Current Treatments for Generalized Pustular Psoriasis: A Narrative Summary of a Systematic Literature Search.

Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients' quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980-September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.

Generalized pustular psoriasis (GPP) is a rare, chronic skin condition characterized by painful, sterile pustules that can occur all over the body. These pustules may also be accompanied by systemic inflammation, which can lead to serious health complications. GPP significantly impacts patients' quality of life and can even be life-threatening. Because the disease is so rare, treatment guidelines have typically been based on those for plaque psoriasis. However, these guidelines do not specifically address the unique needs of GPP. In this review, we analysed the published literature on GPP management, focussing on treatment efficacy, safety and quality of life outcomes. We searched the literature databases Embase and MEDLINE for articles published between 1980 and September 2023. In total, we identified 118 publications on this topic, covering a wide range of therapies; only one of these therapies, spesolimab, reported results from placebo-controlled randomized trials. Based on these trials, spesolimab is now approved for GPP treatment in the USA, Japan, China, the EU and several other countries. Some other therapies are approved exclusively in Japan and Taiwan based on small, open-label studies in the absence of higher-quality data. To date, comparing treatments has been challenging because of different clinical outcomes used to measure effectiveness. However, well-defined endpoints specific to GPP have recently been developed and used in trials. In conclusion, our review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the best treatment strategy.

A practical approach for extracting the photosystem II (PSII) contribution to near-infrared solar-induced chlorophyll fluorescence.

Recent studies have indicated a good potential for using solar-induced chlorophyll fluorescence (SIF) to estimate photosynthetic CO2 assimilation. SIF can be emitted by both Photosystem I (PSI) and Photosystem II (PSII), but it is the SIF signals from PSII which are related to photosynthetic carbon fixation. However, since top-of-canopy SIF observations (SIFTOC) always contain contributions from both photosystems, to mechanistically estimate gross primary productivity (GPP) from SIF, it is essential to extract PSII SIF from SIFTOC. Based on the differences in the relative contribution of PSII across different wavelengths, we propose a practical approach for extracting PSII contribution to SIFTOC at the near-infrared (NIR) band (fPSII_760) using measurements of SIFTOC in the red and NIR spectral regions. A leaf-scale concurrent instrument was developed to assess the response of fPSII_760 under varying environments. For winter-wheat leaves, as light intensity increased from 0 to 400 µmol m-2 s-1, fPSII_760 rose from 0.6 to 0.8; with further increase in light intensity to 1800 µmol m-2 s-1, fPSII_760 consistently decreased to 0.65. There was a slight decreasing trend in fPSII_760 with rising temperatures, with values dropping from 0.65 at 15 °C to 0.61 at 40 °C. We found that variations in fPSII_760 are due to changes in the fluorescence yield of PSII, with the two having a positively proportional relationship. We also estimated canopy-scale fPSII_760 for a winter-wheat study site: fPSII_760 varied from 0.61 to 0.83, with a mean value of 0.78 during the peak growing season. A comparison with eddy covariance-derived GPP reveals that GPP estimated with dynamic fPSII_760 was more accurate than that calculated using fixed fPSII_760, with R2 increasing from 0.6 to 0.84. This study contributes to a deeper understanding of the link between SIF and photosynthetic CO2 assimilation, paving the way for more effective use of SIF to estimate GPP.

Effective Management of Life-Threatening Generalized Pustular Psoriasis Flare With Spesolimab.

