Miracle-dz/UniFAR-FTUs huggingface dataset:
An inquiry‐based approach in large undergraduate labs: Learning, by doing it the “wrong” way

Undergraduate laboratory courses, owing to their larger sizes and shorter time slots, are often conducted in highly structured modes. However, this approach is known to interfere with students' engagement in the experiments. To enhance students' engagement, we propose an alternative mode of running laboratory courses by creating some “disorder” in a previously adopted structure. After performing an experiment in the right way, the students were asked to repeat the experiment but with a variation at certain steps leading to the experiment being done the “wrong” way. Although this approach led to fewer experiments being conducted in a semester, it significantly enhanced the students' involvement. This was also reflected in the students' feedback. The majority of students preferred repeating an experiment with a variant protocol than performing a new experiment. Although we have tested this inquiry‐based approach only for an undergraduate laboratory course in molecular biology, we believe such an approach could also be extended to undergraduate laboratory courses of other subjects.
The Prostate

Correspondence Nobuyuki Hinata, Department of Urology, Kobe University Graduate School of Medicine, 7‐5‐1 Kusunoki‐cho, Kobe 650‐0017, Japan. Email: hinata@med.kobe-u.ac. jp Abstract Background: The optimal extent of lymph node dissection in radical prostatectomy has not been determined. Lymph nodes in the fossa of Marcille, which is an important pelvic lymphatic pathway and candidate for additional dissection, have not been evaluated at the molecular level. Here, we assessed by molecular analysis the presence of occult positive lymph nodes in the fossa of Marcille in patients with clinically localized high‐risk prostate cancer. Methods: Fifty‐two patients with clinically localized high‐risk prostate cancer underwent pelvic lymph node dissection accompanied by robot‐assisted radical prostatectomy. All nodal packets were dissected separately and grouped into right and left obturator, external and internal iliac regions (including common iliac region to ureter crossing), and fossa of Marcille. All lymph nodes were bisected and evaluated by histopathological or molecular analysis using a quantitative reverse transcription‐polymerase chain reaction. The number of positive lymph nodes in the fossa of Marcille and the difference in detection rate were investigated using histopathological and molecular analyses. Perioperative complication rate and predictive factors for biochemical recurrence were evaluated. Results: In the molecular analysis, there were seven positive lymph nodes in the fossa of Marcille in three patients, which were coexistent with positive nodes in other regions. The detection rate of positive lymph nodes was significantly higher using molecular than histopathological analysis (P< .01). Perioperative complication rate within 90 days after the operation was 25.0% and no Clavien‐Dindo grade ≥3 complication was confirmed. Detection of metastasis by histopathological and molecular analysis was a significant factor related to biochemical recurrence in the Cox proportional hazards regression model. Conclusions: No case of positive lymph nodes in the fossa of Marcille that had skipped over other regions was confirmed. Additional lymph node dissection of fossa of Marcille did not lead to complete resection of molecularly positive lymph nodes.
Reinforcement Learning-Based Optimal Stabilization for Unknown Nonlinear Systems Subject to Inputs With Uncertain Constraints

This article presents a novel reinforcement learning strategy that addresses an optimal stabilizing problem for unknown nonlinear systems subject to uncertain input constraints. The control algorithm is composed of two parts, i.e., online learning optimal control for the nominal system and feedforward neural networks (NNs) compensation for handling uncertain input constraints, which are considered as the saturation nonlinearities. Integrating the input–output data and recurrent NN, a Luenberger observer is established to approximate the unknown system dynamics. For nominal systems without input constraints, the online learning optimal control policy is derived by solving Hamilton–Jacobi–Bellman equation via a critic NN alone. By transforming the uncertain input constraints to saturation nonlinearities, the uncertain input constraints can be compensated by employing a feedforward NN compensator. The convergence of the closed-loop system is guaranteed to be uniformly ultimately bounded by using the Lyapunov stability analysis. Finally, the effectiveness of the developed stabilization scheme is illustrated by simulation studies.
Maternal Type 1 Diabetes Reduces Autoantigen-Responsive CD4+ T Cells in Offspring

