Miracle-dz/UniFAR-FTUs huggingface dataset:
Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-Term Results of the Randomized Phase III APBI-IMRT-Florence Trial.

PURPOSE To report the long-term results of external-beam accelerated partial-breast irradiation (APBI) intensity-modulated radiation therapy (IMRT) Florence phase III trial comparing whole-breast irradiation (WBI) to APBI in early-stage breast cancer. PATIENTS AND METHODS The primary end point was to determine the 5-year difference in ipsilateral breast tumor recurrence (IBTR) between 30 Gy in 5 once-daily fractions (APBI arm) and 50 Gy in 25 fractions with a tumor bed boost (WBI arm) after breast-conserving surgery. RESULTS Five hundred twenty patients, more than 90% of whom had characteristics associated with low recurrence risk, were randomly assigned (WBI, n = 260; APBI, n = 260) between 2005 and 2013. Median follow-up was 10.7 years. The 10-year cumulative incidence of IBTR was 2.5% (n = 6) in the WBI and 3.7% (n = 9) in the APBI arm (hazard ratio [HR], 1.56; 95% CI, 0.55 to 4.37; P = .40). Overall survival at 10 years was 91.9% in both arms (HR, 0.95; 95% CI, 0.50 to 1.79; P = .86). Breast cancer-specific survival at 10 years was 96.7% in the WBI and 97.8% in the APBI arm (HR, 0.65; 95% CI, 0.21 to 1.99; P = .45). The APBI arm showed significantly less acute toxicity (P = .0001) and late toxicity (P = .0001) and improved cosmetic outcome as evaluated by both physician (P = .0001) and patient (P = .0001). CONCLUSION The 10-year cumulative IBTR incidence in early breast cancer treated with external APBI using IMRT technique in 5 once-daily fractions is low and not different from that after WBI. Acute and late treatment-related toxicity and cosmesis outcomes were significantly in favor of APBI.
Caregiver burden in familial caregivers and foreign domestic workers of patients with traumatic brain injury in a multi-ethnic Asian population

ABSTRACT Objective The purpose of this study was to investigate the prevalence and risk factors associated with caregiver burden in familial caregivers and foreign domestic workers of patients with severe traumatic brain injury. Methods A total of 77 caregivers were consecutively recruited, who were either familial caregivers or foreign domestic workers. All caregivers were evaluated with the Zarit Burden Index (ZBI), Patient Health Questionnaire-9 (PHQ-9), and General Anxiety Disorder 7-item (GAD-7) scale. Logistic regression analysis was conducted to determine factors associated with caregiver burden. Results The majority of participants were familial caregivers (N = 60), of which 70% experienced significant caregiver burden. In this group, 10.0% caregivers had clinically significant depression and 16.7% caregivers who had clinically significant anxiety. On multivariate analysis, factors found to be associated with caregiver burden were Glasgow Outcome Scale Extended (GOSE) of <7, presence of neuropsychiatric complications, and presence of anxiety. There was also a high prevalence of caregiver burden in foreign domestic workers (29.4%). Conclusion There is a high rate of caregiver burden in both familial caregivers and foreign domestic workers who care for patients with severe traumatic brain injury. Caregivers experiencing stress should also be monitored for the presence of anxiety or depression.
There and Back Again: Leptin Actions in White Adipose Tissue

Leptin is a hormone discovered almost 30 years ago with important implications in metabolism. It is primarily produced by white adipose tissue (WAT) in proportion to the amount of fat. The discovery of leptin was a turning point for two principle reasons: on one hand, it generated promising expectations for the treatment of the obesity, and on the other, it changed the classical concept that white adipose tissue was simply an inert storage organ. Thus, adipocytes in WAT produce the majority of leptin and, although its primary role is the regulation of fat stores by controlling lipolysis and lipogenesis, this hormone also has implications in other physiological processes within WAT, such as apoptosis, browning and inflammation. Although a massive number of questions related to leptin actions have been answered, the necessity for further clarification facilitates constantly renewing interest in this hormone and its pathways. In this review, leptin actions in white adipose tissue will be summarized in the context of obesity.
Overwintering survivorship and growth of young-of-the-year black sea bass Centropristis striata

