Miracle-dz/UniFAR-FTUs huggingface dataset:
Microbial Community Structure and Chemical Constituents in Shinkiku, a Fermented Crude Drug Used in Kampo Medicine

Shinkiku (Massa Medicata Fermentata) is a traditional crude drug used to treat anorexia and dyspepsia of elder patients in east Asia. Shinkiku is generally prepared by the microbial fermentation of wheat and herbs. Shinkiku is also used in Japanese Kampo medicine as a component of 半夏白朮天麻湯 (Hangebyakujutsutemmato). However, the quality of shinkiku varies by manufacture because there are no reference standards to control the quality of medicinal shinkiku. Thus, we aim to characterize the quality of various commercially available shinkiku by chemical and microbial analysis. We collected 13 shinkiku products manufactured in China and Korea and investigated the microbial structure and chemical constituents. Amplicon sequence analysis revealed that Aspergillus sp. was common microorganism in shinkiku products. Digestive enzymes (α-amylase, protease, and lipase), organic acids (ferulic acid, citric acid, lactic acid, and acetic acid), and 39 volatile compounds were commonly found in shinkiku products. Although there were some commonalities in shinkiku products, microbial and chemical characteristic considerably differed as per the manufacturer. Aspergillus sp. was predominant in Korean products, and Korean products showed higher enzyme activities than Chinese products. Meanwhile, Bacillus sp. was commonly detected in Chinese shinkiku, and ferulic acid was higher in Chinese products. Principal component analysis based on the GC-MS peak area of the volatiles also clearly distinguished shinkiku products manufactured in China from those in Korea. Chinese products contained higher amounts of benzaldehyde and anethole than Korean ones. Korean products were further separated into two groups: one with relatively higher linalool and terpinen-4-ol and another with higher hexanoic acid and 1-octen-3-ol. Thus, our study revealed the commonality and diversity of commercial shinkiku products, in which the commonalities can possibly be the reference standard for quality control of shinkiku, and the diversity suggested the importance of microbial management to stabilize the quality of shinkiku.
Appreciating Factors Beyond the Physical in Talent Identification and Development: Insights From the FC Barcelona Sporting Model

FC Barcelona is a multi-sport organization that adopts a talent identification approach that emphasizes the technical, psychological, and perceptual–cognitive attributes. It is unclear within this type of sporting selection model whether the relative age effect (RAE) exists. Consequently, the aim of the study was to evaluate the RAE across multiple sports and age groups at FC Barcelona. The birthdates of all players (n = 6,542) affiliated to each sport [male basketball (n = 1,013), male (n = 3,012) and female (n = 449) soccer, male futsal (n = 761), male handball (n = 999), and male indoor roller hockey (n = 308)] across all age groups from U10 to Senior were recorded. These were then categorized into quartiles from the start of the selection year (Q1 = Jan–Mar; Q2 = Apr–Jun; Q3 = Jul–Sep; Q4 = Oct–Dec) and analyzed for (a) each sport; (b) each age group, irrespective of the sport; and (c) each age group within each sport, using Chi-squared statistics and odds ratios (ORs) with 95% confidence intervals (CIs). Birthdates across the entire club revealed a RAE (Q1 = 46.1%, Q2 = 27.1%, Q3 = 17.1%, and Q4 = 9.7%, χ2 = 29.8, P < 0.01), with OR in Q1, Q2, and Q3 representing a 4.76 (95% CIs: 1.96–11.57), 2.80 (1.12–7.03), and 1.77 (0.67–4.63) increased likelihood for selection when compared to Q4, respectively. Despite FC Barcelona's approach to talent identification and development, the RAE was still present within youth age groups (<18 years old). The current findings provide support that the RAE is more prevalent within regionally popular sports and reduces with increasing age; however, given the talent identification processes within FC Barcelona's sporting model, additional factors beyond the physical attributes, such as enhanced psychological and perceptual–cognitive attributes, in those born earlier in the selection year might further influence the RAE. Consequently, current results provide indirect evidence to suggest that sociological and psychological determinants might be a greater influence on the presence of RAE in sporting environments that prefer to consider technical and perceptual–cognitive attributes in their talent development programs.
Multidimensional Assessment of COVID-19-Related Fears (MAC-RF): A Theory-Based Instrument for the Assessment of Clinically Relevant Fears During Pandemics