Autoimmunity against pancreatic β-cell autoantigens is a characteristic of childhood type 1 diabetes (T1D). Autoimmunity usually appears in genetically susceptible children with the development of autoantibodies against (pro)insulin in early childhood. The offspring of mothers with T1D are protected from this process. The aim of this study was to determine whether the protection conferred by maternal T1D is associated with improved neonatal tolerance against (pro)insulin. Consistent with improved neonatal tolerance, the offspring of mothers with T1D had reduced cord blood CD4+ T-cell responses to proinsulin and insulin, a reduction in the inflammatory profile of their proinsulin-responsive CD4+ T cells, and improved regulation of CD4+ T cell responses to proinsulin at 9 months of age, as compared with offspring with a father or sibling with T1D. Maternal T1D was also associated with a modest reduction in CpG methylation of the INS gene in cord blood mononuclear cells from offspring with a susceptible INS genotype. Our findings support the concept that a maternal T1D environment improves neonatal immune tolerance against the autoantigen (pro)insulin.
Lung Ultrasound to Evaluate Invasive Fungal Diseases after Allogeneic Hematopoietic Stem Cell Transplantation

Invasive fungal diseases (IFDs) are a leading cause of infection-related-mortality after allogeneic hematopoietic stem cell transplantation (HSCT). In this prospective pilot study, we investigated the use of bedside lung ultrasound (US) in IFD management. Ten consecutive hematological patients, who developed pulmonary IFD after HSCT, were included in the study. Standard computed tomography scan and lung US were performed at IFD diagnosis and 10 days after antifungal treatment. The lung US demonstrated a high sensitivity in the detection of lung lesions at IFD diagnosis and in the follow-up examinations. It is of potential clinical relevance for IFD management in hematological patients.
Complete Genome Sequence of Pandoraea pnomenusa TF-18, a Multidrug-Resistant Organism Isolated from the Rhizosphere of Rice (Oryza sativa L. subsp. japonica)

Pandoraea pnomenusa strain TF-18 was isolated from the roots of rice seedlings on selective medium containing four classes of antibiotics for isolation of Burkholderia pseudomallei. Using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing technology, we report here a complete genome of 5,499,432 bases, a GC content of 64.8%, and 4,849 coding sequences. ABSTRACT Pandoraea pnomenusa strain TF-18 was isolated from the roots of rice seedlings on selective medium containing four classes of antibiotics for isolation of Burkholderia pseudomallei. Using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing technology, we report here a complete genome of 5,499,432 bases, a GC content of 64.8%, and 4,849 coding sequences.
The long non-coding RNA Cancer Susceptibility 15 is induced by Isocitrate Dehydrogenase mutations and maintains an immature phenotype in adult acute myeloid leukemia.

We and others recently showed that coordinated expression of long non-coding (lnc)RNA is essential for myeloid differentiation and that, in turn, deregulation of lncRNA contributes to the pathogenesis of acute myeloid leukemia (AML). To better understand the relationship between lncRNA that control granulopoiesis and the block of differentiation in AML blasts, we sequenced stranded, non-poly-A-enriched cDNA libraries that were prepared from healthy human donor bone marrow (deposited under GEO accession number #GSE98946). Within this dataset, expression of the lncRNA Cancer Susceptibility 15 (CASC15) was significantly inversely correlated with myeloid differentiation and highly enriched in myeloblasts, which suggests a role in maintaining stem cell features such as an immature phenotype and/or self-renewal. Due to the reported proto-oncogenic role of CASC15 in childhood AML, we further explored CASC15 in the context of adult AML, especially in patients with mutated isocitrate dehydrogenase (IDH).
Molecular Mechanism of Runx2-Dependent Bone Development

