Miracle-dz/UniFAR-FTUs huggingface dataset:
Bacteriocins as a new generation of antimicrobials: toxicity aspects and regulations

ABSTRACT In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins have been predominantly exploited as food preservatives, they are now receiving increased attention as potential clinical antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the application of bacteriocins, their toxicity and impacts.
LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation

Despite advances in identifying the key immunoregulatory roles of many of the human leukocyte immunoglobulin-like receptor (LILR) family members, the function of the inhibitory molecule LILRB3 (ILT5, CD85a, LIR3) remains unclear. Studies indicate a predominant myeloid expression; however, high homology within the LILR family and a relative paucity of reagents have hindered progress toward identifying the function of this receptor. To investigate its function and potential immunomodulatory capacity, a panel of LILRB3-specific monoclonal antibodies (mAbs) was generated. LILRB3-specific mAbs bound to discrete epitopes in Ig-like domain 2 or 4. LILRB3 ligation on primary human monocytes by an agonistic mAb resulted in phenotypic and functional changes, leading to potent inhibition of immune responses in vitro, including significant reduction in T cell proliferation. Importantly, agonizing LILRB3 in humanized mice induced tolerance and permitted efficient engraftment of allogeneic cells. Our findings reveal powerful immunosuppressive functions of LILRB3 and identify it as an important myeloid checkpoint receptor.
Replication stress at microsatellites causes DNA double-strand breaks and break-induced replication

Short tandemly repeated DNA sequences, termed microsatellites, are abundant in the human genome. These microsatellites exhibit length instability and susceptibility to DNA double-strand breaks (DSBs) due to their tendency to form stable non-B DNA structures. Replication-dependent microsatellite DSBs are linked to genome instability signatures in human developmental diseases and cancers. To probe the causes and consequences of microsatellite DSBs, we designed a dual-fluorescence reporter system to detect DSBs at expanded (CTG/CAG)n and polypurine/polypyrimidine (Pu/Py) mirror repeat structures alongside the c-myc replication origin integrated at a single ectopic chromosomal site. Restriction cleavage near the (CTG/CAG)100 microsatellite leads to homology-directed single-strand annealing between flanking AluY elements and reporter gene deletion that can be detected by flow cytometry. However, in the absence of restriction cleavage, endogenous and exogenous replication stressors induce DSBs at the (CTG/CAG)100 and Pu/Py microsatellites. DSBs map to a narrow region at the downstream edge of the (CTG)100 lagging-strand template. (CTG/CAG)n chromosome fragility is repeat length–dependent, whereas instability at the (Pu/Py) microsatellites depends on replication polarity. Strikingly, restriction-generated DSBs and replication-dependent DSBs are not repaired by the same mechanism. Knockdown of DNA damage response proteins increases (Rad18, polymerase (Pol) η, Pol κ) or decreases (Mus81) the sensitivity of the (CTG/CAG)100 microsatellites to replication stress. Replication stress and DSBs at the ectopic (CTG/CAG)100 microsatellite lead to break-induced replication and high-frequency mutagenesis at a flanking thymidine kinase gene. Our results show that non-B structure–prone microsatellites are susceptible to replication-dependent DSBs that cause genome instability.
An Evolutionary Game Theory Study for Construction and Demolition Waste Recycling Considering Green Development Performance under the Chinese Government’s Reward–Penalty Mechanism

The low efficiency of the closed-loop supply chain in construction and demolition waste (CDW) recycling has restricted the green development of China’s construction industry. Additionally, the government’s reward–penalty mechanism has a huge influence on green development. This study aimed to investigate the effect of green development performance (GDP) and the government’s reward–penalty mechanism on the decision-making process of production and recycling units, as well as to reveal the optimal strategies under different conditions. Therefore, the strategies’ evolutionary paths of production and recycling units were investigated by using evolutionary game theory. Firstly, an evolutionary game model between production units and recycling units was proposed under the government’s reward–penalty mechanism. Then, the evolutionary stability strategies in different scenarios were discussed. Finally, the effects of the relevant parameters on the evolutionary paths of the game model were analyzed using numerical simulations. The main conclusions are as follows. (1) When the range of GDP changes, the evolutionary stable strategy changes accordingly. GDP plays a positive role in promoting the high-quality development of the CDW recycling supply chain, but an increase in GDP can easily lead to the simultaneous motivation of free-riding. (2) The government’s reward–penalty mechanism effectively regulates the decision-making process of production and recycling units. An increase in the subsidy rate and supervision probability helps to reduce free-riding behavior. Moreover, the incentive effect of the subsidy probability on recycling units is more obvious, while the effect of the supervision probability on improving the motivation of active participation for production units is more remarkable. This paper not only provides a decision-making basis to ensure production and recycling units to make optimal strategy choices under different conditions but also provides a reference for the government to formulate a reasonable reward–penalty mechanism that is conducive to a macro-control market.
Survive a Warming Climate: Insect Responses to Extreme High Temperatures.

Global change includes a substantial increase in the frequency and intensity of extreme high temperatures (EHTs), which influence insects at almost all levels. The number of studies showing the ecological importance of EHTs has risen in recent years, but the knowledge is rather dispersed in the contemporary literature. In this article, we review the biological and ecological effects of EHTs actually experienced in the field, i.e., when coupled to fluctuating thermal regimes. First, we characterize EHTs in the field. Then, we summarize the impacts of EHTs on insects at various levels and the processes allowing insects to buffer EHTs. Finally, we argue that the mechanisms leading to positive or negative impacts of EHTs on insects can only be resolved from integrative approaches considering natural thermal regimes. Thermal extremes, perhaps more than the gradual increase in mean temperature, drive insect responses to climate change, with crucial impacts on pest management and biodiversity conservation. Expected final online publication date for the Annual Review of Entomology, Volume 66 is January 11, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Ocular Features and Associated Systemic Findings in SARS-CoV-2 Infection

ABSTRACT Purposes To describe the prevalence of ocular features among COVID-19 patients and their relationship with clinical data, inflammatory markers and respiratory support therapy (including CPAP); to investigate SARS-CoV-2 in ocular secretions of symptomatic patients. Methods 172 COVID-19 patients were evaluated for presence of ocular manifestations. Clinical and laboratory data were also reviewed. Conjunctival swabs were analyzed for SARS-CoV-2 by RT-PCR. Results Forty-five patients (26.2%) reported ocular manifestations. Patients treated with CPAP were more likely to have ocular abnormalities (p <.01). The presence of ocular symptoms was not associated with more significant alterations on blood tests. Conjunctival swabs from patients with suspect conjunctivitis yielded negative results for SARS-CoV-2. Conclusions Ocular features are not infrequent in COVID-19 patients, but the presence of SARS-CoV-2 in ocular secretions is low. Ocular manifestations in hospitalized COVID-19 patients can also be a consequence of respiratory support therapy. Prevention of possible transmission through ocular secretions is still recommended.
ALVAR VEGETATION OF ÖLAND—CHANGES, MONITORING AND RESTORATION

Abstract:Alvars are habitats characterised by thin soils on limestone bedrock. The largest alvar area in the world is the Stora Alvaret, Öland (25,500 hectares), which is characterised by the presence of several plant communities of high conservation value. Emigration at the end of the nineteenth century reduced land-use intensity resulting in scrub encroachment, mainly by Juniperus communis L. This later accelerated, leading to abandonment because grazing in the low-productivity pastures was uneconomic. Monitoring in permanent plots over a twenty-year period (1971-91) showed an increase in juniper cover over time and a clear correlation with a decline of other vascular plant species. This resulted in a gradual loss of both a valuable mosaic structure and a high level of bio-diversity in the landscape. An EU funded LIFE project (1996-99), which examined the effects of grazing and scrub clearance, is outlined. Various management techniques were tested and evaluated, providing valuable information for the present large-scale restoration and management programme supported by the European Union agri-environment schemes. In 1994 less than 60% of the Stora Alvaret was grazed. By 2005 this had increased to 98%. The reintroduction of grazing has resulted in a significant increase in the abundance of twelve out of 72 vascular species in permanent plots (1997-2001). Sheep and cattle numbers increased in Öland during the last decade, whereas they decreased in Sweden as a whole over the same period. Sixteen nature reserves have been established in Stora Alvaret, and a functioning alvar pasture landscape has been re-established. Almost all alvars in Öland have been designated as Natura 2000 areas.
Improved Parkinsons disease motor score in a single-arm open-label trial of febuxostat and inosine

Supplemental Digital Content is available in the text Abstract Background: Cellular energetics play an important role in Parkinsons disease etiology, but no treatments directly address this deficiency. Our past research showed that treatment with febuxostat and inosine increased blood hypoxanthine and ATP in healthy adults, and a preliminary trial in 3 Parkinson's disease patients suggested some symptomatic improvements with no adverse effects. Methods: To examine the efficacy on symptoms and safety in a larger group of Parkinsons disease patients, we conducted a single-arm, open-label trial at 5 Japanese neurology clinics and enrolled thirty patients (nmales = 11; nfemales = 19); 26 patients completed the study (nmales = 10; nfemales = 16). Each patient was administered febuxostat 20 mg and inosine 500 mg twice-per-day (after breakfast and dinner) for 8 weeks. The primary endpoint was the difference of MDS-UPDRS Part III score immediately before and after 57 days of treatment. Results: Serum hypoxanthine concentrations were raised significantly after treatment (Pre = 11.4 μM; Post = 38.1 μM; P < .0001). MDS-UPDRS Part III score was significantly lower after treatment (Pre = 28.1 ± 9.3; Post = 24.7 ± 10.8; mean ± SD; P = .0146). Sixteen adverse events occurred in 13/29 (44.8%) patients, including 1 serious adverse event (fracture of the second lumbar vertebra) that was considered not related to the treatment. Conclusions: The results of this study suggest that co-administration of febuxostat and inosine is relatively safe and effective for improving symptoms of Parkinsons disease patients. Further controlled trials need to be performed to confirm the symptomatic improvement and to examine the disease-modifying effect in long-term trials.
Apremilast in dermatology: A review of literature

Apremilast is an orally administered small molecule that specifically inhibits the phosphodiesterase‐4 enzyme and modulates the immune system by increasing the levels of intracellular cyclic adenosine monophosphate (cAMP) and inhibiting IL‐2 & 8, interferon‐γ and tumor necrosis factor (TNF) production. It is FDA approved for the treatment of psoriasis, psoriatic arthritis, and oral ulcers of Behcet's disease. More recently, apremilast has been used off‐label to treat varied dermatological diseases where systemic corticosteroids or immunosuppressive agents were not effective. We review the efficacy and safety of apremilast in the treatment of aphthous stomatitis, Behçet's disease, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus in cases where standard treatment has failed.
Fecal microbiota transplantation therapy for Parkinson's disease

Abstract Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (all P < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.
[Meta-analysis of direct anterior approach and other approaches for hemiarthroplasty in elderly patients with femoral neck fracture].

OBJECTIVE To systematically evaluate the clinical efficacy of high-quality direct anterior approach (DAA) and other approaches for the treatment of elderly patients with femoral neck fracture. METHODS Literatures published in English or Chinese about the direct anterior approach and other approaches for hemiarthroplasty in femoral neck fracture were searched on Cochrane Library, PubMed, EMBASE, Web of science, Wanfang, CNKI databases from their establishment to May 2019. According to the inclusion and exclusion criteria, two researchers independently screened the literatures, and extracted the data. The quality of RCT were evaluated by Cochrane Risk of Bias Assessment Tool, and non-RCT were evaluated by the NOS scale. Meta-analysis was performed using the RevMan 5.3 software. RESULTS A total of 9 articles were included with 901 cases, in which 429 cases used DAA, and 472 used other approaches. DAA had a significantly lower dislocation rate compared to subgroup of posterior and posterolateral approach [OR=0.19, 95%CI (0.06, 0.61), P=0.005]. No significant differences were found between DAA group and subgroup of direct lateral and anterolateral approach[OR=1.08, 95%CI(0.20, 5.76), P=0.93]. Also there were no relevant differences between the DAA group and control in infection rate[OR=1.07, 95%CI(0.47, 2.43), P=0.88], perioperative fracture rate[OR=0.95, 95%CI(0.36, 2.50), P=0.92], re operation rate[OR=0.76, 95%CI(0.30, 1.89), P=0.55], overall complication rate [OR=0.88, 95%CI (0.63, 1.22), P=0.44], mortality [OR=1.33, 95%CI (0.84, 2.11), P=0.23], operative time[MD=1.43, 95%CI(-5.85, 8.71), P=0.70]. CONCLUSION The current evidenceindicates that the DAA was associated with a significantly lower dislocation rate compared to posterior capsular approaches for hemiarthroplasty. There was no significant difference in dislocation rate with the lateral and anterolateral approach.
Breaking the breach in Latin America: A pilot study of mechanical thrombectomy in the public healthcare system in Chile

Background Mechanical Thrombectomy (MT) is the standard of care for treatment of large vessel occlusion stroke. Until the beginning of 2020 MT was not funded nor widely implemented at the public healthcare level in Chile. Objective To describe the results of a pilot program created to provide access to public MT in Santiago - Chile. Methods Analysis from a prospectively collected database of MT cases performed between September 2017 and September 2019 in one center. A stroke network was developed with a single MT capable stroke center and five primary stroke centers. The primary efficacy endpoint was the rate of functional independence (mRS 0-2) at 90 days. Successful reperfusion was defined as 2 b-3 according to the thrombolysis in cerebral infarction scale. Safety outcomes include the rates of symptomatic intracranial hemorrhage and 90-day mortality. Results A total of 100 patients were treated over the study period. Their mean age was 62.8 ± 11.8 years and median baseline National Institute of Health Stroke Scale (NIHSS) measurement was 17. Seventy-seven percent of the patients received intra venous thrombolysis. Successful reperfusion was achieved in 95% of the cases. NIHSS at 24 hours showed a median drop of 7 points from baseline (p < 0.00001) and 50% of the follow-up patients were functionally independent at 90 days. Symptomatic Intracerebral hemorrhage occurred in 5% of the patients and 90-day all case mortality was 11%. Conclusions We demonstrated the feasibility of a publicly funded MT program in Chile, with similar results as other international randomized control trials.
Autotaxin loss accelerates intestinal inflammation by suppressing TLR4‐mediated immune responses

Autotaxin (ATX) converts lysophosphatidylcholine and sphingosyl‐phosphorylcholine into lysophosphatidic acid and sphingosine 1‐phosphate, respectively. Despite the pivotal function of ATX in lipid metabolism, mechanisms by which ATX regulates immune and inflammatory disorders remain elusive. Here, using myeloid cell lineage‐restricted Atx knockout mice, we show that Atx deficiency disrupts membrane microdomains and lipid rafts, resulting in the inhibition of Toll‐like receptor 4 (TLR4) complex formation and the suppression of adaptor recruitment, thereby inhibiting TLR4‐mediated responses in macrophages. Accordingly, TLR4‐induced innate immune functions, including phagocytosis and iNOS expression, are attenuated in Atx‐deficient macrophages. Consequently, Atx−/− mice exhibit a higher bacterial prevalence in the intestinal mucosa compared to controls. When combined with global Il10−/− mice, which show spontaneous colitis due to the translocation of luminal commensal microbes into the mucosa, myeloid cell lineage‐restricted Atx knockout accelerates colitis development compared to control littermates. Collectively, our data reveal that Atx deficiency compromises innate immune responses, thereby promoting microbe‐associated gut inflammation.
Association between Accreditation and In-Hospital Mortality in Patients with Major Cardiovascular Diseases in South Korean Hospitals: Pre-Post Accreditation Comparison

The direct impact of hospital accreditation on patients’ clinical outcomes is unclear. The purpose of this study was to evaluate whether mortality within 30 days of hospitalization for acute myocardial infarction (AMI), ischemic stroke (IS), and hemorrhagic stroke (HS) differed before and after hospital accreditation. This study targeted patients who had been hospitalized for the three diseases at the general hospitals newly accredited by the government in 2014. Thirty-day mortality rates of three years before and after accreditation were compared. Mortality within 30 days of hospitalization for the three diseases was lower after accreditation than before (7.34% vs. 6.15% for AMI; 4.64% vs. 3.80% for IS; and 18.52% vs. 15.81% for HS). In addition, hospitals that meet the criteria of the patient care process domain have a statistically lower mortality rate than hospitals that do not. In the newly accredited Korean general hospital, it was confirmed that in-hospital mortality rates of major cardiovascular diseases were lower than before the accreditation.
Acceptability and Feasibility of Best Practice School Lunches by Elementary School-Aged Children in a Serve Setting: A Randomized Crossover Trial

Background: National School Lunch Program (NSLP) standards have improved school lunch dietary quality (DQ), however, further improvements could be made. Acceptability and feasibility of higher DQ are potential barriers. Thus, the purpose is to compare acceptability and feasibility of best practice (BPSL, optimizing DQ) with typical school lunches (TSL, meeting minimum NSLP standards) served separately and concurrently. Methods: Forty elementary school-aged participants were recruited for a randomized crossover trial. Participants attended three meal conditions (MC) choosing one of two meal types—MC1) BPSL1/BPSL2, MC2) TSL1/TSL2, MC3) BPSL/TSL. Acceptability included taste test surveys, weighted plate waste assessments, and hunger scales. Feasibility included meal cost, time, and skill and equipment requirements. Results: There were no significant differences in total taste test score, average total plate waste, or change in hunger (ps > 0.017) before or after adjusting for covariates. TSL was selected significantly more often in MC3 (TSL = 83.3%, BPSL = 16.7%, p = 0.001). Meal cost (p = 0.783) and skill and equipment requirements were not significantly different between meal types. BPSL required significantly longer preparation time (TSL = 60 ± 25 min, BPSL = 267 ± 101 min, p = 0.026). Conclusions: Results indicate few differences in acceptability and feasibility between BPSL and TSL. This study could inform decision and policy-makers seeking to improve school lunch DQ and acceptance of higher DQ meals.