Miracle-dz/UniFAR-FTUs huggingface dataset:
Current and future therapeutic approaches for the treatment of small cell lung cancer

ABSTRACT Introduction: Small-cell lung cancer (SCLC) is a very aggressive disease characterized by a high response rate to first-line chemotherapy, but most patients relapse within 1 year with disappointing results to second-line treatments. Chemotherapy has reached a plateau of effectiveness and new therapeutic strategies are needed to change the natural history of SCLC. Areas covered: This review will focus on the current results and the future development of the therapeutic approaches for the treatment of SCLC. Expert commentary: Immunotherapy is becoming a new frontier for the management of SCLC with preliminary interesting results. To date, no targeted drugs have been approved for clinical practice but several novel agents are in an advanced stage of clinical development in SCLC.
Enhanced Adult Neurogenesis Increases Brain Stiffness: In Vivo Magnetic Resonance Elastography in a Mouse Model of Dopamine Depletion

The mechanical network of the brain is a major contributor to neural health and has been recognized by in vivo magnetic resonance elastography (MRE) to be highly responsive to diseases. However, until now only brain softening was observed and no mechanism was known that reverses the common decrement of neural elasticity during aging or disease. We used MRE in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) mouse model for dopaminergic neurodegeneration as observed in Parkinson’s disease (PD) to study the mechanical response of the brain on adult hippocampal neurogenesis as a robust correlate of neuronal plasticity in healthy and injured brain. We observed a steep transient rise in elasticity within the hippocampal region of up to over 50% six days after MPTP treatment correlating with increased neuronal density in the dentate gyrus, which could not be detected in healthy controls. Our results provide the first indication that new neurons reactively generated following neurodegeneration substantially contribute to the mechanical scaffold of the brain. Diagnostic neuroimaging may thus target on regions of the brain displaying symptomatically elevated elasticity values for the detection of neuronal plasticity following neurodegeneration.
Effects of Bacterial Community Members on the Proteome of the Ammonia-Oxidizing Bacterium Nitrosomonas sp. Strain Is79

ABSTRACT Microorganisms in the environment do not exist as the often-studied pure cultures but as members of complex microbial communities. Characterizing the interactions within microbial communities is essential to understand their function in both natural and engineered environments. In this study, we investigated how the presence of a nitrite-oxidizing bacterium (NOB) and heterotrophic bacteria affect the growth and proteome of the chemolithoautotrophic ammonia-oxidizing bacterium (AOB) Nitrosomonas sp. strain Is79. We investigated Nitrosomonas sp. Is79 in co-culture with Nitrobacter winogradskyi, in co-cultures with selected heterotrophic bacteria, and as a member of the nitrifying enrichment culture G5-7. In batch culture, N. winogradskyi and heterotrophic bacteria had positive effects on the growth of Nitrosomonas sp. Is79. An isobaric tag for relative and absolute quantification (iTRAQ) liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach was used to investigate the effect of N. winogradskyi and the co-cultured heterotrophic bacteria from G5-7 on the proteome of Nitrosomonas sp. Is79. In co-culture with N. winogradskyi, several Nitrosomonas sp. Is79 oxidative stress response proteins changed in abundance, with periplasmic proteins increasing and cytoplasmic proteins decreasing in abundance. In the presence of heterotrophic bacteria, the abundance of proteins directly related to the ammonia oxidation pathway increased, while the abundance of proteins related to amino acid synthesis and metabolism decreased. In summary, the proteome of Nitrosomonas sp. Is79 was differentially influenced by the presence of either N. winogradskyi or heterotrophic bacteria. Together, N. winogradskyi and heterotrophic bacteria reduced the oxidative stress for Nitrosomonas sp. Is79, which resulted in more efficient metabolism. IMPORTANCE Aerobic ammonia-oxidizing microorganisms play an important role in the global nitrogen cycle, converting ammonia to nitrite. In their natural environment, they coexist and interact with nitrite oxidizers, which convert nitrite to nitrate, and with heterotrophic microorganisms. The presence of nitrite oxidizers and heterotrophic bacteria has a positive influence on the growth of the ammonia oxidizers. Here, we present a study investigating the effect of nitrite oxidizers and heterotrophic bacteria on the proteome of a selected ammonia oxidizer in a defined culture to elucidate how these two groups improve the performance of the ammonia oxidizer. The results show that the presence of a nitrite oxidizer and heterotrophic bacteria reduced the stress for the ammonia oxidizer and resulted in more efficient energy generation. This study contributes to our understanding of microbe-microbe interactions, in particular between ammonia oxidizers and their neighboring microbial community.
Role of FcαR EC2 region in extracellular membrane localization

