Miracle-dz/UniFAR-FTUs huggingface dataset:
RNA based individualized drug selection in breast cancer patients without patient-matched normal tissue

Background While standard RNA expression tests stratify patients into risk groups, RNA-Seq can guide personalized drug selection based on expressed mutations, fusion genes, and differential expression (DE) between tumor and normal tissue. However, patient-matched normal tissue may be unavailable. Additionally, biological variability in normal tissue and technological biases may confound results. Therefore, we present normal expression reference data for two sequencing methods that are suitable for breast biopsies. Results We identified breast cancer related and drug related genes that are expressed uniformly across our normal samples. Large subsets of these genes are identical for formalin fixed paraffin embedded samples and fresh frozen samples. Adipocyte signatures were detected in frozen compared to formalin samples, prepared by surgeons and pathologists, respectively. Gene expression confounded by adipocytes was identified using fat tissue samples. Finally, immune repertoire statistics were obtained for healthy breast, tumor and fat tissues. Conclusions Our reference data can be used with patient tumor samples that are asservated and sequenced with a matching aforementioned method. Coefficients of variation are given for normal gene expression. Thus, potential drug selection can be based on confidently overexpressed genes and immune repertoire statistics. Materials and Methods Normal expression from formalin and frozen healthy breast tissue samples using Roche Kapa RiboErase (total RNA) (19 formalin, 9 frozen) and Illumina TruSeq RNA Access (targeted RNA-Seq, aka TruSeq RNA Exome) (11 formalin, 1 frozen), and fat tissue (6 frozen Access). Tumor DE using 10 formalin total RNA tumor samples and 1 frozen targeted RNA tumor sample.
Multiscale analysis of architecture, cell size and the cell cortex reveals cortical F-actin density and composition are major contributors to mechanical properties during convergent extension

ABSTRACT The large-scale movements that construct complex three-dimensional tissues during development are governed by universal physical principles. Fine-grained control of both mechanical properties and force production is crucial to the successful placement of tissues and shaping of organs. Embryos of the frog Xenopus laevis provide a dramatic example of these physical processes, as dorsal tissues increase in Young's modulus by six-fold to 80 Pascal over 8 h as germ layers and the central nervous system are formed. These physical changes coincide with emergence of complex anatomical structures, rounds of cell division, and cytoskeletal remodeling. To understand the contribution of these diverse structures, we adopt the cellular solids model to relate bulk stiffness of a solid foam to the unit size of individual cells, their microstructural organization, and their material properties. Our results indicate that large-scale tissue architecture and cell size are not likely to influence the bulk mechanical properties of early embryonic or progenitor tissues but that F-actin cortical density and composition of the F-actin cortex play major roles in regulating the physical mechanics of embryonic multicellular tissues. Highlighted Article: Application of the cellular solids model to Xenopus dorsal isolates reveals that F-actin cortex composition, in the form of F-actin cross-linking, plays a major role in bulk mechanics during neurulation.
Do the children born after assisted reproductive technology have an increased risk of birth defects? A systematic review and meta-analysis

Abstract Background: Assisted reproductive technologies (ARTs) have made great progress. However, whether tube baby born after ART were at an increased risk of birth defects is not clear. Objective: To assess whether the ART increases the risk of birth defects in children born after ART. Search strategy: Medline, Google Scholar, and the Cochrane Library were searched. Selection criteria: Clinical trials that evaluate the risk of birth defect in children born after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and natural conceptions (NC) were included. The primary outcome was the prevalence of birth defects. Data collection and analysis: The relative risk was used as the summary measure with random effects model. We assessed heterogeneity between studies using the I 2 index. Main results: Totally 46 studies were included. The pooled relative risk (RR) estimated suggested there was an increased risk of birth defects in ART compared with the NC group (RR: 1.40; 95% CI 1.31–1.49). Twenty and fifteen studies were included to compare the risk of birth defects between NC and IVF/ICSI, respectively. The results indicated that both IVF and ICSI increase the risk of birth defects (IVF: RR 1.25; 95% CI 1.12–1.40; ICSI: RR 1.29; 95% CI 1.14–1.45). When subgroup according to plurality, 22 studies assessed the risk of birth defects after ART or NC in singletons and 15 studies evaluated the risk of birth defects in twins. The pooled RRs were 1.41 (95% CI 1.30–1.52) and 1.18 (95% CI 0.98–1.42), respectively. Conclusions: Children born after ART were at an increased risk of birth defects compared with NC. There was no difference in birth defects risk between ART twins and NC twins.
Motivators of adherence to integrated management among patients with chronic kidney disease: A qualitative study

