farley Emma , Stein Nils , Haddad Alexander , Chauss Daniel , Mutlu Ayse Sena , Wang Meng C. , Young Neil D. , Hildebrandt Evin , Cheng Hans H. , Knight Christopher J. , Burnham Theresa L. U. , Hovel Kevin A. , Beel Andrew J. , Mattei Pierre-Jean , Kornberg Roger D. , Warren Wesley C. , Cary Gregory , Gómez-Skarmeta José Luis , Hinman Veronica , Lindblad-Toh Kerstin , Di Palma Federica , Maeshima Kazuhiro , Multani Asha S. , Pathak Sen , Nel-Themaat Liesl , Behringer Richard R. , Kaur Parwinder , Medema René H. , van Steensel Bas , de Wit Elzo , Onuchic José N. , Di Pierro Michele , Lieberman Aiden Erez , Rowland Benjamin D.
Published: May 2021

Organismal evolution of the 3D genome

The conformation of chromosomes within the nucleus can reflect a cell's type or state. However, studies of the conservation and evolutionary history of the mechanisms regulating genome structure across species are lacking. Hoencamp
et al.
mapped three-dimensional (3D) genome organization in 24 eukaryote species, including animals, fungi, and plants. At interphase, species' telomeres and centromeres either clustered across chromosomes or oriented in a polarized state maintaining individual chromosomal territories within the cell, a difference attributed to condensin II. An experimental loss of condensin II in human cells promotes the formation of centromere clusters but has no effect on loop or compartment formation. Whether the structure of the 3D genome varies across species may thus depend on whether they carry a functional condensin II gene.

Science
, abe2218, this issue p.
984
Navigating space in the mammalian brain
Authors: Wood Emma R. , Dudchenko Paul A.
Published: May 2021

A study of bats reveals how hippocampal place cells code large-scale environments
Campylobacter fetus septicemia with concurrent salpingitis
Authors: Brown W J , Sautter R
Published: May 2021

Campylobacter fetus was isolated from the blood of a nonpregnant young woman who had a clinical diagnosis of salpingitis. A description of the isolate of C. fetus is given. An increasing awareness of human infections and capability of growing this microaerophilic organism should contribute to our understanding of the incidence and virulence of this bacterium.
Application of freeze-dried monkey erythrocytes to measles viral hemagglutination and hemagglutination-inhibition tests
Authors: Iwasa S , Yoshida I , Ito H , Hori M
Published: May 2021

Erthrocytes collected from monkey species including grivet, rhesus, and cynomolgus monkeys were stabilized by fixation with glutaraldehyde of a low concentration and were freeze-dried in vacuo. These freeze-dried erythrocytes were compared with fresh erythrocytes for measles viral hemagglutination and hemagglutination inhibition and could be used in both tests instead of fresh erythrocytes. They maintained their initial appearance and sensitivity to measles viral hemagglutinins after storage at 4 degrees C for 4 months more.
Aeromonas hydrophila in acute diarrheal disease: detection of enterotoxin and biotyping of strains
Authors: Ljungh A , Popoff M , Wadstrom T
Published: May 2021

Eleven isolates of Aeromonas species from human stool cultures were found to produce enterotoxin activity as determined by assay of culture filtrates in rabbit intestinal loops and rabbit skin and on adrenal Y1 cells. Hemolysin(s) and a cytotoxic protein were found to interfere in all three assay systems but could be inactivated upon heating at 56 degrees C or by specific antihemolysin. Biotyping of each isolate was performed with a conventional test system and with API 50E and APIZYM kit systems (Analytab, Inc.). No single test of the more than 70 biochemical reactions investigated was found to correlate with enterotoxigenicity in the strains of Aeromonas hydrophila examined. All strains were found to belong to ideal phenotypes of A. hydrophila, but each strain possessed its own biochemical profile.
Superoxide dismutase in Bacteroides fragilis and related Bacteroides species
Authors: Carlsson J , Wrethén J , Beckman G
Published: May 2021

Superoxide dismutase (SOD) activity was demonstrated in cell-free extracts of Bacteroides fragilis, Bacteroides vulgatus, Bacteroides distasonis, Bacteroides ovatus, and Bacteroides thetaiotaomicron. The strains were grown under anaerobic conditions in Trypticase soy broth, and the specific activity of SOD in the extracts was, in most strains, higher than in cell-free extracts of Escherichia coli B grown under anaerobic conditions. Isoelectric focusing of the extracts in polyacrylamide gel demonstrated distinct forms of SOD in the different species.
Reproducibility of interpretation of the test for antibody-coated bacteria in urinary sediment
Authors: Schaberg D R , Haley R W , Terry P M , McGowan J E
Published: May 2021

The direct immunofluorescence technique for detecting antibody-coated bacteria in urinary sediment is felt to be useful in distinguishing infection of the kidney from infection of the bladder. An independent, blind multiple-reading system was used to measure interobserver variability in the evaluation of slides of urinary sediments for antibody-coated bacteria. Three independent observers agreed unanimously on first reading in 88% of 253 specimens. When compared with the majority opinion, the sensitivity and specificity of an individual reading were 91 and 95%, respectively.
Microscopic and bacteriological comparison of paired sputa and transtracheal aspirates
Authors: Geckler R W , Gremillion D H , McAllister C K , Ellenbogen C
Published: May 2021

