Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Lactate Dehydrogenase in Identifying Relapse for Patients With Stage I Testicular Cancer on Surveillance

Purpose: Tumor markers alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase assume a key role in the management of testicular germ cell tumors. While alpha-fetoprotein and human chorionic gonadotropin have modest sensitivity and specificity for germ cell tumors, lactate dehydrogenase has weak sensitivity and specificity. We explored the utility of lactate dehydrogenase in identifying relapse among stage I seminomatous and nonseminomatous germ cell tumors on surveillance. Materials and Methods: Patients with a history of stage I testicular germ cell tumors were identified from a prospectively maintained database at the Princess Margaret Cancer Centre from December 1980 to May 2021 and surveyed according to established institutional algorithm guidelines. The utility of lactate dehydrogenase elevation to independently detect germ cell tumor relapse was examined. Results: Among 1,014 seminoma and 676 nonseminomatous germ cell tumor patients, 176 and 176 patients relapsed with a median time to relapse of 13.6 and 8.9 months, respectively. Imaging alone was the most common mode of relapse detection in 144 and 74 of seminoma and nonseminomatous germ cell tumor patients, respectively. Lactate dehydrogenase was elevated in 49 cases of seminoma and 38 cases of nonseminomatous germ cell tumors at relapse, but was never the sole relapse indicator. Among 350 seminoma and 311 nonseminomatous germ cell tumor patients who never relapsed, 210 and 233, respectively, had at least 1 elevated lactate dehydrogenase value. Conclusions: Lactate dehydrogenase alone did not independently contribute to early relapse detection in stage I seminoma or nonseminomatous germ cell tumor. Elevated lactate dehydrogenase values were documented in a high proportion of nonrelapsing seminoma and nonseminomatous germ cell tumor cases.
Endothelial cell polarity and extracellular matrix composition require functional ATP6AP2 during developmental and pathological angiogenesis

The (Pro)renin receptor ([P]RR), also known as ATP6AP2, is a single-transmembrane protein that is implicated in a multitude of biological processes. However, the exact role of ATP6AP2 during blood vessel development remains largely undefined. Here, we use an inducible endothelial cell–specific (EC-specific) Atp6ap2-KO mouse model to investigate the role of ATP6AP2 during both physiological and pathological angiogenesis in vivo. We observed that postnatal deletion of Atp6ap2 in ECs results in cell migration defects, loss of tip cell polarity, and subsequent impairment of retinal angiogenesis. In vitro, Atp6ap2-deficient ECs similarly displayed reduced cell migration, impaired sprouting, and defective cell polarity. Transcriptional profiling of ECs isolated from Atp6ap2 mutant mice further indicated regulatory roles in angiogenesis, cell migration, and extracellular matrix composition. Mechanistically, we provided evidence that expression of various extracellular matrix components is controlled by ATP6AP2 via the ERK pathway. Furthermore, Atp6ap2-deficient retinas exhibited reduced revascularization in an oxygen-induced retinopathy model. Collectively, our results demonstrate a critical role of ATP6AP2 as a regulator of developmental and pathological angiogenesis.
C1-inhibitor influence on platelet activation by thrombin receptors agonists

Introduction Protease activated receptors 1 (PAR1) and 4 (PAR4) agonists are used to study platelet activation. Data on platelet activation are extrapolated across experimental settings. C1-inhibitor (C1INH) is a protease inhibitor present in plasma but not in isolated platelet suspensions. Here we show that C1INH affects platelet activation through PAR1 and PAR4 agonists. Methods Platelets were isolated from healthy donor whole blood and then labeled with anti-CD62P and PAC1 antibodies. The platelet suspensions were exposed to PAR1 agonists SFLLRN, TFLLR and TFLLRN; PAR4 agonists AYPGKF and GYPGQV; ADP and thrombin. Flow-cytometric measurements were performed in 5, 10 and 15 min after activation. Results 0.25 mg/ml C1INH addition made platelets to faster expose CD62P and glycoprotein IIb/IIIa complex after activation with PAR1 agonists. Conversely, C1INH addition led to inhibition of platelet activation with PAR4 agonists and thrombin. Activation with ADP was not affected by C1INH. Conclusions Our results suggest that C1INH can modify platelet activation in the presence of synthetic PAR agonists used in platelet research. These observations may be relevant to the development of new methods to assess platelet function.
American Cochlear Implant Alliance Task Force Guidelines for Clinical Assessment and Management of Adult Cochlear Implantation for Single-Sided Deafness

