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An editorial is presented that discusses the significance of timely diagnosis and treatment for anti-factor H antibody-associated aHUS, highlighting the effectiveness of eculizumab and the need for standardization in anti-FH antibody testing. It notes that while some studies advocate for its use as a primary treatment, further multicenter research is necessary to refine management strategies and establish effective treatment protocols.

Background: Lupus nephritis (LN) is a very severe manifestation of lupus. There is no consensus on which treatment goals should be achieved to protect kidney function in children with LN. Methods: We retrospectively analyzed trends of commonly used laboratory biomarkers of 428 patients (≤ 18 years old) with biopsy-proven LN class ≥ III. We compared data of patients who developed stable kidney remission from 6 to 24 months with those who did not. Results: Twenty-five percent of patients maintained kidney stable remission while 75% did not. More patients with stable kidney remission showed normal hemoglobin and erythrocyte sedimentation rate from 6 to 24 months compared to the group without stable kidney remission. eGFR ≥ 90 ml/min/1.73m2 at onset predicted the development of stable kidney remission (93.8%) compared to 64.7% in those without stable remission (P < 0.00001). At diagnosis, 5.9% and 20.2% of the patients showed no proteinuria in the group with and without stable kidney remission, respectively (P = 0.0001). dsDNA antibodies decreased from onset of treatment mainly during the first 3 months in all groups, but more than 50% of all patients in both groups never normalized after 6 months. Complement C3 and C4 increased mainly in the first 3 months in all patients without any significant difference. Conclusions: Normal eGFR and the absence of proteinuria at onset were predictors of stable kidney remission. Significantly more children showed normal levels of Hb and erythrocyte sedimentation rate (ESR) from 6 to 24 months in the group with stable kidney remission. [ABSTRACT FROM AUTHOR]

Background: Furosemide stress test (FST) is a novel functional biomarker for predicting severe acute kidney injury (AKI); however, pediatric studies are limited. Methods: Children 3 months to 18 years of age admitted to the intensive care unit (ICU) of a tertiary care hospital from Nov 2019 to July 2021 were screened and those who developed AKI stage 1 or 2 within 7 days of admission underwent FST (intravenous furosemide 1 mg/kg). Urine output was measured hourly for the next 6 h; a value > 2 ml/kg within the first 2 h was deemed furosemide responsive. Other biomarkers like plasma neutrophil gelatinase-associated lipocalin (NGAL) and proenkephalin (PENK) were also evaluated. Results: Of the 480 admitted patients, 51 developed AKI stage 1 or 2 within 7 days of admission and underwent FST. Nine of these patients were furosemide non-responsive. Thirteen (25.5%) patients (eight of nine from FST non-responsive group) developed stage 3 AKI within 7 days of FST, nine (17.6%) of whom (seven from non-responsive group) required kidney support therapy (KST). FST emerged as a good biomarker for predicting stage 3 AKI and need for KST with area-under-the-curve (AUC) being 0.93 ± 0.05 (95% CI 0.84–1.0) and 0.96 ± 0.03 (95% CI 0.9–1.0), respectively. FST outperformed NGAL and PENK in predicting AKI stage 3 and KST; however, the combination did not improve the diagnostic accuracy. Conclusions: Furosemide stress test is a simple, inexpensive, and robust biomarker for predicting stage 3 AKI and KST need in critically ill children. Further research is required to identify the best FST cut-off in children. [ABSTRACT FROM AUTHOR]

Purpose: To describe the clinical features, management, and long-term outcome of Infectious crystalline keratopathy (ICK). Methods: The medical records of clinically diagnosed and microbiologically proven cases of ICK were reviewed from January 2011 to December 2022. Clinical characteristics include the presence of whitish needle-like projections with branching, limited to anterior-mid stroma. Keratoplasty being the most common risk factor, graft-related microbial keratitis during the same period was also studied. The demography, clinical profile, microbiology, treatment, and outcome were analyzed, and compared with secondary graft infiltrate(GI). Results: Medical records of 24 cases with ICK were reviewed. The mean age was 49.3 ± 20.1 years, with 15(62.5%) males. Prior keratoplasty was done in 18 (75%) cases, with a mean graft size of 10.1 ± 1.5 mm, and mean interval between the last graft and presentation was 9.7 ± 6.2 (3–90) months. In comparison to GI (n = 24), ICK patients (n = 18,75%) were less symptomatic, presented late (7.3 ± 6.5 days vs 16.3 ± 19.4, p = 0.003), using frequent topical steroids (> 3 times/day, p = 0.006), smaller infiltrate size < 4 mm (p = 0.008), central (p = 0.02), less associated with epithelial defect (p = 0.0001), hypopyon (p = of 0.0002), corneal perforation (p = 0.0006), and surgical management (p = 0.03). On microbiology, 22 (91.6%) ICK cases were culture positive, 14 (63.6%) gram-positive, 3 (13.6%) gram-negative, 2 (9%) mixed bacteria, and 3 (13.6%) fungus, comparable with GI. Conclusion: ICK affects poor ocular surfaces usually following keratoplasty with larger graft size, the use of steroids being the most common association, and it responds to medical management as compared to GI. [ABSTRACT FROM AUTHOR]

Radio frequency (RF) is perceived as one of the most popular wireless transmission candidate in the last decade however due to ever-increasing current generation bandwidth demands; it becomes incompetent to fulfil the requirements. A futuristic and high speed data transmission technique is replacing RF nowadays i.e. Free space optical communication (FSOC) because of its great potentials. Future generation communication systems require competent FSOC technology to sustain wireless traffic in 5G and 6G services. Because the features of FSOC and RF are complimentary, combining the two technologies is seen as a potential way to enable future communication systems. Hybrid RF/FSOC is a good way to overcome the limits of separate systems while still taking use of the beneficial aspects of each technology. Wireless systems use e.g. in hybrid RF/FSOC can increase individual network performance in terms of performance, dependability, and economical operations. In this work, a detailed review on FSOC systems is presented by doing the extensive literature review of reported research. Review covered key ideas consisting all sorts of FSOC systems, FSOC design with multiple and single beams, as part of the evaluation. The examination of rainfall and hazy effects on FSO signal transmission is also included in the review. The key benefits, future potential, and obstacles that must be addressed in order to successfully implement FSOC for 5G paradigms are presented. [ABSTRACT FROM AUTHOR]

Background: Plasma exchanges (PEX) and immunosuppression are the cornerstone of management of anti-factor H (FH) antibody-associated atypical hemolytic uremic syndrome (aHUS), particularly if access to eculizumab is limited. The duration of therapy with PEX for anti-FH aHUS is empirical. Methods: We compared the efficacy of abbreviated PEX protocol (10–12 sessions) in a prospective cohort of patients diagnosed with anti-FH aHUS (2020–2022), to standard PEX protocol (20–22 sessions) in a historical cohort (2016–2019; n = 65). Efficacy was defined as 70% decline in anti-FH titers or fall to ≤ 1300 AU/ml at 4 weeks. Patients in both cohorts received similar immunosuppression with oral prednisolone, IV cyclophosphamide (5 doses) and mycophenolate mofetil. Outcomes included efficacy, rates of hematological remission and adverse kidney outcomes at 1, 3 and 6 months. Results: Of 23 patients, 8.2 ± 2.1 years old enrolled prospectively, two were excluded for significant protocol deviation. PEX was abbreviated in 18/21 (86%) patients to 11.5 ± 3.3 sessions. Abbreviation failed for lack of hematological remission by day 14 (n = 2) and persistent neurological manifestations (n = 1). All patients in whom PEX was abbreviated achieved > 70% reduction in anti-FH titers at day 28. The percentage fall in anti-FH titers was similar for the abbreviated vs. standard PEX protocols at 1, 3 and 6 months. At last follow-up, at median 50 months and 25 months for standard and abbreviated cohorts, the estimated GFR was similar at 104.8 ± 29.1 vs. 93.7 ± 53.4, respectively (P = 0.42). Conclusion: Abbreviation of the duration of PEX is feasible and efficacious in reducing anti-FH titers. Short-term outcomes were comparable in patients managed by abbreviated and standard PEX protocols. [ABSTRACT FROM AUTHOR]

Improving the machining efficiency in form of better surface quality and improved tool life is always challenging. This is due to the high amount of heat produced during machining. Hence effective measures are required to control the heat generated. In this response, conventional coolants are applied to achieve cooling and lubricating effect in machining. However, these cutting fluids affect the operator's health and environmental resources. Considering this, the aim of the work is to assess the role of minimum quantity lubrication (MQL) compared to dry and flood cooling. The turning tests are performed under the defined machining environments to find the most suitable combination of parameters to minimize the tool wear and surface roughness. The Taguchi orthogonal arrays are incorporated to evaluate the 27 different combinations of variable working parameters and assess them. The lubricating conditions are varied as per the experimental design. Three different lubricating conditions are used: dry lubrication, flood lubrication and MQL. A statistical analysis of obtained results is performed to understand the effect of machining variables on output responses. A multi-response optimization is conducted to minimize surface roughness and tool wear by utilizing Grey relational analysis. Finally, the most suitable combination of parameters is suggested based on the obtained grey relational grade. [ABSTRACT FROM AUTHOR]

Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1–3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision–language pretraining for pathology7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.Prov-GigaPath, a whole-slide pathology foundation model pretrained on a large dataset containing around 1.3 billion pathology images, attains state-of-the-art performance in cancer classification and pathomics tasks. [ABSTRACT FROM AUTHOR]

Background: The etiology of atypical hemolytic uremic syndrome (aHUS) is unknown in 30–40% of patients. Anti-factor B (FB) antibodies are reported in C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN), though not in aHUS. Methods: We screened patients < 18-year-old from cohorts of aHUS and C3G/idiopathic IC-MPGN. Anti-FB IgG antibodies were measured by ELISA and confirmed by Western blot. Normative levels were based on antibody levels in 103 healthy blood donors. Results: Prevalence of anti-FB antibodies was 9.7% (95% CI 6.1–14.5%; n = 21) in 216 patients with aHUS, including 11.5% (95% CI 6.4–18.5%; n = 14) in anti-FH associated aHUS and 11.8% (95% CI 4.4–23.9%; n = 6) in patients without a definitive genetic or autoimmune etiology. Patients with significant genetic variants did not show anti-FB antibodies. In patients with concomitant anti-FB and anti-FH antibodies, median anti-FH titers were higher (11,312 AU/mL vs. 4920 AU/mL; P = 0.04). Anti-FB antibody titer correlated with disease severity (hemoglobin and platelets; P < 0.05), declined following plasma exchange and increased during relapse. While 4/64 patients with C3G (6.3%) and 1/17 with IC-MPGN showed anti-FB antibodies, titers were higher in aHUS (544.8 AU/mL vs. 1028.8 AU/mL; P = 0.003). Conclusion: Anti-FB antibodies are present in 6–10% of patients with aHUS and C3G/IC-MPGN, with higher titers in the former. The diagnostic and therapeutic implication of anti-FB antibodies in aHUS needs confirmation and further studies. The study shows propensity for autoantibody generation and co-existence of multiple risk factors for aHUS in Indian children. [ABSTRACT FROM AUTHOR]

We present updated, evidence-based clinical practice guidelines from the Indian Society of Pediatric Nephrology (ISPN) for the management of urinary tract infection (UTI) and primary vesicoureteric reflux (VUR) in children. These guidelines conform to international standards; Institute of Medicine and AGREE checklists were used to ensure transparency, rigor, and thoroughness in the guideline development. In view of the robust methodology, these guidelines are applicable globally for the management of UTI and VUR. Seventeen recommendations and 18 clinical practice points have been formulated. Some of the key recommendations and practice points are as follows. Urine culture with > 104 colony forming units/mL is considered significant for the diagnosis of UTI in an infant if the clinical suspicion is strong. Urine leukocyte esterase and nitrite can be used as an alternative screening test to urine microscopy in a child with suspected UTI. Acute pyelonephritis can be treated with oral antibiotics in a non-toxic infant for 7–10 days. An acute-phase DMSA scan is not recommended in the evaluation of UTI. Micturating cystourethrography (MCU) is indicated in children with recurrent UTI, abnormal kidney ultrasound, and in patients below 2 years of age with non-E. coli UTI. Dimercaptosuccinic acid scan (DMSA scan) is indicated only in children with recurrent UTI and high-grade (3–5) VUR. Antibiotic prophylaxis is not indicated in children with a normal urinary tract after UTI. Prophylaxis is recommended to prevent UTI in children with bladder bowel dysfunction (BBD) and those with high-grade VUR. In children with VUR, prophylaxis should be stopped if the child is toilet trained, free of BBD, and has not had a UTI in the last 1 year. Surgical intervention in high-grade VUR can be considered for parental preference over antibiotic prophylaxis or in children developing recurrent breakthrough febrile UTIs on antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

Breast cancer, a prominent contributor to global cancer-related deaths, is a substantial health obstacle for women. Of all the several types of breast cancers, invasive ductal carcinoma is the most prevalent histological subtype, which includes ductal carcinoma, inflammatory breast cancer, invasive lobular carcinoma, and breast carcinoma. Although there have been improvements in traditional treatment methods, it is still crucial to develop more accurate and efficient therapies. CRISPR technology, which stands for clustered, regularly interspaced short palindromic repeats, has become a ground-breaking tool in the fight against breast cancer. This article provides an overview on the prospective application of CRISPR technology to explore breast cancer and its capacity to transform the identification and therapy of breast carcinoma. Presently, the research community is actively exploring targeted approaches to utilize CRISPR for the purpose of selectively modifying crucial genes linked to breast cancer, surmounting resistance to therapy, and improving the precision of diagnostic methods. Researchers are utilizing the accuracy and CRISPR technology's adaptability to create new tactics & strategies for addressing breast cancer and triple negative breast carcinoma (TNBC), providing renewed optimism for patients and healthcare practitioners. [ABSTRACT FROM AUTHOR]

Non-quasi-static small-signal models are essential for exploring the high-frequency (HF) behavior of the FinFET. In this paper, we propose a modified small-signal model for a multi-fin (MF) FinFET to extract the intrinsic and extrinsic parameters using Y-parameters extracted from TCAD. The gate resistance plays a significant role in optimizing the HF behavior with the varying numbers of fins in the MF configuration. We also test the model's accuracy with increasing temperature up to 425 K. Using well-calibrated TCAD models, we further analyze the analog and linearity figures of merit, including cutoff frequency (f T ), the maximum frequency of oscillation (f max ), transconductance (g m ) and higher-order derivatives such as g m 2 , g m 3 , VIP 2 , and VIP 3 . Thus, the behavior of intrinsic and extrinsic parasitic resistance and capacitance is worth exploring to determine the device operation in the frequency range of >100 GHz. [ABSTRACT FROM AUTHOR]

Non-specific symptoms and difficulty in collecting urine specimens make the diagnosis of urinary tract infection (UTI) challenging in children. However, timely diagnosis and initiation of therapy are essential to prevent complications. Children with recurrent UTIs require detailed evaluation and follow-up for optimal management. We report key updates from the revised evidence-based practice guidelines of the Indian Society of Pediatric Nephrology for UTIs and primary vesicoureteric reflux. [ABSTRACT FROM AUTHOR]

A retrospective study of 24 neonates to evaluate the feasibility and efficacy of high frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) for transferring critically ill neonates to tertiary neonatal intensive care, who were transported by road ambulance was done. Efficacy was measured by clinical improvement, patient safety was assessed by comparing cardiorespiratory indicators before and after transport, and adverse events during transport. Significant oxygenation improvement was observed in neonates transported with HFOV ± iNO compared to earlier ventilator settings. Pre- and post-transport vital signs were stable, and no transport-related deaths occurred. A substantial rise in median SpO2 was seen after transfer [86 (81, 91) vs. 93 (89, 97) before transport, p <0.001]. Twelve of twenty-one newborns who received nitric oxide demonstrated significant improvement in oxygenation index (a 10% decrease from prior value). Overall survival was 70.8%, however non-transfer or inadequate respiratory treatment may have exacerbated mortality. [ABSTRACT FROM AUTHOR]

Purpose: A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication. Methods: Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1–2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters. Results: Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months. Conclusion: The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months. Trial Registry: ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016. [ABSTRACT FROM AUTHOR]

Free space optical communication (FSO) is thriving with greater pace nowadays due to its ability to support high speed, greater capacity, improved security, ease of installation, not having of Electromagnetic interference (EMI) and unlicensed spectrum. Atmospheric turbulence like Rain, Fog, and Haze is a prominent issue in FSO system that adversely affects the performance. This paper presents the demonstration of a multibeam FSO system operating at 1.25 Gbps in several haze types, including hazardous, very unhealthy, sensitive, good, moderate, and unhealthy. Additionally, BER and Q factor comparisons are made across three distinct pulse formats: carrier suppressed RZ (CSRZ), return to zero (RZ), and non-return to zero (NRZ). Utmost goal for the deployment of multibeam FSO is to get high received power and to compensate attenuation arising from haze effects. Results revealed that CSRZ performed exceptionally well as compared to NRZ and RZ. [ABSTRACT FROM AUTHOR]