Ninety-six sputum specimens from patiens with pneumonia were microscopically screened for leukocytes and buccal squamous epithelial (BSE) cells. Cultures of these specimens were compared with cultures of paired transtracheal aspirates (TTA). Agreement between sputa with less than 25 BSE cells per 100X field and TTA was good (79%). Only 27% of the specimens with greater than 25 BSE cells per 100X field agreed with TTA. Sixty-six of the sputa were of group 5 quality, i.e., greater than 25 leukocytes and less than 10 BSE cells per 100X field. A potential pathogen growing in one of these specimens was 94% predictive of growth in the TTA. If a group 5 sputum was negative for a potential pathogen, there was a 45% chance that a fastidious organism had been overgrown or overlooked. The presence of definite lower tract secretions in group 5 sputa as determined by visualizing bronchial epithelial cells and alveolar macrophages did not significantly increase the diagnostic value of these specimens. Microscopic screening of sputum before culture with rejection of selected specimens can increase the value of sputum in determining the etiology of bacterial pneumonia.
Fluorescent-antibody studies on selected strains of Bacteroides fragilis subspecies fragilis
Authors: Abshire R L , Lombard G L , Dowell V R
Published: May 2021

Antisera against seven strains of Bacteroides fragilis subspecies fragilis were produced from dense suspensions of whole cells. These sera exhibited high agglutination titers with homologous antigens. Reciprocal cross-reactions in agglutination tests with each immunizing strain yielded lower titers. Both the indirect and direct fluorescent-antibody techniques were used to evaluate these reagents in the serological identification of 24 defined strains of B. fragilis subspecies fragilis. Subspecies and even strain specificities were noted with particular antisera. A pooled antiserum and conjugate were prepared and studied. Study results showed that specific and high-titered antisera against strains within this subspecies can be produced by the methods described herein and that possibly more than one serotype exists within the seven strains studied. The development of more antibody pools will be necessary to encompass a wider antigenic coverage before the fluorescent-antibody technique can be relied upon altogether for serologically identifying isolates of B. fragilis subspecies fragilis. Test data showed that the indirect method of fluorescent-antibody staining with whole antiserum is an excellent means of identifying strains of this organism.
Characterization of ten species of mycobacteria by reaction-gas-liquid chromatography
Authors: Ohashi D K , Wade T J , Mandle R J
Published: May 2021

The methanolic tetramethylammonium hydroxide whole-cell lysates of nine species of mycobacteria and the "rhodochrous complex" were examined by gas-liquid chromatography. The gas chromatographic patterns produced 10 characteristic chromatographic groups that corresponded to the 10 species studied. The gas chromatograms of Mycobacterium tuberculosis were very easily distinguished from the other mycobacterial strains by high levels of a component that eluted much later than the other components. The remaining nine species could be distinguished on the basis of characteristic components and by different amounts of components common to more than one species. This study demonstrated that direct gas-liquid chromatographic characterization of M. tuberculosis and other myobacterial species was not only feasible but practical in the clinical laboratory.
Enzymatic and hemolytic properties of Propionibacterium acnes and related bacteria
Authors: Hoeffler U
Published: May 2021

The production of chondroitin sulfatase, hyaluronidase, deoxyribonuclease, gelatinase, phosphatase, lecithinase, and hemolysins was examined in 95 strains of Propionibacterium acnes and four related species of anaerobic, respectively, microaerophilic coryneform bacteria (P. avidum, P. lymphophilum, P. granulosum, and Corynebacterium minutissimum). All enzymes could be demonstrated in at least one representative of the species tested. Those Propionibacterium species most frequently found in acne vulgaris lesions, i.e., P. acnes and P. granulosum, proved to be the most active organisms concerning the production of the enzymes tested. P. avidum, on the other hand, showed the highest rate of hemolytic activity.
Improved chicken embryo cell culture plaque assay for scrub typhus rickettsiae
Authors: Woodman D R , Grays R , Weiss E
Published: May 2021

The plaque technique for three strains of Rickettsia tsutsugamushi in chicken embryo cell cultures was greatly improved by modifying the trypsinizing procedure and employing homologous chicken serum in the overlay medium.
Localization of a repressive sequence contributing to B-cell specificity in the immunoglobulin heavy-chain enhancer
Authors: Weinberger J , Jat P S , Sharp P A
Published: May 2021

The immunoglobulin heavy-chain enhancer is a cis-acting element which activates transcription of nearby genes only in cells of the lymphoid lineage. To identify the minimal sequences necessary to impart cell type transcriptional specificity, we tested the activity of several deletions and internal mutations in the mu enhancer. Experiments involving measurement of both chloramphenicol acetyltransferase activity and RNA levels indicated the presence of a dominant repressor element within the mu enhancer. This repressive activity was detected in fibroblasts but not in myeloma cells. Removal or disruption of this repressor element revealed the presence of elements within the mu enhancer that activate transcription in fibroblasts. Thus, enhancer tissue specificity is in part due to the composite of both constitutive activation and cell-type-specific repressive activity. The possible biological roles of this phenomenon are discussed.
Neurodevelopmental outcome following hypoxic ischaemic encephalopathy and therapeutic hypothermia is related to right ventricular performance at 24-hour postnatal age
Authors: Giesinger Regan E , El Shahed Amr I , Castaldo Michael P , Bischoff Adrianne R , Chau Vann , Whyte Hilary E A , El-Khuffash Afif Faisal , Mertens Luc , McNamara Patrick J
Published: May 2021

Objective

Our aim was to determine whether right ventricular (RV) dysfunction at 24-hour postnatal age predicts adverse developmental outcome among patients with hypoxic ischaemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH).