The indications for cochlear implantation have expanded to include individuals with profound sensorineural hearing loss in the impaired ear and normal hearing (NH) in the contralateral ear, known as single-sided deafness (SSD). There are additional considerations for the clinical assessment and management of adult cochlear implant candidates and recipients with SSD as compared to conventional cochlear implant candidates with bilateral moderate to profound sensorineural hearing loss. The present report reviews the current evidence relevant to the assessment and management of adults with SSD. A systematic review was also conducted on published studies that investigated outcomes of cochlear implant use on measures of speech recognition in quiet and noise, sound source localization, tinnitus perception, and quality of life for this patient population. Expert consensus and systematic review of the current literature were combined to provide guidance for the clinical assessment and management of adults with SSD.
Acute Effects of a Haptic Anchor System on Postural Sway of Individuals with Parkinson’s Disease: A Preliminary Study

Some investigators have demonstrated that an anchor system can improve postural control in elderly persons during balance tasks, but none have reported on the use of this approach in individuals with Parkinson’s disease (PD). Therefore, we aimed to evaluate the effect of an anchor system on postural sway in elderly individuals with (n = 13) and without (n = 14) PD. In this cross-sectional study, we measured postural sway with a force platform based on the Clinical Test of Sensory Interaction of Balance (CTSIB). We calculated center of pressure (COP) parameters, as a function of time, based on the ellipse sway area (cm2) and evaluated self-efficacy for postural control based on the degree of difficulty in each task. With the anchor system (i.e., handheld ropes attached to weights on the floor), we observed a significant reduction in the ellipse sway area in the semi-tandem position among individuals with PD (p = .04). For participants without PD, there was no significant difference in sway with or without the anchor system in all positions. Also, for participants with PD, there was an improvement in self-efficacy for postural control associated with the anchor system in several positions while there was only a self-efficacy improvement with the anchor system in the semi-tandem position for those without PD. Acute use of a haptic anchor system reduced postural sway in the semi-tandem position in individuals with PD, and the anchor system generally improved postural control self-efficacy for body sway in individuals with PD.
Satellite glia modulate sympathetic neuron survival, activity, and autonomic function

Satellite glia are the major glial cells in sympathetic ganglia, enveloping neuronal cell bodies. Despite this intimate association, the extent to which sympathetic functions are influenced by satellite glia in vivo remains unclear. Here, we show that satellite glia are critical for metabolism, survival, and activity of sympathetic neurons and modulate autonomic behaviors in mice. Adult ablation of satellite glia results in impaired mTOR signaling, soma atrophy, reduced noradrenergic enzymes, and loss of sympathetic neurons. However, persisting neurons have elevated activity, and satellite glia-ablated mice show increased pupil dilation and heart rate, indicative of enhanced sympathetic tone. Satellite glia-specific deletion of Kir4.1, an inward-rectifying potassium channel, largely recapitulates the cellular defects observed in glia-ablated mice, suggesting that satellite glia act in part via K+-dependent mechanisms. These findings highlight neuron–satellite glia as functional units in regulating sympathetic output, with implications for disorders linked to sympathetic hyper-activity such as cardiovascular disease and hypertension.
Value of security: modeling time-dependent phenomena and weather conditions

Deterministic security criteria provide a degree of security that may be insufficient under some operating conditions and excessive for others. To determine an appropriate level of security, one should perform a probabilistic cost/benefit analysis that balances the cost of the security margin against its benefits, i.e. the expected societal cost of the avoided outages. This paper shows how a previously published method based on Monte Carlo simulation can be enhanced to take into account time-dependent phenomena such a cascade tripping of elements due to overloads, malfunction of the protection system and potential power system instabilities. In addition, the importance of using failure rates that reflect the weather conditions is discussed. Studies based on the south-western part of the transmission network of England and Wales demonstrate the validity of the models that have been developed.
Spatial–temporal pattern of propagation in amyotrophic lateral sclerosis and effect on survival: A cohort study

