Miracle-dz/UniFAR-FTUs huggingface dataset:
A Foreign Body Response-on-a-Chip Platform Invasive Therapeutics

Understanding the foreign body response (FBR) and desiging strategies to modulate such responses represent a grand challenge for implant devices and biomaterials. Here we report the development of a microfluidic platform, i.e., the FBR-on-a-chip (FBROC) for modeling the cascade of events during immune cell response to implants. Our platform modeled the native implant microenvironment where the implants were interfaced directly with surrounding tissues, as well as vasculature with circulating immune cells. Our study demonstrated that the release of cytokines such as monocyte chemoattractant protein 1 (MCP-1) from the extracellular matrix (ECM)-like hydrogels in the bottom tissue chamber induced the circulating monocytes in the vascular channel; resulting trans-endothelial migration of these monocytes towards the hydrogels, thus mimicking implant-induced inflammation. Data using patient-derived peripheral blood mononuclear cells further revealed inter-patient differences in such foreign body response, highlighting the potential of this platform for monitoring FBR in a personalized manner. Our prototype FBROC platform provides an enabling strategy to interrogate foreign body response on various implants, including novel biomaterials and engineered tissue constructs, in a physiologically relevant and individual-specific manner.
A replication competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity.

BACKGROUND Immunization with replication-competent recombinant vectors provides exposure to transgene-encoded antigens in the context of inflammation that may drive more potent and durable immunity compared to non-replicating vaccines. To understand the features of a replicating vaccine that drive such responses we tested a replication-competent adenovirus type 4 encoding influenza virus H5 hemagglutinin (Ad4-H5-Vtn) administered by an oral capsule or via a tonsillar swab or nasal spray. METHODS Viral shedding from the nose, mouth, and rectum was measured by PCR and culture. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition assay (PVEI), microneutralization (MN), and hemagglutinin inhibition (HAI). RESULTS Ad4-H5-Vtn DNA was shed from most upper respiratory tract (URT)-immunized volunteers for 2-4 weeks, but cultured from only 60% of participants with a median duration of one day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood and IgG and IgA in nasal, cervical and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAb) to H5 which remained stable at week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AE) were mild, and peak NAb titer was associated with overall AE frequency or duration. Serum neutralizing antibody titers could be boosted to very high levels 2-5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine. CONCLUSION Replicating Ad4 delivered to the URT causes prolonged exposure to antigen, drives durable systemic and mucosal immunity, and is a promising platform for the induction of immunity against viral surface glycoprotein targets. TRIAL REGISTRATION ClinicalTrials.gov NCT01443936, NCT01806909. FUNDING Intramural and Extramural Research Programs of the NIAID, NIH; and the Centers of Influenza Virus Research and SurveillanceFunding. Intramural and Extramural Research Programs of the NIAID, NIH; and the Centers of Influenza Virus Research and Surveillance.
Prognosis of Laparoscopic Surgery for Colorectal Cancer in Middle-Aged Patients: A Propensity Score-Matched Analysis

Background: The prognosis of middle-aged patients with CRC treated by laparoscopic resection (LR) is unclear. This study aimed to evaluate the survival outcomes of LR compared with open resection (OR) for patients with CRC and 45-65 years of age.Methods: This retrospective cohort study used the data from a database of all consecutive colorectal resections performed between January 2009 and December 2017. Propensity score matching (PSM) was done to handle the selection bias based on age, gender, body mass index (BMI), tumor location, AJCC stage, and admission year. Univariate and multivariate COX regression model was used to identify risk factors of overall survival (OS) and progression-free survival (PFS). Results: After PSM, 217 patients were included in each group. There were no differences in OS and PFS between the two groups (all P>0.05). There was less blood loss for LR (P<0.001), but the other complications were similar between the two groups. The multivariate analysis showed that high histological grade (hazard ratio [HR]=2.262, 95%CI: 1.334-3.836, P=0.002), stage III (HR=1.744, 95%CI: 2.360-25.406, P=0.001), stage IV (HR=47.905, 95%CI: 14.430-159.033, P<0.001), and adjuvant therapy (HR=0.547, 95%CI: 0.358-0.838, P=0.006) were independently associated with OS. High preoperative CEA (HR=1.585, 95%CI: 1.049-2.394, P=0.029), high histological grade (HR=2.128, 95%CI: 1.272-3.558, P=0.004), stage III (HR=5.562, 95%CI: 1.980-15.624, P=0.001), and stage IV (HR=26.338, 95%CI: 9.090-76.315, P<0.001), were independently associated with OS. LR was not associated with OS and PFS.Conclusions: In middle-aged patients with CRC, OR and LR have similar survival outcomes and complications.
Stage-Specific Expression Profiles of Anti-Müllerian Hormone and its Type II Receptor in Germ Cells during Spermatogenic Cycle of Rats

