Miracle-dz/UniFAR-FTUs huggingface dataset:
Invasive Infection With emm3/ST15 Streptococcus pyogenes: The First Case Report From China and Complete Genome Analysis

Streptococcus pyogenes (GAS) may cause severe invasive disease with a high fatality rate, especially M3-type strains, which are less common in China. Here, we report the first emm3/ST15 invasive GAS infection case in China. The patient was diagnosed with severe skin and soft tissue infection (SSTI) and septicaemia caused by one GAS strain. Antibiotic susceptibility tests showed that the isolate was susceptible to all tested drugs. Antimicrobial therapy was then applied, and the patient fully recovered and was discharged from the hospital on Day 43. Whole-genome sequencing was carried out using the Illumina and Oxford Nanopore platforms and revealed this to be the first emm3/ST15-type GAS invasive infection in China. The closely related emm3/ST15-type GAS strains are MGAS315 from the United States and M3-b from Japan. Our finding is a warning that we should pay attention to invasive M3-type GAS infections in China and indicates the global spread of the highly virulent emm3/ST15 GAS strain.
Infant-Directed Speech From a Multidimensional Perspective: The Interplay of Infant Birth Status, Maternal Parenting Stress, and Dyadic Co-regulation on Infant-Directed Speech Linguistic and Pragmatic Features

Infant-directed speech (IDS), the particular form of spontaneous language observed in interactions between parents and their infants, is a crucial aspect of the mother-infant interaction and an index of the attunement of maternal linguistic input to her infant communicative abilities and needs during dyadic interactions. The present study aimed to explore linguistic and pragmatic features of IDS during mother-infant interactions at 3-month of infant age. The effects of infant (birth status: preterm vs. full-term birth), maternal (perceived parenting stress) and dyadic (dyadic co-regulation) factors on IDS were explored. Results evidenced few differences between the groups on IDS linguistic characteristics. Moreover, observing the interaction of birth status and dyadic co-regulation, full-term mothers varied their IDS pragmatic features according to the quality of co-regulation while preterm mothers did not. Parenting stress was associated to specific linguistic IDS features independently from the birth status. Findings are discussed underling implications for the study of preterm dyads interactions and the importance to consider the interplay of several factors in affecting the quality of IDS.
Plasticity of NK cells in Cancer

Natural killer (NK) cells are crucial to various facets of human immunity and function through direct cytotoxicity or via orchestration of the broader immune response. NK cells exist across a wide range of functional and phenotypic identities. Murine and human studies have revealed that NK cells possess substantial plasticity and can alter their function and phenotype in response to external signals. NK cells also play a critical role in tumor immunity and form the basis for many emerging immunotherapeutic approaches. NK cells can directly target and lyse malignant cells with their inherent cytotoxic capabilities. In addition to direct targeting of malignant cells, certain subsets of NK cells can mediate antibody-dependent cellular cytotoxicity (ADCC) which is integral to some forms of immune checkpoint-blockade immunotherapy. Another important feature of various NK cell subsets is to co-ordinate anti-tumor immune responses by recruiting adaptive and innate leukocytes. However, given the diverse range of NK cell identities it is unsurprising that both pro-tumoral and anti-tumoral NK cell subsets have been described. Here, NK cell subsets have been shown to promote angiogenesis, drive inflammation and immune evasion in the tumor microenvironment. To date, the signals that drive tumor-infiltrating NK cells towards the acquisition of a pro- or anti-tumoral function are poorly understood. The notion of tumor microenvironment-driven NK cell plasticity has substantial implications for the development of NK-based immunotherapeutics. This review will highlight the current knowledge of NK cell plasticity pertaining to the tumor microenvironment. Additionally, this review will pose critical and relevant questions that need to be addressed by the field in coming years.
High Prevalence of Nutritional Risk Among Pulmonary Patients Living on the Tibetan Plateau