The integrated management of chronic kidney disease (CKD) demands significant changes, as patients need to adhere to dialysis, medication, and dietary and fluid restrictions. Therefore, there is a need to identify the motivators of adherence to improve the quality of life of these patients. The aim of the present study was to explore the motivators of adherence to integrated management among patients with CKD in South Africa. A phenomenological design was used. A sample size of 12 participants was selected according to data saturation. The purposive sampling method was used to select the participants. Data were collected with the help of a semistructured interview schedule developed from the literature. A thematic framework analysis was conducted to identify the motivators of adherence to integrated management; these were found to be family support, anxiety about eligibility for kidney transplant, support of other patients, awareness of complications associated with non-adherence to integrated management, and fear of being removed from the CKD program. Identified motivators could be used to develop specific interventions that address or foster adherence behavior as a requirement for integrated management.
A Comparative Analysis of Microbial DNA Preparation Methods for Use With Massive and Branching Coral Growth Forms

In the last two decades, over 100 studies have investigated the structure of the coral microbiome. However, as yet there are no standardized methods applied to sample preservation and preparation, with different studies using distinct methods. There have also been several comparisons made of microbiome data generated across different studies, which have not addressed the influence of the methodology employed over each of the microbiome datasets. Here, we assess three different preservation methods; salt saturated dimethyl sulfoxide (DMSO) – EDTA, snap freezing with liquid nitrogen and 4% paraformaldehyde solution, and two different preparation methodologies; bead beating and crushing, that have been applied to study the coral microbiome. We compare the resultant bacterial assemblage data for two coral growth forms, the massive coral Goniastrea edwardsi and the branching coral Isopora palifera. We show that microbiome datasets generated from differing preservation and processing protocols are comparable in composition (presence/absence). Significant discrepancies between preservation and homogenization methods are observed in structure (relative abundance), and in the occurrence and dominance of taxa, with rare (low abundance and low occurrence) phylotypes being the most variable fraction of the microbial community. Finally, we provide evidence to support chemical preservation with DMSO as effective as snap freezing samples for generating reliable and robust microbiome datasets. In conclusion, we recommend where possible a standardized preservation and extraction method be taken up by the field to provide the best possible practices for detailed assessments of symbiotic and conserved bacterial associations.
Feasibility and initial outcomes of a multifaceted prevention programme of melioidosis in diabetic patients in Ubon Ratchathani, northeast Thailand

