bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of angiotensin type 2 receptor attenuates testosterone-induced hypertension and uterine vascular resistance in pregnant rats
Authors: Mishra Jay S , Kumar Sathish
Published: March 2021

Preeclampsia is a pregnancy-related hypertensive disorder with unclear mechanisms. While hypersensitivity to angiotensin II via vasoconstrictive angiotensin type-1 receptor (AT1R) is observed in preeclampsia, the importance of vasodilatory angiotensin type-2 receptor (AT2R) in the control of vascular dysfunction is less clear. We assessed whether AT1R, AT2R, and endothelial nitric oxide synthase (eNOS) expression are altered in placental vessels of preeclamptic women and tested if ex vivo incubation with AT2R agonist Compound 21 (C21; 1 μM) could restore AT1R, AT2R, and eNOS balance. Further, using a rat model of gestational hypertension induced by elevated testosterone, we examined whether C21 (1 μg/kg/day, oral) could preserve AT1R and AT2R balance and improve blood pressure, uterine artery blood flow, and vascular function. Western blots revealed that AT1R protein level was higher while AT2R and eNOS protein were reduced in preeclamptic placental vessels, and AT2R agonist C21 decreased AT1R and increased AT2R and eNOS protein levels in preeclamptic vessels. In testosterone dams, blood pressure was higher, and uterine artery blood flow was reduced, and C21 treatment reversed these levels similar to those in controls dams. C21 attenuated the exaggerated Ang II contraction and improved endothelium-dependent vasorelaxation in uterine arteries of testosterone dams. These C21-mediated vascular effects were associated with decreased AT1R and increased AT2R and eNOS protein levels. C21 also increased serum nitrate/nitrite and bradykinin production in testosterone dams and attenuated the fetoplacental growth restriction. Thus, AT1R upregulation and AT2R downregulation are observed in preeclampsia and testosterone model, and increasing AT2R activity could help restore AT1R and AT2R balance and improve gestational vascular function.
Unusual Localization of Blood-Borne Loa loa Microfilariae in the Skin Depends on Microfilarial Density in the Blood: Implications for Onchocerciasis Diagnosis in Coendemic Areas
Authors: Niamsi-Emalio Yannick , Nana-Djeunga Hugues C , Chesnais Cédric B , Pion Sébastien D S , Tchatchueng-Mbougua Jules B , Boussinesq Michel , Basáñez María-Gloria , Kamgno Joseph
Published: March 2021

Background

The diagnostic gold standard for onchocerciasis relies on identification and enumeration of (skin-dwelling) Onchocerca volvulus microfilariae (mf) using the skin snip technique (SST). In a recent study, blood-borne Loa loa mf were found by SST in individuals heavily infected with L. loa, and microscopically misidentified as O. volvulus due to their superficially similar morphology. This study investigates the relationship between L. loa microfilarial density (Loa MFD) and the probability of testing SST positive.

Methods

A total of 1053 participants from the (onchocerciasis and loiasis coendemic) East Region in Cameroon were tested for (1) Loa MFD in blood samples, (2) O. volvulus presence by SST, and (3) Immunoglobulin (Ig) G4 antibody positivity to Ov16 by rapid diagnostic test (RDT). A Classification and Regression Tree (CART) model was used to perform a supervised classification of SST status and identify a Loa MFD threshold above which it is highly likely to find L. loa mf in skin snips.

Results

Of 1011 Ov16-negative individuals, 28 (2.8%) tested SST positive and 150 (14.8%) were L. loa positive. The range of Loa MFD was 0–85 200 mf/mL. The CART model subdivided the sample into 2 Loa MFD classes with a discrimination threshold of 4080 (95% CI, 2180–12 240) mf/mL. The probability of being SST positive exceeded 27% when Loa MFD was >4080 mf/mL.

Conclusions

The probability of finding L. loa mf by SST increases significantly with Loa MFD. Skin-snip polymerase chain reaction would be useful when monitoring onchocerciasis prevalence by SST in onchocerciasis–loiasis coendemic areas.
Cytomegalovirus reactivation in left ventricular assist device patients: case series and literature review
Authors: Abohelwa Mostafa M , Hassan Mona Ali , Zahnan Jad , Sfeir Pierre , El Zakhem Aline , Skouri Hadi
Published: March 2021

Background 

Cytomegalovirus (CMV) reactivation after placing left ventricular assist device (LVAD) is not a well-known entity with few cases reported in the literature. Here, we are presenting three cases of CMV reactivation after placing LVAD. A literature review of all reported cases in the literature was done.

Case summary 

Three cases of advanced heart failure with reduced ejection fraction (Stage D9) had placed (LVAD) at the American University of Beirut Medical Center, a tertiary care centre in Lebanon. Within the first 2 weeks after LVAD implantation, the three patients spiked a high-grade fever for which sepsis workup was done, and antibiotics were initiated. Despite the escalating antibiotic regimens, the three patients had a persistent high-grade fever. The negative cultures and the continuous fever prompted an investigation for other causes of fever. Therefore, CMV polymerase chain reaction in blood was performed and revealed high titres. Patients received a full course of treatment with ganciclovir. The fever and the CMV titres declined after completing the antiviral therapy with better clinical outcomes. This raises the concern of CMV reactivation in LVAD patients.

