Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogenetic Reclassification of Vertebrate Melatonin Receptors To Include Mel1d

The circadian and seasonal actions of melatonin are mediated by high affinity G-protein coupled receptors (melatonin receptors, MTRs), classified into phylogenetically distinct subtypes based on sequence divergence and pharmacological characteristics. Three vertebrate MTR subtypes are currently described: MT1 (MTNR1A), MT2 (MTNR1B), and Mel1c (MTNR1C / GPR50), which exhibit distinct affinities, tissue distributions and signaling properties. We present phylogenetic and comparative genomic analyses supporting a revised classification of the vertebrate MTR family. We demonstrate four ancestral vertebrate MTRs, including a novel molecule hereafter named Mel1d. We reconstructed the evolution of each vertebrate MTR, detailing genetic losses in addition to gains resulting from whole genome duplication events in teleost fishes. We show that Mel1d was lost separately in mammals and birds and has been previously mistaken for an MT1 paralogue. The genetic and functional diversity of vertebrate MTRs is more complex than appreciated, with implications for our understanding of melatonin actions in different taxa. The significance of our findings, including the existence of Mel1d, are discussed in an evolutionary and functional context accommodating a robust phylogenetic assignment of MTR gene family structure.
The Nuclear Localization of the DnaJ-Like Zinc Finger Domain-Containing Protein EDA3 Affects Seed Development in Arabidopsis thaliana

The DnaJ-like zinc finger domain-containing proteins are involved in different aspects of plastid function and development. Some of these proteins were recently reported to have dual subcellular localization in the nucleus and plastids. One member of this family, PSA2 (AT2G34860), was found to localize to the thylakoid lumen and regulate the assembly of photosystem I (PSI). However, PSA2 was also annotated as Embryo sac Development Arrest 3 (EDA3) from the observation that its embryo sac development was arrested at the two-nuclear stage. In this study, we characterized the eda3 mutant, and demonstrated that, as compared with the wild-type (WT) plants, the mutant has shorter siliques, fewer siliques per plant, and fewer seeds per silique. Both aborted and undeveloped ovules were observed in siliques of the mutant. By immunoblot analysis, we found that, different from the chloroplast localization in mature leaves, EDA3 localizes in the nucleus in seeds. A nuclear localization signal was identified from the deduced amino acid sequence of EDA3, and also proved to be sufficient for directing its fusion peptide into the nucleus.
One-Year Effects of Omega-3 Treatment on Fatty Acids, Oxylipins, and Related Bioactive Lipids and Their Associations with Clinical Lipid and Inflammatory Biomarkers: Findings from a Substudy of the Vitamin D and Omega-3 Trial (VITAL)

Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL). VITAL is a randomized double-blind trial of 840 mg/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) vs. placebo among 25,871 individuals. Small polar bioactive lipid features, oxylipins and FAs from plasma and red blood cells were measured using three independent assaying techniques at baseline and one year. The Women’s Health Study (WHS) was used for replication with dietary n-3 intake. Randomized n-3 treatment led to changes in 143 FAs, oxylipins and bioactive lipids (False Discovery Rate (FDR) < 0.05 in VITAL200, validated (p-values < 0.05)) in WHS with increases in 95 including EPA, DHA, n-3 docosapentaenoic acid (DPA-n3), and decreases in 48 including DPA-n6, dihomo gamma linolenic (DGLA), adrenic and arachidonic acids. N-3 related changes in the bioactive lipidome were heterogeneously associated with changes in clinical lipid and inflammatory biomarkers. N-3 treatment significantly modulates the bioactive lipidome, which may contribute to its clinical benefits.
Cat fleas in flux: Rampant gene duplication, genome size plasticity, and paradoxical Wolbachia infection

