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This article presents a case study of a family with a rare immune disorder caused by a mutation in the IL-6R gene. The disorder is characterized by recurrent infections, elevated IgE levels, and eosinophilia. The affected individuals in this study, who were from India, had similar laboratory and immunological profiles. The study also identified a specific mutation in the IL6R gene in the affected individuals. The children in the study were successfully treated with cotrimoxazole prophylaxis. The authors suggest that IL-6R deficiency should be considered in patients with similar symptoms and a history of consanguinity. [Extracted from the article]

This article discusses the familial aggregation of diffuse cutaneous systemic sclerosis (dcSSc), a rare autoimmune connective tissue disease. The study focuses on a family with dcSSc and identifies a variant in the C1r gene, which encodes a proteolytic subunit in the complement system. The presence of this gene variant, along with a susceptible HLA haplotype and specific autoantibodies, may contribute to the development and clinical course of dcSSc. The study highlights the importance of genetic factors in the etiology of SSc and suggests the need for further research to understand the mechanisms involved. [Extracted from the article]

Monogenic causes are increasingly being recognized in patients with lupus, especially in early‐onset disease. We herein report a boy with a novel mutation in the DNase 2 (DNASE2) gene presenting with monogenic lupus. A 6‐year‐old boy with a global developmental delay with microcephaly presented with chronic febrile illness with anemia, rash, polyarthritis, renal involvement, and hepatosplenomegaly. Laboratory investigations revealed positive antinuclear antibody, high anti‐dsDNA antibody titers, hypocomplementemia, hypergammaglobulinemia, nephrotic range proteinuria, and diffuse proliferative glomerulonephritis. Magnetic resonance imaging of brain showed altered signal intensity in subcortical white matter in bilateral fronto‐parieto‐temporal lobes. Targeted next‐generation sequencing revealed a novel pathogenic variant in DNASE2. He was treated with oral prednisolone, mycophenolate mofetil, cyclosporine, and hydroxychloroquine and is doing well on follow up. DNASE2 deficiency has been reported as a rare genetic cause of monogenic lupus. DNASE2 deficiency should be suspected in patients with early‐onset lupus with polyarthritis, erythematous rash, and neurological involvement. [ABSTRACT FROM AUTHOR]

Taking the examples of Hurricane Florence (2018) over the Carolinas and Hurricane Harvey (2017) over the Texas Gulf Coast, the study attempts to understand the performance of slab, single‐layer Urban Canopy Model (UCM), and Building Environment Parameterization (BEP) in simulating hurricane rainfall using the Weather Research and Forecasting (WRF) model. The WRF model simulations showed that for an intense, large‐scale event such as a hurricane, the model quantitative precipitation forecast over the urban domain was sensitive to the model urban physics. The spatial and temporal verification using the modified Kling‐Gupta efficiency and Method for Object based Diagnostic and Evaluation in Time Domain suggests that UCM performance is superior to the BEP scheme. Additionally, using the BEP urban physics scheme over UCM for landfalling hurricane rainfall simulations has helped simulate heavy rainfall hotspots. Plain Language Summary: In the wake of the continuing threat of urban flooding following landfalling hurricanes, understanding the possible interplay between the urban landscape and hurricane rainfall is an emerging research area. Prior studies have shown that the micro‐climate of the urban regions can modify rain over the city centers and periphery. However, most urban rainfall modification studies have considered thunderstorms and local convective storms in developing this understanding. However, an intriguing question is whether the urban land surface has any feedback on rainfall due to large systems such as hurricanes. This question was addressed here using a state‐of‐the‐art weather model considering three different representations of urban surfaces. The analysis showed that the simulated hurricane rainfall corresponding to Florence (2018) and Harvey (2017) is sensitive to the choice of the urban model physics used. The results suggest that the model better simulates the environmental conditions and spatial distribution of rainfall using single‐layer urban physics. Key Points: Quantitative Precipitation Forecasts over urban areas from landfalling hurricanes are sensitive to urban representation in Weather Research and Forecasting (WRF) simulationsThe consideration of urban physics in the WRF model simulation helped improve the urban rainfall simulationsRepresenting urban morphology helped simulated heavy rain hotpots and simpler physics better simulated regional rains [ABSTRACT FROM AUTHOR]

