Natural history of pathologically confirmed pulmonary subsolid nodules with deep learning-assisted nodule segmentation.

OBJECTIVE: To explore the natural history of pulmonary subsolid nodules (SSNs) with different pathological types by deep learning-assisted nodule segmentation. METHODS: Between June 2012 and June 2019, 95 resected SSNs with preoperative long-term follow-up were enrolled in this retrospective study. SSN detection and segmentation were performed on preoperative follow-up CTs using the deep learning-based Dr. Wise system. SSNs were categorized into invasive adenocarcinoma (IAC, n = 47) and non-IAC (n = 48) groups; according to the interval change during the preoperative follow-up, SSNs were divided into growth (n = 68), nongrowth (n = 22), and new emergence (n = 5) groups. We analyzed the cumulative percentages and pattern of SSN growth and identified significant factors for IAC diagnosis and SSN growth. RESULTS: The mean preoperative follow-up was 42.1 ± 17.0 months. More SSNs showed growth or new emergence in the IAC than in the non-IAC group (89.4% vs. 64.6%, p = 0.009). Volume doubling time was non-significantly shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days, p = 0.077). Median mass doubling time was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). Lobulated sign (p = 0.002) and SSN mass (p = 0.004) were significant factors for differentiating IACs. IACs showed significantly higher cumulative growth percentages than non-IACs in the first 70 months of follow-up. The growth pattern of SSNs may conform to the exponential model. The initial volume (p = 0.042) was a predictor for SSN growth. CONCLUSIONS: IACs appearing as SSNs showed an indolent course. The mean growth rate was larger for IACs than for non-IACs. SSNs with larger initial volume are more likely to grow. KEY POINTS: • Invasive adenocarcinomas (IACs) appearing as subsolid nodules (SSNs), with a mean volume doubling time (VDT) of 1436.0 ± 1188.2 days and median mass doubling time (MDT) of 821.7 days, showed an indolent course. • The VDT was shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days), but the difference was not significant (p = 0.077). The median MDT was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). • SSNs with lobulated sign and larger mass (> 390.5 mg) may very likely be IACs. SSNs with larger initial volume are more likely to grow.

Application of the microRNA-302/367 cluster in cancer therapy.

As a novel class of noncoding RNAs, microRNAs (miRNAs) can effectively silence their target genes at the posttranscriptional level. Various biological processes, such as cell proliferation, differentiation, and motility, are regulated by miRNAs. In different diseases and different stages of disease, miRNAs have various expression patterns, which makes them candidate prognostic markers and therapeutic targets. Abnormal miRNA expression has been detected in numerous neoplastic diseases in humans, which indicates the potential role of miRNAs in tumorigenesis. Previous studies have indicated that miRNAs are involved in nearly the entire process of tumor development. MicroRNA-302a, miR-302b, miR-302c, miR-302d, and miR-367 are members of the miR-302/367 cluster that plays various biological roles in diverse neoplastic diseases by targeting different genes. These miRNAs have been implicated in several unique characteristics of cancer, including the evasion of growth suppressors, the sustained activation of proliferative signaling, the evasion of cell death and senescence, and the regulation of angiogenesis, invasion, and metastasis. This review provides a critical overview of miR-302/367 cluster dysregulation and the subsequent effects in cancer and highlights the vast potential of members of this cluster as therapeutic targets and novel biomarkers.

Long-term follow-up of persistent pulmonary pure ground-glass nodules with deep learning-assisted nodule segmentation.

