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Objectives: This study aimed to review the case records and report the outcomes of open and laparoscopic adrenalectomy (LA) cases. Methods: This retrospective study included patients who underwent adrenal surgery from January 2010 to December 2020 at Sultan Qaboos University, Muscat, Oman. Demographic details, indications, surgical approaches, intra-operative data, complications, final pathology and outcome at the last follow-up were analysed. Results: A total of 52 patients underwent 61 adrenalectomies; six patients had a bilateral procedure while three patients had to undergo revision surgery resulting in a total of 55 individual procedures. Open adrenalectomy (OA) was performed on 11 patients and 44 patients underwent LA. Most patients (n = 27) were obese with a body mass index >30. Functional adenoma was excised in 36 patients with final diagnosis of Conn’s syndrome in 15, pheochromocytoma in 13 and Cushing’s syndrome in nine patients. Five patients had surgery for oncological indications. Non-functional adenoma was excised in 13 patients, with a mean size of 8.9 cm (range: 4–15 cm). The mean duration of surgery was less in laparoscopic procedure compared to open (199 versus 246 minutes). The mean estimated blood loss in LA was significantly less (108 versus 450 mL; P

The spinal cord has a poor ability to regenerate after an injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treating a spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface on the other side. When the cells are cultured on OPF via chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to that of the multichannel scaffold control, which is likely due to the greater number of axons growing across it. The immune cell number (microglia or hemopoietic cells: 50–120 cells/mm2 in all conditions), scarring (5–10% in all conditions), and ECM deposits (Laminin or Fibronectin: approximately 10–20% in all conditions) were equal in all conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery. This study provides a hydrogel scaffold construct that can be used in vitro for cell characterization or in vivo for future neuroprosthetics, devices, or cell and ECM delivery.

Machine learning is a powerful tool that is increasingly being used in many research areas, including neuroscience. The recent development of new algorithms and network architectures, especially in the field of deep learning, has made machine learning models more reliable and accurate and useful for the biomedical research sector. By minimizing the effort necessary to extract valuable features from datasets, they can be used to find trends in data automatically and make predictions about future data, thereby improving the reproducibility and efficiency of research. One application is the automatic evaluation of micrograph images, which is of great value in neuroscience research. While the development of novel models has enabled numerous new research applications, the barrier to use these new algorithms has also decreased by the integration of deep learning models into known applications such as microscopy image viewers. For researchers unfamiliar with machine learning algorithms, the steep learning curve can hinder the successful implementation of these methods into their workflows. This review explores the use of machine learning in neuroscience, including its potential applications and limitations, and provides some guidance on how to select a fitting framework to use in real-life research projects.

BackgroundCongenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide.Methods/FindingsIn our ongoing USA feasibility/efficacy clinical trial, data collated with other ongoing and earlier published results proved high performance of an Immunochromatographic-test(ICT) that enables accurate, rapid diagnosis/treatment, establishing new paradigms for care. Overall results from patient blood and/or serum samples tested with ICT compared with gold-standard-predicate-test results found ICT performance for 4606 sera/1876 blood, 99.3%/97.5% sensitive and 98.9%/99.7% specific. However, in the clinical trial the FDA-cleared-predicate test initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon’s Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO ASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening.Conclusions/SignificanceThis novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories.Author’s SummaryToxoplasmosis is a major health burden for developed and developing countries, causing damage to eyes and brain, loss of life and substantial societal costs. Prompt diagnosis in gestational screening programs enables treatment, thereby relieving suffering, and leading to > 14-fold cost savings for care. Herein, we demonstrate that using an ICT that meets WHO ASSURED-criteria identifying persons with/without antibody toToxoplasma gondiiin sera and whole blood with high sensitivity and specificity, is feasible to use in USA clinical practice. We find this new approach can help to obviate the problem of detection of false positive anti-T.gondiiIgM results for those without IgG antibodies toT.gondiiwhen this occurs in present, standard of care, predicate USA FDA cleared available assays. Thus, this accurate test facilitates gestational screening programs and a global initiative to diagnose and thereby prevent and treatT.gondiiinfection. This minimizes likelihood of false positives (IgG and/or IgM) while maintaining maximum sensitivity. When isolated IgM antibodies are detected, it is necessary to confirm and when indicated continue follow up testing in ∼2 weeks to establish seroconversion. Presence of a positive ICT makes it likely that IgM is truly positive and a negative ICT makes it likely that IgM will be a false positive without infection. These results create a new, enthusiastically-accepted, precise paradigm for rapid diagnosis and validation of results with a second-line test. This helps eliminate alarm and anxiety about false-positive results, while expediting needed treatment for true positive results and providing back up distinguishing false positive tests.

