Miracle-dz/UniFAR-FTUs huggingface dataset:
HPV16 induces penile intraepithelial neoplasia and squamous cell carcinoma in transgenic mice: first mouse model for HPV‐related penile cancer

Penile cancer is an under‐studied disease that occurs more commonly in developing countries and 30–50% of cases show high‐risk human papillomavirus (HPV) infection. Therapeutic advances are slow, largely due to the absence of animal models for translational research. Here, we report the first mouse model for HPV‐related penile cancer. Ten‐week‐old mice expressing all the HPV16 early genes under control of the cytokeratin 14 (Krt14) gene promoter and matched wild‐type controls were exposed topically to dimethylbenz(a)anthracene (DMBA) or vehicle for 16 weeks. At 30 weeks of age, mice were sacrificed for histological analysis. Expression of Ki67, cytokeratin 14, and of the HPV16 oncogenes E6 and E7 was confirmed using immunohistochemistry and quantitative PCR, respectively. HPV16‐transgenic mice developed intraepithelial lesions including condylomas and penile intraepithelial neoplasia (PeIN). Lesions expressed cytokeratin 14 and the HPV16 oncogenes E6 and E7 and showed deregulated cell proliferation, demonstrated by Ki67‐positive supra‐basal cells. HPV16‐transgenic mice exposed to DMBA showed increased PeIN incidence and squamous cell carcinoma. Malignant lesions showed varied histological features closely resembling those of HPV‐associated human penile cancers. Wild‐type mice showed no malignant or pre‐malignant lesions even when exposed to DMBA. These observations provide the first experimental evidence to support the etiological role of HPV16 in penile carcinogenesis. Importantly, this is the first mouse model to recapitulate key steps of HPV‐related penile carcinogenesis and to reproduce morphological and molecular features of human penile cancer, providing a unique in vivo tool for studying its biology and advancing basic and translational research. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Efficacy and Safety of Two Fixed-Dose Combinations of Tramadol Hydrochloride and Diclofenac Sodium in Postoperative Dental Pain.

OBJECTIVE To evaluate the analgesic efficacy and safety of tramadol hydrochloride/diclofenac sodium fixed-dose combination 25 mg/25 mg (FDC 25/25) and 50 mg/50 mg (FDC 50/50) vs tramadol 50 mg (T50) and diclofenac 50 mg (D50) monotherapies in acute postoperative dental pain. SETTING Eight sites across Mexico. SUBJECTS Adults (N = 829) with moderate to severe pain after third molar extraction. DESIGN Prospective, randomized, double-blind, diclofenac- and tramadol-controlled, parallel-group, noninferiority, phase 3 trial. METHODS Subjects were randomized to receive three doses (one every eight hours) of oral FDC 25/25, FDC 50/50, T50, or D50 over a 24-hour period. Pain intensity and pain relief were evaluated frequently over the 24 hours postdose. Secondary measures included peak pain relief, onset, and duration of effect. The primary objective was to compare the analgesic efficacy and safety of FDC 50/50 or analgesic noninferiority of FDC 25/25 vs D50 or T50. The primary efficacy end point was total pain relief over four hours after dose 1 (TOTPAR4). RESULTS TOTPAR4 scores showed that FDC 25/25 was noninferior (P < 0.0001, delta = 1.5) and FDC 50/50 was superior (P < 0.0001) to the individual components. All secondary efficacy measures supported these results. The safety profile of FDC 25/25 and FDC 50/50 was consistent with the known safety profile of D50 and T50 monotherapies, with no unexpected safety findings observed. CONCLUSIONS Tramadol/diclofenac FDC 25/25 and FDC 50/50 provide superior analgesia for acute pain after third molar extraction than either of the individual components. Minor adverse effects appeared to be related to the higher doses of tramadol.
Sperm-cell ultrastructure of North American sturgeons. IV. The pallid sturgeon (Scaphirhynchus albus Forbes and Richardson, 1905)

