Miracle-dz/UniFAR-FTUs huggingface dataset:
Achieving industrial ammonia synthesis rates at near-ambient conditions through modified scaling relations on a confined dual site

Significance The Haber–Bosch process is of significance in producing fertilizer for agricultural needs and to avoid worldwide mass starvation. Designing a state-of-the-art catalyst to achieve a mild-condition Haber–Bosch process represents a great challenge because it consumes 1 to 2% of annual energy usage worldwide. We propose a theoretical strategy with a confined dual site to achieve an ammonia synthesis rate two to three orders of magnitude higher than the commercial Ru catalyst under the same reaction conditions. This work will open pathways for developing catalysts for the Haber–Bosch process that can operate under milder conditions. The production of ammonia through the Haber–Bosch process is regarded as one of the most important inventions of the 20th century. Despite significant efforts in optimizing the process, it still consumes 1 to 2% of the worldwide annual energy for the high working temperatures and pressures. The design of a catalyst with a high activity at milder conditions represents another challenge for this reaction. Herein, we combine density functional theory and microkinetic modeling to illustrate a strategy to facilitate low-temperature and -pressure ammonia synthesis through modified energy-scaling relationships using a confined dual site. Our results suggest that an ammonia synthesis rate two to three orders of magnitude higher than the commercial Ru catalyst can be achieved under the same reaction conditions with the introduction of confinement. Such strategies will open pathways for the development of catalysts for the Haber–Bosch process that can operate at milder conditions and present more economically viable alternatives to current industrial solutions.
Evaluation of the AV7909 Anthrax Vaccine Toxicity in Sprague Dawley Rats Following Three Intramuscular Administrations

AV7909 is a next-generation anthrax vaccine under development for post-exposure prophylaxis following suspected or confirmed Bacillus anthracis exposure, when administered in conjunction with the recommended antibacterial regimen. AV7909 consists of the FDA-approved BioThrax® vaccine (anthrax vaccine adsorbed) and an immunostimulatory Toll-like receptor 9 agonist oligodeoxynucleotide adjuvant, CPG 7909. The purpose of this study was to evaluate the potential systemic and local toxicity of AV7909 when administered via repeat intramuscular injection to the right thigh muscle (biceps femoris) to male and female Sprague Dawley rats. The vaccine was administered on Days 1, 15, and 29 and the animals were assessed for treatment-related effects followed by a 2-week recovery period to evaluate the persistence or reversibility of any toxic effects. The AV7909 vaccine produced no apparent systemic toxicity based on evaluation of clinical observations, body weights, body temperature, clinical pathology, and anatomic pathology. Necrosis and inflammation were observed at the injection sites as well as in regional lymph nodes and adjacent tissues and were consistent with immune stimulation. Antibodies against B. anthracis protective antigen (PA) were detected in rats treated with the AV7909 vaccine, confirming relevance of this animal model for the assessment of systemic toxicity of AV7909. In contrast, sera of rats that received saline or soluble CPG 7909 alone were negative for anti-PA antibodies. Overall, 3 intramuscular immunizations of Sprague Dawley rats with AV7909 were well tolerated, did not induce mortality or any systemic adverse effects, and did not result in any delayed toxicity.
Emergent canine visceral leishmaniasis in Argentina: Comparative diagnostics and relevance to proliferation of human disease

