Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering a Humanised Niche to Support Human Haematopoiesis in Mice: Novel Opportunities in Modelling Cancer

Despite the bone marrow microenvironment being widely recognised as a key player in cancer research, the current animal models that represent a human haematopoietic system lack the contribution of the humanised marrow microenvironment. Here we describe a murine model that relies on the combination of an orthotopic humanised tissue-engineered bone construct (ohTEBC) with patient-specific bone marrow (BM) cells to create a humanised bone marrow (hBM) niche capable of supporting the engraftment of human haematopoietic cells. Results showed that this model supports the engraftment of human CD34+ cells from a healthy BM with human haematopoietic cells migrating into the mouse BM, human BM compartment, spleen and peripheral blood. We compared these results with the engraftment capacity of human CD34+ cells obtained from patients with multiple myeloma (MM). We demonstrated that CD34+ cells derived from a diseased BM had a reduced engraftment potential compared to healthy patients and that a higher cell dose is required to achieve engraftment of human haematopoietic cells in peripheral blood. Finally, we observed that hematopoietic cells obtained from the mobilised peripheral blood of patients yields a higher number of CD34+, overcoming this problem. In conclusion, this humanised mouse model has potential as a unique and patient-specific pre-clinical platform for the study of tumour–microenvironment interactions, including human bone and haematopoietic cells, and could, in the future, serve as a drug testing platform.
Metabolic effects of air pollution exposure and reversibility.

Particulate matter < 2.5 micrometers (PM2.5) air pollution is the world's leading environmental risk factor contributing to mortality through cardiometabolic pathways. In this study, we modeled early life exposure using chow-fed C57BL/6J male mice, exposed to real-world inhaled concentrated PM2.5 (~10 times ambient levels / ~60-120ug/m3) or filtered air over 14 weeks. We investigated PM2.5 effects on phenotype, transcriptome and chromatin accessibility, compared the effects with a prototypical high-fat diet (HFD) stimulus, and examined cessation of exposure on reversibility of phenotype. Exposure to PM2.5 impaired glucose and insulin tolerance, reduced energy expenditure and 18FDG-PET uptake in brown adipose tissue. Multiple differentially expressed gene (DEG) clusters in pathways involving metabolism and circadian rhythm were noted in insulin responsive tissues. Although the magnitude of transcriptional change seen with PM2.5 was lower than HFD, the degree of alteration in chromatin accessibility after PM2.5 exposure was significant. A novel chromatin remodeler SMARCA5 (SWI/SNF complex) was regulated in response to PM2.5 with cessation of exposure associated with reversal of insulin resistance, restoration of chromatin accessibility/nucleosome positioning near transcription start sites (TSS) and exposure induced changes in the transcriptome including SMARCA5, indicating pliable epigenetic control mechanisms following exposure cessation.
Antibiotic Susceptibility Testing (AST) Reports: A Basis for Environmental/Epidemiological Surveillance and Infection Control Amongst Environmental Vibrio cholerae

Distribution, investigation, surveillance and control (DISC) of cholera outbreaks in endemic/non-endemic regions has been a concerted approach towards the management of the causal pathogen. Relevant organization, government, health systems and the public have implemented several steps towards controlling the menace, yet pathogen continues to occur with diverse phenotypes/genotypes of high clinical and epidemiological relevance. The study determines antibiotic susceptibility/resistance pattern of Vibrio cholerae isolates retrieved from six domestic water sources between March and August 2018. Serological and molecular typing methods (polymerase chain reaction or PCR) were used to confirm the isolates identity. Antibiotic susceptibility testing was conducted using six commonly employed antibiotics of V. cholerae according to the recommendation of Clinical Laboratory Standard and European Committee for Antimicrobial Susceptibility Testing with other relevant antibiotics of investigative epidemiology and infection control, employing both disc diffusion test and PCR gene detection. Samples presumptive counts ranged between 1.10 to 7.91 log10 CFU/mL. Amongst the 759 presumptive isolates retrieved, sixty-one were confirmed as V. cholerae which were further serogrouped as Non-O1/Non-O139 V. cholerae. Various V. cholerae resistant phenotypes/genoytypes were detected vis: carbapenemase (CR-Vc; 31.1%/5.3%). New Delhi Metallobetalactamase (NDM-1-Vc; 23.0%/42.5%), extended spectrum betalactamase (ESBL-Vc; 42.6%/blaTEM:86,7%), chloramphenicol resistance (62.3%/Flor: 46.2%}, tetracycline resistance (70.5%/46.7%), AmpC resistance (21.0 (34.4%/56.7%)) and various other resistant genotypes/phenotypes. It was observed that more than 50% of the confirmed V. cholerae isolates possess resistance to two or more antibiotic classes/groups with multiple antibiotic resistance index (MARI) ranging from 0.031 to 0.5. This observation provides necessary information and updates for surveillance, planning and implementation of control strategies for cholera. It would also encourage decision making, formulation of policy by the government and cholera control authorities.
Sleeping Beauty-engineered CAR T cells achieve anti-leukemic activity without severe toxicities.

