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Background: Acute exacerbations of chronic rhinosinusitis (AECRS) are thought to arise from common viral infections progressing to secondary bacterial infections. However, the pathophysiology of AECRS remains poorly understood due to a lack of prospective longitudinal studies. Methods: We conducted a one‐year prospective longitudinal study involving chronic rhinosinusitis (CRS) adults. At baseline, we assessed subjective symptom scores using a validated upper respiratory infection questionnaire (WURSS), sinonasal outcome testing scores (SNOT‐22), and endoscopic scores (modified Lund‐Kennedy score). Every 2 weeks, we contacted subjects to collect WURSS and SNOT‐22 scores. If WURSS scores were ≥1 and SNOT‐22 scores were ≥ 8.9 compared with baseline, subjects underwent an AECRS assessment. We identified rhinovirus (RV) incidence through viral nasal brushings at each visit and bacterial infection through bacterial swabs if mucus scores were ≥1. Results: Thiry‐five of 80 CRS subjects reported at least one AECRS episode during the year, predominantly occurring in the fall and winter seasons. RV infections were detected in 8 of 35 cases, bacterial infections in 17 of 35, and co‐occurring infections in 7 of 35. All subjects with AECRS visits exhibited significantly higher endoscopic scores compared with baseline. Subjects with co‐occurring RV and bacterial infections demonstrated higher disease severity compared with those with either RV or bacterial infection, or no infection. Conclusions: In a one‐year prospective longitudinal study involving CRS adults, we identified significant risk factors for AECRS including seasonality and the presence of RV and bacterial infections. These data suggest a standard definition of AECRS and the need to target RV and bacterial infections if we are to help reduce disease severity. [ABSTRACT FROM AUTHOR]

Purpose: The inclusion of ranibizumab biosimilars into National Health Service England commissioning recommendations published in 2022 created a need for expert guidance to optimize treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) who otherwise may not have received first-line ranibizumab. This article provides a consensus treatment pathway supporting timely identification and management of a suboptimal response to these therapies, thereby aiming to facilitate clinically meaningful outcomes and efficient management of service capacity under specific circumstances where ranibizumab biosimilars may be initiated as a first-line treatment. Methods: Two structured round-table meetings of UK medical retina specialists were held in person and virtually on September 22 and November 3, 2022, respectively. These meetings were organized and funded by Bayer. Results: The panel provided guidance on the implementation of an early treatment optimization pathway in cases where ranibizumab biosimilars are used as a first-line treatment, including recommendations on patient suitability and capacity requirements, and criteria for identification and strategies for management of a suboptimal response. The panel discussed the role of aflibercept treatment and its potential benefits and outlined recommendations on switching ranibizumab biosimilar suboptimal responders to an aflibercept treat-and-extend regimen, where appropriate. Conclusion: Developed by a retinal expert panel, this early treatment optimization pathway provides guidance to facilitate optimal long-term patient outcomes while addressing capacity and resourcing constraints in circumstances of first-line ranibizumab biosimilar use for nAMD, including how aflibercept may be used in cases with a suboptimal response. Therefore, this fills an important gap in guidance on navigating the new treatment landscape. [ABSTRACT FROM AUTHOR]