Generalized pustular psoriasis (GPP) presents as a severe variant of psoriasis featuring painful, sterile pustules on red skin and can lead to life-threatening complications if left untreated. The disease course is typically unpredictable, with periods of improvement, followed by relapses over extended periods. Managing GPP flares is challenging due to their potential to endanger the patient's life, underscoring the need for treatments that are both fast-acting and highly effective in the case of severe and systematically ill GPP patients. We present a case of a 48-year-old man with an extensive and severe GPP flare (GPP Physician Global Assessment score = 4), experiencing an extensive pustular rash on an erythematous base, intense skin exfoliation, and inflammation as well as systemic symptoms such as fever, hypotension, and general weakness. During the disease course, he developed comorbidities such as depression occurrence and an episode of an acute pulmonary embolism. Initial treatment attempts with acitretin and anakinra were not proved successful. Due to IL-36's significant role in GPP pathophysiology, the patient received treatment involving an IL-36 receptor antagonist (two infusions of 900 mg spesolimab administered one week apart), alongside continued acitretin therapy. This approach led to swift improvement, resolving pustules and skin inflammation and resulting in the patient's gradual recovery. This case highlights spesolimab's potential as a targeted therapy for severe GPP flares resistant to conventional treatments. However, further research is needed to establish its long-term safety and efficacy in managing GPP and related IL-36-mediated diseases.

Soil moisture alters the responses of alpine ecosystem productivity to environmental factors, especially VPD, on the Qinghai-Tibetan Plateau.

Water availability, which can be represented by soil water content (SWC), plays a crucial role in plant growth and productivity across the cold and arid Qinghai-Tibetan Plateau. However, the indirect effects of SWC are less well understood, and a more comprehensive understanding of its regulating effects may enhance the recognition of its importance, as this factor is pivotal for accurately predicting the future response of alpine ecosystems to climate change. In this study, in situ eddy covariance observation data from typical alpine ecosystems and satellite data covering the Qinghai-Tibetan region were used to comprehensively reveal the effects of SWC on ecosystem productivity. The results indicated that SWC played an important role in regulating the responses of gross primary productivity (GPP) to other environmental factors over both time and space, especially in terms of the responses of GPP to vapor pressure deficit (VPD). The regulating effect can be summarized as follows: there was a specific SWC value (SWC = 0.24 m3 m-3 on the Qinghai-Tibetan Plateau) above which SWC was no longer the primary limiting factor. The responses of GPP to certain environmental factors shifted from negative to positive when the SWC increased above this value. The responses of GPP to VPD exhibited the highest sensitivity to the regulating effects of SWC, with a general response pattern found across different temporal and spatial scales. The findings revealed divergent responses of GPP to environmental factors under different SWC conditions and between arid and humid regions, emphasizing the importance of soil water conditions. These findings suggest that water conditions should be given primary consideration in global change studies.

Spesolimab in the Management of Generalized Pustular Psoriasis With Concurrent Bullous Pemphigoid and Psoriasis.

Autoimmune diseases often co-occur due to shared immunological mechanisms, necessitating strategic treatment approaches to manage overlapping conditions without exacerbating each other. A 75-year-old male with a history of psoriasis vulgaris and bullous pemphigoid (BP) developed new-onset pustular psoriasis under systemic corticosteroid therapy, which is known to potentially worsen psoriasis into its pustular form. Histological examination confirmed the diagnosis, showing features typical of pustular psoriasis. The patient was successfully treated with spesolimab, an anti-IL-36 neutralizing antibody, achieving complete remission without aggravating the BP. This case highlights the necessity of cautious treatment selection in patients with multiple autoimmune disorders and underscores the potential role of IL-36 in exacerbating inflammatory responses in BP. Further research into the interaction between IL-36 and BP may provide deeper insights into managing such complex clinical scenarios.

Spesolimab: A Review of the First IL-36 Blocker Approved for Generalized Pustular Psoriasis.

OBJECTIVE: This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP). DATA SOURCES: A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023. STUDY SELECTION AND DATA EXTRACTION: Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included. DATA SYNTHESIS: In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 (P = 0.0005), 0.35 (P = 0.0057), and 0.47 (P = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents. CONCLUSION: Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents.

A Comprehensive Overview of Network Slicing for Improving the Energy Efficiency of Fifth-Generation Networks.

