Miracle-dz/UniFAR-FTUs huggingface dataset:
H2S and reactive sulfur signaling at the host-bacterial pathogen interface

Bacterial pathogens that cause invasive disease in the vertebrate host must adapt to host efforts to cripple their viability. Major host insults are reactive oxygen and reactive nitrogen species as well as cellular stress induced by antibiotics. Hydrogen sulfide (H2S) is emerging as an important player in cytoprotection against these stressors, which may well be attributed to downstream more oxidized sulfur species termed reactive sulfur species (RSS). In this review, we summarize recent work that suggests that H2S/RSS impacts bacterial survival in infected cells and animals. We discuss the mechanisms of biogenesis and clearance of RSS in the context of a bacterial H2S/RSS homeostasis model and the bacterial transcriptional regulatory proteins that act as “sensors” of cellular RSS that maintain H2S/RSS homeostasis. In addition, we cover fluorescence imaging– and MS–based approaches used to detect and quantify RSS in bacterial cells. Last, we discuss proteome persulfidation (S-sulfuration) as a potential mediator of H2S/RSS signaling in bacteria in the context of the writer-reader-eraser paradigm, and progress toward ascribing regulatory significance to this widespread post-translational modification.
Gut sediments in a burrowing mayfly (Ephemeroptera, Hexagenia limbata): their contribution to animal trace element burdens, their removal, and the efficacy of a correction for their presence

Nymphs of the burrowing mayfly Hexagenia limbata were collected in the field, returned to the laboratory, and dissected to remove the gut contents. Concentrations of four trace elements (As, Cd, Cu, Zn) were determined both for the gut contents and for the body. Trace elements in gut contents represented up to 22% of whole animal trace element burdens. Studies of depuration of H. limbata nymphs held in water for up to 48 h indicate that individuals vary substantially in the rate at which they egest gut contents and that 48 h is not sufficient to ensure a complete emptying of the gut. A model developed to compensate for the presence of gut contents in the determination of body trace element burdens was applied to H. limbata. Comparisons of model estimates with actual body burdens (without gut contents) show that the model accurately predicts As and Cu concentrations, but overestimates concentrations of Cd and Zn by as much as 20%. We suggest that the biases in the model result from assuming that: (a) trace.
Evaluating the suitability of supra-POpeak verification trials after ramp-incremental exercise to confirm the attainment of maximum O2 uptake.

During exhaustive ramp-incremental cycling tests, the incidence of O2 uptake (V̇O2) plateaus is low. To verify the attainment of maximum V̇O2 (V̇O2max), it is recommended that a trial at a power output (PO) corresponding to 110% of the ramp-derived peak (POpeak) is performed. It remains unclear whether verification trials set at this PO can be tolerated for long enough to allow attainment of V̇O2max. Eleven recreationally-trained individuals performed five ramp tests of varying slope (5, 10, 15, 25, 30 W·min-1), each followed, in series, by two verification trials: the 1st at 110%POpeak of the 25 W·min-1 ramp and the 2nd at 110% POpeak attained in the preceding ramp test. Exercise duration of the 1st verification trial was on average 81±15 s (CV=9±3%) versus 162±32, 121±24, 103±15, and 73±10 s for the 2nd verification trials at 110% of POpeak of the 5, 10, 15, and 30 W·min-1 ramp tests, respectively (P<0.05). Compared to the highest V̇O2 recorded during ramp tests, V̇O2 from the subsequent verification trials were not different for the 5, 10, and 15 W·min-1 ramp tests (P>0.05), but lower for the 25 and 30 W·min-1 ramp tests (P<0.05). Verification trials at 110%POpeak of rapidly-incrementing ramp tests (i.e., 25 W·min-1) were not sustained for long enough to allow the attainment of V̇O2max. With commonly used rapidly-incrementing ramp tests engendering exhaustion within 8-12 min, verification trials
Regulation of Retinal Melanopsin on Lens-induced Myopia in Guinea Pigs.

