Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of the biodegradative and adaptive potential of the novel polychlorinated biphenyl degrader Rhodococcus sp. WAY2 revealed by its complete genome sequence

The complete genome sequence of Rhodococcus sp. WAY2 (WAY2) consists of a circular chromosome, three linear replicons and a small circular plasmid. The linear replicons contain typical actinobacterial invertron-type telomeres with the central CGTXCGC motif. Comparative phylogenetic analysis of the 16S rRNA gene along with phylogenomic analysis based on the genome-to-genome blast distance phylogeny (GBDP) algorithm and digital DNA–DNA hybridization (dDDH) with other Rhodococcus type strains resulted in a clear differentiation of WAY2, which is likely a new species. The genome of WAY2 contains five distinct clusters of bph, etb and nah genes, putatively involved in the degradation of several aromatic compounds. These clusters are distributed throughout the linear plasmids. The high sequence homology of the ring-hydroxylating subunits of these systems with other known enzymes has allowed us to model the range of aromatic substrates they could degrade. Further functional characterization revealed that WAY2 was able to grow with biphenyl, naphthalene and xylene as sole carbon and energy sources, and could oxidize multiple aromatic compounds, including ethylbenzene, phenanthrene, dibenzofuran and toluene. In addition, WAY2 was able to co-metabolize 23 polychlorinated biphenyl congeners, consistent with the five different ring-hydroxylating systems encoded by its genome. WAY2 could also use n-alkanes of various chain-lengths as a sole carbon source, probably due to the presence of alkB and ladA gene copies, which are only found in its chromosome. These results show that WAY2 has a potential to be used for the biodegradation of multiple organic compounds.
Insight into the molecular sex dimorphism of ischaemic stroke in rat cerebral cortex: Focus on neuroglobin, sex steroids and autophagy

Including sex is of paramount importance in preclinical and clinical stroke researches, and molecular studies dealing in depth with sex differences in stroke pathophysiology are needed. To gain insight into the molecular sex dimorphism of ischaemic stroke in rat cerebral cortex, male and female adult rats were subjected to transient middle cerebral artery occlusion. The expression of neuroglobin (Ngb) and other functionally related molecules involved in sex steroid signalling (oestrogen and androgen receptors), steroidogenesis (StAR, TSPO and aromatase) and autophagic activity (LC3B‐II/LC3B‐I ratio, UCP2 and HIF‐1α) was assessed in the ipsilateral ischaemic and contralateral non‐ischaemic hemispheres. An increased expression of Ngb was detected in the injured female cerebral cortex. In contrast, increased expression of oestrogen receptor α, GPER, StAR, TSPO and UCP2, and decreased androgen receptor expression were detected in the injured male cortex. In both sexes, the ischaemic insult induced an upregulation of LC3B‐II/‐I ratio, indicative of increased autophagy. Therefore, the cerebral cortex activates both sex‐specific and common molecular responses with neuroprotective potential after ischaemia–reperfusion, which globally results in similar stroke outcome in both sexes. Nonetheless, these different potential molecular targets should be taken into account when neuroprotective drugs aiming to reduce brain damage in ischaemic stroke are investigated.
Increased Oscillatory Frequency of Sleep Spindles in Combat-Exposed Veteran Men with Post-Traumatic Stress Disorder.