Clarification of propagation patterns in amyotrophic lateral sclerosis (ALS) is challenging, but understanding these has implications for individual prognostication and clinical trial design. However, systematic knowledge in this area is lacking. The aim of this study was to characterize the spatial and temporal features of propagation patterns in ALS, and to evaluate the association between propagation patterns and survival.
Multiple potential strategies for the application of nisin and derivatives

Abstract Nisin is a naturally occurring bioactive small peptide produced by Lactococcus lactis subsp. lactis and belongs to the Type A (I) lantibiotics. Due to its potent antimicrobial activity, it has been broadly employed to preserve various food materials as well as to combat a variety of microbial pathogens. The present review discusses the antimicrobial properties of nisin and different types of their derivatives employed to treat microbial pathogens with a detailed underlying mechanism of action. Several alternative strategies such as combination, conjugation, and nanoformulations have been discussed in order to address several issues such as rapid degradation, instability, and reduced activity due to the various environmental factors that arise in the applications of nisin. Furthermore, the evolutionary relationship of many nisin genes from different nisin-producing bacterial species has been investigated. A detailed description of the natural and bioengineered nisin variants, as well as the underlying action mechanisms, has also been provided. The chemistry used to apply nisin in conjugation with natural or synthetic compounds as a synergetic mode of antimicrobial action has also been thoroughly discussed. The current review will be useful in learning about recent and past research that has been performed on nisin and its derivatives as antimicrobial agents.
Exploiting breakdown in nonhost effector–target interactions to boost host disease resistance

Significance Plant nonhost resistance (NHR) prevents infection by all members of most microbial species, but its molecular mechanisms are not well understood. We found that effector proteins from the potato blight pathogen Phytophthora infestans, which enhance infection in host plants, fail to enhance susceptibility in nonhost Arabidopsis. These P. infestans effectors often failed to interact with Arabidopsis orthologs of their potato target proteins, whereas many interactions were detected between these Arabidopsis orthologs and effectors from its adapted pathogen Hyaloperonospora arabidopsidis. Thus, breakdown in effector–target interactions in distantly related nonhost plants is likely a key component of NHR. Importantly, we demonstrate that exploiting this breakdown and expressing nonhost target orthologs in host plants provide a strategy to prevent crop disease.
Effects of plant growth retardant daminozide (Alar) on neuromuscular co-ordination behavior in Drosophila melanogaster

ABSTRACT Daminozide (alar), a plant growth retardant, is used in different fruit orchard to make fruits attractive and reduce pre-harvest losses. Previously data demonstrated that acute daminozide exposure affected reproductive fitness and produced neurodegeneration in Drosophila melanogaster. The goal of this study was to determine whether continuous exposure to daminozide affects neuromuscular co-ordination in D. melanogaster as manifested in various behavioral responses. Fruit flies were exposed to 200 or 400 mg/L concentration of daminozide for two successive generations. Treated D. melanogaster were examined for the behaviors indicative of neuromuscular coordination and cognitive abilities, that include climbing, social interaction, adult grooming, migration, flight, male aggression, and adult courtship. Aberrant behavioral responses were noted among treated D. melanogaster of both sexes as evidenced by the following parameters: reduction in flight duration, abnormal social interaction, altered copulatory acts, and over-aggressiveness. Data suggest that daminozide produces impairment in neuromuscular coordination and cognitive ability in Drosophila, which was reflected as altered behavioral patterns. As Drosophila is considered as a reliable in vivo model utilized in toxicity testing, our findings may help us to anticipate and monitor potential daminozide-induced toxicity in animals and humans.
Does Sleep Quality Influence Recovery Outcomes After Postconcussive Injury in Children and Adolescents?