Runx2 is an essential transcription factor for skeletal development. It is expressed in multipotent mesenchymal cells, osteoblast-lineage cells, and chondrocytes. Runx2 plays a major role in chondrocyte maturation, and Runx3 is partly involved. Runx2 regulates chondrocyte proliferation by directly regulating Ihh expression. It also determines whether chondrocytes become those that form transient cartilage or permanent cartilage, and functions in the pathogenesis of osteoarthritis. Runx2 is essential for osteoblast differentiation and is required for the proliferation of osteoprogenitors. Ihh is required for Runx2 expression in osteoprogenitors, and hedgehog signaling and Runx2 induce the differentiation of osteoprogenitors to preosteoblasts in endochondral bone. Runx2 induces Sp7 expression, and Runx2, Sp7, and canonical Wnt signaling are required for the differentiation of preosteoblasts to immature osteoblasts. It also induces the proliferation of osteoprogenitors by directly regulating the expression of Fgfr2 and Fgfr3. Furthermore, Runx2 induces the proliferation of mesenchymal cells and their commitment into osteoblast-lineage cells through the induction of hedgehog (Gli1, Ptch1, Ihh), Fgf (Fgfr2, Fgfr3), Wnt (Tcf7, Wnt10b), and Pthlh (Pth1r) signaling pathway gene expression in calvaria, and more than a half-dosage of Runx2 is required for their expression. This is a major cause of cleidocranial dysplasia, which is caused by heterozygous mutation of RUNX2. Cbfb, which is a co-transcription factor that forms a heterodimer with Runx2, enhances DNA binding of Runx2 and stabilizes Runx2 protein by inhibiting its ubiquitination. Thus, Runx2/Cbfb regulates the proliferation and differentiation of chondrocytes and osteoblast-lineage cells by activating multiple signaling pathways and via their reciprocal regulation.
Early caregiving quality predicts consistency of competent functioning from middle childhood to adolescence following early psychosocial deprivation

Abstract Adverse developmental outcomes for some children following institutional care are well established. Removal from institutional care and placement into families can promote recovery. However, little is known about how positive outcomes are sustained across adolescence among children with histories of severe deprivation. The present study examined the caregiving conditions that are associated with attaining and maintaining competent functioning (i.e., outcomes within typical levels) from middle childhood to adolescence following exposure to early institutional care. The participants included children with and without a history of institutional care who had competence assessed at ages 8, 12, and 16 years across seven domains: family relationships, peer relationships, academic performance, physical health, mental health, substance use (ages 12 and 16 years only), and risk-taking behavior. The participants were grouped based on whether they were always versus not always competent and never versus ever competent at ages 8 through 16 years. Adolescents with a history of institutional care were less likely to be consistently competent than those who were family reared. Among those who were exposed to early institutional rearing, maintaining competent functioning from 8 to 16 years was associated with spending less time in institutions and receiving higher-quality caregiving early in life. Ensuring high quality early caregiving may promote competent functioning following early deprivation.
The cost of deer to trees: changes in resource allocation from growth-related traits and phenolic content to structural defence

Background and aims – Plants may use various defence mechanisms to protect their tissues against deer browsing and the allocation of resources to defence may trade-off with plants’ growth. In a context of increasing deer populations in European forests, understanding the resource allocation strategies of trees is critical to better assess their ability to face an increasing browsing pressure. The aim of this study was to determine how deer removal affects the resource allocation to both defensive and growth-related traits in field conditions for three tree species (Abies alba, Picea abies and Fagus sylvatica). Methods – We compared eight pairs of fenced-unfenced plots to contrast plots with and without browsing pressure. The pairs were set up in 2005 and 2014 to compare different fencing duration. We measured leaf and shoot traits related to the defence against herbivores (phenolic content, structural resistance, C:N ratio) and to the investment in plants’ growth and productivity (specific leaf area and nutrient content). Key results – For the three species, the structural resistance of leaves and shoots was negatively correlated with SLA, nutrient content and phenolic content. For Abies alba, exclusion of deer decreased shoot structural resistance in favour of higher nutrient content, SLA and phenolic content. The fencing duration had no effect on the different measured traits. Conclusions – Our results support the assumption of a trade-off between structural defence and growth-related traits at the intraspecific scale for the three studied species. We also confirmed the hypothesis that exposure to deer browsing is involved in the resource allocation of woody species. For Abies alba, fencing led to a change in resource allocation from structural defence to growth-related traits and chemical defence.
DNA double strand break repair in Escherichia coli perturbs cell division and chromosome dynamics