Background Nutritional risk is associated with adverse clinical outcomes and is more prevalent among pulmonology patients than among patients in other departments. High-altitude environments can affect patients with chronic respiratory diseases, but evidence of the prevalence of nutritional risk among hospitalized patients with respiratory diseases in high-altitude areas is limited. This study aimed to investigate the nutritional risk and status of inpatients with different major respiratory diagnoses permanently living on the Tibetan Plateau (≥3,000 m above sea level). Methods In this cross-sectional study, we consecutively recruited inpatients admitted to the Department of Respiratory and Critical Care Medicine at the Tibet Autonomous Region People's Hospital of Lhasa between November 2020 and May 2021. We used the Nutrition Risk Screening (NRS) 2002 tool to assess nutritional risk among these patients. An NRS 2002 score ≥3 points indicates nutritional risk; a score ≥5 indicates high nutritional risk. According to NRS-2002 scores, patients were divided into three groups (NRS-2002 0–2, 3–4, and ≥5). The differences in age, sex, major respiratory diagnoses, comorbidities, body mass index, and laboratory findings among the groups were analyzed. Results A total of 289 eligible Tibetan patients were enrolled in the study, and 46.1% (133/246) of them were at nutritional risk (NRS-2002 score ≥3). Twenty-one (7.3%) patients were at high nutritional risk (NRS-2002 score ≥5). The proportions of patients at nutritional risk were relatively high among patients with lung cancer (58.8%), interstitial lung disease (58.3%), pulmonary embolism (52.9%), and tuberculosis (50.0%). Laboratory findings showed that patients with NRS-2002 scores of 3–4 and ≥5 had lower red blood cell counts, serum albumin and hemoglobin levels, and higher C-reactive protein (CRP) levels than those with NRS-2002 scores < 3. Conclusion The prevalence of nutritional risk was high among pulmonology department inpatients permanently living on the Tibetan Plateau. Patients with lung cancer, interstitial lung disease, pulmonary embolism or tuberculosis were more likely to have nutritional risk than patients with other diagnoses. The nutritional risk of inpatients in the respiratory department in the plateau area should not be ignored, and patients at high nutritional risk should receive timely intervention.
Advancing the Understanding of Acupoint Sensitization and Plasticity Through Cutaneous C-Nociceptors

Acupoint is the key area for needling treatment, but its physiology is not yet understood. Nociceptors, one of the responders in acupoints, are responsible for acupuncture manipulation and delivering acupuncture signals to the spinal or supraspinal level. Recent evidence has shown that various diseases led to sensory hypersensitivity and functional plasticity in sensitized acupoints, namely, acupoint sensitization. Neurogenic inflammation is the predominant pathological characteristic for sensitized acupoints; however, the underlying mechanism in acupoint sensitization remains unclear. Recent studies have reported that silent C-nociceptors (SNs), a subtype of C nociceptors, can be “awakened” by inflammatory substances released by sensory terminals and immune cells under tissue injury or visceral dysfunction. SNs can transform from mechano-insensitive nociceptors in a healthy state to mechanosensitive nociceptors. Activated SNs play a vital role in sensory and pain modulation and can amplify sensory inputs from the injured tissue and then mediate sensory hyperalgesia. Whether activated SNs is involved in the mechanism of acupoint sensitization and contributes to the delivery of mechanical signals from needling manipulation remains unclear? In this review, we discuss the known functions of cutaneous C nociceptors and SNs and focus on recent studies highlighting the role of activated SNs in acupoint functional plasticity.
The Association of Body Mass Index With Mortality Among Pulmonary Hypertension Patients: A Systematic Review and Meta-Analysis of Cohort Studies

Objective To run a systematic review and meta-analysis of related studies on body mass index (BMI) and the risk of death among pulmonary hypertension (PH) patients, as well as, to shed light on the shape and strength of the dose-response association. Methods Studies published up to Jun 2021 in scientific databases such as Scopus, and PubMed as well as Google Scholar were searched. Cohort studies that reported risk estimates for at least two categories of BMI or per certain increase in BMI in relation to mortality in PH patients were included. Summary relative risks were determined with random effects models. Non-linear relationship was discovered with dose-response analysis. Results All in all, 15 cohort studies were selected. The number of participants was 127,215 out of which 73,999 were reported dead. The summary RR for mortality per a 5-unit increment in BMI was 0.83 (95% confidence interval 0.77–0.89; I2 = 75.6%, n = 9) among PH patients. There was a non-linear dose-response relation between BMI and mortality in PH patients (Pnon−linearity < 0.001), with the lowest risk being at BMI 32–38 kg/m2. Conclusion Higher BMI is related to decreased risk of mortality among PH patients and the lowest point of the curve was seen at BMI 32–38.
Filling Defect of Ipsilateral Transverse Sinus in Acute Large Artery Occlusion