Objective: To describe the demographics and clinical profile of Herpes Simplex Virus (HSV) Keratitis in patients presenting to a multi-tier ophthalmology hospital network in South India. Methods: We have reviewed the medical records of all patients having a clinical diagnosis of any form of HSV keratitis, seen between May 2012 and August 2020 across the L V Prasad Eye Institute network. All the further analyses of the groups were performed using the keywords used for making the diagnosis of HSV keratitis and the data were collected from the electronic medical record system. Results: There were a total of 8308 (N = 8897 eyes) patients. Male: female ratio was 5368 (64.61%):2940 (35.39%). Unilateral involvement was in 7719 (92.91%) patients. The most common age group affected was between the third to fifth decades of life with 1544 (18.58%). 3708 (1.68%) eyes had mild visual impairment (< 20/70) while the rest of them had moderate to severe visual impairment as observed mainly (p ≤ 0.01) in Necrotizing stromal keratitis. 7314 (82.21%) eyes had normal intraocular pressure (10–21 mm Hg) while raised most commonly in keratouveitis (P ≤ 0.01). Epithelial Keratitis, Immune Stromal Keratitis, Endotheliitis, Neurotrophic keratopathy and Keratouveitis were observed in 1875 (17.22%) eyes, 5430 (61.03%) eyes, in 129(1.45%) eyes, 1188 (13.35%) eyes, 148 (1.66%) eyes and 256 (2.88%) eyes respectively. Conclusion: Based on our institute-based data, the most common type of HSV keratitis is Immune stromal keratitis followed by epithelial keratitis. Although not representative of the general population, this data provide useful insights related to HSV keratitis from India. [ABSTRACT FROM AUTHOR]

Background: Children with lupus have a higher chance of nephritis and worse kidney outcome than adult patients. Methods: We retrospectively analyzed clinical presentation, treatment and 24-month kidney outcome in a cohort of 382 patients (≤ 18 years old) with lupus nephritis (LN) class ≥ III diagnosed and treated in the last 10 years in 23 international centers. Results: The mean age at onset was 11 years 9 months and 72.8% were females. Fifty-seven percent and 34% achieved complete and partial remission at 24-month follow-up, respectively. Patients with LN class III achieved complete remission more often than those with classes IV or V (mixed and pure). Only 89 of 351 patients maintained stable complete kidney remission from the 6th to 24th months of follow-up. eGFR ≥ 90 ml/min/1.73 m2 at diagnosis and biopsy class III were predictive of stable kidney remission. The youngest and the oldest age quartiles (2y—9y, 5m) (14y, 2m—18y,2m) showed lower rates of stable remission (17% and 20.7%, respectively) compared to the two other age groups (29.9% and 33.7%), while there was no difference in gender. No difference in achieving stable remission was found between children who received mycophenolate or cyclophosphamide as induction treatment. Conclusion: Our data show that the rate of complete remission in patients with LN is still not high enough. Severe kidney involvement at diagnosis was the most important risk factor for not achieving stable remission while different induction treatments did not impact outcome. Randomized treatment trials involving children and adolescents with LN are needed to improve outcome for these children. [ABSTRACT FROM AUTHOR]

Background: Severity of acute kidney injury (AKI) confers higher odds of mortality. Timely recognition and early initiation of preventive measures may help mitigate the injury further. Novel biomarkers may aid in the early detection of AKI. The utility of these biomarkers across various clinical settings in children has not been evaluated systematically. Objective: To synthesize the currently available evidence on different novel biomarkers for the early diagnosis of AKI in pediatric patients. Data sources: We searched four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies published between 2004 and May 2022. Study eligibility criteria: Cohort and cross-sectional studies evaluating the diagnostic performance of biomarkers in predicting AKI in children were included. Participants and interventions: Participants in the study included children (aged less than 18 years) at risk of AKI. Study appraisal and synthesis methods: We used the QUADAS-2 tool for the quality assessment of the included studies. The area under the receiver operating characteristics (AUROC) was meta-analyzed using the random-effect inverse-variance method. Pooled sensitivity and specificity were generated using the hierarchical summary receiver operating characteristic (HSROC) model. Results: We included 92 studies evaluating 13,097 participants. Urinary NGAL and serum cystatin C were the two most studied biomarkers, with summary AUROC of 0.82 (0.77–0.86) and 0.80 (0.76–0.85), respectively. Among others, urine TIMP-2*IGFBP7, L-FABP, and IL-18 showed fair to good predicting ability for AKI. We observed good diagnostic performance for predicting severe AKI by urine L-FABP, NGAL, and serum cystatin C. Limitations: Limitations were significant heterogeneity and lack of well-defined cutoff value for various biomarkers. Conclusions and implications of key findings: Urine NGAL, L-FABP, TIMP-2*IGFBP7, and cystatin C showed satisfactory diagnostic accuracy in the early prediction of AKI. To further improve the performance of biomarkers, they need to be integrated with other risk stratification models. Systematic review registration: PROSPERO (CRD42021222698). [ABSTRACT FROM AUTHOR]

Manufacturing sector is always looking for higher level of automation in various operations. However, a few key challenges affects the whole machining process from being fully automated. One of these problems is the computerized tool wear monitoring. Automatic tool condition monitoring is becoming increasingly important in the metal cutting industry due to the wear on the tool impacts the efficiency of the manufactured component. Tool wear and life are major factors that influence part quality. To evaluate the useful life of the tool, most industries rely on historical data. Tool wear may be measured in two ways: directly and indirectly. The tool wear measured using the indirect approach uses parameter that impact tool life. Tool wear is traditionally assessed using microscope, which is time-consuming method. Direct method such as computer vision system is fast and reliable approach to monitor the condition of tool during machining. The goal of this research is to employ computer vision techniques to automate flank wear assessment, predict flank wear, and improve tool life prediction. The process of measuring and monitoring tool wear is automated using computer vision techniques using industrial camera with telecentric lens. Different algorithms related to feed forward back propagation neural network: Levenberg - Marquardt algorithm, Bayesian regularization and scaled conjugate gradient are utilized to predict the tool life. Performance evaluation of these algorithms is done to find most accurate algorithm for tool wear prediction system. The presented approach helps industries to detect the status of tool wear and can be a potential approach for estimating tool life in turning operations. [ABSTRACT FROM AUTHOR]

Background: Thrombotic microangiopathy (TMA) is usually caused due to dysregulation of the alternative complement pathway. Rarely, thrombotic microangiopathy is caused by non-complement mediated mutations in diacylglycerol kinase epsilon (DGKE); information about therapy and outcome of these patients is limited. Methods: Medical records of patients, younger than 18 years, diagnosed with TMA and variants in DGKE were reviewed to include 12 patients from seven centers. Genetic studies included targeted exome sequencing and multiplex-ligation dependent probe amplification of CFH-CFHR5. Results: Patients presented at a median age of 11 (7.5, 12.3) months; all were younger than 2 years. All patients had an infectious prodrome; enteroinvasive, enteropathogenic, and enterotoxigenic Escherichia coli were detected in two patients with diarrhea. Chief features included those of microangiopathic hemolysis (n = 11), microscopic hematuria (n = 10), nephrotic range proteinuria (n = 10), hypoalbuminemia (n = 6), elevated total cholesterol (n = 6), and hypocomplementemia (n = 4). Histopathology showed thrombotic microangiopathy (n = 4), overlapping with membranoproliferative pattern of injury (n = 1). At median 3.3 years of follow-up, significant hypertension and/or proteinuria (40%), relapses (66.7%), and death or progression to CKD (60%) were common. Genetic sequencing showed 13 homozygous and compound heterozygous variants (7 pathogenic, 3 likely pathogenic) located throughout DGKE; 11 variants were novel. Conclusions: This case series highlights the need to suspect DGKE nephropathy in young patients with TMA, especially those with severe proteinuria. Medium-term outcomes are unsatisfactory with risk of relapses, progressive kidney failure, and death. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is a potentially modifiable risk factor in patients with chronic kidney disease (CKD). Information on the safety and efficacy of statins in pediatric CKD is limited. Methods: Patients with CKD stage 2–5 and aged 5–18 years with low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL and/or non-high-density lipoprotein cholesterol (non-HDL-C) > 145 mg/dL were enrolled from September 2019 to February 2021. All patients were administered atorvastatin 10 mg/day, which was escalated to 20 mg/day if LDL-C remained > 100 mg/dL and/or non-HDL-C > 120 mg/dL at 12 weeks. Proportion of patients achieving target lipid levels (LDL-C ≤ 100 mg/dL and non-HDL-C ≤ 120 mg/dL) and adverse events were assessed at 24 weeks. Results: Of 31 patients enrolled, target lipid levels were achieved in 45.2% (95% CI 27.8–63.7%) at 24 weeks; 22 patients required dose escalation to 20 mg at 12 weeks. There was no difference in median lipid level reduction with 10 (n = 9) versus 20 mg/day (n = 22, P = 0.3). Higher baseline LDL-C (OR 1.06, 95% CI 1.00–1.11) and older age (OR 36.5, 95% CI 2.57–519.14) were independent predictors of failure to achieve target lipid levels with 10 mg/day atorvastatin. None had persistent rise in AST/ALT > 3 times upper normal limit (UNL) or CPK > 10 times UNL. No differences were noted in adverse events due to atorvastatin 10 or 20 mg/day. Conclusion: Atorvastatin (10–20 mg/day) administered for 24 weeks was safe and effectively reduced LDL-C and non-HDL-C in children with CKD stages 2–5. Patients with higher baseline LDL-C required higher doses to achieve the target. [ABSTRACT FROM AUTHOR]

