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Purpose: To investigate and compare the dimensional characteristics of Descemet membrane endothelial keratoplasty (DMEK) scrolls in single-scroll and double-scroll conformations at various ages and velocities., Methods: DMEK tissues from three donor pairs (ages 47, 62, and 69) were used to compare single-scroll and double-scroll widths under different velocities. Tissues were randomized and manipulated into single-scroll or double-scroll conformation using a syringe pump connected to an hourglass-shaped glass tube. All scrolls were passed through the tube at three different velocities set by syringe pump settings, and high-speed videography at 2000 frames per second captured scroll dimensions. Scroll dimensions were measured using IDT Motion Studio software., Results: Single-scrolled DMEK tissue was narrower than double-scrolled tissue across all donor ages. Double-scrolled tissue width remained relatively unchanged regardless of age or velocity. Significant differences in scroll width between single and double scrolls were observed in the 47-year-old donor tissue at all velocities (P <0.001). Significant scroll width differences between single and double scrolls were observed in the 62-year-old donor tissue at medium and high velocities (P = 0.03 and P = 0.01, respectively). In the 69-year-old donor tissue, significant differences in scroll width between single and double scrolls were observed only at high velocities (P = 0.003). Single-scroll width decreased with increasing velocity for 47-year-old and 62-year-old donor tissues (P <0.001, P = 0.03), but not for the 69-year-old donor tissue (P = 1.0)., Conclusions: There is a significant difference in scroll width between single-scrolled and double-scrolled tissues at high speeds. These differences become less significant as scrolls increase in age and velocity decreases., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

This study evaluates different machine learning algorithms in detecting and identifying drones using radar data from a 60 GHz millimeter-wave sensor. These signals were collected from a bionic bird and two drones, namely DJI Mavic and DJI Phantom 3 Pro, which were represented in complex form to preserve amplitude and phase information. The first benchmarks used four algorithms, namely long short-term memory (LSTM), gated recurrent unit (GRU), one-dimensional convolutional neural network (Conv1D), and Transformer, and they were benchmarked for robustness under noisy conditions, including artificial noise types like white noise, Pareto noise, impulsive noise, and multipath interference. As expected, Transformer outperformed other algorithms in terms of accuracy, even on noisy data; however, in certain noise contexts, particularly Pareto noise, it showed weaknesses. For this purpose, we propose Multimodal Transformer, which incorporates more statistical features-skewness and kurtosis-in addition to amplitude and phase data. This resulted in a improvement in detection accuracy, even under difficult noise conditions. Our results demonstrate the importance of noise in processing radar signals and the benefits afforded by a multimodal presentation of data in detecting unmanned aerial vehicle and birds. This study sets up a benchmark for state-of-the-art machine learning methodologies for radar-based detection systems, providing valuable insight into methods of increasing the robustness of algorithms to environmental noise.