Although anti-Müllerian hormone (AMH) is present in seminiferous tubules, its physiological roles in testis remain unclear. We defined expression patterns of AMH and its type II receptor (AMHR2) in germ cells during spermatogenic cycles. To this end, we performed in situ hybridization of Amh and Amhr2, and immunohistochemical staining using antibodies against AMH and AMHR2 in testes from rats aged 10, 15, 21, 35, and 49 days (d). In addition, quantitative RT-PCR analyses were performed to determine relative expression levels of Amh, Amhr2, synaptonemal complex protein 1 (Scp1) and round spermatid basic protein 1 (Rsbn1), and Smads 1, 5, and 8 in germ cells isolated from 49d testes. In 49d testes, synthesis of AMH and AMHR2 corresponded with spermatocyte expression of Amh and Amhr2. Spermatocytes of stages VII-XIV synthesized AMH, and AMH staining was decreased in round spermatids and was not detectable in elongated spermatids. Spermatocytes of stages VII-XIV synthesized AMHR2, and round and elongated spermatids continued expressing AMHR2. The strongest staining of AMH was observed in spermatocytes at stage VIII, and that of AMHR2 was observed in round spermatids at the same stage. When isolated germ cells were cultured with anti-AMH antibody, expression levels of Amh and Amhr2 were significantly increased, those of Smads 1, 5 and Scp1 increased simultaneously, and that of Rsbn1 decreased. We speculate that the AMH-SMADs axis is associated with morphological change from round to elongated spermatids at stage VIII.
Effect of application of a PVP-iodine solution before and during subgingival ultrasonic instrumentation on post-treatment bacteraemia: a randomized single-centre placebo-controlled clinical trial.

BACKGROUND To assess the effect of concomitant subgingival rinsing with 10% PVP-iodine during subgingival instrumentation on the prevalence and magnitude of bacteraemia of oral origin. MATERIALS AND METHODS Subgingival instrumentation was performed with water or PVP-iodine rinse in patients with periodontitis. Prior to instrumentation, subjects gargled for 1 min with the allocated liquid. Pockets were then rinsed for 1 min and subgingivally instrumented with liquid-cooled (water/PVP-iodine) ultrasonic scalers (1 min). Two minutes later, a blood sample from the arm vein was drawn using a lysis centrifugation blood culture system for quantitative microbiological analysis. Non-parametric statistical tests were performed to assess differences in the prevalence and extent of bacteraemia between groups. RESULTS Of the 19 samples in each group, oral-borne bacteraemia was detected in 10 of the control and 2 of the test samples. With an average of 3.0 [1; 5] colony forming units, significantly less bacteria and bacteraemia were found in the test group compared to the controls (12.2 [1; 46]) (p = 0.003). Anaerobic bacteria were not found in the test group. CONCLUSIONS Bacteraemia after subgingival instrumentation with concomitant PVP-iodine rinsing is reduced but not eliminated. Therefore, it might be recommended for patients at a high risk of endocarditis or infection of endoprostheses. However, preventive antibiotic treatment should not be omitted.
Title : Region-specific microRNA alterations in marmosets carrying SLC 6 A 4 polymorphisms are associated with anxiety-like behavior