BACKGROUND Chimeric antigen receptor (CAR) T cell immunotherapy has achieved complete remission and durable response in highly refractory patients. However, logistical complexity and high costs of manufacturing autologous viral products limit CAR T cell availability. METHODS We reported the early results of a phase I/II trial in B-cell acute lymphoblastic leukemia (B-ALL) patients relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) using donor-derived CD19 CAR T cells generated with the Sleeping Beauty (SB) transposon and differentiated into cytokine induced killer cells (CIK). RESULTS The cellular product was produced successfully for all patients from the donor peripheral blood (PB) and consisted mostly of CD3+ lymphocytes with 43% CAR expression. Four pediatric and 9 adult patients were infused with a single dose of CAR T cells. Toxicities reported were two grade I and a grade II cytokine release syndrome (CRS) cases at the highest dose, in the absence of graft-versus-host disease (GvHD), neurotoxicity, or dose-limiting toxicities. Six out of 7 patients, receiving the highest doses, achieved CR and CRi at day 28. Five out of 6 patients in CR were also minimal residual disease (MRD)-negative. Robust expansion was achieved in the majority of the patients. CAR T cells were measurable by transgene copy PCR up to 10 months. Integration site analysis showed a positive safety profile and highly polyclonal repertoire in vitro and at early time points after infusion. CONCLUSION SB-engineered CAR T cells expand and persist in pediatric and adult B-ALL patients relapsed after HSCT. Anti-leukemic activity was achieved without severe toxicities. TRIAL REGISTRATION clinicaltrials.gov NCT03389035. FUNDING This study was supported by grants from AIRC; CRUK; FC AECC; Ministero della salute; FRRB.
Clinical and Radiologic Outcomes of Combined Use of Biocomposite and PEEK Suture Anchors during Arthroscopic Rotator Cuff Repair: A Prospective Observational Study

The aim of the current study was to evaluate the functional and radiologic outcomes of biocompatible non-absorbable PEEK (polyetheretherketone) and biocomposite (poly-L-lactic acid/poly(lactic-co-glycolic acid) 70% + β-tricalcium phosphate) anchors, especially in terms of perianchor cyst formation during the first six months postoperatively. We prospectively analysed 29 patients who underwent arthroscopic rotator cuff repair between March and May 2019. Both PEEK and biocomposite suture anchors were used as lateral anchors in one body. Clinical outcomes were assessed using the shoulder range of motion (ROM), visual analogue scale (VAS) for pain and satisfactory score, American Shoulder and Elbow Surgeons (ASES) score, and Simple Shoulder Test (SST). All these were obtained in patients preoperatively at 3 and 6 months after surgery. The imaging evaluation included perianchor cyst formation, anchor absorption, repaired cuff integrity, and retear pattern. All functional outcomes significantly improved over time. The biocomposite anchor had a statistically significant tendency to form higher grades of fluid collection at 3 months after surgery. However, the perianchor cyst reduced by the sixth postoperative month. Six months postoperatively, the functional outcomes were improved after rotator cuff repair and similar degrees of perianchor cyst formation were observed, regardless of the suture anchor material used.
Feeding deterrence of anthraquinone, anthracene, and anthrone to rice-eating birds