Background: Migraine is the most common complex neurological disorder, affecting over a billion people worldwide. Neurogenic inflammation has long been recognized as a key factor in the pathophysiology of migraine though little research has been directed to investigating whether inflammation is greatest in migraine with aura or without, and whether inflammation is a permanent state in migraine or whether is an event related transitory state. Thus, the primary aim of this single-centre, retrospective study was to explore the potential clinical utility of the Serial Systemic Immune-Inflammatory Indices (SSIIi) as a comparative measure of duration and severity of inflammation derived from routine blood cell counts in migraine patients with aura and no-aura both within an acute inpatient setting and as outpatients. Specifically, we assessed the role of two serial white blood cell counts to calculate the SSIIi using the formula: neutrophil count x platelet count/lymphocyte count) between aura and no-aura migraine patients at time of admission to a tertiary care centre in Melbourne, Australia, and following 24 h post admission versus comparable serial measures in 20 out patients with migraine and ongoing symptoms., Main Body: A retrospective analysis was conducted of medical records using baseline demographics and brain imaging findings from 186 migraine hospitalized in-patients who had at least two sets of white blood cell counts drawn within 24 h following their admission to the emergency department of Western Health a tertiary care center in Melbourne, Australia, over an 18-month period. Patients were categorized as having migraine with aura (MA) (N = 67) or without aura (MO) (N = 119) according to ICHD-3 criteria and compared to 2 serial measures in stable in-community acute migraineur controls (N = 20). A mixed-design ANOVA showed a significant main effect of SSIIi between patients with migraine with aura (MA) and migraine without aura (MO) during acute inpatient presentation, in comparison to a convenience sample of outpatients with migraine (MA and MO)., Conclusion: SSIIi levels were significantly lower in patients with migraine with aura (MA), compared to MO. MA showed a greater, though non-significant, decrease between the two measurements compared to those with migraine without aura (MO) and outpatient controls, whose SSIIi levels remained consistently higher. The control group displayed similar findings to MO inpatients, suggesting persistent systemic inflammation in a subset of migraine patients regardless of in patient or outpatient of presentation and highlighting the need for future studies to more rigorously evaluate the role of systemic inflammation in migraine pathophysiology, chronicity, and progression though the multiple phases of migraine including the interictal phase., Competing Interests: Declarations. Ethical approval: Ethical approval was received from Western Health IRB, Australia with approval number QA2014/24. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Respiratory syncytial virus (RSV) causes most of the cases of bronchiolitis and thousands of deaths annually, particularly in infants less than 6 months old. In Catalonia (Spain), infants born between April 2023 and March 2024 aged 0-6 months during their first RSV season have been candidates to receive nirsevimab, the novel monoclonal antibody against RSV, since October 2023. We aimed to analyse the dynamics of all-causes bronchiolitis diagnoses and RSV community infections in the current season and compare them to pre-nirsevimab epidemics. We collected epidemiological data from the Information System for Surveillance of Infections in Catalonia (SIVIC) on daily all-causes bronchiolitis clinical diagnoses and RSV-confirmed cases provided by rapid antigen tests in primary care practices. We calculated the rate ratio (RR) for the incidence of all-causes bronchiolitis for children aged 0-11 m-old with respect to 12-35 m-old between September 2014 and January 2024. We analysed the RR of the incidence of RSV-confirmed infection for 0-11 m-old and 12-35 m-old with respect to the > 35 m-old, from January 2021 to January 2024. We then computed the relative difference of the RR, designated as percentage of reduction of risk, between season 2023/2024 and former epidemics. With a global coverage recorded rate for nirsevimab of 82.2% in January 2024, the age-specific 0-11 m-old RR (95% CI) of RSV infection incidence for > 35 m-old was 1.7 (1.5-2.0) in season 2023/2024. The RR (95% CI) had been 7.4 (5.6-9.9), 8.8 (6.9-11.3), and 7.1 (5.7-8.9) in 2020/2021, 2021/2022, and 2022/2023, respectively. Regarding the incidence of all-causes bronchiolitis for the 0-11 m-old group compared to the 12-35 m-old, the pre-pandemic (2014/2015-2019/2020) and 2022/2023 RR (95% CI) were 9.4 (9.2-9.6) and 6.0 (5.7-6.2), respectively, significantly higher than the RR of 3.6 (3.4-3.8) for the most recent season, 2023/2024. Conclusion: Concurring with the introduction of nirsevimab, the risk of RSV infection for infants aged 0-11 m-old compared to > 35 m-old has been reduced by 75.6% (73.4-77.5) in last season, and the risk for all-causes bronchiolitis for 12-35 m-old by 61.9% (60.9-62.9) from the pre-pandemic period and by 39.8% (39.3-40.2) from the 2022/2023 epidemic, despite high RSV community transmission, especially in older infants What is Known: • RSV is responsible for approximately 70% of bronchiolitis cases and causes severe disease, particularly in infants < 6 months of age. • Nirsevimab effectiveness against RSV-associated disease, particularly hospitalisations, was expected to be around 80%; other Spanish regions, such as Galicia and Valencia, and European countries including Luxembourg and Germany, have already reported good results in implementing nirsevimab to prevent RSV-associated hospitalisations and PICU stays. What is New: • We provide insight into the community incidence of RSV and all-causes bronchiolitis for season 2023/2024, when nirsevimab has been introduced to the Catalan population, using.   primary healthcare data, which enabled us to assess the burden of RSV infections and bronchiolitis in the commonly seasonally saturated primary healthcare practices. • Our study reveals that the risk of all-causes bronchiolitis for infants aged 0-11 m-old compared to older infants was reduced by 40% compared to the previous season and 62% compared to pre-pandemic standards, and for RSV infection it was reduced by 76%., (© 2024. The Author(s).)