OBJECTIVE: To investigate the natural history of persistent pulmonary pure ground-glass nodules (pGGNs) with deep learning-assisted nodule segmentation. METHODS: Between January 2007 and October 2018, 110 pGGNs from 110 patients with 573 follow-up CT scans were included in this retrospective study. pGGN automatic segmentation was performed on initial and all follow-up CT scans using the Dr. Wise system based on convolution neural networks. Subsequently, pGGN diameter, density, volume, mass, volume doubling time (VDT), and mass doubling time (MDT) were calculated automatically. Enrolled pGGNs were categorized into growth, 52 (47.3%), and non-growth, 58 (52.7%), groups according to volume growth. Kaplan-Meier analyses with the log-rank test and Cox proportional hazards regression analysis were conducted to analyze the cumulative percentages of pGGN growth and identify risk factors for growth. RESULTS: The mean follow-up period of the enrolled pGGNs was 48.7 ± 23.8 months. The median VDT of the 52 pGGNs having grown was 1448 (range, 339-8640) days, and their median MDT was 1332 (range, 290-38,912) days. The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p < 0.001). The growth pattern of pGGNs may conform to the exponential model. Lobulated sign (p = 0.044), initial mean diameter (p < 0.001), volume (p = 0.003), and mass (p = 0.023) predicted pGGN growth. CONCLUSIONS: Persistent pGGNs showed an indolent course. Deep learning can assist in accurately elucidating the natural history of pGGNs. pGGNs with lobulated sign and larger initial diameter, volume, and mass are more likely to grow. KEY POINTS: • The pure ground-glass nodule (pGGN) segmentation accuracy of the Dr. Wise system based on convolution neural networks (CNNs) was 96.5% (573/594). • The median volume doubling time (VDT) of 52 pure ground-glass nodules (pGGNs) having grown was 1448 days (range, 339-8640 days), and their median mass doubling time (MDT) was 1332 days (range, 290-38,912 days). The mean time to growth in volume was 854 ± 675 days (range, 116-2856 days). • The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p values < 0.001). The growth pattern of pure ground-glass nodules may conform to exponential model.

In vitro evaluation of decontamination effects on mechanical properties of fibrin membrane.

Background: Tissue engineering has been investigated as a potential method for healing traumatized tissues. Biomaterials are material devices or implants used to repair or replace native body tissues and organs. The present study was conducted to evaluate the effects of decontamination methods on biological/mechanical properties and degradation/adhesion test of the platelet-rich fibrin (PRF) membranes to compare these properties with intact membranes as a biological biomaterial. Methods: The in vitro degradation tests were conducted by placing the equal sizes of (i) intact PRF membrane, (ii) PRF membrane sterilized by autoclave (iii), ultraviolet (UV), and (iiii) gamma irradiation in phosphate buffer solution on a shaker. The degradation profiles were expressed. Adhesion test was performed by counting adhered mouse fibroblast and sterilized fibrin membrane was compared to normal fibrin membrane by different sterilization methods. Results: The preliminary findings of sterilized PRF membranes showed that UV exposure (p<0.05) and autoclaved fibrin membranes (p<0.01) have significantly lower degradability compared to normal fibrin membranes. Gamma irradiation is similar to normal membrane in degradability. Cell adherence in all groups of fibrin membrane was significantly lower than the group without membrane, but there was no significant difference between intact and sterilized groups of fibrin membranes. Conclusion: Sterilization of fibrin membrane with different protocols does not have any adverse effects on cell adhesion; however, cell adherence is naturally very weak even in normal membranes. Also, it seems that ultraviolet ray polymerizes fibrin filaments and merges them to each other and increases the ability of fibrin membrane against degradation. Autoclaved fibrin membrane content proteins are denatured because of pressure and heat and show an increase in hardness and stability against degradation.

Ventricular Fibrillation Is a Sign of Life.

Ventricular fibrillation (VF) is a deadly rhythm problem. With asystole, it represents one of the most extreme emergencies that may engage vital prognosis within only few minutes if appropriated treatment is not instituted. It is learned in all medical schools worldwide that VF is not compatible with consciousness and sustained life. Moreover, at 37°C, and without restauration of cardiac flow, VF may be responsible for severe and most often irreversible brain damage after 3 minutes.

The Development of Plant Genome Sequencing Technology and Its Conservation and Application in Endangered Gymnosperms.

