A global initiative on addressing bioinformatics' grand challenges.

The Bioinformatics Grand Challenges Consortium (BGCC) is a collaborative effort to address the most pressing challenges in bioinformatics. Initially focusing on education and training, the consortium successfully defined seven key grand challenges and is actively developing actionable solutions for these challenges. Building on this foundation, the BGCC plans to broaden its focus to include additional grand challenges in emerging areas.

Author Correction: Spatially resolved steady-state negative capacitance.

In this Letter, the first name of author Bhagwati Prasad was misspelled Bhagawati. This error has been corrected online.

Spatially resolved steady-state negative capacitance.

Negative capacitance is a newly discovered state of ferroelectric materials that holds promise for electronics applications by exploiting a region of thermodynamic space that is normally not accessible1-14. Although existing reports of negative capacitance substantiate the importance of this phenomenon, they have focused on its macroscale manifestation. These manifestations demonstrate possible uses of steady-state negative capacitance-for example, enhancing the capacitance of a ferroelectric-dielectric heterostructure4,7,14 or improving the subthreshold swing of a transistor8-12. Yet they constitute only indirect measurements of the local state of negative capacitance in which the ferroelectric resides. Spatial mapping of this phenomenon would help its understanding at a microscopic scale and also help to achieve optimal design of devices with potential technological applications. Here we demonstrate a direct measurement of steady-state negative capacitance in a ferroelectric-dielectric heterostructure. We use electron microscopy complemented by phase-field and first-principles-based (second-principles) simulations in SrTiO3/PbTiO3 superlattices to directly determine, with atomic resolution, the local regions in the ferroelectric material where a state of negative capacitance is stabilized. Simultaneous vector mapping of atomic displacements (related to a complex pattern in the polarization field), in conjunction with reconstruction of the local electric field, identify the negative capacitance regions as those with higher energy density and larger polarizability: the domain walls where the polarization is suppressed.

Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma.

BACKGROUND: Children with moderate-to-severe asthma continue to have disease complications despite the receipt of standard-of-care therapy. The monoclonal antibody dupilumab has been approved for the treatment of adults and adolescents with asthma as well as with other type 2 inflammatory diseases. METHODS: In this 52-week phase 3, randomized, double-blind, placebo-controlled trial, we assigned 408 children between the ages of 6 and 11 years who had uncontrolled moderate-to-severe asthma to receive a subcutaneous injection of dupilumab (at a dose of 100 mg for those weighing ≤30 kg and 200 mg for those weighing >30 kg) or matched placebo every 2 weeks. All the children continued to receive a stable dose of standard background therapy. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second (ppFEV1) at week 12 and in the score on the Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) at week 24. End points were evaluated in the two primary efficacy populations who had either a type 2 inflammatory asthma phenotype (≥150 blood eosinophils per cubic millimeter or a fraction of exhaled nitric oxide of ≥20 ppb at baseline) or a blood eosinophil count of at least 300 cells per cubic millimeter at baseline. RESULTS: In patients with the type 2 inflammatory phenotype, the annualized rate of severe asthma exacerbations was 0.31 (95% confidence interval [CI], 0.22 to 0.42) with dupilumab and 0.75 (95% CI, 0.54 to 1.03) with placebo (relative risk reduction in the dupilumab group, 59.3%; 95% CI, 39.5 to 72.6; P<0.001). The mean (±SE) change from baseline in the ppFEV1 was 10.5±1.0 percentage points with dupilumab and 5.3±1.4 percentage points with placebo (mean difference, 5.2 percentage points; 95% CI, 2.1 to 8.3; P<0.001). Dupilumab also resulted in significantly better asthma control than placebo (P<0.001). Similar results were observed in the patients with an eosinophil count of at least 300 cells per cubic millimeter at baseline. The incidence of serious adverse events was similar in the two groups. CONCLUSIONS: Among children with uncontrolled moderate-to-severe asthma, those who received add-on dupilumab had fewer asthma exacerbations and better lung function and asthma control than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; Liberty Asthma VOYAGE ClinicalTrials.gov number, NCT02948959.).

Complete mitochondrial genomes of edible mushrooms: features, evolution, and phylogeny.

