The expanding amyloid family: Structure, stability, function, and pathogenesis.

The hidden world of amyloid biology has suddenly snapped into atomic-level focus, revealing over 80 amyloid protein fibrils, both pathogenic and functional. Unlike globular proteins, amyloid proteins flatten and stack into unbranched fibrils. Stranger still, a single protein sequence can adopt wildly different two-dimensional conformations, yielding distinct fibril polymorphs. Thus, an amyloid protein may define distinct diseases depending on its conformation. At the heart of this conformational variability lies structural frustrations. In functional amyloids, evolution tunes frustration levels to achieve either stability or sensitivity according to the fibril's biological function, accounting for the vast versatility of the amyloid fibril scaffold.

3D Nanocrystallography and the Imperfect Molecular Lattice.

Crystallographic analysis relies on the scattering of quanta from arrays of atoms that populate a repeating lattice. While large crystals built of lattices that appear ideal are sought after by crystallographers, imperfections are the norm for molecular crystals. Additionally, advanced X-ray and electron diffraction techniques, used for crystallography, have opened the possibility of interrogating micro- and nanoscale crystals, with edges only millions or even thousands of molecules long. These crystals exist in a size regime that approximates the lower bounds for traditional models of crystal nonuniformity and imperfection. Accordingly, data generated by diffraction from both X-rays and electrons show increased complexity and are more challenging to conventionally model. New approaches in serial crystallography and spatially resolved electron diffraction mapping are changing this paradigm by better accounting for variability within and between crystals. The intersection of these methods presents an opportunity for a more comprehensive understanding of the structure and properties of nanocrystalline materials.

Theoretical Prediction and Experimental Verification of IrOx Supported on Titanium Nitride for Acidic Oxygen Evolution Reaction.

Reducing iridium (Ir) catalyst loading for acidic oxygen evolution reaction (OER) is a critical strategy for large-scale hydrogen production via proton exchange membrane (PEM) water electrolysis. However, simultaneously achieving high activity, long-term stability, and reduced material cost remains challenging. To address this challenge, we develop a framework by combining density functional theory (DFT) prediction using model surfaces and proof-of-concept experimental verification using thin films and nanoparticles. DFT results predict that oxidized Ir monolayers over titanium nitride (IrOx/TiN) should display higher OER activity than IrOx while reducing Ir loading. This prediction is verified by depositing Ir monolayers over TiN thin films via physical vapor deposition. The promising thin film results are then extended to commercially viable powder IrOx/TiN catalysts, which demonstrate a lower overpotential and higher mass activity than commercial IrO2 and long-term stability of 250 h to maintain a current density of 10 mA cm-2. The superior OER performance of IrOx/TiN is further confirmed using a proton exchange membrane water electrolyzer (PEMWE), which shows a lower cell voltage than commercial IrO2 to achieve a current density of 1 A cm-2. Both DFT and in situ X-ray absorption spectroscopy reveal that the high OER performance of IrOx/TiN strongly depends on the IrOx-TiN interaction via direct Ir-Ti bonding. This study highlights the importance of close interaction between theoretical prediction based on mechanistic understanding and experimental verification based on thin film model catalysts to facilitate the development of more practical powder IrOx/TiN catalysts with high activity and stability for acidic OER.

Recommendations for asthma monitoring in children: A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Electron Diffraction of 3D Molecular Crystals.

Electron crystallography has a storied history which rivals that of its more established X-ray-enabled counterpart. Recent advances in data collection and analysis have sparked a renaissance in the field, opening a new chapter for this venerable technique. Burgeoning interest in electron crystallography has spawned innovative methods described by various interchangeable labels (3D ED, MicroED, cRED, etc.). This Review covers concepts and findings relevant to the practicing crystallographer, with an emphasis on experiments aimed at using electron diffraction to elucidate the atomic structure of three-dimensional molecular crystals.

Intravenous magnesium sulfate for asthma exacerbations in children: Systematic review with meta-analysis.

