Miracle-dz/UniFAR-FTUs huggingface dataset:
The complete mitochondrial genomes of Opisthoplatia orientalis and Blaptica dubia (Blattodea: Blaberidae)

Abstract The first complete mitochondrial genome in Blaberidae has been reported in this research. Opisthoplatia orientalis (Blaberidae, Epilamprinae) known as ground cockroach with golden edge is distributed in East and South Asia and widely used for thrombolytic therapy in China. Meanwhile, Blaptica dubia (Blaberidae, Blaberinae) has been adopted as feeder insect for various kinds of pets all over the world. In the present study, we investigated the complete mitochondrial genome of O. orientalis and B. dubia, and the mitogenome is 18 724 and 17 340 bp in length, respectively. The circular molecule consists of 13 protein coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a non-coding control region, with an AT content of 75.7% for O. orientalis and 72.8% for B. dubia. A preliminary phylogenetic analysis has been carried out with 11 related species and the status of these two species is further confirmed.
Impact of Preexisting Hepatitis C Virus Genotype 6 NS3, NS5A, and NS5B Polymorphisms on the In Vitro Potency of Direct-Acting Antiviral Agents

HCV genotype 6 (GT-6) is found predominantly in East and Southeast Asia. Clinical studies have focused on patients infected with hepatitis C virus (HCV) GT-6a, where high sustained virologic response (SVR) rates to direct-acting antivirals (DAAs) have been achieved. ABSTRACT HCV genotype 6 (GT-6) is found predominantly in East and Southeast Asia. Clinical studies have focused on patients infected with hepatitis C virus (HCV) GT-6a, where high sustained virologic response (SVR) rates to direct-acting antivirals (DAAs) have been achieved. However, GT-6 is highly diverse, with 29 reported subtypes. We explored the diversity of GT-6 polymorphisms at residues associated with DAA resistance, their impact on DAA in vitro potency when evaluated in a GT-6a consensus replicon, and their association with specific GT-6 subtypes. GT-6 sequences from 25 patient-derived samples and 105 sequences from the U.S. HCV database were compared, and substitutions at resistance-associated residue positions were phenotyped against different DAAs. Preexisting resistance-associated substitutions (RASs) to NS3 protease (A156V and D168E) and NS5B nucleotide (L159F and S282C) inhibitors were rare (<4%). Preexisting RASs to NS5A inhibitors were common, especially at L28 (A/F/G/M/T/V) and R30 (E/N/S). In vitro susceptibilities of NS5A-L28A and -L28T were dramatically reduced against all tested NS5A drugs (90% effective concentration [EC90] range, 119 to 2,032 nM) compared with susceptibilities against a GT-6a consensus replicon (EC90 range, 0.1 to 19 nM). These L28 RASs preexisted in combination with R30S (EC90 [L28A-R30S] of ≥720 nM or EC90 [L28T-R30S] of ≥128 nM against tested DAAs) or as L28T-L31I (EC90 [tested DAAs] of >5,000 nM) and were detected in evaluated GT-6b and -6f sequences. NS5A-L28A-R30A, observed in GT-6r, did not replicate. In conclusion, HCV GT-6b, GT-6f, and GT-6r sequences harbored highly resistant RASs to all evaluated NS5A drugs. Therefore, monitoring SVR in patients infected with these GT-6 subtypes treated with NS5A drug-containing regimens is suggested to confirm any association between noted NS5A polymorphisms and treatment failure.
Genome Sequencing of Cladobotryum protrusum Provides Insights into the Evolution and Pathogenic Mechanisms of the Cobweb Disease Pathogen on Cultivated Mushroom