Design

Neonates≥35 weeks with HIE/TH were enrolled in a physiological study in the neonatal period (n=46) and either died or underwent neurodevelopmental follow-up at 18 months (n=43). The primary outcome was a composite of death, diagnosis of cerebral palsy or any component of the Bayley Scores of Infant Development III<70. We hypothesised that tricuspid annulus plane systolic excursion (TAPSE) <6 mm and/or RV fractional area change (RV-FAC) <0.29 would predict adverse outcome.

Results

Nine patients died and 34 patients were followed up at a mean age of 18.9±1.4 months. Both indices of RV systolic performance were abnormal in 15 (35%) patients, TAPSE <6 mm only was abnormal in 4 (9%) patients and RV-FAC <0.29 only was abnormal in 5 (12%) patients (19 had with normal RV function). Although similar at admission, neonates with RV dysfunction had higher cardiovascular and neurological illness severity by 24 hours than those without and severe MRI abnormalities (70% vs 53%, p=0.01) were more common. On logistic regression, TAPSE <6 mm (OR 3.6, 95% CI 1.2 to 10.1; p=0.017) and abnormal brain MRI [OR 21.7, 95% CI 1.4 to 336; p=0.028) were independently associated with adverse outcome. TAPSE <6 mm predicted outcome with a 91% sensitivity and 81% specificity.

Conclusions

The role of postnatal cardiovascular function on neurological outcomes among patients with HIE who receive TH merits further study. Quantitative measurement of RV function at 24 hours may provide an additional neurological prognostic tool.
Fifteen-minute consultation: How to approach the withdrawal of neonatal intensive care
Authors: Premadeva Irnthu , Gardham Alice , Faller Adele , Selkirk Lisa
Published: May 2021

Withdrawal of life-sustaining support on the neonatal unit presents a set of unique challenges specific in this age group of patients. This article aims to provide an overview of the key factors that should be considered during this process. It explores the practicalities of care delivery that reflects the psychological impact of undergoing end-of-life care on parents and team members. It will also highlight the role of clinical genetics that can be used to understand the underlying disease pathology and therefore can be a valuable tool in the difficult decision-making process.
Nicotinic ganglionic acetylcholine receptor autoantibodies associated with paraneoplastic disease in a neuropsychiatric patient
Authors: Stauffer Catherine , Llano Daniel A , Kitten Suzanna
Published: May 2021

Nicotinic ganglionic acetylcholine receptor autoantibodies (alpha-3-AChR Ab) are associated with paraneoplastic syndromes when present in low elevations. These antibodies can be tested for as part of an autoimmune encephalopathy panel in neuropsychiatric patients; a mildly elevated titre of alpha-3-AChR Ab that may start as an incidental finding can lead to the diagnosis of a previously undetected cancer. While alpha-3-AChR Ab are most typically associated with thymomas and small cell lung cancer, the presence of these antibodies can suggest a diverse range of other cancers. This case presents a patient with longstanding neuropsychiatric symptoms and possible functional hypothyroidism for whom a low elevation in alpha-3-AChR Ab led to the finding of papillary thyroid carcinoma.
Where to go to in chlamydia control? From infection control towards infectious disease control
Authors: van Bergen Jan E A M , Hoenderboom Bernice Maria , David Silke , Deug Febe , Heijne Janneke C M , van Aar Fleur , Hoebe Christian J P A , Bos Hanna , Dukers-Muijrers Nicole H T M , Götz Hannelore M , Low Nicola , Morré Servaas Antonie , Herrmann Bjőrn , van der Sande Marianne A B , de Vries Henry J C , Ward Helen , van Benthem Birgit H B
Published: May 2021

Objectives

The clinical and public health relevance of widespread case finding by testing for asymptomatic chlamydia infections is under debate. We wanted to explore future directions for chlamydia control and generate insights that might guide for evidence-based strategies. In particular, we wanted to know the extent to which we should pursue testing for asymptomatic infections at both genital and extragenital sites.

Methods

We synthesised findings from published literature and from discussions among national and international chlamydia experts during an invitational workshop. We described changing perceptions in chlamydia control to inform the development of recommendations for future avenues for chlamydia control in the Netherlands.

Results

Despite implementing a range of interventions to control chlamydia, there is no practice-based evidence that population prevalence can be reduced by screening programmes or widespread opportunistic testing. There is limited evidence about the beneficial effect of testing on pelvic inflammatory disease prevention. The risk of tubal factor infertility resulting from chlamydia infection is low and evidence on the preventable fraction remains uncertain. Overdiagnosis and overtreatment with antibiotics for self-limiting and non-viable infections have contributed to antimicrobial resistance in other pathogens and may affect oral, anal and genital microbiota. These changing insights could affect the outcome of previous cost–effectiveness analysis.