Background and Purpose Cerebral venous systems play a key role in regulating stroke outcomes. We aimed to elucidate the effect of the transverse sinus (TS) filling patterns on edema expansion and neurological outcomes in patients with acute large artery occlusion (LAO). Materials and Methods We recruited consecutive patients with acute M1 middle cerebral artery and/or internal carotid artery occlusion who underwent pretreatment computed tomographic perfusion (CTP). On the reconstructed 4-dimensional computed tomographic angiography derived from CTP, the filling defect of the ipsilateral transverse sinus (FDITS) was defined as the length of contrast filling defect occupying at least half of the ipsilateral TS. An unfavorable outcome was defined as having a modified Rankin Scale (mRS) score of 3–6 at 3 months. Results A total of 318 patients were enrolled in the final analysis and 70 (22.0%) patients had baseline FDITS. The presence of FDITS was associated with the baseline NIHSS (odds ratio [OR] 1.119; 95% CI, 1.051–1.192; p < 0.001) and poor arterial collaterals (OR 3.665; 95% CI 1.730–7.766; p = 0.001). In addition, FDITS was associated with 24-h brain edema expansion (OR 7.188; 95% CI, 3.095–16.696; p < 0.001) and 3-month unfavorable outcome (OR 8.143; 95% CI 2.547–26.041; p < 0.001) independent of arterial collateral status. In the subgroup analysis of patients with FDITS who received reperfusion therapy, no significant difference was found in the rate of edema expansion and unfavorable outcome between non-reperfusion and reperfusion subgroups (both p > 0.05). Conclusion Filling defect of the ipsilateral transverse sinus was associated with edema expansion and an unfavorable outcome irrespective of the baseline arterial collateral status in patients with acute LAO, indicating that FDITS may be an important stroke-related prognostic imaging marker.
Open Innovation and Team Leaders’ Innovation Traits

Abstract Open innovation has transformed internal novel resource allocation and facilitated diverse interorganizational cooperation models. Previous studies have investigated open innovation archetypes and their formation. However, most researchers have neglected the crucial role that team leaders play in integrating internal and external resources and connecting creative ideas in open innovation. This study investigated the influence of open innovation archetypes and team leaders’ innovation traits on team performance. On the basis of the literature review, the analytical hierarchy process was applied to construct a framework for assessing and selecting team leaders in open innovation. The analysis was completed based on samples from 45 valid respondents (88% return rate) in Taiwan’s high-tech industry. The study results suggested that innovation knowledge is the most crucial innovation criterion for a leader, particularly core knowledge and advanced knowledge. Among the various sub-criteria, extrinsic motivation was the second most important sub-criterion. Leaders with strong innovation motivations are suitable to lead inbound open innovation projects.
Gut Microbiota Dysbiosis Induced by Decreasing Endogenous Melatonin Mediates the Pathogenesis of Alzheimer’s Disease and Obesity