Cladobotryum protrusum is one of the mycoparasites that cause cobweb disease on cultivated edible mushrooms. However, the molecular mechanisms of evolution and pathogenesis of C. protrusum on mushrooms are largely unknown. Here, we report a high-quality genome sequence of C. protrusum using the single-molecule, real-time sequencing platform of PacBio and perform a comparative analysis with closely related fungi in the family Hypocreaceae. The C. protrusum genome, the first complete genome to be sequenced in the genus Cladobotryum, is 39.09 Mb long, with an N50 of 4.97 Mb, encoding 11,003 proteins. The phylogenomic analysis confirmed its inclusion in Hypocreaceae, with its evolutionary divergence time estimated to be ~170.1 million years ago. The genome encodes a large and diverse set of genes involved in secreted peptidases, carbohydrate-active enzymes, cytochrome P450 enzymes, pathogen–host interactions, mycotoxins, and pigments. Moreover, C. protrusum harbors arrays of genes with the potential to produce bioactive secondary metabolites and stress response-related proteins that are significant for adaptation to hostile environments. Knowledge of the genome will foster a better understanding of the biology of C. protrusum and mycoparasitism in general, as well as help with the development of effective disease control strategies to minimize economic losses from cobweb disease in cultivated edible mushrooms.
Review of Leipzig protocol for intravenous insulin infusion in pediatric patients with type 1 diabetes during intercurrent illness and surgery

Continuous intravenous (IV) insulin infusion therapy minimizes blood glucose (BG) fluctuations and prevents metabolic deterioration in pediatric patients with type 1 diabetes (T1D) during intercurrent illness and surgery. However, data on the adequate fluid and insulin substitution in this situation is rare. We evaluated the effectiveness and safety of IV insulin therapy according to our local protocol.
Neurophysiology of human touch and eye gaze in therapeutic relationships and healing: a scoping review

Objective: The primary objective of this scoping review was to examine and map the range of neurophysiological impacts of human touch and eye gaze, and consider their potential relevance to the therapeutic relationship and to healing. Introduction: Clinicians, and many patients and their relatives, have no doubt as to the efficacy of a positive therapeutic relationship; however, much evidence is based on self-reporting by the patient or observation by the researcher. There has been little formal exploration into what is happening in the body to elicit efficacious reactions in patients. There is, however, a growing body of work on the neurophysiological impact of human interaction. Physical touch and face-to-face interaction are two central elements of this interaction that produce neurophysiological effects on the body. Inclusion criteria: This scoping review considered studies that included cognitively intact human subjects in any setting. This review investigated the neurophysiology of human interaction including touch and eye gaze. It considered studies that have examined, in a variety of settings, the neurophysiological impacts of touch and eye gaze. Quantitative studies were included as the aim was to examine objective measures of neurophysiological changes as a result of human touch and gaze. Methods: An extensive search of multiple databases was undertaken to identify published research in the English language with no date restriction. Data extraction was undertaken using an extraction tool developed specifically for the scoping review objectives. Results: The results of the review are presented in narrative form supported by tables and concept maps. Sixty-four studies were included and the majority were related to touch with various types of massage predominating. Only seven studies investigated gaze with three of these utilizing both touch and gaze. Interventions were delivered by a variety of providers including nurses, significant others and masseuses. The main neurophysiological measures were cortisol, oxytocin and noradrenaline. Conclusions: The aim of this review was to map the neurophysiological impact of human touch and gaze. Although our interest was in studies that might have implications for the therapeutic relationship, we accepted studies that explored phenomena outside of the context of a nurse-patient relationship. This allowed exploration of the boundary of what might be relevant in any therapeutic relationship. Indeed, only a small number of studies included in the review involved clinicians (all nurses) and patients. There was sufficient consistency in trends evident across many studies in regard to the beneficial impact of touch and eye gaze to warrant further investigation in the clinical setting. There is a balance between tightly controlled studies conducted in an artificial (laboratory) setting and/or using artificial stimuli and those of a more pragmatic nature that are contextually closer to the reality of providing nursing care. The latter should be encouraged.
Bioturbation of peanut worms Sipunculus nudus on the composition of prokaryotic communities in a tidal flat as revealed by 16S rRNA gene sequences