Conclusion

The balance between benefits and harms of widespread testing to detect asymptomatic chlamydia infections is changing. The opinion of our expert group deviates from the existing paradigm of ‘test and treat’ and suggests that future strategies should reduce, rather than expand, the role of widespread testing for asymptomatic chlamydia infections.
The Rabinowitz minimal periodic solution conjecture
Authors: Long Yiming
Published: May 2021

In 1978, Rabinowitz proved the existence of a non-constant [Formula: see text]-periodic solution for nonlinear Hamiltonian systems on [Formula: see text] with Hamiltonian function being super-quadratic at the infinity and zero for any given [Formula: see text]. Since the minimal period of this solution may be [Formula: see text] for some positive integer [Formula: see text], he proposed the question whether there exists a solution with [Formula: see text] as its minimal period for such a Hamiltonian system. This is the so-called Rabinowitz minimal periodic solution conjecture. In the last more than 40 years, this conjecture has been deeply studied by many mathematicians. But under the original structural conditions of Rabinowitz, the conjecture is still open when [Formula: see text]. In this paper, I give a brief survey on the studies of this conjecture and hope to lead to more interests on it.
DVCC+ Based Immittance Function Simulators Including Grounded Passive Elements Only
Authors: Unuk Tayfun , Yuce Erkan
Published: May 2021

Eight new immittance function simulators (IFSs) with only grounded passive elements are proposed in this paper. All of the IFSs consist of only two DVCC+s and a minimum number of passive components without needing any passive element matching constraints. Each of the proposed IFSs can provide one of [Formula: see text]L with series [Formula: see text]R and [Formula: see text]L with parallel [Formula: see text]R. As an application example, a second-order mixed-mode (MM) multifunction filter is developed from the proposed +L with series +R and +L with parallel +R. Furthermore, a proportional integral derivative (PID) controller is derived from the proposed +L with series +R. Many simulation results through the SPICE program and several experimental ones are included to verify the theory.
Nitrate-induced improvements in exercise performance are coincident with exuberant changes in metabolic genes and the metabolome in zebrafish (Danio rerio) skeletal muscle
Authors: Keller Rosa M. , Beaver Laura M. , Reardon Patrick N. , Prater Mary C. , Truong Lisa , Robinson Matthew M. , Tanguay Robyn L. , Stevens Jan F. , Hord Norman G.
Published: May 2021

We show that skeletal muscle nitrate concentration is higher with supplementation at rest and was lower in groups with increasing exercise duration in a zebrafish model. The higher availability of nitrate at rest is associated with upregulation of key nutrient-sensing genes and greater availability of energy-producing metabolites (i.e., ATP, phosphocreatine, glycolytic intermediates). Overall, nitrate supplementation may lower oxygen cost of exercise through improved fuel availability resulting from metabolic programming of muscle prior to exercise.
Comparative Study of the Silver Nanoparticle Synthesis Ability and Antibacterial Activity of the Piper Betle L. and Piper Sarmentosum Roxb. Extracts
Authors: Nguyen Ngoc Hoi , Nhi Tran Thi Yen , Van Nhi Ngo Thi , Cuc Tran Thi Thu , Tuan Pham Minh , Nguyen Dai Hai
Published: May 2021

Piper betle (P. betle) and Piper sarmentosum (P. sarmentosum) are the two members of the Piper genus, have been reported to be rich in phytochemicals and essential oils, which showed strong reducing power, antibacterial, and antifungal activities. P. betle recently has been studied and applied in several commercial products in the antimicrobial respect, meanwhile its relatives, P. sarmentosum has been lesser-known in this field. In this study, the two Piper species—P. betle and P. sarmentosum were studied to compare their ability in silver nanoparticle synthesis and efficacy in antibacterial activity. P. betle and P. sarmentosum were extracted by distilled water at different temperatures and times. Subsequently, their total reducing capacity was determined by DPPH scavenging and Folin-Ciocalteu assays to choose the appropriate extraction conditions. The silver nanoparticle solutions prepared by the extracts of P. betle (Pb.ext) and P. sarmentosum (Ps.ext) were characterized by Dynamic light scattering (DLS), Zeta potential, UV-vis, and Fourier-transform infrared (FTIR) measurements. Finally, the antibacterial activity of the synthesized silver nanoparticle solutions was tested against Escherichia coli using the agar diffusion well–variant method. The Pb.ext showed stronger reducing power with higher total polyphenol content (~125 mg GAE/mL extract) and better DPPH activity (IC50~1.45%). Both the green synthesized silver nanoparticle solutions (Pb.AgNP and Ps.AgNP) performed significantly stronger antibacterial activity on Escherichia coli compared to their initial extracts. Antibacterial tests revealed that Ps.AgNP showed remarkably better growth inhibition activity as compared to Pb.AgNP. This study would contribute useful and important information to the development of antibacterial products based on green synthesized silver nanoparticles fabricated by the extracts of P. betle and P. sarmentosum.
Inbag Morcellation Applied to the Laparoscopic Surgery of Leiomyoma: A Randomized Controlled Trial
Authors: Bensouda-Miguet Chloe , Nohuz Erdogan , Cerruto Emanuele , Buenerd Annie , Nadaud Beatrice , Moret Stephanie , Chene Gautier
Published: May 2021