BackgroundCervical cancer is a major public health problem in India, where access to prevention programmes is low. The World Health Organization-Strategic Advisory Group of Experts recently updated their recommendation for human papillomavirus (HPV) vaccination to include a single-dose option in addition to the two-dose option, which could make HPV vaccination programmes easier to implement and more affordable.MethodsWe combined projections from a type-specific HPV transmission model and a cancer progression model to assess the health and economic effects of HPV vaccination at national and state-level in India. The models used national and state-specific Indian demographic, epidemiological and cost data, and single-dose vaccine efficacy and immunogenicity data from the IARC India vaccine trial with 10-year follow-up. We compared single- and two-dose HPV vaccination for a range of plausible scenarios regarding single-dose vaccine protection, coverage and catch-up.ResultsUnder the base-case scenario of life-long protection of single-dose vaccination in 10-year-old girls with 90% coverage, the incremental cost-effectiveness ratio (ICER) of nationwide vaccination relative to no vaccination was $405 per DALY averted and lay below an opportunity-cost based threshold of 30% Indian GDP per capita in each state (state-specific ICER range: $67 to $593 per DALY averted). The ICER of two-dose vaccination versus no vaccination and versus single-dose vaccination was $1403 and minimum $2279 per DALY averted, respectively.ConclusionsNationwide introduction of single-dose HPV vaccination in India is highly likely to be cost-effective whereas extending the number of doses from one to two would have a less favourable profile.FundingBill & Melinda Gates Foundation.What is already known in this topicIn 2020, the World Health Organization (WHO) launched a global call for elimination of cervical cancer as a public health problem, of which HPV vaccination is a key pillar. However, access to HPV vaccination in India is still very low.In April 2022, the WHO Strategic Advisory Group of Experts (SAGE) issued a recommendation for countries to update their dosing schedules to include a single-dose option. Single-dose HPV vaccination is likely to be more affordable and would greatly facilitate the implementation of HPV vaccination.The key questions for India are whether, with a realistic cost-effectiveness threshold (30% GDP per capita), single-dose HPV vaccination would be a cost-effective intervention; and whether two-dose vaccination could still be affordable and worthwhile compared to a single-dose schedule, given the uncertainty in its initial efficacy and long-term protection.What this study addsWe used state-specific cancer incidence and locally collected cost data and built plausible vaccination efficacy scenarios based on the IARC India trial to inform the cost-effectiveness estimates.Single-dose vaccination in India would be cost-effective under a cost-effectiveness threshold of 30% of the Indian GDP per capita and the annual budget impact would be less than 10% of the cost of the current Indian universal childhood vaccination programme.Even though there was substantial heterogeneity, we confirmed that single-dose vaccination would be cost-effective across all Indian states.Catch-up single-dose vaccination to age 15 or 20 is a cost-effective strategy. However, the decision to implement catch-up will depend on the willingness of the health authorities to support a higher initial investment. We found two-dose vaccination to have a less favourable cost-effectiveness profile.How this study might affect research practice and policySingle-dose vaccination achieved a better balance between health benefits and financial burden than two-dose vaccination, even after taking into account uncertainty in the level of protection provided by single-dose HPV vaccination.Our results could be used by Indian health authorities at the national and state-level to inform their decision and planning of the implementation of HPV vaccination in India and could convey several lessons for other low and middle income countries.