Discussion 

This case series and literature review highlight the epidemiology, incidence, and management of CMV reactivation among LVAD patients. Awareness about this clinical entity should be raised, especially with the increase of LVAD surgeries.
Yeasts as a promising delivery platform for DNA and RNA vaccines
Authors: Silva Anna Jéssica Duarte , de Macêdo Larissa Silva , Leal Lígia Rosa Sales , de Jesus André Luiz Santos , Freitas Antonio Carlos
Published: March 2021

Yeasts are considered a useful system for the development of vaccines for human and veterinary health. Species such as Saccharomyces cerevisiae and Pichia pastoris have been used successfully as host organisms for the production of subunit vaccines. These organisms have been also explored as vaccine vehicles enabling the delivery of antigens such as proteins and nucleic acids. The employed species possess a GRAS status (Generally Recognized as Safe) for the production of therapeutic proteins, besides promoting immunostimulation due to the properties of their wall cell composition. This strategy allows the administration of nucleic acids orally and a specific delivery to professional antigen-presenting cells (APCs). In this review, we seek to outline the development of whole yeast vaccines (WYV) carrying nucleic acids in different approaches in the medical field, as well as the immunological aspects of this vaccine strategy. The data presented here reveal the application of this platform in promoting effective immune responses in the context of prophylactic and therapeutic approaches.
Genetic Drift Dominates Genome-Wide Regulatory Evolution Following an Ancient Whole-Genome Duplication in Atlantic Salmon
Authors: Verta Jukka-Pekka , Barton Henry J , Pritchard Victoria , Primmer Craig R
Published: March 2021

Whole-genome duplications (WGD) have been considered as springboards that potentiate lineage diversification through increasing functional redundancy. Divergence in gene regulatory elements is a central mechanism for evolutionary diversification, yet the patterns and processes governing regulatory divergence following events that lead to massive functional redundancy, such as WGD, remain largely unknown. We studied the patterns of divergence and strength of natural selection on regulatory elements in the Atlantic salmon (Salmo salar) genome, which has undergone WGD 100–80 Ma. Using ChIPmentation, we first show that H3K27ac, a histone modification typical to enhancers and promoters, is associated with genic regions, tissue-specific transcription factor binding motifs, and with gene transcription levels in immature testes. Divergence in transcription between duplicated genes from WGD (ohnologs) correlated with difference in the number of proximal regulatory elements, but not with promoter elements, suggesting that functional divergence between ohnologs after WGD is mainly driven by enhancers. By comparing H3K27ac regions between duplicated genome blocks, we further show that a longer polyploid state post-WGD has constrained regulatory divergence. Patterns of genetic diversity across natural populations inferred from resequencing indicate that recent evolutionary pressures on H3K27ac regions are dominated by largely neutral evolution. In sum, our results suggest that post-WGD functional redundancy in regulatory elements continues to have an impact on the evolution of the salmon genome, promoting largely neutral evolution of regulatory elements despite their association with transcription levels. These results highlight a case where genome-wide regulatory evolution following an ancient WGD is dominated by genetic drift.
“At Least We Could Give Our Input”: Underrepresented Student Narratives on Conventional and Guided Inquiry-Based Laboratory Approaches
Authors: Hernandez Tess , Donnelly-Hermosillo Dermot F , Person Eric , Hansen Alexandria K
Published: March 2021

Synopsis

Policy documents continually stress the need to develop a scientifically literate and diverse workforce. One commonly recommended way to achieve these goals is through the redesign of introductory level science courses to foster students’ interest in science. Such redesigns take advantage of a myriad of evidence-based strategies such as inquiry and context-based approaches that place students at the center of learning. In this study, we report on interviews of 10 female students participating in a zoo-context guided-inquiry laboratory structure within an introductory chemistry course. Half of these students were taking the laboratory for the first time (first-experience, n = 5), and half were taking the laboratory a second time (second-experience; n = 5), having failed the course in a conventional format a previous semester. The conventional laboratory format was designed to reinforce lecture content with prescriptive-style laboratories while the zoo-based guided-inquiry laboratory structure was focused on supporting student-designed investigations tied to zoo exhibits. Using interviews, we sought to understand students’ experiences and how such experiences could inform future laboratory iterations. Through inductive thematic analysis, we found three themes describing student experiences in both laboratory environments—classroom relationships, relevancy of the work, and ownership of the experiments. This work describes the nuances across student perspectives of laboratory approaches and the implications of these findings for iterations to laboratory structures toward greater student science interest, both for conventional and guided-inquiry approaches.
Host Genetic Risk Factors for Chlamydia trachomatis-Related Infertility in Women
Authors: Zheng Xiaojing , Zhong Wujuan , O’Connell Catherine M , Liu Yutong , Haggerty Catherine L , Geisler William M , Anyalechi Gloria E , Kirkcaldy Robert D , Wiesenfeld Harold C , Hillier Sharon L , Steinkampf Michael P , Hammond Karen R , Fine Jason , Li Yun , Darville Toni
Published: March 2021

Background

Chlamydia trachomatis (Ct) infection ascending to the upper genital tract can cause infertility. Direct association of genetic variants as contributors is challenging because infertility may not be diagnosed until years after infection. Investigating the intermediate trait of ascension bridges this gap.