Objective. To evaluate the efficacy and safety of an endoscopic bag during laparoscopic morcellation of leiomyoma or myomatous uterus. Materials and Methods. A total of 48 patients with symptomatic leiomyoma were randomized for laparoscopic morcellation in two groups: group A with a specific endoscopic bag or group B without any bag. The primary outcome measure was the detection of smooth muscle cells from washing after power morcellation determined by peritoneal cytology and immunohistochemistry (IHC). Results. Cytology and IHC from group A did not revealed any smooth muscle cells, while 29% of cases (7/24) from group B were positive (p = .009). The duration of the surgical procedure was the same in both groups. The duration of positioning the bag did not change significantly during the study. Only in one case the use of the bag was difficult due to a low pneumoperitoneum. Conclusions. The use of a morcellation bag is efficient to prevent the spread of smooth muscle cells during the morcellation of leiomyoma or myomatous uterus. This study confirms the feasibility and the safety of the laparoscopic inbag morcellation versus open morcellation.
Efficacy and Safety of Banxia Formulae for Insomnia: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials
Authors: Lin Yan-Hua , Chen Cong , Zhao Xiu , Mao Yi-Fei , Xiang Guang-Xin , Yang Meng-Qi , Song Yong-Mei
Published: May 2021

Objective. To systematically evaluate the efficacy and safety of Banxia (Pinellia Tuber) formulae in the treatment of insomnia compared with those of conventional western medicines. Methods. Randomized controlled trials (RCTs) evaluating the efficacy and safety of Banxia formulae in the treatment of insomnia were searched from the following databases: PubMed, Cochrane Library, EMBASE, the China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang database. The literature collected was from the time when the databases were established to April 2020. Quality assessment and meta-analysis were conducted by using Cochrane bias risk assessment tool and RevMan 5.2, respectively. Publication bias was assessed by Egger’s test. Results. Fourteen RCTs with 910 participants were identified. A total of 46 traditional Chinese medicines involving 2 different dosage forms were used in the included studies. Meta-analysis indicated that Banxia formulae had more significant effects on improving the total effective rate (RR = 1.23, 95% CI 1.16 to 1.31), Pittsburgh Sleep Quality Index (PSQI, MD = −1.05, 95% CI −1.63 to −0.47), and the TCM syndrome score (SMD = −0.78, 95% CI −1.18 to −0.39). Meanwhile, on reducing adverse events, Banxia formulae also showed an advantage (RR = 0.48, 95% CI 0.24 to 0.93). Conclusion. According to the current studies, the efficacy of Banxia formulae in the treatment of insomnia is better than that of the conventional western medicines, and its safety is relatively stable. However, due to the limitations of this study, further research and evaluation are needed.
The Active Frequency Control Strategy of the Wind Power Based on Model Predictive Control
Authors: Chen Ya-ling , Liu Yin-peng , Sun Xiao-fei
Published: May 2021

In this paper, an active frequency control strategy of wind turbines based on model predictive control is proposed by using the power margin of wind turbines operating in load shedding mode. The frequency response model of the microgrid system with the load shedding of the wind turbines is used to predict the output power and system frequency deviation of the wind turbine. According to the prediction information, the output power control signal of the model predictive controller in the wind turbine can be optimized. On this basis, a wind turbine active participation frequency control strategy based on model predictive control is designed by rolling prediction and optimization. The wind turbine power control signal after the strategy is used to adjust the output power of the wind turbine and balance the change of the active power of the system to reduce the frequency deviation.
Inferences for Weibull Fréchet Distribution Using a Bayesian and Non-Bayesian Methods on Gastric Cancer Survival Times
Authors: EL-Sagheer Rashad M. , Shokr Ethar M. , Mahmoud Mohamed A. W. , El-Desouky Beih S.
Published: May 2021

In this article, based on progressively type-II censored schemes, the maximum likelihood, Bayes, and two parametric bootstrap methods are used for estimating the unknown parameters of the Weibull Fréchet distribution and some lifetime indices as reliability and hazard rate functions. Moreover, approximate confidence intervals and asymptotic variance-covariance matrix have been obtained. Markov chain Monte Carlo technique based on Gibbs sampler within Metropolis–Hasting algorithm is used to generate samples from the posterior density functions. Furthermore, Bayesian estimate is computed under both balanced square error loss and balanced linear exponential loss functions. Simulation results have been implemented to obtain the accuracy of the estimators. Finally, application on the survival times in years of a group of patients given chemotherapy and radiation treatment is presented for illustrating all the inferential procedures developed here.
NEIL3 Prevents Senescence in Hepatocellular Carcinoma by Repairing Oxidative Lesions at Telomeres during Mitosis
Authors: Zhao Zhenjun , Gad Helge , Benitez-Buelga Carlos , Sanjiv Kumar , Xiangwei Hua , Kang He , Feng Mingxuan , Zhao Zhicong , Berglund Ulrika Warpman , Xia Qiang , Helleday Thomas
Published: May 2021