Lifestyle choices, external environment, aging, and other factors influence the synthesis of melatonin. Although the physiological functions of melatonin have been widely studied in relation to specific organs, the systemic effects of endogenous melatonin reduction has not been reported. This study evaluates the systemic changes and possible pathogenic risks in an endogenous melatonin reduction (EMR) mouse model deficient in the rate limiting enzyme in melatonin production, arylalkylamine N-acetyltransferase (Aanat) gene. Using this model, we identified a new relationship between melatonin, Alzheimer’s disease (AD), and gut microbiota. Systematic changes were evaluated using multi-omics analysis. Fecal microbiota transplantation (FMT) was performed to examine the role of gut microbiota in the pathogenic risks of EMR. EMR mice exhibited a pan-metabolic disorder, with significant transcriptome changes in 11 organs, serum metabolome alterations as well as microbiota dysbiosis. Microbiota dysbiosis was accompanied by increased gut permeability along with gut and systemic inflammation. Correlation analysis revealed that systemic inflammation may be related to the increase of Ruminiclostridium_5 relative abundance. 8-month-old EMR mice had AD-like phenotypes, including Iba-1 activation, A β protein deposition and decreased spatial memory ability. Moreover, EMR mice showed decreased anti stress ability, under high-fat diet, EMR mice had greater body weight and more obvious hepatic steatosis compared with WT group. FMT improved gut permeability, systemic inflammation, and AD-related phenotypes, while reducing obesity in EMR mice. Our findings suggest EMR causes systemic changes mediated by gut microbiota dysbiosis, which may be a pathogenic factor for AD and obesity, we further proved the gut microbiota is a potential target for the prevention and treatment of AD and obesity.
Repurposing of FDA Approved Drugs Against SARS-CoV-2 Papain-Like Protease: Computational, Biochemical, and in vitro Studies

The pandemic caused by SARS-CoV-2 (SCoV-2) has impacted the world in many ways and the virus continues to evolve and produce novel variants with the ability to cause frequent global outbreaks. Although the advent of the vaccines abated the global burden, they were not effective against all the variants of SCoV-2. This trend warrants shifting the focus on the development of small molecules targeting the crucial proteins of the viral replication machinery as effective therapeutic solutions. The PLpro is a crucial enzyme having multiple roles during the viral life cycle and is a well-established drug target. In this study, we identified 12 potential inhibitors of PLpro through virtual screening of the FDA-approved drug library. Docking and molecular dynamics simulation studies suggested that these molecules bind to the PLpro through multiple interactions. Further, IC50 values obtained from enzyme-inhibition assays affirm the stronger affinities of the identified molecules for the PLpro. Also, we demonstrated high structural conservation in the catalytic site of PLpro between SCoV-2 and Human Coronavirus 229E (HCoV-229E) through molecular modelling studies. Based on these similarities in PLpro structures and the resemblance in various signalling pathways for the two viruses, we propose that HCoV-229E is a suitable surrogate for SCoV-2 in drug-discovery studies. Validating our hypothesis, Mefloquine, which was effective against HCoV-229E, was found to be effective against SCoV-2 as well in cell-based assays. Overall, the present study demonstrated Mefloquine as a potential inhibitor of SCoV-2 PLpro and its antiviral activity against SCoV-2. Corroborating our findings, based on the in vitro virus inhibition assays, a recent study reported a prophylactic role for Mefloquine against SCoV-2. Accordingly, Mefloquine may further be investigated for its potential as a drug candidate for the treatment of COVID.
Adult Female Sleep During Hypoxic Bed Rest

Purpose Hypobaric hypoxic habitats are currently being touted as a potential solution to minimise decompression procedures in preparation for extra vehicular activities during future space missions. Since astronauts will live in hypoxic environments for the duration of such missions, the present study sought to elucidate the separate and combined effects of inactivity [simulated with the experimental bed rest (BR) model] and hypoxia on sleep characteristics in women. Methods Twelve women (Age = 27 ± 3 year) took part in three 10-day interventions, in a repeated measures cross-over counterbalanced design: (1) normobaric normoxic BR (NBR), (2) normobaric hypoxic BR (HBR; simulated altitude of 4,000 m), and (3) normobaric hypoxic ambulatory (HAMB; 4,000 m) confinement, during which sleep was assessed on night 1 and night 10 with polysomnography. In addition, one baseline sleep assessment was performed. This baseline assessment, although lacking a confinement aspect, was included statistically as a fourth comparison (i.e., pseudo normobaric normoxic ambulatory; pNAMB) in the present study. Results Hypoxia decreased sleep efficiency (p = 0.019), increased N1% sleep (p = 0.030), decreased N3 sleep duration (p = 0.003), and increased apnea hypopnea index (p < 0.001). BR impaired sleep maintenance, efficiency, and architecture [e.g., N2% sleep increased (p = 0.033)]. Specifically, for N3% sleep, the effects of partial pressure of oxygen and activity interacted. Hypoxia decreased N3% sleep both when active (pNAMB vs HAMB; p < 0.001) and inactive (NBR vs HBR; p = 0.021), however, this decrease was attenuated in the inactive state (–3.8%) compared to the active state (–10.2%). Conclusion A 10-day exposure to hypoxia and BR negatively impacted sleep on multiple levels as in macrostructure, microstructure and respiratory functioning. Interestingly, hypoxia appeared to have less adverse effects on sleep macrostructure while the participants were inactive (bed ridden) compared to when ambulatory. Data were missing to some extent (i.e., 20.8%). Therefore, multiple imputation was used, and our results should be considered as exploratory.
3,5,3′-Triiodothyronine–Loaded Liposomes Inhibit Hepatocarcinogenesis Via Inflammation-Associated Macrophages

