Miracle-dz/UniFAR-FTUs huggingface dataset:
Temporospatial distribution and transcriptional profile of retinal microglia in the oxygen‐induced retinopathy mouse model

Myeloid cells such as resident retinal microglia (MG) or infiltrating blood‐derived macrophages (Mϕ) accumulate in areas of retinal ischemia and neovascularization (RNV) and modulate neovascular eye disease. Their temporospatial distribution and biological function in this process, however, remain unclarified. Using state‐of‐the‐art methods, including cell‐specific reporter mice and high‐throughput RNA sequencing (RNA Seq), this study determined the extent of MG proliferation and Mϕ infiltration in areas with retinal ischemia and RNV in Cx3cr1CreERT2:Rosa26‐tdTomato mice and examined the transcriptional profile of MG in the mouse model of oxygen‐induced retinopathy (OIR). For RNA Seq, tdTomato‐positive retinal MG were sorted by flow cytometry followed by Gene ontology (GO) cluster analysis. Furthermore, intraperitoneal injections of the cell proliferation marker 5‐ethynyl‐2′‐deoxyuridine (EdU) were performed from postnatal day (p) 12 to p16. We found that MG is the predominant myeloid cell population while Mϕ rarely appears in areas of RNV. Thirty percent of retinal MG in areas of RNV were EdU‐positive indicating a considerable local MG cell expansion. GO cluster analysis revealed an enrichment of clusters related to cell division, tubulin binding, ATPase activity, protein kinase regulatory activity, and chemokine receptor binding in MG in the OIR model compared to untreated controls. In conclusion, activated retinal MG alter their transcriptional profile, exhibit considerable proliferative ability and are by far the most frequent myeloid cell population in areas of ischemia and RNV in the OIR model thus presenting a potential target for future therapeutic approaches.
Association Between Renin-Angiotensin System Blockade Discontinuation and All-Cause Mortality Among Persons With Low Estimated Glomerular Filtration Rate.

Importance It is uncertain whether and when angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) treatment should be discontinued in individuals with low estimated glomerular filtration rate (eGFR). Objective To investigate the association of ACE-I or ARB therapy discontinuation after eGFR decreases to below 30 mL/min/1.73 m2 with the risk of mortality, major adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD). Design, Setting, and Participants This retrospective, propensity score-matched cohort study included 3909 patients from an integrated health care system that served rural areas of central and northeastern Pennsylvania. Patients who initiated ACE-I or ARB therapy from January 1, 2004, to December 31, 2018, and had an eGFR decrease to below 30 mL/min/1.73 m2 during therapy were enrolled, with follow-up until January 25, 2019. Exposures Individuals were classified based on whether they discontinued ACE-I or ARB therapy within 6 months after an eGFR decrease to below 30 mL/min/1.73 m2. Main Outcomes and Measures The association between ACE-I or ARB therapy discontinuation and mortality during the subsequent 5 years was assessed using multivariable Cox proportional hazards regression models, adjusting for patient characteristics at the time of the eGFR decrease in a propensity score-matched sample. Secondary outcomes included MACE and ESKD. Results Of the 3909 individuals receiving ACE-I or ARB treatment who experienced an eGFR decrease to below 30 mL/min/1.73 m2 (2406 [61.6%] female; mean [SD] age, 73.7 [12.6] years), 1235 discontinued ACE-I or ARB therapy within 6 months after the eGFR decrease and 2674 did not discontinue therapy. A total of 434 patients (35.1%) who discontinued ACE-I or ARB therapy and 786 (29.4%) who did not discontinue therapy died during a median follow-up of 2.9 years (interquartile range, 1.3-5.0 years). In the propensity score-matched sample of 2410 individuals, ACE-I or ARB therapy discontinuation was associated with a higher risk of mortality (hazard ratio [HR], 1.39; 95% CI, 1.20-1.60]) and MACE (HR, 1.37; 95% CI, 1.20-1.56), but no statistically significant difference in the risk of ESKD was found (HR, 1.19; 95% CI, 0.86-1.65). Conclusions and Relevance The findings suggest that continuing ACE-I or ARB therapy in patients with declining kidney function may be associated with cardiovascular benefit without excessive harm of ESKD.
Postural Control While Listening in Younger and Middle-Aged Adults