To understand the impacts of peanut worms Sipunculus nudus on the prokaryotic community composition in a tidal flat, an onsite investigation was conducted in Suixi in the Beibu Gulf (109.82E, 21.35N) in the burrow sediments, non‐burrow sediments and the sediments without peanut worm disturbance (control). The16S rRNA gene Illumina MiSeq sequencing was used to investigate the microbial communities and their response to bioturbation by S. nudus in a sandy tidal flat. A total of 18 bacteria phyla were detected, and Proteobacteria and Cyanobacteria constituted the majority of the prokaryotic community in the samples. The distribution of the relative abundances of genera showed that approximately 6.99%–17% of the reads in the samples were classified into 25 known genera. Sulfate‐reducing bacteria (Desulfococcus and Desulfosarcina) were the most abundant taxa, followed by Thermodesulfovibrionaceae LCP‐6, indicating that sulfate reduction is the main process in the sandy tidal flat. The abundances of Desulfococcus, LCP‐6 and Cyanobacterium in the non‐burrow sediment were greater than in the burrow sediment, suggesting that the anoxic condition is more suitable for Desulfococcus and LCP‐6 when the activity of S. nudus is absent. The biomass of Cyanobacterium was decreased by the feeding bioturbation of S. nudus. Meanwhile, the relative abundance of the Bacteroidetes Luteimonas in the burrow sediments was significantly greater than in the non‐burrow sediment, and there was a strong relationship between S. nudus bioturbation and increased in oxygen contents and oxidation‐reduction potentials in the burrow sediment. The abundances of Desulfococcus and LCP‐6 were greater in the middle layer (20–30 cm) than in the top layer in the non‐burrow sediment. However, the middle and bottom layers (20–30, 30–40 cm) had higher abundances of these genera than did the upper layers (0–10, 10–20 cm) in the burrow sediments. The abundances of the Fusobacteria Propionigenium and the Spirochaetes Spirochaeta were greater in the middle and bottom layers (20–30 cm, 30–40 cm) than in the top layers (0–10, 10–20 cm) in the burrow sediment, but this phenomenon was not found in the non‐burrow sediment. This study demonstrates that bioturbation by S. nudus plays an important role in reshaping the bacterial community composition in intertidal regions.
Thrombus perviousness is not associated with first-pass revascularization using stent retrievers

Background and purpose Recent studies suggest that thrombus imaging characteristics such as Hounsfield unit (HU) and perviousness assessed on noncontrast computed tomography (NCCT) and CT angiography (CTA) can predict successful recanalization. We assessed whether these thrombus imaging characteristics could predict successful first-pass recanalization. Methods We retrospectively reviewed cases of mechanical thrombectomy over a three-year period in which patients received a multiphase CTA and were treated with a stent retriever on first pass. Thrombus attenuation, thrombus enhancement on arterial- and delayed-phase CTA and percentage washout were calculated and their association with first-pass recanalization, successful recanalization and distal embolic complications was studied. Results Fifty-two mechanical thrombectomy patients were included. First-pass recanalization was achieved in 59.6% and complete revascularization (Thrombolysis in Cerebral Infarction scale 2b/3) was achieved in 84.6%. There was no correlation between first-pass recanalization with thrombus density on NCCT (p = 0.94), percentage enhancement on arterial (p = 0.61) and delayed-phase CTA (p = 0.23) or thrombus length (p = 0.16). There was no correlation between number of passes and either thrombus density on NCCT (p = 0.91) or percentage enhancement on arterial- (p = 0.79) and delayed-phase (p = 0.14) CTA or thrombus length (p = 0.34). Clot length was significantly higher in patients with distal embolic complications than in those without (18.5 ± 7.9 vs 11.4 ± 6.6 mm, p = 0.005). Conclusions Our data suggest that thrombus imaging characteristics on multiphase CTA cannot predict first-pass recanalization or successful revascularization in acute ischemic stroke patients treated with stent retrievers. Longer clot length was associated with higher risk of distal embolic complications.
Chemical Diversity and Biological Activities of Marine Sponges of the Genus Suberea: A Systematic Review

