Miracle-dz/UniFAR-FTUs huggingface dataset:
Usher syndrome type 1-associated gene, pcdh15b, is required for photoreceptor structural integrity in zebrafish

ABSTRACT Blindness associated with Usher syndrome type 1 (USH1) is typically characterized as rod photoreceptor degeneration, followed by secondary loss of cones. The mechanisms leading to blindness are unknown because most genetic mouse models only recapitulate auditory defects. We generated zebrafish mutants for one of the USH1 genes, protocadherin-15b (pcdh15b), a putative cell adhesion molecule. Zebrafish Pcdh15 is expressed exclusively in photoreceptors within calyceal processes (CPs), at the base of the outer segment (OS) and within the synapse. In our mutants, rod and cone photoreceptor integrity is compromised, with early and progressively worsening abnormal OS disc growth and detachment, in part due to weakening CP contacts. These effects were attenuated or exacerbated by growth in dark and bright-light conditions, respectively. We also describe novel evidence for structural defects in synapses of pcdh15b mutant photoreceptors. Cell death does not accompany these defects at early stages, suggesting that photoreceptor structural defects, rather than overt cell loss, may underlie vision deficits. Thus, we present the first genetic animal model of a PCDH15-associated retinopathy that can be used to understand the aetiology of blindness in USH1. This article has an associated First Person interview with the first author of the paper.
Nighttime Waking to Smoke, Stress, and Nicotine Addiction

ABSTRACT Introduction Up to one-half of cigarette smokers may wake up during the night and smoke. This behavior may result in greater likelihood of cessation failure, clinically relevant sleep difficulties, and a range of health issues. Whereas the scientific literature has often attributed this behavior to nicotine dependence, up to 85% of smokers who wake at night and smoke attribute this behavior to factors other than nicotine. This study examines the relations between nicotine dependence, psychological distress, perceived stress, and waking at night to smoke. Methods A total of 351 adult smokers from the Pennsylvania Adult Smoking Study (PASS) completed self-report surveys and provided saliva for the evaluation of cotinine values. Survey instruments included measures of nicotine addiction, perceived stress, a broad measure of global psychological distress, and a range of demographic factors. Results Logistic regression demonstrated that nicotine addiction, psychological distress, and perceived stress were all related to waking at night to smoke, but cotinine levels were not. Mediation models found that psychological distress had a direct relation to waking at night to smoke, even when considering nicotine addiction and other causes of sleep disturbances (e.g., apnea and chronic physical pain). Alternative moderation and mediation models were conducted but did not support other plausible associations between variables. Conclusions Waking at night to smoke is likely the result of both nicotine dependence and psychological distress. Given that cotinine levels were not associated with waking at night, the mechanisms of how nicotine dependence may affect waking at night need further investigation.
Validation of in vitro models for smoke exposure of primary human bronchial epithelial cells.

RATIONALE The bronchial epithelium is constantly challenged by inhalative insults including cigarette smoke (CS), a key risk factor for lung disease. In vitro exposure of bronchial epithelial cells using CS extract (CSE) is a widespread alternative to whole CS (wCS) exposure. However, CSE exposure protocols vary considerably between studies, precluding direct comparison of applied doses. Moreover, they are rarely validated in terms of physiological response in vivo and the relevance of the findings is often unclear. METHODS We tested six different exposure settings in primary human bronchial epithelial cells (phBECs), including five CSE protocols in comparison with wCS exposure. We quantified cell-delivered dose and directly compared all exposures using expression analysis of 10 well-established smoke-induced genes in bronchial epithelial cells. CSE exposure of phBECs was varied in terms of differentiation state, exposure route, duration of exposure, and dose. Gene expression was assessed by quantitative Real-Time PCR (qPCR) and Western Blot analysis. Cell type-specific expression of smoke-induced genes was analyzed by immunofluorescent analysis. RESULTS Three surprisingly dissimilar exposure types, namely chronic CSE treatment of differentiating phBECs, acute CSE treatment of submerged basal phBECs, and wCS exposure of differentiated phBECs performed best, resulting in significant upregulation of seven (chronic CSE) and six (acute wCS, acute submerged CSE exposure) out of 10 genes. Acute apical or basolateral exposure of differentiated phBECs with CSE was much less effective despite similar doses used. CONCLUSIONS Our findings provide guidance for the design of human in vitro CS exposure models in experimental and translational lung research.
Passages in culture and stimulation conditions influence protein expression of primary fibroblasts