Background: Medications are commonly used to treat co-occurring psychopathology in persons with borderline personality disorder (BPD)., Aims: To systematically review and integrate the evidence of medications for treatment of co-occurring psychopathology in people with BPD, and explore the role of comorbidities., Method: Building on the current Cochrane review of medications in BPD, an update literature search was done in March 2024. We followed the methods of this Cochrane review, but scrutinised all identified placebo-controlled trials post hoc for reporting of non BPD-specific ('co-occurring') psychopathology, and explored treatment effects in subgroups of samples with and without defined co-occurring disorders. GRADE ratings were done to assess the evidence certainty., Results: Twenty-two trials were available for quantitative analyses. For antipsychotics, we found very-low-certainty evidence (VLCE) of an effect on depressive symptoms (standardised mean difference (SMD) -0.22, P = 0.04), and low-certainty evidence (LCE) of an effect on psychotic-dissociative symptoms (SMD -0.28, P = 0.007). There was evidence of effects of anticonvulsants on depressive (SMD -0.44, P = 0.02; LCE) and anxious symptoms (SMD -1.11, P < 0.00001; VLCE). For antidepressants, no significant findings were observed (VLCE). Exploratory subgroup analyses indicated a greater effect of antipsychotics in samples including participants with co-occurring substance use disorders on psychotic-dissociative symptoms ( P = 0.001)., Conclusions: Our findings, based on VLCE and LCE only, do not support the use of pharmacological interventions in people with BPD to target co-occurring psychopathology. Overall, the current evidence does not support differential treatment effects in persons with versus without defined comorbidities. Medications should be used cautiously to target co-occurring psychopathology.

This study aimed to evaluate the utilization of drugs with pharmacogenomic guidelines (PGx-drugs) for personalized dosing in pediatric leukemia. A retrospective observational study of pediatric leukemia patients admitted between 2009-2019 at a single-center academic children's hospital was conducted to determine PGx-drug exposure within 3 years of diagnosis. Along with baseline demographic and clinical characteristics of these patients, data regarding dates of diagnosis, relapse, death were collected. During the study period, inclusion criteria were met by 714 patients. The most frequently given medications were ondansetron (96.1%), morphine (92.2%), and allopurinol (85.3%) during the study period. In this cohort, 82% of patients received five or more PGx-drugs. Patients diagnosed with acute myeloid leukemia and leukemia unspecified were prescribed more PGx-drugs than other types of leukemia. There was a significant relationship between age at diagnosis and the number of PGx-drugs prescribed. Adolescents and adults both received a median of 10 PGx-drugs, children received a median of 6 PGx-drugs, and infants received a median of 7 PGx-drugs ( p  < 0.001). Patients with recurrent leukemia had significantly more PGx-drugs prescribed compared to those without recurrent disease, 10 drugs and 6 drugs, respectively ( p  < 0.001). Patients diagnosed with childhood leukemia are high utilizers of PGx-drugs. There is a vital need to understand how PGx testing may be utilized to optimize treatment and enhance quality of life. Preemptive PGx testing is a tool that aids in optimization of drug therapy and decreases the need for later treatment modifications. This can result in financial savings from decreased health-care encounters.