Marine natural products (MNPs) continue to be in the spotlight in the global drug discovery endeavor. Currently, more than 30,000 structurally diverse secondary metabolites from marine sources have been isolated, making MNPs a profound, renewable source to investigate novel drug compounds. Marine sponges of the genus Suberea (family: Aplysinellidae) are recognized as producers of bromotyrosine derivatives, which are considered distinct chemotaxonomic markers for the marine sponges belonging to the order Verongida. This class of compounds exhibits structural diversity, ranging from simple monomeric molecules to more complex molecular scaffolds, displaying a myriad of biological and pharmacological potentialities. In this review, a comprehensive literature survey covering the period of 1998–2018, focusing on the chemistry and biological/pharmacological activities of marine natural products from marine sponges of the genus Suberea, with special attention to the biogenesis of the different skeletons of halogenated compounds, is presented.
Serum albumin‐coated bone allograft (BoneAlbumin) results in faster bone formation and mechanically stronger bone in aging rats

Serum albumin‐coated bone allografts (BoneAlbumin) have successfully supported bone regeneration in various experimental models by activating endogenous progenitors. However, the effect of tissue aging, linked to declining stem cell function, has yet to be explicitly examined within the context of BoneAlbumin's regenerative capacity. Stem cell function was tested with an in vitro attachment assay, which showed that albumin coating increases stem cell attachment on demineralized bone surfaces in an aging cell population. Bone regeneration was investigated in vivo by creating critical size bone defects on the parietal bones of aging female rats. Demineralized bone matrices with and without serum albumin coating were used to fill the defects. Bone regeneration was determined by measuring the density and the size of the remaining bone defect with computed tomography (CT). Microcomputed tomography (MicroCT) and mechanical testing were performed on the parietal bone explants. In vivo CT and ex vivo microCT measurements showed better regeneration with albumin‐coated grafts. Additionally, the albumin‐coated group showed a twofold increase in peak fracture force compared with uncoated allografts. In the present study, serum albumin‐coated demineralized bone matrices successfully supported faster and functionally superior bone regeneration in aging rats. Because stem cell function, a key contributor of bone remodelling, decreases with age and serum albumin is an effective activator of endogenous progenitor cells, this method could be an effective and safe adjuvant in bone regeneration of aging adult and osteo‐compromised populations.
Significant Strain Variation in the Mutation Spectra of Inbred Laboratory Mice

Abstract Mutation provides the ultimate source of all new alleles in populations, including variants that cause disease and fuel adaptation. Recent whole genome sequencing studies have uncovered variation in the mutation rate among individuals and differences in the relative frequency of specific nucleotide changes (the mutation spectrum) between populations. Although parental age is a major driver of differences in overall mutation rate among individuals, the causes of variation in the mutation spectrum remain less well understood. Here, I use high-quality whole genome sequences from 29 inbred laboratory mouse strains to explore the root causes of strain variation in the mutation spectrum. My analysis leverages the unique, mosaic patterns of genetic relatedness among inbred mouse strains to identify strain private variants residing on haplotypes shared between multiple strains due to their recent descent from a common ancestor. I show that these strain-private alleles are strongly enriched for recent de novo mutations and lack signals of widespread purifying selection, suggesting their faithful recapitulation of the spontaneous mutation landscape in single strains. The spectrum of strain-private variants varies significantly among inbred mouse strains reared under standardized laboratory conditions. This variation is not solely explained by strain differences in age at reproduction, raising the possibility that segregating genetic differences affect the constellation of new mutations that arise in a given strain. Collectively, these findings imply the action of remarkably precise nucleotide-specific genetic mechanisms for tuning the de novo mutation landscape in mammals and underscore the genetic complexity of mutation rate control.
Metabolomic approach to key metabolites characterizing postmortem aged loin muscle of Japanese Black (Wagyu) cattle