To prevent the transmission of damaged genomic material between generations, cells require a system for accommodating DNA repair within their cell cycles. We have previously shown that Escherichia coli cells subject to a single, repairable site-specific DNA double-strand break (DSB) per DNA replication cycle reach a new average cell length, with a negligible effect on population growth rate. We show here that this new cell size distribution is caused by a DSB repair-dependent delay in completion of cell division. This delay occurs despite unperturbed cell size regulated initiation of both chromosomal DNA replication and cell division. Furthermore, despite DSB repair altering the profile of DNA replication across the genome, the time required to complete chromosomal duplication is invariant. The delay in completion of cell division is accompanied by a DSB repair-dependent delay in individualization of sister nucleoids. We suggest that DSB repair events create inter-sister connections that persist until those chromosomes are separated by a closing septum.
rosthesis–patient mismatch in the mitral position: Old oncept, new evidences

T revious studies have demonstrated that prosthesis–patient mismatch (PPM) is associated with inferior hemodynamics, less regression of left ventricular hypertrophy, more cardiac events, and higher mortality rates after aortic valve eplacement. However, the hemodynamic and clinical impact of PPM after itral valve replacement (MVR) are relatively unexplored. The elegant study resented by Lam and colleagues in this issue of the Journal is indeed one of the rst reports to demonstrate that PPM is associated with worse outcome after MVR. he main findings of this study are that (1) the incidence of mitral PPM is much igher than previously believed; (2) it is associated with a 4-fold increase in the risk f congestive heart failure after MVR; and (3) it independently affects postoperative urvival. Mitral PPM is actually not a new concept. In the first report of mitral PPM ublished in 1981, Rahimtoola and Murphy described the case of a patient who emained symptomatic and had persistent pulmonary artery hypertension and proressive right-sided failure after MVR. In the early 1990s, Dumesnil and coleagues demonstrated the existence of a relationship between the indexed effecive orifice area (EOA) and the transvalvular pressure gradient in normally unctioning prostheses implanted in the mitral position. These findings are consisent with the concept that PPM occurs when the EOA of the prosthesis is too small n relation to the patient’s body size, resulting in an abnormally high postoperative radient. In patients with an aortic prosthesis, previous studies consistently ound a strong correlation between the indexed EOA and the postoperative ransprosthetic gradients measured at rest or during exercise. However, as rst reported by Dumesnil and colleagues in 1990, and confirmed by Li and olleagues in 2005, the correlation between the indexed EOA and the mean ransprosthetic pressure gradients is lower in patients with mitral prostheses (r .50) than in patients with aortic prostheses (r 0.75). In this context, it should be mphasized that the hemodynamics of the mitral valve are more sensitive to the hronotropic conditions than are those of the aortic valve and that these conditions ay vary extensively from one patient to another. This difference may help explain he lower correlation between indexed EOA and pressure gradients that is observed n mitral prostheses. Subsequently, in a retrospective study of 56 patients who nderwent MVR, we observed that the indexed mitral valve EOA correlated better ith systolic pulmonary arterial pressure than with transprosthetic pressure gradints; this finding is consistent with the fact that pulmonary arterial pressure is robably less influenced by chronotropic conditions than are pressure gradients. In his study, we also found that mitral PPM is a frequent occurrence after MVR and hat it is associated with persisting pulmonary hypertension. Given that pulmonary ypertension may cause right-sided failure and is an important risk factor for orbidity and mortality in patients with cardiovascular diseases, the next logical
Assessing Appropriate ICT with ARIS case in Mozambique