Facet joint violation by pedicle screws may lead to adjacent-segment disease and postoperative pain. Previous studies have reported the incidence of rostral facet joint violation using various pedicle screw insertion techniques. However, the incidence of facet joint violations with robotic guidance has not been determined. To investigate and compare the incidence of rostral facet joint violation by pedicle screws under robotic guidance and computerized tomography (CT) navigation guidance. Retrospective matched cohort. All patients who underwent robotic-assisted lumbar fusion at a major spine center up until 2023 were retrospectively identified and matched 1:3 to patients undergoing CT navigation guidance based by on age, sex, rostral vertebral level, and length of construct. Inclusion criteria consisted of age greater than 18 years, bilateral pedicle screw fixation, and presence of a postoperative CT scan of the lumbar spine or abdomen/pelvis at any point in the postoperative period. Rostral facet joint violations. Descriptive statistics were used to compare cohorts: frequencies, chi-squared analysis for categorical variables, and t-test for continuous variables. A total of 408 rostral pedicle screws were implanted in 204 patients (Robot: 102; Navigation: 306). Overall, 13 (12.3%) rostral facet joint violations were observed in the robot cohort and 75 (24.5%) in the navigation cohort (p=.01). Specifically, fewer robotic violations were observed at the L2 (3.5% vs 32.1%, p=.003) and L3 levels (3.9% vs 18.1%, p=.08) compared to navigation. No difference was observed at L4 and L5. Bilateral violations are significantly reduced with robotic approaches (5.3% vs 14.4%, p=.03). Lastly, more facet joint violations were observed during open approaches (robot: 18.8%, navigation: 27.3%) than percutaneous approaches (robot: 11.6%, navigation: 7.1%) in both groups (p<.001). The rate of L4 facet violations was 18.8% in the robotic cohort and 27.3% in the navigation cohort. The rate of L5 facet violations was 31.3% in the robotic cohort and 29.2% in the navigation cohort. Use of robotic assistance in lumbar pedicle screws significantly reduced the rate of rostral facet joint violations compared to navigation guidance at L2 and L3 levels, but not at L4 and L5, with facet violations approaching nearly one-third of the patients at L5 screws. Rostral facet violations can play a significant role in adjacent segment degeneration and disease. Technical factors and trajectory issues likely play a role and addressing these components should minimize unintended facet violation and proximal adding on. [ABSTRACT FROM AUTHOR]

Introduction: The Coronavirus Disease-2019 (COVID-19) pandemic has halted the progress of India made towards the ambition of achieving Tuberculosis (TB)-free status by 2025. Steps taken to control the disease have affected many national health programs, including those for TB. Aim: To understand the delays in diagnosing and initiating therapy among TB patients receiving Antitubercular Therapy (ATT) during the early COVID-19 pandemic period. Materials and Methods: This was a cross-sectional study conducted in the Sonepat District of Haryana state, India. The study was conducted among 20% of the total Nikshay Portal-notified TB patients who received treatment from the public sector in the second and third quarters of 2020. Data was collected using a pretested semistructured schedule consisting of variables related to demography, past medical history, symptoms leading to TB diagnosis, place of diagnosis, time between symptom onset and diagnosis, duration taken for initiating therapy, and reasons for delays. The Chi-square test and Fisher's exact test were used to test the significance of the differences. A p-value <0.05 was considered significant. Results: 'Diagnostic Time delay' was observed among 86 (35.1%) of the participants, with a 30-day median delay. 'ATT initiation delays' were observed in 51 (20.8%) with a four-day median delay, and 23 (8.6%) of patients reported at least one episode of treatment interruption. 'Being diagnosed for other diseases' 70 (28.6%) and 'ignoring symptoms' 28 (11.4%) constituted the major reasons for 'Diagnostic time delay'. The non availability of drugs 11 (47.8%) and discomfort with drugs 07 (30.4%) were the major reasons for treatment interruption. Conclusion: Ignorance of symptoms and suspicion of other diseases constituted diagnostic delays, and therapy initiations were prolonged more during the pandemic period. [ABSTRACT FROM AUTHOR]

Blood–brain barrier (BBB) injury and dysfunction following infection with the human immunodeficiency virus (HIV) enables viral entry into the brain, infection of resident brain cells, neuronal injury and subsequent neurodegeneration leading to HIV-associated neurocognitive disorders (HAND). Although combination antiretroviral therapy has significantly reduced the incidence and prevalence of acquired immunodeficiency syndrome and increased the life expectancy of people living with HIV, the prevalence of HAND remains high. With aging of people living with HIV associated with increased comorbidities, the prevalence of HIV-related central nervous system (CNS) complications is expected to remain high. Considering the principal role of the brain endothelium in HIV infection of the CNS and HAND, the purpose of this manuscript is to review the current literature on the pathobiology of the brain endothelium structural and functional dysregulation in HIV infection, including in the presence of HIV-1 and viral proteins (gp120, Tat, Nef, and Vpr). We summarize evidence from human and animal studies, in vitro studies, and associated mechanisms. We further summarize evidence of synergy or lack thereof between commonly abused substances (cocaine, methamphetamine, alcohol, tobacco, opioids, and cannabinoids) and HIV- or viral protein-induced BBB injury and dysfunction. [ABSTRACT FROM AUTHOR]

