Label-free optical imaging for brain cancer assessment.

Advances in label-free optical imaging offer a promising avenue for brain cancer assessment, providing high-resolution, real-time insights without the need for radiation or exogeneous agents. These cost-effective and intricately detailed techniques overcome the limitations inherent in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scans by offering superior resolution and more readily accessible imaging options. This comprehensive review explores a variety of such methods, including photoacoustic imaging (PAI), optical coherence tomography (OCT), Raman imaging, and IR microscopy. It focuses on their roles in the detection, diagnosis, and management of brain tumors. By highlighting recent advances in these imaging techniques, the review aims to underscore the importance of label-free optical imaging in enhancing early detection and refining therapeutic strategies for brain cancer.

Let's talk about sex: Mechanisms of neural sexual differentiation in Bilateria.

In multicellular organisms, sexed gonads have evolved that facilitate release of sperm versus eggs, and bilaterian animals purposefully combine their gametes via mating behaviors. Distinct neural circuits have evolved that control these physically different mating events for animals producing eggs from ovaries versus sperm from testis. In this review, we will describe the developmental mechanisms that sexually differentiate neural circuits across three major clades of bilaterian animals-Ecdysozoa, Deuterosomia, and Lophotrochozoa. While many of the mechanisms inducing somatic and neuronal sex differentiation across these diverse organisms are clade-specific rather than evolutionarily conserved, we develop a common framework for considering the developmental logic of these events and the types of neuronal differences that produce sex-differentiated behaviors. This article is categorized under: Congenital Diseases > Stem Cells and Development Neurological Diseases > Stem Cells and Development.

PTEN is both an activator and a substrate of chaperone-mediated autophagy.

PTEN is a crucial negative regulator of the INS/PI3K/AKT pathway and is one of the most commonly mutated tumor suppressors in cancer. Global overexpression (OE) of PTEN in mice shifts metabolism to favor oxidative phosphorylation over glycolysis, reduces fat mass, and extends the lifespan of both sexes. We demonstrate that PTEN regulates chaperone-mediated autophagy (CMA). Using cultured cells and mouse models, we show that PTEN OE enhances CMA, dependent upon PTEN's lipid phosphatase activity and AKT inactivation. Reciprocally, PTEN knockdown reduces CMA, which can be rescued by inhibiting class I PI3K or AKT. Both PTEN and CMA are negative regulators of glycolysis and lipid droplet formation. We show that suppression of glycolysis and lipid droplet formation downstream of PTEN OE depends on CMA activity. Finally, we show that PTEN protein levels are sensitive to CMA and that PTEN accumulates in lysosomes with elevated CMA. Collectively, these data suggest that CMA is both an effector and a regulator of PTEN.

LAMP2A, and other chaperone-mediated autophagy related proteins, do not decline with age in genetically heterogeneous UM-HET3 mice.

Chaperone-mediated autophagy (CMA) selectively degrades proteins that are crucial for glycolysis, fatty acid metabolism, and the progression of several age-associated diseases. Several previous studies, each of which evaluated males of a single inbred mouse or rat strain, have reported that CMA declines with age in many tissues, attributed to an age-related loss of LAMP2A, the primary and indispensable component of the CMA translocation complex. This has led to a paradigm in the field of CMA research, stating that the age-associated decline in LAMP2A in turn decreases CMA, contributing to the pathogenesis of late-life disease. We assessed LAMP2A levels and CMA substrate uptake in both sexes of the genetically heterogeneous UM-HET3 mouse stock, which is the current global standard for the evaluation of anti-aging interventions. We found no evidence for age-related changes in LAMP2A levels, CMA substrate uptake, or whole liver levels of CMA degradation targets, despite identifying sex differences in CMA.

Sodium Alginate-Aldehyde Cellulose Nanocrystal Composite Hydrogel for Doxycycline and Other Tetracycline Removal.