ABSTRACT The FcαR receptor (CD89) binds to the constant region of Immunoglobulin (Ig) A to mediate mucosal immunity [1–2]. FcαR consist of five exons: two that code for the signal peptide regions S1 & S2, two for the extracellular regions EC1 and EC2, and the final exon for the transmembrane/cytoplasmic tail region [3]. Previously, we reported that the EC1 region plays an essential role for extracellular membrane localization of the receptor [4], where the absence of EC1 would prevent the variants from localizing to the cell surface, even with a full signal peptide. In the case of FcαR Variant 4 (lacking the S2 region only), there was some “leakiness” to membrane surface localization.
Getting Ahead of Illness

Background. Metaphors influence judgments and decisions in nonmedical contexts. Objective. First, to investigate whether describing the flu metaphorically increases an individual’s willingness and interest in getting a flu vaccination, and second, to explore possible mediators and moderators of the effect that metaphors might have on vaccination intentions. Materials and Methods. Three studies, each using a between-subjects manipulation in which the flu was described literally (as a virus) or metaphorically (as a beast, riot, army, or weed), were conducted. A total of 167 psychology undergraduates (study 1) and 300 and 301 online participants (studies 2 and 3, respectively) were included. Studies 1 through 3 examined vaccination behavioral intentions, absolute risk, comparative risk, perceived flu severity, and recent flu and flu vaccination experience. Studies 2 and 3 assessed vaccination e-mail reminder requests and global affect. Study 3 evaluated affective reactions, personal control, and understanding of the flu. Results. Describing the flu metaphorically increased individuals’ willingness to get vaccinated (studies 1–3), while the impact of metaphors on requests to receive an e-mail reminder to get vaccinated was unclear (studies 2 and 3). These results were moderated by vaccination frequency in study 2, such that the effects were found among individuals who occasionally receive flu vaccinations but not among individuals who never or always receive flu vaccinations. Metaphor use did not significantly impact any of the hypothesized mediators: perceived absolute risk, comparative risk, flu severity, affect, personal control, or understanding of the flu. Limitations include convenience samples and measuring behavioral intentions but not actual vaccination behavior. Conclusions. Describing the flu virus metaphorically in decision aids or information campaigns could be a simple, cost-effective way to increase vaccinations against the flu.
Medical costs for the treatment of cervical cancer at central hospitals in Vietnam

ABSTRACT Cervical cancer remains the second most common cancer amongst female aged 15 to 44 years old in Vietnam. We estimated medical costs for the treatment of cervical cancer patients. We employed the standard costing approach and health care provider perspective. We first computed the unit cost of 22 medical services related to cervical cancer treatments and then, based on standard cervical cancer treatment protocols, we estimated the cost of nine treatment scenarios for cervical cancer patients. We found that the medical costs for treatment of cervical cancers at central hospitals in Vietnam increased as the cancer progresses into later stages.
Rectal NSAIDs in the prevention of post‐endoscopic retrograde cholangiopancreatography pancreatitis in unselected patients: Systematic review and meta‐analysis

Efficacy of rectal non‐steroidal anti‐inflammatory drugs (NSAIDs) for post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prophylaxis in unselected patients remained controversial. The aim of the present study was to evaluate the efficacy of rectal NSAIDs in the prevention of PEP in unselected patients.
Human subthalamic nucleus activity during non-motor decision making

Recent studies have implicated the subthalamic nucleus (STN) in decisions that involve inhibiting movements. Many of the decisions that we make in our daily lives, however, do not involve any motor actions. We studied non-motor decision making by recording intraoperative STN and prefrontal cortex (PFC) electrophysiology as participants perform a novel task that required them to decide whether to encode items into working memory. During all encoding trials, beta band (15–30 Hz) activity decreased in the STN and PFC, and this decrease was progressively enhanced as more items were stored into working memory. Crucially, the STN and lateral PFC beta decrease was significantly attenuated during the trials in which participants were instructed not to encode the presented stimulus. These changes were associated with increase lateral PFC-STN coherence and altered STN neuronal spiking. Our results shed light on why states of altered basal ganglia activity disrupt both motor function and cognition.
Arterial compliance probe for local blood pulse wave velocity measurement