Safe, effective bird repellents are needed as seed treatments and for many other agricultural uses. Quinones are distributed widely in nature and many have predator defense and antiherbivory functions. One compound, 9,10-anthraquinone, was identified as a bird repellent in the 1940s, but is not registered for use in the United States. We evaluated it and 2 structurally related compounds, anthrone and anthracene, for repellency to rice-eating birds. In choice tests with individually caged red-winged blackbirds (Agelaius phoeniceus) anthraquinone and anthrone produced comparable reductions in consumption of treated rice at rates of 0.05, 0.10, and 0.25% (g/g). At 0.50%, however, only anthraquinone suppressed consumption of untreated rice as well as treated rice. Anthracene was least effective of the 3 compounds and was tested only at 0.50%. In 1-cup tests, consumption of anthraquinone-treated rice by individual blackbirds was suppressed at 0.10, 0.25, and 0.50%. Rice consumption by individually caged female boat-tailed grackles (Quiscalus major) exposed to the 0.50% treatment was similar to that of redwings at the 0.10% treatment. In choice tests of 3-bird groups in large flight enclosures, red-winged blackbirds discriminated strongly against 0.25% anthraqunione-treated rice. Observations of videotaped birds revealed no evidence of contact irritation or unpleasant taste; rather post-ingestive illness, as evidenced by one vomiting bird, suggests that anthraquinone repellency is due to learned behavior.
Comparison of Outcome of Close Reduction Versus Open Reduction in Treatment of Comminuted Mandibular Fracture

Objective: To assess the efficiency of open reduction & internal fixation versus close reduction with maxillomandibular fixation for the treatment of Comminuted mandibular fractures. Study Design and Duration: This comparative study was carried out at Oral & Maxillofacial Surgery Department, Liaquat University of Medical & Health Science Jamshoro/Hyderabad, from November 2017 to October 2018. Material and Methods: Total 60 patients after diagnosis of Comminuted mandibular fracture with age range from 18 to 45years of either gender were included. All the patients were divided in two groups, Group A was treated with open reduction with internal fixation and Group B was treated with closed reduction with maxillomandibular fixation. Each patient had called for follow-up after 2nd week, 4th week, and 6th week. On follow-up postoperative infection, malocclusion, non-union/malunion of fracture fragments, facial asymmetry, exposed plates and sequestration of devitalized bone were documented Results: Total 60 patients were included and divided in 2 groups, in patients of group A mean age was found 32.22±5.12 years and mean age of the patients of Group B was 30.34±4.55 years. Males were found in the majority i.e 51 out of 60 patients while female were 9. Open reduction with internal fixation showed significant better outcome as compared to close reduction in the terms of complications, p-value 0.03. Conclusion: It was concluded that the open reduction with internal fixation is most effective reliable management technique with very low rates of early and late complication for the treatment of Comminuted fractures of the mandible as compared to close reduction.
Influence of dl-3-N-butylphthalide on infarction size in rats with acute myocardial infarction.

OBJECTIVE To study the influence of dl-3-N-butylphthalide (NBP) on infarction size in rats with acute myocardial infarction (AMI). METHODS AMI model was established by ligation of the left anterior descending artery. A total of 36 healthy male Sprague-Dawley rats (weight, 180 t, 180 ght, 180 ligation of left anterior descending artery. A total of 36 healthy males were assigned to model group, sham-operation (SO) group, and the NBP group (n=12 each). The rats in the NBP group were treated with intraperitoneal injection administration of 60 mg/kg/body weight NBP once a day. The rats in the other groups were given distilled water of the same volume. The MI area in each group was detected by TTC staining. The concentrations of CK-MB and LDH were detected. The concentrations of TNF-α, IL-6, MDA, and SOD were measured by ELISA. RESULTS Compared with the SO group, the myocardial infarct sizes in the model group and the NBP group were significantly increased (P<0.001), and the infarct size in the NBP group was lower than that in the model group (280.6±5.82% vs. 37.74±10.18%, P<0.05). The levels of TNF-α in the NBP group and model group were significantly increased compared with that in the SO group (P<0.001), while the level of TNF-α in the NBP group was significantly lower than that in the model group (29.01±0.81 pg/mg prot vs. 37.727 pg/mg prot, P<0.05). The level of IL-6 in the model group and NBP group was significantly higher than that in the SO group, and it was lower than that in the model group (24.13 group wamg prot vs. 27.53 pg/mg prot, P<0.05). The levels of MDA in the model group and the NBP group were significantly higher (<0.001), and the level of NBP group was lower than that of the model group (4.10 group wnmol/mg prot vs. 4.774.774. nmol/mg prot, P<0.05). The levels of SOD in the model group and NBP group were lower (P<0.001), and the SOD level in the NBP group was higher than that of the model group (53.490.001), and prot vs. 38.068. 06he SOD prot (P<0.05). CONCLUSION NBP can reduce the infarct size in SD rats with AMI.
The Impact of Some North American Migrants at Fruiting Trees in Panama