Human studies have consistently reported that stress-related disorders such as depression and anxiety impinge on the activity of emotion regulation networks including the ventromedial prefrontal cortex (vmPFC). However, molecular heterogeneity within the vmPFC and how these differences affect emotion regulation and behavior have not been elucidated. Marmosets have emerged as a powerful model in translational neuroscience to investigate molecular underpinnings of complex behaviors. Here, we took advantage of naturally occurring genetic polymorphisms in marmoset SLC6A4 gene that have been linked to anxiety-like behaviors. Using FACSsorted cells from different brain regions, we revealed that marmosets bearing different SLC6A4 variants exhibit distinct miRNAs signatures specifically in neurons of vmPFC area 32, but not in those of closely related vmPFC area 25. We also identified DCC, a gene linked to anxiety and depression, as a downstream target of miRNAs deregulated in area 32. Significantly, we showed that levels of DCC and miRNAs in area 32 were highly correlated to anxiety-like behaviors as well as to the response to citalopram and 5-HT2a antagonists. Our findings establish links between genetic variants, molecular alterations localized to specific vmPFC regions and complex behavioral/pharmacological responses, providing new mechanistic insights into genebehavior relationships underlying human psychopathology.
Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator

Previously our computational modeling studies (Phillips et al., 2019) proposed that neuronal persistent sodium current (INaP) and calcium-activated non-selective cation current (ICAN) are key biophysical factors that, respectively, generate inspiratory rhythm and burst pattern in the mammalian preBötzinger complex (preBötC) respiratory oscillator. Here, we experimentally tested and confirmed three predictions of the model from new simulations concerning the roles of INaP and ICAN: (1) INaP and ICAN blockade have opposite effects on the relationship between network excitability and preBötC rhythmic activity; (2) INaP is essential for preBötC rhythmogenesis; (3) ICAN is essential for generating the amplitude of rhythmic output but not rhythm generation. These predictions were confirmed via optogenetic manipulations of preBötC network excitability during graded INaP or ICAN blockade by pharmacological manipulations in neonatal mouse slices in vitro. Our results support and advance the hypothesis that INaP and ICAN mechanistically underlie rhythm and inspiratory burst pattern generation, respectively, in the isolated preBötC.
Impact of SLC43A3 /ENBT1 expression and function on 6-mercaptopurine transport and cytotoxicity in human acute lymphoblastic leukemia cells

6-Mercaptopurine (6-MP) is used extensively in the treatment of acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases. Our lab determined previously, using a recombinant HEK293 cell model, that the SLC43A3 -encoded equilibrative nucleobase transporter 1 (ENBT1) transports 6-MP into cells and significantly impacts the cytotoxicity of 6-MP in that model. To further investigate the clinical relevance of this finding, we now extend this work to an analysis of the impact of SLC43A3 /ENBT1 expression and function on 6-MP uptake and cytotoxicity in leukemic lymphoblasts, the therapeutic target of 6-MP in ALL. A panel of ALL cell lines was assessed for SLC43A3 /ENBT1 expression, ENBT1 function, and sensitivity to 6-MP. There was a significant difference in SLC43A3 expression among the cell lines that positively correlated with the rate of ENBT1-mediated 6-MP uptake. Cells with the lowest expression of SLC43A3 (SUP-B15: V max - 22 ± 5 pmol/µl/s) were also significantly less sensitive to 6-MP induced cytotoxicity than were the highest expressing cells (ALL-1: V max - 69 ± 10 pmol/µl/s). Furthermore, knockdown of ENBT1 using shRNAi in RS4;11 cells caused a significant decrease in ENBT1-mediated 6-MP uptake (V max : RS4;11 - 40 ± 4 pmol/µl/s; RS4;11 shRNAi - 26 ± 3 pmol/µl/s) and 6-MP cytotoxicity (EC 50 : RS4;11: 0.58 ± 0.05 µM; RS4;11 shRNAi: 1.44 ± 0.59 µM). This study showed that ENBT1 is a major contributor to 6-MP uptake in leukemia cell lines, and may prove to be a biomarker for the therapeutic efficacy of 6-MP in patients with ALL.
SOIL AND WATER CONSERVATION POLICIES IN THE ULUGURU MOUNTAINS, TANZANIA

Proper use of soil and water resources in major stream source areas is vital both for the short- term advantage of the local economy and for the long- term advantage of the whole community. This paper is a case study of official conservation policies and their impact on the partly deforested and densely settled stream-source area of the Uluguru mountains of Tanzania. Conservation policy in this area has been marked by radical shifts of emphasis and direction. These are described and analysed. Such a review of past ex- periences, together with newly-available technical data presented in papers which follow, forms a basis for comment concerning the future conservation measures in this area.
Update for the Performance of CT Coronary Angiography Evidence-Based Application and Technical Guidance According to Current Consensus Guidelines and Practical Advice from the Clinical Routine Update zur Durchführung der CT-Koronarangiografie

Background Coronary CT angiography (cCTA) is a class 1 recommendation in the current guidelines by the European Society of Cardiology (ESC) for excluding significant coronary artery stenosis. To achieve optimal image quality at a low radiation dose, the imaging physician may choose different acquisition modes. Therefore, the consensus guidelines
A multiple three-step color phase-shifting method for 3D shape measurement

This paper proposes a new multiple three-step color phase-shifting method for measuring 3D shape of objects. Firstly, multiple color fringe patterns are designed and projected onto the object surface by a projector. Distorted fringe patterns on the object surface are captured by a digital camera, and intensities of each pixel in the red, green and blue channels are obtained from the captured color images. Phase values of all pixels are calculated by the phase-shifting method from the obtained RGB intensities. Then, the phase-unwrapping technique is applied to convert phase values to the height of the object surface. Finally, an integrated program is developed by combining phase-shifting process and phase-unwrapping process. With the developed program, several measurement examples are investigated. From the measurement result, it shows that better 3D shape results can be obtained from the proposed method.
Reduced orbitofrontal and temporal grey matter in a community sample of maltreated children.

BACKGROUND Childhood maltreatment is strongly associated with increased risk of psychiatric disorder. Previous neuroimaging studies have reported atypical neural structure in the orbitofrontal cortex, temporal lobe, amygdala, hippocampus and cerebellum in maltreated samples. It has been hypothesised that these structural differences may relate to increased psychiatric vulnerability. However, previous studies have typically recruited clinical samples with concurrent psychiatric disorders, or have poorly characterised the range of maltreatment experiences and levels of concurrent anxiety or depression, limiting the interpretation of the observed structural differences. METHODS We used voxel-based morphometry to compare grey matter volume in a group of 18 children (mean age 12.01 years, SD = 1.4), referred to community social services, with documented and well-characterised experiences of maltreatment at home and a group of 20 nonmaltreated children (mean age 12.6 years, SD = 1.3). Both groups were comparable on age, gender, cognitive ability, ethnicity and levels of anxiety, depression and posttraumatic stress symptoms. We examined five a priori regions of interest: the prefrontal cortex, temporal lobes, amygdala, hippocampus and cerebellum. RESULTS Maltreated children, compared to nonmaltreated peers, presented with reduced grey matter in the medial orbitofrontal cortex and the left middle temporal gyrus. CONCLUSIONS The medial orbitofrontal cortex and the middle temporal gyrus have been implicated in reinforcement-based decision-making, emotion regulation and autobiographical memory, processes that are impaired in a number of psychiatric disorders associated with maltreatment. We speculate that grey matter disturbance in these regions in a community sample of maltreated children may represent a latent neurobiological risk factor for later psychopathology and heightened risk taking.
Spatio-temporal Pattern of Specialization of Sunbird-flower Networks on Mt. Cameroon