Background Visceral leishmaniasis (VL) is a zoonotic protozoal vector-borne disease that is a major public health challenge. In Argentina, canine (CVL) and human visceral leishmaniasis (HVL) have recently emerged. There is a lack of standardised diagnostic tests for CVL, which hinders control of CVL and HVL. Methodology/Principal findings Sampling was carried out in Puerto Iguazú, Argentina, comprising 190 asymptomatic, oligosymptomatic and polysymptomatic dogs. The following diagnostics were applied: microscopy of lymph node aspirate (LNA); three immunochromatographic rapid diagnostic tests (RDTs), prototype rK28-ICT, rK39-ICT (both Coris BioConcept), commercial rK39 (InBios); ELISA for IgG, IgG1 and IgG2, against rK28, rK39 or crude lysate antigen. DNA detection and analysis, with 30 dogs, was of the ITS1 region using skin samples, and loop-mediated isothermal amplification (LAMP; Eiken Loopamp) of buffy coat, skin scrape or LNA. 15.4% of dogs were positive by LNA microscopy. The rK28 RDT had higher seropositivity rate (61%) than either a prototype rK39 RDT (31.4%) or commercial rK39 RDT (18.8%), without cross-reactivity with six other pathogens. IgG anti-rK39 ELISA antibody titres, but not IgG2, were positively correlated with number of clinical signs. LAMP with LNA had a higher positivity rate than PCR; buffy coat sampling was more sensitive than skin scrape. ITS1 confirmed Leishmania (Leishmania) infantum as the agent of CVL. Leishmania (Viannia) spp. was detected in skin samples from two dogs, compatible with Leishmania (Viannia) braziliensis. Conclusions/Significance Seroprevalence confirmed rapid increase in CVL in Puerto Iguazú. The rK28 RDT test potentially has great value for improved point-of-care diagnosis. Given cost reduction and accessibility, commercial LAMP may be applicable to buffy coat. RDT biomarkers of CVL clinical status are required to combat spread of CVL and HVL. The presence of Viannia, perhaps as an agent of human mucocutaneous leishmaniasis (MCL), highlights the need for vigilance and surveillance.
Changes in the Transverse Dimension of the Maxillary Arch of 5-Year-Olds Born With UCLP Since the Introduction of Nationwide Guidance

Objective: To determine whether the transverse dimensions of the maxillary arch of 5-year-old children with unilateral cleft lip and palate (UCLP) have changed following centralization of cleft services in the United Kingdom. Design: Retrospective cross-sectional study. Setting: Digital analysis of UCLP maxillary dental casts. Participants: All available maxillary dental casts from 5-year-old participants of the Clinical Standards Advisory Group (CSAG, N = 114) and Cleft Care UK (CCUK, N = 175) studies. Interventions: Quantitative measurements of the intercanine width (ICW), intermolar width (IMW), and the distance from the midline to the greater and lesser side canine (GC/LC) and greater side and lesser side second primary molar (GE/LE). Degree measurements of the greater and lesser arch form angles, arch length, anterior palatal depth (APD), and posterior palatal depth were also measured. Main outcome: Differences between the transverse dimensions of the maxillary arch for the CSAG and CCUK cohorts. Results: In 5 (ICW, IMW, LC, LE, and APD) of the 11 measurements, there was a statistically significant difference between the CSAG and CCUK cohorts. In all of these, the CCUK values were greater than CSAG. Conclusions: There have been small but positive improvements for the transverse maxillary dimensions since centralization of the UK cleft service.
PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection

Type 2 cytokines promote epithelial changes that help to expel worms during intestinal helminth infection. Oyesola et al. show that prostaglandin D2 and its receptor CRTH2 are novel negative regulators of this response, dampening the Type 2 cytokine–mediated program.
On the Accuracy of Clinical Insertion Angle Predictions With a Surgical Planning Platform for Cochlear Implantation

Hypothesis: Various studies over the last few decades have shown that the cochlea is not a uniform structure, but that its size and shape may vary quite substantially in between subjects. The surgical planning platform enables the user to quickly approximate the size of a cochlea within clinical imaging data by measuring the basal cochlear diameters A and B. It also allows for contact specific insertion angle predictions for MED-EL cochlear implant electrode arrays based on this individual anatomy approximation. The proposed, retrospective study was performed to evaluate the accuracy of these predictions. Methods: Preoperative CBCT scans of N = 91 MED-EL cochlear implant patients with different types of FLEX electrode arrays (flexible, thin, and straight arrays) were evaluated using a planning module. Both the initial version (based on an equation proposed by Escudé et al.) as well as a novel, recently proposed approach (called elliptic-circular approximation) was employed. All predictions were then compared to the actual insertion angles which were derived from postoperative CBCT images of the same patient. Results: Most prediction deviations of the investigated cases stayed below 45deg for all electrode arrays and both prediction methods. In general, prediction deviations increased from base to apex were found to be larger for longer electrode arrays. Hardly any significant differences between the two prediction methods were observed. However, particularly large deviations were found for the Escudé method and could be substantially deceased with the updated elliptic-circular approximation approach. Conclusions: The new platform version with its updated prediction module allows to reliably predict insertion angles even for cochlear anatomies with slightly unusual features and shapes.
Self-Management Micro-Video Health Education Program for Hemodialysis Patients