BACKGROUND: Asthma is the most prevalent chronic disease in children and constitutes a significant healthcare burden. First-line therapy for acute asthma exacerbations is well established. However, secondary treatments, including intravenous magnesium sulfate (IV-MgSO4), remain variable due to scarcity of data on its efficacy and safety. OBJECTIVE: To assess the effectiveness and safety of IV-MgSO4 as a second line of treatment in managing children with asthma exacerbations. METHODS: We searched five databases from inception until April 2023 on randomized clinical trials of IV-MgSO4 in children with acute asthma exacerbations. The primary outcomes were hospitalization rate and length, and change in the severity score. Secondary outcomes included percentage increase in peak expiratory flow rate (PEFR), hospital re-admission rate, need and length for pediatric intensive care unit (PICU) treatment, and adverse effects. Meta-analysis was performed for three outcomes with estimated odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs). RESULTS: Eleven studies met the final criteria. In comparison to control, administration of IV-MgSO4 was associated with a reduced hospitalization risk (OR 0.15; 95%CI: 0.03, 0.73) in four studies, and improvement of lung function (MD 26.77% PEFR; 95%CI: 18.41, 54.79) in two studies. There were no significant differences in the length of stay between groups. Due to heterogeneity, a narrative synthesis of other outcomes was performed. CONCLUSION: The use of IV-MgSO4 demonstrated a reduction in the hospitalization rate and PEFR improvement in children with asthma exacerbations. Adverse effects were rare. Further well-designed studies are needed to better determine the efficacy and safety profile of IV-MgSO4.

Association of respiratory virus types with clinical features in bronchiolitis: Implications for virus testing strategies. A systematic review and meta-analysis.

BACKGROUND: Bronchiolitis is a leading cause of infant hospitalization, linked to respiratory syncytial virus (RSV) and rhinovirus (RV). Guidelines lack specific viral testing for bronchiolitis management. To establish effective management strategies, it is crucial to assess whether specific respiratory virus types are correlated with distinct examination features. METHODS: Through a systematic search of three databases, 21 studies were qualitatively analyzed, with 18 used for meta-analysis. Various outcomes like wheezing on auscultation, fever, atopic traits, and infection severity were evaluated. RESULTS: RSV-positive bronchiolitis was associated with a higher need for oxygen supplementation (OR 1.78, 95% CI 1.04-3.02) in 5 studies, while RV-positive bronchiolitis was more frequently linked to personal history of eczema (OR 0.60, 95% CI 0.41-0.88) in 6 studies. No significant differences were observed in the other outcomes examined. CONCLUSIONS: Bronchiolitis caused by RSV or RV presents with similar clinical features. Despite the associations between RSV-positive bronchiolitis and need for oxygen supplementation, and RV-positive bronchiolitis and a history of eczema, our study shows that viral etiology of bronchiolitis cannot be determined solely based on clinical presentation. Tailored management strategies, informed by accurate viral testing, seem crucial in clinical practice for enhancing patient outcomes in severe bronchiolitis.

Reactance inversion in moderate to severe persistent asthma: low birth weight, prematurity effect, and bronchodilator response.

INTRODUCTION: Reactance inversion (RI) has been associated with impaired peripheral airway function in persistent asthma. However, there is little to no data about the difference between asthmatic children with and without RI. This study aimed to detect clinical and lung function differences in moderate-severe asthmatic children with and without RI. METHODS: This study was conducted between 2021 and 2022 in asthmatic school-age children. Impulse oscillometry (IOS) and spirometry were performed according to ATS/ERS standards. RESULTS: A total of 62 patients, with a mean age of 8.4 years, 54.8% were males and were divided into three groups: group 1 (32.3%) with no RI, group 2 (27.4%) with RI but disappearing after bronchodilator test and group 3 (40.3%) with persistent RI after bronchodilator test. Children in groups 2 and 3 had significantly lower birth weights than in group 1. Group 2 had lower gestational age compared to group 1. FEV1 and FEF25-75 of forced vital capacity were significantly lower in groups 2 and 3. In group 3, R5, AX, R5-20, and R5-R20/R5 ratios were significantly higher. Bronchodilator responses (BDR) in X5c, AX, and R5-R20 were significantly different between groups and lower in group 3. CONCLUSION: RI is frequently found in children with moderate-severe persistent asthma, particularly in those with a history of prematurity or low birth weight. In some patients, RI disappears after the bronchodilator test; however, it, persists in those with the worst pulmonary function. RI could be a small airway dysfunction marker.