Background: Fleas (Insecta: Siphonaptera) are small flightless parasites of birds and mammals; their blood-feeding can transmit many serious pathogens (i.e. the etiological agents of bubonic plague, endemic and murine typhus). The lack of flea genome assemblies has hindered research, especially comparisons to other disease vectors. Accordingly, we sequenced the genome of the cat flea, Ctenocephalides felis, an insect with substantial human health and veterinary importance across the globe. Results: By combining Illumina and PacBio sequencing with Hi-C scaffolding techniques, we generated a chromosome-level genome assembly for C. felis. Unexpectedly, our assembly revealed extensive gene duplication across the entire genome, exemplified by ~38% of protein-coding genes with two or more copies and over 4,000 tRNA genes. A broad range of genome size determinations (433-551 Mb) for individual fleas sampled across different populations supports the widespread presence of fluctuating copy number variation (CNV) in C. felis. Similarly broad genome sizes were also calculated for individuals of Xenopsylla cheopis (Oriental rat flea), indicating that this remarkable "genome-in-flux" phenomenon could be a siphonapteran-wide trait. Nevertheless, cat flea genomes have not experienced substantial inflation due to rampant CNV, nor do we find a significant reduction in gene families as has been described for other parasites. Quizzically, individual fleas were found to be co-infected with parasitic and symbiotic Wolbachia, both of which are novel strains unique to C. felis. Conclusion: Rampant CNV in C. felis has dire implications for gene-targeting pest control measures and stands to complicate standard normalization procedures utilized in comparative transcriptomics analysis. Coupled with paradoxical co-infection with novel Wolbachia endosymbionts, which are potential tools for blocking pathogen transmission, these oddities highlight a unique and underappreciated human disease vector.
Successful Treatment of Psychiatric Symptoms after Traumatic Brain Injury Using Deep Brain Stimulation to the Anterior Limb of Internal Capsule-Nucleus Accumbens

Psychiatric symptoms are common after traumatic brain injury (TBI), and some patients have poor drug therapeutic efficacy. We report a successfully treated case of psychiatric symptoms after TBI using deep brain stimulation (DBS) to the anterior limb of internal capsule (ALIC)-nucleus accumbens (NAc) in a 76-year-old woman. The patient suffered from auditory hallucination, mood changes, and insomnia caused by TBI. Psychological test assessment showed the scores of Hamilton Anxiety Scale, Hamilton Depression Scale and Positive and Negative Syndrome Scale were 30, 35, and 96 respectively. Head magnetic resonance imaging scan showed right temporal lobe encephalomalacia. Head magnetic resonance spectroscopy (MRS) showed bilateral basal ganglia choline increased relatively. After DBS to the ALIC-NAc, the target parameters were adjusted. The psychiatric symptoms were completely improved and the result of head MRS was normal in the end. The current report declares that DBS is reversible, adjustable and safe in the treatment of psychiatric symptoms caused by TBI. DBS to the ALIC-NAc should be considered as a possible treatment choice once a patient showed psychiatric symptoms after TBI.
An improved sequential auction with complementarity for pricing the construction land quota

The paradox between idle homesteads in rural areas and the shortage of construction land in urban areas is concerning. Hence, local governments encourage farmers to reclaim their idle homesteads and farmlands to generate quota. However, the current quota price, which is based on the land reclamation cost, is often inadequate to motivate farmers. This study proposed that the construction land quota and construction land are complementary items, and hence, their pricing should be studied simultaneously instead of independently. Therefore, the classical sequential auction model with complementarity was improved using the core characteristics of quota transactions and those were applied to design optimal pricing mechanisms. Subsequently, the influence of relevant factors on the bidding price was analysed. The results indicated that the bidding price decreases with an increase in the number of bidders and that a bidder’s revenue is at a loss when they acquire the quota but fail to obtain the land; hence, the revenue probability is lost. However, bidding prices increase when the fine of delaying construction increases. To raise the quota price and encourage relatively more farmers to reclaim their idle homesteads, local governments should appropriately increase the delaying construction fines or repurchase the quota at a premium from the bidder who acquires the quota but fails to obtain the land, which is beneficial for easing conflict between construction land demands and farmland protection and for promoting the sustainable development of China’s social economy.
Interrater Reliability in the Measurement of Flow Characteristics on Color-Coded Quantitative DSA of Brain AVMs