SIGNIFICANCE Investigation of the mechanism and the role of melanopsin in lens-induced myopia is necessary to find out potential targets in the prevention of myopia development. PURPOSE We aimed to study the effect and mechanism of retinal melanopsin on lens-induced myopia in guinea pigs, as well as the interactions between melanopsin and other myopic regulation neurotransmitters such as dopamine and melatonin, and to explore the possible role of melanopsin in the prevention of myopia development. METHODS Twenty-day-old tricolor guinea pigs were randomly divided into four groups: control group, defocus group, defocus + AA92593 group, and defocus + dimethyl sulfoxide (DMSO) group. The defocus eyes wore -6.00 D lens. In the defocus + AA92593 group, the vitreous cavities were injected with melanopsin antagonist AA92593. In the defocus + DMSO group, the vitreous cavities were injected with 5% DMSO as the administration control. The expression of retinal melanopsin protein was measured with immunofluorescence staining and Western blot. The content of dopamine and melatonin in the retina was determined by the high-performance liquid chromatography electrochemical method. RESULTS Compared with the defocus group, intravitreal injection of AA92593 resulted in increased axial length of the defocus eyes (defocus, 8.05 ± 0.09 mm; defocus + AA92593, 8.15 ± 0.11 mm; P = .008), lower refractive degree (defocus, -1.98 ± 0.82 D; defocus + AA92593, -2.59 ± 0.97 D; P = .05), decreased relative expression of retinal melanopsin protein (defocus, 0.67 ± 0.11; defocus + AA92593, 0.20 ± 0.06; P < .0001), and increased melatonin content in the defocus eyes (defocus, 0.38 ± 0.09 ng/mg; defocus + AA92593, 0.55 ± 0.13 ng/mg; P = .01), but it had no obvious effect on dopamine content (defocus, 0.64 ± 0.18 ng/mg; defocus + AA9259, 0.61 ± 0.17 ng/mg; P > .99). The melatonin content of retina in the defocus + AA92593 group was correlated with refractive error (Pearson correlation coefficient = -0.68, P = .006) and eye axis length (Pearson correlation coefficient = 0.74, P = .02). CONCLUSIONS Retinal melanopsin has inhibitory effect on lens-induced myopia development in guinea pigs, and such effect may be related to retinal melatonin.
News Feature: Finding a vaccine for misinformation

With deliberate deception a growing threat online, social scientists are devising ways to fight back with “cognitive inoculations” In early March, after a wave of coronavirus cases struck a Muslim congregation in India, the hashtag #CoronaJihad went viral on Indian Twitter, and Islamophobic messages began to surge on social media. In one case, a false video showed purportedly Muslim men licking plates—allegedly to spread the novel coronavirus (COVID-19). In reality, these men belonged to a community that strongly discourages wasting food. No one knows who crafted these false messages, or why. But anti-Muslim attacks increased after their release. Hoping to fight an epidemic of misinformation, some researchers have demonstrated the promise of “inoculating” people with training videos and games even before those people are exposed to misinformation. Image credit: Dave Cutler (artist). It’s hardly an isolated example. Misinformation has been rife during the pandemic—ranging from rumors about the virus being an escaped bioweapon to specious reports of a miracle cure doctors won’t tell you about. Of course, this is only the latest flavor of fakery, which includes high-profile efforts such as climate-change denialism, antivaccine agitation (1), and Russian attempts to erode trust in the 2016 election. In every case, says Emma Spiro, a sociologist who is studying coronavirus misinformation at the University of Washington in Seattle, the risk is that “people may use the false information as the basis for decision making and actions that endanger themselves and others. ” Experts sometimes distinguish between mis information, which is simply wrong and may even be an honest mistake, and dis information, which is formulated with an intent to deceive. Whatever the name, stemming the onslaught can seem like a losing battle. Researchers, tech companies, journalists, and fact checkers have been trying to debunk misinformation for years. But researchers have found that this …
Risk of Breast Cancer Associated with Estrogen DNA Adduct Biomarker