Objectives: The motivation for this research is to determine whether a listening-while-balancing task would be sensitive to quantifying listening effort in middle age. The premise behind this exploratory work is that a decrease in postural control would be demonstrated in challenging acoustic conditions, more so in middle-aged than in younger adults. Design: A dual-task paradigm was employed with speech understanding as one task and postural control as the other. For the speech perception task, participants listened to and repeated back sentences in the presence of other sentences or steady-state noise. Targets and maskers were presented in both spatially-coincident and spatially-separated conditions. The postural control task required participants to stand on a force platform either in normal stance (with feet approximately shoulder-width apart) or in tandem stance (with one foot behind the other). Participants also rated their subjective listening effort at the end of each block of trials. Results: Postural control was poorer for both groups of participants when the listening task was completed at a more adverse (vs. less adverse) signal-to-noise ratio. When participants were standing normally, postural control in dual-task conditions was negatively associated with degree of high-frequency hearing loss, with individuals who had higher pure-tone thresholds exhibiting poorer balance. Correlation analyses also indicated that reduced speech recognition ability was associated with poorer postural control in both single- and dual-task conditions. Middle-aged participants exhibited larger dual-task costs when the masker was speech, as compared to when it was noise. Individuals who reported expending greater effort on the listening task exhibited larger dual-task costs when in normal stance. Conclusions: Listening under challenging acoustic conditions can have a negative impact on postural control, more so in middle-aged than in younger adults. One explanation for this finding is that the increased effort required to successfully listen in adverse environments leaves fewer resources for maintaining balance, particularly as people age. These results provide preliminary support for using this type of ecologically-valid dual-task paradigm to quantify the costs associated with understanding speech in adverse acoustic environments.
Flexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation

The activity of Ca2+/calmodulin-dependent protein kinase II (CaMKII) depends on the balance between activating and inhibitory autophosphorylation (Thr 286 and Thr 305/306, respectively, in the human α isoform). Variation in the lengths of the flexible linkers that connect the kinase domains of CaMKII to a central oligomeric hub could alter transphosphorylation rates within a holoenzyme, thereby affecting the balance of autophosphorylation outcomes. Using a single-molecule assay for visualization of CaMKII phosphorylation on glass, we show that the balance of autophosphorylation is flipped between CaMKII-α and CaMKII-β, the two principal isoforms in the brain. CaMKII-α, with a ∼30 residue kinase-hub linker, readily acquires activating autophosphorylation, which we show is resistant to removal by phosphatases. CaMKII-β, with a ∼200 residue kinase-hub linker, is biased towards inhibitory autophosphorylation. Thus, the responsiveness of CaMKII to calcium signals can be tuned by varying the relative levels of the α and β isoforms.
Iridoids and cycloartane saponins from mussaenda pilosissima valeton and their inhibitory NO production in BV2 cells

Abstract One new iridoid glycoside (1), shanzhiside N-L-phenylalanyl ester along with seven known compounds, mussaenoside (2), shanzhiside methyl ester (3), barlerin (4), mussaendodise G (5), mussaendodise U (6), mussaendodise P (7), and mussaglaoside B (8) have been isolated from Mussaenda pilosissima Valeton. Their chemical structures were elucidated by spectroscopic methods, 1 D-, 2 D-NMR, and mass spectra. Compounds 1-7 showed significant inhibitory activity on LPS-stimulated NO production in BV2 cells with the IC50 values ranging from 43.5 to 65.2 µM. Graphical Abstract
Traumatizing Oneself-Deep Wrist Injuries Self-Inflicted with Suicidal Intention are Associated with More Severe PTSD Symptomatology than Similar Injuries from Accidents.