Objective: To determine whether objective parameters of sleep quality differ throughout recovery between children and adolescents who experienced an early return to school (RTS) and those who had a delayed RTS or did not return at all during the study period. Setting: Sleep parameters reflective of sleep quality were evaluated in participants' natural sleeping habitat throughout 9 weeks postinjury. Participants: Ninety-four children and adolescents (aged 5-18 years) with diagnosed concussion. Design: Prospective cohort. Participants followed RTS protocols. Main Measures: Actigraphy-derived estimates of total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), average arousal length (AAL), and number of arousals (NOAs) per hour were assessed. The length of time from injury until RTS was determined for each participant. Participants were categorized into an early RTS or delayed RTS group based on their time to RTS. Results: Both TST and SE were significantly greater in the early RTS group. WASO duration, AAL, and NOAs were significantly greater in the delayed RTS group. Differences between RTS groups were most apparent during weeks 1 to 5 postinjury. Conclusions and Clinical Implications: Participants who returned to school earlier had significantly better objective sleep quality than participants who experienced a delayed RTS. This study provides evidence in support of a relationship between sleep quality and time to RTS in children and adolescents with concussion. Considering early monitoring of sleep, education regarding sleep hygiene, and access to age-appropriate sleep interventions may be helpful in pediatric concussion recovery.
A Functional Region Decomposition Method to Enhance fNIRS Classification of Mental States

Functional near-infrared spectroscopy (fNIRS) classification of mental states is of important significance in many neuroscience and clinical applications. Existing classification algorithms use all signal-collected brain regions as a whole, and brain sub-region contributions have not been well investigated. This paper proposes a functional region decomposition (FRD) method to incorporate brain sub-region contributions and enhance fNIRS classification of mental states. Specifically, the method iteratively decomposes the brain region into multiple sub-regions to maximize their contributions with respect to the validation accuracy and coverage of brain sub-regions. Then for the fNIRS data in brain sub-regions, features are extracted and classified to output the predictions. The final predictions are determined by fusing predictions from multiple brain sub-regions with stacking. Experiments on a publicly available fNIRS dataset showed that the proposed functional region decomposition method led to 9.01% and 10.58% increase of classification accuracy for the methods related to slope-based features and mean concentration change features, respectively. Therefore, the proposed method can decompose the brain region into sub-regions with respect to their functional contributions and fundamentally enhance the performance of mental state classification.
Aquibacillus saliphilus sp. nov., a moderately halophilic bacterium isolated from a grey saltern.

A novel moderately halophilic bacterium, designated strain KHM2T, was isolated from the sediment of a grey solar saltern located on Sinui Island, Shinan, Republic of Korea. Cells were rod-shaped, endospore-forming, Gram-stain-positive, motile and facultative anaerobic. Strain KHM2T performed anaerobic respiration using nitrates and did not produce glucose acids, indicating the absence of fermentation. Strain KHM2T grew at 10-45 °C (optimum, 37 °C), pH 6.0-10.0 (optimum, pH 8.0) and with 1.0-20.0 % (w/v) NaCl (optimum, 10.0%). Based on 16S rRNA gene sequence similarity and chemotaxonomic properties, strain KHM2T was assigned to the genus Aquibacillus, with high 16S rRNA gene sequence similarity to Aquibacillus halophilus B6BT (98.2%) and less than 96.8 % similarity to the other recognized members of the genus Aquibacillus. The polar lipid profile consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG) and one unidentified phospholipid (PL). Major fatty acids were anteiso-C15 : 0 and anteiso-C17 : 0. The average nucleotide identity and digital DNA-DNA hybridization values of strain KHM2T with A. halophilus B6BT were 77.6 and 22.0 %, respectively. Based on the results of polyphasic analysis, strain KHM2T is proposed to represent a bacterial species within the genus Aquibacillus with the name Aquibacillus saliphilus sp. nov. The type strain is KHM2T (=KACC 19068T=NBRC 112577T).
Nucleotide excision repair removes thymidine analog 5-ethynyl-2′-deoxyuridine from the mammalian genome