BACKGROUND AND PURPOSE: Hemodynamic features of brain AVMs may portend increased hemorrhage risk. Previous studies have suggested that MTT is shorter in ruptured AVMs as assessed on quantitative color-coded parametric DSA. This study assesses the interrater reliability of MTT measurements obtained using quantitative color-coded DSA. MATERIALS AND METHODS: Thirty-five color-coded parametric DSA images of 34 brain AVMs were analyzed by 4 neuroradiologists with experience in interventional neuroradiology. Hemodynamic features assessed included MTT of the AVM and TTP of the dominant feeding artery and draining vein. Agreement among the 4 raters was assessed using the intraclass correlation coefficient. RESULTS: The interrater reliability among the 4 raters was poor (intraclass correlation coefficient = 0.218; 95% CI, 0.062–0.414; P value = .002) as it related to MTT assessment. When the analysis was limited to cases in which the raters selected the same image to analyze and selected the same primary feeding artery and the same primary draining vein, interrater reliability improved to fair (intraclass correlation coefficient = 0.564; 95% CI, 0.367–0.717; P < .001). CONCLUSIONS: Interrater reliability in deriving color-coded parametric DSA measurements such as MTT is poor so minor differences among raters may result in a large variance in MTT and TTP results, partly due to the sensitivity and 2D nature of the technique. Reliability can be improved by defining a standard projection, feeding artery, and draining vein for analysis.
Virulence mismatches in index hosts shape the outcomes of cross-species transmission

Significance Emerging disease epidemics often result from a pathogen establishing transmission in a novel host species. However, for reasons that remain poorly understood, most cross-species transmissions fail to establish in the newly infected species. Examining experimental cross-species inoculations of rabies virus, we show that host and viral factors predict differences in disease progression in ways that are expected to impact the likelihood of onward transmission. Disease progression was accelerated and virus excretion decreased when the reservoir and novel host were physiologically or genetically more dissimilar. These insights may help to explain and predict host shifts in rabies and other zoonotic viruses and highlight meta-analyses of experimental inoculation data as a powerful and generalizable approach for understanding the dynamics of index infections. Whether a pathogen entering a new host species results in a single infection or in onward transmission, and potentially an outbreak, depends upon the progression of infection in the index case. Although index infections are rarely observable in nature, experimental inoculations of pathogens into novel host species provide a rich and largely unexploited data source for meta-analyses to identify the host and pathogen determinants of variability in infection outcomes. We analyzed the progressions of 514 experimental cross-species inoculations of rabies virus, a widespread zoonosis which in nature exhibits both dead-end infections and varying levels of sustained transmission in novel hosts. Inoculations originating from bats rather than carnivores, and from warmer- to cooler-bodied species caused infections with shorter incubation periods that were associated with diminished virus excretion. Inoculations between distantly related hosts tended to result in shorter clinical disease periods, which are also expected to impede onward transmission. All effects were modulated by infection dose. Taken together, these results suggest that as host species become more dissimilar, increased virulence might act as a limiting factor preventing onward transmission. These results can explain observed constraints on rabies virus host shifts, describe a previously unrecognized role of host body temperature, and provide a potential explanation for host shifts being less likely between genetically distant species. More generally, our study highlights meta-analyses of experimental infections as a tractable approach to quantify the complex interactions between virus, reservoir, and novel host that shape the outcome of cross-species transmission.
Association between C‐reactive protein and polypoidal choroidal vasculopathy: a systematic review and meta‐analysis