How Much Protection Does a Collar Provide? Assessing Risk of Early Periprosthetic Femur Fractures Following Total Hip Arthroplasty in Elderly Patients.

BACKGROUND: Periprosthetic fractures (PPFs) account for approximately 25% of early revisions following total hip arthroplasty (THA). Cemented femoral fixation is associated with a lower-risk of PPF, and collared-cementless stems may reduce the risk as well. The objective of this study was to compare early-PPF rates between cemented, collared-cementless, and non-collared cementless stems in elderly patients. METHODS: A consecutieve-series of 11,522 primary THAs performed between 2016 and 2021 at our institution in patients >65 years of age was identified. Stem types used were categorized as cemented, collared-cementless, or non-collared cementless. Patients undergoing THA who had cemented-stems were older, more commonly women, and more likely to have a posterior-approach. To reduce confounding of patient characteristics, we matched patients in the 3 stem-categories according to age, sex, and body mass index. This generated 3-groups (cemented, collared-cementless, and non-collared cementless) consisting of 936 patients per group. The mean age of these 2,808 patients was 73 years, the mean body mass index was 27, and 67% were women. Logistic regressions were used to evaluate risk-factors for early-PPF. In the entire cohort of primary THA in elderly patients, there were 85 early PPFs (0.7%) over the study period. RESULTS: Non-collared cementless stems were associated with an increased risk of early PPF (OR: 3.11; P = .03) compared to collared-cementless stems. There were no early PPFs in the matched cemented cohort, 6 early PPFs in the matched collared-cementless cohort, and 16 early-PPFs in the matched non-collared cementless cohort (0% versus 0.64% versus 1.71%, P < .001). CONCLUSIONS: In this large-series of patients >65 years of age undergoing primary THA, cemented stem fixation had the lowest incidence of early PPF, but collared-cementless stems had a nearly 3-fold decrease in risk for early PPF compared to non-collared cementless stems.

Contribution of the Medial Iliofemoral Ligament to Hip Stability After Total Hip Arthroplasty Through the Direct Anterior Approach.

BACKGROUND: Dislocation after total hip arthroplasty (THA) is a primary reason for THA revision. During THA through the direct anterior approach (DAA), the iliofemoral ligament, which provides the main resistance to external rotation (ER) of the hip, is commonly partially transected. We asked: (1) what is the contribution of the medial iliofemoral ligament to resisting ER after DAA THA? and (2) how much resistance to ER can be restored by repairing the ligament? METHODS: A fellowship-trained surgeon performed DAA THA on 9 cadaveric specimens. The specimens were computed tomography scanned before and after implantation. Prior to testing, the ER range of motion of each specimen to impingement in neutral and 10° of extension was computationally predicted. Each specimen was tested on a 6-degrees-of-freedom robotic manipulator. The pelvis was placed in neutral and 10° of extension. The femur was externally rotated until it reached the specimen's impingement target. Total ER torque was recorded with the medial iliofemoral ligament intact, after transecting the ligament, and after repair. Torque at extremes of motion was calculated for each condition. To isolate the contribution of the native ligament, the torque for the transected state was subtracted from both the native and repaired conditions. RESULTS: The medial iliofemoral ligament contributed an average of 68% (range, 34 to 87) of the total torque at the extreme of motion in neutral and 80% (58 to 97) in 10° of extension. The repaired ligament contributed 17% (1 to 54) of the total torque at the extreme of motion in neutral and 14% (5 to 38) in 10° of extension, restoring on average 18 to 25% of the native resistance against ER. CONCLUSIONS: The medial iliofemoral ligament was an important contributor to the hip torque at the extreme of motion during ER. Repairing the ligament restored a fraction of its ability to generate torque to resist ER.