Background: Coexisting genetic variants in patients with anti-factor H (FH)-associated atypical hemolytic uremic syndrome (aHUS) have implications for therapy. We estimated the prevalence of complement genetic variants in children with anti-FH aHUS from a prospective nationwide cohort and determined if significant genetic variants impact long-term kidney outcomes. Methods: Of 436 patients in the database, 77 consecutive patients, 21 with a relapse and 9 with kidney failure and/or death were included. Targeted sequencing, using a 27-gene panel including CFH, CFI, CFB, C3, CD46, PLG, DGKE, and THBD and multiplex ligation-dependent probe amplification of CFH-CFHR region, was performed. The adverse outcome was eGFR < 30 ml/min/1.73 m2 or death. Results: Patients had high anti-FH titers 5670 (2177–13,545) AU/ml, relapsing course (42.1%), and adverse outcomes (19.6%). Variants, chiefly of unknown significance, were found in 7 (6.5%; 95% CI 3.1–13.2%); a pathogenic variant was found in one patient. Homozygous deletion of CFHR1 was present in 91.6% compared to 9.8% in 184 healthy controls. Plasma exchanges and immunosuppression showed a trend of improving outcomes, independent of genetic defects (HR 0.32; P = 0.070). Meta-analysis of 18 studies (384 patients) showed that the pooled prevalence of pathogenic and likely pathogenic variants was 3% (95% CI 0–8%). Of 37 total variants in the meta-analysis, 7 (18.9%) each were pathogenic and likely pathogenic; others were variants of unknown significance. Conclusions: Significant variants in complement regulatory genes are rare in patients with anti-FH-associated aHUS. Irrespective of genetic defects, plasma exchanges and immunosuppression showed a statistical trend to improved outcomes. [ABSTRACT FROM AUTHOR]

Background: Various laboratory parameters like C-reactive protein (CRP), Cortisol, and Von Willebrand factor antigen have been evaluated independently in foreseeing outcomes of cirrhotic patients. As these parameters lack cost-effectiveness in a rural setup, there is a need for a cost effective and feasible prognostic marker for cirrhotic patients. The present study was aimed at evaluating the role of Absolute Eosinophil Count (AEC) as a prognostic marker in cirrhotic patients. Methods: This cross-sectional study was conducted at a rural tertiary care teaching hospital in central India from August 2019 to September 2021. AEC was measured from counter report as a part of automated complete blood counts. Child-Turcotte-Pugh (CTP) score and Model for end stage liver disease (MELD) score were calculated at the time of admission. AEC levels on admission were correlated with mortality and with CTP score and MELD score. Results: A total of 110 patients were enrolled with mean age of 46.37 ± 11.6 years. AEC was the significant predictor of mortality at cut off point of ≤ 120 with 80.30% (AUC 0.803; 95% CI: 0.716 to 0.873). AEC was the significant predictor of CTP score ≥ 11 at cut off point of ≤ 148 (AUC 0.726; 95% CI: 0.633 to 0.807). AEC was the significant predictor of MELD score ≥ 25 at cut off point of ≤ 136 (AUC 0.74; 95% CI: 0.647 to 0.819). Significant negative correlation was seen between AEC with Child–Pugh score and MELD score with correlation coefficient of -0.257 and -0.258. Conclusion: Low level of AEC on admission fairly predicted raised CTP score and MELD score on admission. Low AEC levels predicted increased mortality in cirrhotic patients making it a cheap and reliable prognostic marker in a rural setup. [ABSTRACT FROM AUTHOR]

One of the essential elements of automated and intelligent machining processes is accurately predicting tool life. It also helps in achieving the goal of producing quality products with reduced production costs. This work proposes a computer vision-based tool wear monitoring and tool life prediction system using machine learning methods. Gradient-boosted trees and support vector machine (SVM) techniques are used to predict tool life. The experimental investigation on the CNC machine is conducted to study the applicability of the proposed tool wear monitoring system. Experiments are performed using workpiece material made of alloy steel and PVD-coated cutting inserts, and flank wear is monitored. An imaging system consisting of an industrial camera, lens, and LED ring light is mounted on the machine to capture tool wear zone images. Images are then processed by algorithms developed in MATLAB®. Boosted tree methods and the SVM methodology have 96% and 97% prediction accuracy, respectively. Validation tests are carried out to determine the accuracy of proposed models. It is observed that the prediction accuracy of boosted three and SVM is good, with a maximum error of 5.89% and 7.56%, respectively. The outcome of the study established that the developed system can monitor the tool wear with good accuracy and can be adopted in industries to optimize the utilization of tool inserts. [ABSTRACT FROM AUTHOR]

Purpose: To study the challenges of managing microbial keratitis(MK) during the COVID19 pandemic related lockdown and assess the outcomes of treatment at a tertiary cornea service. Methods: Retrospective, non comparative study of electronic medical records of MK presenting to a network of four tertiary care cornea services. The medical history, presenting clinical features, microbiology work up and treatment outcomes were analyzed. The primary outcome measure was final outcome at last follow up. Secondary outcomes measures were non-compliance to treatment due to travel restrictions, therapeutic PKP not done due non availability of corneal tissues. Results- MK was noted in 330 eyes of 330 patients between April and May 2020. Of these 237(71.8%) were males. Median age was 45 years(IQR, 33-56). Low socioeconomic status noted in 102(30.9%). Patients travelling beyond the district from where the hospital was located comprised of 64.9%(n=214). At a median follow up of 32 days(IQR, 9-54), 118(35.8%) patients had resolved, with medical management, 73(22.1%) patients were under active treatment, 139(42.1%) were lost to follow up. Sixty-six patients(20%) were non-compliant to treatment of which 59 could not follow appointment schedule due to travel restrictions. Therapeutic PKP (TPK) was planned in 48/128 (37.5%) patients, but was performed in only 34/48 (70.8%) due to non-availability of donor corneas. Conclusions: Abnormal social circumstances due to the COVID pandemic and the ensuing impediments to travel for access to health care affected compliance to treatment of ocular emergencies such as microbial keratitis. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is common in critically ill patients, affecting almost one in four critically ill children and one in three neonates. Higher stages of AKI portend worse outcomes. Identifying AKI timely and instituting appropriate measures to prevent and manage severe AKI is important, since it is independently associated with mortality. Methods to predict severe AKI should be applied to all critically ill patients. Assessment of volume status to prevent the development of fluid overload is useful to prevent adverse outcomes. Patients with metabolic or clinical complications of AKI need prompt kidney replacement therapy (KRT). Various modes of KRT are available, and the choice of modality depends most on the technical competence of the center, patient size, and hemodynamic stability. Given the significant risk of chronic kidney disease, patients with AKI require long-term follow-up. It is important to focus on improving awareness about AKI, incorporate AKI prevention as a quality initiative, and improve detection, prevention, and management of AKI with the aim of reducing acute and long-term morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Lupus nephritis (LN) has variable prevalence, severity, and outcomes across the world. Objectives: This review compares the outcomes of childhood LN in low- and middle-income countries (LMICs) and high-income countries (HICs) and aims to summarize long-term outcomes of pediatric LN from LMICs. Data sources: A systematic literature search, conducted in PubMed, EMBASE, and Cochrane database in the last 30-years from January 1992, published in the English language, identified 113 studies including 52 from lower (n = 1336) and upper MICs (n = 3014). Study eligibility criteria: Cohort studies or randomized controlled trials, of patients ≤ 18 years of age (or where such data can be separately extracted), with > 10 patients with clinically or histologically diagnosed LN and outcomes reported beyond 12 months were included. Participants and interventions: Patients ≤ 18 years of age with clinically or histologically diagnosed LN; effect of an intervention was not measured. Study appraisal and synthesis methods: Two authors independently extracted data. We separately analyzed studies from developed countries (high income countries; HIC) and developing countries (LMICs). Middle-income countries were further classified as lower and upper MICs. Meta-analyses of data were performed by calculating a pooled estimate utilizing the random-effects model. Test for heterogeneity was applied using I2 statistics. Publication bias was assessed using funnel plots. Results: Kidney remission was similar across MICs and HICs with 1-year pooled complete remission rates of 59% (95% CI 51–67%); one third of patients had kidney flares. The pooled 5-year survival free of stage 5 chronic kidney disease (CKD5) was lower in MICs, especially in lower MICs compared to HICs (83% vs. 93%; P = 0.002). The pooled 5-year patient survival was significantly lower in MICs than HICs (85% vs. 94%; P < 0.001). In patients with class IV LN, the 5-and 10-year respective risk of CKD5 was 14% and 30% in MICs; corresponding risks in HICs were 8% and 17%. Long-term data from developing countries was limited. Sepsis (48.8%), kidney failure (14%), lupus activity (18.1%), and intracranial hemorrhage/infarct (5.4%) were chief causes of death; mortality due to complications of kidney failure was more common in lower MICs (25.6%) than HICs (6.4%). Limitations: The review is limited by heterogenous approach to diagnosis and management that has changed over the period spanning the review. World Bank classification based on income might not correlate with the standards of medical care. The overall quality of evidence is low since included studies were chiefly retrospective and single center. Conclusions and implications of key findings: Challenges in LMICs include limited access to pediatric nephrology care, dialysis, increased risk of infection-induced mortality, lack of frequent monitoring, and non-compliance due to cost of therapy. Attention to these issues might update the existing data and improve patient follow-up and outcomes. Systematic review registration number: PROSPERO 2022 number: CRD42022359002, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359002 [ABSTRACT FROM AUTHOR]

