Miracle-dz/UniFAR-FTUs huggingface dataset:
Distribution of insecticide resistance and mechanisms involved in the arbovirus vector Aedes aegypti in Laos and implication for vector control

Background The yellow fever mosquito Aedes aegypti is the major vector of dengue, yellow fever, Zika, and Chikungunya viruses. Worldwide vector control is largely based on insecticide treatments but, unfortunately, vector control programs are facing operational challenges due to mosquitoes becoming resistant to commonly used insecticides. In Southeast Asia, resistance of Ae. aegypti to chemical insecticides has been documented in several countries but no data regarding insecticide resistance has been reported in Laos. To fill this gap, we assessed the insecticide resistance of 11 Ae. aegypti populations to larvicides and adulticides used in public health operations in the country. We also investigated the underlying molecular mechanisms associated with resistance, including target site mutations and detoxification enzymes putatively involved in metabolic resistance. Methods and results Bioassays on adults and larvae collected in five provinces revealed various levels of resistance to organophosphates (malathion and temephos), organochlorine (DDT) and pyrethroids (permethrin and deltamethrin). Synergist bioassays showed a significant increased susceptibility of mosquitoes to insecticides after exposure to detoxification enzyme inhibitors. Biochemical assays confirmed these results by showing significant elevated activities of cytochrome P450 monooxygenases (P450), glutathione S-transferases (GST) and carboxylesterases (CCE) in adults. Two kdr mutations, V1016G and F1534C, were detected by qPCR at low and high frequency, respectively, in all populations tested. A significant negative association between the two kdr mutations was detected. No significant association between kdr mutations frequency (for both 1534C and 1016G) and survival rate to DDT or permethrin (P > 0.05) was detected. Gene Copy Number Variations (CNV) were detected for particular detoxification enzymes. At the population level, the presence of CNV affecting the carboxylesterase CCEAE3A and the two cytochrome P450 CYP6BB2 and CYP6P12 were significantly correlated to insecticide resistance. Conclusions These results suggest that both kdr mutations and metabolic resistance mechanisms are present in Laos but their impact on phenotypic resistance may differ in proportion at the population or individual level. Molecular analyses suggest that CNV affecting CCEAE3A previously associated with temephos resistance is also associated with malathion resistance while CNV affecting CYP6BB2 and CYP6P12 are associated with pyrethroid and possibly DDT resistance. The presence of high levels of insecticide resistance in the main arbovirus vector in Laos is worrying and may have important implications for dengue vector control in the country.
A Subset of Colorectal Cancers with Cross-Sensitivity to Olaparib and Oxaliplatin

Purpose: Defects in the homologous recombination (HR) repair pathway are of clinical interest due to sensitivity of HR-deficient cells to PARP inhibitors. We were interested in defining PARP vulnerability in patients with metastatic colorectal cancer (mCRC) carrying KRAS and BRAF mutations who display poor prognosis, have limited therapeutic options, and represent an unmet clinical need. Experimental Design: We tested colorectal cancer cell lines, patient-derived organoids (PDO), and patient-derived xenografts (PDX) enriched for KRAS and BRAF mutations for sensitivity to the PARP inhibitor olaparib, and the chemotherapeutic agents oxaliplatin and 5-fluorouracil (5-FU). Genomic profiles and DNA repair proficiency of colorectal cancer models were compared with pharmacologic response. Results: Thirteen of 99 (around 13%) colorectal cancer cell lines were highly sensitive to clinically active concentrations of olaparib and displayed functional deficiency in HR. Response to PARP blockade was positively correlated with sensitivity to oxaliplatin in colorectal cancer cell lines as well as patient-derived organoids. Treatment of PDXs with olaparib impaired tumor growth and maintenance therapy with PARP blockade after initial oxaliplatin response delayed disease progression in mice. Conclusions: These results indicate that a colorectal cancer subset characterized by poor prognosis and limited therapeutic options is vulnerable to PARP inhibition and suggest that PDO-based drug-screening assays can be used to identify patients with colorectal cancer likely to benefit from olaparib. As patients with mCRC almost invariably receive therapies based on oxaliplatin, “maintenance” treatment with PARP inhibitors warrants further clinical investigation.
Genetic polymorphisms of ACE I/D, IL-1β G > A and IL-4 VNTR among Egyptian subjects with rheumatoid arthritis

