Miracle-dz/UniFAR-FTUs huggingface dataset:
Implementation of the WHO manual for Robson classification: an example from Sri Lanka using a local database for developing quality improvement recommendations

Objectives This study aimed at describing the use of a prospective database on hospital deliveries for analysing caesarean section (CS) practices according to the WHO manual for Robson classification, and for developing recommendations for improving the quality of care (QoC). Design Observational study. Setting University Obstetric Unit at De Soysa Hospital for Women, the largest maternity unit in Sri Lanka. Data collection and analysis For each childbirth, 150 variables were routinely collected in a standardised form and entered into a database. Data were routinely monitored for ensuring quality. Information on deliveries occurring from July 2015 to June 2017 were analysed according the WHO Robson classification manual. Findings were discussed internally to develop quality improvement recommendations. Results 7504 women delivered in the hospital during the study period and at least one maternal or fetal pathological condition was reported in 2845 (37.9%). The CS rate was 30.0%, with 11.9% CS being performed prelabour. According to the Robson classification, Group 3 and Group 1 were the most represented groups (27.0% and 23.1% of population, respectively). The major contributors to the CS rate were group 5 (29.6%), group 1 (14.0%), group 2a (13.3%) and group 10 (11.5%). The most commonly reported indications for CS included abnormal cardiotocography/suspected fetal distress, past CS and failed progress of labour or failed induction. These suggested the need for further discussion on CS practices. Overall, 18 recommendations were agreed on. Besides updating protocols and hands-on training, activities agreed on included monitoring and supervision, criterion-based audits, risk management meetings and appropriate information for patients, and recommendations to further improve the quality of data. Conclusions This study provides an example on how the WHO manual for Robson classification can be used in an action-oriented manner for developing recommendations for improving the QoC, and the quality of data collected.
Impact of Diet and/or Exercise Intervention on Infrapatellar Fat Pad Morphology: Secondary Analysis from the Intensive Diet and Exercise for Arthritis (IDEA) Trial

Objectives: The infrapatellar fat pad (IPFP) represents intra-articular adipose tissue that may contribute to intra-articular inflammation and pain by secretion of proinflammatory cytokines. Here we examined the impact of weight loss by diet and/or exercise interventions on the IPFP volume. Methods: Intensive Diet and Exercise for Arthritis (IDEA) was a single-blinded, single-center, 18-month, prospective, randomized controlled trial that enrolled 454 overweight and obese older adults with knee pain and radiographic osteoarthritis. Participants were randomized to 1 of 3 groups: exercise-only control (E), diet-induced weight loss (D), and diet-induced weight loss + exercise (D+E). In a subsample (n = 106; E: n = 36, D: n = 35, and D+E: n = 35), magnetic resonance images were acquired at baseline and at the 18-month follow-up, from which we analyzed IPFP volume, surface areas, and thickness in this secondary analysis. Results: The average weight loss amounted to 1.0% in the E group, 10.5% in the D group, and 13.0% in the D+E group. A significant (p < 0.01) reduction in IPFP volume was observed in the E (2.1%), D (4.0%), and D+E (5.2%) groups. The IPFP volume loss in the D+E group was significantly greater than that in the E group (p < 0.05) when not adjusting for parallel comparisons. Across intervention groups, there were significant correlations between IPFP volume change, individual weight loss (r = 0.40), and change in total body fat mass (dual-energy X-ray absorptiometry; r = 0.44, n = 88) and in subcutaneous thigh fat area (computed tomography; r = 0.32, n = 82). Conclusions: As a potential link between obesity and knee osteoarthritis, the IPFP was sensitive to intervention by diet and/or exercise, and its reduction was correlated with changes in weight and body fat.
Stem Cells for Bone Regeneration: Current State and Future Directions

Abstract Mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes, each of which is important for musculoskeletal tissue regeneration and repair. Reconstruction and healing of bony defects remains a major clinical challenge. Even as surgical practices advance, some severe cases of bone loss do not yield optimal recovery results. New techniques involving implantation of stem cells and tissue-engineered scaffolds are being developed to help improve bone and cartilage repair. The invasiveness and low yield of harvesting MSCs from the bone marrow (BMSCs) has led to the investigation of alternatives, including adipose-derived mesenchymal stem cells (ASCs). A review of the literature yielded several studies concerning the use of BMSCs and ASCs for the treatment of bone defects in both in vitro and in vivo models. Although both ASCs and BMSCs have demonstrated bone regenerative capabilities, BMSCs have outperformed ASCs in vitro. Despite these in vitro study findings, in vivo study results remain variable. Analysis of the literature seems to conclude there is no significant difference between bone regeneration using ASCs or BMSCs in vivo. Improved study design and standardization may enhance the application of these studies to patient care in the clinical setting.
SULTR3s Function in Chloroplast Sulfate Uptake and Affect ABA Biosynthesis and the Stress Response1

The sultr3 quintuple mutant unequivocally demonstrates that sulfate transporter subfamily 3 is responsible for more than half of the chloroplast sulfate uptake and influences downstream sulfate assimilation and ABA biosynthesis as well as sulfate-induced stomatal closure. Plants are major sulfur reducers in the global sulfur cycle. Sulfate, the major natural sulfur source in soil, is absorbed by plant roots and transported into plastids, where it is reduced and assimilated into Cys for further metabolic processes. Despite its importance, how sulfate is transported into plastids is poorly understood. We previously demonstrated using single Arabidopsis (Arabidopsis thaliana) genetic mutants that each member of the sulfate transporter (SULTR) subfamily 3 was able to transport sulfate across the chloroplast envelope membrane. To resolve the function of SULTR3s, we constructed a sultr3 quintuple mutant completely knocking out all five members of the subfamily. Here we report that all members of the SULTR3 subfamily show chloroplast membrane localization. Sulfate uptake by chloroplasts of the quintuple mutant is reduced by more than 50% compared with the wild type. Consequently, Cys and abscisic acid (ABA) content are reduced to ∼67 and ∼20% of the wild-type level, respectively, and strong positive correlations are found among sulfate, Cys, and ABA content. The sultr3 quintuple mutant shows obvious growth retardation with smaller rosettes and shorter roots. Seed germination of the sultr3 quintuple mutant is hypersensitive to exogenous ABA and salt stress, but is rescued by sulfide supplementation. Furthermore, sulfate-induced stomatal closure is abolished in the quintuple mutant, strongly suggesting that chloroplast sulfate is required for stomatal closure. Our genetic analyses unequivocally demonstrate that sulfate transporter subfamily 3 is responsible for more than half of the chloroplast sulfate uptake and influences downstream sulfate assimilation and ABA biosynthesis.
Psychosocial assessment of potential retinal prosthesis trial participants

As the field of retinal prostheses advances, volunteers are required for device trials, and optimal participant recruitment is vital for intervention success. The aims of this study were: (i) to select tests that assess the psychosocial aspects of visual impairment and develop a psychosocial assessment protocol for persons who may be eligible for participation in retinal prostheses trials; (ii) to investigate correlations between these tests; and (iii) to determine associations between psychosocial factors and a person's interest in participating in a retinal prosthesis (bionic eye) trial.
First Report of Beet pseudo yellows virus in Strawberry in the United States: A Second Crinivirus Able to Cause Pallidosis Disease.

During efforts to characterize strawberry pallidosis disease, we identified a single strawberry plant that indexed positive for pallidosis disease by grafting but it was not infected with the Strawberry pallidosis associated virus (SPaV) based on reverse transcription-polymerase chain reaction (1). Leaves of this plant were grafted onto Fragaria vesca UC-4 and UC-5 and F. virginiana UC-10 and UC-11 indicator plants. The F. vesca plants remained asymptomatic, while the F. virginiana plants gave typical pallidosis symptoms that included marginal leaf chlorosis and epinasty. The combination of these symptoms on F. virginiana and lack of symptoms on F. vesca is used to define pallidosis disease (1). We extracted dsRNA from the original plant, and synthesized and cloned cDNA as previously described (2). Sequence analysis revealed several clones that corresponded to the published sequence of the Beet pseudo yellows virus (BPYV) heat shock protein 70 homolog gene (HSP70h). We transferred the isolate to Nicotiana benthamiana by using the whitefly vector, Trialeuroides vaporariorum, and then reisolated and cloned dsRNA from the infected N. benthamiana. Here we present the complete sequence of the HSP70h and minor coat protein (CPm) genes of the strawberry isolate of BPYV (GenBank Accession Nos. AY 267369 and AY 268107, respectively). Oligonucleotide primers BP CPm F (5' TTCATATTAAGGATGCGCAGA 3') and BP CPm R (5' TGAAAG- ATGTCCACTAATGATA 3') were designed to amplify a 334-nucleotide fragment of the CPm gene of the strawberry isolate of BPYV. Using this primer set, we were able to verify the presence of BPYV in 1- to 3-year-old plants from the major strawberry producing areas of the United States, including California, Oregon, and the Mid-Atlantic States. Infection rates were highest near Watsonville, CA where more than 20% of plants tested were infected with BPYV. To our knowledge, this is the first report of BPYV infecting strawberry. BPYV and the closely related SPaV (2) pose new concerns for the U.S. strawberry industry. Studies are currently underway to determine the effects of these two viruses on strawberry vigor and productivity. References: (1) N. W. Frazier and L. L. Stubbs. Plant Dis. Rep. 53:524, 1969. (2) I. E. Tzanetakis et al. (Abstr.) Phytopathology 92:S82, 2002.
Discovery and Characterization of Bukakata orbivirus (Reoviridae:Orbivirus), a Novel Virus from a Ugandan Bat

While serological and virological evidence documents the exposure of bats to medically-important arboviruses, their role as reservoirs or amplifying hosts is less well-characterized. We describe a novel orbivirus (Reoviridae:Orbivirus) isolated from an Egyptian fruit bat (Rousettus aegyptiacus leachii) trapped in 2013 in Uganda and named Bukakata orbivirus. This is the fifth orbivirus isolated from a bat, however genetic information had previously only been available for one bat-associated orbivirus. We performed whole-genome sequencing on Bukakata orbivirus and three other bat-associated orbiviruses (Fomede, Ife, and Japanaut) to assess their phylogenetic relationship within the genus Orbivirus and develop hypotheses regarding potential arthropod vectors. Replication kinetics were assessed for Bukakata orbivirus in three different vertebrate cell lines. Lastly, qRT-PCR and nested PCR were used to determine the prevalence of Bukakata orbivirus RNA in archived samples from three populations of Egyptian fruit bats and one population of cave-associated soft ticks in Uganda. Complete coding sequences were obtained for all ten segments of Fomede, Ife, and Japanaut orbiviruses and for nine of the ten segments for Bukakata orbivirus. Phylogenetic analysis placed Bukakata and Fomede in the tick-borne orbivirus clade and Ife and Japanaut within the Culicoides/phlebotomine sandfly orbivirus clade. Further, Bukakata and Fomede appear to be serotypes of the Chobar Gorge virus species. Bukakata orbivirus replicated to high titers (106–107 PFU/mL) in Vero, BHK-21 [C-13], and R06E (Egyptian fruit bat) cells. Preliminary screening of archived bat and tick samples do not support Bukakata orbivirus presence in these collections, however additional testing is warranted given the phylogenetic associations observed. This study provided complete coding sequence for several bat-associated orbiviruses and in vitro characterization of a bat-associated orbivirus. Our results indicate that bats may play an important role in the epidemiology of viruses in the genus Orbivirus and further investigation is warranted into vector-host associations and ongoing surveillance efforts.
Epithelial-to-Mesenchymal Transition Defines Feedback Activation of Receptor Tyrosine Kinase Signaling Induced by MEK Inhibition in KRAS-Mutant Lung Cancer.

UNLABELLED KRAS is frequently mutated in lung cancer. Whereas MAPK is a well-known effector pathway of KRAS, blocking this pathway with clinically available MAPK inhibitors is relatively ineffective. Here, we report that epithelial-to-mesenchymal transition rewires the expression of receptor tyrosine kinases, leading to differential feedback activation of the MAPK pathway following MEK inhibition. In epithelial-like KRAS-mutant lung cancers, this feedback was attributed to ERBB3-mediated activation of MEK and AKT. In contrast, in mesenchymal-like KRAS-mutant lung cancers, FGFR1 was dominantly expressed but suppressed by the negative regulator Sprouty proteins; MEK inhibition led to repression of SPRY4 and subsequent FGFR1-mediated reactivation of MEK and AKT. Therapeutically, the combination of a MEK inhibitor (MEKi) and an FGFR inhibitor (FGFRi) induced cell death in vitro and tumor regressions in vivo These data establish the rationale and a therapeutic approach to treat mesenchymal-like KRAS-mutant lung cancers effectively with clinically available FGFR1 and MAPK inhibitors. SIGNIFICANCE Adaptive resistance to MEKi is driven by receptor tyrosine kinases specific to the differentiation state of the KRAS-mutant non-small cell lung cancer (NSCLC). In mesenchymal-like KRAS-mutant NSCLC, FGFR1 is highly expressed, and MEK inhibition relieves feedback suppression of FGFR1, resulting in reactivation of ERK; suppression of ERK by MEKi/FGFRi combination results in tumor shrinkage. Cancer Discov; 6(7); 754-69. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 681.
MroQ Is a Novel Abi-Domain Protein That Influences Virulence Gene Expression in Staphylococcus aureus via Modulation of Agr Activity

Numerous factors have, to date, been identified as playing a role in the regulation of Agr activity in Staphylococcus aureus, including transcription factors, antisense RNAs, and host elements. Herein we investigated the product of SAUSA300_1984 (termed MroQ), a transmembrane Abi-domain/M79 protease-family protein, as a novel effector of this system. ABSTRACT Numerous factors have, to date, been identified as playing a role in the regulation of Agr activity in Staphylococcus aureus, including transcription factors, antisense RNAs, and host elements. Herein we investigated the product of SAUSA300_1984 (termed MroQ), a transmembrane Abi-domain/M79 protease-family protein, as a novel effector of this system. Using a USA300 mroQ mutant, we observed a drastic reduction in proteolysis, hemolysis, and pigmentation that was fully complementable. This appears to result from diminished agr activity, as transcriptional analysis revealed significant decreases in expression of both RNAII and RNAIII in the mroQ mutant. Such effects appear to be direct, rather than indirect, as known agr effectors demonstrated limited alterations in their activity upon mroQ disruption. A comparison of RNA sequencing data sets for both mroQ and agr mutants revealed a profound overlap in their regulomes, with the majority of factors affected being known virulence determinants. Importantly, the preponderance of alterations in expression were more striking in the agr mutant, indicating that MroQ is necessary, but not sufficient, for Agr function. Mechanism profiling revealed that putative residues for metalloprotease activity within MroQ are required for its Agr-controlling effect; however, this was not wielded at the level of AgrD processing. Virulence assessment demonstrated that both mroQ and agr mutants exhibited increased formation of renal abscesses but decreased skin abscess formation alongside diminished dermonecrosis. Collectively, we present the characterization of a novel agr effector in S. aureus which would appear to be a direct regulator, potentially functioning via interaction with the AgrC histidine kinase.
Multiple-Joint Isokinetic Dynamometry: A Critical Review.

Dvir, Z and Müller, S. Multiple-joint isokinetic dynamometry: a critical review. J Strength Cond Res XX(X): 000-000, 2018-Angular isokinetic dynamometry (AID) is widely regarded as the gold standard for dynamic muscle performance testing. Based on the rotational movement of its actuator, AID targets "single-joint" (knee, shoulder, hip, etc.) configurations namely measurement of muscle potential while it moves the lever arm-limb assembly ostensibly around a single fixed axis. On the other hand, the application of multiple-joint isokinetic dynamometry (MID) is relatively narrow, both in research and in practice. This situation is due, possibly, to the fact that these dynamometers are generally more limited in scope namely to testing/conditioning of combined hip, knee, ankle motion (leg press), combined shoulder, elbow motion, and lifting motion patterns, despite the fact that all 3 are associated with higher functionality. However, with the emerging importance of MID, this critical review takes a fresh look at its various aspects including the terminology and classification of multiple-joint isokinetic dynamometers; the problem of scaling namely the need to adjust the range of motion and linear velocities to subjective anthropometric measures; specific technical and methodological issues that underlie the valid application of these dynamometers; available reference values; and the reproducibility of MID-based test findings. Analysis of these topics indicates that MID may validly and effectively be applied for the assessment and conditioning of specific muscle action patterns. However, there is a clear need for standardization of tests and for conditioning protocols alongside research into the use of this method in various clinical cohorts.
A Programmable Framework for Validating Data Planes

Due to the emerging trend of programmable network hardware, developers have begun to explore ways to accelerate various applications and services. As a result, there is a pressing need for new tools and techniques for debugging network devices. This paper presents NetDebug, a fully programmable hardware-software framework for validating and real-time debugging of programmable data planes. We describe validation use cases, compare our design to alternative solutions, and present a preliminary evaluation using a prototype implementation.
The Dual Impact of Early and Concurrent Life Stress on Adults’ Diurnal Cortisol Patterns: A Prospective Study

Major life stress often produces a flat diurnal cortisol slope, an indicator of potential long-term health problems. Exposure to stress early in childhood or the accumulation of stress across the life span may be responsible for this pattern. However, the relative impact of life stress at different life stages on diurnal cortisol is unknown. Using a longitudinal sample of adults followed from birth, we examined three models of the effect of stress exposure on diurnal cortisol: the cumulative model, the biological-embedding model, and the sensitization model. As its name implies, the cumulative model focuses on cumulative life stress. In contrast, the biological-embedding model implicates early childhood stress, and the sensitization model posits that current life stress interacts with early life stress to produce flat diurnal cortisol slopes. Our analyses are consistent with the sensitization model, as they indicate that the combination of high stress exposure early in life and high current stress predict flat diurnal cortisol slopes. These novel findings advance understanding of diurnal cortisol patterns and point to avenues for intervention.
Submolecular dissection reveals strong and specific binding of polyamide–pyridostatin conjugates to human telomere interface

Abstract To modulate biological functions, G-quadruplexes in genome are often non-specifically targeted by small molecules. Here, specificity is increased by targeting both G-quadruplex and its flanking duplex DNA in a naturally occurring dsDNA–ssDNA telomere interface using polyamide (PA) and pyridostatin (PDS) conjugates (PA-PDS). We innovated a single-molecule assay in which dissociation constant (Kd) of the conjugate can be separately evaluated from the binding of either PA or PDS. We found Kd of 0.8 nM for PA-PDS, which is much lower than PDS (Kd ∼ 450 nM) or PA (Kd ∼ 35 nM). Functional assays further indicated that the PA-PDS conjugate stopped the replication of a DNA polymerase more efficiently than PA or PDS. Our results not only established a new method to dissect multivalent binding into actions of individual monovalent components, they also demonstrated a strong and specific G-quadruplex targeting strategy by conjugating highly specific duplex-binding molecules with potent quadruplex ligands.
Ablation of the X-linked retinitis pigmentosa 2 (Rp2) gene in mice results in opsin mislocalization and photoreceptor degeneration.

PURPOSE Mutations in the RP2 gene are associated with 10% to 15% of X-linked retinitis pigmentosa (XLRP), a debilitating disorder characterized by the degeneration of retinal rod and cone photoreceptors. The molecular mechanism of pathogenesis of photoreceptor degeneration in XLRP-RP2 has not been elucidated, and no treatment is currently available. This study was undertaken to investigate the pathogenesis of RP2-associated retinal degeneration. METHODS We introduced loxP sites that flank exon 2, a mutational hotspot in XLRP-RP2, in the mouse Rp2 gene. We then produced Rp2-null allele using transgenic mice that expressed Cre-recombinase under control of the ubiquitous CAG promoter. Electroretinography (ERG), histology, light microscopy, transmission electron microscopy, and immunofluorescence microscopy were performed to ascertain the effect of ablation of Rp2 on photoreceptor development, function, and protein trafficking. RESULTS Although no gross abnormalities were detected in the Rp2(null) mice, photopic (cone) and scotopic (rod) function as measured by ERG showed a gradual decline starting as early as 1 month of age. We also detected slow progressive degeneration of the photoreceptor membrane discs in the mutant retina. These defects were associated with mislocalization of cone opsins to the nuclear and synaptic layers and reduced rhodopsin content in the outer segment of mutant retina prior to the onset of photoreceptor degeneration. CONCLUSIONS Our studies suggest that RP2 contributes to the maintenance of photoreceptor function and that cone opsin mislocalization represents an early step in XLRP caused by RP2 mutations. The Rp2(null) mice should serve as a useful preclinical model for testing gene- and cell-based therapies.