Aetiological processes of polypoidal choroidal vasculopathy (PCV) remains poorly understood, but several studies indicate that immunity may play a role and report elevated levels of systemic C‐reactive protein (CRP). In this systematic review and meta‐analysis, we summarize available evidence in the field. We searched the databases PubMed/MEDLINE, EMBASE, Web of Science and the Cochrane Central on 19 March 2020. Two independent authors reviewed the studies and extracted data. Two independent authors reviewed the studies, extracted data and evaluated risk of bias within individual studies. Studies were reviewed in the text qualitatively and measures of association were included for quantitative analyses. Results from univariate analyses and multivariate‐adjusted analyses were included for separate meta‐analyses to evaluate whether the association was only due to factors associated with PCV. Four studies (246 patients with PCV and 2861 control individuals) were identified and included for a qualitative and quantitative analysis. Increased CRP was associated with PCV when pooling both univariate measures (OR 3.54, 95% CI: 2.13–5.89, p < 0.0001) and multivariate‐adjusted measures (OR 3.05, 95% CI: 1.56–5.98, p = 0.0011). Sensitivity analyses confirmed robustness of the results. Increased CRP is associated to PCV, even after adjusting for demographics, lifestyle factors and co‐morbidities. Clinical value of CRP in relation to PCV remains unclear, but the association gives much needed insight into the aetiology of a poorly understood disease.
A CRISPR-Cas9 screen identifies mitochondrial translation as an essential process in latent KSHV infection of human endothelial cells

Significance Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, one of the most common neoplasms in sub-Saharan Africa. There is no direct treatment for the latent state of the virus in tumors. Therefore, we sought to identify host cell targets essential to support proliferation and survival of cells latently infected with KSHV. A genome-wide CRISPR-Cas9 knockout screen to test the requirement of all human genes during KSHV latency identified host factors involved in mitochondrial translation as necessary for proliferation of latently infected endothelial cells. Antibiotics targeting bacterial ribosomes are able to selectively inhibit the proliferation of KSHV latently infected cells. Our findings provide insights into the essential function of mitochondria during latent KSHV infection. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL). The main proliferating component of KS tumors is a cell of endothelial origin termed the spindle cell. Spindle cells are predominantly latently infected with only a small percentage of cells undergoing viral replication. As there is no direct treatment for latent KSHV, identification of host vulnerabilities in latently infected endothelial cells could be exploited to inhibit KSHV-associated tumor cells. Using a pooled CRISPR-Cas9 lentivirus library, we identified host factors that are essential for the survival or proliferation of latently infected endothelial cells in culture, but not their uninfected counterparts. Among the many host genes identified, there was an enrichment in genes localizing to the mitochondria, including genes involved in mitochondrial translation. Antibiotics that inhibit bacterial and mitochondrial translation specifically inhibited the expansion of latently infected endothelial cells and led to increased cell death in patient-derived PEL cell lines. Direct inhibition of mitochondrial respiration or ablation of mitochondrial genomes leads to increased death in latently infected cells. KSHV latent infection decreases mitochondrial numbers, but there are increases in mitochondrial size, genome copy number, and transcript levels. We found that multiple gene products of the latent locus localize to the mitochondria. During latent infection, KSHV significantly alters mitochondrial biology, leading to enhanced sensitivity to inhibition of mitochondrial respiration, which provides a potential therapeutic avenue for KSHV-associated cancers.
Tracing gestation and lactation in free ranging gray whales using the stable isotopic composition of epidermis layers

The isotopic composition of baleen whales’ epidermis structural layers can give information about dietary change over time. This study investigated if epidermis layers integrated isotopic values that record physiological changes from gestation to lactation. Epidermis tissues (n = 43) were collected from free ranging lactating female gray whale and calves during the beginning of three breeding seasons. Modelling of δ13C and δ15N values show intra- and inter-individual differences based on epidermal layers, age class and year of sampling. The isotopic composition of mother-calf pairs is correlated, and the estimates of the maximum mother-to-calf isotopic difference was ~1.4‰ for δ13C and between 1 and 1.5‰ for δ15N values. Change in δ15N values among epidermal layers in calves was associated with the transition from fetus to consumption of maternal milk. It is here proposed when lactation influences calf epidermis, δ15N values decrease consistently from the outermost to the innermost layer. However, if a calf was born only few days before collection, epidermis integrates more variable δ15N patterns because gestation still affects the isotopic composition of the layers. The possibility of calculating mother-to-calf nitrogen isotope fractionation, and the regularity of changes between calf layer δ15N values, allowed results of an isotopic clock model to predict the age of each calf when sampled with its mother. This model has the potential to be a straightforward method to estimate the beginning of lactation, therefore calf birth date when direct observations are not feasible. The non-lethal remote collection of epidermis appears to be an effective tool for the study of the physiology of reproduction of baleen whales. The parallel study of the three epidermal structural layers highlighted the importance of considering the unique mother-calf pair physiological status at the time of sampling time when stable isotope results are interpreted.
Use of Cardiac Point-of-Care Ultrasound in the Pediatric Emergency Department