Sperm-cell morphology and ultrastructure in the pallid sturgeon (Scaphirhynchus albus) were examined using transmission and scanning electron microscopy. Metrics and structure were compared with similar metrics obtained from other published descriptions of sturgeon sperm cells. General morphology was found to be similar to that of sperm cells of the white (Acipenser transmontanus), lake (A. fulvescens), stellate (A. stellatus), Chinese (A. sinensis), Russian (A. gueldenstaedti colchicus), and shortnose (A. brevirostrum) sturgeons, which all shared a gradual tapering of the nuclear diameter from posterior to anterior, unlike that of the Atlantic sturgeon (A. oxyrhynchus). The sperm cell of the pallid sturgeon was similar in size to that of the Atlantic sturgeon, being only slightly larger. The sperm cell of the pallid sturgeon differed from those of other sturgeons chiefly in the acrosomal region, where the posterolateral projections (PLP) have the shape of an acute triangle and are arranged in a spiral ab.
Complete recovery of fulminant cytotoxic CD8 T‐cell‐mediated myocarditis after ECMELLA unloading and immunosuppression

A 19‐year‐old woman with no previous cardiac history was admitted to the hospital with third‐degree atrioventricular block and left ventricular dysfunction. Her condition quickly deteriorated to severe biventricular failure and cardiogenic shock requiring mechanical circulatory support. An endomyocardial biopsy revealed lymphocytic myocarditis with no PCR‐detectable viral genomes, with CD8 T‐cell predominance and pro‐inflammatory macrophage expansion shown by myocardial flow cytometry. The therapy consisted of immunosuppression (high‐dose methylprednisolone) and temporary mechanical circulatory support with enhanced ability to achieve left ventricular unloading by combination of extracorporeal membrane oxygenation with Impella (ECMELLA). After 2 weeks of support, complete and sustained recovery from myocarditis was observed.
Cytogenetic analysis in three species from genus Astyanax (Pisces; Characiformes) with a new occurrence of B chromosome in Astyanax paranae

Cytogenetic studies were carried out in three species from genus Astyanax: Astyanax paranae (Tagaçaba Stream and Tauá Stream), Astyanax altiparanae (Iguaçu River and Maringá Stream) and Astyanax fasciatus (Maringá Stream). Both populations of A. paranae featured 2n = 50 chromosomes, although with different karyotype formulae and Ag-nucleolar organizer regions systems. Using the FISH technique in the Tagaçaba population, it was possible to detect rDNA genes in 14 chromosomes and bitelomeric marking in one chromosome. The constitutive heterochromatin pattern also showed differences between the two populations. Moreover, the Tagaçaba population showed macrochromosome B in 50% of analyzed females. Both A. altiparanae populations featured 2n = 50 chromosomes, but also differed in karyotype formula. Both populations featured multiple-NOR systems and quite similar constitutive heterochromatin patterns. For the A. fasciatus population from Maringá Stream, the diploid number was 2n = 46 chromosomes with karyotype formulae 14m, 10sm, 12st and 10a (fundamental number = 82), with single-NOR system and heterochromatin pattern showing evident markers in the telomeric regions of several subtelocentric and acrocentric chromosomes. The data presented for this species differ from some previously analyzed populations with regard to diploid number (2n = 48 chromosomes) and karyotype formula for those with the same diploid number. The present data strengthen the accentuated cytogenetical variability of the genus Astyanax.
How to Get the Best from Low-Cost Particulate Matter Sensors: Guidelines and Practical Recommendations