The introduction of fifth-generation (5G) mobile networks leads to an increase in energy consumption and higher operational costs for mobile network operators (MNOs). Consequently, the optimization of 5G networks' energy efficiency is crucial, both in terms of reducing MNO costs and in terms of the negative environmental impact. However, many aspects of the 5G mobile network technology itself have been standardized, including the 5G network slicing concept. This enables the creation of multiple independent logical 5G networks within the same physical infrastructure. Since the only necessary resources in 5G networks need to be used for the realization of a specific 5G network slice, the question of whether the implementation of 5G network slicing can contribute to the improvement of 5G and future sixth-generation networks' energy efficiency arises. To tackle this question, this review paper analyzes 5G network slicing and the energy demand of different network slicing use cases and mobile virtual network operator realizations based on network slicing. The paper also overviews standardized key performance indicators for the assessment of 5G network slices' energy efficiency and discusses energy efficiency in 5G network slicing lifecycle management. In particular, to show how efficient network slicing can optimize the energy consumption of 5G networks, versatile 5G network slicing use case scenarios, approaches, and resource allocation concepts in the space, time, and frequency domains have been discussed, including artificial intelligence-based implementations of network slicing. The results of the comprehensive discussion indicate that the different implementations and approaches to network slicing pave the way for possible further reductions in 5G MNO energy costs and carbon dioxide emissions in the future.

The Psoriasis Treatment Pipeline: An Overview and Update.

Significant research advances in our understanding of psoriatic disease have led to the development of several highly selective, effective, and safe topical and systemic treatments. These treatments have led to unprecedented levels of disease clearance and control for most patients with psoriasis with cutaneous disease. However, there remains a need for improved treatments for those patients with recalcitrant disease, psoriatic arthritis, or nonplaque disease variants. Recently approved therapies and investigational products in ongoing clinical development programs that target IL-17A/F, IL-23, TYK2, PDE4, AhR or IL-36 cytokine signaling are improving the clinician's ability to care for a broader range of patients affected by psoriasis.

CMIP6 ESMs overestimate greening and the photosynthesis trends in Dryland East Asia.

The Dryland East Asia (DEA) is one of the largest inland arid regions, and vegetation is very sensitive to climate change. The complex environment in DEA with defects of modeling construction make it difficult to simulate and predict changes in vegetation structure and productivity. Here, we use the emergent constraint (EC) method to constrain the future interannual leaf area index (LAI) and gross primary productivity (GPP) trends in DEA, under four scenarios of the latest Sixth Coupled Model Intercomparison Project (CMIP6) model ensemble. LAI and GPP increase in all scenarios in the near term (2015-2050), with continued growth in SSP370 and SSP585 and stasis in SSP126 and SSP245 in the far term (2051-2100). However, after building effective EC relationships, the constrained increasing trends of LAI (GPP) are reduced by 43.5 %-53.9 % (30.5 %-50.0 %) compared with the uncertainties of the original ensemble, which are reduced by 10.0 %-45.7 % (4.6 %-34.3 %). We also extend the EC in moving windows and grid cells, further strengthening the robustness of the constraints, especially by illustrating spatial sources of these emergent relationships. Overestimations of LAI and GPP trends suggest that current CMIP6 models may be insufficient to capture the complex relationships between climate change and vegetation dynamics in DEA; however, these models can be adjusted based on established emergent relationships.

Impact of aerosol concentration changes on carbon sequestration potential of rice in a temperate monsoon climate zone during the COVID-19: a case study on the Sanjiang Plain, China.

The emission reduction of atmospheric pollutants during the COVID-19 caused the change in aerosol concentration. However, there is a lack of research on the impact of changes in aerosol concentration on carbon sequestration potential. To reveal the impact mechanism of aerosols on rice carbon sequestration, the spatial differentiation characteristics of aerosol optical depth (AOD), gross primary productivity (GPP), net primary productivity (NPP), leaf area index (LAI), fraction of absorbed photosynthetically active radiation (FPAR), and meteorological factors were compared in the Sanjiang Plain. Pearson correlation analysis and geographic detector were used to analyze the main driving factors affecting the spatial heterogeneity of GPP and NPP. The study showed that the spatial distribution pattern of AOD in the rice-growing area during the epidemic was gradually decreasing from northeast to southwest with an overall decrease of 29.76%. Under the synergistic effect of multiple driving factors, both GPP and NPP increased by more than 5.0%, and the carbon sequestration capacity was improved. LAI and FPAR were the main driving factors for the spatial differentiation of rice GPP and NPP during the epidemic, followed by potential evapotranspiration and AOD. All interaction detection results showed a double-factor enhancement, which indicated that the effects of atmospheric environmental changes on rice primary productivity were the synergistic effect result of multiple factors, and AOD was the key factor that indirectly affected rice primary productivity. The synergistic effects between aerosol-radiation-meteorological factor-rice primary productivity in a typical temperate monsoon climate zone suitable for rice growth were studied, and the effects of changes in aerosol concentration on carbon sequestration potential were analyzed. The study can provide important references for the assessment of carbon sequestration potential in this climate zone.