The Use of Aspirin for Venous Thromboembolism Prophylaxis in Patients Who Have Morbid Obesity Undergoing Primary and Revision Total Joint Arthroplasty.

BACKGROUND: Venous thromboembolism (VTE) poses a major clinical concern due to its life-threatening nature, and obese and morbidly obese patients are thought to be at an increased risk for VTE. The aims of this study were twofold; first, to explore VTE rates in patients who have a body mass index (BMI) > 40 undergoing primary and revision total joint arthroplasty, and second, to investigate aspirin (ASA) efficacy and safety. METHODS: We identified all patients (n = 4,672) who had a BMI > 40 who underwent primary and revision total joint arthroplasty from 2016 to 2022 at a single academic tertiary care center. Patients were stratified by BMI groups: 40 to 44.9 (n = 3,462), 45 to 49.9 (n = 935), and 50+ (n = 275). The primary outcome was any VTE event within 90 days postoperatively. The secondary outcome consisted of wound complications within 90 days postoperatively. RESULTS: The total VTE rate was 0.4% (n = 21) and did not differ statistically between the BMI groups (0.4 versus 0.4 versus 0.7%, P = .669). The VTEs consisted of 6 deep venous thromboses (DVTs), 14 pulmonary embolisms, and one concomitant deep venous thrombosis and pulmonary embolism. The VTE rates were not statistically different between patients who received aspirin 325 mg 0.5% (n = 9), aspirin 81 mg 0.2% (n = 1), aspirin + anticoagulant (AC) 0.5% (n = 6), and AC alone 0.4% (n = 5) (P = .954). In addition, wound complications did not differ significantly between patients who received ASA 325 mg, ASA 81mg, ASA + AC, or AC alone (1.6 versus 1.0 versus 1.8 versus 1.1%, P = .351). CONCLUSIONS: The use of aspirin 325 and 81 mg was found to have similar VTE rates as aspirin + ACs and ACs alone, with no significant increase in wound complications. In patients who have a BMI > 40, the use of aspirin is a safe option for VTE prophylaxis and should be prescribed in the context of the patient who has other risk factors for VTE.

Clinical Outcomes of Isolated Polyethylene Exchange Versus Full Component Revision for the Management of Instability Following Total Knee Arthroplasty.

BACKGROUND: Instability following total knee arthroplasty (TKA) is a common cause for revision. Isolated polyethylene exchange (IPE) can be performed to increase knee joint stability, but results have been mixed. The purpose of this study was to compare the survivorship and patient-reported outcomes of patients undergoing revision TKA for instability with IPE versus full component revision. METHODS: We reviewed 280 primary TKAs undergoing revision TKA for instability. There were 181 knees that underwent revision with IPE, compared to 99 knees treated with full component revision. The mean follow-up was 32.8 months (range, 24.8 to 82.5). Patient demographics, radiographic parameters, prosthesis constraints, reoperations for instability, and patient-reported outcomes were compared. RESULTS: The survivorship for instability was significantly higher at 2 years (99 versus 92%, P = .024) and 5 years (94 versus 84%, P = .024) for patients undergoing full component revision. Although there was no difference in Knee Injury and Osteoarthritis Outcome Score for Joint Replacements and Veterans RAND 12 physical component scores between the 2 groups at 6 weeks, 1 year, and 2 years after surgery, full revision patients reported greater pain relief (P = .006) and greater improvements in Veterans RAND 12 physical component scores (P = .027) at 1 year and Knee Injury and Osteoarthritis Outcome Score for Joint Replacements scores at 2 years (P = .017) compared to IPE patients. Men were associated with an increased risk for recurrent instability following IPE (hazard ratio 3.3, 95% confidence interval: [1.0 to 10.6]). CONCLUSIONS: Isolated polyethylene exchange was not as reliable or durable compared to full component revision for the management of postoperative instability. These procedures should only be reserved in cases with competent collaterals and when component position, offset, and rotation are optimized.

