Miracle-dz/UniFAR-FTUs huggingface dataset:
Beyond Cholinesterase Inhibition: Developmental Neurotoxicity of Organophosphate Ester Flame Retardants and Plasticizers

Background: To date, the toxicity of organophosphate esters has primarily been studied regarding their use as pesticides and their effects on the neurotransmitter acetylcholinesterase (AChE). Currently, flame retardants and plasticizers are the two largest market segments for organophosphate esters and they are found in a wide variety of products, including electronics, building materials, vehicles, furniture, car seats, plastics, and textiles. As a result, organophosphate esters and their metabolites are routinely found in human urine, blood, placental tissue, and breast milk across the globe. It has been asserted that their neurological effects are minimal given that they do not act on AChE in precisely the same way as organophosphate ester pesticides. Objectives: This commentary describes research on the non-AChE neurodevelopmental toxicity of organophosphate esters used as flame retardants and plasticizers (OPEs). Studies in humans, mammalian, nonmammalian, and in vitro models are presented, and relevant neurodevelopmental pathways, including adverse outcome pathways, are described. By highlighting this scientific evidence, we hope to elevate the level of concern for widespread human exposure to these OPEs and to provide recommendations for how to better protect public health. Discussion: Collectively, the findings presented demonstrate that OPEs can alter neurodevelopmental processes by interfering with noncholinergic pathways at environmentally relevant doses. Application of a pathways framework indicates several specific mechanisms of action, including perturbation of glutamate and gamma-aminobutyric acid and disruption of the endocrine system. The effects may have implications for the development of cognitive and social skills in children. Our conclusion is that concern is warranted for the developmental neurotoxicity of OPE exposure. We thus describe important considerations for reducing harm and to provide recommendations for government and industry decision makers. https://doi.org/10.1289/EHP9285
Underlying conditions contributing to breathlessness in the population

Purpose of review Assessment of underlying conditions that contribute to breathlessness is fundamental for symptom management. This review aims to summarize the knowledge from the past two years on the most common underlying conditions among individuals with breathlessness in the general population and to identify research gaps. Recent findings Nine studies from the last two years were included in the review; two studies systematically assessed underlying conditions among breathless individuals in the general population. The modified Medical Research Council (mMRC) scale was used in eight of nine studies. Respiratory diseases were the main underlying condition (40–57%), of which asthma was the most common (approx. 25%), and chronic obstructive pulmonary disease was particularly strongly associated with breathlessness. Other conditions prevalent among breathless individuals included heart diseases, anxiety, depression, and obesity, and several conditions often co-existed. Summary Breathlessness in the general population is common and associated with several underlying conditions. Respiratory disease is the most commonly reported underlying condition. Refined methods such as machine learning could be useful to study the complex interplay between multiple underlying causes of breathlessness and impact on outcomes such as quality of life and survival.
Awareness-Dependent Normalization Framework of Visual Bottom-up Attention

Although bottom-up attention can improve visual performance with and without awareness to the exogenous cue, whether they are governed by a common neural computation remains unclear. Using a modified Posner paradigm with backward masking, we found that the cueing effect displayed a monotonic gradient profile (Gaussian-like), both with and without awareness, whose scope, however, was significantly wider with than without awareness. This awareness-dependent scope offered us a unique opportunity to change the relative size of the attention field to the stimulus, differentially modulating the gain of attentional selection, as proposed by the normalization model of attention. Therefore, for each human subject (male and female), the stimulus size was manipulated as their respective mean attention fields with and without awareness while stimulus contrast was varied in a spatial cueing task. By measuring the gain pattern of contrast-response functions on the spatial cueing effect derived by visible or invisible cues, we observed changes in the cueing effect consonant with changes in contrast gain for visible cues and response gain for invisible cues. Importantly, a complementary analysis confirmed that subjects' awareness-dependent attention fields can be simulated by using the normalization model of attention. Together, our findings indicate an awareness-dependent normalization framework of visual bottom-up attention, placing a necessary constraint, namely, awareness, on our understanding of the neural computations underlying visual attention. SIGNIFICANCE STATEMENT Bottom-up attention is known to improve visual performance with and without awareness. We discovered that manipulating subjects' awareness can modulate their attention fields of visual bottom-up attention, which offers a unique opportunity to regulate its normalization processes. On the one hand, by measuring the gain pattern of contrast-response functions on the spatial cueing effect derived by visible or invisible cues, we observed changes in the cueing effect consonant with changes in contrast gain for visible cues and response gain for invisible cues. On the other hand, by using the normalization model of attention, subjects' awareness-dependent attention fields can be simulated successfully. Our study supports important predictions of the normalization model of visual bottom-up attention and further reveals its dependence on awareness.
Cell biology of primary cell wall synthesis in plants