This article discusses a collaborative study conducted in Asia to investigate incomplete Kawasaki disease (iKD), a systemic vasculitis that primarily affects children. The study aimed to clarify the clinical picture of iKD in five Asian regions. The results showed that redness at the bacillus Calmette–Guérin (BCG) inoculation site is a useful diagnostic indicator for iKD in Asian children. Additionally, coronary artery abnormalities (CAAs) were found in 19% of the patients, highlighting the need for improvements in additional treatment for iKD. The study acknowledges its limitations, including a small sample size and the potential impact of the COVID-19 pandemic on KD epidemiology. [Extracted from the article]

Background: Juvenile localized scleroderma (JLS) or morphoea, a rare chronic autoimmune disease predominantly affects skin, subcutaneous tissue and occasionally the adjacent muscle, fascia and bone. We report the largest single‐centre cohort of patients with JLS from India. Methods: Patients who were diagnosed to have JLS were enrolled from the Paediatric Dermatology Clinic and the Paediatric Rheumatology Clinic of a tertiary care referral hospital in India. Collected data included details of the clinical profile, laboratory investigations and management. Results: We analysed 84 patients with Juvenile localized scleroderma. Median age of disease onset was 5 years, and median age at diagnosis was 8 years. Commonest subtype was linear scleroderma (57 patients, 67.7%) followed by plaque morphoea and generalized morphoea. Fourteen patients (16.6%) were noted to have extracutaneous manifestations (ECMs). These included arthritis in eight (33.3%), brain parenchymal abnormalities in four (4.7%) and pulmonary involvement in two (8.3%) patients. Antinuclear antibody (ANA) was positive in eight/25 patients (32%; diffuse and speckled pattern in four patients each). One amongst these also had elevated anti‐dsDNA titres. Positive ANA was found to have no association with ECMs (p 1.000). Patients were treated using methotrexate (61 patients; 72.6%), dexamethasone oral mini‐pulse (OMP; 35 patients; 41.6%), calcipotriol (39 patients; 46.4%), topical corticosteroids (32 patients; 38%) and topical tacrolimus (three patients; 3.7%). Using linear regression analysis, administration of dexamethasone OMP and calcipotriol was found to be a predictor of good treatment response (p 0.034 and 0.019, respectively). Conclusion: Early use of systemic corticosteroids along with methotrexate may be more beneficial than methotrexate therapy alone. [ABSTRACT FROM AUTHOR]

Interferon alpha may be used in patients with I IFN- R1 i defect to control mycobacterium infection. Disseminated Mycobacterium fortuitum infection in a young girl with IFN- R1 defect masquerading as histiocytosis Histiocytic presentation of MSMD has rarely been reported in the literature in patients with both I IL-12R 1 i and I IFN- R1 i defects.[[3]] Environmental nontuberculous mycobacteria are one of the signature organisms associated with MSMD. [Extracted from the article]

This paper discusses the umbrella optimizing technique (UOT), a novel approach to track maximum power point (MPP) of a solar photovoltaic (PV) system under partial shading conditions (PSCs).Since PSCs have a direct impact on the power generated by PV modules, many researchers have developed a variety of maximum power point tracking (MPPT) approaches to address this issue. Perturb and Observe (P&O) is a traditional method for tracking the maximum power of a PV module under PSCs. The fundamental issue with this traditional technique is that the algorithm misleads the step size and chases the wrong direction under PSCs to track MPP. The proposed algorithm finds the maximum power peak among several observed peaks caused by partial shading of a PV module. At each instance, the proposed algorithm checks for local or global peaks and adjusts the duty cycle of the inverse SEPIC DC–DC converter accordingly.In experimental study, UOT shows better performance in terms of tracking efficiency, tracking time, output power and output current.It exhibits a power boost of 3.39–4.14% with 9.09–16.66% faster tracking in different PSCs. A comparison of different optimization techniques illustrates that the UOT has higher tracking performance. [ABSTRACT FROM AUTHOR]