A novel composite hydrogel bead composed of sodium alginate (SA) and aldehyde cellulose nanocrystal (DCNC) was developed for antibiotic remediation through a one-step cross-linking process in a calcium chloride bath. Structural and physical properties of the hydrogel bead, with varying composition ratios, were analyzed using techniques such as BET analysis, SEM imaging, tensile testing, and rheology measurement. The optimal composition ratio was found to be 40% (SA) and 60% (DCNC) by weight. The performance of the SA-DCNC hydrogel bead for antibiotic remediation was evaluated using doxycycline (DOXY) and three other tetracyclines in both single- and multidrug systems, yielding a maximum adsorption capacity of 421.5 mg g-1 at pH 7 and 649.9 mg g-1 at pH 11 for DOXY. The adsorption mechanisms were investigated through adsorption studies focusing on the effects of contact time, pH, concentration, and competitive contaminants, along with X-ray photoelectron spectroscopy analysis of samples. The adsorption of DOXY was confirmed to be the synergetic effects of chemical reaction, electrostatic interaction, hydrogen bonding, and pore diffusion/surface deposition. The SA-DCNC composite hydrogel demonstrated high reusability, with more than 80% of its adsorption efficiency remaining after five cycles of the adsorption-desorption test. The SA-DCNC composite hydrogel bead could be a promising biomaterial for future antibiotic remediation applications in both pilot and industrial scales because of its high adsorption efficiency and ease of recycling.

The Use of Music to Manage Burnout in Nurses: A Systematic Review.

OBJECTIVE: There is a high prevalence of burnout in nurses. This systematic review investigates the use of music to manage burnout in nurses. DATA SOURCE: MEDLINE (Ovid), MEDLINE InProcess/ePubs, Embase, APA PsycINFO, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched. STUDY INCLUSION AND EXCLUSION CRITERIA: Full-text articles were selected if the study assessed the use of music to manage burnout in nurses. Burnout was defined according to the International Classification of Diseases 11th Revision. DATA EXTRACTION: Data were extracted using an Excel sheet. The second and third authors independently extracted study characteristics, frequency and type of music engagement, measures of burnout, and burnout outcomes (occupational stress, coping with stress, and related symptoms such as anxiety). DATA SYNTHESIS: Study and outcome data were summarized. RESULTS: The literature search resulted in 2210 articles and 16 articles were included (n = 1205 nurses). All seven cross-sectional studies reported upon nurses' self-facilitated use of music including music listening, playing instruments, and music entertainment for coping or preventing stress, supporting wellbeing, or enhancing work engagement. Externally-facilitated music engagement, including music listening, chanting, percussive improvisation, and song writing, was reported in the four randomized controlled trials and five cohort studies with reductions in burnout outcomes. CONCLUSIONS: Self-facilitated and externally-facilitated music engagement can help to reduce burnout in nurses.

Protocol efficiently measuring the swelling rate of hydrogels.

Hydrogels are polymeric materials which can swell in water and retain a significant fraction of water within their structure without dissolving in water. Swelling rate is one of the most important properties of hydrogels. To measure the swelling rate, the profile of swelling capacity versus time of a hydrogel sample is obtained by performing free-absorbency capacity measurements at consecutive time intervals. Traditionally, either the tea-bag method, the sieve method, or the filtration method is used for the free-absorbency capacity measurements depending on the amount of the available sample and the desired precision. However, each method has its own systematic drawbacks. In this paper, a novel method called sieve filtration method is proposed for the measurement of the swelling rate of hydrogels. A protocol for this method is described in detail. The measurement results obtained from the proposed method and the traditional methods are compared. The proposed method has the following advantages over the traditional methods: •It is more efficient than the traditional methods due to full contact of the hydrogel powders with water or aqueous solution as well as fast and complete removal of excessive fluid from the water-absorbed gel.•It enables repeatable and reproducible measurement of the swelling rate of hydrogels.•It is easy to implement, suitable for various types of hydrogels and aqueous solutions; and it requires small amounts of sample, minimal technical skill, and inexpensive equipment.

Statistical learning for turboshaft helicopter accidents using logistic regression.

