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98). Adjuvant chemotherapy was given in 15% of patients in the VL and 11% in the VS group. During follow-up (median 23 months), no patients presented with local nodal recurrence or on the stapler line (VS group). Three patients on VL and two in VS groups presented with recurrence on the remnant operated lung. New primary pulmonary tumors were diagnosed in 3.3% and 6.3% of patients in the VL and VS groups, respectively.

Despite the short follow-up, our preliminary data shows that local control is comparable for VATS lobectomy and VATS segmentectomy for patients with NSCLC <2 cm.
Despite the short follow-up, our preliminary data shows that local control is comparable for VATS lobectomy and VATS segmentectomy for patients with NSCLC less then 2 cm.
To characterize the clinical presentation of sleep-disordered breathing and respiratory patterns at rest and during a 6-min walk test (6MWT) in children with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome.

Retrospective study of children with ROHHAD who had a diagnostic baseline polysomnography, daytime cardiorespiratory monitoring at rest and a 6MWT. Polysomnography data were also compared with body mass index-, age-, and sex-matched controls.

Of the eight children with ROHHAD, all eight (100%) had obstructive sleep apnea (OSA) and 2/8 (25%) had nocturnal hypoventilation (NH) on their baseline polysomnography. Comparing the ROHHAD group to the control group, there were no significant differences in the median (interquartile range [IQR]) obstructive apnea-hypopnea index (11.1 [4.3-58.4] vs. 14.4 [10.3-23.3] events/h, respectively; p = .78). However, children with ROHHAD showed a significantly higher desaturation index compared to the controlt NH, and oxygen desaturations with central pauses at rest during wakefulness. Interestingly, during daily activities that require submaximal effort, children may not experience oxygen desaturations. Early recognition of respiratory abnormalities and targeted therapeutic interventions are important to limit associated morbidity and mortality in ROHHAD.
To assess the diagnostic utility of metagenomic sequencing in pediatric aerodigestive clinic patients being evaluated for chronic aspiration. We hypothesize that using a metagenomics platform will aid in the identification of microbes not found on standard culture.

Twenty-four children referred to an aerodigestive clinic were enrolled in a prospective, single-site, cross-sectional cohort study. CID44216842 in vitro At the time of clinical evaluation under anesthesia, two samples were obtained an upper airway sample and a sample from bronchoalveolar lavage (BAL). Samples were sent for routine culture and analyzed using Explify® Respiratory, a CLIA Laboratory Developed Test which identifies respiratory commensals and pathogens through RNA and DNA sequencing. Since RNA was sequenced in the course of the metagenomic analysis to identify organisms (RNA viruses and bacteria), the sequencing approach also captured host derived messenger RNA during sample analysis. This incidentally obtained host transcriptomic data were analyzed to ted chronic aspiration.
Neurogranin (NRGN) is a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. Recent studies suggest that NRGN is involved in neuropsychiatric disorders, including schizophrenia, ADHD, and Alzheimer's disease. Previous behavioral studies of Nrgn knockout (Nrgn KO) mice identified hyperactivity, deficits in spatial learning, impaired sociability, and decreased prepulse inhibition, which suggest that these mice recapitulate some symptoms of neuropsychiatric disorders. To further validate Nrgn KO mice as a model of neuropsychiatric disorders, we assessed multiple domains of behavioral phenotypes in Nrgn KO mice using a comprehensive behavioral test battery including tests of homecage locomotor activity and nesting behavior.

Adult Nrgn KO mice (28-54weeks old) were subjected to a battery of comprehensive behavioral tests, which examined general health, nesting behavior, neurological characteristics, motor function, pain sensitivity, locomotor activity, anxiety-like behavior, s were reproduced in the present study. Collectively, the behavioral phenotypes of Nrgn KO mice detected in the present study indicate that Nrgn KO mice are a valuable animal model that recapitulates a variety of symptoms of neuropsychiatric disorders, such as schizophrenia, ADHD, and Alzheimer's disease.
There is limited data on management strategies for chronic pulmonary hypertension (cPH) in chronic lung disease (CLD) of prematurity. Our objective was to evaluate clinical outcomes following a standardized policy, wherein only cPH with right-ventricular (RV) dilatation was treated and diuretics were employed as first-line therapy; cPH without RV-dilatation was managed expectantly.

In this retrospective cohort study, all infants with CLD were categorized as "CLD-only" or "CLD-cPH," using echocardiography at ≥36 weeks postmenstrual age. Intergroup comparison was performed. Regression analysis examined the association between cPH and primary outcome of death or disability at 18-24 months.

Of 128 CLD infants, 48 (38%) had cPH, of which 29 (60%) received diuretics. Symptomatic improvement within 1-week was recorded in 90%. Although CLD-cPH had worse in-hospital respiratory course than CLD-only, all post-discharge respiratory and neurodevelopmental outcomes were similar. cPH was not associated with death or disability (adjusted odds ratio, 1.02; 95% confidence interval, 0.32-3.27). Disease progression treated with sildenafil occurred in 2 (4%) cases. There was no death from respiratory or RV failure.