Objectives: To examine the feasibility, efficacy, and safety of sustained low-efficiency dialysis (SLED) in hemodynamically unstable, critically ill children. Methods: Critically ill patients, 1–18 y old with hemodynamic instability (≥ 1 vasoactive drugs) and severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) in a tertiary care pediatric intensive care unit were prospectively enrolled. Patients weighing ≤ 8 kg or with mean arterial pressure < 5th percentile despite > 3 vasoactive drugs, were excluded. Patients underwent SLED until hemodynamically stable and off vasoactive drugs, or lack of need for dialysis. The primary outcome was the proportion of patients in whom the first session of SLED was initiated within 12 h of its indication and completed without premature (< 6 h) termination. Efficacy was estimated by ultrafiltration, urea reduction ratio (URR), and equilibrated Kt/V. Other outcomes included: changes in hemodynamic scores, circuit clotting, adverse events, and changes in indices on point-of-care ultrasonography and echocardiography. Results: Between November 2018 and March 2020, 18 patients with median age 8.6 y and vasopressor dependency index of 83.2, underwent 41 sessions of SLED. In 16 patients, SLED was feasible within 12 h of indication. No session was terminated prematurely. Ultrafiltration achieved was 4.0 ± 2.2 mL/kg/h, while URR was 57.7 ± 16.2% and eKt/V 1.17 ± 0.56. Hemodynamic scores did not change significantly. Asymptomatic hypokalemia was the chief adverse effect. Sessions were associated with a significant improvement in indices on ultrasound and left ventricular function. Fourteen patients died. Conclusions: SLED is feasible, safe, and effective in enabling KRT in hemodynamically unstable children with severe AKI. [ABSTRACT FROM AUTHOR]

Background: Utilizing a participation burden algorithm developed in a previous study, Tufts CSDD, in collaboration with ZS, led a workshop among 8 pharmaceutical companies to validate the methodology of benchmarking the participation burden of a set of retrospective protocols and comparing these data to a prospective protocol design. Methods: Eight participating companies collected data for 66 retrospective protocols and participation burden scores were calculated for each. Data from one prospective protocol was provided and prospective burden scores were compared to mean retrospective protocol burden for each company. Participating companies provided feedback on data collection process and final reports. Results: Comparisons between retrospective and prospective burden scores revealed higher comparative burden in lab and blood procedures. Companies were able to gather most requested data, but some variables hypothesized to affect burden were not available to sponsors. Time constraints were reported as a challenge throughout the data collection process. Conclusions: Feedback indicated the need for establishing a larger database to enable comparisons between protocols with the same therapeutic area and indication. Investigating the impact of standard of care burden by indication on overall participation burden and encouraging sponsors to collect more accurate data contributing to participation burden at the site level are also important takeaways from this exercise. [ABSTRACT FROM AUTHOR]

Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85–90% of patients attain complete remission of proteinuria within 4–6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70–80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given. [ABSTRACT FROM AUTHOR]

Wireless Sensor networks contain sensor nodes with specialized infrastructure for the purpose of inspection of certain physical conditions at very divergent environments. Usually, physical characteristics of the environment including temperature, humidity, pressure etc. are examined by the sensor nodes. These nodes are generally small sized and light weight. Because of their small size, power supply is very much limited. Careful usage of the limited power supply is a very important factor to be considered during communication of data in the network. With the aim of achieving effective energy usage, several techniques have been applied for the routing of information packets. One such technique is clustering of sensor nodes within the network. It implicates that the nodes organize themselves into groups to form several clusters where each group has a leader of the cluster group called the cluster head. The routing using this clustering technique does not always involve direct transmission. Rather, multi-hop transmission happens usually, with the data firstly being transferred from sensor nodes to their corresponding cluster heads and then later from cluster heads to the sink (Base Station). The cluster head is designated arbitrary or by taking into account various factors which differ according to the different routing protocols. In this paper, a new routing algorithm QBCR (Quadrangle based Clustering Routing Protocol) has been proposed which entails clustering process for routing the data to the base station. This protocol exhibits improvement over conventional routing protocols like LEACH, SEP and DEEC. In this clustering algorithm, division of the zones (clusters) based on the energy levels of the nodes has been carried out in form of quadrangle shaped clusters. The proposed protocol exhibits significant enhancement in the lifetime of the network, stability interval, rate of packet transfer (throughput), and the average energy of the network. The proposed protocol shows an improvement of atleast 50% in all parameters (lifetime of the network, stability interval, rate of packet transfer (throughput) and the average energy of the network) in comparison to the conventional protocols. This proposed protocol is a clear choice over the standard routing protocols wherever it is possible to deploy nodes uniformly in different zones. [ABSTRACT FROM AUTHOR]

Background: Congenital anterior urethral diverticulum (CAUD) is a rare condition in children. This condition can present at any age; however, it is more commonly identified in infants and older children. The patient may present with difficulty in micturition, dribbling of urine, poor urinary stream, or urinary tract infection. Children with large anterior urethral diverticulum with poor spongiosal support may also complain of cystic ventral penile swelling during micturition. Methods: In this series, we report seven such cases of congenital anterior urethral diverticulum treated over a period of 12 years (2008–2020). All cases presented to the Pediatric Surgery Department with dysuria, dribbling of urine, recurrent urinary tract infection, and/or fluctuant ventral penile swelling. They were further evaluated with retrograde urethrography with micturating cysto-urethrogram and cysto-urethroscopy. Results: Three cases had anterior urethral valves that were managed by cystoscopic fulguration of valves. Surprisingly, all these three cases had concomitant posterior urethral valves, while the other four cases presented with relatively larger and saccular anterior urethral diverticulum required excision of the diverticulum and primary urethral reconstruction. Conclusions: The cases with congenital anterior urethral diverticulum secondary to anterior urethral valves may also be associated with posterior urethral valves as seen in our case series. Surgeons should be aware of this association, and both valves should be fulgurated in the same sitting. A larger and saccular anterior urethral diverticulum requires excision and urethroplasty as a definitive procedure. [ABSTRACT FROM AUTHOR]

Using well-calibrated TCAD models, we have exhibited the application of both Dielectric (DE) and Ferroelectric (FE) materials as spacers in Negative Capacitance (NC) FinFET. We have proposed the symmetric (Sym-) and asymmetric (Asym-) FE concentric architecture of NC-FinFET (FEC-NC FinFET) where, the FE spacer is placed upto the FE thickness and the remaining is DE, till spacer height. A thorough evaluation has been made between the two projected FEC-NCFinFET structures and the conventional DE spacer NC-FinFET such that, both the Sym- and Asym-FEC-NCFinFET experiences an increased outer fringing field in the gate (G)-source (S) underlap edge, leading to an excellent veracity over the channel. Both the configuration portrays an enhancement in ON-current (ION) by 12%, the OFF-state current (IOFF) degrades by 50% for symmetric structure and improves by 20% for asymmetric one, over the conventional NC-FinFET. Finally, a relatively superior short channel effect metrics is attained for Asym-FEC-NCFinFET in terms of ION/IOFF ratio, sub-threshold swing (SS), Negative Differential Resistance (NDR) effect and Drain induced barrier lowering (DIBL) phenomenon. [ABSTRACT FROM AUTHOR]