The objective of this work is to advance the understanding of helicopter accidents by examining and quantifying the association between helicopter-specific configurations (number of main rotor blades, number of engines, rotor diameter, and takeoff weight) and the likelihood of accidents. We leverage a dataset of 8,338 turboshaft helicopters in the U.S. civil fleet and 825 accidents from 2005 to 2015. We use the dataset to develop a logistic regression model using the method of purposeful selection, which we exploit for inferential purposes and highlight the novel insights it reveals. For example, one important question for the design and acquisition of helicopters is whether twin-engine turboshaft helicopters exhibit a smaller likelihood of accidents than their single-engine counterparts, all else being equal. The evidence-based result we derive indicates that the answer is contingent on other covariates, and that a tipping point exists in terms of the rotor diameter beyond which the likelihood of accidents of twin-engines is higher (worse) than that of their single-engine counterparts. Another important result derived here is the association between the number of main rotor blades and likelihood of accidents. We found that for single-engine turboshaft helicopters, the four-bladed ones are associated with the lowest likelihood of accidents. We also identified a clear coupling between the number of engines and the rotor diameter in terms of likelihood of accidents. In summary, we establish important relationships between the different helicopter configurations here considered and the likelihood of accident, but these are associations, not causal in nature. The causal pathway, if it exists, may be confounded or mediated by other variables not accounted for here. The results provided here lend themselves to a rich set of interpretive possibilities, and because of their significant safety implications they deserve careful attention from the rotorcraft community.

Maintenance and inspection as risk factors in helicopter accidents: Analysis and recommendations.

In this work, we establish that maintenance and inspection are a risk factor in helicopter accidents. Between 2005 and 2015, flawed maintenance and inspection were causal factors in 14% to 21% of helicopter accidents in the U.S. civil fleet. For these maintenance-related accidents, we examined the incubation time from when the maintenance error was committed to the time when it resulted in an accident. We found a significant clustering of maintenance accidents within a short number of flight-hours after maintenance was performed. Of these accidents, 31% of these accidents occurred within the first 10 flight-hours. This is reminiscent of infant mortality in reliability engineering, and we characterized it as maintenance error infant mortality. The last quartile of maintenance-related accidents occurred after 60 flight-hours following maintenance and inspection. We then examined the "physics of failures" underlying maintenance-related accidents and analyzed the prevalence of different types of maintenance errors in helicopter accidents. We found, for instance, that the improper or incomplete (re)assembly or installation of a part category accounted for the majority of maintenance errors with 57% of such cases, and within this category, the incorrect torquing of the B-nut and incomplete assembly of critical linkages were the most prevalent maintenance errors. We also found that within the failure to perform a required preventive maintenance and inspection task category, the majority of the maintenance programs were not executed in compliance with federal regulations, nor with the manufacturer maintenance plan. Maintenance-related accidents are particularly hurtful for the rotorcraft community, and they can be eliminated. This is a reachable objective when technical competence meets organizational proficiency and the collective will of all the stakeholders in this community. We conclude with a set of recommendations based on our findings, which borrow from the ideas underlying the defense-in-depth safety principle to address this disquieting problem.

The association between EGFR variant III, HPV, p16, c-MET, EGFR gene copy number and response to EGFR inhibitors in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: We examine the potential prognostic and predictive roles of EGFR variant III mutation, EGFR gene copy number (GCN), human papillomavirus (HPV) infection, c-MET and p16INK4A protein expression in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: We analyzed the archival tumor specimens of 53 patients who were treated in 4 phase II trials for R/M SCCHN. Two trials involved the EGFR inhibitor erlotinib, and 2 trials involved non-EGFR targeted agents. EGFRvIII mutation was determined by quantitative RT-PCR, HPV DNA by Linear Array Genotyping, p16 and c-MET protein expression by immunohistochemistry, and EGFR GCN by FISH. RESULTS: EGFRvIII mutation, detected in 22 patients (42%), was associated with better disease control, but no difference was seen between erlotinib-treated versus non-erlotinib treated patients. EGFRvIII was not associated with TTP or OS. The presence of HPV DNA (38%), p16 immunostaining (32%), c-MET high expression (58%) and EGFR amplification (27%), were not associated with response, TTP or OS. CONCLUSION: EGFRvIII mutation, present in about 40% of SCCHN, appears to be an unexpected prognostic biomarker associated with better disease control in R/M SCCHN regardless of treatment with erlotinib. Larger prospective studies are required to validate its significance.

Detection of mosaic RB1 mutations in families with retinoblastoma.