Methods

We identified infertility genome-wide association study (GWAS) loci using deoxyribonucleic acid from Ct-seropositive cisgender women in a tubal factor infertility study and Ct-infected cisgender women from a longitudinal pelvic inflammatory disease cohort with known fertility status. Deoxyribonucleic acid and blood messenger ribonucleic acid from 2 additional female cohorts with active Ct infection and known endometrial infection status were used to investigate the impact of infertility single-nucleotide polymorphisms (SNPs) on Ct ascension. A statistical mediation test examined whether multiple infertility SNPs jointly influenced ascension risk by modulating expression of mediator genes.

Results

We identified 112 candidate infertility GWAS loci, and 31 associated with Ct ascension. The SNPs altered chlamydial ascension by modulating expression of 40 mediator genes. Mediator genes identified are involved in innate immune responses including type I interferon production, T-cell function, fibrosis, female reproductive tract health, and protein synthesis and degradation.

Conclusions

We identified Ct-related infertility loci and their potential functional effects on Ct ascension.
Designing and evaluating contextualized drug–drug interaction algorithms
Authors: Chou Eric , Boyce Richard D , Balkan Baran , Subbian Vignesh , Romero Andrew , Hansten Philip D , Horn John R , Gephart Sheila , Malone Daniel C
Published: March 2021

Objective

Alert fatigue is a common issue with off-the-shelf clinical decision support. Most warnings for drug–drug interactions (DDIs) are overridden or ignored, likely because they lack relevance to the patient’s clinical situation. Existing alerting systems for DDIs are often simplistic in nature or do not take the specific patient context into consideration, leading to overly sensitive alerts. The objective of this study is to develop, validate, and test DDI alert algorithms that take advantage of patient context available in electronic health records (EHRs) data.

Methods

Data on the rate at which DDI alerts were triggered but for which no action was taken over a 3-month period (override rates) from a single tertiary care facility were used to identify DDIs that were considered a high-priority for contextualized alerting. A panel of DDI experts developed algorithms that incorporate drug and patient characteristics that affect the relevance of such warnings. The algorithms were then implemented as computable artifacts, validated using a synthetic health records data, and tested over retrospective data from a single urban hospital.

Results

Algorithms and computable knowledge artifacts were developed and validated for a total of 8 high priority DDIs. Testing on retrospective real-world data showed the potential for the algorithms to reduce alerts that interrupt clinician workflow by more than 50%. Two algorithms (citalopram/QT interval prolonging agents, and fluconazole/opioid) showed potential to filter nearly all interruptive alerts for these combinations.

Conclusion

The 8 DDI algorithms are a step toward addressing a critical need for DDI alerts that are more specific to patient context than current commercial alerting systems. Data commonly available in EHRs can improve DDI alert specificity.
Assessing the statistical training in animal science graduate programs in the United States: survey on statistical training
Authors: Serão Nick V L , Petry Amy L , Sanglard Leticia P , Rossoni-Serão Mariana C , Bundy Jennifer M
Published: March 2021

Statistical analysis of data and understanding of experimental design are critical skills needed by animal science graduate students (ASGS). These skills are even more valuable with the increased development of high-throughput technologies. The objective of this study was to evaluate the perceived statistical training of U.S. ASGS. A survey with 38 questions was shared across U.S. universities, and 416 eligible ASGS from 43 universities participated in this study. The survey included questions on the demographics and overall training, graduate education on statistics, and self-assessment on statistics and career path of ASGS. Several analyses were performed: relationship between perceived received education (PRE; i.e., how ASGS evaluated their graduate education in statistics) and perceived knowledge (PK; i.e., how ASGS evaluated their knowledge in statistics from their education); ranking of statistical topics based on PRE, PK, and confidence in performing statistical analyses (CPSA); cluster analysis of statistical topics for PRE, PK, and CPSA; and factors (demographic, overall training, interest in statistics, and field of study) associated with the overall scores (OS) for PRE, PK, and CPSA. Students had greater (P < 0.05) PRE than PK for most of the statistical topics included in this study. The moderate to high repeatability of answers within statistical topics indicates substantial correlations in ASGS answers between PRE and PK. The cluster analysis resulted in distinct groups of “Traditional” and “Nontraditional” statistical topics. ASGS showed lower (P < 0.05) scores of PRE, PK, and CPSA in “Nontraditional” compared with “Traditional” statistical methods. Several factors were associated (P < 0.05) with the OS of PRE, PK, and CSPA. In general, factors related to greater training and interest in statistics of ASGS were associated with greater OS, such as taking more credits in statistics courses, having additional training in statistics outside the classroom, knowing more than one statistics software, and more. This study provided comprehensive information on the perceived level of education, knowledge, and confidence in statistics in ASGS in the United States. Although objective measurements of their training in statistics are needed, the current study suggests that ASGS have limited statistical training on topics of major importance for the current and future trends of data-driven research in animal sciences.
Hit the road bat! High bat activity on the road verges in Brazilian savanna
Authors: Ramalho Daniel F , Silveira Maurício , Aguiar Ludmilla M S
Published: March 2021

