Miracle-dz/UniFAR-FTUs huggingface dataset:
How to select older patients with acute myeloid leukemia fit for intensive treatment?

Outcomes of the treatment of older patients with acute myeloid leukemia (AML) are unsatisfactory due to a higher incidence of negative patient‐ and disease‐related risk factors connected with aging. Prediction of poor tolerance to aggressive treatment and low response to standard intensive chemotherapy are the main root causes why the treatment decision is challenging. For a long time, negative prognostic factors for treatment outcomes, overall survival, and early death such as the age itself, low‐performance status, high‐comorbidity burden, adverse cytogenetics, and secondary AML have been known, and they are routinely taken into account during therapeutic balance. In consideration of the risk factors and specific laboratory results, prognostic models have been created. Despite the abovementioned facts, the survival of older patients with AML remains very poor, that holds true even for the intensive therapy. For that reason, there is an increased effort to find a better approach how to select patients who would benefit from intensive treatment without decreasing their quality of life through severe complications with risk of high treatment‐related mortality. Based on the results of clinical studies, the geriatric assessment could be the missing step which would help select older patients who are really fit for intensive treatment and who will benefit from it the most. This review focuses on the risk factors that should be taken under advisement when the decision about the treatment is made. With reference to the published information, we propose an algorithm how to identify fit, vulnerable, and frail patients.
Revisiting the association between worldwide implementation of the MPOWER package and smoking prevalence, 2008–2017

Background We revisited the association between progress in MPOWER implementation from 2008 to 2016 and smoking prevalence from 2009 to 2017 and offered an in-depth understanding of differential outcomes for various country groups. Methods We used data from six rounds of the WHO Reports on the Global Tobacco Epidemic and calculated a composite MPOWER Score for each country in each period. We categorised the countries in four initial conditions based on their tobacco control preparedness measured by MPOWER score in 2008 and smoking burden measured by age-adjusted adult daily smoking prevalence in 2006: (1) High MPOWER – high prevalence (HM-HP). (2) High MPOWER – low prevalence (HM-LP). (3) Low MPOWER – high prevalence (LM-HP). (4) Low MPOWER – low prevalence (LM-LP). We estimated the association of age-adjusted adult daily smoking prevalence with MPOWER Score and cigarette tax rates using two-way fixed-effects panel regression models including both year and country fixed effects. Results A unit increase of the MPOWER Score was associated with 0.39 and 0.50 percentage points decrease in adult daily smoking prevalence for HM-HP and HM-LP countries, respectively. When tax rate was controlled for separately from MPOWE, an increase in tax rate showed a negative association with daily smoking prevalence for HM-HP and LM-LP countries, while the MPOWE Score showed a negative association for all initial condition country groups except for LM-LP countries. Conclusion A decade after the introduction of the WHO MPOWER package, we observed that the countries with higher initial tobacco control preparedness and higher smoking burden were able to reduce the adult daily smoking prevalence significantly.
Prevalence rates study of selected isolated non‐Mendelian congenital anomalies in the Hutterite population of Alberta, 1980–2016

A study of the prevalence rates for selected isolated non‐Mendelian congenital anomalies in the Hutterite Brethren of Alberta, Canada was undertaken to further examine longitudinal data in this isolated community that was last reported in 1985 (Lowry et al., 1985), although there are numerous publications on recessive disorders (Boycott et al., 2008; Triggs‐Raine et al., 2016). Cases were ascertained from the Alberta Congenital Anomaly Surveillance System for the years 1997–2016. Since our initial results showed some surprising findings in the Hutterite Brethren, such as zero cases of spina bifida, cleft lip and palate, gastroschisis, and omphalocele, and a significant excess of cases with hypospadias, we extended the study to prior years (1980–1996) for selected anomalies. For the extended study period (1980–2016), there was a significant increased prevalence of hypospadias, tetralogy of Fallot and tricuspid atresia in the Hutterite population, and although not statistically significant, zero cases of cleft lip with cleft palate, gastroschisis and omphalocele were confirmed. Further research is needed to determine the precise effects of rural environmental exposures, lifestyle factors, and genetic associations for selected multifactorial congenital anomalies.
Sesamin attenuates intestinal injury in sepsis via the HMGB1/TLR4/IL-33 signalling pathway

Abstract Context Sepsis is currently one of the leading causes of death in intensive care units (ICUs). Sesamin was previously reported to inhibit inflammation. However, no studies have revealed the impact of sesamin on sepsis. Objective We studied the mechanism underlying the effect of sesamin on the pathophysiology of sepsis through the HMGB1/TLR4/IL-33 signalling pathway. Materials and methods Fifty male BALB/c mice (n = 10 per group) were used to establish a caecal ligation and puncture (CLP) mouse model, and given daily injections of sesamin at a low, middle, or high concentration (25, 50, or 100 μM) during the seven-day study period; survival curves were generated by the Kaplan–Meier method. H&E staining and TUNEL staining were performed to assess changes in intestinal morphology intestinal damage in the mouse intestinal epithelium. Molecules related to the HMGB1/TLR4/IL-33 pathway were assessed by RT-qPCR and Western blotting. Results We found mice in the sepsis group survived for only 4 days, while those treated with sesamin survived for 6–7 days. In addition, sesamin significantly relieved the increase in the levels of MPO (21%, 33.3%), MDA (40.5% and 31.6%), DAO (1.24-fold and 2.31-fold), and pro-inflammatory cytokines such as TNF-α (75% and 79%) and IL-6 (1-fold and 1.67-fold) 24 and 48 h after sepsis induction and downregulated the expression of HMGB1, TLR4, and IL-33 while upregulating the expression of ZO-1 and occludin. Discussion and conclusions Sesamin improved the 7-day survival rate of septic mice, suppressed the inflammatory response in sepsis through the HMGB-1/TLR4/IL-33 signalling pathway, and further alleviated intestinal injury.
Objective masticatory efficiency and subjective quality of masticatory function among patients with periodontal disease.

AIMS To examine patient-centered clinical outcomes for objective masticatory efficiency (OME) and subjective quality of masticatory function (QMF) among periodontitis patients using test methods easily applicable in daily practice. MATERIALS AND METHODS Cross-sectional investigation of patients undergoing supportive periodontal therapy (n=224). Outcomes included OME and QMF related to periodontitis characteristics. RESULTS OME and QMF were associated (x2 = 0.252, p=0.037) and showed highest values in stage 4 according to the new classification of periodontal disease. There were correlations particularly in stage 2 between OME and number of teeth (x2 =-0.317, p<0.001), Quigley-Hein Index (x2 =0.152, p=0.031), attachment level (x2 =0.268, p<0.001), probing depths (x2 =0.185, p=0.006), tooth mobility (x2 =0.147, p=0.031), and functional occlusal units (x2 =-0.423, p<0.001) but not bleeding on probing. A trend existed between QMF and number of teeth (x2 =-0.237, p=0.050) and functional occlusal units (x2 =0.238, p=0.058), but not other periodontal findings. CONCLUSIONS OME and QMF values represent each other and are highest in stage 4. Periodontitis findings influence masticatory efficiency particularly in stage 2, but gingival inflammation does not. Number of teeth and functional occlusal units are associated with QMF while periodontitis findings have less impact. An assessment of mastication should be routinely included into the diagnosis of periodontitis patients in all stages.
Pooled testing for COVID-19 diagnosis by real-time RT-PCR: A multi-site comparative evaluation of 5- & 10-sample pooling

Background & objectives: Public health and diagnostic laboratories are facing huge sample loads for COVID-19 diagnosis by real-time reverse transcription-polymerase chain reaction (RT-PCR). High sensitivity of optimized real-time RT-PCR assays makes pooled testing a potentially efficient strategy for resource utilization when positivity rates for particular regions or groups of individuals are low. We report here a comparative analysis of pooled testing for 5- and 10-sample pools by real-time RT-PCR across 10 COVID-19 testing laboratories in India. Methods: Ten virus research and diagnostic laboratories (VRDLs) testing for COVID-19 by real-time RT-PCR participated in this evaluation. At each laboratory, 100 nasopharyngeal swab samples including 10 positive samples were used to create 5- and 10-sample pools with one positive sample in each pool. RNA extraction and real-time RT-PCR for SARS-CoV-2-specific E gene target were performed for individual positive samples as well as pooled samples. Concordance between individual sample testing and testing in the 5- or 10-sample pools was calculated, and the variation across sites and by sample cycle threshold (Ct) values was analyzed. Results: A total of 110 each of 5- and 10-sample pools were evaluated. Concordance between the 5-sample pool and individual sample testing was 100 per cent in the Ct value ≤30 cycles and 95.5 per cent for Ctvalues ≤33 cycles. Overall concordance between the 5-sample pooled and individual sample testing was 88 per cent while that between 10-sample pool and individual sample testing was 66 per cent. Although the concordance rates for both the 5- and 10-sample pooled testing varied across laboratories, yet for samples with Ct values ≤33 cycles, the concordance was ≥90 per cent across all laboratories for the 5-sample pools. Interpretation & conclusions: Results from this multi-site assessment suggest that pooling five samples for SARS-CoV-2 detection by real-time RT-PCR may be an acceptable strategy without much loss of sensitivity even for low viral loads, while with 10-sample pools, there may be considerably higher numbers of false negatives. However, testing laboratories should perform validations with the specific RNA extraction and RT-PCR kits in use at their centres before initiating pooled testing.
Antimicrobial resistance profile of non-aureus Staphylococci isolates from buffalo, goat and sheep mastitis in the Northeast region of Brazil

Abstract The study described in this Research Communication investigated the genotypic and phenotypic profiles of resistance to beta-lactams and other antimicrobials in non-aureus Staphylococci (NAS) isolated from buffalo, goat and sheep mastitis in the Northeast region of Brazil. A total of 190 isolates were analyzed and 42.3, 43.9 and 23.6% of them were positive for blaZ gene in buffalo, goat and sheep, respectively. Regarding the animal groups, in goats, amoxicillin was the antimicrobial with highest resistance index (72.7%), followed by penicillin G in buffaloes (51.9%) and ampicillin in sheep (43.1%). With regard to multiple antimicrobial resistance, 30.8% of NAS isolates from buffalo milk samples, 25.8% from goats and 25.0% from sheep presented multidrug-resistance. In the minimum inhibitory concentration (MIC) technique, amoxicillin MIC50 and MIC90 were 64 and 128 μg/ml, respectively, among isolates of the three animal species. In conclusion, high rates of resistance to beta-lactams are presented among NAS isolated from mastitis cases in buffaloes, goats and sheep in Northeast region of Brazil. These results provide an alert to animal and human health researchers, suggesting that the frequency of NAS needs to be reduced because they carry resistance genes which might increase the existing levels of antimicrobial resistance.
Roles of miRNA and IncRNA in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancer without effective targeted therapies, which makes its pathogenesis an important target for research. A growing number of studies have shown that non-coding RNA (ncRNA), including microRNA (miRNA) and long non-coding RNA (lncRNA), plays a significant role in tumorigenesis. This review summarizes the roles of miRNA and lncRNA in the progression, diagnosis, and neoadjuvant chemotherapy of TNBC. Aberrantly expressed miRNA and lncRNA are listed according to their roles. Further, it describes the multiple mechanisms that lncRNA shows for regulating gene expression in the nucleus and cytoplasm, and more importantly, describes lncRNA-regulated TNBC progression through complete combining with miRNA at the post-transcriptional level. Focusing on miRNA and lncRNA associated with TNBC can provide new insights for early diagnosis and treatment—they can be targeted in the future as a novel anticancer target of TNBC.
The program evaluation of 'Go‐To Educator Training' on educators' knowledge about and stigma toward mental illness in six Canadian provinces

Schools are well positioned to promote mental health literacy and assist in the early identification of students who may have a mental disorder. However, many educators are unprepared to effectively address these issues. Enhancing this capacity may improve mental health outcomes for students. This report describes the application of a gatekeeper‐type program, the 'Go‐To Educator Training' (GTET), targeting educators whom students naturally gravitate toward for support, designed to improve educators' mental health knowledge and early identification skills and decrease stigma.
The relationship between individual, physical and psychosocial risk factors with musculoskeletal disorders and related disabilities in flight security personnel

Purpose. The purpose of this study was to investigate the relationship between individual, physical and psychosocial risk factors with musculoskeletal disorders and related disability in flight security personnel. Methods. The study was conducted among 316 employees in Iran flight security. To study the prevalence of musculoskeletal disorders, lifestyle, occupational stress, mental workload and disability, the Cornell questionnaire, Walker lifestyle questionnaire, job content questionnaire, NASA task load index and pain disability questionnaire were used, respectively. Data were analyzed using independent-sample t test, one-way analysis of variance, χ2 test and multiple logistic regression. Results. A total 68.35% of participants had musculoskeletal disorders in at least one of their body parts. There was a significant relationship between the parameters of increased age, higher work experience, high body mass index, gender and educational level and the prevalence of musculoskeletal disorders. Also, some components related to healthy lifestyle, occupational stress and mental workload had significant association with mentioned disorders (p < 0.05). Conclusion. The parameters of lifestyle, occupational stress and mental workload are among the most important risk factors for the prevalence of work-related musculoskeletal disorders and related disabilities in flight security personnel. Therefore, corrective measures through controlling individual, physical and psychosocial risk factors are necessary.
Protease inhibitors, inflammatory markers, and their association with outcome in dogs with naturally occurring acute pancreatitis

Abstract Background Acute pancreatitis (AP) presumably is associated with pancreatic protease activation, protease inhibitor (PI) depletion, and inflammatory mediator secretion. Objectives Examine PIs and inflammatory mediator concentrations in dogs with AP and their association with death. Animals Thirty‐one dogs diagnosed with AP based on clinical signs, ultrasonographic findings, and increased canine pancreatic lipase immunoreactivity (cPLI) and 51 healthy control dogs. Methods Antithrombin and α2‐antiplasmin activity (ATA and α2AP, respectively) and concentrations of α1‐proteinase inhibitor (α1PI), α2‐macroglobulin (α2MG), C‐reactive protein (CRP), interleukins (ILs)‐2,6,8 and tumor necrosis factor‐α (TNF‐α) were prospectively measured. Severity of AP was assessed by clinical severity scoring systems. Results Mortality rate was 19%. Antithrombin activity was lower (P = .004) and maximal CRP, IL‐6, and TNF‐α concentrations higher (P < .04) in the AP group compared to the controls, whereas IL‐2, IL‐8, α1PI, and α2AP concentrations did not differ between groups. Serum α2MG concentration was not reliably detected. Serum cPLI, CRP, and IL‐6 concentrations were significantly and positively correlated. The ATA was lower (P = .04), and canine acute pancreatitis severity (CAPS) scores higher (P = .009) in nonsurvivors compared to survivors. Higher CAPS scores were associated (P < .05) with decreased ATA and increased cPLI, CRP, and IL‐6 concentrations. Conclusions and Clinical Importance Systemic inflammation in dogs with AP is manifested by increased inflammatory mediator concentrations, correlating with cPLI and CRP concentrations. Hypoantithrombinemia is associated with death. Serum concentrations of α2AP and α1PI are less useful prognostic markers. The CAPS score is a useful prognostic marker in dogs with AP.
Changes in peripheral blood oxidative stress markers and hepatic gene expression related to oxidative stress in Holstein cows with and without subacute ruminal acidosis during the periparturient period

We investigated changes in peripheral blood metabolites, oxidative stress markers (malondialdehyde, potential antioxidant capacity, and glutathione peroxidase [GPX]), and hepatic gene expression related to oxidative stress in Holstein cows with and without subacute ruminal acidosis (SARA) during the periparturient period. Eighteen multiparous Holstein cows were categorized into SARA (n=9) or non-SARA (n=9) groups depending on whether they developed SARA; reticulo-ruminal pH was <5.6 for more than 3 hr per day, during the 2 weeks after parturition. Blood and liver tissue samples were collected 3 weeks prepartum and 2 and 6 weeks postpartum, with an additional blood sample collected 0 and 4 weeks postpartum. Blood aspartate transaminase (AST) and nonesterified fatty acid (NEFA) increased significantly (P<0.05) after parturition in both groups. GPX activity decreased gradually after parturition in the SARA group. In the SARA group, gene expression of GPX 1 and microsomal glutathione S-transferase 3 (MGST3) decreased significantly (P<0.05), and expression of metallothionein 2A increased significantly (P<0.05) after parturition in the SARA group. Superoxide dismutase 1 and MGST3 decreased significantly (P<0.05) 2 weeks postpartum in the non-SARA group. Gene expression related to oxidative stress was negatively correlated with AST, NEFA and total ketone body levels. Therefore, the hepatic gene expression related to oxidative stress might change associated with a negative energy balance, and might relate the high oxidative stress in the SARA group during periparturient period.
Relationship between 3D Power Doppler Ultrasound and Serum MMP-2 and Ang-2 Levels in Pregnant Women with Preeclampsia.

OBJECTIVE To explore the relationship between 3D power Doppler ultrasound (3D-PDU) and serum MMP-2 and Ang-2 levels in pregnant women with preeclampsia (PE). STUDY DESIGN Comparative analytical study. PLACE AND DURATION OF STUDY The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, China, from October 2017 to January 2020. METHODOLOGY One hundred and thirty-four pregnant women with PE were selected as the research subjects, with 67 cases in mild group and 67 cases in severe group. Sixty-seven healthy primigravidas were selected as normal control group. Serum MMP-2 and Ang-2 were detected. All subjects underwent prenatal 3D-PDU examination, and VI, FI and VFI were measured. RESULTS Compared to normal control group, serum MMP-2 and Ang-2 levels of mild group and severe group decreased successively (all p <0.001); VI, FI, and VFI of mild group and severe group decreased successively (both p <0.001). Pearson correlation analysis showed that serum MMP-2 in pregnant women with PE was positively correlated with VI, FI, VFI (r = 0.940, p <0.001, r = 0.938, p <0.001, and r = 0.921, p <0.001, respectively); and serum Ang-2 was positively correlated with VI, FI, VFI (r = 0.958, p <0.001; r = 0.960; p <0.001; r = 0.945, p <0.001, respectively). CONCLUSION 3D-PDU has a certain application value in the diagnosis of pregnant women with PE, variation tendency of VI, FI and VFI detected by 3D-PDU is closely associated with serum MMP-2 and Ang-2 levels. Key Words: Preeclampsia, Pregnant women, MMP-2, Ang-2, 3D power Doppler ultrasound (3D-PDU).
Lopinavir/ritonavir for the treatment of SARS, MERS and COVID-19: a systematic review.

OBJECTIVE Lopinavir/ritonavir has been used for the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) coronavirus infections. It has been suggested that, based on this experience, this drug should also be studied in SARS-CoV2 infection. MATERIALS AND METHODS We performed a systematic review of the literature regarding the use of lopinavir/ritonavir for the treatment of these three infections. We systematically searched the PubMed database from inception to April 30th, 2020, to identify in-vitro and animal studies and any reports of human use of lopinavir/ritonavir for the treatment of SARS, MERS and COVID-19. We also searched the Clinicatrial.gov to identify ongoing trials. RESULTS Five in-vitro studies evaluated the effect of lopinavir/ritonavir in SARS. Three additional in-vitro studies reported the EC50 of the antiviral activity of lopinavir/ritonavir in MERS. We identified no in vitro studies evaluating the effect of lopinavir/ritonavir on the novel coronavirus. Two retrospective matched-cohort studies reported the use of lopinavir/ritonavir in combination with ribavirin for SARS patients. Three case reports and one retrospective study described the use of lopinavir/ritonavir in MERS. Twenty-two papers describe the use of lopinavir/ritonavir in adult patients with COVID-19. CONCLUSIONS The existing literature does not suffice for assessing whether Lopinavir/ritonavir has any benefit in SARS, MERS or COVID-19.
Histone chaperone FACT represses retrotransposon MERVL and MERVL-derived cryptic promoters

Abstract Endogenous retroviruses (ERVs) were usually silenced by various histone modifications on histone H3 variants and respective histone chaperones in embryonic stem cells (ESCs). However, it is still unknown whether chaperones of other histones could repress ERVs. Here, we show that H2A/H2B histone chaperone FACT plays a critical role in silencing ERVs and ERV-derived cryptic promoters in ESCs. Loss of FACT component Ssrp1 activated MERVL whereas the re-introduction of Ssrp1 rescued the phenotype. Additionally, Ssrp1 interacted with MERVL and suppressed cryptic transcription of MERVL-fused genes. Remarkably, Ssrp1 interacted with and recruited H2B deubiquitinase Usp7 to Ssrp1 target genes. Suppression of Usp7 caused similar phenotypes as loss of Ssrp1. Furthermore, Usp7 acted by deubiquitinating H2Bub and thereby repressed the expression of MERVL-fused genes. Taken together, our study uncovers a unique mechanism by which FACT complex silences ERVs and ERV-derived cryptic promoters in ESCs.