Genome sequencing is widely recognized as a fundamental pillar in genetic research and legal studies of biological phenomena, providing essential insights for genetic investigations and legal analyses of biological events. The field of genome sequencing has experienced significant progress due to rapid improvements in scientific and technological developments. These advancements encompass not only significant improvements in the speed and quality of sequencing but also provide an unparalleled opportunity to explore the subtle complexities of genomes, particularly in the context of rare species. Such a wide range of possibilities has successfully supported the validation of plant gene functions and the refinement of precision breeding methodologies. This expanded scope now includes a comprehensive exploration of the current state and conservation efforts of gymnosperm gene sequencing, offering invaluable insights into their genomic landscapes. This comprehensive review elucidates the trajectory of development and the diverse applications of genome sequencing. It encompasses various domains, including crop breeding, responses to abiotic stress, species evolutionary dynamics, biodiversity, and the unique challenges faced in the conservation and utilization of gymnosperms. It highlights both ongoing challenges and the unveiling of forthcoming developmental trajectories.

Electric-driven membrane poration: A rationale for water role in the kinetics of pore formation.

Electroporation is a well-established technique used to stimulate cells, enhancing membrane permeability by inducing reversible membrane pores. In the absence of experimental observation of the dynamics of pore creation, molecular dynamics studies provide the molecular-level evidence that the electric field promotes pore formation. Although single steps in the pore formation process are well assessed, a kinetic model representing the mathematical description of the electroporation process, is lacking. In the present work we studied the basis of the pore formation process, providing a rationale for the definition of a first-order kinetic scheme. Here, authors propose a three-state kinetic model for the process based on the assessed mechanism of water defects intruding at the water/lipid interface, when applying electric field intensities at the edge of the linear regime. The methodology proposed is based on the use of two robust biophysical quantities analyzed for the water molecules intruding at the water/lipid interface: (i) number of hydrogen bonds; (ii) number of contacts. The final model, sustained by a robust statistical sampling, provides kinetic constants for the transitions from the intact bilayer state to the hydrophobic pore state.

Clinicopathological features of small T1 colorectal cancers.

BACKGROUND: Although small colorectal neoplasms (< 10 mm) are often easily resected endoscopically and are considered to have less malignant potential compared with large neoplasms (≥ 10 mm), some are invasive to the submucosa. AIM: To clarify the clinicopathological features of small T1 colorectal cancers. METHODS: Of 32025 colorectal lesions between April 2001 and March 2018, a total of 1152 T1 colorectal cancers resected endoscopically or surgically were included in this study and were divided into two groups by tumor size: a small group (< 10 mm) and a large group (≥ 10 mm). We compared clinicopathological factors including lymph node metastasis (LNM) between the two groups. RESULTS: The incidence of small T1 cancers was 10.1% (116/1152). The percentage of initial endoscopic treatment in small group was significantly higher than in large group (< 10 mm 74.1% vs ≥ 10 mm 60.2%, P < 0.01). In the surgical resection cohort (n = 798), the rate of LNM did not significantly differ between the two groups (small 12.3% vs large 10.9%, P = 0.70). In addition, there were also no significant differences between the two groups in pathological factors such as histological grade, vascular invasion, or lymphatic invasion. CONCLUSION: Because there was no significant difference in the rate of LNM between small and large T1 colorectal cancers, the requirement for additional surgical resection should be determined according to pathological findings, regardless of tumor size.

CircRNA May Not Be "Circular".

Circular RNA (circRNA) is a novel regulatory non-coding RNA and participates in diverse physiological and pathological processes. However, the structures and molecular mechanisms of circRNAs remain unclear. In this study, taking advantage of openly databases and bioinformatics analysis, we observed lots of internal complementary base-pairing sequences (ICBPS) existed in plenty of circRNAs, especially in extremely long circRNAs (el-circRNAs, > 5,000 nt). The result indicated that circRNA may not be a simple circular structure. In addition, we put forward the hypothesis of "open-close effect" in the transition for specific circRNA from normal state to morbid state. Taken together, our results not only expand the knowledge of circRNAs, but also highlight the potential molecular mechanism of circRNAs.