Edible mushrooms are an important food source with high nutritional and medicinal value. They are a useful source for studying phylogenetic evolution and species divergence. The exploration of the evolutionary relationships among these species conventionally involves analyzing sequence variations within their complete mitochondrial genomes, which range from 31,854 bp (Cordyceps militaris) to 197,486 bp (Grifolia frondosa). The study of the complete mitochondrial genomes of edible mushrooms has emerged as a critical field of research, providing important insights into fungal genetic makeup, evolution, and phylogenetic relationships. This review explores the mitochondrial genome structures of various edible mushroom species, highlighting their unique features and evolutionary adaptations. By analyzing these genomes, robust phylogenetic frameworks are constructed to elucidate mushrooms lineage relationships. Furthermore, the exploration of different variations of mitochondrial DNA presents novel opportunities for enhancing mushroom cultivation biotechnology and medicinal applications. The mitochondrial genomic features are essential for improving agricultural practices and ensuring food security through improved crop productivity, disease resistance, and nutritional qualities. The current knowledge about the mitochondrial genomes of edible mushrooms is summarized in this review, emphasising their significance in both scientific research and practical applications in bioinformatics and medicine.

A new efficient referential genome compression technique for FastQ files.

Hospitals and medical laboratories create a tremendous amount of genome sequence data every day for use in research, surgery, and illness diagnosis. To make storage comprehensible, compression is therefore essential for the storage, monitoring, and distribution of all these data. A novel data compression technique is required to reduce the time as well as the cost of storage, transmission, and data processing. General-purpose compression techniques do not perform so well for these data due to their special features: a large number of repeats (tandem and palindrome), small alphabets, and highly similar, and specific file formats. In this study, we provide a method for compressing FastQ files that uses a reference genome as a backup without sacrificing data quality. FastQ files are initially split into three streams (identifier, sequence, and quality score), each of which receives its own compression technique. A novel quick and lightweight mapping mechanism is also presented to effectively compress the sequence stream. As shown by experiments, the suggested methods, both the compression ratio and the compression/decompression duration of NGS data compressed using RBFQC, are superior to those achieved by other state-of-the-art genome compression methods. In comparison to GZIP, RBFQC may achieve a compression ratio of 80-140% for fixed-length datasets and 80-125% for variable-length datasets. Compared to domain-specific FastQ file referential genome compression techniques, RBFQC has a compression and decompression speed (total) improvement of 10-25%.

Dupilumab leads to better-controlled asthma and quality of life in children: the VOYAGE study.

BACKGROUND: Dupilumab has shown long-term treatment benefits in children with uncontrolled asthma. We assessed in more detail the impact of dupilumab on asthma control and health-related quality of life (HRQoL) in children and their caregivers. METHODS: Children aged 6-11 years with uncontrolled moderate-to-severe type 2 asthma (baseline blood eosinophils ≥150 cells·µL-1 or fractional exhaled nitric oxide ≥20 ppb; n=350) were treated with dupilumab or placebo for 52 weeks in the VOYAGE study. Primary outcomes of these analyses were asthma control (change from baseline in Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) and achieving a clinically meaningful response of ≥0.5 points); proportion of patients achieving well-controlled asthma or better (ACQ-7-IA ≤0.75 points); effect on patients' (Standardised Paediatric Asthma Quality of Life Questionnaire Interviewer-Administered (PAQLQ(S)-IA)) and caregivers' (Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ)) HRQoL; and allergic rhinitis-related QoL. RESULTS: Dupilumab versus placebo significantly improved children's ACQ-7-IA scores by week 4 with sustained improvements through week 52 (least squares mean difference at week 52: -0.44, 95% CI -0.59- -0.30; p<0.0001); a higher proportion achieved a clinically meaningful response (week 52: 86% versus 75%; p=0.0051). At weeks 24 and 52, more children who received dupilumab achieved well-controlled asthma (ACQ-7-IA ≤0.75 points: 61% versus 43%; p=0.0001 and 70% versus 46%; p<0.0001, respectively). Significant improvements in PAQLQ(S)-IA and PACQLQ scores were observed by week 52. CONCLUSIONS: In children aged 6-11 years with moderate-to-severe type 2 asthma, dupilumab treatment was associated with rapid, sustained improvements in asthma control. HRQoL was significantly improved for children and their caregivers.