Low-cost sensors based on the optical particle counter (OPC) are increasingly being used to collect particulate matter (PM) data at high space and time resolution. In spite of their huge explorative potential, practical guidelines and recommendations for their use are still limited. In this work, we outline a few best practices for the optimal use of PM low-cost sensors based on the results of an intensive field campaign performed in Bologna (44°30′ N, 11°21′ E; Italy) under different weather conditions. Briefly, the performances of a series of sensors were evaluated against a calibrated mainstream OPC with a heated inlet, using a robust approach based on a suite of statistical indexes capable of evaluating both correlations and biases in respect to the reference sensor. Our results show that the sensor performance is sensibly affected by both time resolution and weather with biases maximized at high time resolution and high relative humidity. Optimization of PM data obtained is therefore achievable by lowering time resolution and applying suitable correction factors for hygroscopic growth based on the inherent particle size distribution.
Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Single-stranded positive RNA ((+) ssRNA) viruses include several important human pathogens. Some members are responsible for large outbreaks, such as Zika virus, West Nile virus, SARS-CoV, and SARS-CoV-2, while others are endemic, causing an enormous global health burden. Since vaccines or specific treatments are not available for most viral infections, the discovery of direct-acting antivirals (DAA) is an urgent need. Still, the low-throughput nature of and biosafety concerns related to traditional antiviral assays hinders the discovery of new inhibitors. With the advances of reverse genetics, reporter replicon systems have become an alternative tool for the screening of DAAs. Herein, we review decades of the use of (+) ssRNA viruses replicon systems for the discovery of antiviral agents. We summarize different strategies used to develop those systems, as well as highlight some of the most promising inhibitors identified by the method. Despite the genetic alterations introduced, reporter replicons have been shown to be reliable systems for screening and identification of viral replication inhibitors and, therefore, an important tool for the discovery of new DAAs.
Comparative study of the adjuvanticity of Bacillus thuringiensis Cry1Ab protein and cholera toxin on allergic sensitisation and elicitation to peanut

Abstract We aimed to investigate the adjuvanticity of Cry1Ab on allergic sensitisation and elicitation to peanut in mice, in comparison with cholera toxin (CT), a known mucosal Th2 adjuvant. Balb/c mice were gavaged with phosphate buffer saline (PBS) (control), peanut protein extract (PE) alone or PE co-administered either with CT or Cry1Ab. Peanut-specific IgE, IgG1 and IgG2a and Th1/Th2/Th17 cytokine secretion by splenocytes were assayed. Gavaged mice were further challenged with PE. Markers of the immediate and late phases of the allergic reaction were assayed in bronchoalveolar lavages (BAL) fluids collected 10 minutes or 36 hours after airway challenge, respectively. Sensitisation to peanut was only observed in mice receiving PE plus CT, as demonstrated by specific IgE and IgG1 production in sera and secretion of Th2 (and Th17) cytokines by splenocytes. Following challenge, mice sensitised with PE plus CT produced leukotrienes (LT) E4 and C4, then Th2/Th17-cytokines and showed eosinophil/neutrophil influx in BAL. Interestingly, LT production, Th2/Th17 cytokine release and eosinophil influx were also significant in mice gavaged with PE plus Cry-1Ab, but not with PBS or PE alone. Cry1Ab did not demonstrate adjuvant effects on oral sensitisation to peanut. However, this study shows possible adjuvant properties of Cry1Ab on the elicitation of the allergic reaction, at least in the Balb/c mouse model and in the experimental conditions used.
Mortality of newborn pups of the South African fur seal Arctocephalus pusillus pusillus in Namibia

Pup mortality in the South African (Cape) fur seal Arctocephalus pusillus pusillus was measured throughout the pupping seasons over consecutive years (1987–1991) at two large mainland colonies in Namibia. Cumulative rates of mortality were obtained by counting live and dead pups every second day. Most young pups die shortly after birth in November/December each year, following which there is a decline in the rate of mortality. The average rate of mortality from birth to age 30 days at the Atlas Bay colony was 20 per cent. There was little inter-colony variation in the mortality rates of pups over the four years of the study. Differential rates of mortality between the sexes were found, significantly more female pups dying. Environmental factors are influential in the deaths of newborn pups at these mainland colonies, a combination of changes in wind velocity and direction leading to heat stress in pups being the most important.
Growth Responses of Drought Resistant Rice Cultivars to Soil Compaction under Irrigated and Succeeding Non-irrigated Conditions during the Vegetative Stage

