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ObjectiveDuring the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification.MethodsData from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually.ResultsWe analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person.ConclusionsOf the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

A high-velocity fluid stream ejected from an orifice or nozzle is a common mechanism to produce liquid jets in inkjet printers or to produce sprays among other applications. In the present research, we show the generation of liquid jets of controllable direction produced within a sessile water droplet by thermocavitation. The jets are driven by an acoustic shock wave emitted by the collapse of a hemispherical vapor bubble at the liquid-solid/substrate interface. The generated shock wave is reflected at the liquid-air interface due to acoustic impedance mismatch generating multiple reflections inside the droplet. During each reflection, a force is exerted on the interface driving the jets. Depending on the position of the generation of the bubble within the droplet, the mechanical energy of the shock wave is focused on different regions at the liquid-air interface, ejecting cylindrical liquid jets at different angles. The ejected jet angle dependence is explained by a simple ray tracing model of the propagation of the acoustic shock wave inside the droplet.

The most common method to generate optic cavitation involves the focusing of short-pulsed lasers in a transparent liquid media. In this work, we review a novel method of optic cavitation that uses low power CW lasers incident in highly absorbing liquids. This novel method of cavitation is called thermocavitation. Light absorbed heats up the liquid beyond its boiling temperature (spinodal limit) in a time span of microseconds to milliseconds (depending on the optical intensity). Once the liquid is heated up to its spinodal limit (~300°C for pure water), the superheated water becomes unstable to random density fluctuations and an explosive phase transition to vapor takes place producing a fast-expanding vapor bubble. Eventually, the bubble collapses emitting a strong shock-wave. The bubble is always attached to the surface taking a semi-spherical shape, in contrast to that produced by pulsed lasers in transparent liquids, where the bubble is produced at the focal point. Using high speed video (105 frames/s), we study the bubble's dynamic behavior. Finally, we show that heat diffusion determines the water superheated volume and, therefore, the amplitude of the shock wave. A full experimental characterization of thermocavitation is described.

We report on the generation of liquid columns that extend far beyond the traditional Rayleigh-Plateau instability onset. The columns are driven by the acoustic pressure wave emitted after bubble collapse. A high-speed video imaging device, which records images at a rate of up to 105 fps, was employed to follow their dynamics. These bubbles, commonly termed thermocavitation bubbles, are generated by focusing a midpower (275 mW) continuous wavelength laser into a highly absorbing liquid droplet. A simple model of the propagation of the pressure wavefront emitted after the bubble collapse shows that focusing the pressure wave at the liquid-air interface drives the evolution of the liquid columns. Control over the aspect ratio of the liquid column is realized by adjusting the cavitation bubble's size, beam focus position, and droplet volume. © 2013 by Begell House, Inc.

Purpose: Reaching and coordination tasks are widely used in traditional physical rehabilitation programs for individuals with Ataxia. Virtual reality interventions could optimize the motor performance of these individuals; however, the type of virtual interface may influence performance during virtual practice. We aimed to estimate the extent of the effect of different interfaces (webcam and touchscreen) on the motor performance of individuals with various types of genetic ataxia, compared to a control group, during virtual computer game tasks., Methods: Repeated exposure quasi-experimental design, which included seventeen volunteers diagnosed with progressive ataxia between 21 and 64 years of age and sixteen age-matched controls. The virtual game tasks were based on the MoveHero software, performed using different interfaces (webcam or touchscreen). Subgroups of participants with genetic ataxia performed the virtual games using the interfaces in different orders (webcam interface followed by touchscreen interface, or vice-versa). The absolute error (AE), variable error (VE), number of hits, and anticipation were used to reflect the motor performance during the virtual task., Results: Participants with ataxia presented more variable and absolute errors, a lower number of hits, and greater anticipation error than controls (p<0.05). For participants with ataxia, a greater AE was found only in the sequence touchscreen followed by webcam interface (i.e., the sequence webcam before touchscreen presented lower AE)., Conclusion: The group of participants with genetic ataxia presented lower performance than the control group regardless of the interface (webcam or touchscreen). The most interesting observation was that although practicing with the webcam interface offers features that make the task more complex than the touchscreen interface, resulting in lower performance, this interface facilitated performance in a subsequent touchscreen task only in individuals with ataxia, suggesting that a virtual interface engenders greater transfer to other tasks. Registered at Registro Brasileiro de Ensaios Clínicos (ReBEC) database number identifier: RBR-3q685r5., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Graciani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Slower adaptation of the QT interval to sudden changes in heart rate has been identified as a risk marker of ventricular arrhythmia. The gradual changes observed in exercise stress testing facilitates the estimation of the QT-RR adaptation time lag., Methods: The time lag estimation is based on the delay between the observed QT intervals and the QT intervals derived from the observed RR intervals using a memoryless transformation. Assuming that the two types of QT interval are corrupted with either Gaussian or Laplacian noise, the respective maximum likelihood time lag estimators are derived. Estimation performance is evaluated using an ECG simulator which models change in RR and QT intervals with a known time lag, muscle noise level, respiratory rate, and more. The accuracy of T-wave end delineation and the influence of the learning window positioning for model parameter estimation are also investigated., Results: Using simulated datasets, the results show that the proposed approach to estimation can be applied to any changes in heart rate trend as long as the frequency content of the trend is below a certain frequency. Moreover, using a proper position of the learning window for exercise so that data compensation reduces the effect of nonstationarity, a lower mean estimation error results for a wide range of time lags. Using a clinical dataset, the Laplacian-based estimator shows a better discrimination between patients grouped according to the risk of suffering from coronary artery disease., Conclusions: Using simulated ECGs, the performance evaluation of the proposed method shows that the estimated time lag agrees well with the true time lag.