Control of Halogen Atom in Inorganic Metal-Halide Perovskites Enables Large Piezoelectricity for Electromechanical Energy Generation.

Regulating the strain of inorganic perovskites has emerged as a critical approach to control their electronic and optical properties. Here, an alternative strategy to further control the piezoelectric properties by substituting the halogen atom (I/Br) in the CsPbX3 perovskite (X = Cl, Br) structure is adopted. A series of piezoelectric materials with excellent piezoelectric coefficients (d33 ) are unveiled. Iodine-incorporated CsPbBr2 I demonstrates the record intrinsic piezoelectric response (d33 ≈47 pC N-1 ) among all inorganic metal halide perovskites. This leads to an excellent electrical output power of ≈ 0.375 mW (24.8 µW cm-2 N-1 ) in the piezoelectric energy generator (PEG) which is higher than those of the pristine/mixed perovskite references with CsPbX3 (X = I, Br, Cl). With its structural phase remaining unchanged, the strained CsPbBr2 I retains its superior piezoelectricity in both thin film and nanocrystal powder forms, further demonstrating its repeatability and versatility of applications. The origin of high piezoelectricity is found to be due to halogen-induced anisotropic lattice strain in the unit-cell along the c-axis, and octahedral distortion. This study reveals an avenue to design new piezoelectric materials by modifying their halide constituents and paves the way to design efficient PEGs for improved electromechanical energy conversion.

Impact of exacerbations on lung function, resource utilization, and productivity: results from an observational, prospective study in adults with uncontrolled asthma.

Background: Exacerbations have a major impact on the well-being of patients with uncontrolled asthma. This study evaluated lung function, healthcare resource utilization (HCRU), and productivity loss following asthma exacerbations.Methods: This single-center, observational, prospective cohort study recruited US patients presenting clinically with an acute asthma exacerbation; a reference group without exacerbations was included for comparison. Lung function (forced expiratory volume in 1 second [FEV1]) was collected at baseline, daily during Month 1, and monthly for Months 2-5, and reported as FEV1 percent predicted (FEV1pp). HCRU (outpatient visits to a healthcare practitioner, emergency room [ER] visits, and hospitalizations for asthma), oral corticosteroid (OCS) use, and asthma-related work/school absence were collected monthly for 6 months.Results: Overall, 150 patients were recruited (exacerbation: n=102; reference: n=48; mean [SD] age: 42.7 [15.2] and 49.6 [12.4] years; female: 73% and 71%). In both groups, similar trends were observed in FEV1, with significant improvement from baseline to Week 1 (p<0.05), followed by a continuous decline. FEV1p was 7.7% lower at baseline and 8.6% lower at Month 5 in the exacerbation group versus the reference group. The exacerbation group had significantly higher rates of OCS prescription during follow-up versus reference group (p=0.04). Over half (52.9%) of patients in the exacerbation group had a recurrent exacerbation during follow-up, increased HCRU (outpatient visits, ER visits, and hospitalizations), and impaired productivity.Conclusion: Although patients with exacerbations had rapid recovery of lung function, this was not maintained and declined faster than in patients without exacerbations. Additionally, patients experienced increased HCRU after exacerbations.

Genomic analysis and biological characterization of a novel Schitoviridae phage infecting Vibrio alginolyticus.