AbstractWe investigated whether drought resistant rice cultivars exhibit higher dry-matter production under wet and dry compacted soil conditions in the vegetative stage and determined the dominant factors governing resistance to soil compaction. Three rice cultivars, a drought-sensitive Nipponbare, and drought-resistant Senshou and Dular, were grown in pots at four soil bulk densities (SBD) ranging from 1300 to 1600 dry soil kg m−3. Root and shoot dry matter productions was slightly smaller in Nipponbare over the 29 days after sowing under irrigated conditions than in the other cultivars at all SBDs. Senshou and Dular also maintained a higher dry matter production, both in relative and absolute values, than Nipponbare under the condition of withheld irrigation from days 29 — 39 after sowing. The higher stomatal conductance and leaf water potential of these two cultivars were supported by a larger root system which was mostly accompanied by lower top-root ratios in the irrigated and compacted soils. The h.
Aero-Ga2O3 Nanomaterial Electromagnetically Transparent from Microwaves to Terahertz for Internet of Things Applications

In this paper, fabrication of a new material is reported, the so-called Aero-Ga2O3 or Aerogallox, which represents an ultra-porous and ultra-lightweight three-dimensional architecture made from interconnected microtubes of gallium oxide with nanometer thin walls. The material is fabricated using epitaxial growth of an ultrathin layer of gallium nitride on zinc oxide microtetrapods followed by decomposition of sacrificial ZnO and oxidation of GaN which according to the results of X-ray diffraction (XRD) and X-ray photoemission spectroscopy (XPS) characterizations, is transformed gradually in β-Ga2O3 with almost stoichiometric composition. The investigations show that the developed ultra-porous Aerogallox exhibits extremely low reflectivity and high transmissivity in an ultrabroadband electromagnetic spectrum ranging from X-band (8–12 GHz) to several terahertz which opens possibilities for quite new applications of gallium oxide, previously not anticipated.
Editor’s presentation: Staying healthy and fighting cardiovascular disease at the time of COVID

While assertive measures to tackle the contagion are necessary, there are ramifications on other aspects of healthcare and, in particular, the delivery of cardiovascular care which is hampered. In particular, cardiac rehabilitation services, the availability and implementation of which are already poor worldwide, in the present situation may be particularly neglected. In the present issue, two short commentaries are underlining the importance of continuity of care and secondary preventive measures for patients with cardiovascular disease. And staying active and maintaining a physical exercise routine will be essential for mental and physical health. This is the right time for all cardiac rehabilitation providers to explore and implement methods to improve or supplement existing cardiac rehabilitation programmes by the deployment of digital health. A wide range of exercises, such as video or app-guided equipment-free aerobics or strength training, can be performed at home and should be encouraged.
Seniors and mobiles: A qualitative inquiry of mHealth adoption among Singapore seniors

ABSTRACT Objective This study examines how seniors in Singapore use mobile devices for healthcare purposes. Methods Semi-structured interviews with 35 mobile phone users aged between 58–82 years old. Results Seniors regard mobile phones as important personal devices for socialization, security, and emergency purposes. Most of the seniors consider mobile telephony (voice calls and text messaging) as an accessible platform to access healthcare. Perceived usefulness, ease of use, compatibility, technology anxiety, financial cost, and self-efficacy were identified as factors affecting the use of mHealth among seniors. Although a few adopt mHealth applications and mobile Internet for health-information seeking, some younger seniors show enthusiastic attitudes toward its adoption. Additionally, some seniors also have technology anxiety and resistance toward using mHealth applications. Conclusion Seniors use mobile phones for healthcare purposes in their daily life, and its use involves several facilitators and barriers. Interpersonal training is likely to reduce their anxiety and increase mHealth literacy and adoption. Theoretical and practical implications are discussed.
Rapid adaptive evolution of the diapause program during range expansion of an invasive mosquito