BH3 mimetic drugs, which inhibit prosurvival BCL2 family proteins, have limited single-agent activity in solid tumor models. The potential of BH3 mimetics for these cancers may depend on their ability to potentiate the apoptotic response to chemotherapy and targeted therapies. Using a novel class of potent and selective MCL1 inhibitors, we demonstrate that concurrent MEK + MCL1 inhibition induces apoptosis and tumor regression in KRAS-mutant non–small cell lung cancer (NSCLC) models, which respond poorly to MEK inhibition alone. Susceptibility to BH3 mimetics that target either MCL1 or BCL-xL was determined by the differential binding of proapoptotic BCL2 proteins to MCL1 or BCL-xL, respectively. The efficacy of dual MEK + MCL1 blockade was augmented by prior transient exposure to BCL-xL inhibitors, which promotes the binding of proapoptotic BCL2 proteins to MCL1. This suggests a novel strategy for integrating BH3 mimetics that target different BCL2 family proteins for KRAS-mutant NSCLC.Significance:Defining the molecular basis for MCL1 versus BCL-xL dependency will be essential for effective prioritization of BH3 mimetic combination therapies in the clinic. We discover a novel strategy for integrating BCL-xL and MCL1 inhibitors to drive and subsequently exploit apoptotic dependencies of KRAS-mutant NSCLCs treated with MEK inhibitors.See related commentary by Leber et al., p. 1511.This article is highlighted in the In This Issue feature, p. 1494

Supplementary Figure 1-5, Supplementary Tables 1-3

Introduction: Intracranial atherosclerosis-related acute large vessel occlusion (ICAS-LVO) is the dominant cause of acute middle cerebral artery (MCA) occlusions that can be passed with wire or microcatheter but cannot be completely opened (5-15% of all middle cerebral artery (MCA) infarcts). The major challenge of ICAS-LVO is the tendency of reocclusion or cause a residual, fixed severe stenosis rendering the vessel with suboptimal revascularization. These patients carry a poor functional outcome and high mortality despite mechanical thrombectomy (MT). We aimed to externally validate three preidentified markers of ICAS-LVO on early non-contrast computed tomography (NCCT) and CT Angiogram (absent hyperdense MCA sign (HMCAS), Hounsfield measurements (HU ratio≤1.1 and Delta HU Methods: We conducted a retrospective analysis of 77 consecutive patients presenting with acute M1 occlusions undergoing MT. Based on our previous observational experiences, NCCT and CTA patterns that had been associated with ICAS-LVO included the absent HMCAS, HU ratio and Delta HU between site of occlusion and contralateral MCA and CTA truncal occlusion. ICAS-LVO was identified if an occlusion was difficult to cross, had tendency to reocclude after successful recanalization or demonstrated residual fixed severe stenosis. These markers were also compared with reperfusion rates and functional outcomes at 3 months. Results: Out of 77 patients, 13 (16%) had suspected ICAS-LVO. Absent HMCAS had a sensitivity of 91% and specificity of 90% (AUC 0.91), HU ratio ≤1.1 and delta HU 2) at 3 months. Conclusion: Initial non-contrast CT and CTA markers are highly sensitive and specific in predicting atherosclerotic M1 occlusions and significantly associated with failed reperfusion, and poor functional outcomes after mechanical thrombectomy.

Stroke is a prominent and financially burdensome disease. Lacunar strokes are traditionally attributed to small vessel disease rather than cardioemboli, which typically occlude larger arteries. Thus, the benefit of screening for potential sources of cardioemboli in lacunar stroke patients is unclear. We evaluated the clinical utility of the transthoracic echocardiogram performed in patients with lacunar strokes.A single-center retrospective analysis of ischemic stroke patients from January 2013 through December 2017 was performed. Brain magnetic resonance imaging was used to select patients with a single lacunar infarct. Patients presenting with acute symptoms of cardiac disease or an abnormal electrocardiogram were excluded. Transthoracic echocardiogram results were reviewed, and their utility in decision-making was evaluated.Of the 442 patients at our institution diagnosed with ischemic stroke during the inclusion period, 89 met inclusion criteria. Transthoracic echocardiogram detected a patent foramen ovale in 5.6% of patients, mitral annular calcification in 9.0% of patients, and abnormal wall motion in 4.5% of patients. For all patients, there were no findings that prompted anticoagulation, antibiotic, or surgical intervention. The cost of an inpatient transthoracic echocardiogram is $4100, resulting in $364,900 in unnecessary health care spending.Transthoracic echocardiogram appears to have minimal therapeutic value in most patients with lacunar strokes. In stroke patients with no acute symptoms of cardiac disease and a normal electrocardiogram, it may be reasonable to forgo the transthoracic echocardiogram if the brain magnetic resonance imaging shows an isolated lacunar infarct.