Polyautoimmunity or multiple autoimmune syndrome (MAIS) is increasingly being recognized in pediatric clinical practice, often in conjunction with systemic lupus erythematosus (SLE). Besides multi‐organ autoimmunity, children with SLE are often at a higher risk of developing infections including tuberculosis. The tendency to develop infections and multiple autoimmune diseases in childhood SLE often occurs in the absence of monogenic primary immunodeficiency disease. Conversely, children with inborn errors of immunity, of which selective IgA deficiency (sIgAD) is the most common, may develop recurrent infections and autoimmune disorders including SLE. Herein, we report a child with MAIS (including SLE) and sIgAD who developed drug‐resistant tuberculosis, which was managed successfully with second‐line anti‐tubercular drug therapy. To the best of our knowledge, this combination of rare findings has not been reported previously in the pediatric literature. Although a majority of patients with sIgAD are either asymptomatic or have mild infections/autoimmunity, the index child had a myriad of infectious illnesses and multi‐organ autoimmunity. Our case highlights the prudence of thoroughly evaluating children with SLE for other autoimmune diseases and vice versa. Given the higher probability of inherited disorders, including early complement deficiencies and monogenic interferonopathies, in childhood SLE compared with adult SLE, it may be prudent to perform a basic immunological workup (for example, immunoglobulin levels, 50% hemolytic complement) in such patients. A more extensive immunological and genetic evaluation (including next‐generation sequencing) may also be required in the presence of unusual clinical or laboratory features, a positive family history, or a complicated clinical course. [ABSTRACT FROM AUTHOR]

The present study examines the climatological characteristics and possible triggers of rapid intensification (RI) of tropical cyclones (TCs) during 1990–2019 over the North Indian Ocean (NIO). RI is defined as an increase in maximum sustained surface wind speed of 30 knots (15.4 m⋅s−1) or more in a 24 hr duration. In the NIO basin, the threshold of 24 hr intensity change represents the 93rd percentile using a 3‐min sustained wind, while, it is 95th percentile in the Atlantic basin, where 1‐min sustained wind is used. A total of 46 TCs (~38% of the total TCs) have exhibited RI at an average rate of 1–2 TCs year−1 over the NIO. A significant increase of RI‐TCs is seen from the year 2000 onwards over the region. The maximum RI‐TCs occurrence is found in the post‐monsoon season. The majority of TCs (~48%) undergo the RI phase within a 12–24 hr time during the depression stage. About ~35% (26%) of the TCs are retained in the RI phase for the duration of at least 24 hr (36 hr). Most of the RI‐TCs move northwestward (38%) and westward (31%) direction 6 hr before the RI onset with slow/normal translation speeds. During the RI phase, ~72% of TCs travels a distance of ~150–450 km. The TC inner‐core region receives heavy rainfall, and a ~ 3 mm⋅hr−1 increment is noticed 12 hr before the RI to the RI onset. Most of the RI‐TCs made landfall over eastern states of India showing the vulnerability of the regions. Composite analysis demonstrated that higher precipitable water (~55 mm), surface flux (500 W⋅m−2), cyclone heat potential (50–60 kJ⋅cm−2) in the moderate shear (6–8 m⋅s−1) environment favours the RI process. This study highlights the significance of RI‐TCs and triggering conditions for the RI onset over the NIO region. [ABSTRACT FROM AUTHOR]

Most patients die because of asphyxiation caused by obstruction of larynx.2 However, NPPE because of laryngeal edema has not been reported in patients with HAE. Negative pressure pulmonary edema has several causes and mortality may range from 11% to 40%.9 Pathophysiology of NPPE remains enigmatic. Negative pressure pulmonary edema (NPPE) is an uncommon, however, potentially fatal complication due to rapid-onset upper respiratory tract obstruction.1 NPPE is usually observed in critical care and perioperative settings. [Extracted from the article]