Study Design. Retrospective cohort study. Objective. This study compares reoperation rates and complications following single-level anterior lumbar interbody fusion (ALIF)/lateral lumbar interbody fusion (LLIF) and transforaminal lumbar interbody fusion (TLIF)/posterior lumbar interbody fusion (PLIF). Summary of Background Data. ALIF, LLIF, TLIF, and PLIF are widely used for degenerative disc disease. Lumbar interbody fusions have high rates of reoperation, primarily related to adjacent segment pathology and pseudarthrosis. Materials and Methods. The PearlDiver database was queried for patients (2010-2021) who had single-level ALIF/LLIF or TLIF/PLIF with same-day, single-level posterior instrumentation. ALIF/LLIF were combined, and similarly, TLIF/PLIF were combined, given how these operations are indistinguishable from Current Procedural Terminology coding. All patients were followed for ≥ 2 years and excluded if they had spinal traumas, fractures, infections, or neoplasms before surgery. The two cohorts, ALIF/LLIF and TLIF/PLIF, were matched 1:1 based on age, sex, Elixhausercomorbidity index, smoking status, and diabetes. The primary outcome was the incidence of all-cause subsequent lumbar operations. Secondary outcomes included 90-day surgical complications. Results. After 1:1 matching, each cohort contained 14,070 patients. All-cause subsequent lumbar operations were nearly identical at five-year follow-up (9.4% ALIF/LLIF vs. 9.5% TLIF/PLIF, P=0.91). Survival analysis using all-cause subsequent lumbar operations as the endpoint showed an equivalent 10-year survival rate of 86.0% (95%CI: 85.2-86.8). Within 90 days, TLIF/PLIF had more infections (1.3% vs. 1.7%, P=0.007) and dural injuries (0.2% vs. 0.4%, P=0.001). There was no difference in wound dehiscence, hardware complications, or medical complications. Conclusion. As utilized in real-world clinical practice, singlelevel anterolateral versus posterior approaches for interbody fusion have no effect on long-term reoperation rates. [ABSTRACT FROM AUTHOR]

Purpose: Adult stem cells (SCs) with self-renewal and multilineage potential have been reported upon culturing human retinal pigment epithelial (RPE) cells. The current study aimed to identify the location of SCs in human RPE and to elucidate the age-related changes. Methods: Peripheral, equatorial, and central RPE cells from donors of three age groups were analyzed for their sphere-forming, clonal, and label-retaining cell properties. Furthermore, native human RPE flatmounts were immunostained for SC and proliferating cell markers. Results: Cells with higher sphere-forming and clonal ability were identified only in young donors (<30 years) and were restricted to the periphery. Upon culturing, cells from peripheral and equatorial regions had the label-retaining cell (LRC) property. With aging, the LRCs were restricted to the periphery and were reduced. In young donors, Ki67+ proliferating cells were not observed in native RPE. However, such cells were observed in the peripheral RPE of older donors correlating with the need for regeneration. The native RPE cells were negative for SC marker expression. Conclusion: The above findings highlighted the presence of SCs with the ability to proliferate in the peripheral RPE and a reduction in these functional properties of SCs with aging. [ABSTRACT FROM AUTHOR]