Primary treatment of CLD-cPH with diuretics using RV-dilatation as therapeutic threshold, may result in symptomatic improvement, disease stabilization and post-discharge outcomes comparable to infants without cPH.
Primary treatment of CLD-cPH with diuretics using RV-dilatation as therapeutic threshold, may result in symptomatic improvement, disease stabilization and post-discharge outcomes comparable to infants without cPH.
Mutation analysis of circulating tumor DNA (ctDNA) is used for diagnosing lung cancer. This trial aimed to assess the efficacy of afatinib in treatment-naïve patients with lung cancer harboring epidermal growth factor receptor mutations (EGFRm, exon 19 deletions or exon 21 point mutations) detected based on ctDNA.

The primary objective was the objective response rate (ORR) in the response evaluable (RE) population. EGFRm analysis of ctDNA was performed using PANA Mutype. Of the 331 patients screened, ctDNA was positive in 21% (68/331) in the detection of activating EGFRm. Among 81 subjects with tumor EGFRm, 48 showed matched EGFRm in their ctDNA (59% sensitivity).

Therapy with afatinib 40 mg was initiated in 21 (female, 17; adenocarcinoma, 20) patients (intention-to-treat, ITT); dose modifications were made in 15 (71%). The ORR was 74% in the RE population (14/19); 11 patients showed EGFRm only in ctDNA (Group A), whereas 10 exhibited the same EGFRm in their ctDNA and tumor DNA (Group B). There was no s in a real-world setting.
Our findings emphasize that the survival benefit of afatinib treatment can be achieved not only by appropriate dose reduction with frequent and detailed monitoring of toxicities, but also by using noninvasive (ctDNA) assays in a real-world setting.Molecular cages have attracted great attention because of their fascinating topological structures and well-defined functional cavities. These discrete cages were usually fabricated by coordination assembly approach, a process employing directional metal-ligand coordination bonds due to the nature of the divinable coordination geometry and the required lability to encode dynamic equilibrium/error-correction. Compared to these coordination molecular cages with mononulcear metal-nodes, an increasing number of molecular cages featuring dinuclear and then polynuclear metal-cluster nodes have been synthesized. These metal-cluster-based coordination cages (MCCCs) combine the merits of both metal clusters and the cage structure, and exhibit excellent performances in catalysis, separation, host-guest chemistry and so on. In this review, we highlight the syntheses of MCCCs and their potential functions that is donated by the metal-cluster nodes.
Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer's disease (AD), have been reported, but causal relationships are difficult to determine in human studies.

We used structural magnetic resonance imaging in a well-validated non-human primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean vs Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and 20 individual regions of interest (ROIs).

Western diet resulted in greater cortical thicknesses, total brain volumes, and gray matter, and diminished cerebrospinal fluid and white matter volumes. Socially stressed subordinates had smaller whole brain volumes but larger ROIs relevant to AD than dominants.

The observation of increased size of AD-related brain areas is consistent with similar reports of mid-life volume increases predicting increased AD risk later in life. While the biological mechanisms underlying the findings require future investigation, these observations suggest that Western diet and psychosocial stress instigate pathologic changes that increase risk of AD-associated neuropathology, whereas the Mediterranean diet may protect the brain.
The observation of increased size of AD-related brain areas is consistent with similar reports of mid-life volume increases predicting increased AD risk later in life. While the biological mechanisms underlying the findings require future investigation, these observations suggest that Western diet and psychosocial stress instigate pathologic changes that increase risk of AD-associated neuropathology, whereas the Mediterranean diet may protect the brain.Salinomycin, an FDA-approved polyketide drug, was recently identified as a promising anti-tumour and anti-viral lead compound. It is produced by Streptomyces albus, and the biosynthetic gene cluster (sal) spans over 100 kb. The genetic manipulation of large polyketide gene clusters is challenging, and approaches delivering reliable efficiency and accuracy are desired. Herein, a delicate strategy to enhance salinomycin production was devised and evaluated. We reconstructed a minimized sal gene cluster (mini-cluster) on pSET152 including key genes responsible for tailoring modification, antibiotic resistance, positive regulation and precursor supply. These genes were overexpressed under the control of constitutive promoter PkasO* or Pneo . The pks operon was not included in the mini-cluster, but it was upregulated by SalJ activation. After the plasmid pSET152mini-cluster was introduced into the wild-type strain and a chassis host strain obtained by ribosome engineering, salinomycin production was increased to 2.3-fold and 5.1-fold compared with that of the wild-type strain respectively. Intriguingly, mini-cluster introduction resulted in much higher production than overexpression of the whole sal gene cluster. The findings demonstrated that reconstitution of sal mini-cluster combined with ribosome engineering is an efficient novel approach and may be extended to other large polyketide biosynthesis.
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