Roads have direct and indirect impacts on animals present in the surrounding habitats. Bats have extensive foraging ranges which may include roads, and are therefore particularly affected by them. This study aimed to analyze the effects of roads on bat activity and diversity in the Brazilian savanna. Nine transects were established in protected areas in central Brazil with sampling points at 0, 500, 1,000, and 1,500 m away from roads. At each point, we recorded bat echolocation for 12 h and evaluated the influence of road type and distance from the road on bat activity, diversity, and foraging effort. Season, normalized difference vegetation index (NDVI), and distance to water also were included in the models. We found that species richness in the dry season and activity of open space insectivores were significantly higher on road verges than on areas farther from roads, while foraging effort and activity of edge space insectivores were only influenced by season. The activity of edge space insectivores also increased significantly with increasing distance to water during the rainy season. We suggest that bat individuals do not forage near roads, but rather use them as flyways or cross them to forage in sites outside the protected areas, which can increase the risk of collision with vehicles.
Farnesol: An approach on biofilms and nanotechnology
Authors: Costa Adelaide Fernandes , Silva Lívia do Carmo , Amaral Andre Correa
Published: March 2021

Biofilms are important virulence factor in infections caused by microorganisms because of its complex structure, which provide resistance to conventional antimicrobials. Strategies involving the use of molecules capable of inhibiting their formation and also act synergistically with conventional drugs have been explored. Farnesol is a molecule present in essential oils and produced by Candida albicans as a quorum sensing component. This sesquiterpene presents inhibitory properties in the formation of microbial biofilms and synergism with antimicrobials used in clinical practice, and can be exploited even for eradication of biofilms formed by drug-resistant microorganisms. Despite this, farnesol has physical and chemical characteristics that can limit its use, such as high hydrophobicity and volatility. Therefore, nanotechnology may represent an option to improve the efficiency of this molecule in high complex environments such as biofilms. Nanostructured systems present important results in the improvement of treatment with different commercial drugs and molecules with therapeutic or preventive potential. The formation of nanoparticles offers advantages such as protection of the incorporated drugs against degradation, improved biodistribution and residence time in specific treatment sites. The combination of farnesol with nanotechnology may be promising for the development of more effective antibiofilm therapies, as it can improve its solubility, reduce volatility, and increase bioavailability. This review summarizes existing data about farnesol, its action on biofilms, and discusses its encapsulation in nanostructured systems.

Lay Summary

Farnesol is a natural compound that inhibits the formation of biofilms from different microbial species. The encapsulation of this molecule in nanoparticles is a promising alternative for the development of more effective therapies against biofilms.
Spectrum formation in X-ray pulsars at very low mass accretion rate: Monte Carlo approach
Authors: Mushtukov Alexander A , Suleimanov Valery F , Tsygankov Sergey S , Portegies Zwart Simon
Published: March 2021

Recently, it has been discovered that the transition of X-ray pulsars to the low luminosity state ($L\lesssim 10^{35}\, {\rm erg\ \rm s^{-1}}$) is accompanied by a dramatic spectral change. That is, the typical power-law-like spectrum with high-energy cut-off transforms into a two-component structure with a possible cyclotron absorption feature on top of it. It was proposed that these spectral characteristics can be explained qualitatively by the emission of cyclotron photons in the atmosphere of the neutron star caused by collisional excitation of electrons to upper Landau levels and further Comptonization of the photons by electron gas. The electron gas are expected to be overheated in a thin top layer of the atmosphere. In this paper, we perform Monte Carlo simulations of the radiative transfer in the atmosphere of an accreting neutron star while accounting for a resonant scattering of polarized X-ray photons by thermally distributed electrons. The spectral shape is shown to be strongly polarization-dependent in soft X-rays ($\lesssim 10\, {\rm keV}$) and near the cyclotron scattering feature. The results of our numerical simulations are tested against the observational data of the X-ray pulsar A 0535+262 in the low-luminosity state. We show that the spectral shape of the pulsar can be reproduced by the proposed theoretical model. We discuss applications of the discovery to the observational studies of accreting neutron stars.
Identification confusion and blending concealment in the SDSS-DR16 Quasar catalogues – 40 new quasars and 82 false quasars identified
Authors: Flesch Eric Wim
Published: March 2021

The SDSS-DR16 Quasar Superset and pipeline catalogues are searched for undeclared quasars that were concealed by or confused with other objects, usually due to incomplete deblending. 40 such quasars with redshifts are found and herewith presented. Also, 82 entries in the SDSS-DR16Q main quasar catalogue are shown to be non-quasars, some also due to incomplete deblending, especially ‘line poachers’. Other non-quasars are shown to be star spikes or moving stars or other types, and seven new quasars are identified from analysis of ‘unplugged’ spectra. These numbers are tiny compared with the millions of DR16 spectra, but highlight some heretofore overlooked systematics. The deblending issue is discussed throughout.
A new candidate pulsating ULX in NGC 7793
Authors: Quintin E , Webb N A , Gúrpide A , Bachetti M , Fürst F
Published: March 2021

We report here the discovery of NGC 7793 ULX-4, a new transient ultraluminous X-ray source (ULX) in NGC 7793, a spiral galaxy already well known for harbouring several ULXs. This new source underwent an outburst in 2012, when it was detected by XMM–Newton and the Swift X-ray telescope. The outburst reached a peak luminosity of 3.4 × 1039 erg s−1 and lasted for about eight months, after which the source went below a luminosity of 1037 erg s−1; previous Chandra observations constrain the low-state luminosity below ∼2 × 1036 erg s−1, implying a variability of at least a factor 1000. We propose four possible optical counterparts, found in archival HST observations of the galaxy. A pulsation in the XMM–Newton signal was found at 2.52 Hz, with a significance of $\sim 3.4\, \sigma$, and an associated spin-up of $\dot{f} = 3.5\times 10^{-8}$ Hz s−1. NGC 7793 is therefore the first galaxy to host more than one pulsating ULX.
Orbital pericentres and the inferred dark matter halo structure of satellite galaxies
Authors: Robles Victor H , Bullock James S
Published: March 2021