Background Melioidosis is an infection caused by Burkholderia pseudomallei, a Gram-negative bacillus found in soil and water. Diabetes mellitus is the most important risk factor for melioidosis. The recommendations for disease prevention include avoiding direct contact with soil and water, and drinking only boiled or bottled water. Methods A prospective intervention study was conducted to evaluate the feasibility and behavioural outcomes of a multifaceted prevention programme for melioidosis. Participants were diabetic adults in Ubon Ratchathani, northeast Thailand. Ten behavioural support groups consisting of 6 to 10 participants per group were conducted. Twelve behaviour change techniques were used: information about health consequences, credible source, adding objects to the environment, reconstructing the physical environment, instruction on how to perform a behaviour, demonstration of the behaviour, commitment, prompts/cues, self-monitoring of behaviour, goal setting, feedback on behaviour, and social support, and their feasibilities evaluated. Results There were 70 participants, of median age 59 years and 52 (74%) were female. Participants found the intervention beneficial, interesting and engaging. Participants indicated that they liked to watch videos with information about melioidosis delivered by local doctors and patients who survived melioidosis, and videos showing use of over-the-knee boots by local farmers. Participants felt engaged in the sessions that trialed protective gear and that made calendars with individual photographs and self-pledges as a reminder tool. The proportions of participants reporting that they always wore boots while working in rice fields increased from 30% (10/33) to 77% (28/37, p = 0.04), and that they drank only boiled or bottle water increased from 43% (30/70) to 86% (59/69, p<0.001) at 6 months post intervention. Conclusion The programme is highly acceptable to participants, and can support behaviour change. Policy makers should consider implementing the programme in areas where melioidosis is endemic. Making calendars with individual photographs and self-pledges as a reminder tool could be powerful in behaviour change interventions, and further research on this component is needed.
Defective bone repair in diclofenac treated C57Bl6 mice with and without lipopolysaccharide induced systemic inflammation

Bone repair after trauma or surgical intervention involves a tightly regulated cascade of events that starts with hemostasis and an inflammatory response, which are critical for successful healing. Nonsteroidal anti‐inflammatory drugs (NSAID) are routinely prescribed for pain relief despite their potential inhibitory effect on bone repair. The goal of this study was to determine the impact of administration of the non‐selective NSAID diclofenac in the inflammatory phase of bone repair in mice with or without lipopolysaccharide‐induced systemic inflammation. Repair of femoral window defects was characterized using micro computed tomography imaging and histological analyses at 2 weeks postoperative. The data indicate (a) impaired bone regeneration associated with reduced osteoblast, osteoclast, and macrophage activity; (b) changes in the number, activity, and distribution of mast cells in regenerating bone; and (c) impaired angiogenesis due to a direct toxic effect of diclofenac on vascular endothelial cells. The results of this study provide strong evidence to support the conjecture that administration of NSAIDs in the first 2 weeks after orthopaedic surgery disrupts the healing cascade and exacerbates the negative effects of systemic inflammation on the repair process.
Histidine-Rich Glycoprotein Suppresses Hyperinflammatory Responses of Lung in a Severe Acute Pancreatitis Mouse Model

Objectives Severe acute pancreatitis is a highly lethal disease caused by systemic inflammatory response syndrome, leading to multiple organ failure. We recently showed that histidine-rich glycoprotein (HRG) supplemental therapy ameliorated septic acute respiratory distress syndrome due to unnecessary neutrophil activation and immunothrombosis formation. Here, we evaluated the effect of HRG on lung inflammation followed by pancreatitis in a severe acute pancreatitis mouse model. Methods Mice received intraperitoneal injections of cerulein 7 times (100 &mgr;g/kg each) at 1-hour intervals to induce acute pancreatitis. Immediately after the first cerulein injection, phosphate-buffered saline, human serum albumin (20 mg/kg), or HRG (20 mg/kg) was intravenously injected. One hour after the last cerulein injection, phosphate-buffered saline or lipopolysaccharide (5 mg/kg) was intravenously injected into the tail vein. We evaluated lung inflammatory level after pancreatitis. Results We observed significantly decreased plasma HRG levels in an acute pancreatitis mouse model. Histidine-rich glycoprotein treatment inhibited lung edema and the accumulation of neutrophil in severe acute pancreatitis, but HRG did not directly affect pancreatitis. Moreover, HRG suppressed tumor necrosis factor &agr;, inducible nitric oxide synthase, interleukin 6, and neutrophil elastase mRNA expression and myeloperoxidase activity in the lung. Conclusions These data suggested that HRG ameliorated lung inflammation secondary to pancreatitis.
Occurrence of traumatic dental injuries among preschool children with Autism Spectrum Disorder