Perovskite materials are emerging as the most promising and efficient low-cost energy materials for various applications. The construction of heterojunctions has become a field of interest because of their high potential to give off a large amount of energy. Herein, a Z-scheme heterojunction was made between two perovskites (CoTiO3 and CaTiO3) in order to make a cheap material that is good at photocatalysis. Various methods were used to characterize the resulting CoTiO3/CaTiO3 (CCO 75: 25) composite, including XRD, Raman, XPS, HRSEM, HRTEM, BET, and UV-vis. The increased photocatalytic activity of the CoTiO3/CaTiO3 (CCO) composite is attributed to the accelerated charge transfer from O2- to Ti4+ and from Co2+ to Ti4+ ions, revealing the close interfacial contact between CoTiO3 and CaTiO3, and spatial charge transfer within the CoTiO3/CaTiO3 heterojunction. A direct Z-scheme mechanism was developed, and charge transfer properties were verified by the scavenger test and ESR, PL, and EIS analyses. The enhanced degradation rate of k = 0.0373 min-1 is achieved for the CCO 75: 25 composite. Meanwhile, the CCO 75: 25 composite established high photocatalytic stability when recycled for CBZ degradation. This research offers mechanistic and practical views on designing simple and cost-effective materials for pollutant removal. [ABSTRACT FROM AUTHOR]

Introduction. With reliable tests and preventative treatments now available the United Kingdom has introduced a prototype population-based paediatric (ages 3–13) screening programme for type 1 diabetes (T1D). To aid its ethical and sustainable implementation this work explores parental views around the concept of this programme to determine how their involvement might be encouraged and supported. Research Design and Methods. Qualitative interviews were undertaken with 38 parents and the data were analysed using a purposely developed "Burden of Screening" framework, which presented the data within three domains describing the various elements of screening participation; pre-screening tasks designated to participants; factors influencing engagement with screening; and consequences of screening participation. Results. Regarding pre-screening tasks designated to participants, the importance of clear communication about the condition were apparent with parents expressing uncertainty of the benefits of screening against the potential anxiety engendered. In factors influencing their engagement with screening participants described their preference for less invasive testing techniques, the reassurance of structured support from healthcare professionals inherent within the programme, and the potential benefit of peer support. Regarding the consequences of screening participation parents described how a positive result might lead to overly protective behaviours, and anxiety from watching and waiting for the onset of symptomatic T1D. Conclusions. The benefits of T1D screening need to be clearly communicated to facilitate uptake. To this end the use of decision-support tools and better targeted educational materials should be explored. Post-testing, parents expressed preferences for peer support and access to psychological counselling. [ABSTRACT FROM AUTHOR]

AbstractNumerical analysis has been conducted for a solar collector with two circular pipes having semi-circular contact with absorber plate. The tubes are analyzed with and without the inclusion of twisted tape inserts of twist ratio Y = 3 and Y = 4. The comparison between the heat transfer and pressure drop characteristics of a plain tube to that fitted with the twisted tape inserts is done and validated against experimental results with good agreement. Additionally, helical twisted tape is modeled with square- and V-cut to analyze its influence on flow and heat transfer phenomenon. V-cut twisted tape inserts act as turbulence promoters, increasing fluid flow and inducing vortex-like motion. As a result, boundary layer around the absorber plate is disrupted with decrease in stagnation temperature, resulting in better heat transfer and more effective absorption and conversion of solar energy. The Nusselt number, friction factor, and heat transfer coefficient variation with the Reynolds number have been studied for the given heat fluxes. It is found that the Nusselt number of the fluid flowing in the plain tube is increased by 76.44% when the tube is fitted with twisted tape inserts. The pressure drop in the tube is found to increase with the presence of the twisted tapes. The average temperature along the length of the circular tube and absorber plate has also been reported. [ABSTRACT FROM AUTHOR]

The article offers information on recommending an alternative fixation method for arthroscopic knee procedures using medial tibia cortex transosseous sling fixation. Topics discussed include the limitations of current implants such as cost and complications; the advantages of implant-free transosseous suturing; and also mentions about the detailed surgical technique of the proposed method.