Using the phat-ELVIS suite of Milky Way-sized halo simulations, we show that subhalo orbital pericentres, rperi, correlate with their dark matter halo structural properties. Specifically, at fixed maximum circular velocity, Vmax, subhaloes with smaller rperi are more concentrated (have smaller rmax values) and have lost more mass, with larger peak circular velocities, Vpeak, prior to infall. These trends provide information that can tighten constraints on the inferred Vmax and Vpeak values for known Milky Way satellites. We illustrate this using published pericentre estimates enabled by Gaia for the nine classical Milky Way dwarf spheroidal satellites. The two densest dSph satellites (Draco and Ursa Minor) have relatively small pericentres, and this pushes their inferred rmax and Vmax values lower than they would have been without pericentre information. For Draco, we infer $V_{\rm max} = 23.5 \, \pm 3.3$ km s−1 (compared to $27.3 \, \pm 7.1$ km s−1 without pericentre information). Such a shift exacerbates the traditional Too Big to Fail problem. Draco’s peak circular velocity range prior to infall narrows from Vpeak = 21–51 km s−1 without pericentre information to Vpeak = 25–37 km s−1 with the constraint. Over the full population of classical dwarf spheroidals, we find no correlation between Vpeak and stellar mass today, indicative of a high level of stochasticity in galaxy formation at stellar masses below ∼107 M⊙. As proper motion measurements for dwarf satellites become more precise, they should enable useful priors on the expected structure and evolution of their host dark matter subhaloes.
The optical properties of three Type II supernovae: 2014cx, 2014cy, and 2015cz
Authors: Dastidar R , Misra K , Singh M , Pastorello A , Sahu D K , Wang X , Gangopadhyay A , Tomasella L , Zhang J , Bose S , Mo J , Elias-Rosa N , Tartaglia L , Yan S , Kumar Brijesh , Anupama G C , Pandey S B , Rui L , Zhang T , Terreran G , Ochner P , Huang F
Published: March 2021

We present the photometric and spectroscopic analysis of three Type II supernovae (SNe): 2014cx, 2014cy, and 2015cz. SN 2014cx is a conventional Type IIP with shallow slope (0.2 mag/50 d) and an atypical short plateau (∼86 d). SNe 2014cy and 2015cz show relatively large decline rates (0.88 and 1.64 mag/50 d, respectively) at early times before settling to the plateau phase, unlike the canonical Type IIP/L SN light curves. All of them are normal luminosity SN II with an absolute magnitude at mid-plateau of M$_{V,14\mathrm{ cx}}^{50}$=$-16.6\, \pm \, 0.4\, \rm {mag}$, M$_{V,14\mathrm{ cy}}^{50}$=$-16.5\, \pm \, 0.2\, \rm {mag}$, and M$_{V,15\mathrm{ cz}}^{50}$=$-17.4\, \pm \, 0.3\, \rm {mag}$. A relatively broad range of 56Ni masses is ejected in these explosions (0.027–0.070 M⊙). The spectra shows the classical evolution of  SNe  II, dominated by a blue continuum with broad H lines at early phases and narrower metal lines with P Cygni profiles during the plateau. High-velocity H  i features are identified in the plateau spectra of SN 2014cx at 11 600  kms −1, possibly a sign of ejecta-circumstellar interaction. The spectra of SN 2014cy exhibit strong absorption profile of H i similar to normal luminosity events whereas strong metal lines akin to sub-luminous SNe. The analytical modelling of the bolometric light curve of the three events yields similar progenitor radii within errors (478, 507, and 660 R ⊙ for SNe 2014cx, 2014cy, and 2015cz, respectively), a range of ejecta masses (15.0, 22.2, and 20.6 M ⊙ for SNe 2014cx, 2014cy, and 2015cz), and a modest range of explosion energies (3.3–7.2 foe where 1 foe=10 51erg).
Unveiling the broad-band spectral and temporal properties of PKS 0903-57 during its brightest flare
Authors: Shah Zahir , Jithesh V , Sahayanathan S , Iqbal Naseer
Published: March 2021

We carried a detailed spectral and temporal study of blazar PKS 0903-57 using the Fermi-LAT and Swift-XRT/UVOT observations, during its brightest flaring period MJD 58931–58970. During this period, the maximum daily averaged γ-ray flux ($\rm F_{0.1-500\, GeV}$) of $\rm 9.42\times 10^{-6}\, ph\, cm^{-2}\, s^{-1}$ is observed on MJD 58951.5, the highest γ-ray flux detected from PKS 0903-57 till now. Several high-energy (HE) photons ($\gt 10$ GeV) consistent with the source location at high probability (>99 per cent) are detected, and the γ-ray light curve in the active state shows multiple substructures with asymmetric profile. In order to understand the possible physical scenario responsible for the flux enhancement, we carried a detailed broad-band spectral study of PKS 0903-57 by choosing different flux states from its active period. Neglecting the multiband variability in each of the selected time intervals, we could reproduce their averaged broad-band SEDs with a one-zone leptonic model whose parameters were derived with a χ2-fit. We found that the broad-band SED during different flux states can be reproduced by the synchrotron, synchrotron-self-Compton (SSC), and external-Compton (EC) processes. The seed photons for EC process from BLR or IR torus provide acceptable fits to the GeV spectrum in all the flux states; however, the detection of HE photons together with the equipartition condition suggests that the EC/IR process is a more likely scenario. Further, a detailed comparison between the fit parameters shows that the flux enhancement from quiescent-state to the flaring-state is mostly related to increase in the bulk Lorentz factor of the emission region and change in the break energy of the source spectrum.
Synthesis and anticancer activity of mixed ligand 3d metal complexes
Authors: Chu Bo , Mo Xiyu , Chen Zilu , Zhang Mingling , Liang Yuning , Hu Huancheng , Liu Dongcheng , Liang Fupei
Published: March 2021