Objective: To determine the occurrence of traumatic dental injuries (TDIs) among Saudi preschool children with autism spectrum disorder (ASD) and compare it with Saudi preschool children without ASD. Methods: This study was conducted on a randomly selected sample of three to five year old Saudi preschool children in Riyadh, Saudi Arabia. The sample consisted of two groups; a study group (SG) of 257 ASD children, and a control group (CG) of age- and gender-matched 257 children without ASD. Clinical examinations were performed at selected ASD centers and kindergartens to determine the occurrence of TDIs based on modified World Health Organization (WHO) classification system. Results: Out of 514 children examined, 108 (21.0%) had suffered TDIs. The prevalence of TDIs was significantly higher in the SG (25.7%) children than the CG (16.3%) [p=0.012]. The primary maxillary central incisors were the most commonly affected teeth in both the groups; significantly more in CG (72.9%) than SG (50.1%) [p=0.017]. Enamel fracture was the most frequent type of TDI in both the groups; significantly more in CG (29.2%) than SG (21.1%) [p=0.032]. Luxation injuries and tooth avulsions were significantly higher in the SG than the CG (p=0.028). Conclusions: The occurrence of TDIs was higher in Saudi preschool children with ASD than in non-ASD children.
FGF controls epithelial-mesenchymal transitions during gastrulation by regulating cell division and apicobasal polarity

ABSTRACT To support tissue and organ development, cells transition between epithelial and mesenchymal states. Here, we have investigated how mesoderm cells change state in Drosophila embryos and whether fibroblast growth factor (FGF) signaling plays a role. During gastrulation, presumptive mesoderm cells invaginate, undergo an epithelial-to-mesenchymal state transition (EMT) and migrate upon the ectoderm. Our data show that EMT is a prolonged process in which adherens junctions progressively decrease in number throughout the migration of mesoderm cells. FGF influences adherens junction number and promotes mesoderm cell division, which we propose decreases cell-cell attachments to support slow EMT while retaining collective cell movement. We also found that, at the completion of migration, cells form a monolayer and undergo a reverse mesenchymal-to-epithelial transition (MET). FGF activity leads to accumulation of β-integrin Myospheroid basally and cell polarity factor Bazooka apically within mesoderm cells, thereby reestablishing apicobasal cell polarity in an epithelialized state in which cells express both E-Cadherin and N-Cadherin. In summary, FGF plays a dynamic role in supporting mesoderm cell development to ensure collective mesoderm cell movements, as well as proper differentiation of mesoderm cell types. Summary: FGF regulates epithelial-mesenchymal transition in mesoderm to support collective movement at gastrulation and also the reverse, mesenchymal-to-epithelial transition, during which cells acquire apicobasal polarity to support their differentiation into diverse muscle types.
Gaussian Process Regression for Binned Data

Many datasets are in the form of tables of binned data. Performing regression on these data usually involves either reading off bin heights, ignoring data from neighbouring bins or interpolating between bins thus over or underestimating the true bin integrals. In this paper we propose an elegant method for performing Gaussian Process (GP) regression given such binned data, allowing one to make probabilistic predictions of the latent function which produced the binned data. We look at several applications. First, for differentially private regression; second, to make predictions over other integrals; and third when the input regions are irregularly shaped collections of polytopes. In summary, our method provides an effective way of analysing binned data such that one can use more information from the histogram representation, and thus reconstruct a more useful and precise density for making predictions.
Neuronal cell culture from transgenic zebrafish models of neurodegenerative disease