Aims: Identifying children at risk of type 1 diabetes allows education for symptom recognition and monitoring to reduce the risk of diabetic ketoacidosis at presentation. We aimed to explore stakeholder views towards paediatric general population screening for type 1 diabetes in the United Kingdom (UK). Methods: Qualitative interviews were undertaken with 25 stakeholders, including diabetes specialists, policymakers and community stakeholders who could be involved in a future type 1 diabetes screening programme in the UK. A thematic framework analysis was performed using the National Screening Committee's evaluative criteria as the overarching framework. Results: Diabetic ketoacidosis prevention was felt to be a priority and proposed benefits of screening included education, monitoring and helping the family to better prepare for a future with type 1 diabetes. However, diabetes specialists were cautious about general population screening because of lack of evidence for public acceptability. Concerns were raised about the harms of living with risk, provoking health anxiety and threatening the child's right to an 'open future'. Support systems that met the clinical and psychological needs of the family living with risk were considered essential. Stakeholders were supportive of research into general population screening and acknowledged this would be a priority if an immunoprevention agent were licensed in the UK. Conclusions: Although stakeholders suggested the harms of UK paediatric general population screening currently outweigh the benefits, this view would potentially be altered if prevention therapies were licensed. In this case, an evidence‐based screening strategy would need to be formulated and public acceptability explored. [ABSTRACT FROM AUTHOR]

For the latest high density compact devices, thermal management is crucial for their effective heat dissipation and system reliability. In literature, microchannel heat sink has been established as one of the advanced heat transfer techniques to fulfill the cooling demands of high power electronic applications. However, maldistribution in microchannels causes flow induced high temperature zones (FITZ) which reduces the electrical performance owing to electrical-thermal instability of the integrated chips. One way to mitigate the FITZ is by allowing more coolant inlets in these zones. In the current study, this is achieved by redesigning double layer microchannel heat sink (DMCHS) specific to the FITZ of I-type microchannel configuration using additive manufacturing (AM). Two AM microchannels were tested, one is a single layer microchannel heat sink (MCHS) and another one is a curved double layer microchannel (C-DMCHS). The curved channels were introduced in the bottom channels of C-DMCHS to mitigate FITZ compared to conventional DMCHS. AM microchannels are compared for Nusselt number and friction factor characteristics with the conventional straight channels, and heat treated AM microchannels. From experimental observation, Ti64 3D printed microchannel with Graphene oxide (GO-0.12%) nanofluid developed 75.4% more pressure drop than the Ti64 heat treated microchannel. The results additionally show that the C-DMCHS delivered 26.5% lower FITZ temperature than MCHS. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1DM) is a progressive autoimmune disease that starts long before a clinical diagnosis is made. The American Diabetes Association recognizes three stages: stage 1 (normoglycaemic and positive for autoantibodies to β-cell antigens); stage 2 (asymptomatic with dysglycaemia); and stage 3, which is defined by glucose levels consistent with the definition of diabetes mellitus. This Perspective focuses on the management of the proportion of individuals with early stage 3 T1DM who do not immediately require insulin; a stage we propose should be termed stage 3a. To date, this period of non-insulin-dependent T1DM has been largely unrecognized. Importantly, it represents a window of opportunity for intervention, as remaining at this stage might delay the need for insulin by months or years. Extending the insulin-free period and/or avoiding unnecessary insulin therapy are important goals, as there is no risk of hypoglycaemia during this period and the adherence burden on patients of glycaemic monitoring and daily adjustments for diet and exercise is substantially reduced. Recognizing the pressing need for guidance on adequate management of children and adults with stage 3a T1DM, we present our perspective on the subject, which needs to be tested in formal and adequately powered clinical trials. This Perspective discusses potential approaches to managing patients in the early stages of developing type 1 diabetes mellitus, which could enable the initiation of insulin therapy to be delayed in some patients. [ABSTRACT FROM AUTHOR]