Our previously reported copper-based complexes of tropolone show nice antitumor effects, but with high cytotoxicity to normal cells, which is presumably caused by copper ions. Here, we managed to achieve this challenge by using other 3D metals to replace copper ions. We thus prepared four mononuclear 3D metal complexes [M(phen)L2] (M = Mn, Co, Ni, and Zn for 1–4, respectively). Complexes 1 and 4 show selectivity on different cancer cell lines with much lower cytotoxicity to normal cells than cisplatin. The anticancer effects for complexes 2 and 3 on the tested cancer cell lines are very poor. It revealed a tuning effect of different metal ions on the anticancer activities with those for Mn(II) and Zn(II) being much higher than those for Co(II) and Ni(II) in this system. Among them, complex 1 presents a best anticancer effect on HeLa cells comparable to cisplatin. It overcame the afore-mentioned shortage of high cytotoxicity to normal cells for the reported Cu(II) complexes. It revealed from the mechanistic studies that complex 1 mainly induces apoptosis through the mitochondrial pathway by increasing intracellular reactive oxygen species, releasing Ca2+, and activating Caspase 9 and proapoptotic gene Bax.
Rational engineering of a modular bacterial CRISPR–Cas activation platform with expanded target range
Authors: Villegas Kcam Maria Claudia , Tsong Annette J , Chappell James
Published: March 2021

CRISPR–Cas activator (CRISPRa) systems that selectively turn on transcription of a target gene are a potentially transformative technology for programming cellular function. While in eukaryotes versatile CRISPRa systems exist, in bacteria these systems suffer from a limited ability to activate different genes due to strict distance-dependent requirements of functional target binding sites, and require greater customization to optimize performance in different genetic and cellular contexts. To address this, we apply a rational protein engineering approach to create a new CRISPRa platform that is highly modular to allow for easy customization and has increased targeting flexibility through harnessing engineered Cas proteins. We first demonstrate that transcription activation domains can be recruited by CRISPR–Cas through noncovalent protein-protein interactions, which allows each component to be encoded on separate and easily interchangeable plasmid elements. We then exploit this modularity to rapidly screen a library of different activation domains, creating new systems with distinct regulatory properties. Furthermore, we demonstrate that by harnessing a library of circularly permuted Cas proteins, we can create CRISPRa systems that have different target binding site requirements, which together, allow for expanded target range.
Strain in perovskite solar cells: origins, impacts and regulation
Authors: Wu Jinpeng , Liu Shun-Chang , Li Zongbao , Wang Shuo , Xue Ding-Jiang , Lin Yuan , Hu Jin-Song
Published: March 2021

Metal halide perovskite solar cells (PSCs) have seen an extremely rapid rise in power conversion efficiencies in the past few years. However, the commercialization of this class of emerging materials still faces serious challenges, one of which is the instability against external stimuli such as moisture, heat and irradiation. Much focus has deservedly been placed on understanding the different origins of intrinsic instability and thereby enhancing their stability. Among these, tensile strain in perovskite films is an important source of instability that cannot be overcome using conventionally extrinsic stabilization approaches such as encapsulation. Here we review recent progress in the understanding of the origin of strain in perovskites as well as its corresponding characterization methods, and their impacts on the physical properties of perovskites and the performance of PSCs including efficiency and stability. We then summarize the latest advances in strain-regulation strategies that improve the intrinsic stability of perovskites and photovoltaic devices. Finally, we provide a perspective on how to make further progress in stable and high-efficiency PSCs via strain engineering.
Nonclassical Pathogens as Causative Agents of Proctitis in Men who Have Sex With Men
Authors: Chow Eric P F , Lee Darren , Bond Stephanie , Fairley Christopher K , Maddaford Kate , Wigan Rebecca , Fehler Glenda , Lange Sigrid A , De Petra Vesna , Bissessor Melanie , Bradshaw Catriona S , Howden Benjamin P , Hocking Jane S , Williamson Deborah A , Chen Marcus Y
Published: March 2021

Background

This study aimed to identify enteric and sexually acquired rectal pathogens, other than chlamydia and gonorrhea, associated with symptomatic proctitis in men who have sex with men (MSM).

Methods

Anorectal swab samples were obtained from MSM presenting with rectal symptoms and a clinical diagnosis of proctitis at the Melbourne Sexual Health Centre between January 2017 and March 2019. Samples that tested positive for Neisseria gonorrhoeae and Chlamydia trachomatis were excluded. As a comparison group, anorectal samples were also obtained from MSM not reporting symptoms of proctitis between November 2018 and February 2019. Samples from both groups were tested for 15 viral, bacterial, and protozoal enteric pathogens using polymerase chain reaction.