The number of critically ill patients that present to emergency departments across the world continues to rise. In fact, the proportion of critically ill patients in emergency departments is now higher than pre-COVID-19 pandemic levels. [1] The emergency physician (EP) is typically the first physician to evaluate and resuscitate the critically ill patient. Given the continued shortage of intensive care unit (ICU) beds, persistent staff shortages, and overall inefficient hospital throughput, EPs are often tasked with providing intensive care to these patients long beyond the initial resuscitation phase. Prolonged boarding of critically ill patients in the ED is associated with increased ICU and hospital length of stay, increased adverse events, ED staff burnout, decreased patient and family satisfaction, and, most importantly, increased mortality. [2-5]. As such, it is imperative for the EP to be knowledgeable about recent literature in resuscitation and critical care medicine, so that critically ill ED patients can continue to receive the best, most up-to-date evidence-based care. This review summarizes important articles published in 2023 that pertain to the resuscitation and management of select critically ill ED patients. Topics included in this article include cardiac arrest, post-cardiac arrest care, septic shock, rapid sequence intubation, severe pneumonia, transfusions, trauma, and critical procedures., Competing Interests: Declaration of competing interest The authors do not have any financial conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: Speckle tracking echocardiography (STE)-derived measures of myocardial mechanics, referred to herewithin as strain measurements, directly assess myocardial contractility and provide a nuanced assessment of ventricular function. This review provides an overview of strain measurements and their current clinical value and utility in decision making in pediatric cardiology., Recent Findings: Strain measurements are advancing understanding of how cardiac dysfunction occurs in children with acquired and congenital heart disease (CHD). Global strain measurements can detect early changes in cardiac function and are reliable methods of serially monitoring systolic function in children. Global strain measurements are increasingly reported in echocardiographic assessment of ventricular function alongside ejection fraction. Research is increasingly focused on how strain measurements can help improve clinical management, risk stratification, and prognostic insight. Although more research is needed, preliminary studies provide hope that there will be clinical benefit for strain in pediatric cardiology management., Summary: Strain measurements provide a more detailed assessment of ventricular function than conventional measures of echocardiographic functional assessment. Strain measurements are increasingly being used to advance understanding of normal and abnormal myocardial contractility, to increase sensitivity to detect early cardiac dysfunction, and to improve prognostic management in children with acquired and CHD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule that engages T cells to lyse CD19-expressing B cells. Based on a multicenter, open-label, phase 3, randomized clinical trial (Clinical Trials ID: NCT02393859), we aimed to evaluate the cost-effectiveness (CE) of blinatumomab compared to standard consolidation chemotherapy (SC) for the treatment of pediatric patients with high-risk first-relapsed Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) from a Mexico healthcare payer perspective., Methods: A decision-analytic model, a partitioned survival model, was used to estimate the life-years (LYs) and costs over a lifetime horizon. We assumed that patients who remained alive beyond a 5-year period were cured. To account for the lingering impacts of cancer treatment, an excess mortality rate was incorporated into the model. Event-free survival (EFS) and overall survival (OS) were estimated by fitting mixture-cure and standard parametric survival distributions to the time-to-event data from the phase 3 trial. The model accounted for treatment costs, adverse event costs, follow-up costs, subsequent allogeneic hematopoietic stem cell transplantation (alloHSCT) costs, and subsequent treatment costs., Results: Blinatumomab was associated with a lifetime gained of 5.11 years at an incremental cost of $621,111 MXN, relative to SC. The ICER for blinatumomab vs Standard of care was estimated to be $121,526 MXN/LY gained in the base case. Cost-effectiveness was sensitive to varying the time horizon. Blinatumomab had a probability of 99 % of being cost-effective, relative to SC, at the willingness to pay threshold defined in Mexico., Limitations: Health-related quality of life values were not included in the analysis and therefore we did not estimate the quality-adjusted life-years gained., Conclusions: Blinatumomab was associated with greater benefit in terms of OS and EFS relative to SC. Probabilistic, deterministic, and scenario analyses indicate that blinatumomab represents the best value for money. Therefore, blinatumomab administered as part of consolidation therapy in B-ALL pediatric patients with high-risk first relapse is a cost-effective option., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TAM, LG and LMC are employed by Amgen. JPDM has served as a consultant for Amgen and has received research grants from them., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cerebral palsy (CP) is a group of movement disorders that impair posture and mobility, often leading to spasticity and joint contractures. Interventions like serial casting are commonly used to improve joint mobility and manage spasticity in children with CP. However, its effects on the autonomic nervous system (ANS) remain unclear. This study aimed to evaluate the effects of serial casting and ankle-foot orthoses (AFOs) on ANS responses during a virtual reality (VR) standing task, comparing these interventions with a barefoot condition. Thirty children with CP were randomized into three groups ( n = 10 per group): serial casting, AFOs, and barefoot. Heart rate variability (HRV) was used to assess ANS responses across three phases: seated rest, VR task, and recovery. The results showed that the serial casting group exhibited higher sympathetic activity during rest compared to the other groups, but had a reduced sympathetic response during the VR task. Additionally, the serial casting group displayed a more pronounced parasympathetic rebound during recovery, similar to the orthoses and barefoot groups. While serial casting provides essential joint stability, it alters ANS response patterns, leading to heightened sympathetic activation at rest, without providing significant improvements in ANS behavior during physical activity.