One of the essential requirements for intelligent manufacturing is the low cost and reliable predictions of the tool life during machining. It is crucial to monitor the condition of the cutting tool to achieve cost-effective and high-quality machining. Tool conditioning monitoring (TCM) is essential to determining the remaining useful tool life to assure uninterrupted machining to achieve intelligent manufacturing. The same can be done by direct and indirect tool wear measurement and prediction techniques. In indirect methods, the data is acquired from the sensors resulting in some ambiguity, such as noise, reliability, and complexity. However, in direct methods, the data is available in images resulting in significantly less chances of ambiguity with the proper data acquisition system. The direct methods, which provide higher accuracy than indirect methods, involve collecting images of worn tools at different stages of the machining process to predict the tool life. In this context, a novel tool wear prediction system is proposed to examine the progressive tool wear utilizing the artificial neural network (ANN). Experiments were performed on AISI 4140 steel material under dry cutting conditions with carbide inserts. The cutting speed, feed, depth of cut, and white pixel counts are considered as input parameters for the proposed model, and the flank wear along with remaining tool life is predicted as the output. The worn tool images were captured using an industrial camera during the turning operation at regular intervals. The ANN training set predicts the remaining useful tool life, especially the sigmoid function and rectified linear unit (ReLU) activation function of ANN. The sigmoid function showed an accuracy of 86.5%, and the ReLU function resulted in 93.3% accuracy in predicting tool life. The proposed model's maximum and minimum root mean square error (RMSE) is 1.437 and 0.871 min. The outcomes showcased the ability of image processing and ANN modeling as the potential approach for developing a low-cost industrial tool condition monitoring system that can measure tool wear and predict tool life in turning operations. [ABSTRACT FROM AUTHOR]

The article highlights clinical guidelines for the management of nephrotic syndrome. Topics mentioned include the randomized controlled trials for the use of corticosteroid therapy in the management of first episode of nephrotic syndrome, the use of prednisone for the therapy of relapses, and the importance of managing patients with frequent relapse and who are dependent with steroid to lessen the risk of morbidity and the side effects of immunosuppresive medications.

Background: Rituximab and tacrolimus are therapies reserved for patients with frequently relapsing or steroid-dependent nephrotic syndrome who have failed conventional steroid-sparing agents. Given their toxicities, demonstrating non-inferiority of rituximab to tacrolimus may enable choice between these medications. Methods: This investigator-initiated, single-center, open-label, pilot randomized controlled trial examined the non-inferiority of two doses of intravenous (IV) rituximab given one-week apart to oral therapy with tacrolimus (1:1 allocation), in maintaining sustained remission over 12 months follow-up, in patients with difficult-to-treat steroid-sensitive nephrotic syndrome, defined as frequently relapsing or steroid-dependent disease that had failed ≥ 2 steroid-sparing strategies. Secondary outcomes included frequency of relapses, proportion with frequent relapses, time to relapse and frequent relapses, and adverse events (CTRI/2018/11/016342). Results: Baseline characteristics were comparable for 41 patients randomized to receive rituximab (n = 21) or tacrolimus (n = 20). While 55% of patients in each limb were in sustained remission at 1 year, non-inferiority of rituximab to tacrolimus was not demonstrated (mean difference 0%; 95% CI – 30.8%, 30.8%; non-inferiority limit – 20%; P = 0.50). Frequent relapses were more common in patients administered rituximab compared to tacrolimus (risk difference 30%, 95% CI 7.0, 53.0, P = 0.023). Both groups showed similar reductions in relapse rates and prednisolone use. Common adverse events were infusion-related with rituximab and gastrointestinal symptoms with tacrolimus. Conclusions: Therapy with rituximab was not shown to be non-inferior to 12-months treatment with tacrolimus in maintaining remission in patients with difficult-to-treat steroid-sensitive nephrotic syndrome. Frequent relapses were more common with rituximab. While effective, both agents require close monitoring for adverse events. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Objective: To evaluate metabolic and genetic abnormalities in children with nephrolithiasis attending a referral center in North India.Methods: The patients aged 1-18 y old with nephrolithiasis underwent biochemical evaluation and whole-exome sequencing. The authors evaluated for monogenic variants in 56 genes and compared allele frequency of 39 reported polymorphisms between patients and 1739 controls from the GenomeAsia 100 K database.Results: Fifty-four patients, aged 9.1 ± 3.7 y were included. Stones were bilateral in 42.6%, familial in 33.3%, and recurrent in 25.9%. The most common metabolic abnormalities were hypercalciuria (35.2%), hyperoxaluria (24.1%), or both (11.1%), while xanthinuria (n = 3), cystinuria (n = 1), and hyperuricosuria (n = 1) were rare. Exome sequencing identified an etiology in 6 (11.1%) patients with pathogenic/likely pathogenic causative variants. Three variants in MOCOS and one in ATP7B were pathogenic; likely pathogenic variants included MOCOS (n = 2), AGXT, and SLC7A9 (n = 1, each). Causality was not attributed to two SLC34A1 likely pathogenic variants, due to lack of matching phenotype and dominant family history. Compared to controls, allele frequency of the polymorphism TRPV5 rs4252402 was significantly higher in familial stone disease (allele frequency 0.47 versus 0.53; OR 3.2, p = 0.0001).Conclusion: The chief metabolic abnormalities were hypercalciuria and hyperoxaluria. A monogenic etiology was identified in 11% with pathogenic or likely pathogenic variants using a gene panel for nephrolithiasis. Heterozygous missense variants in the sodium-phosphate cotransporter SLC34A1 were common and required evaluation for attributing pathogenicity. Rare polymorphisms in TRPV5 might increase the risk of familial stones. These findings suggest that a combination of metabolic and genetic evaluation is useful for determining the etiology of nephrolithiasis. [ABSTRACT FROM AUTHOR]