Background: It is biologically plausible that genotoxic estrogens, namely estrogen DNA adducts (EDA), have a role in breast cancer development. Support comes from three prior studies that reported elevated concentrations of EDA relative to estrogen metabolites and conjugates (EDA:EMC) in women with breast cancer relative to control women. Methods: In postmenopausal women in the Women's Health Initiative (WHI), EDA:EMC in 191 controls was compared with findings in 194 prediagnosis urine samples from breast cancer cases. EDA:EMC determinations were by mass spectrometry as previously described, and logistic regression was employed to estimate ORs. Results: EDA:EMC did not differ in breast cancer cases compared with controls overall [0.93 (95% confidence interval, 0.71–1.23)], with a mean (SD) of 2.3 (0.8) and 2.4 (1.1) in cases and controls, respectively. Similarly, the ratio did not differ when examined by estrogen receptor or recency of biospecimen collection prior to breast cancer. Conclusions: Despite the demonstrated genotoxic properties of certain catechol estrogens resulting in EDAs, this analysis did not provide evidence for an increased breast cancer risk in relation to an elevated EDA:EMC. Impact: This analysis, conducted prospectively within postmenopausal women in the WHI study, suggests that a strong association between EDA:EMC and breast cancer could be ruled out, as this study was powered to detect an OR of 2.2 or greater.
Synthesis and Apoptotic Activities of New 2(3H)-benzoxazolone Derivatives in Breast Cancer Cells.

BACKGROUND 2(3H)-Benzoxazolone derivatives are preferential structural blocks in pharmacological probe designing with possibility of modifications at various positions on the core structure. Benzoxazolones showed various biological activities such as analgesics, anti-inflammatory and anti-cancer. OBJECTIVE In the present work, we have prepared new Mannich bases of 2(3H)-benzoxazolone derivatives and evaluated their cytotoxicities and proapoptotic properties in MCF-7 breast cancer cell line. METHODS The structures of these compounds were characterized by FT-IR, elemental analysis, 1H and 13C NMR. Cytotoxicities of all the target compounds were investigated by MTT assay. Apoptotic properties of compounds were evaluated by immunocytochemistry using antibodies against to caspase-3, cytochrome-c, FasL and TUNEL assay. RESULTS These two novel compounds, 1 and 2, both have the same piperazine substituent on the nitrogen atom of benzoxazolone and the main difference in the structures of these compounds is the presence of Cl substituent at the 5- position of the benzoxazolone ring. MTT results showed that compound 1 and 2 were effective in terms of reduction of cell viability at 100 µM and 50 µM concentration for 48 h, respectively. As a result of immunohistochemical staining, Fas L and caspase-3 immunoreactivities were significantly increased in MCF-7 cells after treated with compound 1. Additionally, caspase-3 and cytochrome-c immunoreactivities were also increased significantly in MCF-7 cells after treated with compound 2. The number of TUNEL positive cells was significantly higher in MCF-7 cells when compared with control group after treated with both compound 1 and 2. CONCLUSION It could be concluded that N-substituted benzoxazolone derivatives increase potential anti-cancer effects and they could be promising novel therapeutic agents for chemotherapy.
Basic Attributes Tests (BAT) System: Development of an Automated Test Battery for Pilot Selection: (520452006-001)

Abstract : In 1955, the Air Force discontinued apparatus-based testing as a component of its aircrew selection and classification system due to administrative problems. Since then, the Air force has relied on paper-and- pencil test batteries such as the Air Force Officer Qualifying Test to select pilot and navigator trainees. Although the aircrew selection system without apparatus testing has demonstrated a reliable relationship with pilot training outcome, concern with attrition rates in pilot training, along with the development of computer technology, produced a renewed interest in the utility of psychomotor testing. As a result, a computer-based testing system, the Basic Attributes Tests (BAT) system, was developed to assess psychomotor skills, as well as a variety of psychological and cognitive attributes that are believed to be related to flight training performance. The events leading up to the development of the BAT system and its hardware and software specifications are reviewed. A brief summary of validation studies of the various tests also is provided.
Clinician Perceptions of Timing and Presentation of Drug-Drug Interaction Alerts