OBJECTIVE As suicide attempts by definition entail at least some threat to physical integrity and life, they theoretically qualify as an A1 criterion for posttraumatic stress disorder (PTSD). This study uses the unique opportunity of deep wrist injuries to quantify the effect of intentionality on PTSD rates by comparing suicide attempt survivors with patients who sustained accidental injuries similar in mechanism, localization, and extent. METHOD Patients who had been admitted with an acute deep wrist injury from 2008 to 2016 filled out the revised Impact of Event Scale and reported other known PTSD risk factors. Mental morbidity and intentionality of the injury were determined by psychiatric consultation during the index hospitalization. RESULTS Fifty-one patients were followed up (72.5% male, 92.2% Caucasian, mean age at injury 42.3 ± 17.5 years, 72.5% accidental injuries), on average 4.2 ± 2.9 years after their injury. The intentionality of the injury alone predicted the severity of intrusions, avoidance, hyperarousal, and probable PTSD (aOR = 14.0). CONCLUSIONS Traumatization in the context of a suicide attempt may be a hitherto unknown PTSD risk factor. Patients after suicide attempts, especially medically serious attempts, should be monitored for PTSD symptoms.
Expert workshop on the hazards and risks of poorly soluble low toxicity particles

Abstract ‘Lung particle overload’ refers to the impaired lung particle clearance and increased particle retention occurring with high lung doses of poorly soluble low toxicity (PSLT) particles. In rats, lung particle overload is associated with inflammation, epithelial hyperplasia, and, in extreme cases, lung cancer. While the human relevance of rat lung tumors occurring under overload has been questioned, recent regulatory decisions have considered these outcomes evidence of possible human hazard. To better understand the state-of-the-science on PSLT toxicology, an Expert Workshop was held to document agreements and differences amongst a panel of highly experienced scientists and regulators. Key outcomes included: a functional definition of PSLTs; agreement the rat is a sensitive model for PSLT inhalation toxicology; identifying lung inflammation as a critical endpoint for PSLT risk assessment; and, agreement rat lung cancer occurring only under conditions of lung particle overload does not imply a cancer hazard for humans under non-overloading exposures. Moreover, when asked – should PSLTs be considered as human lung carcinogens based on rat data alone (and no supporting data from other species), the expert consensus was: ‘No. However, the experts noted the current default regulatory position on rat lung overload data alone would be the suspicion of human carcinogen hazard. ’ The many areas of the expert agreement provide guidance for design, interpretation, and extrapolating PSLT inhalation toxicology studies. Considering the workshop outcomes, the authors recommend guidelines for evaluation and classification of PSLT be reassessed; and, prior decisions on PSLT hazard classification be revisited to determine if they remain appropriate.
Bias and stereotyping among research and clinical professionals: Perspectives on minority recruitment for oncology clinical trials

In recent years, extensive attention has been paid to the possibility that bias among health care professionals contributes to health disparities. In its 2003 report, the Institute of Medicine concluded that bias against racial minorities may affect communication or care offered. However, to the authors' knowledge, the role of bias within the context of recruitment of racial and ethnic minorities to cancer clinical trials has not been explored to date. Therefore, the authors assessed the experiences of clinical and research personnel related to factors influencing the recruitment of racial and ethnic minorities for cancer clinical trials.
Design and synthesis of a novel peptide for selective detection of cancer cells

Using a minimalist approach, an 11‐residue peptide (Peptide 1) tagged with rhodamine fluorophore was designed and synthesized for selective detection of cancer cells. Peptide 1 contains RGD and NGR motifs to bind, respectively, integrins and aminopeptidase CD13, which are over expressed in cancer cells. Surface tension measurements revealed that peptide 1 possess surface‐active property owing to the overall hydrophobicity and cationic nature of the peptide. Peptide 1 displays cancer cell‐selective binding at ≤5.0 µM concentrations, while peptide 2 (randomized sequence of 1) shows non‐selective binding to normal and cancer cells. Fluorescence microscopy and FACS analysis demonstrated the intracellular localization of peptide 1 in three different cancer cell lines, confirming the role of RGD and NGR motifs. Cytotoxicity assay exhibited the viability of normal and cancer cells up to 100 µM concentrations of peptide 1. Steady‐state fluorescence measurements disclosed the preferential interactions of the peptide 1 with anionic POPC/POPG bilayers rather than with zwitterionic POPC lipid bilayers. Circular dichroism studies showed minimal changes in the secondary structure of peptide 1 upon binding with the anionic lipid bilayers. Peptide 1 is largely unordered, non‐toxic, and useful for identification of cancer cells. Peptide 1 provides a template for designing drug‐loaded peptides for targeted delivery into cancer cells.
Duodenal ulcer promoting gene (DupA), plasticity region genes and sigma factors in H. pyloristrains from Nigeria.