AMONG the major seasonal phenomena potentially affecting neotropical birds is the winter influx of North American migrants. The subject has been much neglected, except for brief general discussions (Morel and Bourliere, 1962; Miller, 1963) or studies restricted to specialized groups (e.g. Willis, 1966). To gain a new quantified estimation of the effect of migrants I studied their use of local food sources, especially fruiting trees, relative to use by residents.
Title Management of crime scene units by Quebec police senior managers: insight on forensic knowledge and understanding of key stakeholders Authors

What do policing leaders think and know of forensic science? Beyond crime scene investigators or detectives, how do police senior managers perceive the role, utility and limitations of forensic science? Very few empirical studies have addressed the issue. Forensic scientsts should be concerned about the perception that law enforcement senior managers have of their discipline for two reasons. First, strategic and financial decision-makers are obviously key players in the overall administration and provision of forensic science, either as a supervisor, money provider or as a customer. Second, literature has highlighted that other actors involved in forensic science underestimate the scope and possibilities offered by forensic science, hence limiting its exploitation and potential. Following interviews with 18 police senior managers from Quebec (Canada), this study shows that they generally restrict forensic science to a reactive discipline whose role and utility is to identify offenders and support the Court. This understanding of forensic science, like that of many others including a significant share of forensic scientists, differs from the perception of other police activities in modern law enforcement agencies where proactive action is sought. Considering these findings and the growing body of literature which calls for forensic science to connect more tightly with policing and security, we advocate a more extensive education of police leaders regarding the scope of forensic science.
Motorcycle accidents: characteristics of victims admitted to public hospitals and circumstances.

Background Motorcycle accidents are a considerable cause of morbidity and mortality in Brazil, with high social and economic costs. Victims are mostly men, young and vulnerable. Objective To characterize motorcycle accident victims and circumstances among patients admitted to a public hospital. Methods We administered a questionnaire to 74 victims of motorcycle accidents in the period from January through July 2018 among patients admitted to a referral hospital for elective orthopedic surgery in Salvador, Bahia, Brazil. Results Most victims were male (98.4%), up to 31 years old (49%), black or brown (84%) and had low educational level (54%). Motorcycling was the occupation of 50.8%. Drinking was less frequent among motorcyclists in the capital compared to the interior of the state (16 vs. 26%) and a larger proportion had a driving license (72 vs. 39%). Conclusion Main victims of motorcycling accident victims were male, with low educational level, and without a driving license. Actions are needed to promote road safety, including educational programs to protect life and reduce the social and economic costs of accidents.
Pentaplex real‐time PCR for differential detection of Yersinia pestis and Y. pseudotuberculosis and application for testing fleas collected during plague epizootics