Checkpoint inhibitors can be a highly effective antitumor therapy but only to a subset of patients, presumably due to immunotherapy resistance. Fluoxetine was recently revealed to inhibit the NLRP3 inflammasome, and NLRP3 inhibition could serve as a target for immunotherapy resistance. Therefore, we evaluated the overall survival (OS) in patients with cancer receiving checkpoint inhibitors combined with fluoxetine. A cohort study was conducted among patients diagnosed with lung, throat (pharynx or larynx), skin, or kidney/urinary cancer treated with checkpoint inhibitor therapy. Utilizing the Veterans Affairs Informatics and Computing Infrastructure, patients were retrospectively evaluated during the period from October 2015 to June 2021. The primary outcome was overall survival (OS). Patients were followed until death or the end of the study period. There were 2316 patients evaluated, including 34 patients who were exposed to checkpoint inhibitors and fluoxetine. Propensity score weighted Cox proportional hazards demonstrated a better OS in fluoxetine-exposed patients than unexposed (HR: 0.59, 95% CI 0.371–0.936). This cohort study among cancer patients treated with checkpoint inhibitor therapy showed a significant improvement in the OS when fluoxetine was used. Because of this study's potential for selection bias, randomized trials are needed to assess the efficacy of the association of fluoxetine or another anti-NLRP3 drug to checkpoint inhibitor therapy. [ABSTRACT FROM AUTHOR]

Tauopathies are a group of neurodegenerative diseases categorised into three types, 3R, 4R, or 3R+4R (mixed) tauopathies, based on the tau isoforms that make up the aberrant filaments. It is supposed that all six tau isoforms share functional characteristics. However, differences in the neuropathological features associated with different tauopathies offer the possibility that disease progression and tau accumulation may vary depending on the isoform composition. The presence or absence of repeat 2 (R2) in the microtubule-binding domain defines the type of isoform, which might influence tau pathology associated with a particular tau isoform. Therefore, our study aimed to identify the differences in the seeding propensities of R2 and repeat 3 (R3) aggregates using HEK293T biosensor cells. We show that the seeding induced by R2 was generally higher than by R3 aggregates, and lower concentrations of R2 aggregates are sufficient to induce seeding. Next, we found that both R2 and R3 aggregates dose-dependently increased triton-insoluble Ser262 phosphorylation of native tau, which is only visible in cells seeded with higher concentrations (12.5 nM or 100 nM) of R2 and R3 aggregates, despite the seeding by the lower concentrations of R2 aggregates after 72 h. However, the accumulation of triton-insoluble pSer262 tau was visible earlier in cells induced with R2 than in R3 aggregates. Our findings suggest that the R2 region may contribute to the early and enhanced induction of tau aggregation and define the difference in disease progression and neuropathology of 4R tauopathies. • The seeding effect of tau R2 is higher than R3 aggregates in K18 (P301S) tau biosensor cells. • Lower concentrations of R2 than R3 aggregates are sufficient to induce seeding of intracellular tau in cells. • Both R2 and R3 aggregates dose-dependently increased the intracellular tau aggregation in cells. • Higher concentrations of R2 and R3 aggregates are needed to induce triton-insoluble pSer262 tau detectable by Western blot. • Differences in seeding by R2 and R3 aggregates highlight the importance of targeting these regions for treating tauopathies. [ABSTRACT FROM AUTHOR]

In this paper, we designed and demonstrated a stimuli-responsive hydrogel that mimics the mass diffusion function of the liver. We have controlled the release mechanism using temperature and pH variations. Additive manufacturing technology was used to fabricate the device with nylon (PA-12), using selective laser sintering (SLS). The device has two compartment sections: the lower section handles the thermal management, and feeds temperature-regulated water into the mass transfer section of the upper compartment. The upper chamber has a two-layered serpentine concentric tube; the inner tube carries the temperature-regulated water to the hydrogel using the given pores. Here, the hydrogel is present in order to facilitate the release of the loaded methylene blue (MB) into the fluid. By adjusting the fluid's pH, flow rate, and temperature, the deswelling properties of the hydrogel were examined. The weight of the hydrogel was maximum at 10 mL/min and decreased by 25.29% to 10.12 g for the flow rate of 50 mL/min. The cumulative MB release at 30 °C increased to 47% for the lower flow rate of 10 mL/min, and the cumulative release at 40 °C climbed to 55%, which is 44.7% more than at 30 °C. The MB release rates considerably increased when the pH dropped from 12 to 8, showing that the lower pH had a major impact on the release of MB from the hydrogel. Only 19% of the MB was released at pH 12 after 50 min, and after that, the release rate remained nearly constant. At higher fluid temperatures, the hydrogels lost approximately 80% of their water in just 20 min, compared to a loss of 50% of their water at room temperature. The outcomes of this study may contribute to further developments in artificial organ design. [ABSTRACT FROM AUTHOR]