Is thyroid core needle biopsy a valid compliment to fine-needle aspiration?

Fine-needle aspiration (FNA) has long been considered the first and an important diagnostic tool in the evaluation of thyroid nodules. The advantages of FNA include simplicity, safety, cost-effectiveness, high diagnostic accuracy, and low complication rate. Nevertheless, limitations associated with FNA include a substantial rate of inconclusive results and indeterminate interpretations. Therefore, core needle biopsy (CNB) of the thyroid gland has been proposed as a complementary or even alternate diagnostic method to evaluate thyroid nodules. Although controversial, a growing number of researchers have reported CNB to be an effective and safe sampling method for thyroid nodules, especially for cases with inadequate or indeterminate FNA yields. Skeptics highlight local pain and bleeding risk. Supporters highlight the potential likelihood of overcoming FNA limitations by obtaining a larger amount of tissue and using architecture and cellular details to guide possible ancillary testing. This review evaluates the indications, advantages, and disadvantages of CNB as compared with FNA of the thyroid gland.

Human ex vivo and in vitro disease models to study food allergy.

Food allergy is a growing global public health concern. As treatment strategies are currently limited to allergen avoidance and emergency interventions, there is an increasing demand for appropriate models of food allergy for the development of new therapeutics. Many models of food allergy rely heavily on the use of animals, and while useful, many are unable to accurately reflect the human system. In order to bridge the gap between in vivo animal models and clinical trials with human patients, human models of food allergy are of great importance. This review will summarize the commonly used human ex vivo and in vitro models of food allergy and highlight their advantages and limitations regarding how accurately they represent the human in vivo system. We will cover biopsy-based systems, precision cut organ slices, and coculture systems as well as organoids and organ-on-a-chip. The availability of appropriate experimental models will allow us to move forward in the field of food allergy research, to search for effective treatment options and to further explore the cause and progression of this disorder.

Biological Processes and Biomarkers Related to Frailty in Older Adults: A State-of-the-Science Literature Review.

The objectives of this literature review were to (1) synthesize biological processes linked to frailty and their corresponding biomarkers and (2) identify potential associations among these processes and biomarkers. In September 2016, PubMed, Cumulative Index to Nursing and Allied Health, Cochrane Library, and Embase were searched. Studies examining biological processes related to frailty in older adults (≥60 years) were included. Studies were excluded if they did not employ specific measures of frailty, did not report the association between biomarkers and frailty, or focused on nonelderly samples (average age < 60). Review articles, commentaries, editorials, and non-English articles were also excluded. Fifty-two articles were reviewed, reporting six biological processes related to frailty and multiple associated biomarkers. The processes (biomarkers) include brain changes (neurotrophic factor, gray matter volume), endocrine dysregulation (growth hormones [insulin-like growth factor-1 and binding proteins], hormones related to glucose and insulin, the vitamin D axis, thyroid function, reproductive axis, and hypothalamic-pituitary-adrenal axis), enhanced inflammation (C-reactive protein, interleukin-6), immune dysfunction (neutrophils, monocytes, neopterin, CD8+CD28-T cells, albumin), metabolic imbalance (micronutrients, metabolites, enzyme-activity indices, metabolic end products), and oxidative stress (antioxidants, telomere length, glutathione/oxidized glutathione ratio). Bidirectional interrelationships exist within and between these processes. Biomarkers were associated with frailty in varied strengths, and the causality remains unclear. In conclusion, frailty is related to multisystem physiological changes. Future research should examine the dynamic interactions among these processes to inform causality of frailty. Given the multifactorial nature of frailty, a composite index of multisystem biomarkers would likely be more informative than single biomarkers in early detection of frailty.