Differences in bird-flower interaction specialization across continents serve as a common example of evolutionary trajectory specificity. While New World hummingbird-flower networks have been subject to numerous studies and are considered highly specialized, our knowledge of network specialization for their Old World counterparts, sunbirds (Nectariniidae), is completely insufficient. A few studies from tropical Africa indicate that sunbird-flower networks are rather generalized. Unfortunately, these studies are limited to dry seasons and high elevations around the tree-line, the environments where also niche-based hypotheses often predict lower resource partitioning. In our study, we explore the specialization of sunbird-flower networks and their spatio-temporal variability on Mt. Cameroon (Cameroon). Using a combination of automatic video recording and personal observations, we constructed eight comprehensive sunbird-flower networks in four forest types occurring in different elevations and in both the dry and wet season. As reported by previous studies the montane forest plants, birds and whole networks were highly generalized. Nevertheless, we observed much higher specialization in forests in lower elevations. The wet season was also characterised by higher, but not significant, specialization. While less specialized flowering trees dominated in dry season networks, more specialized herbs and shrubs were visited during the wet season. Whereas our findings do not support the generally accepted assumption that Old World bird-flower networks are rather generalized, we need further studies to understand the differences in bird-flower specialization on individual continents.
A framework for the automatic description of musical structure using MPEG-7 audio

A great deal of research has been conducted in the area of musical analysis. However, very little has been done with respect to utilising the MPEG-7 metadata standard to describe the structural content of music at a fine level of granularity. The aim of this paper is to provide an overview of the field of structural musical analysis and to present an architecture for the AMUSED system for automated structural analysis and description using the MPEG-7 standard.
PrimeDesign software for rapid and simpli�ed design of prime editing guide RNAs

Prime editing (PE) is a versatile genome editing technology, but design of the required guide RNAs is more complex than for standard CRISPR-based nucleases or base editors. Here we describe PrimeDesign, a user-friendly, end-to-end web application and command-line tool for the design of PE experiments. PrimeDesign can be used for single and combination editing applications, as well as genome-wide and saturation mutagenesis screens. Using PrimeDesign, we constructed PrimeVar, a comprehensive and searchable database that includes candidate prime editing guide RNA (pegRNA) and nicking sgRNA (ngRNA) combinations for installing or correcting >68,500 pathogenic human genetic variants from the ClinVar database. Finally, we used PrimeDesign to design pegRNAs/ngRNAs to install a variety of human pathogenic variants in human cells
CUESTIONES ESTADÍSTICAS SOBRE MODELOS Y CONTRASTES DE AJUSTES POR DEVENGO ANORMALES

During the nineties, the main issue in earnings management research has beenfocused on models? specification to estimate the abnormal component of accruals buttoday it does not exist a generalised consensus about current models. In this paper, wepresent an analysis of statistic and econometric problems associated with themethodology of abnormal accruals to test earnings management hypothesis. It is shownthe main limitations associated with this methodology, and also it is proposed potentialways to mitigate problems of specification and power that imply current models. A lo largo de la decada de los noventa, la linea de investigacion basica del earnings management ha girado en torno a la especificacion de modelos que permitan estimar el componente anormal de los ajustes por devengo sin que hasta la fecha exista un consenso generalizado sobre la validez de los modelos existentes. En el presente trabajo se lleva a cabo un analisis de los problemas estadisticos y econometricos asociados a la metodologia de los ajustes por devengo anormales que se aplican de forma generalizada al contraste sobre earnings management. En las conclusiones se ponen de manifiesto las principales limitaciones asociadas con esta metodologia asi como posibles vias para mitigar los problemas de especificacion y potencia que implican los modelos existentes.
The world of science education: handbook of research in Australasia

The focus of this Handbook is on Australasia (a region loosely recognized as that which includes Australia and New Zealand plus nearby Pacific nations such as Papua New Guinea, Solomon Islands, Fiji, Tonga, Vanuatu, and the Samoan islands) science education and the scholarship that most closely supports this program. The reviews of the research situate what has been accomplished within a given field in Australasian rather than international context. The purpose therefore is to articulate and exhibit regional networks and trends that produced specific forms of science education. The thrust lies in identifying the roots of research programs and sketching trajectories—focusing the changing facade of problems and solutions within regional contexts. The approach allows readers review what has been done and accomplished, what is missing, and what might be done next.