Supplemental digital content is available in the text. Objectives We sought to describe the test characteristics of cardiac point-of-care ultrasound (POCUS) performed by pediatric emergency medicine (PEM) physicians after structured cardiac POCUS training. Methods We evaluated the use of clinically indicated cardiac POCUS by PEM physicians in a single tertiary care pediatric emergency department after implementation of a focused cardiac POCUS training curriculum. The test characteristics of the sonologist interpretation were compared with expert POCUS review, by PEM physicians who have completed PEM POCUS fellowship training, for the assessment of both pericardial effusion and left ventricular systolic dysfunction. Results A total of 1241 cardiac POCUS examinations were performed between July 2015 and December 2017, of which 456 were clinically indicated and underwent expert POCUS review and comprised the study sample. These examinations were performed by 33 different PEM attending sonologists. Chest pain (52%), dyspnea (20%), and tachycardia (18%) were the most common indications for cardiac POCUS. Prevalence of pericardial effusion and global systolic dysfunction based on expert POCUS review were 11% (48/443) and 4% (16/435), respectively. Real-time cardiac POCUS interpretation had a sensitivity and specificity of 100% and 99.5%, respectively, for both pericardial effusion and left ventricular systolic dysfunction when compared with expert POCUS review. Conclusions Cardiac POCUS is both sensitive and specific for identifying pericardial effusion and left ventricular systolic dysfunction when performed by PEM attendings with focused training.
Long term outcomes for elderly patients after emergency intensive care admission: A cohort study

Background Elderly patients (≥ 80 years of age) surviving an episode of critical illness suffer long-term morbidity and risk of mortality. Identifying high risk groups could assist in informing discussions with patients and families. Aim To determine factors associated with long-term survival following ICU admission. Design A cohort study of patients aged ≥ 80 years of age admitted to the ICU as an emergency. Methods Patients admitted from January 2010 to December 2018 were included in the study. Primary outcome was five year survival. Mortality was assessed using a multivariable flexible parametric survival analysis adjusted for demographics, and clinically relevant covariates. Results There were 828 patients. Mean age was 84 years (SD 3.2) and 419 (51%) were male. Patients were categorised into medical (423 (51%)) and surgical (405 (49%)) admissions. Adjusted hazard ratios (aHR) for mortality were highest for serum lactate (>8 mmol/l aHR 2.56 (C.I. 1.79–3.67)), lowest systolic blood pressure (< 70 mmHg aHR 2.04 (C.I. 1.36–3.05)) and pH (< 7.05 aHR 4.70 (C.I 2.67–8.21)). There were no survivors beyond one year with severe abnormalities of pH and lactate (< 7.05 and > 8 mmol/l respectively). Relative survival for medical patients was below that expected for the general population for the duration of the study. Conclusion Overall five-year survival was 27%. For medical and surgical patients it was 19% and 35% respectively. Survival at 30 days and one year was 61% and 46%. The presence of features of circulatory shock predicted poor short and long term survival.
Guidelines for the management of ocular trauma during the COVID-19 pandemic

As the COVID-19 pandemic rages on, India is recording a very high number of new cases daily; even as the country prepares to gradually “unlock”, after months of lockdown. While elective eye surgeries such as uncomplicated cataract surgeries, blepharoplasty and eyelid procedures and refractive surgeries can be planned at a later date; emergency cases pertaining to ocular trauma cannot be deferred. This manuscript gives a brief overview of the general guidelines for the management of ocular trauma during the COVID-19 pandemic.