Background Hepatocellular carcinoma (HCC) is inflammation-related cancer. Persistent inflammatory injury of the liver is an important factor mediating the occurrence and development of liver cancer. Hepatic macrophages play an important role in the inflammatory microenvironment, which mediates tumor immune escape, tumor growth, and metastasis. Previous studies have suggested that L-3,5,3-triiodothyronine (T3) can regulate inflammation; however, its use is associated with serious cardiac side effects, and its role in hepatocarcinogenesis remains unclear. In this study, we aimed to develop an effective T3 delivery system with reduced cardiac toxicity and to explore its effects on HCC occurrence. Methods T3 liposomes (T3-lipo) were prepared using the thin-film hydration method, and their characteristics, including particle size, polydispersity index, zeta potential, encapsulation efficiency, drug loading, drug release, and stability, were evaluated in vitro. We assessed the effect of T3-lipo on hepatocarcinogenesis in diethylnitrosamine (DEN)–induced primary HCC in rats and examined the biodistribution of T3 and T3-lipo by high-performance liquid chromatography–mass spectrometry. Furthermore, we explored the potential molecular mechanism of T3-lipo in hepatocarcinogenesis by immunohistochemistry and immunofluorescence analyses, Bio-Plex assays, real-time polymerase chain reaction analysis, and Western blotting assays. Results Compared with T3, T3-lipo had an enhanced inhibitory effect on hepatocarcinogenesis and reduced cardiac side effects in DEN-induced primary HCC in rats. Mechanistically, T3-lipo were absorbed by hepatic macrophages and regulated the secretion of inflammatory cytokines in macrophages by inhibiting inflammatory signaling pathways. Conclusions T3-lipo may suppress hepatocarcinogenesis by regulating the inflammatory microenvironment in the liver and reduce the cardiac side effects meanwhile.
Radial Seismic Metamaterials Based on Layering Theory: Broadband Shielding of Ultra-Low Frequency Seismic Surface Waves

In this paper, a novel radial seismic metamaterial (LRSM) based on layering theory is proposed. Compared with traditional seismic metamaterials, the structure of LRSM is a periodic array of multi-layer rings distributed along the radial direction. By using the finite element method, the dispersion relationship and displacement vector field of LRSM with different layers are studied, and the influence of structural geometric parameters and circumferential continuity on the band gap characteristics of LRSM is discussed. The frequency domain analysis of finite periodic structure and the three-dimensional transient wave propagation analysis are carried out. The results show that the LRSM has ultra-low frequency broadband characteristics, which is produced by the coupling between the local resonance of the LRSM and the surface wave mode. Comparing three LRSMs with different layers, the initial frequency and bandwidth do not change monotonically with the increase of the number of layers. There is an optimal bandgap characteristic in two layers, and the relative bandwidth can reach 83.9%. The increase of the number causes the change of the structural stiffness, which is caused by the change of the local resonance strength. The position and width of the band gap in the LRSM are very sensitive to the height of the structure. The increase of the height of the LRSM can move the first band gap to the low frequency, and the total bandwidth increases, which is mainly caused by the increase of the equivalent mass of the system with the increase of the height of the structure. Further, it is verified that LRSM can effectively attenuate seismic surface waves of 0.1–20 Hz, and its maximum amplitude attenuation can exceed 85%. The novel periodic structure proposed in this paper can provide new options for the fields of earthquake and low-frequency vibration reduction.