Abstract Background Various reports examined the contribution of ACE I/D, IL-1β G > A and IL-4 VNTR with the susceptibility to RA but with conflicting findings. The goal of this study is to assess the impact of these three variants with the susceptibility, clinical and biochemical markers in addition to different composite indices of RA. Subjects and Methods This case-control survey enclosed 120 RA Egyptian patients who were emulated with 150 healthy controls from the same territory. Their genomic DNA was genotyped utilising the PCR approach. Results RA patients with ACE allele (D) and IL-4 VNTR allele (2 R) were expressively higher emulated with healthy controls (p < .05). Nevertheless, RA patients with IL-1β (A allele) failed to achieve an apparent significant emulated with healthy controls (p > .05). Conclusions This work specifies a noteworthy association for ACE I/D and IL-4 VNTR but not IL-1β G > A polymorphisms with RA susceptibility among Egyptian subjects.
Sacrificial Entrepreneurship: The Political Economy of Queer and Trans of Color Community Arts under Neoliberalism

ABSTRACT This ethnographic study considers the political economy of queer and trans of color community organizations in the context of urban neoliberal governance in Toronto, Canada. While state institutions promote entrepreneurship-based arts funding as a means of economic development, queer and trans of color grassroots initiatives engage with these institutions in ways that compel a reconsideration of the relationship between entrepreneurship and neoliberalism. I propose the concept sacrificial entrepreneurship to identify how the disruption of the neoliberal incitement to personal gain by sacrificing one’s economic well-being is patterned along lines of race, gender and sexuality. Focusing on Unapologetic Burlesque, a queer anti-racist community performance initiative, I show how queer and trans of color grassroots initiatives in Toronto take public resources intended to promote individual profit-making to create minoritized spaces of belonging. Through sacrificial entrepreneurship queer and trans of color subjects simultaneously collude and oppose the unfolding of neoliberal state initiatives.
Donor surfactant protein A2 polymorphism and lung transplant survival

Purpose Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the surfactant protein (SP)-A gene of the donor lung allograft and recipient post-transplant outcome. Methods Lung-transplant patients (n=192) were prospectively followed-up with pulmonary function tests, bronchoscopies with bronchoalveolar lavage and biopsies. Donor lungs were assayed for SP-A1 (6An) and SP-A2 (1An) gene polymorphism using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported. Results SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A0 (n=102) versus 1A1 variant (n=68) or SP-A2 genotype 1A01A0 (n=54) versus 1A0A1 (n=38) had greater survival at 1 year (log-rank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for 1-year survival and diagnosis showed a reduced survival for 1A1 variant and the 1A01A1 genotype. Furthermore, when survival was conditional on 1-year survival no significance was observed, indicating that the survival difference was due to the first year's outcome associated with the 1A1 variant. Conclusion Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A1 had a reduced survival at 1 year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome. Donor genetic polymorphisms of the lung-specific innate defence systems determine post-lung transplant recipient outcome http://bit.ly/2QNpX7Q
The Experience of Land and Water Birth Within the American Association of Birth Centers Perinatal Data Registry, 2012-2017