Presymptomatic Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND AND OBJECTIVES: Intracranial aneurysm rupture is the most devastating complication of autosomal dominant polycystic kidney disease. Whether selective or widespread intracranial aneurysm screening is indicated remains controversial. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Records of 3010 patients with autosomal dominant polycystic kidney disease evaluated at the Mayo Clinic between 1989 and 2017 were reviewed. Those who had presymptomatic magnetic resonance angiography screening were included. RESULTS: Ninety-four intracranial aneurysms were diagnosed in 75 of 812 (9%) patients who underwent magnetic resonance angiography screening. Sex, age, race, and genotype were similar in the groups with and without aneurysms; hypertension and history of smoking were more frequent in the aneurysm group. Twenty-nine percent of patients with aneurysms compared with 11% of those without aneurysms had a family history of subarachnoid hemorrhage (P<0.001). Most aneurysms were small (median diameter =4 mm; range, 2-12 mm); 85% were in the anterior circulation. During a total imaging follow-up of 469 patient-years, de novo intracranial aneurysms were detected in five patients; eight intracranial aneurysms grew (median =2 mm; range, 1-3 mm). During a total clinical follow-up of 668 patient-years, seven patients had preemptive clipping or coil embolization; no intracranial aneurysms ruptured. During a total clinical follow-up of 4783 patient-years in 737 patients with no intracranial aneurysm detected on the first magnetic resonance angiography screening, two patients had an intracranial aneurysm rupture (0.04 per 100 person-years; 95% confidence interval, 0 to 0.10). The rate of intracranial aneurysm rupture in large clinical trials of autosomal dominant polycystic kidney disease was 0.04 per 100 patient-years (95% confidence interval, 0.01 to 0.06). CONCLUSIONS: Intracranial aneurysms were detected by presymptomatic screening in 9% of patients with autosomal dominant polycystic kidney disease, more frequently in those with familial history of subarachnoid hemorrhage, hypertension, or smoking. None of the patients with and two of the patients without aneurysm detection on screening suffered aneurysmal ruptures. The overall rupture rate in our autosomal dominant polycystic kidney disease cohort was approximately five times higher than that in the general population.

Ventricular Fibrillation Is a Sign of Life

ABSTRACT Ventricular fibrillation (VF) is a deadly rhythm problem. With asystole, it represents one of the most extreme emergencies that may engage vital prognosis within only few minutes if appropriated treatment is not instituted. It is learned in all medical schools worldwide that VF is not compatible with consciousness and sustained life. Moreover, at 37°C, and without restauration of cardiac flow, VF may be responsible for severe and most often irreversible brain damage after 3 minutes.

Genética y genómica de la longevidad y el envejecimiento / Genetics and genomics of longevity and aging

El envejecimiento y la longevidad son procesos que involucran una serie de factores genéticos, bioquímicos y ambientales. En esta revisión se tratan algunas cuestiones sobre estos dos procesos biológicos y epigenéticos. Se presentan los genes más importantes en estos procesos, así como se ejemplifican enfermedades que presentan un aceleramiento o falla en la longevidad y el envejecimiento. Se usa el análisis inteligente de datos para hallar interacciones de proteínas/genes que expliquen estos dos fenómenos biológicos.

Aging and longevity are processes that involve a series of genetic, biochemical and environmental factors. This review addresses some issues about these two biological and epigenetic processes. The most important genes in these processes are presented, as well as diseases that present an acceleration or failure in longevity and aging. Intelligent data analysis is used to find protein/gene interactions that explain these two biological phenomena.

Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD: A Secondary Analysis from a Controlled Diet Balance Study.