Background/objectives: Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and impaired motor performance. This study aimed to investigate the effects of transcranial direct current stimulation (tDCS) during virtual reality (VR) tasks on the motor performance of women with FM., Methods: Participants were divided into two groups: Group A received active tDCS for 10 days followed by sham tDCS for 10 days, while Group B received the opposite sequence. Both groups performed VR tasks using MoveHero software (v. 2.4) during the tDCS sessions. Motor performance was assessed by the number of hits (movement with correct timing to reach the targets) and absolute (accuracy measure) and variable (precision measure) errors during VR tasks. Participants were 21 women, aged 30-50 years, and diagnosed with FM., Results: Group A, which received active tDCS first, presented significant improvements in motor performance (number of hits and absolute and variable errors). The benefits of active tDCS persisted into the sham phase, suggesting a lasting neuroplastic effect., Conclusions: tDCS during VR tasks significantly improved motor performance in women with FM, particularly in complex, extensive movements. These findings indicate that tDCS enhances neuroplasticity, leading to sustained motor improvements, making it a promising therapeutic tool in FM rehabilitation.

Objective: To determine if self-reported fatigue, anxiety, depression, cognitive difficulties, health-related quality of life, disease activity scores and neuropsychological battery (NB) cluster into distinct groups in patients with SLE based on symptom intensity and if they change at 1-year follow-up., Methods: This is a retrospective analysis of consecutive consenting patients, followed at a single centre. Patients completed a comprehensive NB, the Beck Anxiety Inventory, Beck Depression Inventory, Fatigue Severity Scale, Short-Form Health Survey Physical Component Summary and Mental Component Summary scores and the Perceived Deficits Questionnaire. Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index 2000. Ward's method was used for clustering and principal component analysis was used to visualise the number of clusters. Stability at 1 year was assessed with kappa statistic., Results: Among 142 patients, three clusters were found: cluster 1 had mild symptom intensity, cluster 2 had moderate symptom intensity and cluster 3 had severe symptom intensity. At 1-year follow-up, 49% of patients remained in their baseline cluster. The mild cluster had the highest stability (77% of patients stayed in the same cluster), followed by the severe cluster (51%), and moderate cluster had the lowest stability (3%). A minority of patients from mild cluster moved to severe cluster (19%). In severe cluster, a larger number moved to moderate cluster (40%) and fewer to mild cluster (9%)., Conclusion: Three distinct clusters of symptom intensity were documented in patients with SLE in association with cognitive function. There was a lower tendency for patients in the mild and severe clusters to move but not moderate cluster over the course of a year. This may demonstrate an opportunity for intervention to have moderate cluster patients move to mild cluster instead of moving to severe cluster. Further studies are necessary to assess factors that affect movement into moderate cluster., Competing Interests: Competing interests: AG reports consulting fees from AbbVie. MB reports support from NIHR Manchester Biomedical Research Centre, Arthritis Society, Lupus Canada and Lupus Foundation of America. MC reports consulting fees from AstraZeneca, Mallinckrodt, GSK, Organon and MitogenDx. SA reports speaker fees from GlaxoSmithKline and AstraZeneca. RG reports grants from Branch Out Neurological Foundation, Australian Research Council, Lupus Research Alliance, VISTA Research, Natural Sciences and Engineering Research Council of Canada (NSERC), INS Board of Governors and Brain Injury Canada Scientific Advisory Committee. JW reports indirect support from multiple drug companies through Lupus 21st Century for meeting attendance., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The T-peak-to-T-end ( T pe ) interval has shown potential in predicting ventricular arrhythmic risk. It is an appealing index to be measured during ischemia since it is less influenced by ST-segment changes than the early part of the T wave. A time-warping-based index, derived from a spatially transformed PCA lead, [Formula: see text], quantifying changes in the T pe morphology, has previously demonstrated utility in tracking repolarization changes induced by a 5-minute ischemia model in humans. The value of [Formula: see text] as a predictor of ventricular fibrillation (VF) episodes is assessed in a porcine model of myocardial ischemia with ischemia maintained for 40 minutes., Methods: From 32 pigs undergoing a coronary occlusion, pre-occlusion and occlusion ECG recordings from 10 pigs suffering a VF episode after 10 min of occlusion (Delayed VF) and 16 that did not had any episode during the recording were analyzed. The [Formula: see text] series was measured by comparing T pe morphologies at different stages of the occlusion relative to the peak-to-end morphology of a baseline T-wave., Results: During baseline, [Formula: see text] remained stationary with an intra-recording median [IQR] value of 1.60 [1.33] ms. During artery occlusion, [Formula: see text] followed a well-marked gradual increasing trend as ischemia progressed, reaching a median of 14.58 [17.72] ms. [Formula: see text] averages were significantly higher ( ) in the VF group than in the Non-VF group at time intervals 0-5, 5-10, 10-15, 15-20, 20-25 min after occlusion onset and at 10-15, 5-10 and 5-0 minutes prior to VF episode, with median values of 12.5, 18.8, 26.8, 24.0, 31.0, 18.6, 25.0 and 28.8 vs 6.3, 7.6, 8.0, 7.8, 7.8, 8.5, 7.2 and 6.0 ms, respectively. The [Formula: see text] interval was also significantly higher in the VF group at all analyzed time periods, but with a lower significance level. Pigs with maximum [Formula: see text] ≥ 20.0 ms and [Formula: see text] ≥ 85.4 ms had significantly higher risk for VF occurring in the early 5-10 minutes interval, with 90.0%/75.0% and 80.0%/69.0% sensitivity/specificity, respectively. Univariate Cox analysis yielded hazard ratios of 12.5 for [Formula: see text] vs 5.5 for [Formula: see text]., Conclusions and Significance: The time-warping-based index, [Formula: see text], is a stronger VF predictor than [Formula: see text] during ischemia in a porcine model, advising for further clinical exploration studies in humans.