ABSTRACT We describe a protocol for culturing neurons from transgenic zebrafish embryos to investigate the subcellular distribution and protein aggregation status of neurodegenerative disease-causing proteins. The utility of the protocol was demonstrated on cell cultures from zebrafish that transgenically express disease-causing variants of human fused in sarcoma (FUS) and ataxin-3 proteins, in order to study amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type-3 (SCA3), respectively. A mixture of neuronal subtypes, including motor neurons, exhibited differentiation and neurite outgrowth in the cultures. As reported previously, mutant human FUS was found to be mislocalized from nuclei to the cytosol, mimicking the pathology seen in human ALS and the zebrafish FUS model. In contrast, neurons cultured from zebrafish expressing human ataxin-3 with disease-associated expanded polyQ repeats did not accumulate within nuclei in a manner often reported to occur in SCA3. Despite this, the subcellular localization of the human ataxin-3 protein seen in cell cultures was similar to that found in the SCA3 zebrafish themselves. The finding of similar protein localization and aggregation status in the neuronal cultures and corresponding transgenic zebrafish models confirms that this cell culture model is a useful tool for investigating the cell biology and proteinopathy signatures of mutant proteins for the study of neurodegenerative disease. Summary: This article describes the optimization and validation of a protocol for culturing of neurons from transgenic zebrafish for the study of neurodegenerative diseases.
Premature Deaths Attributable to Long-term Exposure to Ambient Fine Particulate Matter in the Republic of Korea

Background Ambient fine particulate matter (PM2.5) is the major environmental health risk factor in Korea. Exposure to PM2.5 has been a growing public concern nationwide. With the rapid aging of the Korean population, the health effects attributable to long-term exposure to PM2.5 were expected to increase further in the future. We aimed to estimate premature deaths attributable to long-term exposure to ambient PM2.5 in Korea. Methods A modelled estimation of long-term exposure to PM2.5 was used to calculate the nationwide exposure level. Hazard ratios of long-term exposure to PM2.5 were obtained from a large prospective cohort study in North America. Modified cause of death (CoD) data, which applied the garbage code reclassification algorithm, were used to calculate premature deaths attributable to long-term exposure to PM2.5. Results From 1990 to 2013, the average population-weighted PM2.5 concentration in Korea was 30.2 μg/m3. The estimated number of premature deaths was 17,203 (95% confidence interval [CI], 11,056–22,772). The most common CoD was ischemic stroke (5,382; 3,101–7,403), followed by cancer of trachea, bronchus, and lung (4,958; 2,857–6,820), hemorrhagic stroke (3,452; 1,989–4,748), and ischemic heart disease (3,432; 1,383–5,358). Conclusion Premature deaths due to long-term exposure to PM2.5 accounted for 6.4% of all deaths in Korea. However, individual efforts alone cannot prevent the effects of air pollution. This disease burden study can serve as a basis for the establishment of government policies and budgets and can be used to assess the effectiveness of environmental health policies.
Impact of Critical Care Transesophageal Echocardiography in Medical–Surgical ICU Patients: Characteristics and Results From 274 Consecutive Examinations

Objective: Critical care echocardiography has become an integral tool in the assessment and management of critically ill patients. Critical care transesophageal echocardiography (TEE) offers diagnostic reliability, superior image quality, and an expanded diagnostic scope to transthoracic echocardiography. Despite its favorable attributes, TEE use in North American intensive care units (ICUs) remains relatively undescribed. In this article, we seek to characterize the feasibility, indications, and clinical impact of a critical care TEE program. Design: Retrospective, observational study. Setting: Tertiary care, academic critical care program consisting of 2 hospitals in Ontario, Canada. Participants: Consecutive critical care TEE examinations on ICU patients performed between December 2012 and December 2016 Interventions: None. Measurements and Main Results: Consecutive critical care TEE studies on ICU patients from December 1, 2012, to December 31, 2016, were reviewed. The TEEs performed on cardiac surgery patients and those without reports were excluded. Examination details, including indications, complications, examination complexity (number of views, Doppler techniques), and clinical recommendations were aggregated and analyzed. Two hundred seventy-four TEE studies were performed by 38 operators. Common indications for TEE studies were hemodynamic instability (45.2%), assessment for infective endocarditis (22.2%), and cardiac arrest (20.1%). A change in patient management was proposed following 79.5% of TEE studies. Thirty-eight percent of TEE studies were performed during evening hours or on weekends. There were no mechanical complications. Conclusions: Our observational data support intensivist-performed TEE as being safe and therapeutically influential across a broad range of indications. Our program’s demonstrated feasibility and impact may act as a model for TEE adoption in other North American ICUs.