Abstract Objective Alert presentation of clinical decision support recommendations is a common method for providing information; however, many alerts are overridden suggesting presentation design improvements can be made. This study attempts to assess pediatric prescriber information needs for drug–drug interactions (DDIs) alerts and to evaluate the optimal presentation timing and presentation in the medication ordering process. Methods Six case scenarios presented interactions between medications used in pediatric specialties of general medicine, infectious disease, cardiology, and neurology. Timing varied to include alert interruption at medication selection versus order submission; or was noninterruptive. Interviews were audiotaped, transcribed, and independently analyzed to derive central themes. Results Fourteen trainee and attending clinicians trained in pediatrics, cardiology, and neurology participated. Coders derived 8 central themes from 929 quotes. Discordance exists between medication prescribing frequency and DDI knowledge; providers may commonly prescribe medications for which they do not recognize DDIs. Providers wanted alerts at medication selection rather than at order signature. Alert presentation themes included standardizing text, providing interaction-specific incidence/risk information, DDI rating scales, consolidating alerts, and providing alternative therapies. Providers want alerts to be actionable, for example, allowing medication discontinuation and color visual cues for essential information. Despite alert volume, participants did not “mind being reminded because there is always the chance that at that particular moment (they) do not remember it” and acknowledged the importance of alerts as “essential in terms of patient safety. ” Conclusion Clinicians unanimously agreed on the importance of receiving DDI alerts to improve patient safety. The perceived alert value can be improved by incorporating clinician preferences for timing and presentation.
Multimode Hydraulically Amplified Electrostatic Actuators for Wearable Haptics

The sense of touch is underused in today’s virtual reality systems due to lack of wearable, soft, mm‐scale transducers to generate dynamic mechanical stimulus on the skin. Extremely thin actuators combining both high force and large displacement are a long‐standing challenge in soft actuators. Sub‐mm thick flexible hydraulically amplified electrostatic actuators are reported here, capable of both out‐of‐plane and in‐plane motion, providing normal and shear forces to the user’s fingertip, hand, or arm. Each actuator consists of a fluid‐filled cavity whose shell is made of a metalized polyester boundary and a central elastomer region. When a voltage is applied to the annular electrodes, the fluid is rapidly forced into the stretchable region, forming a raised bump. A 6 mm × 6 mm × 0.8 mm actuator weighs 90 mg, and generates forces of over 300 mN, out‐of‐plane displacements of 500 µm (over 60% strain), and lateral motion of 760 µm. Response time is below 5 ms, for a specific power of 100 W kg−1. In user tests, human subjects distinguished normal and different 2‐axis shear forces with over 80% accuracy. A flexible 5 × 5 array is demonstrated, integrated in a haptic sleeve.
Population dynamics of Daphnia spp. and implications for trophic interactions in a small, monomictic lake

In Lake Oglethorpe, Georgia, USA, herbivorous crustacean zooplankton are abundant and dominate zooplankton biomass in winter, but are scarce throughout most of the summer. We used a 3.5 year study of Daphnia population dynamics to infer when food, predators or temperature constrained growth of this population. Transitions between winter and summer consumer assem- blages are concurrent with seasonal changes in water temperature, thermal structure (stratifi- cation/destratification), resources (autotrophic/heterotrophic-dominated production), and predator abundance and activity (e.g. Lepomis macrochirus and Chaoborus punctipennis). We sampled at weekly or less intervals from April 1992 to September 1995, and determined population abundances for all cladoceran species. For the Daphnia population (Daphnia ambigua + Daphnia parvula), we measured clutch size and length for all individuals. We used average water column temperature (where dissolved oxygen is >1 mg l-1) to estimate egg development time from an empirical model. Estimates of Daphnia population birth and death rate were thus generated from abundance, egg ratio and temperature/dissolved oxygen data. We compared observed birth rate (bobs) with expected birth rate (bexp ± 95% CI; predicted for food-saturated conditions at ambient temperature). For variable (1-13 week) periods between late November and March, 1992-1995, water temperature was the primary factor constraining Daphnia population growth (bobs = bexp). From about April to early November, bobs < bexp suggested food-limited population growth. In spring, summer and early fall (March-October), population densities were several-fold lower than in late fall and winter (November-February). However, all else being equal, egg ratio and population birth rate data would have predicted that Daphnia abundance fluctuates over equivalent ranges in spring and fall. We interpret this discrepancy as evidence for increased rates of extrinsic mortality during the growing season and a seasonal shift in the relative importance of resource and predator regulation. The duration of predator suppression of crustacean population abundance in Lake Oglethorpe and other warm-latitude lakes (~36°N-27°S) is longer (♢3-7 months) than that observed in north temperate lakes (1-2.5 months; 41-52°N).
More than a matter of the heart: the concept of intravascular multimorbidity in cardiac rehabilitation