In temperate climates, the recurring seasonal exigencies of winter represent a fundamental physiological challenge for a wide range of organisms. In response, many temperate insects enter diapause, an alternative developmental program, including developmental arrest, that allows organisms to synchronize their life cycle with seasonal environmental variation. Geographic variation in diapause phenology contributing to local climatic adaptation is well documented. However, few studies have examined how the rapid evolution of a suite of traits expressed across the diapause program may contribute to climatic adaptation on a contemporary timescale. Here, we investigate the evolution of the diapause program over the past 35 years by leveraging a “natural experiment” presented by the recent invasion of the Asian tiger mosquito, Aedes albopictus, across the eastern United States. We sampled populations from two distinct climatic regions separated by 6° of latitude (∼700 km). Using common‐garden experiments, we identified regional genetic divergence in diapause‐associated cold tolerance, diapause duration, and postdiapause starvation tolerance. We also found regional divergence in nondiapause thermal performance. In contrast, we observed minimal regional divergence in nondiapause larval growth traits and at neutral molecular marker loci. Our results demonstrate rapid evolution of the diapause program and imply strong selection caused by differences in winter conditions.
BAX Redistribution Induces Apoptosis Resistance and Selective Stress Sensitivity in Human HCC

Cancer therapies induce differential cell responses, ranging from efficient cell death to complete stress resistance. The BCL-2 proteins BAX and BAK govern the cellular decision between survival and mitochondrial apoptosis. Therefore, the status of BAX/BAK regulation can predict the cellular apoptosis predisposition. Relative BAX/BAK localization was analyzed in tumor and corresponding non-tumor samples from 34 hepatocellular carcinoma (HCC) patients. Key transcriptome changes and gene expression profiles related to the status of BAX regulation were applied to two independent cohorts including over 500 HCC patients. The prediction of apoptotic response was tested using cell lines and polyclonal tumor isolates. Cellular protection from BAX was confirmed by challenging cells with mitochondrial BAX. We discovered a subgroup of HCC with selective protection from BAX-dependent apoptosis. BAX-protected tumors showed enrichment of signaling pathways associated with oxidative stress response and DNA repair as well as increased genetic heterogeneity. Gene expression profiles characteristic to BAX-specific protection are enriched in poorly differentiated HCCs and show significant association to the overall survival of HCC patients. Consistently, addiction to DNA repair of BAX-protected cancer cells caused selective sensitivity to PARP inhibition. Molecular characteristics of BAX-protected HCC were enriched in cells challenged with mitochondrial BAX. Our results demonstrate that predisposition to BAX activation impairs tumor biology in HCC. Selective BAX inhibition or lack thereof delineates distinct subgroups of HCC patients with molecular features and differential response pattern to apoptotic stimuli and inhibition of DNA repair mechanisms.
The role of collective efficacy and co-regulation in medical students’ performance in small group contexts

Purpose This study investigated the role of collective efficacy and co-regulation in terms of students’ performance during small group projects in a medical research program. The effect of collective efficacy in student performance was expected to be mediated by co-regulation. Methods A total of 50 students who enrolled in a medical research program worked on their medical research project in small groups over a period of 9 weeks. After they had submitted their final research project reports as groups at the end of the course, the collective efficacy and co-regulation surveys were conducted online. Results The mediation model was significant and explained 26.61% of the variance in student performance. The total effect of collective efficacy on student performance was significant and the indirect effect through co-regulation was also significant. Conclusion These results suggest that collective efficacy influenced student performance through co-regulation in group learning contexts. Considering the fact that more and more collaborative learning now occurs in medical education, the result of this study can provide significant insights for enhancing students’ performance in small group contexts.
Localization of the photoreceptor for photoperiodism in the stink bug, Plautia crossota stali

The brown‐winged green bug Plautia crossota stali Scott (Heteroptera: Pentatomidae) shows a long‐day photoperiodic response with respect to the control of adult diapause. The location of the photoreceptor for this response was examined by surgical removal of putative photoreceptor organs. Even after both ocelli were removed, the insects responded normally to the photoperiod. After bilateral removal of the compound eyes, the insects developed reproductive organs and the volume of the corpus allatum increased regardless of photoperiod. Therefore, the compound eyes play a major role in the reception of photic information for photoperiodism in P. c. stali. However, because removal of the bilateral compound eyes did not completely prevent the response to photoperiod, photoreceptors other than the compound eyes can also receive photic information for photoperiodism.