Background: Traumatic injury to the long thoracic nerve causes paralysis of the serratus muscle, clinically expressed as winged scapula and functional impairment of the shoulder girdle. Treatment varies according to the severity of the injury, with a focus on early intervention for best results; however, the therapeutic approach remains a challenge at present., Case Description: We present the case of a 32-year-old male patient, athlete, right-handed, presented with bilateral paresis predominantly in the right arm, associated with paresthesia and changes in the coloring of the upper limbs. After being diagnosed with Thoracic Outlet Syndrome and undergoing surgery, vascular symptoms persisted with a significant loss of strength in the right shoulder. Winged scapula was observed and structural lesions were excluded on magnetic resonance imaging. Electromyographic studies confirmed the presumption of traumatic nerve involvement of the long thoracic nerve. Notwithstanding 6 months of physical therapy, there was no improvement, so a nerve transfer from the thoracodorsal nerve to the right long thoracic nerve was chosen. At 12 months, complete resolution of the winged scapula and functional recovery were observed. The patient also experienced a decrease in preoperative pain from 5/10 to 2/10 on the visual analog scale., Conclusion: Nerve transfer from the thoracodorsal nerve to the long thoracic nerve is a safe and effective technique to treat winged scapula due to long thoracic nerve injury., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Objectives: To determine the impact of older donor age (70+ years) on long-term survival and freedom from chronic lung allograft dysfunction in lung transplant (LTx) recipients., Methods: A retrospective single-center study was performed on all LTx recipients from 2002 to 2017 and a modern subgroup from 2013 to 2017. Recipients were stratified into 4 groups based on donor lung age (<18, 18-55, 56-69, ≥70 years). Donor and recipient characteristics were compared using χ 2 tests for differences in proportions and analysis of variance for differences in means. Univariable and multivariable Cox regression was used to describe differences in long-term survival and freedom from chronic lung allograft dysfunction., Results: Between 2002 and 2017, 1600 LTx were performed, 98 of which were performed from donors aged 70 years or older. Recipients of 70+ years donor lungs were significantly older with a mean age of 55.5 ± 12.9 years old (P = .001) and had more Status 3 (urgent) recipients (37.4%, P = .002). After multivariable regression, there were no significant differences in survival or freedom from chronic lung allograft dysfunction between the 4 strata of recipients., Conclusions: Lung transplantation using donors 70 years old or older can be considered when all other parameters suggest excellent donor lung function without compromising short- or long-term outcomes., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI., Methods: Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated., Results: Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI., Conclusion: In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI., Competing Interests: MT is Scientific advisor for Women’s Brain Project, Brain Injury Canada and PSP Canada and reports a relationship via clinical trials with Janssen, Biogen, Avanex, Green Valley and Roche. SA reports honoraria for lectures/speakers fees from GSK and AstraZeneca. DB serves Chair Methodology of the OMERACT Management Group. RG serves on the INS Board of Governors and Brain Injury Canada Scientific Advisory Committee. JW reports a relationship with honoraria for lectures from AstraZeneca, participation on the AstraZeneca Advisory Board, indirect support for meeting attendance/travel from multiples drug companies through Lupus 21st Century and indirect salary support from unrestricted funds given by Pfizer for a research chair in the Division of Rheumatology. ZT reports a relationship in the form of consulting fees from AstraZeneca, GlaxoSmithKline Inc, Merck, Ampel, Sarkana Pharma, AbbVie and UCB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Muñoz-Grajales, Barraclough, Diaz-Martinez, Su, Bingham, Kakvan, Kretzmann, Tartaglia, Ruttan, Choi, Appenzeller, Marzouk, Bonilla, Katz, Beaton, Green, Gladman, Wither and Touma.)