In this article, we present the development and psychometric properties of the Multidimensional Assessment of COVID-19--Related Fears (MAC-RF). The MAC-RF is an eight-item, self-report scale that has been developed to assess clinically relevant domains of fear during the COVID-19 pandemic. The MAC-RF is based on a comprehensive theoretical model conceptualizing fears during the pandemics as resulting from an interaction of bodily, interpersonal, cognitive, and behavioral experiences. The MAC-RF was administered to a sample of 623 Italian adults from the community aged between 18 and 76 years old (M= 35.67, SD= 12.93), along with a measure of current clinical symptoms. Item response theory analyses demonstrated that each item of the MAC-RF provided sufficient information about the underlying construct of fear. The statistical fit of the scale was satisfactory. MAC-RF total scores correlated significantly and positively with total scores on the measure of psychopathology and with the clinical symptom domain scores. A ROC (receiver operating characteristic) curve analysis showed that the MAC-RF total score was sufficiently able to identify cases with high levels of current psychopathology, with an area under the curve of.76. These findings suggest that the MAC-RF can be used to assess pathological fear during pandemics. The English, Italian, and French versions of the MAC-RF are annexed to this article for use by clinicians and health services.
Chemotactic Host-Finding Strategies of Plant Endoparasites and Endophytes

Plants interact with microorganisms in the environment during all stages of their development and in most of their organs. These interactions can be either beneficial or detrimental for the plant and may be transient or long-term. In extreme cases, microorganisms become endoparastic or endophytic and permanently reside within a plant, while the host plant undergoes developmental reprogramming and produces new tissues or organs as a response to the invasion. Events at the cellular and molecular level following infection have been extensively described, however the mechanisms of how these microorganisms locate their plant hosts via chemotaxis remain largely unknown. In this review, we summarize recent findings concerning the signalling molecules that regulate chemotaxis of endoparasitic/endophytic bacteria, fungi, and nematodes. In particular, we will focus on the molecules secreted by plants that are most likely to act as guidance cues for microorganisms. These compounds are found in a wide range of plant species and show a variety of secondary effects. Interestingly, these compounds show different attraction potencies depending on the species of the invading organism, suggesting that cues perceived in the soil may be more complex than anticipated. However, what the cognate receptors are for these attractants, as well as the mechanism of how these attractants influence these organisms, remain important outstanding questions. Host-targeting marks the first step of plant—microorganism interactions, therefore understanding the signalling molecules involved in this step plays a key role in understanding these interactions as a whole.
In vitro Anticoccidial Study of Oregano and Garlic Essential Oils and Effects on Growth Performance, Fecal Oocyst Output, and Intestinal Microbiota in vivo

This study investigated the in vitro effects of Greek oregano and garlic essential oils on inhibition of Eimeria parasites and their in vivo effects on production performance, intestinal bacteria counts, and oocyst output. An inhibition assay was performed in vitro using Eimeria tenella Wisconsin strain sporozoites and Madin-Darby bovine kidney (MDBK) cells. Intracellular sporozoite invasion was quantified by detection of E. tenella DNA using qPCR from cell monolayers harvested at 2 and 24 h post-infection. Parasite invasion was inhibited by the oregano essential oil at the concentration of 100 μg/ml by 83 or 93% after 2 or 24 h, respectively. Garlic essential oil reached a maximum inhibition of 70% after 24 h with the 50 μg/ml concentration. Normal morphology was observed in MDBK cells exposed to concentrations of 100 μl/ml of garlic or oregano for over 24 h. In the in vivo trial, 180 male broiler chicks (45.3 ± 0.7 g) were allocated into two treatments (6 pens of 15 chicks per treatment). Control treatment was fed commercial diets without antibiotics or anticoccidials. The ORE–GAR treatment was fed the same control diets, further supplemented with a premix (1 g/kg feed) containing the oregano (50 g/kg premix) and garlic (5 g/kg premix) essential oils. At day 37, all birds were slaughtered under commercial conditions, and intestinal samples were collected. ORE-GAR treatment had improved final body weight (1833.9 vs. 1.685.9 g; p < 0.01), improved feed conversion ratio (1.489 vs. 1.569; p < 0.01), and reduced fecal oocyst excretion (day 28: 3.672 vs. 3.989 log oocysts/g, p < 0.01; day 37: 3.475 vs. 4.007 log oocysts/g, p < 0.001). In the caecal digesta, ORE-GAR treatment had lower total anaerobe counts (8.216 vs. 8.824 CFU/g; p < 0.01), whereas in the jejunum digesta the ORE-GAR treatment had higher counts of E. coli (5.030 vs. 3.530 CFU/g; p = 0.01) and Enterobacteriaceae (5.341 vs. 3.829 CFU/g; p < 0.01), and lower counts of Clostridium perfringens (2.555 vs. 2.882 CFU/g; p < 0.01). In conclusion, the combined supplementation of oregano and garlic essential oils had a potent anticoccidial effect in vitro and a growth-promoting effect in broilers reared in the absence of anticoccidial drugs.
Effect of Imiquimod on Tachyzoites of Toxoplasma gondii and Infected Macrophages in vitro and in BALB/c Mice