Generalized pustular psoriasis in a toddler with IL36RN mutation: a case report.

Generalized Pustular Psoriasis (GPP) is a dermatological autoinflammatory disease that rarely occurs in children and is associated with complex genetic factors. GPP pathogenesis has been associated with mutations in IL36RN gene, which encodes an interleukin-36 receptor antagonist. GPP usually occurs without a history of psoriasis in the patients or their family members. This case report describes the clinical course of a 3-year-old toddler with GPP. The diagnosis of GPP was confirmed through a comprehensive series of examinations, and genetic testing revealed an IL36RN mutation, providing further insight into the genetic basis of the condition. This case highlights the importance of a genetic perspective for diagnosing GPP, particularly in children.

Successful treatment of generalized pustular psoriasis with guselkumab.

The purpose of the article: Generalized pustular psoriasis (GPP) is a rare auto-inflammatory disease. Patients with GPP may develop life-threatening complications, including sepsis, acute renal failure, neutrophilic cholangitis, high-output congestive heart failure, acute respiratory distress syndrome and death. The therapy of GPP is very limited and the course of the disease is unpredictable.Materials and methods: We report a 60-year-old woman presenting with widespread and confluent erythematous-desquamative plaques with numerous small pustules covering almost 70% of the body surface area. Over the past years patient had undergone different types of conservative treatment regimens including topical therapy, acitretin, cyclosporin, methotrexate and long-term treatment with systemic corticosteroids. Considering the patient's overall clinical condition, we proceed to initiate the biologic therapy with guselkumab.Results: Guselkumab (anti-IL-23) in the standard dose of 100 mg was administered subcutaneously at weeks 0, 4 and followed by a maintenance dose every 8 weeks. The remission of GPP was observed already after 12 weeks of treatment. The maintenance treatment in the period of 18 months shows stable clinical response.Conclusions: Our results support the evidence that guselkumab could provide an effective therapeutic approach in the treatment of GPP.

Therapeutic Potential of Spesolimab-Sbzo in the Management of Generalized Pustular Psoriasis Flares in Adults: Evidence to Date.

Generalized pustular psoriasis (GPP) is a rare, chronic, and severe skin disorder characterized by the eruption of non-infectious pustules on an erythematous background often associated with systemic symptoms. It may appear in association with plaque psoriasis or occur in previously healthy individuals. It differs from psoriasis vulgaris in clinical presentation, immunopathogenesis, histology, and therapeutic strategies. Overexpression of interleukin 36 (IL-36) or a loss-of-function mutation of IL-36 receptor antagonist (IL-36RA) are thought to play a pivotal role in the pathogenesis of this disease. There are currently no globally approved guidelines for the treatment of GPP, and the therapies used so far, with variable results, have given unsatisfactory results. Spesolimab, a selective humanized antibody against the IL-36 receptor that blocks its activation, is the first biologic drug approved in Europe in December 2022 for the treatment of GPP flares. It represents a promising therapy, demonstrating efficacy in reducing disease severity and improving patient outcomes. In our review, we have analyzed the latest advancements and findings regarding the efficacy and safety of spesolimab in the context of GPP management.

Comparative assessment of leaf photosynthetic capacity datasets for estimating terrestrial gross primary productivity.