Purpose: Retrospectively compare image quality, radiologist diagnostic confidence, and time for images to reach PACS for contrast enhanced abdominopelvic CT examinations created on the scanner console by technologists versus those generated automatically by thin-client artificial intelligence (AI) mechanisms.A retrospective PACS search identified adults who underwent an emergency department contrast-enhanced abdominopelvic CT in 07/2022 (Console Cohort) and 07/2023 (Server Cohort). Coronal and sagittal multiplanar reformatted images (MPR) were created by AI software in the Server cohort. Time to completion of MPR images was compared using 2-sample t-tests for all patients in both cohorts. Two radiologists qualitatively assessed image quality and diagnostic confidence on 5-point Likert scales for 50 consecutive examinations from each cohort. Additionally, they assessed for acute abdominopelvic findings. Continuous variables and qualitative scores were compared with the Mann-Whitney U test. A p < .05 indicated statistical significance.Mean[SD] time to exam completion in PACS was 8.7[11.1] minutes in the Console cohort (n = 728) and 4.6[6.6] minutes in the Server cohort (n = 892), p < .001. 50 examinations in the Console Cohort (28 women 22 men, 51[19] years) and Server cohort (27 women 23 men, 57[19] years) were included for radiologist review. Age, sex, CTDlvol, and DLP were not statistically different between the cohorts (all p > .05). There was no significant difference in image quality or diagnostic confidence for either reader when comparing the Console and Server cohorts (all p > .05).Examinations utilizing AI generated MPRs on a thin-client architecture were completed approximately 50% faster than those utilizing reconstructions generated at the console with no statistical difference in diagnostic confidence or image quality.Methods: Retrospectively compare image quality, radiologist diagnostic confidence, and time for images to reach PACS for contrast enhanced abdominopelvic CT examinations created on the scanner console by technologists versus those generated automatically by thin-client artificial intelligence (AI) mechanisms.A retrospective PACS search identified adults who underwent an emergency department contrast-enhanced abdominopelvic CT in 07/2022 (Console Cohort) and 07/2023 (Server Cohort). Coronal and sagittal multiplanar reformatted images (MPR) were created by AI software in the Server cohort. Time to completion of MPR images was compared using 2-sample t-tests for all patients in both cohorts. Two radiologists qualitatively assessed image quality and diagnostic confidence on 5-point Likert scales for 50 consecutive examinations from each cohort. Additionally, they assessed for acute abdominopelvic findings. Continuous variables and qualitative scores were compared with the Mann-Whitney U test. A p < .05 indicated statistical significance.Mean[SD] time to exam completion in PACS was 8.7[11.1] minutes in the Console cohort (n = 728) and 4.6[6.6] minutes in the Server cohort (n = 892), p < .001. 50 examinations in the Console Cohort (28 women 22 men, 51[19] years) and Server cohort (27 women 23 men, 57[19] years) were included for radiologist review. Age, sex, CTDlvol, and DLP were not statistically different between the cohorts (all p > .05). There was no significant difference in image quality or diagnostic confidence for either reader when comparing the Console and Server cohorts (all p > .05).Examinations utilizing AI generated MPRs on a thin-client architecture were completed approximately 50% faster than those utilizing reconstructions generated at the console with no statistical difference in diagnostic confidence or image quality.Results: Retrospectively compare image quality, radiologist diagnostic confidence, and time for images to reach PACS for contrast enhanced abdominopelvic CT examinations created on the scanner console by technologists versus those generated automatically by thin-client artificial intelligence (AI) mechanisms.A retrospective PACS search identified adults who underwent an emergency department contrast-enhanced abdominopelvic CT in 07/2022 (Console Cohort) and 07/2023 (Server Cohort). Coronal and sagittal multiplanar reformatted images (MPR) were created by AI software in the Server cohort. Time to completion of MPR images was compared using 2-sample t-tests for all patients in both cohorts. Two radiologists qualitatively assessed image quality and diagnostic confidence on 5-point Likert scales for 50 consecutive examinations from each cohort. Additionally, they assessed for acute abdominopelvic findings. Continuous variables and qualitative scores were compared with the Mann-Whitney U test. A p < .05 indicated statistical significance.Mean[SD] time to exam completion in PACS was 8.7[11.1] minutes in the Console cohort (n = 728) and 4.6[6.6] minutes in the Server cohort (n = 892), p < .001. 50 examinations in the Console Cohort (28 women 22 men, 51[19] years) and Server cohort (27 women 23 men, 57[19] years) were included for radiologist review. Age, sex, CTDlvol, and DLP were not statistically different between the cohorts (all p > .05). There was no significant difference in image quality or diagnostic confidence for either reader when comparing the Console and Server cohorts (all p > .05).Examinations utilizing AI generated MPRs on a thin-client architecture were completed approximately 50% faster than those utilizing reconstructions generated at the console with no statistical difference in diagnostic confidence or image quality.Conclusion: Retrospectively compare image quality, radiologist diagnostic confidence, and time for images to reach PACS for contrast enhanced abdominopelvic CT examinations created on the scanner console by technologists versus those generated automatically by thin-client artificial intelligence (AI) mechanisms.A retrospective PACS search identified adults who underwent an emergency department contrast-enhanced abdominopelvic CT in 07/2022 (Console Cohort) and 07/2023 (Server Cohort). Coronal and sagittal multiplanar reformatted images (MPR) were created by AI software in the Server cohort. Time to completion of MPR images was compared using 2-sample t-tests for all patients in both cohorts. Two radiologists qualitatively assessed image quality and diagnostic confidence on 5-point Likert scales for 50 consecutive examinations from each cohort. Additionally, they assessed for acute abdominopelvic findings. Continuous variables and qualitative scores were compared with the Mann-Whitney U test. A p < .05 indicated statistical significance.Mean[SD] time to exam completion in PACS was 8.7[11.1] minutes in the Console cohort (n = 728) and 4.6[6.6] minutes in the Server cohort (n = 892), p < .001. 50 examinations in the Console Cohort (28 women 22 men, 51[19] years) and Server cohort (27 women 23 men, 57[19] years) were included for radiologist review. Age, sex, CTDlvol, and DLP were not statistically different between the cohorts (all p > .05). There was no significant difference in image quality or diagnostic confidence for either reader when comparing the Console and Server cohorts (all p > .05).Examinations utilizing AI generated MPRs on a thin-client architecture were completed approximately 50% faster than those utilizing reconstructions generated at the console with no statistical difference in diagnostic confidence or image quality. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) genetic exchange through reassortment has the potential to accelerate viral evolution and has played a critical role in the generation of multiple pandemic strains. For reassortment to occur, distinct viruses must co-infect the same cell. The spatio-temporal dynamics of viral dissemination within an infected host therefore define opportunity for reassortment. Here, we used wild type and synonymously barcoded variant viruses of a pandemic H1N1 strain to examine the within-host viral dynamics that govern reassortment in guinea pigs, ferrets and swine. The first two species are well-established models of human influenza, while swine are a natural host and a frequent conduit for cross-species transmission and reassortment. Our results show reassortment to be pervasive in all three hosts but less frequent in swine than in ferrets and guinea pigs. In ferrets, tissue-specific differences in the opportunity for reassortment are also evident, with more reassortants detected in the nasal tract than the lower respiratory tract. While temporal trends in viral diversity are limited, spatial patterns are clear, with heterogeneity in the viral genotypes detected at distinct anatomical sites revealing extensive compartmentalization of reassortment and replication. Our data indicate that the dynamics of viral replication in mammals allow diversification through reassortment but that the spatial compartmentalization of variants likely shapes their evolution and onward transmission. Virus reassortment drives genetic diversity and evolution and is governed by intra-host dynamics that are less well understood. Here, the authors characterise the within-host dynamics of influenza A virus reassortment in swine, ferrets and guinea pigs, considering their spatial distribution. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of autoantibody generation in anti-factor H (FH) antibody associated atypical hemolytic uremic syndrome (aHUS) is unknown and is perhaps triggered by an infectious or environmental agent. We observed an unusual increase of patients with anti-FH antibody associated aHUS coinciding with the second pandemic wave in New Delhi and suspected that SARS-CoV-2 infection might be a potential trigger. Methods: We screened for SARS-CoV-2 infection using reverse transcriptase polymerase chain reaction (RT-PCR) and serology in 13 consecutive patients with anti-FH antibody associated aHUS during the past year in New Delhi. Results: We report 5 patients, 4–13 years old, who presented with a febrile illness without respiratory symptoms during the second pandemic wave. Of these, 3 patients presented with a relapse 25–85 months following the initial episode of aHUS. SARS-CoV-2 was detected by RT-PCR in 1 patient and by serology in 4 patients (median titer 47.1 cut-off index). Patients had high titers of anti-FH antibodies (median 2,300 AU/ml). Genetic studies, done in 3 of the 5 patients, showed homozygous CFHR1 deletion without other significant genetic abnormalities. Specific management comprised plasma exchanges and oral prednisolone, combined with either cyclophosphamide or mycophenolate mofetil. At median follow-up of 3.3 months, the estimated glomerular filtration rate in 4 patients ranged from 62 to 110 ml/min/1.73 m2; one patient was dialysis-dependent. Conclusion: Increased vigilance is required during the pandemic, especially in patients with anti-FH associated aHUS, who might relapse despite quiescent disease for a prolonged period. [ABSTRACT FROM AUTHOR]

With rapid advancements in the technology, almost all the devices around are becoming smart and contribute to the Internet of Things (IoT) network. When a new IoT device is added to the network, it is important to verify the authenticity of the device before allowing it to communicate with the network. Hence, access control is a crucial security mechanism that allows only the authenticated node to become the part of the network. An access control mechanism also supports confidentiality, by establishing a session key that accomplishes secure communications in open public channels. Recently, blockchain has been implemented in access control protocols to provide a better security mechanism. The foundation of this survey article is laid on IoT, where a detailed description on IoT, its architecture and applications is provided. Further, various security challenges and issues, security attacks possible in IoT and their countermeasures are also provided. We emphasize on the blockchain technology and its evolution in IoT. A detailed description on existing consensus mechanisms and how blockchain can be used to overpower IoT vulnerabilities is highlighted. Moreover, we provide a comprehensive description on access control protocols. The protocols are classified into certificate-based, certificate-less and blockchain-based access control mechanisms for better understanding. We then elaborate on each use case like smart home, smart grid, health care and smart agriculture while describing access control mechanisms. The detailed description not only explains the implementation of the access mechanism, but also gives a wider vision on IoT applications. Next, a rigorous comparative analysis is performed to showcase the efficiency of all protocols in terms of computation and communication costs. Finally, we discuss open research issues and challenges in a blockchain-envisioned IoT network. [ABSTRACT FROM AUTHOR]