Vibrio alginolyticus is a Gram-negative bacterium commonly associated with mackerel poisoning. A bacteriophage that specifically targets and lyses this bacterium could be employed as a biocontrol agent for treating the bacterial infection or improving the shelf-life of mackerel products. However, only a few well-characterized V. alginolyticus phages have been reported in the literature. In this study, a novel lytic phage, named ΦImVa-1, specifically infecting V. alginolyticus strain ATCC 17749, was isolated from Indian mackerel. The phage has a short latent period of 15 min and a burst size of approximately 66 particles per infected bacterium. ΦImVa-1 remained stable for 2 h at a wide temperature (27-75 °C) and within a pH range of 5 to 10. Transmission electron microscopy revealed that ΦImVa-1 has an icosahedral head of approximately 60 nm in diameter with a short tail, resembling those in the Schitoviridae family. High throughput sequencing and bioinformatics analysis elucidated that ΦImVa-1 has a linear dsDNA genome of 77,479 base pairs (bp), with a G + C content of ~ 38.72% and 110 predicted gene coding regions (106 open reading frames and four tRNAs). The genome contains an extremely large virion-associated RNA polymerase gene and two smaller non-virion-associated RNA polymerase genes, which are hallmarks of schitoviruses. No antibiotic genes were found in the ΦImVa-1 genome. This is the first paper describing the biological properties, morphology, and the complete genome of a V. alginolyticus-infecting schitovirus. When raw mackerel fish flesh slices were treated with ΦImVa-1, the pathogen loads reduced significantly, demonstrating the potential of the phage as a biocontrol agent for V. alginolyticus strain ATCC 17749 in the food. KEY POINTS: • A novel schitovirus infecting Vibrio alginolyticus ATCC 17749 was isolated from Indian mackerel. • The complete genome of the phage was determined, analyzed, and compared with other phages. • The phage is heat stable making it a potential biocontrol agent in extreme environments.

Breast cancer: A comparative review for breast cancer detection using machine learning techniques.

Breast cancer is the most common cancer among women globally and presents a significant challenge due to its rising incidence and fatality rates. Factors such as cultural, socioeconomic, and educational barriers contribute to inadequate awareness and access to healthcare services, often leading to delayed diagnoses and poor patient outcomes. Furthermore, fostering a collaborative approach among healthcare providers, policymakers, and community leaders is crucial in addressing this critical women's health issue, reducing mortality rates, alleviating, and the overall burden of breast cancer. The main goal of this review is to explore various techniques of machine learning algorithms to examine high accuracy and early detection of breast cancer for the safe health of women.

Prevalence and Severity Distribution of Type 2 Inflammation-Related Comorbidities Among Patients with Asthma, Chronic Rhinosinusitis with Nasal Polyps, and Atopic Dermatitis.

This observational study assessed the prevalence of co-existing type 2 inflammatory conditions [T2Cs; asthma, atopic dermatitis (AD), allergic rhinitis, and chronic rhinosinusitis with nasal polyps (CRSwNP)] in patients with moderate-to-severe (M/S) type 2 asthma, M/S CRSwNP, or M/S AD, in the real-world setting. Data from 761 physicians in the US and EUR5 were sourced from Adelphi Disease-Specific Programmes covering patients with M/S asthma (n = 899), M/S CRSwNP (n = 683), and M/S AD (n = 1497). At least one T2C was identified in 66%, 69%, and 46% of M/S asthma, M/S CRSwNP, and M/S AD cohorts, respectively, and 24%, 36% and 16% had at least two T2Cs; trends were similar in the US and EUR5. In patients with M/S asthma or M/S CRSwNP, T2Cs commonly presented as mild or moderate. The comorbidity burden suggests that an integrated treatment approach is warranted to address underlying type 2 inflammation in patients with M/S type 2 diseases.

Dupilumab efficacy in patients with chronic rhinosinusitis with nasal polyps with and without allergic rhinitis.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease, which often coexists with allergic rhinitis (AR). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation. Objective: This post hoc analysis investigated the efficacy and safety of dupilumab in patients with severe CRSwNP with or without coexisting AR in the pooled phase III SINUS-24/SINUS-52 studies. Methods: Patients randomized to subcutaneous dupilumab 300 mg (n = 438) or placebo (n = 286) every 2 weeks for 24 (SINUS-24) or 52 weeks (SINUS-52) were analyzed. Pooled data from the first 24 weeks of treatment are presented. Changes from baseline in disease outcome measures and biomarker levels were analyzed by the patient-reported history of AR status. Results: Overall, 338 of 724 patients (46.7%) had AR. Baseline characteristics were generally similar between patients with and those without AR. Dupilumab significantly improved objective and patient-reported measures of CRSwNP, including loss of smell, and reduced systemic and nasal biomarker levels versus placebo at week 24, with no significant treatment difference between patients with and those without AR. Use of systemic corticosteroids and/or sinonasal surgery during treatment was significantly reduced with dupilumab versus placebo, irrespective of AR status (p ≤ 0.0029). The safety profile of dupilumab was similar in patients with and in patients without AR. Conclusion: Dupilumab demonstrated significant improvements in both clinical end points and symptom scores versus placebo in patients with severe CRSwNP, irrespective of comorbid AR status, a common subgroup of patients often associated with poorer CRSwNP outcomes. Clinical trials NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52), www.clinicaltrials.gov.