Tomato ( Solanum lycopersicum L.) domestication and later introduction into Europe resulted in a genetic bottleneck that reduced genetic variation. Crosses with other wild tomato species from the Lycopersicon clade can be used to increase genetic diversity and improve important agronomic traits such as stress tolerance. However, many species in the Lycopersicon clade have intraspecific and interspecific incompatibility, such as gametophytic self-incompatibility and unilateral incompatibility. In this review, we provide an overview of the known incompatibility barriers in Lycopersicon . We begin by addressing the general mechanisms self-incompatibility, as well as more specific mechanisms in the Rosaceae, Papaveraceae, and Solanaceae. Incompatibility in the Lycopersicon clade is discussed, including loss of self-incompatibility, species exhibiting only self-incompatibility and species presenting both self-compatibility and self-incompatibility. We summarize unilateral incompatibility in general and specifically in Lycopersicon , with details on the 'self-compatible x self-incompatible' rule, implications of self-incompatibility in unilateral incompatibility and self-incompatibility-independent pathways of unilateral incompatibility. Finally, we discuss advances in the understanding of compatibility barriers and their implications for tomato breeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Moreels, Bigot, Defalque, Correa, Martinez, Lutts and Quinet.)

Background: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects., Objective: We sought to systematically synthesize the benefits and harms of AD prescription topical treatments., Methods: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s)., Results: The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus., Conclusions: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective., (Copyright © 2023. Published by Elsevier Inc.)

Background: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes., Objective: We sought to systematically synthesize the benefits and harms of AD systemic treatments., Methods: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna)., Results: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain., Conclusions: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The present article proposes an ECG simulator that advances modeling of arrhythmias and noise by introducing time-varying signal characteristics. The simulator is built around a discrete-time Markov chain model for simulating atrial and ventricular arrhythmias of particular relevance when analyzing atrial fibrillation (AF). Each state is associated with statistical information on episode duration and heartbeat characteristics. Statistical, time-varying modeling of muscle noise, motion artifacts, and the influence of respiration is introduced to increase the complexity of simulated ECGs, making the simulator well suited for data augmentation in machine learning. Modeling of how the PQ and QT intervals depend on heart rate is also introduced. The realism of simulated ECGs is assessed by three experienced doctors, showing that simulated ECGs are difficult to distinguish from real ECGs. Simulator usefulness is illustrated in terms of AF detection performance when either simulated or real ECGs are used to train a neural network for signal quality control. The results show that both types of training lead to similar performance.