Background and objectives: Observing biomarkers that affect alternative pathway dysregulation components may be effective in obtaining a new and more rapid diagnostic portrayal of atypical hemolytic uremic syndrome. We have conducted a systematic review on the aHUS biomarkers: C3, C5a, C5b-9, factor B, complement factor B, H, and I, CH50, AH50, d-dimer, as well as anti-CFH antibodies. Methods: An exhaustive literature search was conducted for aHUS patient population plasma/serum, collected/reported at the onset of diagnosis. A total of 60 studies were included with the data on 837 aHUS subjects, with at least one biomarker reported. Results: The biomarkers C3 [mean (SD): 72.1 (35.0), median: 70.5 vs. reference range: 75–175 mg/dl, n = 752]; CH50 [28.3 (32.1), 24.3 vs. 30–75 U/ml, n = 63]; AH50 [27.6% (30.2%), 10% vs. ≥ 46%, n = 23]; and CFB [13.1 (6.6), 12.4, vs. 15.2–42.3 mg/dl, n = 19] were lower among aHUS subjects as compared with the reference range. The biomarkers including C4 [mean (SD): 20.4 (9.5), median: 20.5 vs. reference range: 14–40 mg/dl, n = 343]; C4d [7.2 (6.5), 4.8 vs. ≤ 9.8 μg/ml, n = 108]; CFH [40.2 (132.3), 24.5 vs. 23.6–43.1 mg/dl, n = 123 subjects]; and CFI [8.05 (5.01), 6.55 mg/dl vs. 4.4–18.1 mg/dl, n = 38] were all observed to be within the reference range among aHUS subjects. The biomarkers C5a [mean (SD): 54.9 (32.9), median: 48.8 vs. reference range: 10.6–26.3 mg/dl, n = 117]; C5b-9 [466.0 (401.4), 317 (186–569.7) vs. ≤ 250 ng/ml, n = 174]; Bb [2.6 (2.1), 1.9 vs. ≤ 1.6 μg/ml, n = 77] and d-dimer [246 (65.05), 246 vs. < 2.2 ng/ml, 2, n = 2 subjects] were higher among patients with aHUS compared with the reference range. Conclusion: If a comprehensive complement profile were built using our data, aHUS would be identified by low levels of C3, CH50, AH50, and CFB along with increased levels of C5a, C5b-9, Bb, anti-CFH autoantibodies, and d-dimer. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Objective: Severe edema in children with nephrotic syndrome is often refractory to conventional diuretics. Tolvaptan has been used satisfactorily for managing edema in patients with heart failure and cirrhosis. The safety and efficacy of combination therapy with oral tolvaptan and intravenous (IV) furosemide was assessed in patients with furosemide refractory edema. Methods: Patients, aged 5–18 y with nephrotic syndrome and severe edema, were screened for eligibility. After excluding hypovolemia, patients received IV furosemide (3–4 mg/kg/d) for 48 h. Those refractory to IV furosemide (weight loss < 3%) received tolvaptan (0.5–1 mg/kg once daily) and IV furosemide for the next 48 h. Parameters were compared between 48 h of furosemide alone and combination therapy. Results: A total of 24 patients (18 boys) with mean age of 8.0 ± 3.0 y were enrolled. Urine volume significantly increased with combination therapy as compared to furosemide therapy (mean difference: 1.2 mL/kg/h; 95% CI: 0.8–1.65 mL/kg/h) (p < 0.001). Compared to therapy with furosemide alone, combination therapy resulted in significant reduction in body weight from 26.9 ± 10.3 kg to 24.8 ± 9.7 kg (p < 0.001). Estimated glomerular filtration rate did not change (p = 0.81) but serum sodium increased from 135.7 ± 3.3 mEq/L to 140.4 ± 4.8 mEq/L (p < 0.001) with combination therapy; 2 patients showed asymptomatic hypernatremia. Conclusion: The combination of oral tolvaptan and IV furosemide is effective in augmenting diuresis and reducing weight in patients with furosemide refractory edema but requires monitoring of electrolytes and volume status. [ABSTRACT FROM AUTHOR]

Guidelines recommend initiating supplemental enteral feeding through a nasogastric (NG) or gastrostomy tube (G-tube) in patients with chronic kidney disease who have inadequate oral intake despite repeated nutritional counseling. While G-tube placement is shown to improve both nutritional status and anthropometric indices of children with CKD in developed regions, information from developing countries is lacking. This retrospective report reviewed the impact of G-tube feeding on nutritional intakes and anthropometric parameters over a 1-y follow-up in 5 children with CKD-5D managed at one tertiary care center in India. Gastrostomy feeding facilitated significant increments in caloric and protein intake and was easy and safe. However, G-tube feeding led to additional expenses, and the changes in growth parameters were variable in the short term. A longer follow-up appears necessary to understand its impact on wasting, growth velocity, and stature. [ABSTRACT FROM AUTHOR]

Tripartite motif (TRIM) E3 ligases target specific substrates, including viral proteins, for proteasomal degradation, and are thus essential regulators of the innate antiviral response. TRIM69 ubiquitinates the non-structural NS3 protein of Dengue virus for its degradation by the host machinery. This antiviral strategy abrogates the immunosuppression mediated by the NS2B–NS3 protease complex. To understand how this host-driven antiviral response against Dengue virus, we sought to define the mode of interaction between human TRIM69 and Dengue NS2B–NS3 and the subsequent polyubiquitination of the protease by the E3 ligase. We show that NS2B–NS3Δpro is sufficient as a substrate for ubiquitination by TRIM69 using ELISA and in vitro assays. Using hydrogen–deuterium exchange mass spectrometry (HDXMS), we mapped the interface of the interaction between TRIM69 and NS2B–NS3Δpro, and propose a rationale for the binding and subsequent ubiquitination process. Furthermore, through sequence analysis, we showed that the regions targeted by TRIM69 on the DENV-2 NS3 protease (NS3Δpro) are well conserved across DENV serotypes and other flaviviruses, including Zika virus, West Nile virus, and Japanese encephalitis virus. Our results show the direct interactions of TRIM69 with viral proteins, provide mechanistic insights at a molecular level, and highlight the functional relevance of TRIM69 interacting with the Dengue viral protein. Collectively, our findings suggest that TRIM69 may act as a pan-antiflaviviral restriction factor. [ABSTRACT FROM AUTHOR]

Background: Information on the course of SARS-CoV-2 infection in children with chronic kidney disease (CKD) is limited. Methods: We retrospectively reviewed the presentation and outcomes of SARS-CoV-2 infection in patients with CKD followed at any of the four pediatric nephrology centers in New Delhi from April 2020 to June 2021. Outcomes, including cardiopulmonary and renal complications, were reported in relation to underlying disease category and illness severity at presentation. Results: Underlying illness in 88 patients included nephrotic syndrome (50%), other CKD stages 1–4 (18.2%), CKD 5D (17%), and CKD 5T (14.8%). Thirty-two of 61 patients with symptomatic COVID-19 and 9/27 asymptomatic patients were admitted for median 10 (interquartile range 7–15) days. Seventeen (19.3%) patients developed moderate or severe COVID-19. Systemic complications, observed in 30 (34.1%), included acute kidney injury (AKI, 34.2%), COVID-19 pneumonia (15.9%), unrelated pulmonary disease (2.3%), and shock (4.5%). Nineteen (21.6%) had severe complications (AKI stage 2–3, encephalopathy, respiratory failure, shock). Eight (11%) of twelve (16.4%) patients with severe AKI required dialysis. Three (3.4%) patients, two with steroid-resistant nephrotic syndrome in relapse and one with CKD 1–4, died due to respiratory failure. Univariate logistic regression indicated that patients presenting with nephrotic syndrome in relapse or moderate to severe COVID-19 were at risk of AKI (respective odds ratio, 95%CI: 3.62, 1.01–12.99; 4.58, 1.06–19.86) and/or severe complications (respective odds ratio, 95%CI: 5.92, 1.99–17.66; 61.2, 6.99–536.01). Conclusions: Children with CKD presenting with moderate-to-severe COVID-19 or in nephrotic syndrome relapse are at risk of severe complications, including severe AKI and mortality. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Summary: PREDNOS 2 was a double blind placebo controlled trial done to investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection—related relapses. It evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. At the beginning of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. The primary outcome was the incidence of first upper respi-ratory tract infection-related relapse. The modified intention-to-treat analysis population comprised 271 children (mean (SD) age, 7.6 (3.5) years; 64.2% male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) in the predniso-lone arm and 58 (44.3%) in the placebo arm (adjusted risk difference, 0.02; 95% CI, 0.14 to 0.10; P =0.70). No evidence was found that the treatment effect differed according to background immuno-suppressive treatment. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40–1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81–1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P=0.09). The authors concluded that, results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK and further work is needed to study the inter-ethnic differences in the study response. [ABSTRACT FROM AUTHOR]

The present paper reports 10 patients (9 families) with Fanconi–Bickel syndrome managed during 2010–2021. Patients presented with polyuria, polydipsia, hepatomegaly, rickets, and stunting at a median of 5 (3, 7.3) mo; one had transient neonatal diabetes. Glucosuria, generalized aminoaciduria, β2-microglobinuria, urinary phosphate wasting, and hypercalciuria were present in all patients; 3 patients had nephrocalcinosis. Other metabolic abnormalities included hypertriglyceridemia (n = 5/6), fasting hypoglycemia (n = 5/8), and postprandial hyperglycemia (n = 3/6). Genetic analysis showed 7 homozygous or compound heterozygous variants in SLC2A2. A pathogenic variant c.952G>A, common to 4 patients (3 families), might be a potential hotspot. At a median follow-up of 43 mo, 4 patients died at a median of 25 mo; short stature persisted in all except one patient who showed catch-up growth with uncooked corn-starch diet. The present findings suggest that the Fanconi–Bickel syndrome has a severe phenotype with an unsatisfactory outcome. A high index of suspicion for diagnosis and efforts for facilitation of dietary therapy are necessary. [ABSTRACT FROM AUTHOR]