The maximum Rubisco carboxylation rate normalized to 25 °C (Vcmax25) is a key parameter in terrestrial biosphere models for simulating carbon cycling. Recently, global distributions of Vcmax25 have been derived through various methods and different data, including field measurements, ecological optimality theory (EOT), leaf chlorophyll content (LCC), and solar-induced chlorophyll fluorescence (SIF). However, direct validation poses challenges due to high uncertainty arising from limited ground-based observations. This study conducted an indirect evaluation of four Vcmax25 datasets by assessing the accuracy of gross primary productivity (GPP) simulated using the Biosphere-atmosphere Exchange Process Simulator (BEPS) at both site and global scales. Results indicate that, compared to utilizing Vcmax25 fixed by plant functional types (PFT) derived from field measurements, incorporating Vcmax25 derived from SIF and LCC (SIF + LCC), or solely LCC, into BEPS significantly reduces simulated errors in the annual total GPP, with a 23.2 %-25.1 % decrease in the average absolute bias across 196 FLUXNET2015 sites. Daily GPP for evergreen needleleaf forests, deciduous broadleaf forests, shrublands, grasslands, and croplands shows a 7.8 %-27.6 % decrease in absolute bias, primarily attributed to reduced simulation errors during off-peak seasons of vegetation growth. Conversely, the annual total GPP error simulated using EOT-derived Vcmax25 increases slightly (2.2 %) compared to that simulated using PFT-fixed Vcmax25. This is primarily due to a significant overestimation in evergreen broadleaf forests and underestimation in croplands, despite slight increased accuracy for other PFTs. The global annual GPP simulated using Vcmax25 with seasonal variations (i.e., LCC Vcmax25 and SIF + LCC Vcmax25) yields a 4.3 %-7.3 % decrease compared to that simulated using PFT-fixed Vcmax25. Compared to FLUXCOM and GOSIF GPP products, the GPP simulated based on SIF + LCC Vcmax25 and LCC Vcmax25 demonstrates better consistency (R2 = 0.91-0.93, RMSE = 314.2-376.6 g C m-2 yr-1). This study underscores the importance of accurately characterizing the spatiotemporal variations in Vcmax25 for the accurate simulation of global vegetation productivity.

Exploring Interference Issues in the Case of n25 Band Implementation for 5G/LTE Direct-to-Device NTN Services.

This paper delves into an interference analysis, focusing on the forthcoming Starlink Generation 2 satellites, stated to operate within the 1990-1995 MHz frequency band. The aim is to assess the potential interference from this Starlink system to the satellite receivers of mobile satellite systems (MSSs), which are set to function within the 1980-2010 MHz range, and satellite receivers of the NTN systems, which are planned to operate in the n256 bands, defined by the 3GPP specifications. Through simulation-based evaluations, both single-entry and aggregate interference levels from Starlink to MSSs and NTN systems are comprehensively explored. To estimate the interference impact, several protection criteria were used. The study is in line with the Recommendations of International Telecommunication Union (ITU-R) and common approaches that are used when performing compatibility studies between satellite systems. The findings of this study demonstrate the feasibility of utilizing the n25 band for NTN direct-to-device services.

A novel hybrid modelling framework for GPP estimation: Integrating a multispectral surface reflectance based Vcmax25 simulator into the process-based model.

Terrestrial gross primary productivity (GPP) is the key element in the carbon cycle process. Accurate GPP estimation hinges on the maximum carboxylation rate (Vcmax,025). The high uncertainty in deriving ecosystem-level Vcmax,025 has long hampered efforts toward the performance of the GPP model. Recently studies suggest the strong relationship between spectral reflectance and Vcmax,025. We proposed the multispectral surface reflectance-driven Vcmax,025 simulator using the fully connected deep neural network and built the hybrid modelling framework for GPP estimation by integrating the data-driven Vcmax,025 simulator in the process-based model. The performance of hybrid GPP model was evaluated at 95 flux sites. The result shows that the multispectral surface reflectance-driven Vcmax,025 simulator acquires the satisfactory estimation, with correlation coefficient (R), root mean square error (RMSE) and median absolute percentage error (MdAPE) ranging from 0.34 to 0.80, 14 to 43 µmol m-2 s-1 and 21 % to 66 % across different land cover types, respectively. The hybrid framework generates good GPP estimates with R, RMSE and MdAPE varying from 0.76 to 0.89, 1.79 to 6.16 µmol m-2 s-1 and 27 % to 90 %, respectively. Compared with EVI-driven method, the multispectral surface reflectance significantly improves the Vcmax,025 and GPP estimates, with MdAPE declining by 0.6 %-18 % and 1 % to 21 %, respectively. The Shapley value analysis reveals that red (620-670 nm), near-infrared (841-876 nm) and shortwave infrared (1628-1652 nm and 2105-2155 nm) are the key bands for Vcmax,025 estimation. This study highlights the potential of multispectral surface reflectance for quantifying ecosystem-level Vcmax,025. The new hybrid framework fully extracts the information of all available spectral bands using deep learning to reduce parameter uncertainty while maintains the description of photosynthetic process to ensure its physical reasonability. It can serve as a powerful tool for accurate global GPP estimation.