STUDY OBJECTIVES Sleep disturbances are core symptoms of post-traumatic stress disorder (PTSD), but reliable sleep markers of PTSD have yet to be identified. Sleep spindles are important brain waves associated with sleep protection and sleep-dependent memory consolidation. The present study tested whether sleep spindles are altered in individuals with PTSD and whether the findings are reproducible across nights and subsamples of the study. METHODS Seventy-eight combat-exposed veteran men with (n = 31) and without (n = 47) PTSD completed two consecutive nights of high-density EEG recordings in a laboratory. We identified slow (10-13 Hz) and fast (13-16 Hz) sleep spindles during N2 and N3 sleep stages and performed topographical analyses of spindle parameters (amplitude, duration, oscillatory frequency, and density) on both nights. To assess reproducibility, we used the first 47 consecutive participants (18 with PTSD) for initial discovery and the remaining 31 participants (13 with PTSD) for replication assessment. RESULTS In the discovery analysis, compared to non-PTSD participants, PTSD participants exhibited 1) higher slow-spindle oscillatory frequency over the antero-frontal regions on both nights and 2) higher fast-spindle oscillatory frequency over the centro-parietal regions on the second night. The first finding was preserved in the replication analysis. We found no significant group differences in the amplitude, duration, or density of slow or fast spindles. CONCLUSIONS The elevated spindle oscillatory frequency in PTSD may indicate a deficient sensory-gating mechanism responsible for preserving sleep continuity. Our findings, if independently validated, may assist in the development of sleep-focused PTSD diagnostics and interventions.
The CCR4–NOT complex maintains liver homeostasis through mRNA deadenylation

The CCR4–NOT complex maintains liver homeostasis by fine-tuning levels of mRNAs, including those for transcription factors, cell cycle regulators, DNA damage response proteins, and liver function–related molecules. The biological significance of deadenylation in global gene expression is not fully understood. Here, we show that the CCR4–NOT deadenylase complex maintains expression of mRNAs, such as those encoding transcription factors, cell cycle regulators, DNA damage response–related proteins, and metabolic enzymes, at appropriate levels in the liver. Liver-specific disruption of Cnot1, encoding a scaffold subunit of the CCR4–NOT complex, leads to increased levels of mRNAs for transcription factors, cell cycle regulators, and DNA damage response–related proteins because of reduced deadenylation and stabilization of these mRNAs. CNOT1 suppression also results in an increase of immature, unspliced mRNAs (pre-mRNAs) for apoptosis-related and inflammation-related genes and promotes RNA polymerase II loading on their promoter regions. In contrast, mRNAs encoding metabolic enzymes become less abundant, concomitant with decreased levels of these pre-mRNAs. Lethal hepatitis develops concomitantly with abnormal mRNA expression. Mechanistically, the CCR4–NOT complex targets and destabilizes mRNAs mainly through its association with Argonaute 2 (AGO2) and butyrate response factor 1 (BRF1) in the liver. Therefore, the CCR4–NOT complex contributes to liver homeostasis by modulating the liver transcriptome through mRNA deadenylation.
Psychophysiological Stress Response in an Underwater Evacuation Training

Background: This research aimed to analyze the psychophysiological stress response of air crews in an underwater evacuation training. Materials and Methods: We analyzed in 36 participants (39.06 ± 9.01 years) modifications in the rating of perceived exertion (RPE), subjective stress perception (SSP), heart rate (HR), blood oxygen saturation (BOS), cortical arousal (critical flicker fusion threshold, CFFT), heart rate variability (HRV), spirometry, isometric hand strength (IHS), and short-term memory (ST-M) before and after an underwater evacuation training. Results: The maneuver produced a significant (p ≤ 0.05) increase in the SSP, RPE, Mean HR and maximum HR (Max HR), and a decrease in minimum HR (Min HR) and HRV. Conclusion: An underwater evacuation training produced an increase in the sympathetic nervous system modulation, elevating the psychophysiological stress response of the air crews, not negatively affecting their cortical arousal.
Antiviral Activity of Benzavir-2 against Emerging Flaviviruses

Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 ± 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses: WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.
Successful Treatment of Delayed Methotrexate Clearance Using Glucarpidase Dosed on Ideal Body Weight in Obese Patients