Treatment for toxoplasmosis is not completely successful because of their unwanted side effects, and new treatments are needed. Imiquimod has ability to moderate immune response and used to treat a wide variety of infections and tumors. The aim of the present study was to evaluate the effect of imiquimod on the tachyzoites of T. gondii and infected macrophages in vitro and in BALB/c mice. The viability of T. gondii was assessed in the presence of various concentrations of imiquimod by direct counting after 6 and 24 h. The MTT assay was used to identify the viability of uninfected macrophages. The apoptotic effects were determined with flow cytometry on the tachyzoites and infected macrophages. For evaluation of parasite load in pre-treatment or post-treatment of macrophages Quantitative real time PCR (qPCR) was performed. For in vivo experiments, BALB/c mice received imiquimod before and after challenge with parasites. The mortality rate of mice, parasite numbers in spleen, and the INF-γ and IL-4 cytokine levels in spleen lymphocytes were evaluated. Imiquimod demonstrated anti-Toxoplasma effects by reducing the number of tachyzoites. The results of flow cytometry for drug-treated tachyzoites showed that apoptosis did not rise significantly relative to the control group (p < 0.05). Moreover, apoptosis was enhanced in infected macrophages as the concentration of imiquimod was reduced. The parasitic burden in imiquimod pretreated macrophages was significantly lower than those treated after infection (p < 0.01). A marked reduction was observed in survival rate, parasite load and INF-γ level in BALB/c mice that received imiquimod before parasitic challenge relative to those received drug after parasitic challenge (p < 0.01). Overall, imiquimod in the pretreated group had greater anti-Toxoplasma effects than imiquimod in posttreated group in vitro and in vivo. imiquimod may be considered as a candidate for use against Toxoplasmosis both therapeutically and prophylactically.
Editorial: Origins and Domestication of the Grape

Domestication is the most important genetic process of selection driven by humans that transformed wild forms into domesticated crops modifying morphological and genetic traits. The domesticated grapevine (Vitis vinifera L.) belongs together with about another 70 species to the Vitis genus (Wen et al., 2018) and being one of the oldest and extensively cultivated fruit crops is a fascinating subject for evolutionary studies. Archaeological data suggest that domestication of the grapevine began 6,000–8,000 years ago in the Transcaucasian region, between the Black Sea and Iran, from populations of V. vinifera subsp. sylvestris (Zohary and Hopf, 1993). Starting from the primary center of domestication, cultivated varieties were spread by humans through Southern Greece to the Mediterranean region. This pattern of domestication has been recently confirmed by molecular data (Myles et al., 2011; De Lorenzis et al., 2019) even if some authors have proposed local and circumscribed secondary domestication events in other areas (Rivera-Nunez and Walker, 1989; Grassi et al., 2003; Arroyo-Garcia et al., 2006; Terral et al., 2010). During domestication, humans selected for high yield and rapid growth which led to the nonintentional loss of resilience factors. In grapevine, changes in berry size, sugar content and the shift in sexual system from dioecy to self-pollination were essential for domestication. In the light of this, it would be relevant to go back to the wild progenitor, to identify such factors and make them available for resilience breeding. The resilience factors identified can be directly implemented into breeding strategies targeted to prepare European viticulture for the challenges posed by global climate change. Moreover, there are several intriguing unanswered questions regarding where, when, and how domestication took place. Given the difficulty to infer the number of domestication events that could often be conflated with introgression events with local wild populations (Di Vecchi-Staraz et al., 2009; Zecca et al., 2010; Myles et al., 2011; Zhou et al., 2019), adequate genomic studies that involve local cultivar and wild populations are needed to resolve and understand the process of domestication fully. Nuclear DNA markers have been widely applied to explain the genetic relationships between wild and cultivated grape lineages while the hypervariable regions within plastid intergenic spacers have been used to investigate the maternal lineages involved in the domestication process (ArroyoGarcıá et al., 2002; Grassi et al., 2002; Snoussi et al., 2004; Arroyo-Garcia et al., 2006; DeMattia et al., 2008; Cunha et al., 2009; Zecca et al., 2010; Karatas ̧ et al., 2014). Unfortunately, the low number of markers used and the low variability in grapevine plastid genomes greatly limited domestication studies (Zecca et al., 2020). Today, next-generation sequencing technologies are an extraordinary opportunity to access a large amount of genomic information allowing the debate about the origin
Polylogarithms, multiple zeta values and superstring amplitudes