Introduction: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and psychosocial sequelae of ICANS are diverse and not well defined, posing a challenge for diagnosis and management. The recovery trajectory of the syndrome is uncertain. Patients are rarely examined in this population pretherapy, adding a layer of complexity to specifying symptoms pertinent solely to CAR-T treatment. We present a protocol of a prospective longitudinal research study of adult patients in a single Australian haematology service undergoing CAR-T therapy. The study will describe neurocognitive features specific to ICANS, characterise the underlying syndrome, capture recovery, identify predictors of differential postinfusion outcomes and determine a set of cognitive instruments necessary to monitor patients acutely., Methods and Analysis: This is a prospective longitudinal study that comprises neuropsychological and neurological examinations occurring prior to CAR-T, during the acute post-treatment period, 28 days, 6 months and 12 months post infusion. Data will be sourced from objective psychometric measures, clinical examinations, self-report questionnaires of psychopathology and accounts of subjective cognitive complaint., Ethics and Dissemination: This study aims to guide diagnosis, management and monitoring of neurocognitive features of CAR-T cell therapy. Results of this study will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. All procedures involving human subjects/patients were approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (21/145)., Competing Interests: MAA reports honoraria from AstraZeneca, Janssen, Abbvie, Beigene, Takeda, CSL, Novartis, Kite, Gilead and Roche. Employee of the Walter and Eliza Hall institute which receives Milestone payments in relation to venetoclax. CS reports no disclosures. SvdL reports honoraria from Kite. IR served on scientific advisory boards, received conference travel support and/or speaker honoraria from Roche, Novartis, Merck and Biogen. IR is supported by MS Australia and the Trish Multiple Sclerosis Research Foundation. SR reports no disclosures. FD reports no disclosures. SL reports honoraria from Otsuka and Lundbeck. She has received research support from the National Health and Medical Research Council and Royal Melbourne Hospital. MDowling reports honoraria and conference support from Kite and Gilead and honoraria from Novartis. MDowling also receives royalties from Abbvie in relation to venetoclax via the Walter and Eliza Hall institute. MDickinson reports advisory boards, research funding from Novartis, Kite, BMS and Gilead. TK served on scientific advisory boards for MS International Federation and World Health Organisation, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. SJH reports the following disclosures: AbbVie: consultancy, advisory board; Amgen: consultancy, honoraria, advisory board, research funding; Celgene: consultancy, honoraria, advisory board, research funding; CSL Bering: honoraria; GSK: consultancy, research funding, advisory board; Janssen Cilag: consultancy, honoraria, advisory board, research funding; Novartis: consultancy, honoraria, advisory board, research funding; Roche/Genetec: consultancy, honoraria, advisory board; Takeda: consultancy, honoraria, advisory board; Haemalogix: scientific advisory board, research funding; Sanofi: consultancy/advisory role; Terumo: consultancy/advisory role/expert testimony. CM has received conference travel support from Merck, Novartis and Biogen. He has received research support from the National Health and Medical Research Council, Multiple Sclerosis Australia, The University of Melbourne, The Royal Melbourne Hospital Neuroscience Foundation and Dementia Australia., (Copyright © 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.)

Purpose: The aim of this study was to evaluate Descemet membrane endothelial keratoplasty (DMEK) scroll width and length in relation to variable velocities as the tissue transits through wide and narrow lumen glass tubes., Methods: Sets of DMEK tissue were processed using the Iowa Lions Eye Bank standard DMEK protocol and were passed through 2 glass tube widths at variable speeds. Two hourglass-shaped glass tubes were created, one "wide" and one "narrow." A syringe pump, valve, and pressure gauge were used to modulate tissue speed through each tube. For both tube sizes, DMEK tissue was passed through their lumens with incrementally increasing velocity and visualized with a high-speed camera at frame rates from 1000 to 8000 fps. Scroll width and length were measured using IDT Motion Studio software and digital calipers., Results: There was a significant, indirect correlation between scroll velocity and width in both the wide (R 2 = -0.98, P < 0.001) and narrow (R 2 = -0.84, P < 0.001) tubes. There was a significant, direct correlation between scroll velocity and length in both the wide (R 2 = 0.84, P < 0.001) and narrow (R 2 = 0.83, P < 0.001) tubes. The resting widths of the scrolls were 105% and 207% wider than the wide and narrow tubes, respectively. All transits recorded scroll widths that were equal to or smaller than their respective tube's internal diameter., Conclusions: There is a significant, inverse correlation between DMEK scroll velocity and width as well as a direct correlation between scroll velocity and length, allowing DMEK scrolls to transit through a tube that is narrower than its resting width without sustained lumen wall contact., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: Immune effector cell-associated neurotoxicity syndrome (ICANS) is an important complication of chimeric antigen receptor T-cell (CAR-T) therapy. This study aims to identify the patterns of neurotoxicity among patients with ICANS at a tertiary referral centre in Australia., Methodology: This single-centre, prospective cohort study included all consecutively recruited patients who underwent CAR-T therapy for eligible haematological malignancies. All patients underwent a comprehensive neurological assessment and cognitive screening before CAR-T infusion, during the development of ICANS, and 1 month after treatment. Baseline demographic characteristics, incidence, and neurological patterns of neurotoxicity management were evaluated., Results: Over a 19-month period, 23% (12) of the 53 eligible patients developed neurotoxicity (10/12 [83%] being grade 1). All patients showed changes in handwriting and tremor as their initial presentation. Changes in cognition were manifested in most of the patients, with a more substantial drop noted in their Montreal Cognitive Assessment compared to immune effector cell-associated encephalopathy scores. All manifestations of neurotoxicity were short-lived and resolved within a 1-month period, with a mean duration of 8.2 days (range = 1-33)., Conclusions: The patterns of CAR-T-related neurotoxicity often include change in handwriting, tremor, and mild confusional state, especially early in their evolution. These may remain undetected by routine neurological surveillance. These features represent accessible clinical markers of incipient ICANS., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