Objective Meat quality attributes in postmortem muscle tissues depend on skeletal muscle metabolites. The objective of this study was to determine the key metabolic compounds and pathways that are associated with postmortem aging and beef quality in Japanese Black cattle (JB; a Japanese Wagyu breed with highly marbled beef). Methods Lean portions of Longissimus thoracis (LT: loin) muscle in 3 JB steers were collected at 0, 1, and 14 days after slaughter. The metabolomic profiles of the samples were analyzed by capillary electrophoresis time-of-flight mass spectrometry, followed by statistical and multivariate analyses with bioinformatics resources. Results Among the total 171 annotated compounds, the contents of gluconic acid, gluconolactone, spermidine, and the nutritionally vital substances (choline, thiamine, and nicotinamide) were elevated through the course of postmortem aging. The contents of glycolytic compounds increased along with the generation of lactic acid as the beef aging progressed. Moreover, the contents of several dipeptides and 16 amino acids, including glutamate and aromatic and branched-chain amino acids, were elevated over time, suggesting postmortem protein degradation in the muscle. Adenosine triphosphate degradation also progressed, resulting in the generation of inosine, xanthine, and hypoxanthine via the temporal increase in inosine 5′-monophosphate. Cysteine-glutathione disulfide, thiamine, and choline increased over time during the postmortem muscle aging. In the Kyoto encyclopedia of genes and genomes database, a bioinformatics resource, the postmortem metabolomic changes in LT muscle were characterized as pathways mainly related to protein digestion, glycolysis, citric acid cycle, pyruvate metabolism, pentose phosphate metabolism, nicotinamide metabolism, glycerophospholipid metabolism, purine metabolism, and glutathione metabolism. Conclusion The compounds accumulating in aged beef were shown to be nutritionally vital substances and flavor components, as well as potential useful biomarkers of aging. The present metabolomic data during postmortem aging contribute to further understanding of the beef quality of JB and other breeds.
Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer

In highly aggressive malignancies like pancreatic cancer (PC), patient-derived tumor models can serve as disease-relevant models to understand disease-related biology as well as to guide clinical decision-making. In this study, we describe a two-step protocol allowing systematic establishment of patient-derived primary cultures from PC patient tumors. Initial xenotransplantation of surgically resected patient tumors (n = 134) into immunodeficient mice allows for efficient in vivo expansion of vital tumor cells and successful tumor expansion in 38% of patient tumors (51/134). Expansion xenografts closely recapitulate the histoarchitecture of their matching patients’ primary tumors. Digestion of xenograft tumors and subsequent in vitro cultivation resulted in the successful generation of semi-adherent PC cultures of pure epithelial cell origin in 43.1% of the cases. The established primary cultures include diverse pathological types of PC: Pancreatic ductal adenocarcinoma (86.3%, 19/22), adenosquamous carcinoma (9.1%, 2/22) and ductal adenocarcinoma with oncocytic IPMN (4.5%, 1/22). We here provide a protocol to establish quality-controlled PC patient-derived primary cell cultures from heterogeneous PC patient tumors. In vitro preclinical models provide the basis for the identification and preclinical assessment of novel therapeutic opportunities targeting pancreatic cancer.
Long-term efficacy of different procedures for treatment of varicose veins

Background: Various procedures for the treatment of varicose veins have been shown to have long-term effectiveness, but research has yet to identify the most effective procedure. The aim of this study was to investigate the long-term efficacy of different procedures based on Bayesian network meta-analysis and to rank therapeutic options for clinical decision-making. Methods: Globally recognized databases, namely, MEDLINE, Embase, and Cochrane Central, were searched for randomized controlled trials (RCTs). Quantitative pooled estimation of successful treatment rate (STR) and recurrence rate (RR) was performed to assess the long-term efficacy of each procedure with more than a 1-year follow-up. The surface under the cumulative ranking (SUCRA) probabilities of the P values regarding STR and RR were calculated to rank various procedures. Grades of Recommendations Assessment, Development and Evaluation (GRADE) criteria were utilized for the recommendation of evidence from pairwise direct comparisons. Results: A total of 39 RCTs encompassing a total of 6917 limbs were eligible and provided relative raw data. After quantitative analysis, the CHIVA procedure was determined to have the best long-term efficacy, as it had the highest STR (SUCRA, 0.37). Additionally, the results revealed that CHIVA possessed the highest probability of achieving the lowest long-term RR (SUCRA, 0.61). Moreover, the sensitivity analysis with inconsistency approach clarified the reliability of the main results, and the evidence of most direct comparisons was ranked as high or moderate. Conclusion: CHIVA seemed to have superior clinical benefits on long-term efficacy for treating varicose veins. However, the conclusion still needs additional trials for supporting evidence.