Abstract Building a complex structure such as the cell wall, with many individual parts that need to be assembled correctly from distinct sources within the cell, is a well-orchestrated process. Additional complexity is required to mediate dynamic responses to environmental and developmental cues. Enzymes, sugars, and other cell wall components are constantly and actively transported to and from the plasma membrane during diffuse growth. Cell wall components are transported in vesicles on cytoskeletal tracks composed of microtubules and actin filaments. Many of these components, and additional proteins, vesicles, and lipids are trafficked to and from the cell plate during cytokinesis. In this review, we first discuss how the cytoskeleton is initially organized to add new cell wall material or to build a new cell wall, focusing on similarities during these processes. Next, we discuss how polysaccharides and enzymes that build the cell wall are trafficked to the correct location by motor proteins and through other interactions with the cytoskeleton. Finally, we discuss some of the special features of newly formed cell walls generated during cytokinesis.
Comparison of Radiation Exposure Between Anterior, Lateral, and Posterior Interbody Fusion Techniques and the Influence of Patient and Procedural Factors

Increasing use of interbody fusion techniques has led to greater utilization of intra-operative imaging modalities without detailed understanding of the ramifications of different interbody fusion techniques on radiation. Our study identified novel factors associated with increased radiation usage including lateral technique and more caudal levels. Study Design. Retrospective cohort. Objective. The aim of this study was to elucidate the relative influence of multiple factors on radiation usage for anterior, lateral, and posterior based lumbar interbody fusion techniques. Summary of Background Data. There has been substantial global growth in the performance of lumbar interbody fusions, due to evolution of techniques and approaches and increased attention to sagittal alignment. Utilization of intraoperative imaging guidance has similarly expanded, with a predominance of fluoroscopy and consequent increased radiation exposure. There have been no larger-scale studies examining the role of patient and procedural factors in driving radiation exposure across different interbody techniques. Methods. We used a clinical registry to review all single-level lumbar interbody fusions performed between January 2016 and October 2020. Operative records were reviewed for the amount of radiation exposure during the procedure. Patient age, biologic sex, body mass index (BMI), operative surgeon, surgical level, surgical time, and fusion technique were recorded. Multivariable adjusted analyses using negative binomial regression were used to account for confounding. Results. We included 134 interbody fusions; 80 performed with a posterior approach (TLIF/PLIF), 43 via an anterior approach (ALIF) with posterior pedicle fixation, and 9 performed with a lateral approach (LLIF/XLIF). Average radiation per case was 136.4 mGy (SE 17.3) for ALIF, 108.6 mGy (16.9) for LLIF/XLIF, and 60.5 mGy (7.4) for TLIF/PLIF. We identified lateral approaches, increased BMI, minimally invasive techniques, and more caudal operative levels as significantly associated with increased radiation exposure. Conclusion. We identified several novel drivers of radiation exposure during interbody fusion procedures, including the relative importance of technique and the level at which the fusion is performed. More caudal levels of intervention and lateral based techniques had significantly greater radiation exposure. Level of Evidence: 4
Synthesis, characterization and investigation of tautomeric, potentiometric and antimicrobial properties of a novel unsymmetric Schiff base and its Fe(III) and Ni(II) complexes

Abstract A new unsymmetric Schiff base [(2OH)R-CH=N-(C 6 H 4 )-CH=N-R'(2OH) R=phenyl, R' = naphthyl] with its Fe(III) and Ni(II) complexes were synthesized by a two step method. Diimine Schiff base and its complexes were characterized by elemental analysis, mass spectra, IR, 1 H/ 13 C-NMR spectra, TGA analysis, electronic and magnetic measurements. The phenol-imine and keto-amine tautomerism of the unsymmetric Schiff base was investigated with NMR techniques and UV-visible spectra in different solvents. Also, the protonation constants of the ligand and the stability constants of its Ni(II) and Fe(III) complexes were determined potentiometrically in 1:1(v/v) ethanol-water mixture at an ionic strength of 0.5 mol·L -1 KCl and at 25.0 ± 0.1 o C. The antifungal, antimicrobial activities and the minimum inhibitory concentration (MIC) values of the compounds were evaluated against Escherichia coli (0157:H7), Micrococcus luteus (NRRLB 4975), Bacillus cereus (RSKK 863) and Candida albicans (ATCC 16231).
Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2021;45:379-89)

Copyright © 2021 Korean Diabetes Association https://e-dmj.org This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2021;45:379-89)
Vasopressor Initiation Within 1 Hour of Fluid Loading Is Associated With Increased Mortality in Septic Shock Patients: Analysis of National Registry Data*

OBJECTIVES: To investigate whether administration of a vasopressor within 1 hour of first fluid loading affected mortality and organ dysfunction in septic shock patients. DESIGN: Prospective, multicenter, observational study. SETTING: Sixteen tertiary or university hospitals in the Republic of Korea. PATIENTS: Patients with septic shock (n = 415) were classified into early and late groups according to whether the vasopressor was initiated within 1 hour of the first resuscitative fluid load. Early (n = 149) patients were 1:1 propensity matched to late (n = 149) patients. INTERVENTIONS: None. Measurement and Main Results: The median time from the initial fluid bolus to vasopressor was shorter in the early group (0.3 vs 2.3 hr). There was no significant difference in the fluid bolus volume within 6 hours (33.2 vs 35.9 mL/kg) between the groups. The Sequential Organ Failure Assessment score and lactate level on day 3 in the ICU were significantly higher in the early group than that in the late group (Sequential Organ Failure Assessment, 9.2 vs 7.7; lactate level, 2.8 vs 1.7 mmol/L). In multivariate Cox regression analyses, early vasopressor use was associated with a significant increase in the risk of 28-day mortality (hazard ratio, 1.83; 95% CI, 1.26–2.65). CONCLUSIONS: Vasopressor initiation within 1 hour of fluid loading was associated with higher 28-day mortality in patients with septic shock.
Predicting and Evaluating Treatment Response: Evidence Toward Protracted Response Patterns for Severely Impacted Students With Dyslexia

Great strides have been made in the development of effective methods of instruction for children with dyslexia. However, individual response to treatment varies, and weaknesses persist for some students with dyslexia despite otherwise effective instruction. Continued efforts are needed to support the prospective identification of poor response, particularly in routine intervention settings. The current study addressed whether indicators of dyslexia risk as outlined by hybrid diagnostic models predict response in children who received Tier 3 dyslexia intervention in their schools. The program’s efficacy has been previously documented in remediating reading abilities in children with dyslexia. Data were examined from 115 elementary-age children who received routine Tier 3 dyslexia intervention in their schools. Logistic regression revealed powerful effects of preintervention fluency and gender in predicting response, with weaker effects of decoding and rapid naming. Attention-deficit/hyperactivity disorder status also played a role in predicting response. Phonological awareness and listening-reading comprehension discrepancy did not predict response. Profile analyses indicated near- and far-transfer of skill for the adequate response group, whereas growth in the poor response group was limited to near-transfer. Findings support a continuum of severity that may be associated with less robust growth and generalization over the course of the intervention.
Dimensional determinants for the carcinogenic potency of elongate amphibole particles

Abstract Context Carcinogenic properties of particulates depend, among other factors, on dimensional characteristics that affect their ability to reach sensitive tissue, to be removed or retained, and to interact with the cells. Objective To model mesothelioma and lung cancer potency of amphibole particles based on their dimensional characteristics and mineral habit (asbestiform vs. nonasbestiform) utilizing epidemiological data and detailed size information. Methods The datasets from recently created depository of dimensional information of elongate mineral particles were used to correlate mesothelioma and lung cancer potency with the fraction of particles in a specific size range and the ratio of length and width in different powers. In addition, the cancer potency factors were estimated and compared for 30 asbestiform, 15 nonasbestiform, and 10 mixed datasets. Results For particles longer than 5 µm, the highest correlation with mesothelioma potency was achieved for width <0.22 µm, and with lung cancer <0.28 µm. The statistical power of the correlation was observed to lose significance at a maximum width of 0.6–0.7 µm. Mesothelioma potency correlated with length in the power of 1.9 divided by width in the power of 2.97, lung cancer potency with length in the power of 0.4 divided by width in the power of 1.17. The predicted cancer potencies of asbestiform, nonasbestiform, and mixed categories were significantly different. Conclusion While additional studies in this direction are warranted, this paper should serve as an additional confirmation for the role of fiber dimensions in the carcinogenicity of amphibole elongate mineral particles (EMPs).
Optically Controlled Ultrafast Terahertz Metadevices with Ultralow Pump Threshold.

Arming metasurface with active materials furnishes a feasible solution to dynamically control over terahertz (THz) waves, which is extremely significant for the realization of upcoming sixth generation telecommunications. However, the present active materials are mainly limited to single external driving field, hindering the capability of metasurface for flexible manipulation of THz waves. Besides, less attention has been paid to the energy question how to significantly reduce the pump threshold for achieving the desired function. Here, a germanium (Ge) hybrid Fano metasurface under dual-stimulus control is experimentally demonstrated. Photoexcitation of Ge thin film enables 100% modulation depth of Fano resonance and ultrafast switching time within 10 ps. By adding current-bias, the pump threshold to modulate the metasurface is greatly reduced from 1600 to 200 µJ cm-2 . Different from the optical modulation independent of film thickness, it is found that the current function is in proportion with the thickness of Ge thin film. Moreover, it is demonstrated that compared to the single optical-stimulus, the THz amplitude modulation is increased by 56.3% under dual-stimulus function. This work naturally improves the flexibility and practicality of Ge-based metadevice and inspires more innovations to boost the development of switchable sensing, lasing spacer, and nonlinear systems.
Akkermansia muciniphila Alleviates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by NLRP3 Activation