Overwintering conditions have long been known to affect fish survival and year-class strength as well as determine the poleward range limit of many temperate fishes. Despite this known importance, mechanisms controlling overwintering mortality are poorly understood and the tolerance of marine fishes to the combined effects of winter temperature, salinity, and size is rarely quantified. In recent years, higher abundances of the temperate Serranid, black sea bass Centropristis striata, have been observed at latitudes further north than their traditional range suggesting that warming water temperatures, particularly during winter, may be facilitating the establishment of a population at more northern latitudes. To examine overwintering survival of C. striata, the combined effects of temperature, salinity and body mass were quantified in laboratory experiments. We identified 6°C as the lower incipient lethal temperature for C. striata, below which fish cease feeding, lose weight rapidly and die within 32 days. A short cold exposure experiment indicated that temperatures below 5°C resulted in mortality events that continued even as the temperature increased slowly to 10°C, indicating that even short cold snaps can impact survival and recruitment in this species. Importantly, fish in lower salinity lived significantly longer than fish at higher salinity at both 3°C and 5°C, suggesting that osmoregulatory stress plays a role in overwintering mortality in this species. Size was not a critical factor in determining overwintering survival of young-of-the-year (YOY) C. striata. Overwintering survival of YOY C. striata can be effectively predicted as a function of temperature and salinity and their interaction with an accelerated failure model to project future range limits. Identifying temperature thresholds may be a tractable way to incorporate environmental factors into population models and stock assessment models in fishes.
Impact of Aging and the Electrode-to-Neural Interface on Temporal Processing Ability in Cochlear-Implant Users: Amplitude-Modulation Detection Thresholds

Although cochlear implants (CIs) are a viable treatment option for severe hearing loss in adults of any age, older adults may be at a disadvantage compared with younger adults. CIs deliver signals that contain limited spectral information, requiring CI users to attend to the temporal information within the signal to recognize speech. Older adults are susceptible to acquiring auditory temporal processing deficits, presenting a potential age-related limitation for recognizing speech signals delivered by CIs. The goal of this study was to measure auditory temporal processing ability via amplitude-modulation (AM) detection as a function of age in CI users. The contribution of the electrode-to-neural interface, in addition to age, was estimated using electrically evoked compound action potential (ECAP) amplitude growth functions. Within each participant, two electrodes were selected: one with the steepest ECAP slope and one with the shallowest ECAP slope, in order to represent electrodes with varied estimates of the electrode-to-neural interface. Single-electrode AM detection thresholds were measured using direct stimulation at these two electrode locations. Results revealed that AM detection ability significantly declined as a function of chronological age. ECAP slope did not significantly impact AM detection, but ECAP slope decreased (became shallower) with increasing age, suggesting that factors influencing the electrode-to-neural interface change with age. Results demonstrated a significant negative impact of chronological age on auditory temporal processing. The locus of the age-related limitation (peripheral vs. central origin), however, is difficult to evaluate because the peripheral influence (ECAPs) was correlated with the central factor (age).
The BACH1/Nrf2 Axis in Brain in Down Syndrome and Transition to Alzheimer Disease-Like Neuropathology and Dementia

Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses. Published studies from our laboratories propose that increased oxidative damage occurs early in life in DS population and contributes to age-dependent neurodegeneration. This is the result of damaged, oxidized proteins that belong to degradative systems, antioxidant defense system, neuronal trafficking. and energy metabolism. This review focuses on a key element that regulates redox homeostasis, the transcription factor Nrf2, which is negatively regulated by BACH1, encoded on chromosome 21. The role of the Nrf2/BACH1 axis in DS is under investigation, and the effects of triplicated BACH1 on the transcriptional regulation of Nrf2 are still unknown. In this review, we discuss the physiological relevance of BACH1/Nrf2 signaling in the brain and how the dysfunction of this system affects the redox homeostasis in DS neurons and how this axis may contribute to the transition of DS into DS with AD neuropathology and dementia. Further, some of the evidence collected in AD regarding the potential contribution of BACH1 to neurodegeneration in DS are also discussed.
The Humanistic and Economic Impact of Vaginal Dryness in Premenopausal, Perimenopausal, and Postmenopausal Women.