ABSTRACT Introduction Coronary artery disease (CAD) is the major cause of death of cardiovascular disease. It is initiated by atherosclerosis, which narrows the coronary arteries and limits blood flow and oxygen to the heart. Multiple pathophysiological conditions within the arteries, such as arterial wall thickening, endothelial dysfunction, and arterial stiffening, are associated with the development of atherosclerosis. Areas covered We introduce a new concept of ‘intravascular multimorbidity,’ the presence and integration of multiple pathophysiological conditions within the arteries. We also introduce some measurements of intravascular multimorbidity and discuss how these measurements can be utilized in cardiac rehabilitation (CR). Expert opinion We propose that the measures of intravascular multimorbidity in different arteries may provide information on disease severity and serve as unique prognostic ‘barometers’ to disease progression in patients with CAD. By measuring the underlying disease mechanisms within the arteries and understanding individual variability of disease progression/regression, these measures may also provide a unique prognostic window in CR. The window into intravascular multimorbidity can help guide clinical strategies, for example, assessing progress and appropriate titration of exercise. Intravascular multimorbidity may represent an important opportunity for more researchers and clinical professions to evaluate patients in CR.
Self-rated health and mental health among older incarcerated males

Abstract Objectives Older incarcerated persons are a rapidly growing population with considerable mental health needs. We evaluated perceived worth and meaningfulness in life as mediators in the relationship between self-rated health (SRH) and depression and anxiety. Method Mediation analyses were conducted among 222 older incarcerated males from eight correctional facilities in Connecticut.PHQ-9 and GAD-7 assessed depression and anxiety, respectively. Subscales of the Geriatric Suicidal Ideation Scale (GSIS) measured perceived worth and meaningfulness in life. Results Greater SRH was associated with lower depression and anxiety. More perceived worth and meaningfulness in life were associated with better SRH and lower depression and anxiety. There is evidence of perceived worth and meaningfulness in life mediating the SRH-depression (β = −0.86; 95% CI = −1.32 to −0.48; β= −0.46, 95% CI = −0.82 to −0.17, respectively) and SRH-anxiety (β = −0.71; 95% CI = −1.08 to −0.39; β = −0.34, 95% CI = −0.65 to −0.10) relationships. Conclusion SRH has both direct and indirect effects on depression and anxiety, by working through perceived worth and meaningfulness in life, in older incarcerated males. Assessing SRH, and focusing on ways to maintain self-worth and meaning, may be instrumental in promoting and sustaining their good mental health.
Systems analysis of protein signatures predicting cetuximab responses in KRAS, NRAS, BRAF and PIK3CA wild‐type patient‐derived xenograft models of metastatic colorectal cancer

Antibodies targeting the human epidermal growth factor receptor (EGFR) are used for the treatment of RAS wild‐type metastatic colorectal cancer. A significant proportion of patients remains unresponsive to this therapy. Here, we performed a reverse‐phase protein array‐based (phospho)protein analysis of 63 KRAS, NRAS, BRAF and PIK3CA wild‐type metastatic CRC tumours. Responses of tumours to anti‐EGFR therapy with cetuximab were recorded in patient‐derived xenograft (PDX) models. Unsupervised hierarchical clustering of pretreatment tumour tissue identified three clusters, of which Cluster C3 was exclusively composed of responders. Clusters C1 and C2 exhibited mixed responses. None of the three protein clusters exhibited a significant correlation with transcriptome‐based subtypes. Analysis of protein signatures across all PDXs identified 14 markers that discriminated cetuximab‐sensitive and cetuximab‐resistant tumours: PDK1 (S241), caspase‐8, Shc (Y317), Stat3 (Y705), p27, GSK‐3β (S9), HER3, PKC‐α (S657), EGFR (Y1068), Akt (S473), S6 ribosomal protein (S240/244), HER3 (Y1289), NF‐κB‐p65 (S536) and Gab‐1 (Y627). Least absolute shrinkage and selection operator and binominal logistic regression analysis delivered refined protein signatures for predicting response to cetuximab. (Phospo‐)protein analysis of matched pretreated and posttreated models furthermore showed significant reduction of Gab‐1 (Y627) and GSK‐3β (S9) exclusively in responding models, suggesting novel targets for treatment.