Fertilization and cultivation management promotes soil phosphorus availability by enhancing soil P-cycling enzymes and the phosphatase encoding genes in bulk and rhizosphere soil of a maize crop in sloping cropland.

Fertilization and cultivation managements exert significant effects on crop growth and soil-associated nutrients in croplands. However, there is a lack of knowledge regarding how these practices affect soil phosphorus-cycling enzymes and functional genes involved in regulating global P-cycling, especially under intense agricultural management practices in sloping croplands. A long-term field (15-year) trial was conducted in a 15° sloping field based on five treatments: no fertilizer amendments + downslope cultivation (CK); mixed treatment of mineral fertilizer and organic manure + downslope cultivation (T1); mineral fertilizer alone + downslope cultivation (T2); 1.5-fold mineral fertilizer + downslope cultivation (T3); and mineral fertilizer + contour cultivation (T4). Bulk and rhizosphere soil samples were collected after the maize crop was harvested to determine the P fraction, P-cycling enzymes, and phosphatase-encoding genes. Results indicated that fertilization management significantly increased the inorganic (Pi) and organic soil (Po) P fractions compared to CK, except for NaOH-extractable Po in T1 and T3 in bulk and rhizosphere soils, respectively. For the cultivation treatments, the content of Pi pools in the downslope cultivation of T1 and T3 was significantly larger than that in the contour cultivation of T4 in bulk and rhizosphere soils. However, the content of NaOH-extractable Po in T1 and T3 was lower compared to T4 in bulk soil and vice versa for the NaHCO3-P and HCl-Po fractions in the rhizosphere. We also found that fertilization and cultivation managements significantly increased the activity of acid phosphatase (ACP), alkaline phosphatase (ALP), phytase, phosphodiesterases (PDE), and phoC and phoD gene abundance in bulk and rhizosphere soils, with a larger effect on the activity of ALP and the phosphatase encoding phoD gene, especially in T1 and T3 in the rhizosphere. Soil organic carbon (SOC) and microbial biomass C and P (MBC and MBP) were the main predictors for regulating P-cycling enzymes and phoC- and phoD gene abundance. A strong association of P-cycling enzymes, especially ALP and phytase, and the abundance of phoD genes with the P fraction indicated that the soil P cycle was mainly mediated by microbial-related processes. Together, our results demonstrated that an adequate amount of mineral fertilizer alone or combined with organic fertilizer plus downslope cultivation is more effective in promoting soil P availability by enhancing the activity of ALP, phytase, and phoD genes. This provides valuable information for sustaining soil microbial-regulated P management practices in similar agricultural lands worldwide.

Managing Security of Healthcare Data for a Modern Healthcare System.

The advent of Artificial Intelligence (AI) and the Internet of Things (IoT) have recently created previously unimaginable opportunities for boosting clinical and patient services, reducing costs and improving community health. Yet, a fundamental challenge that the modern healthcare management system faces is storing and securely transferring data. Therefore, this research proposes a novel Lionized remora optimization-based serpent (LRO-S) encryption method to encrypt sensitive data and reduce privacy breaches and cyber-attacks from unauthorized users and hackers. The LRO-S method is the combination of hybrid metaheuristic optimization and improved security algorithm. The fitness functions of lion and remora are combined to create a new algorithm for security key generation, which is provided to the serpent encryption algorithm. The LRO-S technique encrypts sensitive patient data before storing it in the cloud. The primary goal of this study is to improve the safety and adaptability of medical professionals' access to cloud-based patient-sensitive data more securely. The experiment's findings suggest that the secret keys generated are sufficiently random and one of a kind to provide adequate protection for the data stored in modern healthcare management systems. The proposed method minimizes the time needed to encrypt and decrypt data and improves privacy standards. This study found that the suggested technique outperformed previous techniques in terms of reducing execution time and is cost-effective.