Background: Vaginal dryness is a highly prevalent condition. Much of previous research has focused on postmenopausal women. The aim of this study was to evaluate the impact of vaginal dryness on a predominantly premenopausal sample of women. Methods: The study was conducted online. Participants with self-reported vaginal dryness completed the Work Productivity and Activity Impairment (WPAI) scale, and a generic quality-of-life instrument, the assessment of quality of life instrument (AQoL)-4D. Information regarding sociodemographics was also collected. National (United Kingdom) median age-specific weekly wages were used to derive the economic cost of vaginal dryness. Results: A total of 524 women completed the study. The average age was 40.18 years (range 18-70 years) and just under 62% of the sample was premenopausal. Around 40% of women reported severe or very severe vaginal dryness. The average AQoL-4D score was 0.584 (standard deviation [SD]: 0.286) and decreased in line with level of severity (p = 0.014). Quality of life was not related to either age (p = 0.14) or menopausal status (p = 0.055). Of those women in employment (n = 369), 16.5% (SD: 24.3%) of their working hours were lost due to vaginal dryness; work impairment level was 34.4% (SD: 31.8%). The average lost weekly wage was £67.82 (SD: £130.88). The estimated average loss to employers was £82.56 (SD: £109.38) with a total weekly loss of £31,622. Conclusions: This study has shown the significant impact vaginal dryness has on premenopausal and postmenopausal women in terms of quality of life and economic burden, as well as the potential cost of this condition to society.
Letter to the Editor: Metabolomics of Aqueous Humor in Diabetes Mellitus

We have read with great interest the article by Wang et al. entitled ‘‘Metabolomic profile of diabetic retinopathy: a GC-TOFMS-based approach using vitreous and aqueous humor. ’’ The authors identified novel metabolites and disturbed metabolic pathways. This is not the first article presenting the metabolic profiles of aqueous humor (AH), which are characteristic for diabetes mellitus. However, each of those studies identified different metabolic pathways as the most disturbed (Table 1), which might cause some confusion among the readers. We would like to explain these discrepancies and to demonstrate that they represent a characteristic feature of metabolomic studies, rather than a methodological error. The significance of prevention, treatment, and slowing down the progression of diabetic complications raises no doubts in the context of reducing health and economic burden. From an ophthalmological perspective, diabetic retinopathy should be considered a potentially blinding disease. In our article, we emphasized that diabetes might accelerate cataract development and increase complication rates after cataract surgeries. Metabolomic studies aim to identify the underlying mechanisms of disease. The composition of small molecules can be considered a chemical marker of a current phenotype.
Effect of Directional Microphone Technology in Hearing Aids on Neural Correlates of Listening and Memory Effort: An Electroencephalographic Study

The aim of the study was to compare the effect of different spatial noise-processing algorithms in hearing aids on listening effort and memory effort on a subjective, behavioral, and neurophysiological level using electroencephalography (EEG). Two types of directional microphone (DM) technologies for spatial noise processing were chosen: one with a wide directionality (wide DM) and another with a narrower directionality (narrow DM) to accentuate the speech source. Participants with a severe hearing loss were fitted with hearing aids and participated in two EEG experiments. In the first one, participants listened to sentences in cafeteria noise and were asked to rate the experienced listening effort. The second EEG experiment was a listening span task during which participants had to repeat sentence material and then recall the final words of the last four sentences. Subjective listening effort was lower with narrow than wide DM and EEG alpha power was reduced for the narrow DM. The results of the listening span task indicated a reduction in experienced memory effort and better memory performance. During the memory retention phase, EEG alpha level for the narrow relative to the wide DM was reduced. This effect was more pronounced during linguistically difficult sentences. This study extends previous findings, as it reveals a benefit for narrow DM in terms of cognitive performance and memory effort also on a neural level, and when speech intelligibility is almost 100%. Together, this indicates that a narrow and focused DM allows for a more efficient neurocognitive processing than a wide DM.
The Effect of Music and White Noise on Electroencephalographic (EEG) Functional Connectivity in Neonates in the Neonatal Intensive Care Unit