Clinical advances in biological therapy for generalized pustular psoriasis: a review.

INTRODUCTION: In 2022, U.S. Food and Drug Administration (FDA) approved the first biologics, intravenous spesolimab, for acute flare of generalized pustular psoriasis (GPP). The drug works by blocking IL-36 signaling, the key pathway of GPP. Among the known mutations causing GPP, IL36RN mutations are most common, and the presence of IL36RN mutations had been found to affect the clinical manifestations and treatment response of GPP. AREAS COVERED: Literature search was conducted in PubMed, Embase and ClinicalTrials.gov for relevant studies discussing biologic treatment for GPP with special emphasis on larger studies, pediatric group, pregnant women, and the influence of IL36RN mutation on the effectiveness of biologics. EXPERT OPINION: The approval of spesolimab for GPP flare treatment marks a new era. However, whether spesolimab will be placed as the treatment of choice remains unknown, considering its higher cost, lack of direct comparison with existing biologics, and uncertain effects on co-existing plaque-type psoriasis. However, the demonstration of numerically better efficacy for patients carrying pathogenic IL36RN mutations suggests the role of pharmacogenetics in the choices of GPP treatment. Future randomized studies are warranted to investigate the effectiveness and safety of biologics for GPP in pediatric and pregnant groups.

Carbon cycle responses to climate change across China's terrestrial ecosystem: Sensitivity and driving process.

Investigations into the carbon cycle and how it responds to climate change at the national scale are important for a comprehensive understanding of terrestrial carbon cycle and global change issues. Contributions of carbon fluxes to the terrestrial sink and the effects on climate change are still not fully understood. In this study, we aimed to explore the relationship between ecosystem production (GPP/SIF/NDVI) and net ecosystem carbon exchange (NEE) and to investigate the sensitivity of carbon fluxes to climate change at different spatio-temporal scales. Furthermore, we sought to delve into the carbon cycle processes driven by climate stress in China since the beginning of the 21st century. To achieve these objectives, we employed correlation and sensitivity analysis techniques, utilizing a wide range of data sources including ground-based observations, remote sensing observations, atmospheric inversions, machine learning, and model simulations. Our findings indicate that NEE in most arid regions of China is primarily driven by ecosystem production. Climate variations have a greater influence on ecosystem production than respiration. Warming has negatively impacted ecosystem production in Northeast China, as well as in subtropical and tropical regions. Conversely, increased precipitation has strengthened the terrestrial carbon sink, particularly in the northern cool and dry areas. We also found that ecosystem respiration exhibits heightened sensitivity to warming in southern China. Moreover, our analysis revealed that the control of terrestrial carbon cycle by ecosystem production gradually weakens from cold/arid areas to warm/humid areas. We identified distinct temperature thresholds (ranging from 10.5 to 13.7 °C) and precipitation thresholds (approximately 1400 mm yr-1) for the transition from production-dominated to respiration-dominated processes. Our study provides valuable insights into the complex relationship between climate change and carbon cycle in China.

Cutaneous findings and treatments in deficiency of interleukin-36 receptor antagonist (DITRA): A review of the literature.

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.