Patients with hepatocellular carcinoma (HCC) suffer from few treatment options and poor survival rates. Here we report that endonuclease VIII-like protein 3 (NEIL3) is overexpressed in HCC and correlates with poor survival. All six HCC cell lines investigated were dependent on NEIL3 catalytic activity for survival and prevention of senescence, while NEIL3 was dispensable for nontransformed cells. NEIL3-depleted HCC cell lines accumulated oxidative DNA lesions specifically at telomeres, resulting in telomere dysfunctional foci and 53BP1 foci formation. Following oxidative DNA damage during mitosis, NEIL3 relocated to telomeres and recruited apurinic endonuclease 1 (APE1), indicating activation of base excision repair. META-FISH revealed that NEIL3, but not NEIL1 or NEIL2, is required to initiate APE1 and polymerase beta (POLB)-dependent base excision repair at oxidized telomeres. Repeated exposure of NEIL3-depleted cells to oxidizing damage induced chromatin bridges and damaged telomeres. These results demonstrate a novel function for NEIL3 in repair of oxidative DNA damage at telomeres in mitosis, which is important to prevent senescence of HCC cells. Furthermore, these data suggest that NEIL3 could be a target for therapeutic intervention for HCC.

Significance:

This study describes compartmentalization of base excision repair during mitosis that is dependent on NEIL3, APE1, and POLB to repair oxidative damage accumulating at telomeres in hepatocellular carcinoma.
Evaluation of the Small-molecule BRD4 Degrader CFT-2718 in Small-cell Lung Cancer and Pancreatic Cancer Models
Authors: Sun Danlin , Nikonova Anna S. , Zhang Peishan , Deneka Alexander Y. , Fitzgerald Mark E. , Michael Ryan E. , Lee Linda , Lilly Anna C. , Fisher Stewart L. , Phillips Andrew J. , Nasveschuk Christopher G. , Proia David A. , Tu Zhigang , Golemis Erica A.
Published: May 2021

Targeted, catalytic degradation of oncoproteins using heterobifunctional small molecules is an attractive modality, particularly for hematologic malignancies, which are often initiated by aberrant transcription factors and are challenging to drug with inhibitors. BRD4, a member of the bromodomain and extraterminal family, is a core transcriptional and epigenetic regulator that recruits the P-TEFb complex, which includes Cdk9 and cyclin T, to RNA polymerase II (pol II). Together, BRD4 and CDK9 phosphorylate serine 2 (pSer2) of heptad repeats in the C-terminal domain of RPB1, the large subunit of pol II, promote transcriptional elongation. Small-molecule degraders of BRD4 have shown encouraging efficacy in preclinical models for several tumor types but less efficacy in other cancers including small-cell lung cancer (SCLC) and pancreatic cancer. Here, we evaluated CFT-2718, a new BRD4-targeting degrader with enhanced catalytic activity and in vivo properties. In vivo, CFT-2718 has significantly greater efficacy than the CDK9 inhibitor dinaciclib in reducing growth of the LX-36 SCLC patient-derived xenograft (PDX) model and performed comparably to dinaciclib in limiting growth of the PNX-001 pancreatic PDX model. In vitro, CFT-2718 reduced cell viability in four SCLC and two pancreatic cancer models. In SCLC models, this activity significantly exceeded that of dinaciclib; furthermore, CFT-2718 selectively increased the expression of cleaved PARP, an indicator of apoptosis. CFT-2718 caused rapid BRD4 degradation and reduced levels of total and pSer2 RPB1 protein. These and other findings suggest that BRD-mediated transcriptional suppression merits further exploration in the setting of SCLC.
Silylation of Deoxynucleotide Analog Yields an Orally Available Drug with Antileukemia Effects
Authors: Ureshino Hiroshi , Kurahashi Yuki , Watanabe Tatsuro , Yamashita Satoshi , Kamachi Kazuharu , Yamamoto Yuta , Fukuda-Kurahashi Yuki , Yoshida-Sakai Nao , Hattori Naoko , Hayashi Yoshihiro , Kawaguchi Atsushi , Tohyama Kaoru , Okada Seiji , Harada Hironori , Ushijima Toshikazu , Kimura Shinya
Published: May 2021

DNA methyltransferase inhibitors have improved the prognosis of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, because these agents are easily degraded by cytidine deaminase (CDA), they must be administered intravenously or subcutaneously. Recently, two orally bioavailable DNA methyltransferase inhibitors, CC-486 and ASTX727, were approved. In previous work, we developed 5-O-trialkylsilylated decitabines that resist degradation by CDA. However, the effects of silylation of a deoxynucleotide analog and enzymatic cleavage of silylation have not been fully elucidated. Enteric administration of OR21 in a cynomolgus monkey model led to high plasma concentrations and hypomethylation, and in a mouse model, oral administration of enteric-coated OR21 led to high plasma concentrations. The drug became biologically active after release of decitabine (DAC) from OR21 following removal of the 5′-O-trisilylate substituent. Toxicities were tolerable and lower than those of DAC. Transcriptome and methylome analysis of MDS and AML cell lines revealed that OR21 increased expression of genes associated with tumor suppression, cell differentiation, and immune system processes by altering regional promoter methylation, indicating that these pathways play pivotal roles in the action of hypomethylating agents. OR21 induced cell differentiation via upregulation of the late cell differentiation drivers CEBPE and GATA-1. Thus, silylation of a deoxynucleotide analog can confer oral bioavailability without new toxicities. Both in vivo and in vitro, OR21 exerted antileukemia effects, and had a better safety profile than DAC. Together, our findings indicate that OR21 is a promising candidate drug for phase I study as an alternative to azacitidine or decitabine.
Cytidine Deaminase APOBEC3A Regulates PD-L1 Expression in Cancer Cells in a JNK/c-JUN-Dependent Manner
Authors: Zhao Kailiang , Zhang Qiang , Flanagan Sheryl A. , Lang Xueting , Jiang Long , Parsels Leslie A. , Parsels Joshua D. , Zou Weiping , Lawrence Theodore S. , Buisson Rémi , Green Michael D. , Morgan Meredith A.
Published: May 2021