Using light to control transient phases in quantum materials is an emerging route to engineer new properties and functionality, with both thermal and non-thermal phases observed out of equilibrium. Transient phases are expected to be heterogeneous, either through photo-generated domain growth or by generating topological defects, and this impacts the dynamics of the system. However, this nanoscale heterogeneity has not been directly observed. Here we use time- and spectrally resolved coherent X-ray imaging to track the prototypical light-induced insulator-to-metal phase transition in vanadium dioxide on the nanoscale with femtosecond time resolution. We show that the early-time dynamics are independent of the initial spatial heterogeneity and observe a 200 fs switch to the metallic phase. A heterogeneous response emerges only after hundreds of picoseconds. Through spectroscopic imaging, we reveal that the transient metallic phase is a highly orthorhombically strained rutile metallic phase, an interpretation that is in contrast to those based on spatially averaged probes. Our results demonstrate the critical importance of spatially and spectrally resolved measurements for understanding and interpreting the transient phases of quantum materials.

This work proposes an static random access memory (SRAM) with column-based split cell-VSS (CS-CVSS), data-aware write-assist (DAWA), and enhanced read sensing margin in 28-nm FDSOI technology. The proposed CS-CVSS and DAWA techniques improve both half-selected (HS) static noise margin (SNM) and write margin. They also improve HS dynamic noise margin (HS-DNM) by leveraging write through virtual ground with reduced load in the proposed write port. The proposed 3T read port enhances sensing margin by minimizing read bitline leakage through negative gate-to-source voltage regardless of cell data. A 16-kb 9T SRAM test chip demonstrated the minimum operating voltage for write and read operations as 0.47 and 0.25 V, respectively. The minimum energy of 6.72 pJ is achieved at 0.5 V.

Background: Activated microglia release harmful substances to retinal ganglion cells (RGCs), but may also benefit by removing cellular debris and secreting neurotrophic factors. These paradoxical roles remain controversial because the nature and time-course of the injury that defines their role is unknown. The aim of this study was to determine if pharmacological manipulation of microglia to acquire a pro-inflammatory or pro-survival phenotype will exacerbate or enhance neuronal survival after injury.Material and methods: Treated HAP I (highly aggressively proliferating immortalized) microglia were injected into the vitreous or tail vein (T V) of female Sprague-Dawley rats. Retinas were examined at 4-14 days following optic nerve crush (ONC) and the number of surviving RGCs was determined.Results: Injection of untreated HAP I cells resulted in the greater loss of RGCs early after ONC when injected into the vitreous and later after ONC when injected into the T V. LP S activated HAP I cells injected into the vitreous resulted in greater RGC loss with and without injury. When injected into the T V with ONC there was no loss of RGCs 4 days after ONC but greater loss afterwards. Minocycline treated HAP I cells injected into the vitreous resulted in greater RGC survival than untreated HAP I cells. However, when injected into the T V with ONC there was greater loss of RGCs. These results suggest that optic nerve signals attract extrinsic microglia to the retina, resulting in a proinflammatory response.Conclusion: Neuroprotection or cytotoxicity of microglia depends on the type of activation, time course of the injury, and if they act on the axon or cell body. HAPI microglia migrate to the retina or optic nerve following optic nerve injury when injected into the vitreous or tail vein, respectively. Pretreatment with LPS or minocycline differentially effects retinal ganglion cell survival. In most cases, the result late in the injury process is greater retinal ganglion cell loss. We show here that neuroprotection is not solely determined by the microglial activation state but factors such as the environment and time-course of the injury. Culture microglia can be treated in vitro and then injected in vivo. The cells migrate to the site of injury, cell body of retinal ganglion cells if in the vitreous or to the optic nerve if injected in the tail vein. Retinal ganglion cell death is dependent on the location the microglia act, time-course of injury, and activation state. Proinflammatory microglia can be neuroprotective early in the injury when the primary site of action is on the axons whereas hypoactivated microglia are neuroprotective early in injury when they act on the soma. Later in the injury, both become detrimental.