Consumer demand for water birth has grown within an environment of professional controversy. Access to nonpharmacologic pain relief through water immersion is limited within hospital settings across the United States due to concerns over safety. The study is a secondary analysis of prospective observational Perinatal Data Registry (PDR) used by American Association of Birth Center members (AABC PDR). All births occurring between 2012 and 2017 in the community setting (home and birth center) were included in the analysis. Descriptive, correlational, and relative risk statistics were used to compare maternal and neonatal outcomes. Of 26 684 women, those giving birth in water had more favorable outcomes including fewer prolonged first- or second-stage labors, fetal heart rate abnormalities, shoulder dystocias, genital lacerations, episiotomies, hemorrhage, or postpartum transfers. Cord avulsion occurred rarely, but it was more common among water births. Newborns born in water were less likely to require transfer to a higher level of care, be admitted to a neonatal intensive care unit, or experience respiratory complication. Among childbearing women of low medical risk, personal preference should drive utilization of nonpharmacologic care practices including water birth. Both land and water births have similar good outcomes within the community setting.
Less invasive surfactant administration in preterm infants with respiratory distress syndrome—an updated meta-analysis

Background: Less invasive surfactant administration (LISA) seems to have a good application prospect both in experimental models and patients with respiratory distress syndrome (RDS). Data regarding the effect of LISA procedure on RDS are conflicting. Methods: A search was conducted by two investigators involved in this research in PubMed, Embase, and Cochrane databases for studies in English and in Wanfang, VIP, and Cnki databases for Chinese studies (all last launched on December 18, 2018). Odds ratio and weighted mean difference were calculated using a random-effects or fixed-effects model, depending on the data type and heterogeneity of the included studies. Results: The comparison of effectiveness on RDS: (1) with respect to mechanical ventilation (<72 hours) and mechanical ventilation (all time periods). Data showed significant differences between LISA/control groups. (2) With respect to days of mechanical ventilation, data showed no significant differences between LISA/control groups. (3) With respect to bronchopulmonary dysplasia, the analysis showed that there was significant difference between LISA group and control group. (4) Regarding days of supplementary oxygen therapy and hospital stay, no significant differences were found. The comparison of possible complications of RDS: (1) data for mortality, pneumothorax and pulmonary hemorrhage showed no differences in the two groups. (2) Data for retinopathy of preterm comparison showed significant difference between the two groups. (3) Regarding intraventricular hemorrhage/periventricular leukomalacia, significant differences were found between the two groups. Conclusion: Based on the above evidences, LISA is an effective and safe treatment for preterm infants with RDS.
Functional Genomics Identifies Hepatitis-Induced STAT3–TYRO3–STAT3 Signaling as a Potential Therapeutic Target of Hepatoma

Purpose: Hepatitis promotes the development and recurrence of hepatocellular carcinoma (HCC). Receptor tyrosine kinases (RTK) play critical roles in the development of many cancers. We explored the potential roles of RTKs in hepatitis-related liver cancers. Experimental Design: We conducted loss-of-function screening to elucidate the roles of RTKs in the development of HCC in vitro and in vivo. Results: Many RTKs were coexpressed in HCC and were involved in tumor development and growth. Of these, TYRO3 promoted tumor growth and was clinically associated with hepatitis activity and poor prognosis. In mice, chemical-induced hepatitis transcriptionally activated Tyro3 expression via IL-6/IL6R–STAT3 signaling. Moreover, hepatitis-associated apoptotic cells facilitated the presentation of GAS6, a TYRO3 ligand, to further activate TYRO3-mediated signaling. Furthermore, TYRO3 activation elicited intracellular SRC- and STAT3 signaling. In mice, hepatitis and Tyro3 synergistically promoted HCC development. Silencing TYRO3 expression or inhibiting its kinase activity suppressed xenograft HCC growth in nude mice. Conclusions: Many RTKs are simultaneously involved in HCC development. Hepatitis exerts dual effects on the activation of TYRO3-mediated signaling in HCC cells, which further elicits the “TYRO3–STAT3–TYRO3” signaling loop to facilitate tumor growth. Our findings unveil a previously unrecognized link between RTKs and hepatitis-associated HCC and suggest TYRO3 as a marker and therapeutic target for the HCCs with higher hepatitis activity.
Differences in receipt of opioid agonist treatment and time to enter treatment for opioid use disorder among specialty addiction programs in the United States, 2014-17

Background Access to adequate treatment for opioid use disorder (OUD) has been a high priority among American policymakers. Elucidation of the sociodemographic and institutional differences associated with the use, or lack thereof, of opioid agonist therapy (OAT) provides greater clarity on who receives OAT. Timely access to care is a further consideration and bears scrutiny as well. Methods We draw upon data from the Treatment Episode Data Set—Admissions (TEDS-A) to analyse the relationship between sociodemographic and institutional characteristics and the receipt of opioid agonist treatments and time waiting to enter treatment. Results Estimates from logistic regression models highlight certain groups which show lower odds of receipt of OAT, including those in precarious housing arrangements, those unemployed or not otherwise in the labor force, and those referred by drug abuse care providers, educational institutions, employers, and the criminal justice system. Groups which showed higher odds of waiting over a week to enter treatment included those who were separated, divorced, or widowed, those working part-time, and those referred by drug abuse care providers, employers, and the criminal justice system. Conclusion Given the efficacy of OAT and the adverse outcomes associated with long waiting times, coordinated effort is needed to understand why these differences persist and how they may be addressed through appropriate policy responses.
A pilot randomised controlled trial of the management of systolic blood pressure during endovascular thrombectomy for acute ischaemic stroke

It is unknown whether systolic blood pressure augmentation during endovascular thrombectomy improves clinical outcomes. This pilot randomised controlled trial aimed to assess the feasibility of differential systolic blood pressure targeting during endovascular thrombectomy procedures for anterior circulation ischaemic stroke. Fifty‐one eligible patients fulfilling the national criteria for endovascular thrombectomy were randomly assigned to receive either standard or augmented systolic blood pressure management from the start of anaesthesia to recanalisation of the target vessel. Systolic blood pressure targets for the standard and augmented groups were 130–150 mmHg and 160–180 mmHg, respectively. The study achieved all feasibility targets, including a recruitment rate of 3.5 participants per week and median (IQR [range]) of mean systolic blood pressure separation between groups of 139 (135–143 [115–154]) vs. 167 (150–175 [113–188]) mmHg, p < 0.001. Data completeness was 99%. Independent functional recovery at 90 days (modified Rankin Scale 0, 1 or 2) was achieved in 30 (59%) patients, which is consistent with previously published data. There were no safety concerns with trial procedures. In conclusion, a large randomised controlled efficacy trial of standard vs. augmented systolic blood pressure management during endovascular thrombectomy is feasible.
Work Performance Among Informal Caregivers: A Review of the Literature

Objectives: To examine the association between informal caregiving and caregiver work performance. Method: A systematized review of the literature. Results: We found that caregiving has an adverse impact on work performance: caregivers experience substantial work disruptions and negative work performance outcomes, and these findings were consistent across measures. Our synthesis suggests that caregivers miss a significant amount of work and have reductions in productivity due to their caregiving responsibilities. However, significant methodological limitations with the reviewed studies make systematic interpretations and causal determinations challenging. Discussion: Examining the effect of caregiving on work performance is critical to better understand the full impact of caregiving, especially as demand for caregivers increases as the population ages. This comprehensive review suggests that caregiving has a significant negative impact on work performance, although methodological challenges remain in this area of science. These findings should inform both public policy development and workplace benefits design.
PREVALENCE OF YERSINIA AMONG WILD SIKA DEER (CERVUS NIPPON) AND BOARS (SUS SCROFA) IN JAPAN