INTRODUCTION Helicobacter pylori is a principal cause of gastric cancer. The aim of this study was to determine the prevalence and contribution of duodenal ulcer promoting gene A (dupA), the plasticity region genes and sigma factors in relation to their pathological expression of H. pylori infections in the Nigerian population. METHODOLOGY Polymerase Chain Reaction was used to analyze a total of forty-nine H. pylori strains isolated from patients attending various endoscopic units in tertiary hospitals in Nigeria for complete dupA (G27 variant), jhp0917, jhp0918, other plasticity region genes jhp 914/917, jhp0914, jhp0940 and sigma factors. RESULTS PCR results indicated that the prevalence of complete dupA (G27 variants), jhp0917, jhp0918 and other plasticity region genes jhp0914, jhp0914/0917 and jhp0940 in the H. pylori strains were 4%, 53%, 88%, 73%, 12% and 0% respectively. The prevalence values of the sigma factors were 96%, 92%, 80% for rpoN, fliA and rpoD respectively. However, the endoscopic findings showed that erosion, normal mucosal, ulcer, hyperaemic stomach, mucosal atrophy and oedematous stomach in the patients where the H. pylori strains were isolated were 40.8%, 32.7%, 10.2%, 8.2%, 2.0% and 6.1% respectively. There was significant association between jhp0917, jhp914/917 and G27 variant and the endoscopic findings, while other plasticity genes showed no association with the endoscopic findings. CONCLUSION These results suggest that the presence of jhp0917, jhp0914/917 and G27 variant could be used as marker to predict the pathological effect of severity in Nigeria patients with H. pylori infection.
The impact of aging on the subregions of the fusiform gyrus in healthy older adults

The fusiform gyrus is known to decrease in size with increasing age. However, reported findings are inconsistent and existing studies differ in terms of the cohorts examined and/or the methods applied. Here, we analyzed age‐related links in four distinct subregions of the fusiform gyrus through integrating imaging‐based intensity information with microscopically defined cytoarchitectonic probabilities. In addition to age effects we investigated sex effects as well as age‐by‐sex interactions in a relatively large sample of 468 healthy subjects (272 females/196 males) covering a broad age range (42–97 years). We observed significant negative correlations between age and all four subregions of the fusiform gyrus indicating volume decreases over time, albeit with subregion‐specific trajectories. Additionally, we observed significant negative quadratic associations with age for some subregions, suggesting an accelerating volume loss over time. These findings may serve as a frame of reference for future cross‐sectional as well as longitudinal studies, not only for normative samples but also potentially for clinical conditions that present with abnormal atrophy of the fusiform gyrus. We did not detect any significant sex differences or sex‐by‐age interactions, suggesting that the size of the fusiform gyrus is similar in male and female brains and that age‐related atrophy follows a similar trajectory in both men and women.
Quaternized styryl-azinium fluorophores as cellular RNA-binders

The capability of three quaternized styryl-azinium iodides to bind cellular RNA has been tested by means of Fluorescence Confocal Microscopy imaging of stained MCF-7 cells treated with RNase. Their association constants have been estimated through spectrophotometric and fluorimetric titrations with tRNA and compared to their affinity toward DNA. Transient absorption spectroscopy with femtosecond resolution confirmed the binding of the investigated compounds with tRNA and shed new light on the excited state dynamics of their complexes, by revealing a significant lengthening of the lifetime of S_1 upon com-plexation, which parallels the fluorescence quantum yield enhancement.
Special Issue: International Developmental/Life-Course Perspectives and Research on Sexual Offending and Offenders

