Miracle-dz/UniFAR-FTUs huggingface dataset:
Updated survival outcomes of NEJ005/TCOG0902: a randomised phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations

Background The North-East Japan Study Group (NEJ) 005/Tokyo Cooperative Oncology Group (TCOG) 0902 study has reported that first-line concurrent and sequential alternating combination therapies of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (gefitinib) plus platinum-based doublet chemotherapy (carboplatin/pemetrexed) offer promising efficacy with predictable toxicities for patients with EGFR-mutant non-small cell lung cancer. However, overall survival (OS) data were insufficient in the primary report because of the lack of death events. Patients and methods Progression-free survival (PFS) and OS were re-evaluated at the final data cut-off point (March 2017) for the entire population (n=80). Results At the median follow-up time of 35.6 months, 88.8% of patients had progressive disease and 77.5% of patients had died. Median PFS was 17.5 months for the concurrent regimen and 15.3 months for the sequential alternating regimen (P=0.13). Median OS was 41.9 and 30.7 months, respectively (P=0.036). Updated response rates were similar in both groups (90.2% and 82.1%, respectively; P=0.34). Patients with Del19 tumours displayed relatively better OS (median: 45.3 vs 33.3 months, respectively) than those with L858R (31.4 vs 28.9 months, respectively). No severe adverse events, including interstitial lung disease, occurred in the period since the primary report. Conclusions This updated analysis confirms that PFS is improved with first-line combination therapy compared with gefitinib monotherapy and that the concurrent regimen, in particular, offers an OS benefit of 42 months in the EGFR-mutated setting. Our ongoing NEJ009 study will clarify whether this combination strategy can be incorporated into routine clinical practice. Trial registration number UMIN C000002789, Post-results.
Tandem modular protein-based hydrogels as extracellular matrix mimetic biomaterials

ii PREFACE . iv TABLE OF CONTENTS . vi LIST OF TABLES . ix LIST OF FIGURES . x LIST OF SCHEMES . xv LIST OF ABBREVIATIONS . xvi ACKNOWLEDGEMENTS . xviii DEDICATION . xx CHAPTER
Improving SDN Scalability With Protocol-Oblivious Source Routing: A System-Level Study

Software-defined networking (SDN) has been considered as a break-through technology for the next-generation Internet. It enables fine-grained flow control that can make networks more flexible and programmable. However, this might lead to scalability issues due to the possible flow state explosion in SDN switches. SDN-based source routing can reduce the volume of flow-tables significantly by encoding the path information into packet headers. In this paper, we leverage the protocol-oblivious forwarding instruction set to design protocol-oblivious source routing (POSR), which is a protocol-independent, bandwidth-efficient, and flow-table-saving packet forwarding technique. We lay out the packet format for POSR, come up with the packet processing pipelines for realizing unicast, multicast, and link failure recovery, and implement POSR in a protocol-oblivious forwarding-enabled SDN network system. Experiments are then performed in a network testbed, which consists of 14 stand-alone SDN switches, to validate the advantages of POSR. Specifically, we compare POSR with several OpenFlow-based benchmarks for unicast, multicast, and link failure recovery, and confirm that POSR can reduce flow-table utilization effectively, shorten path setup latency and expedite link failure recovery.
Development of a PNA Probe for Fluorescence In Situ Hybridization Detection of Prorocentrum donghaiense

Prorocentrum donghaiense is a common but dominant harmful algal bloom (HAB) species, which is widely distributed along the China Sea coast. Development of methods for rapid and precise identification and quantification is prerequisite for early-stage warning and monitoring of blooms due to P. donghaiense. In this study, sequences representing the partial large subunit rDNA (D1–D2), small subunit rDNA and internal transcribed spacer region (ITS-1, 5.8S rDNA and ITS-2) of P. donghaiense were firstly obtained, and then seven candidate DNA probes were designed for performing fluorescence in situ hybridization (FISH) tests on P. donghaiense. Based on the fluorescent intensity of P. donghaiense cells labeled by the DNA probes, the probe DP0443A displayed the best hybridization performance. Therefore, a PNA probe (PP0443A) analogous to DP0443A was used in the further study. The cells labeled with the PNA probe displayed more intensive green fluorescence than that labeled with its DNA analog. The PNA probe was used to hybridize with thirteen microalgae belonging to five families, i.e., Dinophyceae, Prymnesiophyceae, Raphidophyceae, Chlorophyceae and Bacillariophyceae, and showed no visible cross-reaction. Finally, FISH with the probes PP0443A and DP0443A and light microscopy (LM) analysis aiming at enumerating P. donghaiense cells were performed on the field samples. Statistical comparisons of the cell densities (cells/L) of P. donghaiense in the natural samples determined by FISH and LM were performed using one-way ANOVA and Duncan's multiple comparisons of the means. The P. donghaiense cell densities determined by LM and the PNA probe are remarkably higher than (p<0.05) that determined by the DNA probe, while no significant difference is observed between LM and the PNA probe. All results suggest that the PNA probe is more sensitive that its DNA analog, and therefore is promising for the monitoring of harmful algal blooms of P. donghaiense in the future.
Anal Dysplasia Screening and Treatment in a Southern Human Immunodeficiency Virus Clinic