Dislocation Following Anterior and Posterior Total Hip Arthroplasty in the Setting of Spinal Deformity and Stiffness: Evolving Trends Using a High-Risk Protocol at a Single Tertiary Center.

BACKGROUND: Patients who have spinal stiffness and deformity are at the highest risk for dislocation after total hip arthroplasty (THA). Previous reports of this cohort are limited to antero-lateral and postero-lateral (PL) approaches. We investigated the dislocation rate after direct anterior (DA) and PL approach THA with a contemporary high-risk protocol to optimize stability. METHODS: We investigated patients undergoing THA who had preoperative biplanar imaging from January-December 2019. Patients were identified using radiographic criteria of spinal-stiffness (<10-degree change in sacral slope from standing to seated) and deformity (flatback deformity with >10-degree difference in pelvic incidence and lumbar lordosis). There were 367 patients identified (181 DA, 186 PL). The primary outcome was dislocation rate at 2-years postoperatively. Risk-factors for dislocation were evaluated using logistic regressions (significance level of 0.05). RESULTS: There were 6 (1.6%) dislocations in the entire cohort, with low dislocation rates for both DA (0.6%) and PL-THA (2.7%). We observed increased utilization of dual mobility with larger outer head bearings (>38 mm) with PL-THA (34.4 versus 5.0%, P < .01) and conversely increased utilization of 32-mm femoral-heads with DA-THA (39.4 versus 7.0%, P < .001). Surgical approach (PL) was not a significant risk-factor for dislocation (odds ratio: 5.03, P = .15). Patients who had a history of lumbar-fusion had 8-times higher odds for dislocation (OR: 8.20, P = .020). CONCLUSIONS: To the best of our knowledge, this is the largest series to date evaluating DA and PL-THA in the hip-spine 2B-group. Our results demonstrate lower dislocation rate than expected with either surgical approach using a high-risk protocol.

Perioperative Cefazolin for Total Joint Arthroplasty Patients Who Have a Penicillin Allergy: Is It Safe?

BACKGROUND: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. METHODS: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. RESULTS: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. CONCLUSIONS: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. LEVEL OF EVIDENCE: III.

The John N. Insall Award: Does Melatonin Improve Subjective Sleep Quality After Total Knee Arthroplasty? A Randomized, Placebo-Controlled Trial.

BACKGROUND: Sleep disturbance is a common problem following total knee arthroplasty (TKA). The objective of this study was to determine if exogenous melatonin improves sleep quality following primary TKA. METHODS: A randomized, double-blind, placebo-controlled trial was conducted. A total of 172 patients undergoing unilateral TKA for primary knee osteoarthritis were randomized to receive either 5 mg melatonin (n = 86) or 125 mg vitamin C placebo (n = 86) nightly for 6 weeks. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) at 6 weeks and 90 days postoperatively. Secondary outcomes included 6-week and 90-day patient-reported outcome measures (PROMs), morphine milligram equivalents prescribed, medication compliance, adverse events, and 90-day readmissions. RESULTS: Mean PSQI scores worsened at 6 weeks before returning to the preoperative baseline at 90 days in both groups. There were no differences in PSQI scores between melatonin and placebo groups at 6 weeks (10.2 ± 4.2 versus 10.5 ± 4.4, P = .66) or 90 days (8.1 ± 4.1 versus 7.5 ± 4.0, P = .43). Melatonin did not improve the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, Lower Extremity Activity Scale, Visual Analog Scale for pain, or Veterans Rand 12 Physical Component Score or Mental Component Score at 6 weeks or 90 days. Poor sleep quality was associated with worse PROMs at 6 weeks and 90 days on univariate and multivariable analyses, but melatonin did not modify these associations. There were no differences in morphine milligram equivalents prescribed, medication compliances, adverse events, or 90-day readmissions between both groups. CONCLUSIONS: Exogenous melatonin did not improve subjective sleep quality or PROMs at 6 weeks or 90 days following TKA. Poor sleep quality was associated with worse patient-reported function and pain. Our results do not support the routine use of melatonin after TKA.

The Impact of Noise and Brightness on Object Detection Methods.