Results

Anorectal samples from 499 men with symptomatic proctitis and 506 asymptomatic men were analyzed. Age, HIV status, and pre-exposure prophylaxis (PrEP) use did not differ between men with proctitis and asymptomatic men. Treponema pallidum was more common in men with proctitis (risk difference [RD], 3.6%; 95% CI, 2.0%–5.2%). Most men with anorectal T. pallidum presented with painful anal primary infections. Shigella spp. was more common among men with proctitis compared with asymptomatic men (RD, 1.8%; 95% CI, 0.1%–3.5%). Most men with Shigella did not report diarrhea. Mycoplasma genitalium was more common in men with proctitis (RD, 4.3%; 95% CI, 1.1%–7.5%). Herpes simplex virus (HSV)–1 (RD, 10.1%; 95% CI, 6.8%–13.3%) and HSV-2 (RD, 7.2%; 95% CI, 4.5%–10.0%) were more common with proctitis.

Conclusions

Testing for T. pallidum, Shigella, and HSV should be considered in MSM presenting with symptomatic proctitis. These data provide support for M. genitalium as a significant cause of proctitis. A comprehensive diagnostic evaluation is required for MSM with proctitis.
Advocating for Mobile Music Technology
Authors: Pisano Dominic
Published: March 2021

The chapter reviews the benefits of implementing mobile technology in the music classroom. Matters relating to integrating mobile devices in the traditional music rehearsal setting and addressing new learning opportunities in music and media arts are presented. A detailed schedule of a class day with incorporating music technology is offered. Strategies for financing and maintaining mobile technology, as well as ways to avoid common implementation minefields, are given. A large selection of suggested apps useful in the rehearsal space is given. Further, the chapter includes practical, real-world strategies from the field to help teachers successfully adventure into the world of mobile technology in the music classroom.
Freedom and Fusion
Authors: Gioia Ted
Published: March 2021

The avant-garde (or “free jazz”) musicians who came to the forefront of jazz during the late 1950s and early 1960s mounted a revolutionary movement that challenged all the conventions of the idiom, aligning their innovations with the progressive social and political changes of the era. This chapter looks at the leading exponents of the music, including Ornette Coleman, Cecil Taylor, and Albert Ayler. But just when jazz seemed ready to sever completely its relationship with a mainstream audience, a new movement known as fusion (or jazz-rock fusion) attempted to broaden the music’s appeal by drawing on the new sounds of electrified commercial styles. Miles Davis, previously seen as an advocate of bebop, cool jazz, and other jazz movements, emerged as the leader of this new approach, signaled by the release of his hit album Bitches Brew. In the 1970s, a different kind of fusion style emerged, associated with the ECM record label in Germany, which combined jazz with ingredients drawn from classical music, world music, and other sources. This chapter traces the history of these contrasting styles and their major exponents, including Keith Jarrett, Pat Metheny, Chick Corea, Herbie Hancock, and the band Weather Report
Implications for Policy and Practice
Authors: Magnuson Doug , Jansson Mikael , Benoit Cecilia
Published: March 2021

Chapter 9 illustrates the circumstances of the authors’ street-involved youth sample at the time of the last data collection point, further implications of early life trauma, and the unfairness of social policy, with suggestions for helping street-involved youth reintegrate into mainstream social institutions more easily. The youth at this point in their lives were either stable and engaged, stable and unengaged, unstable and engaged, or unstable and unengaged. Only youth in the last category were truly in difficulty, but youth in the other three categories were often left out of supports that other young people take for granted. This points to the mismatch between age and social structure, and in part this is a consequence of education, work, and social services not being responsive to their life circumstances or focused on short-term goals rather than inclusion.
Five Functions, and Two Kinds, of Mens Rea
Authors: Simester A P
Published: March 2021

This chapter sketches how mens rea serves at least five different functions, which can be grouped into two broad categories. Within the first category, it helps to establish that the defendant’s offence was an instance of culpable wrongdoing. It does this in three different ways. First, and most obviously, it contributes to findings of culpability. Secondly, it can help to identify what kind of action a person is performing: in these cases, the finding of mens rea is integral to the moral wrongness of the action for which a person is being held responsible. Thirdly, mens rea affects the availability of justifications. Whether a person’s pro tanto wrong was, all things considered, wrongful—unjustified—and an instance of wrongdoing—depends on the reasons why they did it. The other broad category concerns the principle of legitimate enactment. Mens rea has important roles to play in articulating, and notifying, the limits of citizens’ freedom. More specifically, a fourth function of mens rea is to secure fair warning to defendants, ensuring they have sufficient advance notice that, by their conduct, they risk violating the criminal law. Finally, mens rea plays a key mediating role in criminalization, being part of the trade-off between the protection of potential victims and the preservation of liberties for potential defendants.
Commonality and Diversity in Administrative Justice: Fin de siècle
Authors: Cananea Giacinto della
Published: March 2021

There is variety of opinion about the origins and development of administrative law. The studies collected in this volume seek to contribute to a better understanding its development in a period of crucial importance; that is, the last decade of the nineteenth century and the first decade of the twentieth century. This chapter is divided into three parts. The first explains the choices made concerning the timeframe, the methodology, and the selection of legal systems. The focus then shifts to four main features that characterized administrative laws in those years, including the variety of judicial mechanisms, the more liberal policy on standing, the gradual reinforcement of procedural constraints on the exercise of powers by public authorities, and the abandonment of immunity. The chapter concludes with discussion of commonality and diversity between administrative laws in Europe.
The Extended Foundation of the Caribbean Court of Justice between Decolonisation and Globalisation
Authors: Caserta Salvatore
Published: March 2021

This chapter deals with the extended process of creation of the Caribbean Court of Justice (CCJ) arguing that, different from what often stated in the literature, the Court is the institutional crystallisation of two long-enduring movements within the Caribbean legal field. One of these two movements is linked to the development of early regionalism, and ties into the Court’s origins as a regional economic institution aimed at reviving the Caribbean Common Market (CARICOM). The other is a movement related to the long-lasting process of Caribbean decolonisation from the United Kingdom, as the CCJ is also intended to be a regional Supreme Court to replace the Privy Council as the apex court of the former British West Indian colonies. The chapter also analyses the window of opportunity leading to the creation of the Court, most notably the clash between different generations of Caribbean legal elites and their own respective disagreements with the Judicial Committee of the Privy Council on death penalty issues and, more generally, on how to handle the judicial system of the Caribbean countries.
The Efficacy of Hyaluronic Acid for Carpal Tunnel Syndrome: A Randomized Double-Blind Clinical Trial
Authors: Su Yu-Chi , Shen Yu-Ping , Li Tsung-Ying , Ho Tsung-Yen , Chen Liang-Cheng , Wu Yung-Tsan
Published: March 2021

Objectives

To investigate the effect of hyaluronic acid (HA) in patients diagnosed with mild or moderate carpal tunnel syndrome (CTS).

Design

A prospective randomized, double-blinded control study with 6 months of follow-up.

Setting

Rehabilitation outpatient clinic of one single medical center.

Subjects

Thirty-five participants with mild or moderate CTS.

Methods

Participants were enrolled and randomly assigned to HA or control groups. The HA group received one ultrasound-guided perineural injection of 2.5 mL HA while the control group received 2.5 mL normal saline injection through in-plane, long-axis approach to separate the median nerve from the flexor retinaculum via nerve hydrodissection. Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) scores were the primary outcome, while secondary outcomes included the numeric rating scale (NRS), electrophysiological domains, and the cross-sectional area of the median nerve. The assessment was conducted prior to injection and during the second week and 1-, 3-, and 6-months post-injection.

Results

Thirty-two patients (17 wrists in HA group and 15 wrists in control group) completed the study. Compared with the control group, the HA group did not show significantly superior outcomes, except in BCTQ and NRS at the second week post-injection (all P < .0125).

Conclusions

A single ultrasound guided perineural HA injection may have short-term therapeutic efficacy for mild or moderate CTS; however, the 2-weeks superior efficacy was not beneficial for chronic neuropathy. Further studies with larger sample sizes are required to verify its therapeutic efficacy.
Social trauma as a contributory factor in Filipino’s vaccine hesitancy
Authors: Vergara Raymond John D
Published: March 2021

Despite of the Government’s effort to persuade the public to participate in its vaccination program against COVID-19, vaccine hesitancy remains to be a big challenge in the Philippines. While various efforts were undertaken to promote the safety and efficacy of vaccines against COVID-19, it is imperative that the Philippine government considers social traumas as a factor in vaccine hesitancy. This study proposes Judith Herman’s stages of trauma recovery as a possible framework that could be utilize by the government in its drive to increase public trust.
The role of trimethoprim/sulfametoxazole in reducing relapses and risk of infections in ANCA-associated vasculitis: a meta-analysis
Authors: Monti Sara , Delvino Paolo , Riboli Mattia , Rebuffi Chiara , Xoxi Blerina , De Silvestri Annalisa , Montecucco Carlomaurizio
Published: March 2021

Objectives

To assess available evidence from randomized controlled trials (RCTs) and observational studies including a control group regarding the role of trimethoprim/sulfametoxazole (TMP/SMX) in reducing the relapse rate in patients with granulomatosis with polyangiitis (GPA) and the risk of infections in patients with ANCA-associated vasculitis (AAV).

Methods

MEDLINE, EMBASE, The Cochrane Library databases, Scopus, Web of Science and ClinicalTrials.gov were searched from inception until 15 January 2020 to identify controlled studies assessing the role of TMP/SMX in reducing the rate of relapse in patients with GPA (primary outcome) and the number and/or severity of infections in patients with AAV (secondary outcome). Two reviewers independently selected eligible studies and extracted data. Cumulative risk ratios (RRs) with 95% CI were calculated using a random effect meta-analysis.

Results

Eight studies were selected out of 2907 records. Seven studies (520 patients) (of which two were RCTs) assessed the role of TMP/SMX in the relapse rate in patients with GPA. TMP/SMX was not associated with a reduced risk of relapse (RR = 1.15, 95% CI: 0.51, 2.55; I2 = 78.5%; P < 0.001). Sensitivity analysis according to the dose of TMP/SMX (960 mg twice daily vs three times/week) confirmed the results. One retrospective cohort study (192 patients) was identified demonstrating a significant reduction of severe infections in patients with AAV receiving prophylaxis with TMP/SMX in association with rituximab.

Conclusion

TMP/SMX was not associated with a reduced risk of relapse in patients with GPA. TMP/SMX might be useful in the reduction of infectious complications.

Prospero database registration code

CRD42019118983.