Background Persistent human papillomavirus infection in human immunodeficiency virus (HIV)-infected individuals has been strongly associated with anal squamous cell carcinoma. The incidence of anal squamous cell carcinoma continues to increase in this population despite advances in HIV therapy. There are few studies describing the prevalence of anal cancer precursors, treatment outcomes, and associated factors among HIV-infected populations in the southern United States. Methods A retrospective chart review was performed on 355 HIV-infected patients from a Southern HIV clinic who were 18 years or older and had received at least one anal Pap smear. Demographic and clinical variables were collected. Descriptive statistics, single variable, and multivariate logistic regression analysis were performed to evaluate for predictors of high-grade squamous intraepithelial lesion (HSIL). Odds ratios and 95% confidence intervals were constructed for independent measures. Results After the first anal Pap smear, 38.3% (70/183) of patients with abnormal results were lost to follow-up. Comparing patients with biopsy proven HSIL versus low-grade squamous intraepithelial lesions, patients were less likely to have HSIL if they had a higher CD4 count (odds ratio, 0.81; 95% confidence interval, 0.72–0.93; P = 0.0022). Treatment success after the first round of treatment for topical and infrared coagulation therapy was 36.7% (18/49, all therapy types), and of those who achieved biopsy proven treatment success at follow-up screening, 94.4% (17/18) required subsequent therapy. Conclusions Patients with a higher CD4 count were less likely to have HSIL. CD4 nadir, number of sexual partners, and race/ethnicity were not significantly associated with the presence of HSIL.
Security and Privacy Analysis of Mobile Health Applications: The Alarming State of Practice

Recent advances in hardware and telecommunications have enabled the development of low cost mobile devices equipped with a variety of sensors. As a result, new functionalities, empowered by emerging mobile platforms, allow millions of applications to take advantage of vast amounts of data. Following this trend, mobile health applications collect users health-related information to help them better comprehend their health status and to promote their overall wellbeing. Nevertheless, health-related information is by nature and by law deemed sensitive and, therefore, its adequate protection is of substantial importance. In this paper we provide an in-depth security and privacy analysis of some of the most popular freeware mobile health applications. We have performed both static and dynamic analysis of selected mobile health applications, along with tailored testing of each application’s functionalities. Long term analyses of the life cycle of the reviewed apps and our general data protection regulation compliance auditing procedure are unique features of the present paper. Our findings reveal that the majority of the analyzed applications do not follow well-known practices and guidelines, not even legal restrictions imposed by contemporary data protection regulations, thus jeopardizing the privacy of millions of users.
Effects of common cold and concomitant administration of nasal decongestant on the pharmacokinetics and pharmacodynamics of nasal glucagon in otherwise healthy participants: A randomized clinical trial

Nasal glucagon (NG) is a nasally‐administered glucagon powder, absorbed through the nasal mucosa, designed for treatment of severe hypoglycaemia. This study evaluated the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of NG in otherwise healthy participants with common colds and after recovery from cold symptoms, with and without concomitant nasal decongestant.
Towards non-invasive brain-computer interface for hand/arm control in users with spinal cord injury

Spinal cord injury (SCI) can disrupt the communication pathways between the brain and the rest of the body, restricting the ability to perform volitional movements. Neuroprostheses or robotic arms can enable individuals with SCI to move independently, improving their quality of life. The control of restorative or assistive devices is facilitated by brain-computer interfaces (BCIs), which convert brain activity into control commands. In this paper, we summarize the recent findings of our research towards the main aim to provide reliable and intuitive control. We propose a framework that encompasses the detection of goal-directed movement intention, movement classification and decoding, error-related potentials detection and delivery of kinesthetic feedback. Finally, we discuss future directions that could be promising to translate the proposed framework to individuals with SCI.
Fine-Scale Spatial Variability of Pedestrian-Level Particulate Matters in Compact Urban Commercial Districts in Hong Kong