The gut microbiota and host immune response interaction influences the progression of intestinal inflammatory disease. As a well-recognized next-generation probiotic, Akkermansia muciniphila has been proved to play a crucial role in the progression of colitis, but its underlying mechanism remains inconclusive. ABSTRACT Akkermansia muciniphila has been proved to play a crucial role in the progression of colitis, but its underlying mechanism remains inconclusive. In this study, we aim to investigate the effect of A. muciniphila on the development of acute colitis and explore the underlying mechanism. We found that the fecal level of A. muciniphila was decreased in ulcerative colitis (UC) patients compared to the healthy people in the GMrepo database. Oral administration of A. muciniphila strain BAA-835 significantly ameliorated the symptoms in dextran sulfate sodium (DSS)-induced acute colitis, evidenced by decreased body weight loss, colon length shortening, and colon histological inflammatory score. In addition, the number of goblet cells and the mucin family were enhanced after A. muciniphila treatment. Furthermore, proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein 1 (MCP-1) had a downward trend. Mechanistically, the expression of NLRP3, caspase-1 p20, and IL-1β p17 were upregulated in A. muciniphila-treated mice. Additionally, the colon tissues from high-A. muciniphila UC patients had a higher NLRP3 expression than that from low-A. muciniphila UC patients. Moreover, the upregulation of NLRP3 was observed in mouse macrophage Raw264.7 cells and bone marrow-derived macrophage (BMDM) cells after incubation with A. muciniphila. To clarify whether the protective effect of A. muciniphila in colitis depends on NLRP3, we performed the NLRP3-deficient assay in NLRP3−/− mice in vivo. The evidence showed that NLRP3 deficiency eliminated the protective effects of A. muciniphila in acute colitis. In conclusion, A. muciniphila alleviates DSS-induced acute colitis by NLRP3 activation, which enriches the mechanism and provides a new prospect for the probiotic-based treatment of colitis. IMPORTANCE The gut microbiota and host immune response interaction influences the progression of intestinal inflammatory disease. As a well-recognized next-generation probiotic, Akkermansia muciniphila has been proved to play a crucial role in the progression of colitis, but its underlying mechanism remains inconclusive. We found that oral administration of A. muciniphila strain BAA-835 significantly ameliorated the symptoms of acute colitis. Mechanistically, the expression of NLRP3 was upregulated in the A. muciniphila group, and the protective effect of A. muciniphila in colitis depends on NLRP3 activation. This enriches the mechanism and provides a new prospect for the probiotic-based treatment of colitis, which would promote a deeper understanding of the complex characteristics of A. muciniphila and provide guidance for the treatment of human colitis in the future.
Prognostic impact of chronological age on efficacy of immune checkpoint inhibitors in non‐small‐cell lung cancer: Real‐world data from 86 173 patients

Immune checkpoint inhibitors (ICIs) have become standard pharmacological therapies in patients with non‐small‐cell lung cancer (NSCLC). Because elderly patients with NSCLC are often excluded from clinical trials as a result of lower functional capacity or comorbidities, the prognostic impact of chronological age on the efficacy of ICIs is unclear. The National Cancer Database was queried for stage IV NSCLC patients between 2014 and 2015. Associations between ICI therapy and clinical characteristics were assessed using chi‐squared tests. Kaplan–Meier curves were compared using the log‐rank test. A Cox proportional hazards model was used to identify clinical characteristics predictive of overall survival (OS). This study included 24 136 patients with stage IV NSCLC aged ≥75 years and 62 037 patients with stage IV NSCLC aged <75 years. Patients aged ≥75 years treated with ICIs had significantly longer OS than those not treated with ICIs (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.58–0.64, p < 0.0001). The corresponding HR in patients aged <75 years was 0.67 (95% CI 0.65–0.68, p < 0.0001). Cox modeling confirmed the survival benefit of ICI therapy in patients aged ≥75 years (HR for patients not receiving ICIs 1.63 [95% CI: 1.55–1.71], p < 0.0001). The corresponding HR in patients aged <75 years was 1.47 (95% CI 1.43–1.51, p < 0.0001). Chronological age does not appear to negatively impact the survival benefit of ICI therapy in patients with stage IV NSCLC according to this large real‐world database analysis.