I am very excited to be introducing you to my special issue for Sexual Abuse, focusing on “International Developmental/Life-Course Perspectives and Research on Sexual Offending and Offenders. ” As readers of this journal are well aware, there has been a considerable amount of literature that has documented that the sexual recidivism rates of persons with sexual offense histories are very low, persons with sexual offense histories do not tend to specialize in a specific type of sex offense or sex offenses in general, and that the continuity of sexual offending behavior from adolescence into adulthood is also rare (Piquero et al., 2012; Reingle, 2012; Zimring et al., 2007). Furthermore, these empirical “facts” are identifiable in research in countries all over the world (Cortoni et al., 2010; Hanson, 2002; Nisbet et al., 2004; Piquero et al., 2012; Zimring et al., 2007). Having said this, what has been slower to develop in this area of research is an overarching theoretical scaffolding or framework to contextualize these research findings and to inform further empirical inquiry. This gap in the literature was one of the driving features behind the development of an international “Sex Offenders in and out of Crime” symposium that was hosted in Brussels, Belgium, in March 2018. This symposium was widely attended by academics, practitioners, and members of the community. As this symposium broadly focused on the criminal careers of persons with sexual offense histories, longitudinal analyses, risk/protective factors, continuity, onset, desistance, and so on, it soon led to rich discussions and conversations and an interest and need in brainstorming methods for disseminating these kind of developmentally/life-course-informed studies. These conversations and inquiries ultimately led to the development of the call-for-papers for this special issue.
Comparative Characterization of Aroma Compounds in Silver Carp (Hypophthalmichthys molitrix), Pacific Whiting (Merluccius productus) and Alaska Pollock (Theragra chalcogramma) Surimi by Aroma Extract Dilution Analysis, Odor Activity Value, and Aroma Recombination Studies.

Aroma compounds in three surimi samples, made from fresh-water Silver Carp (Hypophthalmichthys molitrix), salt-water Pacific Whiting (Merluccius productus) and Alaska Pollock (Theragra chalcogramma), were characterized by aroma extract dilution analysis, odor activity value, and odor recombination study. Results demonstrated that the most potent aroma-active compounds in the surimi were hexanal, (Z)-4-heptenal, (Z)-4-decenal, (E,Z)-2,6-nonadienal, (E,E)-2,4-nonadienal, (E,Z)-2,4-decadienal, (E,E)-2,4-decadienal, (E,E,Z)-2,4,6-nonatrienal, (E,Z,Z)-2,4,7-tridecatrienal, and (E)-4,5-epoxy-(E)-2-decenal, contributing fishy, green, oily, or metallic odors. The other aroma contributors in surimi were 1-octen-3-one, 1-octen-3-ol, dimethyl disulfide, dimethyl trisulfide, and methional. 2-Acetyl-1-pyrroline, giving a typical popcorn note, could also be an important aroma contributor due to high FD factor. Pacific Whiting surimi sample and Alaska Pollock surimi sample both had higher levels of dimethyl trisulfide and methional, whereas Silver Carp surimi sample had more (E,Z)-2,4-decadienal. In general, Silver Carp surimi sample had more aldehydes contributing stronger "river water, fishy" and "grassy, green" aromas. In contrast, salt-water surimi showed stronger "sea breeze-like" and "sulfur-like" odors.
Individual Differences in Attitude Consistency Over Time: The Personal Attitude Stability Scale

This research finds evidence for reliable individual differences in people’s perceived attitude stability that predict the actual stability of their attitudes over time. Study 1 examines the reliability and factor structure of an 11-item Personal Attitude Stability Scale (PASS). Study 2 establishes test–retest reliability for the PASS over a 5-week period. Studies 3a and 3b demonstrate the convergent and discriminant validity of the PASS in relation to relevant existing individual differences. Studies 4 and 5 show that the PASS predicts attitude stability following a delay period across several distinct topics. Across multiple attitude objects, for people with high (vs. low) scores on the PASS, Time 1 attitudes were more predictive of their Time 2 attitudes, indicative of greater attitudinal consistency over time. The final study also demonstrates that the PASS predicts attitude stability above and beyond other related scales.