Edge Computing for Effective and Efficient Traffic Characterization.

Traffic flow analysis is essential to develop smart urban mobility solutions. Although numerous tools have been proposed, they employ only a small number of parameters. To overcome this limitation, an edge computing solution is proposed based on nine traffic parameters, namely, vehicle count, direction, speed, and type, flow, peak hour factor, density, time headway, and distance headway. The proposed low-cost solution is easy to deploy and maintain. The sensor node is comprised of a Raspberry Pi 4, Pi camera, Intel Movidius Neural Compute Stick 2, Xiaomi MI Power Bank, and Zong 4G Bolt+. Pre-trained models from the OpenVINO Toolkit are employed for vehicle detection and classification, and a centroid tracking algorithm is used to estimate vehicle speed. The measured traffic parameters are transmitted to the ThingSpeak cloud platform via 4G. The proposed solution was field-tested for one week (7 h/day), with approximately 10,000 vehicles per day. The count, classification, and speed accuracies obtained were 79.8%, 93.2%, and 82.9%, respectively. The sensor node can operate for approximately 8 h with a 10,000 mAh power bank and the required data bandwidth is 1.5 MB/h. The proposed edge computing solution overcomes the limitations of existing traffic monitoring systems and can work in hostile environments.

Meibomian Gland Dysfunction Is Associated with Low Levels of Immunoglobulin Chains and Cystatin-SN.

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography-tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulated. The largest change was observed in cystatin-SN, which was downregulated in MGD and correlated negatively with tear meniscus height. The downregulation of cystatin-SN was confirmed with targeted mass spectrometry by single reaction monitoring (SRM). Eighteen immunoglobulin components involved in B cell activation, phagocytosis, and complement activation were downregulated in MGD including Ig alpha-1 chain C region, immunoglobulin J chain, immunoglobulin heavy variable 3-15, and Ig mu chain C region. The changes in cystatin-SN and immunoglobulin chains are likely to result from the inflammatory changes related to tear film evaporation, and future studies may assess their association with the meibum quality.

Antibacterial and Antibiofilm Activity of Ficus carica-Mediated Calcium Oxide (CaONPs) Phyto-Nanoparticles.

The significance of nanomaterials in biomedicines served as the inspiration for the design of this study. In this particular investigation, we carried out the biosynthesis of calcium oxide nanoparticles (CaONPs) by employing a green-chemistry strategy and making use of an extract of Ficus carica (an edible fruit) as a capping and reducing agent. There is a dire need for new antimicrobial agents due to the alarming rise in antibiotic resistance. Nanoparticles' diverse antibacterial properties suggest that they might be standard alternatives to antimicrobial drugs in the future. We describe herein the use of a Ficus carica extract as a capping and reducing agent in the phyto-mediated synthesis of CaONPs for the evaluation of their antimicrobial properties. The phyto-mediated synthesis of NPs is considered a reliable approach due to its high yield, stability, non-toxicity, cost-effectiveness and eco-friendliness. The CaONPs were physiochemically characterized by UV-visible spectroscopy, energy-dispersive X-ray (EDX), scanning-electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). The biological synthesis of the calcium oxide nanoparticles revealed a characteristic surface plasmon resonance peak (SPR) at 360 nm in UV-Vis spectroscopy, which clearly revealed the successful reduction of the Ca2+ ions to Ca0 nanoparticles. The characteristic FTIR peak seen at 767 cm-1 corresponded to Ca-O bond stretching and, thus, confirmed the biosynthesis of the CaONPs, while the scanning-electron micrographs revealed near-CaO aggregates with an average diameter of 84.87 ± 2.0 nm. The antibacterial and anti-biofilm analysis of the CaONPs showed inhibition of bacteria in the following order: P. aeruginosa (28 ± 1.0) > S. aureus (23 ± 0.3) > K. pneumoniae (18 ± 0.9) > P. vulgaris (13 ± 1.6) > E. coli (11 ± 0.5) mm. The CaONPs were shown to considerably inhibit biofilm formation, providing strong evidence for their major antibacterial activity. It is concluded that this straightforward environmentally friendly method is capable of synthesizing stable and effective CaONPs. The therapeutic value of CaONPs is indicated by their potential as a antibacterial and antibiofilm agents in future medications.