This study investigates the impact of direct versus indirect initialization of soil moisture (SM) and soil temperature (ST) on monsoon depressions (MDs) and heavy rainfall simulations over India. SM/ST products obtained from high‐resolution, land data assimilation system (LDAS) are used in the direct initialization of land surface conditions in the ARW modeling system. In the indirect method, the initial SM is sequentially adjusted through the flux‐adjusting surface data assimilation system (FASDAS). These two approaches are compared with a control experiment (CNTL) involving climatological SM/ST conditions for eight MDs at 4‐km horizontal resolution. The surface fields simulated by the LDAS run showed the highest agreement, followed by FASDAS for relatively dry June cases, but the error is high (~15–30%) for the relatively wet August cases. The moisture budget indicates that moisture convergence and local influence contributed more to rainfall. The surface‐rainfall feedback analysis reveals that surface conditions and evaporation have a dominant impact on the rainfall simulation and these couplings are notable in LDAS runs. The contiguous rain area (CRA) method indicates better performance of LDAS for very heavy rainfall distribution, and the location (ETS > 0.2), compared to FASDAS and CNTL. The pattern error contributes the maximum to the total rainfall error, and the displacement error is more in August cases' rainfall than that in June cases. Overall analyses indicated that the role of land conditions is significantly high in the drier month (June) than a wet month (August), and direct initialization of SM/ST fields yielded improved MD and heavy rain simulations. Key Points: Direct initialization of SM/ST is more effective than the sequential/indirect initialization in the ARW modelLand conditions and evaporation control postlandfall rainfall, and land surface and rainfall coupling are sensitive to the former land stateMD movement and postlandfall rainfall show significant improvement when the SM/ST conditions are initialized from LDAS products [ABSTRACT FROM AUTHOR]

Using Tropical Rainfall Measuring Mission rain estimates the relationship between rainfall and intensity changes in tropical cyclones (TCs) over the North Indian Ocean (NIO) based on 71 TCs during 1997–2017 is investigated. The axisymmetric analyses revealed that climatologically the Bay of Bengal (BoB) TCs produce extremely heavy rainfall (~9–10 mm⋅hr−1) and Arabian Sea TCs produce very heavy rainfall (~7–8 mm⋅hr−1) in the storm inner core region (0–100 km). The inner‐core region receives three times higher rainfall than the outer region (100–300 km). The left‐forward sector experiences the maximum rainfall for any TC intensity over the NIO basin. A significant increase (decrease) in the rain rate is seen during normal to rapid intensification (weakening) phase. A notable decrease in rainfall of ~4.3 mm⋅hr−1 is observed for the rapidly weakening TCs. Slow‐moving TCs are generally stronger and produce heavy rainfall (2–4 mm⋅hr−1) up to ~300 km storm radius. As the translation speed increases, rainfall gradually shifts from rear to the forward sector of the TC. The asymmetry (wavenumber‐1) in TC rainfall structures revealed that rainfall maximum is located in the left‐forward sector for almost all intensity stages. The amplitude of wave number‐1 asymmetry in TC rainfall shows cyclonic shift as the TC intensity increases and is particularly prevalent in the BoB region. These analyses would be helpful as a baseline for evaluating the performance of numerical models and to identify the vulnerable areas for TC heavy rainfall. [ABSTRACT FROM AUTHOR]