Objective: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function., Methods: SLE patients ages 18-65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and χ2 tests., Results: Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P < 0.03) compared with subtype B. Subtype A also had greater levels of subjective cognitive function (P < 0.001), disease burden/damage (P < 0.04), HRQoL (P < 0.001) and psychiatric measures (P < 0.001) compared with subtype B., Conclusion: This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multifactorial phenotypes exist. Those with greater disease burden, from SLE-specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately this will aid our understanding of personalized CI trajectories and identification of appropriate treatments., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Variations in the dispersion of ventricular repolarization can be quantified by T-wave time-warping based index, d w . However, the early phase of the T-wave can be affected by ST-segment changes during ischemia. We hypothesized that restricting d w to the T-wave peak-to-end ( T pe ) would circumvent this limitation while still quantifying variations in repolarization dispersion. A total of 101 ECG recordings from patients undergoing coronary occlusion, together with their control recordings, were analyzed. A series of d w values was calculated by quantifying the T pe morphological variations between the T-waves at different occlusion stages and a baseline T-wave. We introduced a normalized version of d w , R d , reflecting variations of d w during occlusion relative to control recordings ( R d = 1 corresponds to the same level of variation). The d w series followed a gradually increasing trend with occlusion time, reaching median [range] R d values of 9.44 [1.01, 80.74] at the occlusion end. R d at occlusion end was significantly higher than threshold values of 1, 2, 5, and 10 in 94.1%, 85.11%, 64.4% and 48.5% of patients, respectively. The spatial lead-wise analysis of d w showed distinct distributions depending on the occluded artery, suggesting a relation with the ischemia location. The relative variation R with ischemia of index d w (9.4) is greater than that of the T-wave amplitude (7.7), T pe interval (2.7) and T-wave width (3.0). In conclusion, d w tracks ischemic-induced variations in repolarization dispersion in a more robust manner than classical indexes, avoiding the impact of ST segment elevation/depression or early T-wave distortions, thus warranting further clinical studies.

We aimed to assess the impact of allocation concealment and blinding on the results of coronavirus disease 2019 (COVID-19) trials, using the World Health Organization COVID-19 database (to February 2022). We identified 488 randomized trials comparing drug therapeutics with placebo or standard care in patients with COVID-19. We performed random-effects meta-regressions comparing the results of trials with and without allocation concealment and blinding of health-care providers and patients. We found that, compared with trials with allocation concealment, trials without allocation concealment may estimate treatments to be more beneficial for mortality, mechanical ventilation, hospital admission, duration of hospitalization, and duration of mechanical ventilation, but results were imprecise. We did not find compelling evidence that, compared with trials with blinding, trials without blinding produce consistently different results for mortality, mechanical ventilation, and duration of hospitalization. We found that trials without blinding may estimate treatments to be more beneficial for hospitalizations and duration of mechanical ventilation. We did not find compelling evidence that COVID-19 trials in which health-care providers and patients are blinded produce different results from trials without blinding, but trials without allocation concealment estimate treatments to be more beneficial compared with trials with allocation concealment. Our study suggests that lack of blinding may not always bias results but that evidence users should remain skeptical of trials without allocation concealment., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Corticosteroids are used to manage pain after surgical tooth extractions. The authors assessed the effect of corticosteroids on acute postoperative pain in patients undergoing surgical tooth extractions of mandibular third molars., Types of Studies Reviewed: The authors conducted a systematic review and meta-analysis. The authors searched the Epistemonikos database, including MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the US clinical trials registry (ClinicalTrials.gov) from inception until April 2023. Pairs of reviewers independently screened titles and abstracts, then full texts of trials were identified as potentially eligible. After duplicate data abstraction, the authors conducted random-effects meta-analyses. Risk of bias was assessed using Version 2 of the Cochrane Risk of Bias tool and certainty of the evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation approach., Results: Forty randomized controlled trials proved eligible. The evidence suggested that corticosteroids compared with a placebo provided a trivial reduction in pain intensity measured 6 hours (mean difference, 8.79 points lower; 95% CI, 14.8 to 2.77 points lower; low certainty) and 24 hours after surgical tooth extraction (mean difference, 8.89 points lower; 95% CI, 10.71 to 7.06 points lower; very low certainty). The authors found no important difference between corticosteroids and a placebo with regard to incidence of postoperative infection (risk difference, 0%; 95% CI, -1% to 1%; low certainty) and alveolar osteitis (risk difference, 0%; 95% CI, -3% to 4%; very low certainty)., Practical Implications: Low and very low certainty evidence suggests that there is a trivial difference regarding postoperative pain intensity and adverse effects of corticosteroids administered orally, submucosally, or intramuscularly compared with a placebo in patients undergoing third-molar extractions., (Copyright © 2023 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Sudden cardiac death is the leading cause of death among cardiovascular diseases. Markers for patient risk stratification focusing on QT-interval dynamics in response to heart-rate (HR) changes can be characterized in terms of parametric QT to RR dependence and QT/RR hysteresis. The QT/RR hysteresis can be quantified by the time delay the QT interval takes to accommodate for the HR changes. The exercise stress test has been proposed as a proper test, with large HR dynamics, to evaluate the QT/RR hysteresis. The present study aims at evaluating several time-delay estimators based on noise statistic (Gaussian or Laplacian) and HR changes profile at stress test (gradual transition change). The estimator's performance was assessed on a simulated QT transition contaminated by noise and in a clinical study including patients affected by coronary arteries disease (CAD). As expected, the Laplacian and Gaussian estimators yield the best results when noise follows the respective distribution. Further, the Laplacian estimator showed greater discriminative power in classifying different levels of cardiac risk in CAD patients, suggesting that real data fit better the Laplacian distribution than the Gaussian one. The Laplacian estimator appears to be the choice for time-delay estimation of QT/RR hysteresis lag in response to HR changes in stress test.Clinical Relevance-The proposed time-delay estimator of QT/RR hysteresis lag improves its significance as biomarkers for coronary artery diseases risk stratification.