ICT projects in developing countries need to integrate requirements of the local context in order to be successful. Appropriate Technology (AT) has been applied in many domains to deliver technological solutions that are suitable to the local contexts for which they are intended. The Appropriate ICT framework has adopted the principles of AT within the domain of ICT. This paper assesses the Appropriate ICT framework in the context of developing and implementing an Academic Registry Information System (ARIS) in Mozambique, and proposes an enhancement to the Appropriate ICT framework in order to facilitate further research on appropriate ICT tools and methods.
Painful Movements and Mobility after Urological Surgery: Studying the Feasibility of Pre-operative Exercise, A New Mobility Test and a Randomised Controlled Trial Protocol with Cystectomy Patients in Intensive Care [ISRCTN32898285]

Background: Cystectomy and ileal neobladder are standard procedures in bladder cancer treatment. Regaining mobility quickly after surgery, however, is aggravated by the facts that median laparotomy is used to access the abdomen, and that there are severe tissue violations during surgery. These result in post-operative movement-related pain and in restrictions of functional mobility. Movement patterns, which were self-evident before surgery, cause severe pain or even cannot be performed. Motor exercise with urological patients, before they undergo surgery, seems to be helpful to overcome such restrictions faster. Thus, regeneration could be supported. Methods: We planned a randomised controlled trial to study the effects of patient education based on the Viv-Arte conception, a kinesthetic mobilisation framework. In addition, we designed a new mobility test (MOTPA – Mobility Test for Patients in Acute Care) for subtle discrimination of the regeneration progress. The target group included patients scheduled for cystectomy in an intensive care setting. The primary outcomes were functional mobility (MOTPA), pain (visual analog scale) and post-surgical hospital residence time (intensive and general care units). Conclusions: Preliminary results show that the study design and the test are feasible. In-depth data analysis is to be published. Expanding the field of application of both training and test is to be discussed. Trial registration: Current Controlled Trials ISRCTN32898285
Treatment of Basal Cell Carcinoma Via Binary Ethosomes of Vismodegib: In Vitro and In Vivo Studies

Vismodegib (VMD) is a hedgehog inhibitor which indicated for basal cell skin cancer (BCC). This work focuses on investigating the influence of isopropyl alcohol additive for topical delivering and targeting of VMD-loaded binary ethosomes for BCC treatment. Different binary ethosome formulae were prepared based on Box-Behnken design using different concentrations of phospholipid (A), cholesterol (B) and isopropyl alcohol/total alcohol ratio (C). The prepared formulae were characterized for %entrapment efficiency (R1), vesicle size (R2), %release (R3) and steady-state flux (R4). Increasing A, B and C resulted in significant increase of R1 and R2 and significant decrease of R3 and R4. The optimization was achieved and the optimum formula was selected to investigate its anti-tumour efficacy in vivo. The optimum formula showed a localized VMD and consequently a significant anti-tumour activity compared with oral VMD. Briefly, VMD-loaded binary ethosome gel could be an effective treatment of BCC with lower side effects. Graphical abstract Graphical abstract
THE EFFECTS OF ANGLE OF ATTACK ON 3-DIMENSIONAL TURNING DIFFUSER ON BAFFLE PERFORMANCES

The aim of installing baffles is to reduce or eliminate, if possible, secondary flow which exists mostly at the inner wall of the turning diffuser. Furthermore, other than distortion at the inner wall, 3-dimensional turning diffuser has secondary flow at both left and right wall. This was due to the diffusing activities which were not only in x-y direction but in y-z direction as well. Experiment on 3-dimensional turning diffuser with baffle has been conducted using airfoil baffle with AOA=17o. Present study focuses on changing angle of attack of the installed baffle and their effects on flow uniformity and pressure recovery using numerical approach. The baffle was rotated 3o clockwise and anti-clockwise resulting in AOA=20o and AOA=14o respectively. Qualitative and quantitative comparison was discussed in this paper. AOA=14o offers higher quality of flow structure as compared to AOA= 20o, but still could not surpass the performance using preliminary design baffle with AOA= 17o. The abnormality of flow in AOA=20o resulting in higher pressure loss, thus affecting pressure recovery. The optimum configuration can be developed if the effort of improving the airfoil design could be enhance in future works.