Significance We discovered that the thymidine analog EdU, which is widely used in the analysis of DNA replication, DNA repair, and cell proliferation, is processed as “damage” in the human genome by the nucleotide excision repair system. EdU is unique in inducing DNA strand break and cell death of transformed cell lines. Our finding that EdU in DNA is processed in human cells as damage by nucleotide excision repair raises the possibility that such reaction causes a futile cycle of excision and reincorporation into the repair patch, leading to eventual cell death. Such a futile cycle leading to apoptosis makes EdU a potential candidate for the treatment of glioblastomas without serious side effects on postmitotic normal neural cells of the brain.
A weakened AMOC may prolong greenhouse gas–induced Mediterranean drying even with significant and rapid climate change mitigation

Significance The Mediterranean is a projected hot spot for climate change, with significant warming and rainfall reductions. We use climate model ensembles to explore whether these Mediterranean rainfall declines could be reversed in response to greenhouse gas reductions. While the summer Mediterranean rainfall decline is reversed, winter rainfall continues to decline. The continued decline results from prolonged weakening of Atlantic Ocean poleward heat transport that combines with greenhouse gas reductions to cool the subpolar North Atlantic, inducing atmospheric circulation changes that favor continued Mediterranean drying. This is a potential “surprise” in the climate system, whereby changes in one component (Atlantic Ocean circulation) alter how another component (Mediterranean rainfall) responds to greenhouse gas reductions. Such surprises could complicate climate change mitigation efforts.
Introduction to Early Universe Cosmology

Observational cosmology is in its "golden age" with a vast amount of recent data on the distribution of matter and light in the universe. This data can be used to probe theories of the very early universe. It is small amplitude cosmological fluctuations which encode the information about the very early universe and relate it to current data. Hence, a central topic in these lectures is the "theory of cosmological perturbations", the theory which describes the generation of inhomogeneities in the very early universe and their evolution until the current time. I will apply this theory to three classes of models of the very early universe. The first is "Inflationary Cosmology", the current paradigm for understanding the early evolution of the universe. I will review the successes of inflationary cosmology, but will also focus on some conceptual challenges which inflationary cosmology is facing, challenges which motivate the search for possible alternatives. I will introduce two alternative scenarios, the "Matter Bounce" model and "String Gas Cosmology", and I will discuss how cosmological fluctuations which can explain the current data are generated in those models.
Serotonergic mechanisms associated with experimental models of hypoxia: A systematic review

The aim of this systematic review was to explore and discuss the literature concerning the effects of hypoxia or anoxia during the perinatal period on the serotoninergic network in rodents, through mechanisms that lead to changes in serotonergic neurons, levels, segments of central nervous system affected, 5‐HT transporter, and 5‐HT receptor.
Contribution of keratinocytes to dermal fibrosis

Purpose of review The cellular pathogenesis of fibrotic disorders including systemic sclerosis (SSc) remains largely speculative. Currently, the altered function of endothelial cells and fibroblasts under the influence of an inappropriate immune response are considered central pathogenic events in SSc. Adding to this complexity, novel evidence here reviewed suggests that keratinocytes may concur in the development of skin fibrosis. Recent findings Epidermal equivalents (EE) generated from primary SSc keratinocytes display a distinct gene expression program when compared to healthy donor (HD) EE. SSc-EE, among others, exhibited enhanced oxidative and metabolic response pathways. Immunohistochemical studies demonstrated similarities between SSc-EE and SSc epidermis including altered keratinocyte differentiation, enhanced expression of activation markers, and reduced rate of basal keratinocytes proliferation. SSc-EE supernatants more than HD-EE modified the inflammatory and extracellular matrix deposition/resorption program of dermal fibroblasts. Further evidence indicated that the relative lack rather than the excess of interleukin-25 in keratinocytes may contribute to enhanced dermal fibrotic changes. Overall, these data support keratinocyte-intrinsic SSc-related modifications. Summary Improved methods for engineering epidermal and skin equivalents are helping to address the question whether keratinocyte alterations in SSc are primary and capable to dysregulate dermal homeostasis or secondary following dermal fibrotic changes.