Arterial compliance and vessel wall dynamics are significant in vascular diagnosis. We present the design of arterial compliance probes for measurement of local pulse wave velocity (PWV). Two designs of compliance probe are discussed, viz (a) a magnetic plethysmograph (MPG) based probe, and (b) a photoplethysmograph (PPG) based probe. The ability of the local PWV probes to consistently capture carotid blood pulse waves is verified by in-vivo trials on few volunteers. The probes could reliably perform repeatable measurements of local PWV from carotid artery along small artery sections less than 20 mm. Further, correlation between the measured values of local PWV using probes and various measures of blood pressure (BP) was also investigated. The study indicates that such arterial compliance probes have strong potential in cuff less BP monitoring.
A Challenge for the Seed Mixture Refuge Strategy in Bt Maize: Impact of Cross-Pollination on an Ear-Feeding Pest, Corn Earworm

To counter the threat of insect resistance, Bacillus thuringiensis (Bt) maize growers in the U.S. are required to plant structured non-Bt maize refuges. Concerns with refuge compliance led to the introduction of seed mixtures, also called RIB (refuge-in-the-bag), as an alternative approach for implementing refuge for Bt maize products in the U.S. Maize Belt. A major concern in RIB is cross-pollination of maize hybrids that can cause Bt proteins to be present in refuge maize kernels and negatively affect refuge insects. Here we show that a mixed planting of 5% nonBt and 95% Bt maize containing the SmartStax traits expressing Cry1A.105, Cry2Ab2 and Cry1F did not provide an effective refuge for an important above-ground ear-feeding pest, the corn earworm, Helicoverpa zea (Boddie). Cross-pollination in RIB caused a majority (>90%) of refuge kernels to express ≥ one Bt protein. The contamination of Bt proteins in the refuge ears reduced neonate-to-adult survivorship of H. zea to only 4.6%, a reduction of 88.1% relative to larvae feeding on ears of pure non-Bt maize plantings. In addition, the limited survivors on refuge ears had lower pupal mass and took longer to develop to adults.
A Randomized Trial of High‐Flow Oxygen Therapy in Infants with Bronchiolitis

BACKGROUND High‐flow oxygen therapy through a nasal cannula has been increasingly used in infants with bronchiolitis, despite limited high‐quality evidence of its efficacy. The efficacy of high‐flow oxygen therapy through a nasal cannula in settings other than intensive care units (ICUs) is unclear. METHODS In this multicenter, randomized, controlled trial, we assigned infants younger than 12 months of age who had bronchiolitis and a need for supplemental oxygen therapy to receive either high‐flow oxygen therapy (high‐flow group) or standard oxygen therapy (standard‐therapy group). Infants in the standard‐therapy group could receive rescue high‐flow oxygen therapy if their condition met criteria for treatment failure. The primary outcome was escalation of care due to treatment failure (defined as meeting ≥3 of 4 clinical criteria: persistent tachycardia, tachypnea, hypoxemia, and medical review triggered by a hospital early‐warning tool). Secondary outcomes included duration of hospital stay, duration of oxygen therapy, and rates of transfer to a tertiary hospital, ICU admission, intubation, and adverse events. RESULTS The analyses included 1472 patients. The percentage of infants receiving escalation of care was 12% (87 of 739 infants) in the high‐flow group, as compared with 23% (167 of 733) in the standard‐therapy group (risk difference, ‐11 percentage points; 95% confidence interval, ‐15 to ‐7; P<0.001). No significant differences were observed in the duration of hospital stay or the duration of oxygen therapy. In each group, one case of pneumothorax (<1% of infants) occurred. Among the 167 infants in the standard‐therapy group who had treatment failure, 102 (61%) had a response to high‐flow rescue therapy. CONCLUSIONS Among infants with bronchiolitis who were treated outside an ICU, those who received high‐flow oxygen therapy had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy. (Funded by the National Health and Medical Research Council and others; Australian and New Zealand Clinical Trials Registry number, ACTRN12613000388718.)
On First-Order Meta-Learning Algorithms