Delayed methotrexate (MTX) elimination after treatment with high‐dose (HD) MTX may result in life‐threatening toxicities as well as acute kidney injury (AKI). Treatment includes administration of glucarpidase, an enzyme that rapidly inactivates MTX. Dosing of glucarpidase is based on body weight; however, recommendations for dosage adjustments in obese patients are lacking. We describe three obese adult patients (body mass index [BMI] range 31–43 kg/m2) who received HD‐MTX following all precautions for its treatment. Although peak MTX concentrations were within the expected range (308–368 µmol/L), MTX concentrations after 24 hours or later were markedly increased (97, 52, and 19 µmol/L, respectively). Two patients experienced AKI. After a single intravenous dose of glucarpidase 4000 units (50 units/kg on the basis of ideal body weight [IBW]) was administered to each patient 38, 46, and 60 hours, respectively, after the start of MTX, MTX concentrations dropped quickly to 1.37, 0.07, and 0.03 µmol/L, respectively, and further decreased steadily. Over time, clinical status and renal function improved in all patients. Glucarpidase is a highly hydrophilic molecule with a volume of distribution of 3.6 L, representing the intravascular volume of an adult. Therefore, we used IBW for glucarpidase dose calculations, allowing us to reduce the dose that would have been determined by using total body weight. This approach resulted in a rapid decrease of MTX serum concentrations and may reduce treatment costs of this highly expensive drug.
A knock‐in mouse model for KCNQ2‐related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment

Early onset epileptic encephalopathy with suppression‐burst is one of the most severe epilepsy phenotypes in human patients. A significant proportion of cases have a genetic origin, and the most frequently mutated gene is KCNQ2, encoding Kv7.2, a voltage‐dependent potassium channel subunit, leading to so‐called KCNQ2‐related epileptic encephalopathy (KCNQ2‐REE). To study the pathophysiology of KCNQ2‐REE in detail and to provide a relevant preclinical model, we generated and described a knock‐in mouse model carrying the recurrent p.(Thr274Met) variant.
Community’s extent of use and approval of extended pharmacy services in community pharmacies in Southwest Ethiopia

Background The emergence of chronic diseases as major causes of disability and death has necessitated the introduction of new strategies to effectively address the ever-changing nature of public health problems. As a result, the role of community pharmacies in promoting public health is growing in recent years through the provision of extended pharmacy services. This study was conducted with the aim of assessing community’s extent of use and approval of extended pharmacy services at community pharmacies in Bonga town, Southwest Ethiopia. Materials and methods Community based cross-sectional study was conducted in Bonga town, Southwest Ethiopia, on households selected by systematic random sampling. Data was collected using semi-structured questionnaire. Data was collected by personally delivering questionnaires to respondents in selected households. Results of the study were described by frequency, mean and standard deviation (SD). Binary logistic analysis was performed to identify potential associations between dependent and independent variables. Results Out of 356 individuals included in the study, 58.4% recalled visiting community pharmacy premises during the previous six months. Out of these, 34.6% visited the community pharmacies to get extended pharmacy services. College educated participants were 19.4 times more likely to have used extended pharmacy services as compared to illiterate individuals whereas those who earn monthly income more than 5000 Ethiopian Birr were 3.6 times more likely than those with monthly income of 2000 Ethiopian Birr or less. Of the total participants, 91.3% approved the provision of extended pharmacy services in community pharmacies. Conclusion The extent of community’s use of extended pharmacy services at community pharmacies was found to be low. Nevertheless, majority of the study subjects approved the provision of extended pharmacy services at community pharmacies. Efforts to improve the practice of extended pharmacy service provision at community pharmacies should be made by all stake holders.
Predicting Speech Perception in Older Listeners with Sensorineural Hearing Loss Using Automatic Speech Recognition