Self-management in hemodialysis patients is critical for optimal health outcomes. This study aimed to examine the effects of a theory-based micro-video health education program on the improvement of self-management, hemodialysis knowledge, and self-efficacy in hemodialysis patients. This quasi-experimental study employed a two group, pre- and post-test design. The sample was 80 hemodialysis patients from a dialysis center. The participants were assigned in a 1:1 ratio to receive routine care or a 3-month micro-video health education program. Between-group comparison showed that patients in the intervention group had significantly greater improvement in hemodialysis knowledge than those in the control group (p < .05). However, no significant group differences were observed in terms of self-management and self-efficacy. Within-group comparison showed that the overall self-management level of patients in both groups improved significantly, particularly in problem-solving skills and self-care dimensions. Therefore, micro-video health education can improve the self-management and hemodialysis knowledge in Chinese patients undergoing hemodialysis. Trial Registration: Registered at ClinicalTrials.gov with study number (ChiCTR1800018172; http://www.chictr.org.cn/index.aspx).
Ankle Angle but Not Knee Angle Influences Force Fluctuations During Plantar Flexion

Abstract The purpose of the study was to evaluate the influence of changes in ankle- and knee-joint angles on force steadiness and the discharge characteristics of motor units (MU) in soleus when the plantar flexors performed steady isometric contractions. Submaximal contractions (5, 10, 20, and 40% of maximum) were performed at two ankle angles (75° and 105°) and two knee angles (120° and 180°) by 14 young adults. The coefficient of variation of force decreased as the target force increased from 5 to 20% of maximal force, then remained unaltered at 40%. Independently of knee angle, the coefficient of variation for force at the ankle angle of 75° (long length) was always less (p<0.05) than that at 105° (shorter length). Mean discharge rate, discharge variability, and variability in neural activation of soleus motor units were less (p<0.05) at the 75° angle than at 105°. It was not possible to record MUs from medial gastrocnemius at the knee angle of 120° due to its minimal activation. The changes in knee-joint angle did not influence any of the outcome measures. The findings underscore the dominant role of the soleus muscle in the control of submaximal forces produced by the plantar flexor muscles.
Is Preexisting Cervical Degeneration a Risk Factor for Poor Prognosis in Whiplash-Associated Disorder?

ABSTRACT Background: The term whiplash describes the acceleration-deceleration mechanism of injury to the cervical spine. Whiplash injuries present with a variety of clinical and psychological manifestations, collectively termed as whiplash-associated disorders (WADs). Although largely self-limiting, some patients may experience long-lasting symptoms. This review aimed to summarize the current literature regarding the predictive value of cervical degeneration in the prognosis of patients with WAD. Methods: A comprehensive search of the literature was performed. Nine studies were identified, including 894 patients, with an age range between 16 and 76 years. Results: A statistically significant association was found between moderate facet joint degeneration and nonrecovery. Although no association was established between isolated disc degeneration and nonrecovery, total cervical degeneration (facet joint + disc degeneration) was shown to correlate with nonrecovery. All included studies demonstrated the lack of correlation between preexisting disc degeneration and clinical outcomes. Four studies showed a significant correlation between cervical degeneration and poor prognosis following whiplash injury. A significantly higher proportion of patients who remained symptomatic at 2 years following a whiplash injury had preexisting degenerative changes. Conclusions: This review highlights the presence of significant variability in the existing literature concerning WAD in terms of study methodology, definitions of cervical degeneration, and outcome measures. Degenerative changes of the facet joint lead to alterations in its biomechanics. Several cadaveric, biomechanical, and clinical studies have demonstrated facet joints as a source of pain in patients with chronic WAD. We present moderate evidence to suggest that preexisting facet joint degeneration is a negative prognostic indicator for long-lasting symptoms in WAD. Conversely, preexisting disc degeneration is not associated with chronicity of WAD symptoms. We propose facet joint instability due to facet joint capsule rupture as a potential mechanism for nonrecovery. Further studies are needed to inform our knowledge of the long-term sequelae of WAD among patients with preexisting cervicalspine degeneration.
The safety and efficacy of erlotinib and ramucirumab combination in EGFR-mutant non-small-cell lung cancer

ABSTRACT Introduction EGFR-tyrosine kinase inhibitors (TKIs) changed the natural history of EGFR-mutant advanced NSCLC patients, but acquired resistance is inevitable. New strategies are being tested to overcome or prevent the emergence of resistance mechanisms to first-line TKIs, among which combinations of TKIs with antiangiogenic agents. Areas covered We performed a literature search for preclinical and clinical data on the interplay and dual inhibition of EGFR/VEGF pathways, particularly in EGFR-mutant NSCLC. We then focused on RELAY, a placebo-controlled phase 3 trial evaluating ramucirumab combined to erlotinib in treatment-naïve advanced EGFR-mutant NSCLC patients. This article aims to summarize efficacy and safety of the ramucirumab-erlotinib combination in this setting. Expert opinion RELAY confirmed the clinical relevance of combining EGFR and VEGF(R)-targeting therapies, previously investigated in smaller phase 2–3 trials of erlotinib and bevacizumab. However, the meaningful PFS benefit observed in the ramucirumab + erlotinib arm is counterbalanced by the toxicity profile of ramucirumab and the need for bimonthly infusions. Pending OS results are, therefore, critical to assess the real benefit from this combination, especially as first-line osimertinib has improved survival in EGFR-mutant NSCLC patients and will probably remain the pivotal EGFR-TKI in this setting. However, its heterogeneous efficacy across subgroups paves the way for osimertinib-based combinations, which are being investigated in ongoing trials.
Operationalizing Social Environments in Cognitive Aging and Dementia Research: A Scoping Review

Background: Social environments are a contributing determinant of health and disparities. This scoping review details how social environments have been operationalized in observational studies of cognitive aging and dementia. Methods: A systematic search in PubMed and Web of Science identified studies of social environment exposures and late-life cognition/dementia outcomes. Data were extracted on (1) study design; (2) population; (3) social environment(s); (4) cognitive outcome(s); (5) analytic approach; and (6) theorized causal pathways. Studies were organized using a 3-tiered social ecological model at interpersonal, community, or policy levels. Results: Of 7802 non-duplicated articles, 123 studies met inclusion criteria. Eighty-four studies were longitudinal (range 1–28 years) and 16 examined time-varying social environments. When sorted into social ecological levels, 91 studies examined the interpersonal level; 37 examined the community/neighborhood level; 3 examined policy level social environments; and 7 studies examined more than one level. Conclusions: Most studies of social environments and cognitive aging and dementia examined interpersonal factors measured at a single point in time. Few assessed time-varying social environmental factors or considered multiple social ecological levels. Future studies can help clarify opportunities for intervention by delineating if, when, and how social environments shape late-life cognitive aging and dementia outcomes.
Human macrophages utilize a wide range of pathogen recognition receptors to recognize Legionella pneumophila, including Toll-Like Receptor 4 engaging Legionella lipopolysaccharide and the Toll-like Receptor 3 nucleic-acid sensor