Fibroblasts (Fb) are key effector cells in systemic sclerosis (SSc). Fb stimulation with transforming growth factor beta 1 (TGF‐β1) is considered as a positive control in studies assessing fibrogenesis. The lack of standardization of TGF‐β1 stimulation might be responsible for discrepancies in experiments performed in different conditions. Using quantitative proteomics analysis, we evaluated the impact of changes in experimental conditions on proteomic profiles of primary Fb. Principal component analysis (PCA) identified several groups of differentially expressed proteins influenced by cell passage, culture medium, and both concentration and duration of exposure to TGF‐β1 stimulation. Bioinformatics analysis revealed that late passages expressed proteins involved in senescence. TGF‐β1 concentration and time of stimulation were correlated with the expression of proteins involved in the fibrogenesis and inflammatory processes. These data underline the need for standardization of culture conditions to allow inter‐data comparisons in future in vitro studies, especially when using “omics” approaches.
In‐Situ Electronegativity and the Bridging of Chemical Bonding Concepts

Abstract One challenge in chemistry is the plethora of often disparate models for rationalizing the electronic structure of molecules. Chemical concepts abound, but their connections are often frail. This work describes a quantum‐mechanical framework that enables a combination of ideas from three approaches common for the analysis of chemical bonds: energy decomposition analysis (EDA), quantum chemical topology, and molecular orbital (MO) theory. The glue to our theory is the electron energy density, interpretable as one part electrons and one part electronegativity. We present a three‐dimensional analysis of the electron energy density and use it to redefine what constitutes an atom in a molecule. Definitions of atomic partial charge and electronegativity follow in a way that connects these concepts to the total energy of a molecule. The formation of polar bonds is predicted to cause inversion of electronegativity, and a new perspective of bonding in diborane and guanine−cytosine base‐pairing is presented. The electronegativity of atoms inside molecules is shown to be predictive of pK a.
Simulated herbivory enhances leaky sex expression in the dioecious herb Mercurialis annua

Abstract Background and Aims Plant reproductive traits are widely understood to be responsive to the selective pressures exerted by pollinators, but there is also increasing evidence for an important role for antagonists such as herbivores in shaping these traits. Many dioecious species show leaky sex expression, with males and females occasionally producing flowers of the opposite sex. Here, we asked to what extent leakiness in sex expression in Mercurialis annua (Euphorbiaceae) might also be plastically responsive to simulated herbivory. This is important because enhanced leakiness in dioecious populations could lead to a shift in both the mating system and in the conditions for transitions between combined and separate sexes. Methods We examined the effect of simulated herbivory on the sexual expression of males and females of M. annua in two experiments in which different levels of simulated herbivory led to enhanced leakiness in both sexes. Key Results We showed that leaky sex expression in both males and females of the wind-pollinated dioecious herb M. annua is enhanced in response to simulated herbivory, increasing the probability for and the degree of leakiness in both sexes. We also found that leakiness was greater in larger females but not in larger males. Conclusions We discuss hypotheses for a possible functional link between herbivory and leaky sex expression, and consider what simulated herbivory-induced leakiness might imply for the evolutionary ecology of plant reproductive systems, especially the breakdown of dioecy and the evolution of hermaphroditism.
Strategies for Antibiotic Administration for Bowel Preparation Among Patients Undergoing Elective Colorectal Surgery: A Network Meta-analysis.

Importance There are discrepancies in guidelines on preparation for colorectal surgery. While intravenous (IV) antibiotics are usually administered, the use of mechanical bowel preparation (MBP), enemas, and/or oral antibiotics (OA) is controversial. Objective To summarize all data from randomized clinical trials (RCTs) that met selection criteria using network meta-analysis (NMA) to determine the ranking of different bowel preparation treatment strategies for their associations with postoperative outcomes. Data Sources Data sources included MEDLINE, Embase, Cochrane, and Scopus databases with no language constraints, including abstracts and articles published prior to 2021. Study Selection Randomized studies of adults undergoing elective colorectal surgery with appropriate aerobic and anaerobic antibiotic cover that reported on incisional surgical site infection (SSI) or anastomotic leak were selected for inclusion in the analysis. These were selected by multiple reviewers and adjudicated by a separate lead investigator. A total of 167 of 6833 screened studies met initial selection criteria. Data Extraction and Synthesis NMA was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by multiple independent observers and pooled in a random-effects model. Main Outcomes and Measures Primary outcomes were incisional SSI and anastomotic leak. Secondary outcomes included other infections, mortality, ileus, and adverse effects of preparation. Results A total of 35 RCTs that included 8377 patients were identified. Treatments compared IV antibiotics (2762 patients [33%]), IV antibiotics with enema (222 patients [3%]), IV antibiotics with OA with or without enema (628 patients [7%]), MBP with IV antibiotics (2712 patients [32%]), MBP with IV antibiotics with OA (with good IV antibiotic cover in 925 patients [11%] and with good overall antibiotic cover in 375 patients [4%]), MBP with OA (267 patients [3%]), and OA (486 patients [6%]). The likelihood of incisional SSI was significantly lower for those receiving IV antibiotics with OA with or without enema (rank 1) and MBP with adequate IV antibiotics with OA (rank 2) compared with all other treatment options. The addition of OA to IV antibiotics, both with and without MBP, was associated with a reduction in incisional SSI by greater than 50%. There were minimal differences between treatments in anastomotic leak and in any of the secondary outcomes. Conclusions and Relevance This NMA demonstrated that the addition of OA to IV antibiotics were associated with a reduction in incisional SSI by greater than 50%. The results support the addition of OA to IV antibiotics to reduce incisional SSI among patients undergoing elective colorectal surgery.
Perceptions of Postpartum Teaching and Knowledge of Warning Signs among Black Mothers

The postpartum period is the time of highest risk for maternal death. Quality postpartum education is important to minimize risk. We assessed the postpartum education given to Black mothers on post-birth warning signs by conducting a cross-sectional survey of 80 Black women who had given birth in the previous 12 months. Participants completed an electronic questionnaire, and data were analyzed using descriptive and regression models. On average, educational needs were reported by 20 participants as being unmet, 27 as being met, and 30 as being more than met. Only 54.4% of the participants reported receiving education about postpartum warning signs. The percentage of participants able to identify each sign ranged from 11.4% to 35.4%. No participants identified more than five of the nine warning signs, and 25% identified none. Knowledge of post-birth warning signs was significantly associated with the delivery hospital, household income, and education on warning signs before discharge.
Effect of Fascia Implantation and Controlled Release of Basic Fibroblast Growth Factor for Muscle Atrophy in Rat Laryngeal Paralysis

Objective To improve lateral thyroarytenoid (TA) muscle atrophy after laryngeal paralysis, reconstruction of the vascular network of the atrophied muscle is necessary. We therefore evaluated whether the controlled release of basic fibroblast growth factor (bFGF) with autologous fascia implantation could affect vascular reconstruction in the lateral TA muscle. Study Design Animal experiment. Setting Laboratory. Methods Unilateral laryngeal paralysis was induced in 20 rats. The rats were implanted with autologous fascia and a gelatin hydrogel sheet with or without 1 µg of bFGF (fascia and bFGF + fascia groups; n = 5 each) and with only a gelatin hydrogel sheet with bFGF (bFGF group: n = 5). Another group remained untreated (n = 5) at 4 months after paralysis. At 3 months since transplantation, intra- and intergroup comparisons of the muscle volumes and total area of blood vessels in the lateral TA muscle were performed. Results When compared with the untreated group, the bFGF + fascia group showed a significant increase in muscle volume (P =.0008) and vascular area (P =.0002) in the lateral TA muscle, whereas the other 2 treated groups demonstrated an insufficient effect. Conclusion bFGF + fascia implantation showed histologic improvement in severe laryngeal paralysis. We demonstrated that the decrease in lateral TA muscle mass after paralysis might be countered by the reconstruction of the vascular network. Our findings indicate that hypovascular and denervated areas of the laryngeal muscle can be regenerated by the implantation of growth factors and scaffolds with surgical stress. Level of evidence 5.
In Vitro Efficacy of Gentamicin Alone and in Combination with Ceftriaxone, Ertapenem, and Azithromycin against Multidrug-Resistant Neisseria gonorrhoeae

Antimicrobial-resistant Neisseria gonorrhoeae is a major global public health concern. New treatment options are urgently needed to successfully treat multidrug-resistant (MDR) Neisseria gonorrhoeae infections. ABSTRACT This study was conducted to determine the in vitro activities of gentamicin alone and in combination with ceftriaxone, ertapenem, and azithromycin against multidrug-resistant (MDR) Neisseria gonorrhoeae isolates. A total of 407 clinical isolates from Nanjing, China, obtained in 2016 to 2017, had MICs determined for gentamicin using the agar dilution method. MDR status was ascribed to 97 strains that displayed decreased susceptibility or resistance to extended-spectrum cephalosporins (ESCs) (ceftriaxone [MIC, ≥0.125 mg/liter] and cefixime [MIC, ≥0.25 mg/liter]), plus resistance to at least two of the following antimicrobials: penicillin (MIC, ≥2 mg/liter), ciprofloxacin (MIC, ≥1 mg/liter), and azithromycin (MIC, ≥1 mg/liter). MDR strains underwent MIC determinations for antimicrobial combinations using the antimicrobial gradient epsilometer test (Etest). Results that ranged from synergy to antagonism were interpreted using the fractional inhibitory concentration (FICI). All 407 gonococcal isolates were susceptible to gentamicin; MICs ranged from 2 mg/liter to 16 mg/liter. Synergy was demonstrated in 16.5% (16/97), 27.8% (27/97), and 8.2% (8/97) of MDR strains when gentamicin was combined with ceftriaxone (geometric mean [GM] FICI, 0.747), ertapenem (GM FICI, 0.662), and azithromycin (GM FICI, 1.021), respectively. No antimicrobial antagonism was observed with any combination tested against MDR strains; overall, antimicrobial combinations were indifferent. The GM MICs of gentamicin were reduced by 2.63-, 3.80-, and 1.98-fold when tested in combination with ceftriaxone, ertapenem, and azithromycin, respectively. The GM MICs of the three additional antimicrobials individually were reduced by 3-, 2.57-, and 1.98-fold, respectively, when each was tested in combination with gentamicin. Gentamicin alone was effective in vitro against N. gonorrhoeae, including MDR isolates. Combination testing of MDR strains showed lower MICs against gentamicin and each of three antimicrobials (ceftriaxone, ertapenem, and azithromycin) when used in combination. IMPORTANCE Antimicrobial-resistant Neisseria gonorrhoeae is a major global public health concern. New treatment options are urgently needed to successfully treat multidrug-resistant (MDR) Neisseria gonorrhoeae infections. This study showed that gentamicin maintained excellent in vitro susceptibility against clinical gonococcal isolates collected in 2016 and 2017, including MDR isolates. Combinations of gentamicin plus ertapenem, ceftriaxone, and azithromycin produced synergistic effects against certain MDR isolates. No antagonism was observed in any of the antimicrobial combinations, which may prove useful to guide clinical testing of combination therapies.
Maternal childhood trauma and prenatal stressors are associated with child behavioral health

Abstract Maternal adversity and prenatal stress confer risk for child behavioral health problems. Few studies have examined this intergenerational process across multiple dimensions of stress; fewer have explored potential protective factors. Using a large, diverse sample of mother–child dyads, we examined associations between maternal childhood trauma, prenatal stressors, and offspring socioemotional-behavioral development, while also examining potential resilience-promoting factors. The Conditions Affecting Neurocognitive Development and Learning and Early Childhood (CANDLE) study prospectively followed 1503 mother–child dyads (65% Black, 32% White) from pregnancy. Exposures included maternal childhood trauma, socioeconomic risk, intimate partner violence, and geocode-linked neighborhood violent crime during pregnancy. Child socioemotional-behavioral functioning was measured via the Brief Infant Toddler Social Emotional Assessment (mean age = 1.1 years). Maternal social support and parenting knowledge during pregnancy were tested as potential moderators. Multiple linear regressions (N = 1127) revealed that maternal childhood trauma, socioeconomic risk, and intimate partner violence were independently, positively associated with child socioemotional-behavioral problems at age one in fully adjusted models. Maternal parenting knowledge moderated associations between both maternal childhood trauma and prenatal socioeconomic risk on child problems: greater knowledge was protective against the effects of socioeconomic risk and was promotive in the context of low maternal history of childhood trauma. Findings indicate that multiple dimensions of maternal stress and adversity are independently associated with child socioemotional-behavioral problems. Further, modifiable environmental factors, including knowledge regarding child development, can mitigate these risks. Both findings support the importance of parental screening and early intervention to promote child socioemotional-behavioral health.
Carbon flows from trade in harvested wood products using different accounting approaches

Abstract Carbon flow in forest products trade will affect the report of a country's carbon stock. This will have an impact on a country's contribution of carbon flows. Based on the analysis of China’s forest product trade, this paper uses the stock-change approach, the production approach and the atmospheric-flow approach to calculate the changes of China's forest products trade carbon flows. Different carbon flow measurement approaches have very different results. From the perspective of the contribution of forest products to carbon flow, the production approach of calculation for forest products trade carbon flow has the largest contribution to atmospheric carbon flows. However, the calculation results of the stock-change approach and the atmospheric-flow approach are just the opposite, that is, the calculation for forest products trade has a negative contribution to China's carbon sinks, and forest products trade has become a source of carbon emissions.
Effects of tobacco compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on the expression of epigenetically regulated genes in lung carcinogenesis

ABSTRACT Cigarette smoking is a major cause of lung cancer. Although tobacco smoking-induced genotoxicity has been well established, there is apparent lack of abundance functional epigenetic effects reported On cigarette smoke-induced lung carcinogenesis. The aim of this study was to determine effects of intratracheal administration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) utilizing target gene expression DNA methylation patterns in lung tissues of mice following twice weekly for 8 weeks treatment. An unbiased approach where genomic regions was undertaken to assess early methylation changes within mouse pulmonary tissues. A methylated-CpG island recovery assay (MIRA) was performed to map the DNA methylome in lung tissues, with the position of methylated DNA determined using a Genome Analyzer (MIRA-SEQ). Alterations in epigenetic-regulated target genes were confirmed with quantitative reverse transcription-PCR, which revealed 35 differentially hypermethylated genes including Cdkn1C, Hsf4, Hnf1a, Cdx1, and Hoxa5 and 30 differentially hypomethylated genes including Ddx4, Piwi1, Mdm2, and Pce1 in NNK-exposed lung tissue compared with controls. The main pathway of these genes for mediating biological information was analyzed using the Kyoto Encyclopedia of Genes and Genomes database. Among them, Rssf1 and Mdm2 were closely associated with NNK-induced lung carcinogenesis. Taken together, our data provide valuable resources for detecting cigarette smoke-induced lung carcinogenesis.