The development of nucleoside deaminase-containing base editors realized targeted single base change with high efficiency and precision. Such nucleoside deaminases include adenosine and cytidine deaminases, which can catalyze adenosine-to-inosine (A-to-I) and cytidine-to-uridine (C-to-U) conversion respectively. These nucleoside deaminases are under the spotlight because of their vast application potential in gene editing. Recent advances in the engineering of current nucleoside deaminases and the discovery of new nucleoside deaminases greatly broaden the application scope and improve the editing specificity of base editors. In this review, we cover current knowledge about the deaminases used in base editors, including their key structural features, working mechanisms, optimization, and evolution.

Nucleoside deaminases: the key players in base editing toolkit.

Biophysics Reports

Guillain-Barr&#xe9; syndrome (GBS) is a potentially devastating yet treatable disorder. A classically postinfectious, immune-mediated, monophasic polyradiculoneuropathy, it is the leading global cause of acquired neuromuscular paralysis. In most cases, the immunopathological process driving nerve injury is ill-defined. Diagnosis of GBS relies on clinical features, supported by laboratory findings and electrophysiology. Although previously divided into primary demyelinating or axonal variants, this dichotomy is increasingly challenged, and is not endorsed by the recent European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines. Intravenous immunoglobulin and plasma exchange remain the primary modalities of treatment, regardless of the electrophysiological subtype. Most patients recover, but approximately one-third require mechanical ventilation, and 5% die. Disease activity and treatment response are currently monitored through interval neurological examination and outcome measures, and the potential role of fluid biomarkers is under ongoing scrutiny. Novel potential therapies for GBS are being explored but none have yet modified clinical practice. This review provides a comprehensive update on the pathological and clinical aspects of GBS for clinicians and scientists.

Guillain-Barré syndrome: A comprehensive review.

European Journal of Neurology

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.

Endocrine Reviews

Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one's own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath-Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.

Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.

International Journal of Molecular Sciences

Diabetic kidney disease (DKD) is a major microvascular complication of both type 1 and type 2 diabetes. DKD is characterised by injury to both glomerular and tubular compartments, leading to kidney dysfunction over time. It is one of the most common causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Persistent high blood glucose levels can damage the small blood vessels in the kidneys, impairing their ability to filter waste and fluids from the blood effectively. Other factors like high blood pressure (hypertension), genetics, and lifestyle habits can also contribute to the development and progression of DKD. The key features of renal complications of diabetes include morphological and functional alterations to renal glomeruli and tubules leading to mesangial expansion, glomerulosclerosis, homogenous thickening of the glomerular basement membrane (GBM), albuminuria, tubulointerstitial fibrosis and progressive decline in renal function. In advanced stages, DKD may require treatments such as dialysis or kidney transplant to sustain life. Therefore, early detection and proactive management of diabetes and its complications are crucial in preventing DKD and preserving kidney function.

Diabetes and Renal Complications: An Overview on Pathophysiology, Biomarkers and Therapeutic Interventions.

Biomedicines

Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired AKI, which seriously threatens the health of patients. To date, the precise pathogenesis of CI-AKI has remained not clear and may be related to the direct cytotoxicity, hypoxia and ischemia of medulla, and oxidative stress caused by iodine contrast medium, which have diverse physicochemical properties, including cytotoxicity, permeability and viscosity. The latest research shows that microRNAs (miRNAs) are also involved in apoptosis, pyroptosis, and autophagy which caused by iodine contrast medium (ICM), which may be implicated in the pathogenesis of CI-AKI. Unfortunately, effective therapy of CI-AKI is very limited at present. Therefore, effective prevention of CI-AKI is of great significance, and several preventive options, including hydration, antagonistic vasoconstriction, and antioxidant drugs, have been developed. Here, we review current knowledge about the features of iodine contrast medium, the definition, pathogenesis, molecular mechanism, risk factors, prevention and treatment of CI-AKI.

Contrast-induced acute kidney injury: a review of definition, pathogenesis, risk factors, prevention and treatment.

BMC Nephrology

Postoperative pulmonary complications (PPCs) are associated with postoperative mortality and prolonged hospital stay. Although intraoperative mechanical ventilation (MV) is a risk factor for PPCs, strategies addressing weaning from MV are understudied. In this systematic review, we evaluated weaning strategies and their effects on postoperative pulmonary outcomes.

Our protocol was registered on PROSPERO (CRD42022379145). Eligible studies included randomised controlled trials and observational studies of adults weaned from MV in the operating room. Primary outcomes included atelectasis and oxygenation; secondary outcomes included lung volume changes and PPCs. Risk of bias was assessed using the Cochrane Risk of Bias (RoB2) tool, and quality of evidence with the GRADE framework.

Screening identified 14 randomised controlled trials including 1719 patients; seven studies were limited to the weaning phase and seven included interventions not restricted to the weaning phase. Strategies combining pressure support ventilation (PSV) with positive end-expiratory pressure (PEEP) and low fraction of inspired oxygen (FiO2 ) improved atelectasis, oxygenation, and lung volumes. Low FiO2 improved atelectasis and oxygenation but might not improve lung volumes. A fixed-PEEP strategy led to no improvement in oxygenation or atelectasis; however, individualised PEEP with low FiO2 improved oxygenation and might be associated with reduced PPCs. Half of included studies are of moderate or high risk of bias; the overall quality of evidence is low.

There is limited research evaluating weaning from intraoperative MV. Based on low-quality evidence, PSV, individualised PEEP, and low FiO2 may be associated with reduced postoperative pulmonary outcomes.

Weaning from mechanical ventilation in the operating room: a systematic review.

British Journal of Anaesthesia

The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP.

This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading of Recommendations, Assessment, Development and Evaluations). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations.

The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis.

With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made.

Nucleoside deaminases: the key players in base editing toolkit.

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