Significance: The number of injections administered has increased dramatically worldwide due to vaccination campaigns following the COVID-19 pandemic, creating a problem of disposing of syringes and needles. Accidental needle sticks occur among medical and cleaning staff, exposing them to highly contagious diseases, such as hepatitis and human immunodeficiency virus. In addition, needle phobia may prevent adequate treatment. To overcome these problems, we propose a needle-free injector based on thermocavitation., Aim: Experimentally study the dynamics of vapor bubbles produced by thermocavitation inside a fully buried 3D fused silica chamber and the resulting high-speed jets emerging through a small nozzle made at the top of it. The injected volume can range from ∼ 0.1 to 2    μ L per shot. We also demonstrate that these jets have the ability to penetrate agar skin phantoms and ex-vivo porcine skin., Approach: Through the use of a high-speed camera, the dynamics of liquid jets ejected from a microfluidic device were studied. Thermocavitation bubbles are generated by a continuous wave laser (1064 nm). The 3D chamber was fabricated by ultra-short pulse laser-assisted chemical etching. Penetration tests are conducted using agar gels (1%, 1.25%, 1.5%, 1.75%, and 2% concentrations) and porcine tissue as a model for human skin., Result: High-speed camera video analysis showed that the average maximum bubble wall speed is about 10 to 25 m/s for almost any combination of pump laser parameters; however, a clever design of the chamber and nozzle enables one to obtain jets with an average speed of ∼ 70    m / s . The expelled volume per shot (0.1 to 2    μ l ) can be controlled by the pump laser intensity. Our injector can deliver up to 20 shots before chamber refill. Penetration of jets into agar of different concentrations and ex-vivo porcine skin is demonstrated., Conclusions: The needle-free injectors based on thermocavitation may hold promise for commercial development, due to their cost and compactness., (© 2023 The Authors.)

Latency is a major barrier towards virus elimination in HIV-1-infected individuals. Yet, the mechanisms that contribute to the maintenance of HIV-1 latency are incompletely understood. Here we describe the Schlafen 12 protein (SLFN12) as an HIV-1 restriction factor that establishes a post-transcriptional block in HIV-1-infected cells and thereby inhibits HIV-1 replication and virus reactivation from latently infected cells. The inhibitory activity is dependent on the HIV-1 codon usage and on the SLFN12 RNase active sites. Within HIV-1-infected individuals, SLFN12 expression in PBMCs correlated with HIV-1 plasma viral loads and proviral loads suggesting a link with the general activation of the immune system. Using an RNA FISH-Flow HIV-1 reactivation assay, we demonstrate that SLFN12 expression is enriched in infected cells positive for HIV-1 transcripts but negative for HIV-1 proteins. Thus, codon-usage dependent translation inhibition of HIV-1 proteins participates in HIV-1 latency and can restrict the amount of virus release after latency reversal., (© 2023. The Author(s).)