A formalism is provided to calculate tree amplitudes in open superstring theory for any multiplicity at any order in the inverse string tension. We point out that the underlying world‐sheet disk integrals share substantial properties with color‐ordered tree amplitudes in Yang‐Mills field theories. In particular, we closely relate world‐sheet integrands of open‐string tree amplitudes to the Kawai‐Lewellen‐Tye representation of supergravity amplitudes. This correspondence helps to reduce the singular parts of world‐sheet disk integrals – including their string corrections – to lower‐point results. The remaining regular parts are systematically addressed by polylogarithm manipulations.
When Innate Immunity Meets Angiogenesis—The Role of Toll-Like Receptors in Endothelial Cells and Pulmonary Hypertension

Toll-like receptors serve a central role in innate immunity, but they can also modulate cell function in various non-immune cell types including endothelial cells. Endothelial cells are necessary for the organized function of the vascular system, and part of their fundamental role is also the regulation of immune function and inflammation. In this review, we summarize the current knowledge of how Toll-like receptors contribute to the immune and non-immune functions of the endothelial cells.
Evolution of Obligate Siblicide in Boobies. 1. A Test of the Insurance-Egg Hypothesis

Obligate siblicide, the unconditional killing of an individual by its sibling, occurs in a small number of bird species. Although clutches of two eggs are frequently laid, obligate siblicide eliminates the younger hatchling before it reaches the age of independence. The phenomenon presents a challenge to adaptationist evolutionary theory because parents produce chicks that are virtually certain to be killed and because surviving offspring actively sacrifice the inclusive-fitness increment represented by the victim. Dorward's (1962) insurance-egg hypothesis explains the production of a second egg as insurance against the first egg's failure. The insurance-egg hypothesis predicts that, if a second egg sometimes produces a fledgling after a first egg fails, then the evolution of insurance-egg production in single-chick species is governed by the ratio of the benefit of the increased probability of producing a hatchling to the cost of egg production. A field study of the obligately siblicidal masked booby (Sula dactylatra) demonstrated that second eggs contribute a surviving hatchling after the first egg's failure in 19.2% of two-egg clutches. The primary source of hatching failure was exceptionally high infertility or early embryonic death. Not all single-chick booby species produce insurance eggs, however, and the prediction of the insurance-egg hypothesis that the occurrence of insurance eggs is associated with the high benefit-to-cost ratio was supported by a compilation of booby breeding parameters. Because females make similar relative investments in each egg, the cost of insurance eggs is assumed to be constant across species, but benefits differ: hatching success in obligately siblicidal species ranges from 51% to 61%, whereas that in single-egg species is at least 85%.
A New Animal Model for Pathological Subcutaneous Fibrosis: Surgical Technique and in vitro Analysis