The purpose of this study is to investigate whether listening to music and white noise affects functional connectivity on scalp electroencephalography (EEG) in neonates in the neonatal intensive care unit. Nine neonates of ≥34 weeks’ gestational age, who were already undergoing clinical continuous EEG monitoring in the neonatal intensive care unit, listened to lullaby-like music and white noise for 1 hour each separated by a 2-hour interval of no intervention. EEG segments during periods of music, white noise, and no intervention were band-pass filtered as delta (0.5-4 Hz), theta (4-8 Hz), lower alpha (8-10 Hz), upper alpha (10-13 Hz), beta (13-30 Hz), and gamma (30-45 Hz). Synchronization likelihood was used as a measure of connectivity between any 2 electrodes. In theta, lower alpha, and upper alpha frequency bands, the synchronization likelihood values yielded statistical significance with sound (music, white noise and no intervention) and with edge (between any 2 electrodes) factors. In theta, lower alpha, and upper alpha frequency bands, statistical significance was obtained between music and white noise (t = 3.12, 3.32, and 3.68, respectively; P < .017), and between white noise and no intervention (t = 4.51, 3.09, and 2.95, respectively, P < .017). However, there was no difference between music and no intervention. Although limited by a small sample size and the 1-time only auditory intervention, these preliminary results demonstrate the feasibility of EEG connectivity analyses even at bedside in neonates on continuous EEG monitoring in the neonatal intensive care unit. They also point to the possibility of detecting significant changes in functional connectivity related to the theta and alpha bands using auditory interventions.
The role of Shh signalling pathway in central nervous system development and related diseases

Sonic hedgehog (Shh) plays important roles in developmental of vertebrate animal central nervous system (CNS), and Gli is its downstream signal molecule. Shh signalling is essential for pattern formation, cell‐fate specification, axon guidance, proliferation, survival and differentiation of neurons in CNS development. The abnormal signalling pathway of Shh leads to the occurrence of many nervous system diseases. The mechanism of Shh signalling is complex and remains incompletely understood. Nevertheless, studies have revealed that Shh signalling pathway is classified into canonical and non‐canonical pathways. Here we review the role of the Shh signalling pathway and its impact in CNS development and related diseases. Specifically, we discuss the role of Shh in the spinal cord and brain development, cell differentiation and proliferation in CNS and related diseases such as brain tumour, Parkinson's diseases, epilepsy, autism, depression and traumatic brain injury. We also highlight future directions of research that could help to clarify the mechanisms and consequences of Shh signalling in the process of CNS development and related diseases.
School-Level Efforts to Address Sexual Health and Risky Sexual Behavior Among Students in Texas Alternative High Schools

We compared sexual/reproductive health services and sexuality education topics provided in Texas alternative high schools (AHSs) with the prevalence of sexual risk behaviors among students in AHS. Using cross-sectional data from convenience samples of 14 principals, 14 lead health educators, and 515 students, we calculated descriptive statistics for 20 services and 15 sexuality education topics provided by AHSs and seven sexual risk behaviors among students in AHS. AHSs provided few sexual/reproductive health services and limited educational content, despite high levels of sexual risk taking among students. For example, no AHSs taught students about proper condom use, yet 84% of students have had sex. Findings provide preliminary evidence of unmet needs for school-based sexual/reproductive health services and comprehensive sexuality education in AHS settings. Future investigation with larger, representative samples is needed to assess the provision of sexual/reproductive health services and sexuality education in AHSs and monitor sexual risk behaviors in the AHS population.
Cell-specific expression of ENACα gene by FOXA1 in the glucocorticoid receptor pathway