The present study reports the implementation of novel nanoplatelets-based vanadium pent oxide (V2O5)-xerogel for the application of conjugate cooling in densely packed electronic devices. An integrated heat sink is made up of copper with a channel width of 490 µm and is shrink-fitted into aluminium block that acts as a heat spreader. V2O5-xerogel is synthesized by melt quenching process and characterized based on field emission scanning electron microscope, transmission electron microscope, and X-ray diffraction to analyse the surface morphology of the particles. Studies related to the stability of the nanofluids for different concentrations are discussed in this paper. Furthermore, a study on the effect of pulsating flow in microchannel is performed for different flow rates. As a result, a maximum enhancement of 17% in heat transfer coefficient was observed for the concentration of 0.4 mass% with a flow rate of 200 mL min-1 compared to a pure fluid. Finally, the results reveal that the xerogel is a potential working fluid for heat transfer applications involving microscale devices. [ABSTRACT FROM AUTHOR]

Tumorigenesis, which involves the uncontrolled proliferation and differentiation of cells, has been observed to imitate a variety of pathways vital to embryonic development, motivating cancer researchers to explore the genetic origins of these pathways. The pluripotency gene regulatory network is an established collection of genes that induces stemness in embryonic cells. Dysregulation in the expression genes of the pluripotency gene networks including OCT4, SOX2, NANOG and REX1 have been implicated in tumor development, and have been observed to result in poorer patient outcomes. The p53 pathway is a highly important regulatory process in a multitude of cell types, including embryonic, and the tumor suppressor gene TP53 is widely regarded as being one of the most important genes involved in tumorigenesis. Dysregulations in TP53 expression, along with altered expression of developmentally originating p53 regulators such as MDM2 and MDM4 have been implicated in various cancers, leading to poorer prognosis. Epithelial–mesenchymal transition (EMT), the process allowing epithelial cells to undergo biochemical changes to mesenchymal phenotypes, also plays a vital role in the fate of both embryonic and neoplastic cells. Genes that regulate EMT such as Twist1, SOX9 and REX1 have been associated with an increased occurrence of EMT in cancer cells, leading to enhanced cell stemness, proliferation and metastasis. The class of RNA that does not encode for proteins, known as non-coding RNA, has been implicated in a variety of cellular processes and emerging research has shown that its dysregulation can lead to uncontrolled cell proliferation and differentiation. Genes that have been shown to play a role in this dysregulation include PIWIL1, LIN28A and LIN28B, and have been associated with poorer patient outcomes and more aggressive cancer subtypes. The identification of these developmentally regulated genes in tumorigenesis has proved to play an advantageous role in cancer diagnosis and prognosis, and has provided researchers with a multitude of new target mechanisms for novel chemotherapeutic research. [ABSTRACT FROM AUTHOR]