Abstract: We examined the prevalence of Yersinia, including pathogenic species such as Yersinia enterocolitica and Yersinia pseudotuberculosis, among wild sika deer (Cervus nippon) and boars (Sus scrofa) captured in Japan. The prevalence of Yersinia in the wild deer was 75% (207/277) and in the boars was 74% (40/54). A total of 417 isolates of nine Yersinia species were isolated from the animals examined: the largest number of isolates (48%, 200/417) were Y. enterocolitica biotype 1A. Pathogenic Y. enterocolitica 1B/O:8 were also isolated from two deer, and Y. pseudotuberculosis serogroups 3 and 4 were isolated from two boars and a deer, respectively. The pathogenic Y. enterocolitica 1B/O:8 isolates carried four virulence genes (ail, ystA, yadA, and virF), and Y. pseudotuberculosis serogroups 3 and 4 isolates carried three virulence genes (inv, yadA, and lcrF). Although the Y. enterocolitica 1B/O:8 and Y. pseudotuberculosis isolates were sensitive to almost all the antimicrobials tested, the two Y. enterocolitica 1B/O:8 isolates were resistant to azithromycin and ampicillin, and the three Y. pseudotuberculosis isolates were resistant only to azithromycin. These findings suggested that wild deer and boars might be important reservoirs for the agent causing human yersiniosis.
Tinnitus, hearing loss and inflammatory processes in an older Portuguese population

Abstract Objective: Tinnitus is associated with various conditions such as presbycusis, infectious, autoimmune and many other diseases. Our study aims to identify an association between inflammatory markers and the presence of tinnitus or hearing loss (HL). Design: Exploratory study including a structured interview, complete ENT observation, audiological and inflammatory markers evaluation. Study Sample: Sixty women and 54 men (55 to 75 years) from the Portuguese population, with or without sensory presbycusis and/or tinnitus. Results: IL10 levels were significantly lower in participants with tinnitus than in those without tinnitus. Moreover, TGF-β was lower in older participants (p = 0.034), IL1α was higher in participants with tonal tinnitus (p = 0.033), and IL2 was lower in participants who reported partial or complete residual inhibition (p = 0.019). Additionally, we observed a negative correlation between tinnitus duration and IL10 levels (r= −.281), and between HSP70 levels and tinnitus loudness (r= −.377). TNF-α and HSP70 levels appears to be sensitive to the time when samples were collected (morning or afternoon). Conclusions: The results of our study showing fluctuations in inflammatory markers along the hearing loss process, reinforce the idea that inflammatory mechanisms are involved in hearing loss pathogenesis but also in tinnitus. IL10 levels appear significantly altered in tinnitus but not in hearing loss.
Report of a new six-panel flow cytometry marker for early differential diagnosis of APL from HLA-DR negative Non-APL leukemia

Abstract Although AML-M3 (APL) and HLA-DR negative non-APL are characterized by negative HLA-DR antigen, they are different entities with similar morphology in some cases. The aim of this study is the precise, differential diagnosis of APL from HLA-DR negative non-APL by flow cytometry to narrow the diagnosis window. Bone marrow or blood samples of 580 AML patients were analyzed, and flow cytometry and molecular analysis were performed for the diagnosis of blood disorders. In 105 HLA-DR negative AML patients, expression of HLA-DR, CD33, CD117, CD11b, CD64, CD34, CD9 and myeloperoxidase staining pattern were evaluated. Fifty-six patients were diagnosed with APL, and 49 patients were diagnosed with HLA-DR negative non-APL. The APL blasts expressed CD33, CD117, CD64, and CD9 in 100%, 80.3%, 94.6%, and 100% of the cases, respectively. HLA-DR negative non-APL blasts expressed CD33, CD117, CD64 and CD9 in 75.5%, 59.1%, 32.6%, and 73.4% of the cases, respectively. APL cells were negative for HLA-DR, CD11b, and CD34 in 96.4%, 94.6%, and 91.0%, respectively. Blasts in HLA-DR negative non M3-AML were negative for CD11b, CD117, and CD34 in 77.5%, 40.9%, and 22.4%, respectively. We also investigated myeloperoxidase (MPO) staining pattern and found strong diffuse reaction in APL cells while HLA-DR negative non-APL cells showed focal positive reaction. In all of the APL patients, except for one, PML/RARA translocation was positive, and in another case with HLA-DR negative non-APL, PML/RARA and other translocations were not detected. The six-panel combination profile rapidly and specifically identifies APL from other HLA-DR negative AML.