The application of deep learning to image and video processing has become increasingly popular nowadays. Employing well-known pre-trained neural networks for detecting and classifying objects in images is beneficial in a wide range of application fields. However, diverse impediments may degrade the performance achieved by those neural networks. Particularly, Gaussian noise and brightness, among others, may be presented on images as sensor noise due to the limitations of image acquisition devices. In this work, we study the effect of the most representative noise types and brightness alterations on images in the performance of several state-of-the-art object detectors, such as YOLO or Faster-RCNN. Different experiments have been carried out and the results demonstrate how these adversities deteriorate their performance. Moreover, it is found that the size of objects to be detected is a factor that, together with noise and brightness factors, has a considerable impact on their performance.

Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.

Activation and Conversion of Methane to Syngas over ZrO2/Cu(111) Catalysts near Room Temperature.

Enzymatic systems achieve the catalytic conversion of methane at room temperature under mild conditions. In this study, varying thermodynamic and kinetic parameters, we show that the reforming of methane by water (MWR, CH4 + H2O → CO + 3H2) and the water-gas shift reaction (WGS, CO + H2O → H2 + CO2), two essential processes to integrate fossil fuels toward a H2 energy loop, can be achieved on ZrO2/Cu(111) catalysts near room temperature. Measurements of ambient-pressure X-ray photoelectron spectroscopy and mass spectrometry, combined with density functional calculations and kinetic Monte Carlo simulations, were used to study the behavior of the inverse oxide/metal catalysts. The superior performance is associated with a unique zirconia-copper interface, where multifunctional sites involving zirconium, oxygen, and copper work coordinatively to dissociate methane and water at 300 K and move forward the MWR and WGS processes.

Prospecting for natural products by genome mining and microcrystal electron diffraction.

More than 60% of pharmaceuticals are related to natural products (NPs), chemicals produced by living organisms. Despite this, the rate of NP discovery has slowed over the past few decades. In many cases the rate-limiting step in NP discovery is structural characterization. Here we report the use of microcrystal electron diffraction (MicroED), an emerging cryogenic electron microscopy (CryoEM) method, in combination with genome mining to accelerate NP discovery and structural elucidation. As proof of principle we rapidly determine the structure of a new 2-pyridone NP, Py-469, and revise the structure of fischerin, an NP isolated more than 25 years ago, with potent cytotoxicity but hitherto ambiguous structural assignment. This study serves as a powerful demonstration of the synergy of MicroED and synthetic biology in NP discovery, technologies that when taken together will ultimately accelerate the rate at which new drugs are discovered.

Risk for recurrence of symptomatic upper-extremity deep vein thrombosis in patients without cancer: Analysis of three RIETE cohorts.

BACKGROUND: The natural history of patients with a pacemaker-related upper-extremity deep vein thrombosis (UEDVT) has not been consistently studied. METHODS: We used the RIETE registry data to compare the outcomes during anticoagulation and after its discontinuation in noncancer patients with symptomatic UEDVT associated with a pacemaker, other catheters, or no catheter. The major outcome was the composite of symptomatic pulmonary embolism or recurrent DVT. RESULTS: As of February 2022, 2578 patients with UEDVT were included: 156 had a pacemaker-related UEDVT, 557 had other catheters, and 1865 had no catheter. During anticoagulation, 61 patients (2.3%) developed recurrent VTE, 38 had major bleeding (1.4%), and 90 died (3.4%). After its discontinuation, 52 patients (4.4%) had recurrent acute venous thromboembolism (VTE) and six had major bleeding (0.5%). On multivariable analysis, there were no differences among subgroups in the rates of VTE recurrences or major bleeding during anticoagulation. After its discontinuation, patients with a pacemaker-related UEDVT had a higher risk for VTE recurrences than those with no catheter (adjusted OR: 4.59; 95% CI: 1.98-10.6). CONCLUSIONS: Patients with pacemaker-related UEDVT are at increased risk for VTE recurrences after discontinuing anticoagulation. If our findings are validated in adequately designed trials, this may justify changes in the current recommendations on the duration of anticoagulation.