Background: Humans are social beings. Older adults more commonly endorse social engagement than physical health when describing successful aging. Deficits in social support have been associated with a wide variety of adverse health outcomes in older age, ranging from physical health to depression and self-harm. In this study, we attempt to identify the relative contributions of subjective social isolation (loneliness) and objective social isolation, measured as support network type, to depression and well-being among the community-dwelling elderly. Therefore, the objective of the study was to estimate the prevalence of loneliness and depression and to know the relationship between social network type, loneliness, and depression among the community-dwelling elderly. Subjects and Methods: A cross-sectional study was done for a period of 6 months. Individuals aged 60 years and above were included and severely ill and bed-ridden patients were excluded from the study. Sampling method used was population proportion to size with sample size of 290. The participants were interviewed using a semistructured questionnaire, where demographic and personal data and social network pattern were collected. Depression was assessed using the Geriatric Depression Scale. Data were analyzed using Statistical Package for the Social Sciences Software, 22.0 version. Descriptive statistics like percentage, mean, and standard deviation were applied. Inferential statistical tests such as the Chi-square test were applied to find out the association and expressed it as statistically significant at a P value < 0.05. Results: Among the study participants, 44.3% were lonely, 19.4% felt hopeless, and only 38% felt satisfaction in life and happiness. "Suggestive Depression" was seen among 48.6% and "Persistent Depressive Mood" was seen in about 20.2% of participants. Loneliness explained the excess risk of depression in the widowed. Similarly, 38.2% had a nonintegrated social network and 32% had integrated social network who also reported being lonely. Conclusion: Loneliness and social networks both independently affect mood and well-being in the elderly, underlying a very significant proportion of depressed mood. [ABSTRACT FROM AUTHOR]

This paper proposes a life test method and a model to predict the time to failure of LED drivers with electrolytic capacitors at the output stage that experience cycled power/thermal conditions. Based on failure rate estimation methods and field studies, degradation of aluminum electrolytic capacitors can be considered a potential point of failure in LED drivers and other power electronic applications. It is essential to identify failure modes, causes, and precursors of failure of electrolytic capacitors to design reliable power electronic circuits and estimate the useful lifetime of the designed drivers for a given application. LED drivers are exposed to elevated temperatures, on-off switching, and cycled thermal conditions like other power electronic converters. Past studies have investigated the parametric degradation of electrolytic capacitors under constant thermal stresses but not under cycled thermal conditions commonly found in lighting applications. Therefore, temperature and thermal cycling were selected as acceleration factors to study the effects of power/thermal cycling on the life of electrolytic capacitors in LED drivers. The accelerated life test showed that the LED driver's useful life had an inverse exponential relationship to the operating temperature of the output capacitor. The thermally cycled conditions did not indicate additional failure mechanisms introduced due to thermal cycling within the tested temperature range. Based on the experimental results, we developed a mathematical modeling technique to estimate the time to failure of LED drivers due to the electrolytic capacitor's parametric degradation with different operating profiles. • Electrolyte evaporation is the main failure mechanism in LED driver electrolytic capacitors. • Cycled power/thermal impacts on capacitor life in circuits lack extensive prior research. • Studied effects of power/thermal cycling on LED driver output and overall lifespan. • Proposed a life test method for predicting LED driver capacitor failures under thermal cycling. • Developed a method to estimate failure time from capacitor degradation under various profiles. [ABSTRACT FROM AUTHOR]

Objective The objective was to ascertain factors among deliveries complicated by shoulder dystocia (SD) and neonatal brachial plexus palsy (NBPP). Methods At 11 hospitals, deliveries complicated by SD were identified. The inclusion criteria were vaginal delivery of non-anomalous, singleton at 34–42 weeks. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated. Receiver operating characteristic (ROC) curves were created to evaluate the predictive value of the models for NBPP. Results Of the 62,939 individuals who delivered vaginally, 1,134 (1.8%) had SD and met other inclusion criteria. Among the analytic cohort, 74 (6.5%) had NBPP. The factor known before delivery which was associated with NBPP was diabetes (aOR = 3.87; 95% CI = 2.13–7.01). After delivery, the three factors associated with NBPP were: (1) birthweight of at least 4000 g (aOR = 1.83; 95% CI = 1.05–3.20); (2) calling for help during the SD (aOR = 4.09, 95% CI = 2.29–7.30), and (3) the duration of SD ≥120 sec (aOR = 2.47, 95% CI = 1.30–4.69). The AUC under the ROC curve for these independent factors was 0.79 (95% CI = 0.77 − 0.82). Conclusions Few factors were identified that were associated with NBPP after SD, but they could not reliably predict which neonates will experience the complication. [ABSTRACT FROM AUTHOR]