Objectives: Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies., Methods: Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤-1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use., Results: A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD., Conclusion: AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The authors assessed the clinical effectiveness of analgesics to manage acute pain after dental extractions and pain associated with irreversible pulpitis in children., Types of Studies Reviewed: The authors searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and US Clinical Trials registry from inception through November 2020. They included randomized controlled trials comparing any pharmacologic interventions with each other and a placebo in pediatric participants undergoing dental extractions or experiencing irreversible pulpitis. After duplicate screening and data abstraction, the authors conducted random-effects meta-analyses. They assessed risk of bias using the Cochrane Risk of Bias 2.0 tool and certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach., Results: The authors included 6 randomized controlled trials reporting 8 comparisons. Ibuprofen may reduce pain intensity compared with acetaminophen (mean difference [MD], 0.27 points; 95% CI, -0.13 to 0.68; low certainty) and a placebo (MD, -0.19 points; 95% CI, -0.58 to 0.21; low certainty). Acetaminophen may reduce pain intensity compared with a placebo (MD, -0.13 points; 95% CI, -0.52 to 0.26; low certainty). Acetaminophen and ibuprofen combined probably reduce pain intensity compared with acetaminophen alone (MD, -0.75 points; 95% CI, -1.22 to -0.27; moderate certainty) and ibuprofen alone (MD, -0.01 points; 95% CI, -0.53 to 0.51; moderate certainty). There was very low certainty evidence regarding adverse effects., Practical Implications: Several pharmacologic interventions alone or in combination may provide a beneficial effect when managing acute dental pain in children. There is a paucity of evidence regarding the use of analgesics to manage irreversible pulpitis., (Copyright © 2023 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate whether a change in the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria threshold score affects accurate classification of SLE cases compared to disease-based control subjects. We evaluated a range of threshold scores to determine the score that maximizes the accurate classification of early SLE., Methods: We conducted a cross-sectional study comparing SLE cases and control patients. A EULAR/ACR criteria score was calculated using baseline information. Sensitivity, specificity, positive likelihood ratios (+LRs), and negative likelihood ratios (-LRs) with 95% CIs were used to evaluate operating characteristics. Threshold scores of 6 to 12 were evaluated in subjects with early disease (ie, disease duration of ≤ 5 years). +LRs > 10 and -LRs < 0.1 provide evidence to rule in or rule out SLE., Results: A total of 2764 patients were included: 1980 SLE cases who fulfilled either the ACR or Systemic Lupus International Collaborating Clinics criteria and 784 control subjects. The EULAR/ACR SLE criteria had a sensitivity of 98% (95% CI 97-98), a specificity of 99% (95% CI 98-100), a +LR of 95.5 (95% CI 48.0-190), and a -LR 0.03 (95% CI 0.02-0.03). The criteria operated well in those with early disease, in women, in men, and in White, Black, Chinese, and Filipino people. A score of 10 maximized the accurate classification of patients with early disease (+LR 174.4, 95% CI 43.8-694.6; -LR 0.03, 95% CI 0.02-0.04). An increase in the threshold score from 10 to 11 resulted in significant worsening in the -LR (threshold score 10: -LR 0.03, 95% CI 0.02-0.03 vs threshold score 11: -LR 0.05, 95% CI 0.04-0.06)., Conclusion: The EULAR/ACR SLE classification criteria threshold score of 10 performs well, particularly among those with early disease and across sexes and ethnicities., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: Screening for cognitive impairment (CI) in systemic lupus erythematosus (SLE) relies on the American College of Rheumatology (ACR) neuropsychological battery (NB). By studying the concurrent criterion validity, our goal was to assess the Montreal Cognitive Assessment (MoCA) as a screening tool for CI compared to the ACR-NB and to evaluate the added value of the MoCA to the Automated Neuropsychological Assessment Metrics (ANAM)., Methods: A total of 285 adult SLE patients were administered the ACR-NB, MoCA, and ANAM. For the ACR-NB, patients were classified as having CI if there was a Z score of ≤-1.5 in ≥2 domains. The area under the curve (AUC) and sensitivities/specificities were determined. A discriminant function analysis was applied to assess the ability of the MoCA to differentiate between CI, undetermined CI, and non-CI patients., Results: CI was not accurately identified by the MoCA compared to the ACR-NB (AUC of 0.66). Sensitivity and specificity were poor at 50% and 69%, respectively, for the cutoff of 26, and 80% and 45%, respectively, for the cutoff of 28. The MoCA had a low ability to identify CI status. The addition of the MoCA to the ANAM led to improvement on the AUC by only 2.5%., Conclusion: The MoCA does not have adequate concurrent criterion validity to accurately identify CI in patients with SLE. The low specificity of the MoCA may lead to overdiagnosis and concern among patients. Adding the MoCA to the ANAM does not substantially improve the accuracy of the ANAM. These results do not support using the MoCA as a screening tool for CI in patients with SLE., (© 2022 American College of Rheumatology.)