Upon acquiring two unique plasmids (pMT1 and pPCP1) and genome rearrangement during the evolution from Yersinia pseudotuberculosis, the plague causative agent Y. pestis is closely related to Y. pseudotuberculosis genetically but became highly virulent. We developed a pentaplex real‐time PCR assay that not only detects both Yersinia species but also differentiates Y. pestis strains regarding their plasmid profiles. The five targets used were Y. pestis‐specific ypo2088, caf1, and pst located on the chromosome, plasmids pMT1 and pPCP1, respectively; Y. pseudotuberculosis‐specific chromosomal gene opgG; and 18S ribosomal RNA gene as an internal control for flea DNA. All targets showed 100% specificity and high sensitivity with limits of detection ranging from 1 fg to 100 fg, with Y. pestis‐specific pst as the most sensitive target. Using the assay, Y. pestis strains were differentiated 100% by their known plasmid profiles. Testing Y. pestis and Y. pseudotuberculosis‐spiked flea DNA showed there is no interference from flea DNA on the amplification of targeted genes. Finally, we applied the assay for testing 102 fleas collected from prairie dog burrows where prairie dog die‐off was reported months before flea collection. All flea DNA was amplified by 18S rRNA; no Y. pseudotuberculosis was detected; one flea was positive for all Y. pestis‐specific targets, confirming local Y. pestis transmission. Our results indicated the assay is sensitive and specific for the detection and differentiation of Y. pestis and Y. pseudotuberculosis. The assay can be used in field investigations for the rapid identification of the plague causative agent.
The ability of piglets 4 to 8 weeks old to digest and perform on diets containing two contrasting sources of non-starch polysaccharide.

Twelve Large White × Landrace boars, initial mean live weight (kg) 5·51 (s.e. 0·8) were offered cereal-based diets containing 0 (diet C) or 150 g sugar-beet pulp per kg (containing no molasses or other additive) (diet 15SB) and the indigestible marker titanium dioxide from 21 to 57 days of age. The daily intakes, live-weight gains and food conversion ratios of the piglets were monitored from day 28. The apparent digestibilities of nitrogen (N), gross energy (GE) and non-starch polysaccharides (NSP) were measured on days 32 and 56. There were no significant differences either in voluntary intakes, or in the daily live-weight gains and food conversion ratios between the two diets. Likewise, there were no significant differences in the apparent digestibility of N and GE of the two diets. However, the capacity at 56 days of age to digest N from diet 15SB was greater than at 32 days of age. The apparent digestibility of total NSP at both 32 and 56 days of age was significantly greater for diet 15SB (averaging 0·75) than for diet C (averaging 0·54) ( P P P P P
Interpreting OLS EstimandsWhen Treatment Effects Are Heterogeneous: Smaller Groups Get LargerWeights

Applied work often studies the effect of a binary variable (“treatment”) using linear models with additive effects. I study the interpretation of the OLS estimands in such models when treatment effects are heterogeneous. I show that the treatment coefficient is a convex combination of two parameters, which under certain conditions can be interpreted as the average treatment effects on the treated and untreated. The weights on these parameters are inversely related to the proportion of observations in each group. Reliance on these implicit weights can have serious consequences for applied work, as I illustrate with two well-known applications. I develop simple diagnostic tools that empirical researchers can use to avoid potential biases. Software for implementing these methods is available in R and Stata. In an important special case, my diagnostics only require the knowledge of the proportion of treated units. JEL Classification: C21, C31
THE ADAPTIVE SIGNIFICANCE OF SOME SIZE TRENDS IN ISLAND BIRDS

Species of animals living on islands may have morphological characteristics not possessed by their mainland counterparts, a fact which was recognized by Wallace (1881). He remarked that in the Celebes: "Nearly thirty species of butterflies, belonging to three different families, have a common modification in the shape of their wings by which they can be distinguished at a glance from their allies in any other island or country whatever, and all these are larger than the representative forms inhabiting most of the adjacent islands. " Among birds there is an apparently undisputed tendency for island forms to have a plumage more drab than that of their most closely related mainland forms (Murphy and Chapin, 1929; Murphy, 1938; Amadon, 1953; Grant, 1965a). It has also been reported that island birds have long bills (Murphy, loc. cit.; Chapman, 1940; Amadon, loc. cit.) and long wings, the latter being interpreted as an indication of large body-size (Mayr and Vaurie, 1948; Amadon, loc. cit.). Yet these trends of large size in island birds are not universal, since there are reports of opposite trends (Hesse et al., 1937; Bourne, 1955). For instance Bourne (loc. cit.) has pointed out that many of the birds of the Cape Verde islands have smaller dimensions than their mainland counterparts. He considered this to be a "character of sedentary species which is often particularly well shown by insular forms. " Furthermore, even if a size trend among island birds can be demonstrated, its significance has yet to be explained satisfactorily. Attempts to interpret the greater bill-length and winglength of island birds have been unable to