The objective of this study was to provide proof of concept that the speech intelligibility in quiet of unaided older hearing-impaired (OHI) listeners can be predicted by automatic speech recognition (ASR). Twenty-four OHI listeners completed three speech-identification tasks using speech materials of varying linguistic complexity and predictability (i.e., logatoms, words, and sentences). An ASR system was first trained on different speech materials and then used to recognize the same speech stimuli presented to the listeners but processed to mimic some of the perceptual consequences of age-related hearing loss experienced by each of the listeners: the elevation of hearing thresholds (by linear filtering), the loss of frequency selectivity (by spectrally smearing), and loudness recruitment (by raising the amplitude envelope to a power). Independently of the size of the lexicon used in the ASR system, strong to very strong correlations were observed between human and machine intelligibility scores. However, large root-mean-square errors (RMSEs) were observed for all conditions. The simulation of frequency selectivity loss had a negative impact on the strength of the correlation and the RMSE. Highest correlations and smallest RMSEs were found for logatoms, suggesting that the prediction system reflects mostly the functioning of the peripheral part of the auditory system. In the case of sentences, the prediction of human intelligibility was significantly improved by taking into account cognitive performance. This study demonstrates for the first time that ASR, even when trained on intact independent speech material, can be used to estimate trends in speech intelligibility of OHI listeners.
High incidence of Hepatitis C virus infection observed in the PROUD study of HIV pre‐exposure prophylaxis

HIV negative men who have sex with men (MSM) who access pre-exposure prophylaxis (PrEP) report sexual behaviours that could place them at high risk of hepatitis C virus infection (HCV). We report HCV prevalence and incidence from the PROUD trial of PrEP.PROUD was an open-label, wait-list design randomised trial of HIV PrEP for MSM.Participants were recruited between November 2012 and April 2014, and follow-up continued to October 2016. Initial HCV testing followed national guidelines, with screening "on indication", but was replaced by routine quarterly screening in the latter part of the study.We estimated HCV seroprevalence at enrolment and incidence overall and according to calendar year.544 participants were recruited to PROUD. 133 (24.4%) were screened for HCV at enrolment, and 490 (90.1%) were tested at least once during follow-up. Seroprevalence at enrolment was 2.1% (11/530; 95% CI: 1.0-3.7%). Median follow-up time was 2.6 (IQR: 2.1-3.0) years and total follow-up of 1188.8 person years (PY). Twenty-five participants had a new HCV infection during the trial, yielding an incidence rate of 2.1 per 100 PY (25/1188.8; 95% CI: 1.4-3.1), of which three were re-infections. There was some evidence that HCV incidence increased over calendar time (P-value for trend=0.09), reaching an estimated 4.0 per 100 PY (95% CI: 2.0-8.1)in 2016. In conclusion, participants in PROUD had a high, and possibly increasing, incidence of HCV infection. This high incidence of HCV supports the 2018 BHIVA/BASHH recommendation for quarterly HCV testing among HIV-negative MSM using PrEP in the UK.
Use of En Face Optical Coherence Tomography to Monitor Papilledema in Idiopathic Intracranial Hypertension: A Pilot Study

Background: En face optical coherence tomography (OCT) uses the data acquired during OCT of the optic disc, which typically is used to determine measurements of the peripapillary retinal nerve fiber layer (ppRNFL), to generate a coronal composite fundus image rather than a cross-sectional image. En face OCT has been reported to identify retinal changes related to papilledema in idiopathic intracranial hypertension (IIH) but has not been evaluated for monitoring papilledema. This study aimed to assess the reliability and validity of en face OCT for monitoring papilledema. Methods: Using the Pearson correlation coefficient (R), these measurements were compared with ppRNFL thickness as well as average diameter and estimated area. Four fellowship-trained neuro-ophthalmologists were asked to qualitatively rank en face images by the area of optic disc edema while masked from all other clinical data. Rankings were compared with ppRNFL thickness as a gold standard and with en face OCT characteristics using the Pearson correlation coefficient (R). Results: Experts were able to correctly identify an increase in average ppRNFL thickness >10 µm with a mean (SD) of 91% (±7%) accuracy. A ranking error among experts corresponded to a mean (standard error) change in the ppRNFL thickness of 6 (±6) µm. The mean Pearson correlation coefficient by the area of disc edema among experts was 0.92 (±0.13). Conclusions: Multiple objective parameters of en face OCT of optic disc edema have an excellent correlation with ppRNFL thickness. These results suggest that en face OCT is a valid clinical tool for monitoring papilledema in IIH.
Maternal and Child Health Bureau’s Autism Research Program