Introduction: The glucocorticoid receptor (GR) is one of the most widely studied ligand-dependent nuclear receptors. The combination of transcriptional regulatory factors required for the expression of individual genes targeted by GR varies across cell types; however, the mechanisms underlying this cell type–specific regulation of gene expression are not yet clear. Methods: Here, we investigated genes regulated by GR in two different cell lines, A549 and ARPE-19, and examined how gene expression varied according to the effect of pioneer factors using RNA-seq and RT-qPCR. Results: Our RNA-seq results identified 19 and 63 genes regulated by GR that are ARPE-19-specific and A549-specific, respectively, suggesting that GR induces the expression of different sets of genes in a cell type–specific manner. RT-qPCR confirmed that the epithelial sodium channel (ENACα) gene is an ARPE-19 cell-specific GR target gene, whereas the FK506 binding protein 5 (FKBP5) gene was A549 cell-specific. There was a significant decrease in ENACα expression in FOXA1-deficient ARPE-19 cells, suggesting that FOXA1 might function as a pioneer factor enabling the selective expression of ENACα in ARPE-19 cells but not in A549 cells. Conclusion: These findings indicate that ENACα expression in ARPE-19 cells is regulated by FOXA1 and provide insights into the molecular mechanisms of cell type–specific expression of GR-regulated genes.
A randomised controlled comparison of video versus instructor-based compression only life support training

Background and Aims: Sudden cardiac deaths remain a major health problem worldwide. Most of these cases generally involve out of hospital cardiac arrest, making the role of bystander resuscitation very crucial. In the developing countries, illiteracy and scarcity of health professionals is a great barrier to cardiopulmonary resuscitation (CPR) training. Video-based CPR training can offer an easily accessible modality in these situations. Hence, this study was conducted with an aim to assess the efficacy of video-based training in comparison to the traditional instructor-based CPR training in layman. Methods: This prospective cross-over observational study included 109 undergraduate university students attending voluntary resuscitation training and were randomly divided into two groups of video-based demonstration (VBD) and instructor-based demonstration (IBD) of compression only life support (COLS). They were then assessed for psychomotor skill development (Laerdal Simpad Plus Q-CPR) and perception about the quality of training methodology as primary and secondary objectives, respectively. Results: Population characteristics were similar in both the groups. In the VBD, scene safety was performed by 95.2% and call for help by 97.6%, and by 76.1% each in the IBD group (P < 0.05). Response to compression time (RCT) was significantly shorter in VBD (35 ± 9 sec) as compared to IBD (54 ± 14 sec) (P < 0.001). However, the proportion of participants performing response check, correct site identification, and other parameters were comparable. Conclusion: Video-based COLS training significantly decreased the RCT by 35% compared to traditional instructor-based training. However, other features of high-quality CPR remain comparable.
Endophytic microbes: A novel source for biologically/pharmacologically active secondary metabolites

Endophytes, microorganisms that reside internal tissues of all plant species, are a proven source of novel organic natural molecules, presumed to emphasizing the frontiers of drug discovery. Next to the clinically acknowledged antineoplastic agent, taxol, endophyte research has yielded potential drug, given compounds with antimicrobial, antioxidant, antiviral, antidiabetic, anti-alzheimer's disease and immunosuppressant etc. These evidences arises a hope to combat incurable diseases, drug resistance, other challenges related to human health. The potential of finding new drugs that may be effective candidates for treating newly developing diseases in humans is great. This paper focuses particularly need for new useful compounds from endophytes, the recent role of new disease, recent scenario of screening approach for novel drug and their pharmacological interest. It also describes these compounds by different functions, including some examples that illustrate the potential for human use.