Particulate matters (PM) at the pedestrian level significantly raises the health impacts in the compact urban environment of Hong Kong. A detailed investigation of the fine-scale spatial variation of pedestrian-level PM is necessary to assess the health risk to pedestrians in the outdoor environment. However, the collection of PM data is difficult in the compact urban environment of Hong Kong due to the limited amount of roadside monitoring stations and the complicated urban context. In this study, we measured the fine-scale spatial variability of the PM in three of the most representative commercial districts of Hong Kong using a backpack outdoor environmental measuring unit. Based on the measurement data, 13 types of geospatial interpolation methods were examined for the spatial mapping of PM2.5 and PM10 with a group of building geometrical covariates. Geostatistical modelling was adopted as the basis of spatial interpolation of the PM. The results show that the original cokriging with the exponential kernel function provides the best performance in the PM mapping. Using the fine-scale building geometrical features as covariates slightly improves the interpolation performance. The study results also imply that the fine-scale, localized pollution emission sources heavily influence pedestrian exposure to PM.
Quantitative assessment of videolaryngostroboscopic images in patients with glottic pathologies

Abstract Introduction: Digital imaging techniques enable exploration of novel visualization modalities of the vocal folds during phonation and definition of parameters, facilitating more precise diagnosis of voice disorders. Aim: Application of computer vision algorithms for analysis of videolaryngostroboscopic (VLS) images aimed at qualitative and quantitative description of phonatory vibrations. Materials and methods: VLS examinations were conducted for 45 females, including 15 subjects with vocal nodules, 15 subjects with glottal incompetence, and 15 normophonic females. The recorded VLS images were preprocessed, the glottis area was segmented out, and the glottal cycles were identified. The glottovibrograms were built, and then the glottal area waveforms (GAW) were quantitatively described by computing the following parameters: open quotient (OQ), closing quotient (CQ), speed quotient (SQ), minimal relative glottal area (MRGA), and a new parameter termed closure difference index (CDI). Results: Profiles of the glottal widths assessed along the glottal length differentiated the study groups (P < 0.001). Moreover, it was shown that the OQ, CQ, CDI, and MRGA indices can be considered as viable parameters for quantifying kinematics of the vocal folds for normophonic subjects and patients with diagnosed vocal nodules and glottal incompetence (P < 0.001). Conclusions: Computer image processing and analysis methods applied to videolaryngostroboscopic images allow for their quantitative assessment. Computation of the size-related and time-related parameters characterizing glottic pathologies is of interest for evidence-based voice diagnostics. Results of the performed ROC curve analysis suggest that the evaluated parameters can distinguish patients with voice disorders from normophonic subjects.
Maternal exercise upregulates mitochondrial gene expression and increases enzyme activity of fetal mouse hearts

Maternal exercise during pregnancy has been shown to improve the long‐term health of offspring in later life. Mitochondria are important organelles for maintaining adequate heart function, and mitochondrial dysfunction is linked to cardiovascular disease. However, the effects of maternal exercise during pregnancy on mitochondrial biogenesis in hearts are not well understood. Thus, the purpose of this study was to test the hypothesis that mitochondrial gene expression in fetal myocardium would be upregulated by maternal exercise. Twelve‐week‐old female C57BL/6 mice were divided into sedentary and exercise groups. Mice in the exercise group were exposed to a voluntary cage‐wheel from gestational day 1 through 17. Litter size and individual fetal weights were taken when pregnant dams were sacrificed at 17 days of gestation. Three to four hearts from the same group were pooled to study gene expression, protein expression, and enzyme activity. There were no significant differences in litter size, sex distribution, and average fetal body weight per litter between sedentary and exercised dams. Genes encoding mitochondrial biogenesis and dynamics, including nuclear respiratory factor‐1 (Nrf1), Nrf2, and dynamin‐related GTPase termed mitofusin‐2 (Mfn2) were significantly upregulated in the fetal hearts from exercised dams. Cytochrome c oxidase activity and ATP production were significantly increased, while the hydrogen peroxide level was significantly decreased in the fetal hearts by maternal exercise. Our results demonstrate that maternal exercise initiated at day 1 of gestation could transfer the positive mitochondrial phenotype to fetal hearts.
Species Richness and Trophic Diversity Increase Decomposition in a Co-Evolved Food Web