Programmed death-ligand 1 (PD-L1) promotes tumor immune evasion by engaging the PD-1 receptor and inhibiting T-cell activity. While the regulation of PD-L1 expression is not fully understood, its expression is associated with tumor mutational burden and response to immune checkpoint therapy. Here, we report that Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) is an important regulator of PD-L1 expression. Using an APOBEC3A inducible expression system as well as siRNA against endogenous APOBEC3A, we found that APOBEC3A regulates PD-L1 mRNA and protein levels as well as PD-L1 cell surface expression in cancer. Mechanistically, APOBEC3A-induced PD-L1 expression was dependent on APOBEC3A catalytic activity as catalytically dead APOBEC3A mutant (E72A) failed to induce PD-L1 expression. Furthermore, APOBEC3A-induced PD-L1 expression was dependent on replication-associated DNA damage and JNK/c-JUN signaling but not interferon signaling. In addition, we confirmed the relevance of these finding in patient tumors as APOBEC3A expression and mutational signature correlated with PD-L1 expression in multiple patient cancer types. These data provide a novel link between APOBEC3A, its DNA mutagenic activity and PD-L1-mediated antitumoral immunity. This work nominates APOBEC3A as a mechanism of immune evasion and a potential biomarker for the therapeutic efficacy of immune checkpoint blockade.

Implications:

APOBEC3A catalytic activity induces replication-associated DNA damage to promote PD-L1 expression implying that APOBEC3A-driven mutagenesis represents both a mechanism of tumor immune evasion and a therapeutically targetable vulnerability in cancer cells.
Gamma Knife Radiosurgery for High-Grade Gliomas: Single-Center Experience of Six Years in China
Authors: Zhao Ming , Fu Xiangping , Zhang Zhiwen , Ma Liang , Wang Xiaopeng , Li Xuexiu
Published: May 2021

Objective: The aim of this study was to evaluate the efficacy of Gamma Knife radiosurgery (GKRS) as a salvage therapy for high-grade glioma in our center. Methods: A total of 167 patients with malignant glioma were treated with GKRS in our Gamma Knife Center between January 2013 and December 2017; 140 patients (85 males and 55 females) were followed up and enrolled in our study. A single lesion was found in 110 cases, and multiple lesions were found in 30 cases; 108 cases received a single therapy, and in 32 cases, at least 2 GKRSs were performed. The median tumor volume was 13.5 cm3. The mean radiation dosage was 14.35 Gy (range, 6–18 Gy). MRI was performed regularly. The RANO criteria and Cox analysis were used to evaluate the therapeutic efficiency. Results: Follow-up MRI showed the local control rate was 61.4% at 3 months after GKRS, 25.0% at 6 months, and 7.1% at 12 months. The mean and median progression-free survival (PFS) periods were 8.6 (95% CI, 6.3–11.0) and 4 (95% CI, 3.5–4.5) (range, 1–60) months, respectively. The overall survival (OS) after GKRS was 3–62 months, with a mean of 16.7 (95% CI, 14.6–18.9) months, and the median survival was 13 (95% CI, 12.1–13.9) months. The 1-, 2-, and 5-year survival rates were 51.4, 10.0, and 2.9%, respectively. No severe complications occurred. Cox regression showed that glioma pathology was closely related to prognosis (p < 0.05). The Karnofsky Performance Score had little influence on PFS (p > 0.05) but influenced OS significantly (p < 0.05). Conclusion: GKRS can be used to effectively treat malignant brain glioma and can therefore be used as an alternative treatment option.
Developmental Profile of Social Communication: Findings in Typical Developing Greek Children
Authors: Vogindroukas Ioannis , Chelas Evripidis Nikolaos , Petridis Nikolaos E.
Published: May 2021

Objectives: The Developmental Profile of Social Communication (DPSC) is based on the communication and language development in children with social communication difficulties. DPSC facilitates understanding of the challenges these children face in social interaction, communication, and linguistic development. It utilizes clinician and parent responses to build the developmental profiles of individuals. The profile allows clinicians to determine the therapeutic goals for improved cooperation and communication in various contexts. In addition, it provides insight into the parents’ perspective. The aim of this study is to present the preliminary results of the DPSC in typically developing Greek children. Methods: The DPSC, a 112-item questionnaire, was administered to 357 parents of typically developing children aged 2–7.5 years using a 3-scale rating of answers. It was applied electronically via Google forms, and parents were able to ask for clarification on questions. All answers were categorized and then analyzed under independent variables. Results: Descriptive and hypothesis testing were used to summarize participant characteristics and performance. Findings suggest that children >7.5 years tended to develop most of the rated skills of DPSC adequately. Conclusions: It was determined that the DPSC questionnaire is an easily administered tool that enables the evaluation of the social communication abilities of children of different ages.
Association of Carotid Artery Endothelial Signal Intensity Gradient with Unilateral Large Artery Ischemic Stroke
Authors: Lee Chan-Hyuk , Lee Sang Hyuk , Cho Young I. , Jeong Seul-Ki
Published: May 2021