In ultrafast electron diffraction (UED) experiments, accurate retrieval of time-resolved structural parameters, such as atomic coordinates and thermal displacement parameters, requires an accurate scattering model. Unfortunately, kinematical models are often inaccurate even for relativistic electron probes, especially for dense, oriented single crystals where strong channeling and multiple scattering effects are present. This article introduces and demonstrates dynamical scattering models tailored for quantitative analysis of UED experiments performed on single-crystal films. As a case study, we examine ultrafast laser heating of single-crystal gold films. Comparison of kinematical and dynamical models reveals the strong effects of dynamical scattering within nm-scale films and their dependence on sample topography and probe kinetic energy. Applying to UED experiments on an 11 nm thick film using 750 keV electron probe pulses, the dynamical models provide a tenfold improvement over a comparable kinematical model in matching the measured UED patterns. Also, the retrieved lattice temperature rise is in very good agreement with predictions based on previously measured optical constants of gold, whereas fitting the Debye-Waller factor retrieves values that are more than three times lower. Altogether, these results show the importance of dynamical scattering theory for quantitative analysis of UED and demonstrate models that can be practically applied to single-crystal materials and heterostructures., 13 pages, 7 figures

It was previously reported that coronavirus caused myocardial injury in hospitalized patients. However, delayed cardiac involvement in symptomatic patient recovery from COVID-19 is not yet well known. The objective of this study was to evaluate cardiac involvement by using cardiac magnetic resonance (CMR) in symptomatic post-COVID-19 recovered patients. Thirty (30) patients who recovered from COVID-19 and had recently reported cardiac symptoms were studied in a prospective observational study performed at Popular Medical College Hospital, Dhaka, Bangladesh from March 2021 to September 2021. They underwent CMR examinations. CMR scanning protocol included the following: black blood, cine sequence, both short-axis and long-axis, T2-weight short tau inversion recovery (STIR) sequence, T2- weighted imaging (T2WI) and late gadolinium enhancement (LGE) and quantitative mapping sequences-native T1/T2 mapping and post-contrast T1 mapping. Myocardial edema and late gadolinium enhancement were assessed in all patients. Quantitative evaluation of native T1/T2 and ECV value and cardiac function were evaluated. There were 30 people in all in this study. The average age of the participants in the study was 36.6 years. Fourteen (46.6%) of the patients had abnormal cardiac MRI results, while the remaining 15(53.3%) had negative CMR findings. Among positive findings patients, 8(57.1%) of 14 had increased T2 signal. Increased myocardial edema was found in the same no of patients, involving 53.2% (128 of 224) of LV segments. Only 2 cases (2 of 14) showed mid myocardial and subepicardial LGE, involving 18 of 224, 8.03% of myocardial segments. Global native T1, T2 and ECV values are significantly elevated in all CMR positive findings patients. Native T1 1231ms (IQR: 1281.25-1257.5 versus 1155.5 (IQR: 1137.25-1172.75), T2 40 (IQR: 34.5-43.25) versus 35.5 (IQR: 34-37), ECV 31 (29.75-33.25) versus 23.5 (21.25-24.0), p0.001; p0.011 and p0.001 respectively. Reduced RV functional were found in positive as compared with negative CMR findings patients, EF, 32.05 (IQR: 25.25-39.0) versus 54.5 (IQR: 52.0-57.75) and EDV, 117.5 (IQR: 102.0-134.25) versus 95.0 (IQR: 71.75-99.75), p0.001 and p0.001 respectively. In this study cardiac involvement was found in the post-COVID-19 recovered patient with cardiac symptoms. Cardiac MRI findings included myocardial edema, fibrosis and reduced right ventricular function. So attention should be paid to symptomatic post-COVID-19 recovered patients.

Respiratory complications are one of the biggest challenges following cardiac surgery, which can lead to hypoxia and acute respiratory failure (ARF). The aim of this study to identify the factors led to BiPAP application for postoperative respiratory complications and its effectiveness as the main outcome measures after cardiac surgery.It was a retrospective cohort study with consecutive sampling technique. A total of 335 postcardiac surgery patients medical record was reviewed who were underwent for surgery from November 1, 2018 to November 30, 2019. 265 patients were finalized for the recruitment, five patients were excluded before the final analysis. Data of 260 patients were analyzed for compiling of results.The mean age was 59 years. 196 (75.4%) patients were males and females were 64 (24.6%). Mean weight was 72 kg and mean body mass index (BMI) 26.67 kg/mBiPAP is effective to treat ARF and other respiratory complications after adult cardiac surgeries. High BMI, atelectasis, and pneumonia are also the independent factors causing ARF. BiPAP can be a successful tool for preventing the adverse effects of postoperative pulmonary complications after cardiac surgery.

The spinal cord has poor ability to regenerate after injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treat spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface chemistry on the other side. When the cells are cultured on OPF with the chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to the multichannel scaffold control, likely due to the greater number of axons growing across. Inflammation, scarring, and ECM deposits were equal across conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery.