Explore the vast range of titles available.

Rare genetic diseases are rare by themselves with prevalence of 1 in 25,000, but collectively they are a significant cause of morbidity and mortality. Till date, collectively there are more than 9,000 rare diseases documented, which impose a devastating impact on patients, their families, and the healthcare system, including enormous societal burden. Obtaining a conclusive diagnosis for a patient with a rare genetic disease can be long and gruelling. For some patients it takes months or years to receive a definite diagnosis, and around 50% of the patients remain undiagnosed even with expert clinical and advanced high-end laboratory investigations. Owing to the large population and practice of consanguinity the Indian population is a pool of indigenous variants and unreported phenotypes or diseases. A mission program on pediatric rare diseases is an unparalleled initiative to study unique clinical conditions via the use of latest state-of-art technologies and with the combination of a mulit-omics approach. Our initiative will not only provide diagnosis to patients with rare disease but also build a platform for translational research for rare disease screening, management, and treatment.

Pediatric (PARDS) and neonatal (NARDS) acute respiratory distress syndrome have different age-specific characteristics and definitions. Trials on surfactant for ARDS in children and neonates have been performed well before the PARDS and NARDS definitions and yielded conflicting results. This is mainly due to heterogeneity in study design reflecting historic lack of pathobiology knowledge. We reviewed the available clinical and preclinical data to create an expert consensus aiming to inform future research steps and advance the knowledge in this area. Eight trials investigated the use of surfactant for ARDS in children and ten in neonates, respectively. There were improvements in oxygenation (7/8 trials in children, 7/10 in neonates) and mortality (3/8 trials in children, 1/10 in neonates) improved. Trials were heterogeneous for patients’ characteristics, surfactant type and administration strategy. Key pathobiological concepts were missed in study design. Consensus with strong agreement was reached on four statements: There are sufficient preclinical and clinical data to support targeted research on surfactant therapies for PARDS and NARDS. Studies should be performed according to the currently available definitions and considering recent pathobiology knowledge. PARDS and NARDS should be considered as syndromes and should be pre-clinically studied according to key characteristics, such as direct or indirect (primary or secondary) nature, clinical severity, infectious or non-infectious origin or patients’ age. Explanatory should be preferred over pragmatic design for future trials on PARDS and NARDS. Different clinical outcomes need to be chosen for PARDS and NARDS, according to the trial phase and design, trigger type, severity class and/or surfactant treatment policy . We advocate for further well-designed preclinical and clinical studies to investigate the use of surfactant for PARDS and NARDS following these principles.

Plant-specific transcription factor NAC proteins play essential roles in many biological processes such as development, senescence, morphogenesis, and stress signal transduction pathways. In the NAC family, some members function as transcription activators while others act as repressors. In the present study we found that though the full-length GmNAC20 from soybean did not have transcriptional activation activity, the carboxy-terminal activation domain of GmNAC20 had high transcriptional activation activity in the yeast assay system. Deletion experiments revealed an active repression domain with 35 amino acids, named NARD (NAC Repression Domain), in the d subdomain of NAC DNA-binding domain. NARD can reduce the transcriptional activation ability of diverse transcription factors when fused to either the amino-terminal or the carboxy-terminal of the transcription factors. NARD-like sequences are also present in other NAC family members and they are functional repression domain when fused to VP16 in plant protoplast assay system. Mutation analysis of conserved amino acid residues in NARD showed that the hydrophobic LVFY motif may partially contribute to the repression function. It is hypothesized that the interactions between the repression domain NARD and the carboxy-terminal activation domain may finally determine the ability of NAC family proteins to regulate downstream gene expressions.

This study aimed to evaluate whether high-frequency oscillatory ventilation (HFOV) could reduce mortality and the incidence of bronchopulmonary dysplasia (BPD) of perinatal-onset neonatal acute respiratory distress syndrome (NARDS) compared with conventional mechanical ventilation (CMV). Medical records were collected and retrospectively analyzed. Among the 700 neonates with NARDS who needed invasive ventilation, 501 (71.6%) received CMV, while 199 (28.4%) received HFOV. One-to-one propensity score matching (127:127) was used to match the baseline characteristics of patients who received CMV and HFOV. The results showed that birth weight and oxygenation index (OI) were independently associated with mortality in the multivariate logistic regression. No significant differences were observed in mortality or the incidence of BPD between the two groups. The incidence of intraventricular hemorrhage (IVH) and ventilation-free days were significantly lower in the HFOV group than in the CMV group (3.9 vs 11.80%, p=0.02; 15.226 vs 20.967 days, p=0.01). There were no significant differences between the two groups regarding other secondary outcomes.Conclusion: HFOV was associated with a decreased incidence of IVH in infants with NARDS compared with CMV. However, there were significantly more VFDs in the CMV group than in the HFOV group, and HFOV did not appear to be superior to CMV in decreasing the mortality and incidence of BPD in infants with NARDS.What is Known:• The diagnostic criteria of neonatal acute respiratory distress syndrome (Montreux criteria) were established in 2017.• To date, studies comparing high-frequency oscillatory ventilation and conventional mechanical ventilation in the treatment of neonatal acute respiratory distress syndrome are insufficient.What is New:• High-frequency oscillatory ventilation did not appear to be superior to conventional mechanical ventilation in decreasing the mortality and incidence of bronchopulmonary dysplasia in infants with moderate-to-severe perinatal-onset neonatal acute respiratory distress syndrome.• High-frequency oscillatory ventilation was associated with a decreased incidence of intraventricular hemorrhage in infants with moderate-to-severe perinatal-onset acute respiratory distress syndrome compared with conventional mechanical ventilation.