Cytokines made by macrophages play a critical role in determining the course of Legionella pneumophila infection. Prior murine-based modeling indicated that this cytokine response is initiated upon recognition of L. pneumophila by a subset of Toll-like receptors, namely TLR2, TLR5, and TLR9. Through the use of shRNA/siRNA knockdowns and subsequently CRISPR/Cas9 knockouts (KO), we determined that TRIF, an adaptor downstream of endosomal TLR3 and TLR4, is required for full cytokine secretion by human primary and cell-line macrophages. By characterizing a further set of TLR KO’s in human U937 cells, we discerned that, contrary to the viewpoint garnered from murine-based studies, TLR3 and TLR4 (along with TLR2 and TLR5) are in fact vital to the macrophage response in the early stages of L. pneumophila infection. This conclusion was bolstered by showing that i) chemical inhibitors of TLR3 and TLR4 dampen the cytokine output of primary human macrophages and ii) transfection of TLR3 and TLR4 into HEK cells conferred an ability to sense L. pneumophila. TLR3- and TLR4-dependent cytokines promoted migration of human HL-60 neutrophils across an epithelial layer, pointing to the biological importance for the newfound signaling pathway. The response of U937 cells to L. pneumophila LPS was dependent upon TLR4, a further contradiction to murine-based studies, which had concluded that TLR2 is the receptor for Legionella LPS. Given the role of TLR3 in sensing nucleic acid (i.e., dsRNA), we utilized newly-made KO U937 cells to document that DNA-sensing by cGAS-STING and DNA-PK are also needed for the response of human macrophages to L. pneumophila. Given the lack of attention given them in the bacterial field, C-type lectin receptors were similarly examined; but, they were not required. Overall, this study arguably represents the most extensive, single-characterization of Legionella-recognition receptors within human macrophages.
Near-Pan-neutralizing, Plasma Deconvoluted Antibody N49P6 Mimics Host Receptor CD4 in Its Quaternary Interactions with the HIV-1 Envelope Trimer

Binding to target cell CD4 is the first crucial step required for HIV-1 infection. Thus, the CD4-binding site (CD4bs) is one of the most accessible sites for antibodies (Abs). ABSTRACT The first step in HIV-1 entry is the attachment of the envelope (Env) trimer to target cell CD4. As such, the CD4-binding site (CD4bs) remains one of the few universally accessible sites for antibodies (Abs). We recently described a method of isolating Abs directly from the circulating plasma and described a panel of broadly neutralizing Abs (bnAbs) from an HIV-1 “elite neutralizer” referred to as patient N49 (N49 Ab lineage [M. M. Sajadi, A. Dashti, Z. R. Tehrani, W. D. Tolbert, et al., Cell 173:1783–1795.e14, 2018, https://doi.org/10.1016/j.cell.2018.03.061]). Here, we describe the molecular details of antigen recognition by N49P6, an Ab of the N49 lineage that recapitulates most of the neutralization breadth and potency of the donor’s plasma IgG. Our studies done in the context of monomeric and trimeric antigens indicate that N49P6 combines many characteristics of known CD4bs-specific bnAbs with features that are unique to the N49 Ab lineage to achieve its remarkable neutralization breadth. These include the omission of the CD4 Phe43 cavity and dependence instead on interactions with highly conserved gp120 inner domain layer 3. Interestingly, when bound to BG505 SOSIP, N49P6 closely mimics the initial contact of host receptor CD4 to the adjacent promoter of the HIV-1 Env trimer to lock the trimer in the closed conformation. Altogether, N49P6 defines a new class of near-pan-neutralizing, plasma deconvoluted CD4bs Abs that we refer to as the N49P series. The details of the mechanisms of action of this new Ab class pave the way for the next generation of HIV-1 bnAbs that can be used as vaccine components of therapeutics. IMPORTANCE Binding to target cell CD4 is the first crucial step required for HIV-1 infection. Thus, the CD4-binding site (CD4bs) is one of the most accessible sites for antibodies (Abs). However, due to steric constraints, only a few Abs are capable of targeting this site. Here, we show that the exceptional neutralization breadth and potency of N49P6, a near-pan-neutralizing Ab targeting the CD4bs isolated from the plasma of an HIV-1 “elite neutralizer,” patient N49, are due to its signature combination of more typical CD4bs Ab-binding characteristics with unique interactions with the highly conserved gp120 inner domain. In addition, we also present a structural analysis of N49P6 in complex with the BG505 SOSIP trimer to show that N49P6 exhibits remarkable breadth in part by mimicking CD4’s quaternary interaction with the neighboring gp120 protomer. In its mode of antigen interaction, N49P6 is unique and represents a new class of CD4bs-specific bnAbs.