BACKGROUND AND OBJECTIVES: Twenty-four-hour urine phosphorus is commonly used as a surrogate measure for phosphorus intake and absorption in research studies, but its reliability and accuracy are unproven in health or CKD. This secondary analysis sought to determine the reliability and accuracy of 24-hour urine phosphorus as a biomarker of phosphorus intake and absorption in moderate CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eight patients with stage 3-4 CKD participated in 2-week balance studies with tightly controlled phosphorus and calcium intakes. Thirteen 24-hour urine collections per patient were analyzed for variability and reliability of 24-hour urine phosphorus and phosphorus-to-creatinine ratio. The accuracy of 24-hour urine phosphorus to predict phosphorus intake was determined using a published equation. The relationships of 24-hour urine phosphorus with phosphorus intake, net absorption, and retention were determined. RESULTS: There was wide day-to-day variation in 24-hour urine phosphorus within and among subjects (coefficient of variation of 30% and 37%, respectively). Two 24-hour urine measures were needed to achieve ≥75% reliability. Estimating dietary phosphorus intake from a single 24-hour urine resulted in underestimation up to 98% in some patients and overestimation up to 79% in others. Twenty-four-hour urine phosphorus negatively correlated with whole-body retention but was not related to net absorption. CONCLUSIONS: From a sample of eight patients with moderate CKD on a tightly controlled dietary intake, 24-hour urine phosphorus was highly variable and did not relate to dietary phosphorus intake or absorption, rather it inversely related to phosphorus retention.

Sketching Biological Phenomena and Mechanisms.

In many fields of biology, both the phenomena to be explained and the mechanisms proposed to explain them are commonly presented in diagrams. Our interest is in how scientists construct such diagrams. Researchers begin with evidence, typically developed experimentally and presented in data graphs. To arrive at a robust diagram of the phenomenon or the mechanism, they must integrate a variety of data to construct a single, coherent representation. This process often begins as the researchers create a first sketch, and it continues over an extended period as they revise the sketch until they arrive at a diagram they find acceptable. We illustrate this process by examining the sketches developed in the course of two research projects directed at understanding the generation of circadian rhythms in cyanobacteria. One identified a new aspect of the phenomenon itself, whereas the other aimed to develop a new mechanistic account. In both cases, the research resulted in a paper in which the conclusion was presented in a diagram that the authors deemed adequate to convey it. These diagrams violate some of the normative "cognitive design principles" advanced by cognitive scientists as constraints on successful visual communication. We suggest that scientists' sketching is instead governed by norms of success that are broadly explanatory: conveying the phenomenon or mechanism.

O período do dia não influencia o desempenho físico de homens praticantes de treinamento com pesos / Day period fails to affect the physical performance of males who practice weight lifting

O objetivo deste estudo é avaliar o desempenho de praticantes de treinamento com pesos em diferentes períodos do dia. A amostra foi composta por 10 homens treinados (24,4 ± 2,7anos, 80,6 ± 12,7 kg, 180,0 ± 10,8 cm), submetidos ao teste de uma repetição máxima (1RM) para determinação de carga máxima, no exercício supino no banco horizontal. Em seguida, três encontros foram destinados para realização do teste de resistência de força a 80% de 1RM, realizados em diferentes períodos do dia, de maneira aleatória. A análise de variância (ANOVA one-way) foi utilizada para verificar as médias dos grupos nos períodos distintos. Não foram encontradas diferenças no desempenho, independente do horário do dia, manhã (25 ± 4 repetições), tarde (26 ± 7 repetições) e noite (26 ± 7 repetições) em relação ao desempenho obtido (P > 0,05). Assim, sugere-se que o período do dia não influencia o desempenho da força e fadiga de indivíduos jovens treinados.

To evaluate the performance of weight lifterS at different periods of the day. Method: sample comprised 10 trained males (24.4± 2.7 years, 80.6±12.7kg, 180.0±10.8cm) who underwent maximum repetition test (MRT) to determine maximum load, by supine exercise, on a horizontal bench. Three sessions were employed to test force resistance at 80% MRT, at random, at different periods of the day. One way ANOVA was employed to verify means of groups within distinct periods. There was no difference in performance with regard to day period: morning (25 ± 4 repetitions), afternoon (26 ± 7 repetitions) and evening (26 ± 7 repetitions) with regard to performance (P > 0.05). It may be suggested that the period of the day does not affect force performance and fatigue of trained young people.