Neonatal Acute Respiratory Distress Syndrome (NARDS) is a severe respiratory crisis threatening neonatal life. We aim to identify changes in the lung-gut microbiota and lung-plasma tryptophan metabolites in NARDS neonates to provide a differentiated tool and aid in finding potential therapeutic targets. Lower respiratory secretions, faeces and plasma were collected from 50 neonates including 25 NARDS patients (10 patients with mild NARDS in the NARDS_M group and 15 patients with moderate-to-severe NARDS in the NARDS_S group) and 25 control patients screened based on gestational age, postnatal age and birth weight. Lower airway secretions and feces underwent 16S rRNA gene sequencing to understand the microbial communities in the lung and gut, while lower airway secretions and plasma underwent LC-MS analysis to understand tryptophan metabolites in the lung and blood. Correlation analyses were performed by comparing differences in microbiota and tryptophan metabolites between NARDS and control, NARDS_S and NARDS_M groups. Significant changes in lung and gut microbiota as well as lung and plasma tryptophan metabolites were observed in NARDS neonates compared to controls. and were increased in the lungs of NARDS neonates, whereas , and were reduced. in the lungs decreased in NARDS_S neonates. Indole-3-carboxaldehyde decreased in the lungs of NARDS neonates, whereas levels of 3-hydroxykynurenine, indoleacetic acid, indolelactic acid, 3-indole propionic acid, indoxyl sulfate, kynurenine, and tryptophan decreased in the lungs of the NARDS_S neonates. Altered microbiota was significantly related to tryptophan metabolites, with changes in lung microbiota and tryptophan metabolites having better differentiated ability for NARDS diagnosis and grading compared to gut and plasma. Significant changes occurred in the lung-gut microbiota and lung-plasma tryptophan metabolites of NARDS neonates. Alterations in lung microbiota and tryptophan metabolites were better discriminatory for the diagnosis and grading of NARDS.

This book provides readers with the skills they need to write computer codes that simulate convection, internal gravity waves, and magnetic field generation in the interiors and atmospheres of rotating planets and stars. Using a teaching method perfected in the classroom, Gary Glatzmaier begins by offering a step-by-step guide on how to design codes for simulating nonlinear time-dependent thermal convection in a two-dimensional box using Fourier expansions in the horizontal direction and finite differences in the vertical direction. He then describes how to implement more efficient and accurate numerical methods and more realistic geometries in two and three dimensions. In the third part of the book, Glatzmaier demonstrates how to incorporate more sophisticated physics, including the effects of magnetic field, density stratification, and rotation. Featuring numerous exercises throughout, this is an ideal textbook for students and an essential resource for researchers. Describes how to create codes that simulate the internal dynamics of planets and stars Builds on basic concepts and simple methods Shows how to improve the efficiency and accuracy of the numerical methods Describes more relevant geometries and boundary conditions Demonstrates how to incorporate more sophisticated physics

Lichtman critiques the argument of Mike Meurer and Craig Nard by arguing that both were wrong to think that the doctrine of equivalents is a redundant mechanism, and they are therefore wrong to conclude that the normative justification for the doctrine must come from its institutional implications rather than its effect in patent scope. On his part he concludes three virtues of the doctrine of equivalents: it can expand patent scope to cover variations on an invention, lowers the costs of claim drafting, and brings additional information to the question of patent scope.

In 1718, Jean-Baptiste Benard, Sieur de la Harpe, departed St. Malo in Brittany for the New World. La Harpe, a member of the French bourgeoisie, arrived at Dauphin Island on the Gulf coast to take up the entrepreneurial concession provided by the director of the French colony, Jean Baptiste Lemoyne de Bienville, La Harpe's charge was to open a trading post on the Red River just above a Caddoan village not far from present-day Texarkana. Following the establishment of this post, La Harpe ventured farther north to extend his trade market into the region occupied by the Wichita Indians. Here he encountered a Tawakoni village with an estimated 6,000 inhabitants, a number that swelled to 7,000 during the ten-day visit. Despite years of ethnohistoric and archaeological research, no scholar had successfully established where this important meeting took place. Then in 1988, George Odell and his crew surveyed and excavated an area 13 miles south of Tulsa, along the Arkansas River, that revealed undeniable association of Native American habitation refuse with 18th-century European trade goods. Odell here presents a full account of the presumed location of the Tawakoni village as revealed through the analysis of excavated materials from nine specialist collaborators. In a strikingly well written narrative report, employing careful study and innovative analysis supported by appendixes containing the excavation data, Odell combines documentary history and archaeological evidence to pinpoint the probable site of the first European contact with North American Plains Indians.

  \"Basically, ([Cummings] coach Chas Criss) just told us we had to step it up,\" Cavaliers guard Nard Currie said. \"If we swing the ball around better, make some shots, we'd be up and the game would be over.\" \"I kept saying, 'Trust, run the ball, move the ball.' And eventually we kept swinging it and swinging it and we started making shots,\" Criss said. \"It's amazing how that works. You move the ball, somebody makes a jump shot.\" \"Basically, Coach always tells me to keep shooting because he knows I'm a good shooter,\" Currie said. \"But this season, it hasn't really been the best shooting season for me. So he told me to keep shooting and eventually I'll find my shot.\"