HRSA’s MCHB autism spectrum disorder and other developmental disabilities research program plays a critical role in addressing autism research disparities. OBJECTIVES: To provide an overview and quantitatively demonstrate the reach of the Health Resources and Services Administration’s Maternal and Child Health Bureau autism research program. METHODS: We reviewed program reports and internal data from 59 autism research grantees. The US federal Interagency Autism Coordinating Committee’s strategic plan questions were used as a framework to highlight the contributions of the autism research program in advancing the field. RESULTS: The autism research program grantees advance research in several ways. Grantees have strengthened the evidence for autism interventions by conducting 89 studies at 79 distinct research sites. A total of 212 708 participants have enrolled in autism research program studies and 361 researchers have contributed to furthering autism research. The program addresses topics that align with the majority of the Interagency Autism Coordinating Committee’s priority topic areas, including advancements in treatments and interventions, services and supports, and identifying risk factors. Grantee products include 387 peer-reviewed publications, 19 tools, and 13 practice guidelines for improving care and intervention practices. CONCLUSIONS: The autism research program has contributed to medical advances in research, leveraged innovative training platforms to provide specialized training, and provided access to health services through research-based screening and diagnostic procedures. Autism research program studies have contributed to the development of evidence-based practice guidelines, informed policy guidelines, and quality improvement efforts to bolster advancements in the field. Although disparities still exist, the Health Resources and Services Administration’s Maternal and Child Health Bureau can reduce gaps in screening and diagnosis by targeting interventions to underserved populations including minority and rural communities.
Combating COVID-19 with Chloroquine

the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/4.0/), which permits noncommercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com doi:10.1093/jmcb/mjaa015 Journal of Molecular Cell Biology (2020), 12(4), 249–250 | 249 Published online April 1, 2020
Epidemiological Correlations Between Head and Neck Cancer and Hepatitis B Core Antibody Positivity

Background/Aim: Hepatitis B core (HBc) antibody positivity indicates a history of hepatitis B virus (HBV) infection and latent infection. Patients and Methods: We conducted a retrospective case-control study of 512 and 495 head and neck cancer (HNC) and non-HNC patients treated at the Okayama University Hospital, Head and Neck Cancer Center from 2008-2017. Demographic data and risk factors that might affect HNC diagnosis were analyzed to assess their effects. Results: Cancer diagnosis was found to correlate with HBc antibody positivity [odds ratio (OR)=1.50, 95% confidence interval (CI)=1.09-2.08], smoking (OR=3.03, 95%CI=2.16-4.25), and a previous history of cancer (OR=4.12, 95%CI=2.79-6.09). The HBs antigen positivity rate in both groups was very close to that observed in the general Japanese population. The HBc antibody positivity rate was very high only in the HNC group. Conclusion: HBc antibody positivity and HNC are epidemiologically correlated.
Potential Anticancer Effect of Calcium-mediated Src Degradation on Hormone-dependent Breast Cancer

Background/Aim: The antitumor effect of sustained calcium supply on Src degradation was investigated in the context of hormone-dependent breast cancer, followed by elucidation of the underlying mechanisms. Materials and Methods: Hormone-dependent T-47D breast cancer cells were used. Lactate calcium salt (LCS) was used as the source of sustained calcium supply, and the applicable concentration of LCS was determined by the colorimetric MTT assay. LCS-mediated deactivation of downstream signaling via Src degradation was identified by western blot and immunocytochemistry. Results: Calcium-mediated degradation of Src decreased survival signaling via phosphoinositide 3-kinase and protein kinase B and resulted in significant inhibition of the clonogenic ability of hormone-dependent breast cancer cells. Tumor volume was significantly decreased in response to LCS injection in a heterotopic xenograft model, and immuno histochemistry revealed tumor necrosis. Conclusion: Sustained supply of calcium inhibited survival signaling via degradation of Src in hormone-dependent breast cancer cells.