The RB1 gene mutation detection rate in 1,020 retinoblastoma families was increased by the use of highly sensitive allele specific-PCR (AS-PCR) to detect low-level mosaicism for 11 recurrent RB1 CGA>TGA nonsense mutations. For bilaterally affected probands, AS-PCR increased the RB1 mutation detection sensitivity from 92.6% to 94.8%. Both RB1 oncogenic changes were detected in 92.7% of sporadic unilateral tumors (357/385); 14.6% (52/357) of unilateral probands with both tumor mutations identified carried one of the tumor mutations in blood. Mosaicism was evident in 5.5% of bilateral probands (23 of 421), in 3.8% of unilateral probands (22 of 572), and in one unaffected mother of a unilateral proband. Half of the mosaic mutations were only detectable by AS-PCR for the 11 recurrent CGA>TGA mutations, and not by standard sequencing. This suggests that significant numbers of low-level mosaics with other classes of RB1 mutations remain unidentified by current technology. We show that the use of linkage analysis in a two-generation retinoblastoma family resulted in the erroneous conclusion that a child carried the parental mutation, because the founder parent was mosaic for the RB1 mutation. Of 142 unaffected parental pairs tested, only one unaffected parent of a proband (0.7%) showed somatic mosaicism for the proband's mutation, in contrast to an overall 4.5% somatic mosaicism rate for retinoblastoma probands, suggesting that mosaicism for an RB1 mutation is highly likely to manifest as retinoblastoma.

Patterns of missplicing caused by RB1 gene mutations in patients with retinoblastoma and association with phenotypic expression.

We have analyzed RNA from retinoblastoma patients and unaffected carriers with various RB1 gene mutations to determine the patterns of missplicing and associations with phenotypic expression. Most sequence alterations in or in the neighborhood of conserved splice signals that we tested resulted in simple exon skipping (15 mutations) or intron inclusion (new acceptor AG-sites, four mutations) as expected. Two mutations resulted in skipping of a neighboring exon (exon 11), a complex pattern indicating competition for correct lariat formation. We observed no activation of a cryptic splice site but found that a recurrent missense mutation in exon 7 creates a new splice site (two families). RT-PCR analysis enabled us to confirm the presence and to characterize the transcriptional consequences of gross insertions and deletions in the RB1 gene in six patients, including two patients with mutational mosaicism. We also used RT-PCR analysis to search for unknown mutations in 15 patients and identified three oncogenic point mutations deep in introns. Two of these mutations are recurrent thus indicating that, despite the vast extent of the introns of the RB1 gene, few bases are effective targets for oncogenic mutations. When analyzing associations between phenotypic expression (16 families) and mutational consequences we observed no link to the presence or absence of a premature termination codon in the mutant transcript. However, the location of a mutation relative to the splice sequence has a strong and consistent influence on phenotypic expression.

Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma.

Timely molecular diagnosis of RB1 mutations enables earlier treatment, lower risk, and better health outcomes for patients with retinoblastoma; empowers families to make informed family-planning decisions; and costs less than conventional surveillance. However, complexity has hindered clinical implementation of molecular diagnosis. The majority of RB1 mutations are unique and distributed throughout the RB1 gene, with no real hot spots. We devised a sensitive and efficient strategy to identify RB1 mutations that combines quantitative multiplex polymerase chain reaction (QM-PCR), double-exon sequencing, and promoter-targeted methylation-sensitive PCR. Optimization of test order by stochastic dynamic programming and the development of allele-specific PCR for four recurrent point mutations decreased the estimated turnaround time to <3 wk and decreased direct costs by one-third. The multistep method reported here detected 89% (199/224) of mutations in bilaterally affected probands and both mutant alleles in 84% (112/134) of tumors from unilaterally affected probands. For 23 of 27 exons and the promoter region, QM-PCR was a highly accurate measure of deletions and insertions (accuracy 95%). By revealing those family members who did not carry the mutation found in the related proband, molecular analysis enabled 97 at-risk children from 20 representative families to avoid 313 surveillance examinations under anesthetic and 852 clinic visits. The average savings in direct costs from clinical examinations avoided by children in these families substantially exceeded the cost of molecular testing. Moreover, health care savings continue to accrue, as children in succeeding generations avoid unnecessary repeated anaesthetics and examinations.