The Bay of Bengal (BoB) exhibits notable seasonal variations in tropical cyclone heat potential (TCHP), barrier layer thickness (BLT) and sea‐surface temperature (SST). These parameters also undergo profound changes in the presence of tropical cyclones (TCs). The composite structures of these ocean parameters as a function of the season of TC formation, intensity, and translation speed are unknown and are developed in the present study. Composite structures are examined based on 1,222 instantaneous samples from 83 TCs during 2003–2016 using INCOIS‐GODAS analyses. A BLT of 10–30 m and TCHP of 40–80 kJ/cm2 favours TC intensification in the central BoB. The multivariate regression of BLT and TCHP appears to be better for TC intensity up to 64 knots and is highly underestimated for the stronger TCs (>64 knots). The TC right‐rear sector experiences significant changes in TCHP anomaly (TCHPA) as the intensity increases. The TCHPA ranges ∼10–15, ∼20–25 and ∼25–30 kJ/cm2 when a TC is at Cyclone Storm (CS), Severe Cyclonic Storm (SCS) and Very SCS (VSCS) stages respectively. The maximum TCHPA is generally aligned along the TC track during the post‐monsoon season. Slow‐moving TCs produce maximum TCHPA cooling of ∼20 kJ/cm2 within 250 km storm radius in the rear sector, while it is less and away from the storm centre for normal and fast‐movers. The seasonal changes showed opposite relations between BLT and TCHP from pre‐ to post‐monsoon seasons during the TC intensification. TC‐induced SST cooling is maximum (∼0.5–1.2 °C) in the inner core for the strong (VSCS and above) and slow‐moving TCs. The cooling decreases with an increase in the translation speed and is more pronounced in the pre‐monsoon season. This study provides a baseline to verify and understand the limitations of the models, and also develop a climatological perspective of BoB TCs. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is emerging as the most common medium vessel vasculitis in children. Recurrence of KD (0.8%‐3.0%) is unusual and not commonly reported. Objective: To study the clinico‐laboratory profile of children with recurrent KD. Methods: Case records of 714 children with KD, registered from January 1994 to April 2018 in the Pediatric Rheumatology Clinic at the Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research Chandigarh, were reviewed and data were analyzed for children having had recurrent KD. Results: Seven (0.98%) children (five boys; two girls) had recurrent KD in our cohort of 714 patients. Mean age at diagnosis was 4.3 years (range, 2‐9 years). Six (85.7%) had recurrence of KD within 1.5 years. Incomplete KD was more common during recurrence (71.4%) as compared to the first episode (33.3%). Five children with recurrent KD developed desquamation during the first week of illness. Laboratory investigations did not show any significant difference during the two episodes of KD. Six of the seven children in the first episode received treatment with intravenous immunoglobulin (IVIG). Five of the seven children received IVIG during recurrence. One child had transient left main coronary artery ectasia during the first episode of KD as well as during recurrence and it normalized after treatment on both occasions. Conclusion: Recurrences in KD are unusual. Over a period of 24 years the recurrence rate in our cohort of children with KD was 0.98%. Further, children with recurrences tended to have milder and incomplete form of the disease. [ABSTRACT FROM AUTHOR]

Abstract: Kawasaki disease (KD) is a medium vessel vasculitis with predilection for coronary arteries. Due to lack of a reliable confirmatory laboratory test, the diagnosis of KD is based on a constellation of clinical findings that appear in a typical temporal sequence. These diagnostic criteria have been modified from time to time and the most recent guidelines have been proposed by the American Heart Association (AHA) in 2017. However, several children may have incomplete or atypical forms of KD and the diagnosis can often be difficult, especially in infants and young children. In this review, we have detailed the steps involved in arriving at a diagnosis of KD and also highlight the important role of echocardiography in diagnosis and management of children with KD. [ABSTRACT FROM AUTHOR]

We report on four children with localized scleroderma (morphea) and thrombocytopenia. All four had the en coup de sabre subtype of morphea and had varying degrees of thrombocytopenia (8 × 109/L to 120 × 109/L). None of them had major bleeding manifestations, and thrombocytopenia resolved with treatment of morphea. (One patient was also given an injection of anti-D immunoglobulin.) We propose that thrombocytopenia associated with localized scleroderma is usually benign and requires no specific therapy. [ABSTRACT FROM AUTHOR]

Abstract: In general, the activation of extracellular recognition kinase (ERK) cascade is implicated in exerting tumorigenic effects. Conversely, recent studies suggest that ERK activation may also have role in DNA-damage induced apoptosis [Wang, X., Martindale, J.L. and Holbrook, N.J. (2000) Requirement for ERK activation in cisplatin-induced apoptosis. J. Biol. Chem. 275, 39435–39443; Schweyer S., Soruri A., Meschter O., Heintze A., Zschunke F., Miosge N., Thelen P., Schlott T., Radzun H.J. and Fayyazi, A. (2004) Cisplatin-induced apoptosis in human malignant testicular germ cell lines depends on MEK/ERK activation. Br. J. Cancer 91, 589–598]. Here we observed an essential requirement of ERK activation in carboplatin (Carb) induced apoptosis in SiHa and CaSki cells. Under similar treatment conditions p53 was also involved in Carb induced apoptosis in these cells. Therefore, we investigated the relation between p53 and ERK in Carb induced apoptosis in these cells. Abrogation of p53 transactivation activity by pifithrinα or dominant-negative mutant of p53 resulted in decrease in activation of ERK in Carb treated cells. The present study for the first time proposes that p53 may act as one of the upstream regulators of ERK activation for the induction of apoptosis in Carb treated cervical cancer cells. [Copyright &y& Elsevier]