This paper considers meta-learning problems, where there is a distribution of tasks, and we would like to obtain an agent that performs well (i.e., learns quickly) when presented with a previously unseen task sampled from this distribution. We analyze a family of algorithms for learning a parameter initialization that can be fine-tuned quickly on a new task, using only first-order derivatives for the meta-learning updates. This family includes and generalizes first-order MAML, an approximation to MAML obtained by ignoring second-order derivatives. It also includes Reptile, a new algorithm that we introduce here, which works by repeatedly sampling a task, training on it, and moving the initialization towards the trained weights on that task. We expand on the results from Finn et al. showing that first-order meta-learning algorithms perform well on some well-established benchmarks for few-shot classification, and we provide theoretical analysis aimed at understanding why these algorithms work.
Frequency of COL4A3/COL4A4 Mutations amongst Families Segregating Glomerular Microscopic Hematuria and Evidence for Activation of the Unfolded Protein Response. Focal and Segmental Glomerulosclerosis Is a Frequent Development during Ageing

Familial glomerular hematuria(s) comprise a genetically heterogeneous group of conditions which include Alport Syndrome (AS) and thin basement membrane nephropathy (TBMN). Here we investigated 57 Greek-Cypriot families presenting glomerular microscopic hematuria (GMH), with or without proteinuria or chronic kidney function decline, but excluded classical AS. We specifically searched the COL4A3/A4 genes and identified 8 heterozygous mutations in 16 families (28,1%). Eight non-related families featured the founder mutation COL4A3-p.(G1334E). Renal biopsies from 8 patients showed TBMN and focal segmental glomerulosclerosis (FSGS). Ten patients (11.5%) reached end-stage kidney disease (ESKD) at ages ranging from 37-69-yo (mean 50,1-yo). Next generation sequencing of the patients who progressed to ESKD failed to reveal a second mutation in any of the COL4A3/A4/A5 genes, supporting that true heterozygosity for COL4A3/A4 mutations predisposes to CRF/ESKD. Although this could be viewed as a milder and late-onset form of autosomal dominant AS, we had no evidence of ultrastructural features or extrarenal manifestations that would justify this diagnosis. Functional studies in cultured podocytes transfected with wild type or mutant COL4A3 chains showed retention of mutant collagens and differential activation of the unfolded protein response (UPR) cascade. This signifies the potential role of the UPR cascade in modulating the final phenotype in patients with collagen IV nephropathies.
Facial Trustworthiness Judgments in Children with ASD Are Modulated by Happy and Angry Emotional Cues

Appearance-based trustworthiness inferences may reflect the misinterpretation of emotional expression cues. Children and adults typically perceive faces that look happy to be relatively trustworthy and those that look angry to be relatively untrustworthy. Given reports of atypical expression perception in children with Autism Spectrum Disorder (ASD), the current study aimed to determine whether the modulation of trustworthiness judgments by emotional expression cues in children with ASD is also atypical. Cognitively-able children with and without ASD, aged 6–12 years, rated the trustworthiness of faces showing happy, angry and neutral expressions. Trust judgments in children with ASD were significantly modulated by overt happy and angry expressions, like those of typically-developing children. Furthermore, subtle emotion cues in neutral faces also influenced trust ratings of the children in both groups. These findings support a powerful influence of emotion cues on perceived trustworthiness, which even extends to children with social cognitive impairments.
Health Outcomes and Cost Impact of the New WHO 2013 Guidelines on Prevention of Mother-to-Child Transmission of HIV in Zambia