Dupilumab improves health related quality of life: Results from the phase 3 SINUS studies.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2-mediated inflammatory disease with high symptom burden and reduced health-related quality of life (HRQoL). This report aimed to comprehensively understand the effects of dupilumab on domains of HRQoL, their individual elements, and health status in patients with severe CRSwNP from phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) trials. METHODS: Patients were randomized to dupilumab (n = 438) or placebo (n = 286) for 24 weeks (SINUS-24), or 52 weeks (SINUS-52). Disease-specific HRQoL using 22-item sino-nasal outcome test (SNOT-22), and health status using EuroQoL-visual analog scale (EQ-VAS) was evaluated in the pooled intention-to-treat (ITT) population (Week 24), SINUS-52 ITT (Week 52) and in the subgroups with/without asthma; non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD); and prior sinus surgery. RESULTS: At baseline, patients had poor disease-specific HRQoL and general health status and identified "Decreased sense of smell/taste" and "Nasal blockage" as the most important symptoms. Dupilumab significantly improved SNOT-22 total, domain (Nasal, Sleep, Function, Emotion, and Ear/facial), and 22-item scores, and EQ-VAS, at Week 24 vs placebo (all p < .0001), with continued improvements to Week 52 in SINUS-52. Improvements occurred irrespective of comorbid asthma, NSAID-ERD, or prior surgery. A significantly greater proportion of dupilumab-treated patients exceeded clinically meaningful thresholds for SNOT-22 total score and EQ-VAS vs placebo (all subgroups p < .05 except patients without surgery at Week 24). CONCLUSIONS: Dupilumab treatment led to significant clinically meaningful improvements across all aspects of disease-specific HRQoL, and general health status in patients with severe CRSwNP.

Outcome of left main stem percutaneous coronary intervention in a UK nonsurgical center: A 5-year clinical experience.

OBJECTIVES: To evaluate the outcome of unprotected left main stem (LMS) percutaneous coronary intervention (PCI) in a large UK nonsurgical center. BACKGROUND: PCI on unprotected LMS is increasingly regarded as a viable alternative to coronary artery bypass grafting (CABG) with comparable outcome and safety profile in select groups. The safety and efficacy of unprotected LMS PCI without on-site surgical back up has not been reported. METHODS: Data on all unprotected LMS PCI performed between January 2011 and December 2015, was collected from the local PCI database and electronic patient records. In hospital and 1-year major adverse cardiovascular events (MACE) (all-cause mortality, myocardial infarction [MI], stroke, and target vessel revascularization [TVR]) was recorded. RESULTS: 249 patients had unprotected LMS intervention during the study period. 77% of patients (n = 192) were male and mean age was 70 ± 12 years. 31% (n = 78) of cases were elective, 44% (n = 109) NSTEMI, and 25% (n = 62) STEMI. Anatomical distribution: 19% (n = 47) ostial left main, 31% (n = 77) shaft, and 50% (n = 125) bifurcation. The mean SYNTAX score was 24.4 ± 10.6. 22% (n = 55) of patients had severe LV impairment preprocedure and 13% (n = 33) were in cardiogenic shock at presentation. 35% (14%) required IABP support. The vast majority (98.4%) of procedures were successful. No patients required emergency transfer for CABG surgery. There were 25 (10%) in-hospital deaths. 68% of in-hospital deaths occurred in patients undergoing primary PCI for STEMI. 72% of patients who died were in cardiogenic shock at presentation. The 12-month MACE rate was 17.2%. Death occurred in 11.6%, MI in 2.4%, TVR in 2.4%, and stroke in 0.8% of patients. CONCLUSION: These results highlight the safety and efficacy of unprotected LMS PCI in a high volume non-surgical center.