Background: Common carotid artery (CCA) and internal carotid artery (ICA) are aligned linearly, but their hemodynamic role in ischemic stroke has not been studied in depth. Objectives: We aimed to investigate whether CCA and ICA endothelial shear stress (ESS) could be associated with the ischemic stroke of large artery atherosclerosis (LAA). Methods: We enrolled consecutive patients with unilateral ischemic stroke of LAA and healthy controls aged >60 years in the stroke center of Jeonbuk National University Hospital. All patients and controls were examined with carotid artery time-of-flight magnetic resonance angiography, and their endothelial signal intensity gradients (SIGs) were determined, as a measure of ESS. The effect of right or left unilateral stroke on the association between carotid artery endothelial SIG and ischemic stroke of LAA was assessed. Results: In total, the results from 132 patients with ischemic stroke of LAA and 121 controls were analyzed. ICA endothelial SIG showed significant and independent associations with the same-sided unilateral ischemic stroke of LAA, even after adjusting for the potential confounders including carotid stenosis, whereas CCA endothelial SIG showed a significant association with the presence of the ischemic stroke of LAA. Conclusion: Although CCA and ICA are located with continuity, the hemodynamics and their roles in large artery ischemic stroke should be considered separately. Further studies are needed to delineate the pathophysiologic roles of ESS in CCA and ICA for large artery ischemic stroke.
Caspase-11 Noncanonical Inflammasome: A Novel Key Player in Murine Models of Neuroinflammation and Multiple Sclerosis
Authors: Yi Young-Su
Published: May 2021

Inflammasomes are intracellular protein complexes consisting of the pattern recognition receptors and inflammatory molecules in the inflamed cells. In response to various ligands, inflammasomes play a pivotal role to execute the inflammatory responses by inducing the pyroptosis and the secretion of pro-inflammatory cytokines, interleukin (IL)-1β, and IL-18. Unlike canonical inflammasomes, including NOD-like receptor family inflammasomes, such as NLRP1, NLRP3, NLRC4, and absence in melanoma 2 inflammasomes, noncanonical inflammasomes, such as mouse caspase-11 and human caspase-4/5 were recently discovered, and their roles in the inflammatory responses have been poorly understood. However, emerging studies have been successfully demonstrating the regulatory roles of these noncanonical inflammasomes on inflammatory responses and the pathogenesis of inflammatory/autoimmune diseases. This review summarizes and discusses the recent studies investigating the regulatory roles of the caspase-11 noncanonical inflammasome in neuroinflammation and the pathogenesis of multiple sclerosis (MS), which provides the insight for the validation of caspase-11 noncanonical inflammasome to develop novel and promising therapeutics for MS.
Funcionalidade e qualidade de vida de pessoas com esclerose lateral amiotrófica e percepção da sobrecarga e apoio social de cuidadores informais
Authors: Gomes Crystian Moraes Silva , Zuqui Aline Caus , Schiavo Kellen Valladão , Oliveira Jonaina Fiorim Pereira de
Published: May 2021

Objetivo: Esta pesquisa tem como objetivo mensurar a funcionalidade e qualidade de vida de pacientes com Esclerose Lateral Amiotrófica (ELA) e fornecer evidências sobre a possível sobrecarga de cuidados gerados aos seus cuidadores informais. Método: Trata-se de um estudo descritivo exploratório do tipo quantitativo, com delineamento transversal. A amostra do estudo foi composta por 24 participantes, sendo 12 pacientes com ELA e 12 cuidadores informais, recrutados em um Centro Especializado de Reabilitação. Foram administrados aos indivíduos com ELA os instrumentos: Questionário sobre Informações Demográficas; Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R); Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) e aos cuidadores: Questionário de Avaliação da Sobrecarga do Cuidador Informal (QASCI); Escala de Apoio Social do Medical Outcomes Study (MOS). Resultados: Foram encontradas fortes correlações entre ALSFRS-R e ALSAQ-40 (r = - 0.709 e p < 0.010), entre o domínio Atividades de Vida Diária e a ALSFRS-R (r = - 0.877 e p < .001), entre os domínios da QASCI e MOS, Mecanismo de Eficácia e de Controle e Apoio material (r = - 0.598 e p < 0.040), Satisfação com o Papel e com o Familiar e Apoio Afetivo (r = - 0.604 e p < 0.037), e Suporte Familiar e Interação Social Positiva (r = - 0.683 e p < 0.014). Conclusão: A funcionalidade e a qualidade de vida do paciente com ELA influenciam na provisão de cuidados, o suporte social percebido foi uma variável moderadora da sobrecarga de estresse dos cuidadores.
Nonalcoholic Fatty Liver Disease: An Emerging Driver of Cardiac Arrhythmia
Authors: Chen Ze , Liu Jiayi , Zhou Feng , Li Haomiao , Zhang Xiao-Jing , She Zhi-Gang , Lu Zhibing , Cai Jingjing , Li Hongliang
Published: May 2021

Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.