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Cardiopulmonary bypass and previous thoracic interventions were not risk factors in patients with pleural effusions who were treated with thoracentesis only, and forced expiratory volume in 1 second improved after drainage; however, repeat percutaneous or surgical interventions did not impart a similar benefit. Pleural complications were associated with worse survival.

Pleural complications are common after lung transplantation and are associated with worse allograft function and survival. These complications are likely secondary to other underlying clinical problems. Malnourishment and size mismatch are modifiable risk factors.
Pleural complications are common after lung transplantation and are associated with worse allograft function and survival. These complications are likely secondary to other underlying clinical problems. Malnourishment and size mismatch are modifiable risk factors.
Clinical staging of lung cancer may not reliably predict nodal disease, and its accuracy in The Society of Thoracic Surgeons General Thoracic Surgery Database is not described.

Among anatomic pulmonary resections for stages I to III lung cancer with complete clinical and pathologic staging (2012-2017), the accuracy of invasive mediastinal staging (IMS) was compared with noninvasive mediastinal staging only. Accuracy, defined as concordance between clinical and pathologic nodal status, was examined using logistic regression to determine factors associated with clinical nodal (cN) accuracy. Variation in accuracy across centers was recorded and categorized.

We included 39,516 patients with stages I to III pulmonary cancer (adenocarcinoma, 66%; squamous, 23%; neuroendocrine, 5%; mixed, 3.3%; other, 2.4%), of whom 90.4% had cN0 disease. IMS was performed in 32.4%. The IMS group had more central tumors (14.8% vs 6.0%, P < .001) and cN1-2 (15.7% vs 6.8%, P < .001). Nodal accuracy was 79.8%. Although read more had a lower nodal accuracy for cN0-2 disease (74.6% vs 82.6%, P<.001), IMS had higher accuracy when comparing patients with cN1-2 disease (53.9% vs 46.9%, P < .001). In multivariable analysis central tumors (odds ratio, 0.47; 95% confidence interval, 0.43-0.51) and >cN0 disease (odds ratio, 0.25; 95% confidence interval, 0.22-0.29) were associated with lower accuracy. Accuracy of IMS in the top 20 centers was 94.4% and in the bottom 20, 70.9%.

Staging accuracy in lung cancers selected for initial resection declines with >cN0 and central tumors. Noninvasive staging in tumors without cN involvement misses nearly 20% of cN1-2. Center-specific accuracy is a target for quality improvement.
cN0 and central tumors. Noninvasive staging in tumors without cN involvement misses nearly 20% of cN1-2. Center-specific accuracy is a target for quality improvement.Although much is known about the biochemical regulation of glycolytic enzymes, less is understood about how they are organized inside cells. We systematically examine the dynamic subcellular localization of glycolytic protein phosphofructokinase-1/PFK-1.1 in Caenorhabditis elegans. We determine that endogenous PFK-1.1 localizes to subcellular compartments in vivo. In neurons, PFK-1.1 forms phase-separated condensates near synapses in response to energy stress from transient hypoxia. Restoring animals to normoxic conditions results in cytosolic dispersion of PFK-1.1. PFK-1.1 condensates exhibit liquid-like properties, including spheroid shapes due to surface tension, fluidity due to deformations, and fast internal molecular rearrangements. Heterologous self-association domain cryptochrome 2 promotes formation of PFK-1.1 condensates and recruitment of aldolase/ALDO-1. PFK-1.1 condensates do not correspond to stress granules and might represent novel metabolic subcompartments. Our studies indicate that glycolytic protein PFK-1.1 can dynamically form condensates in vivo.Mechanosensation of cells is an important prerequisite for cellular function, e.g., in the context of cell migration, tissue organization, and morphogenesis. An important mechanochemical transducer is the actin cytoskeleton. In fact, previous studies have shown that actin cross-linkers such as α-actinin-4 exhibit mechanosensitive properties in their binding dynamics to actin polymers. However, to date, a quantitative analysis of tension-dependent binding dynamics in live cells is lacking. Here, we present a, to our knowledge, new technique that allows us to quantitatively characterize the dependence of cross-linking lifetime of actin cross-linkers on mechanical tension in the actin cortex of live cells. We use an approach that combines parallel plate confinement of round cells, fluorescence recovery after photobleaching, and a mathematical mean-field model of cross-linker binding. We apply our approach to the actin cross-linker α-actinin-4 and show that the cross-linking time of α-actinin-4 homodimers increases approximately twofold within the cellular range of cortical mechanical tension, rendering α-actinin-4 a catch bond in physiological tension ranges.As a reaction-diffusion system strongly affected by temperature, early fly embryos surprisingly show highly reproducible and accurate developmental patterns during embryogenesis under temperature perturbations. To reveal the underlying temperature compensation mechanism, it is important to overcome the challenge in quantitative imaging on fly embryos under temperature perturbations. #link# Inspired by microfluidics generating temperature steps on fly embryos, here we design a microfluidic device capable of ensuring the normal development of multiple fly embryos as well as achieving real-time temperature control and fast temperature switches for quantitative live imaging with a home-built two-photon microscope. We apply this system to quantify the temperature compensation of the morphogen Bicoid (Bcd) gradient in fly embryos. The length constant of the exponential Bcd gradient reaches the maximum at 25°C within the measured temperatures of 18-29°C and gradually adapts to the corresponding value at new temperatures upon a fast temperature switch. The relaxation time of such an adaptation becomes longer if the temperature is switched in a later developmental stage. This age-dependent temperature compensation could be explained if the traditional synthesis-diffusion-degradation model is extended to incorporate the dynamic change of the parameters controlling the formation of Bcd gradients.
The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. link2 However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone.

MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (11) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managedl Institute for Health Research Health Technology Assessment Programme.
Patients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK.

We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case-fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models.

319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92ised risk tables for patients with cancer, considering age, sex, and tumour subtype. Our results could be useful to assist physicians in informed risk-benefit discussions to explain COVID-19 risk and enable an evidenced-based approach to national social isolation policies.

University of Birmingham and University of Oxford.
University of Birmingham and University of Oxford.Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. We enrolled healthy newborns and children with metabolic diseases or hearing loss (106 participants total). ES confirmed the participant's underlying diagnosis in 15 out of 17 (88%) children with metabolic disorders and in 5 out of 28 (∼18%) children with hearing loss. We discovered actionable findings in four participants that would not have been detected by standard NBS. A subset of parents was eligible to receive additional information for their child about childhood-onset conditions with low or no clinical actionability, clinically actionable adult-onset conditions, and carrier status for autosomal-recessive conditions. We found pathogenic variants associated with hereditary breast and/or ovarian cancer in two children, a likely pathogenic variant in the gene associated with Lowe syndrome in one child, and an average of 1.8 reportable variants per child for carrier results. These results highlight the benefits and limitations of using genomic sequencing for NBS and the challenges of using such technology in future precision medicine approaches.More than 100 genetic etiologies have been identified in developmental and epileptic encephalopathies (DEEs), but correlating genetic findings with clinical features at scale has remained a hurdle because of a lack of frameworks for analyzing heterogenous clinical data. Here, we analyzed 31,742 Human Phenotype Ontology (HPO) terms in 846 individuals with existing whole-exome trio data and assessed associated clinical features and phenotypic relatedness by using HPO-based semantic similarity analysis for individuals with de novo variants in the same gene. link3 Gene-specific phenotypic signatures included associations of SCN1A with "complex febrile seizures" (HP 0011172; p = 2.1 × 10-5) and "focal clonic seizures" (HP 0002266; p = 8.9 × 10-6), STXBP1 with "absent speech" (HP 0001344; p = 1.3 × 10-11), and SLC6A1 with "EEG with generalized slow activity" (HP 0010845; p = 0.018). Of 41 genes with de novo variants in two or more individuals, 11 genes showed significant phenotypic similarity, including SCN1A (n = 16, p less then 0.
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