Fibrosis is a condition that affects the connective tissue in an organ or tissue in the restorative or responsive phase as a result of injury. The consequences of excessive fibrotic tissue growth may lead to various physiological complications of deformity and impairment due to hypertrophic scars, keloids, and tendon adhesion without understating the psychological impact on the patient. However, no method accurately quantifies the rate and pattern of subcutaneous induced hypertrophic fibrosis. We, therefore, devised a rodent excisional model to evaluate the extent of fibrosis with talc. Tissue specimens were set on formalin, and paraffin sections for histological, immunohistochemical, and molecular analysis talc was used to induce the fibroproliferative mechanism typical of hypertrophic scars. This pathway is relevant to the activation of inflammatory and fibrotic agents to stimulate human hypertrophic scarring. This model reproduces morpho-functional features of human hypertrophic scars to investigate scar formation and assess potential anti-scarring therapies.
Durable Complete Response to Alectinib in a Lung Adenocarcinoma Patient With Brain Metastases and Low-Abundance EML4-ALK Variant in Liquid Biopsy: A Case Report

EML4-ALK fusions are targetable oncogenic drivers in a subset of advanced non-small cell lung cancer (NSCLC) patients that can benefit from selected ALK inhibitors. Precise detection of ALK fusions may yield critical information for selection of appropriate therapy and hence improve patient survival. Analysis of circulating tumor DNA (ctDNA) in liquid biopsies using next generation sequencing (NGS) prior to or during treatment hold great promise for disease monitoring and treatment guidance of various cancers including NSCLC. Herein, we report a case of a 21-year-old advanced lung adenocarcinoma patient with a low abundance (0.03%) of EML4-ALK rearrangement identified in plasma ctDNA upon progression on two lines of chemotherapy that demonstrated long-term complete response to alectinib (>13 months) including metastatic brain tumors. Patient's clinical and pathologic characteristics, computerized tomography (CT) scans and brain magnetic resonance imaging (MRI) were reviewed retrospectively. Taken together, our report not only reinforces the translational utility of NGS-based genomic sequencing of liquid biopsy in guiding clinical practice, but also highlights the superior efficacy of alectinib than chemotherapy in ALK+ NSCLC with brain metastases, albeit at a low variant allele abundance.
Stop hedging your bets: reasons for non-adherence to a tri-modality regimen in the treatment of esophageal cancer in a multidisciplinary setting.

Background In locally-advanced esophageal cancer (LAEC), providers' concerns regarding eventual surgical candidacy can persuade physicians to defer to definitive doses of 50 Gy or higher preoperatively. We report the successful completion rate of tri-modality therapy (TMT) (documented at the outset) and reasons for TMT non-adherence at a large multi-disciplinary esophageal program. Methods LAEC patients diagnosed 2007-2016 from a prospective institutional database were subdivided into CRT/S+ [completed chemoradiation (CRT) and surgery] and CRT/S- (CRT and no subsequent surgery) groups. Chart review provided surgery non-adherence reasons. Results A total of 283 patients met planned TMT criteria: 164 (58.0%) patients received 50 or 50.4 Gy CRT, 27 patients (9.5%) received greater than 50.4 Gy, and 92 patients received less than 50 Gy (32.5%, only 8 patients received CRT to 41.4 Gy); 221 (78.1%) completed surgery (CRT/S+), while 62 (21.9%) failed to advance to surgery (CRT/S-): 25 of 62 CRT/S- patients (40.3%) evidenced metastatic progression before surgery, 4 (6.5%) were deemed unresectable intraoperatively, 4 (6.5%) expired prior to planned surgery (3 from unknown causes, 1 suicide), 8 (12.9%) experienced significant CRT-related medical decompensation and were withdrawn from surgical consideration, 16 (25.8%) voluntarily declined surgery post-CRT (largely due to long-term quality of life concerns), and 5 (8.1%) failed to advance for unknown reasons. Four of the 16 patients who voluntarily declined surgery after CRT received less than 50 Gy. The 22.2% of CRT/S+ patients achieved pathologic complete response (21.6% for adenocarcinoma and 29.0% for squamous cell carcinoma). Conclusions Our institution's 78% surgery completion rate among TMT-indicated patients highlights the benefits of upfront multidisciplinary care. Metastatic disease development most commonly truncated TMT with a low rate failing due to medical decompensation. Given the number of patients who voluntarily declined surgery following CRT, TMT counseling and involvement of a patient advocate are paramount prior to treatment planning.