Ecological communities show great variation in species richness, composition and food web structure across similar and diverse ecosystems. Knowledge of how this biodiversity relates to ecosystem functioning is important for understanding the maintenance of diversity and the potential effects of species losses and gains on ecosystems. While research often focuses on how variation in species richness influences ecosystem processes, assessing species richness in a food web context can provide further insight into the relationship between diversity and ecosystem functioning and elucidate potential mechanisms underpinning this relationship. Here, we assessed how species richness and trophic diversity affect decomposition rates in a complete aquatic food web: the five trophic level web that occurs within water-filled leaves of the northern pitcher plant, Sarracenia purpurea. We identified a trophic cascade in which top-predators — larvae of the pitcher-plant mosquito — indirectly increased bacterial decomposition by preying on bactivorous protozoa. Our data also revealed a facultative relationship in which larvae of the pitcher-plant midge increased bacterial decomposition by shredding detritus. These important interactions occur only in food webs with high trophic diversity, which in turn only occur in food webs with high species richness. We show that species richness and trophic diversity underlie strong linkages between food web structure and dynamics that influence ecosystem functioning. The importance of trophic diversity and species interactions in determining how biodiversity relates to ecosystem functioning suggests that simply focusing on species richness does not give a complete picture as to how ecosystems may change with the loss or gain of species.
Differential Expression of miRNAs in Response to Topping in Flue-Cured Tobacco (Nicotiana tabacum) Roots

Background Topping is an important cultivating measure for flue-cured tobacco, and many genes had been found to be differentially expressed in response to topping. But it is still unclear how these genes are regulated. MiRNAs play a critical role in post-transcriptional gene regulation, so we sequenced two sRNA libraries from tobacco roots before and after topping, with a view to exploring transcriptional differences in miRNAs. Methodology/Principal Findings Two sRNA libraries were generated from tobacco roots before and after topping. Solexa high-throughput sequencing of tobacco small RNAs revealed a total of 12,104,207 and 11,292,018 reads representing 3,633,398 and 3,084,102 distinct sequences before and after topping. The expressions of 136 conserved miRNAs (belonging to 32 families) and 126 new miRNAs (belonging to 77 families) were determined. There were three major conserved miRNAs families (nta-miR156, nta-miR172 and nta-miR171) and two major new miRNAs families (nta-miRn2 and nta-miRn26). All of these identified miRNAs can be folded into characteristic miRNA stem-loop secondary hairpin structures, and qRT-PCR was adopted to validate and measure the expression of miRNAs. Putative targets were identified for 133 out of 136 conserved miRNAs and 126 new miRNAs. Of these miRNAs whose targets had been identified, the miRNAs which change markedly (>2 folds) belong to 53 families and their targets have different biological functions including development, response to stress, response to hormone, N metabolism, C metabolism, signal transduction, nucleic acid metabolism and other metabolism. Some interesting targets for miRNAs had been determined. Conclusions/Significance The differential expression profiles of miRNAs were shown in flue-cured tobacco roots before and after topping, which can be expected to regulate transcripts distinctly involved in response to topping. Further identification of these differentially expressed miRNAs and their targets would allow better understanding of the regulatory mechanisms for flue-cured tobacco response to topping.
A comparison of propofol–midazolam and midazolam alone for sedation in endobronchial ultrasound‐guided transbronchial needle aspiration: a retrospective cohort study

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is a new, minimally invasive, bronchoscopic technique used in the evaluation of inthrathoracic lymph nodes.Use of sedation drugs before the procedure differs among centres. There is no standardization about sedation before EBUS‐TBNA.We used a policy decision to shift from use of propofol with midazolam vs midazolam alone in a large tertiary hospital to evaluate the diagnostic yield and safety of EBUS‐TBNA procedure.
Position paper on olfactory dysfunction.

BACKGROUND Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.
Safer Muslim motherhood: Social conditions and maternal mortality in the Muslim world

ABSTRACT The greatest variation in maternal mortality is among poor countries and wealthy countries that rely on emergency obstetric technology to save a woman’s life during childbirth. However, substantial variation in maternal mortality ratios (MMRs) exists within and among poor countries with uneven access to advanced obstetric services. This article examines MMRs across the Muslim world and compares the impact of national wealth, female education, and skilled birth attendants on maternal mortality. Understanding how poor countries have lowered MMRs without access to expensive obstetric technologies suggests that certain social variables may act protectively to reduce the maternal risk for life-threatening obstetric complications that would require emergency obstetric care.
Almost Sure and Moment Exponential Stability of Regime-Switching Jump Diffusions

This work is devoted to almost sure and moment exponential stability of regime-switching jump diffusions. The Lyapunov function method is used to derive sufficient conditions for stabilities for general nonlinear systems, which further helps to derive easily verifiable conditions for linear systems. For one-dimensional linear regime-switching jump diffusions, necessary and sufficient conditions for almost sure and $p$th moment exponential stabilities are presented. Several examples are provided for illustration.