This study aimed to correlate the values of liver markers with oxidative stress markers in patients with multidrug-resistant tuberculosis in the Brazilian Amazon. A total of 30 patients from the Tuberculosis clinic of a referral hospital were admitted to the study. Whole blood samples were collected for analysis of liver enzyme values and oxidative stress markers by spectrophotometry. The prevalence was male (60%) and the 18-29 age group was the most affected. Patients with multidrug-resistant tuberculosis presented catalase values with a median equal to 6.94 U/gHb and for glutathione, the median was equal to 14.76 µg∕ml. As for the values of liver enzymes (AST, ALT, Gamma-GT and Alkaline phosphatase) the patients had medians equal to 60.50 (U/L); 80 (U/L); 54 (U/L); and 100 (U/L) respectively (p<0.0001). The results suggest a hepatotoxic effect of the drug, which recommends further studies with a larger number of samples in order to investigate the predictors of liver damage in patients with multidrug-resistant tuberculosis.

Introduction: Dietary patterns (DPs) are associated with overall nutritional status and may alter the clinical prognosis of tuberculosis. This interaction can be further intricated by dysglycemia (i.e., diabetes or prediabetes). Here, we identified DPs that are more common with tuberculosis-dysglycemia and depicted their association with tuberculosis treatment outcomes., Methods: A prospective cohort study of persons with tuberculosis and their contacts was conducted in Peru. A food frequency questionnaire and a multidimensional systems biology-based analytical approach were employed to identify DPs associated with these clinical groups. Potential independent associations between clinical features and DPs were analyzed., Results: Three major DPs were identified. TB-dysglycemia cases more often had a high intake of carbohydrates (DP1). Furthermore, DP1 was found to be associated with an increased risk of unfavorable TB outcomes independent of other factors, including dysglycemia., Conclusion: Our findings suggest that the evaluation of nutritional status through DPs in comorbidities such as dysglycemia is a fundamental action to predict TB treatment outcomes. The mechanisms underlying the association between high intake of carbohydrates, dysglycemia, and unfavorable tuberculosis treatment outcomes warrant further investigation., 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 Arriaga, Araújo-Pereira, Andrade, Queiroz, Fernandes, Sales, Aliaga, Shivakoti, Lecca, Calderon and Andrade.)

Despite the global importance of species with C4 photosynthesis, there is a lack of consensus regarding C4 performance under fluctuating light. Contrasting hypotheses and experimental evidence suggest that C4 photosynthesis is either less or more efficient in fixing carbon under fluctuating light than the ancestral C3 form. Two main issues have been identified that may underly the lack of consensus: neglect of evolutionary distance between selected C3 and C4 species and use of contrasting fluctuating light treatments. To circumvent these issues, we measured photosynthetic responses to fluctuating light across 3 independent phylogenetically controlled comparisons between C3 and C4 species from Alloteropsis, Flaveria, and Cleome genera under 21% and 2% O2. Leaves were subjected to repetitive stepwise changes in light intensity (800 and 100 µmol m-2 s-1 photon flux density) with 3 contrasting durations: 6, 30, and 300 s. These experiments reconciled the opposing results found across previous studies and showed that (i) stimulation of CO2 assimilation in C4 species during the low-light phase was both stronger and more sustained than in C3 species; (ii) CO2 assimilation patterns during the high-light phase could be attributable to species or C4 subtype differences rather than photosynthetic pathway; and (iii) the duration of each light step in the fluctuation regime can strongly influence experimental outcomes., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)