Background Countries are currently progressing towards the elimination of new paediatric HIV infections by 2015. WHO published new consolidated guidelines in June 2013, which now recommend either ‘Antiretroviral drugs (ARVs) for women living with HIV during pregnancy and breastfeeding (Option B)’ or ‘Lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women living with HIV (Option B+)’, while de facto phasing out Option A. This study examined health outcomes and cost impact of the shift to WHO 2013 recommendations in Zambia. Methods A decision analytic model was developed based on the national health system perspective. Estimated risk and number of cases of HIV transmission to infants and to serodiscordant partners, and proportions of HIV-infected pregnant women with CD4 count of ≤350 cells/mm3 to initiate ART were compared between 2010 Option A and the 2013 recommendations. Total costs of prevention of mother-to-child transmission of HIV (PMTCT) services per annual cohort of pregnant women, incremental cost-effectiveness ratio (ICER) per infection averted and quality-adjusted life-year (QALY) gained were examined. Results Our analysis suggested that the shift from 2010 Option A to the 2013 guidelines would result in a 33% reduction of the risk of HIV transmission among exposed infants. The risk of transmission to serodiscordant partners for a period of 24 months would be reduced by 72% with ‘ARVs during pregnancy and breastfeeding’ and further reduced by 15% with ‘Lifelong ART’. The probability of HIV-infected pregnant women to initiate ART would increase by 80%. It was also suggested that while the shift would generate higher PMTCT costs, it would be cost-saving in the long term as it spares future treatment costs by preventing infections in infants and partners. Conclusion The shift to the WHO 2013 guidelines in Zambia would positively impact health of family and save future costs related to care and treatment.
Suppressive effect of nobiletin and epicatechin gallate on fructose uptake in human intestinal epithelial Caco-2 cells

Abstract Inhibition of excessive fructose intake in the small intestine could alleviate fructose-induced diseases such as hypertension and non-alcoholic fatty liver disease. We examined the effect of phytochemicals on fructose uptake using human intestinal epithelial-like Caco-2 cells which express the fructose transporter, GLUT5. Among 35 phytochemicals tested, five, including nobiletin and epicatechin gallate (ECg), markedly inhibited fructose uptake. Nobiletin and ECg also inhibited the uptake of glucose but not of L-leucine or Gly-Sar, suggesting an inhibitory effect specific to monosaccharide transporters. Kinetic analysis further suggested that this reduction in fructose uptake was associated with a decrease in the apparent number of cell-surface GLUT5 molecules, and not with a change in the affinity of GLUT5 for fructose. Lastly, nobiletin and ECg suppressed the permeation of fructose across Caco-2 cell monolayers. These findings suggest that nobiletin and ECg are good candidates for preventing diseases caused by excessive fructose intake. Graphical abstract Nobiletin and ECg inhibited fructose uptake in human intestinal epithelial-like Caco-2 cells presumably by affecting GLUT5.
Cardiorenal Syndrome: The Clinical Cardiologists’ Perspective

The term cardiorenal syndrome has evolved over the years. The understanding of the interactions between these two organ systems has led to better recognition and treatment strategies. As cardiovascular mortality is high in individuals with renal dysfunction, it is imperative to understand the pathophysiology behind the disease process. This knowledge may better serve these patients with this syndrome and improve their outcomes. In this review, we examine the key issues of the cardiorenal syndrome from a cardiologist’s perspective.
Bioactive Glass Nanoparticles as a New Delivery System for Sustained 5-Fluorouracil Release: Characterization and Evaluation of Drug Release Mechanism

Bioactive glass nanoparticles were synthesized and tested for the first time as a new delivery system for sustained 5-fluorouracil (5-FU) release. They were characterized by TEM, DTA, TGA, and FT-IR. The porosity % and specific surface area of glass nanoparticles were 85.59% and 378.36 m2/g, respectively. The in vitro bioactivity evaluation confirmed that bioactive glass disks prepared from these nanoparticles could induce hydroxyapatite layer over their surfaces in simulated body fluid. The in vitro drug release experiment indicated that glass nanoparticles could serve as long-term local delivery vehicles for sustained 5-FU release. The release profile of 5-FU showed an initial fast release stage followed by a second stage of slower release. The initial burst release of 5-FU in the first day was about 23% (28.92 mg·L−1) of the total amount of loaded 5-FU, while the final cumulative percentage of the 5-FU released after 32 days was about 45.6% (57.31 mg·L−1) of the total amount of loaded 5-FU. The application of different mathematical models indicated that 5-FU was released by diffusion controlled mechanism and suggested that its release rate was dependent on glass particles dissolution, changes of surface area as well as diameter of glass particles, and concentration of loaded drug.