CamTrapAsia: A dataset of tropical forest vertebrate communities from 239 camera trapping studies.

Information on tropical Asian vertebrates has traditionally been sparse, particularly when it comes to cryptic species inhabiting the dense forests of the region. Vertebrate populations are declining globally due to land-use change and hunting, the latter frequently referred as "defaunation." This is especially true in tropical Asia where there is extensive land-use change and high human densities. Robust monitoring requires that large volumes of vertebrate population data be made available for use by the scientific and applied communities. Camera traps have emerged as an effective, non-invasive, widespread, and common approach to surveying vertebrates in their natural habitats. However, camera-derived datasets remain scattered across a wide array of sources, including published scientific literature, gray literature, and unpublished works, making it challenging for researchers to harness the full potential of cameras for ecology, conservation, and management. In response, we collated and standardized observations from 239 camera trap studies conducted in tropical Asia. There were 278,260 independent records of 371 distinct species, comprising 232 mammals, 132 birds, and seven reptiles. The total trapping effort accumulated in this data paper consisted of 876,606 trap nights, distributed among Indonesia, Singapore, Malaysia, Bhutan, Thailand, Myanmar, Cambodia, Laos, Vietnam, Nepal, and far eastern India. The relatively standardized deployment methods in the region provide a consistent, reliable, and rich count data set relative to other large-scale pressence-only data sets, such as the Global Biodiversity Information Facility (GBIF) or citizen science repositories (e.g., iNaturalist), and is thus most similar to eBird. To facilitate the use of these data, we also provide mammalian species trait information and 13 environmental covariates calculated at three spatial scales around the camera survey centroids (within 10-, 20-, and 30-km buffers). We will update the dataset to include broader coverage of temperate Asia and add newer surveys and covariates as they become available. This dataset unlocks immense opportunities for single-species ecological or conservation studies as well as applied ecology, community ecology, and macroecology investigations. The data are fully available to the public for utilization and research. Please cite this data paper when utilizing the data.

Long-Term Effectiveness of Anti-IL4R Therapy Following Suboptimal Response to Anti-IL5/5R Therapy in Severe Eosinophilic Asthma.

BACKGROUND: Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). A suboptimal response to anti-IL5/5R mAbs is seen in some patients with ongoing evidence of T2 inflammation. OBJECTIVE: To understand whether targeting IL-13 pathways with dupilumab in these patients may lead to better clinical outcomes. METHODS: We performed a retrospective analysis of the extended clinical effectiveness of dupilumab up to 2 years of treatment in patients with SEA who had not responded adequately to anti-IL5/5R biologics. Ability to achieve clinical remission and change in the remission domains of exacerbation rate (AER), maintenance oral corticosteroid dose (mOCS), lung function (FEV1) and asthma control (ACQ6) were recorded. RESULTS: Thirty-seven patients (mean age 41, 70% female) were included in the analysis. The mean (SD) AER fell by almost 90% from 3.16(1.28) at dupilumab initiation to 0.35(0.72) after 1 year. The median (IQR) mOCS dose (n=20) fell from 10(5-25) mg to 0 (0-5) mg at 1 year, with 14/20 (70%) able to stop prednisolone altogether. Clinical remission was achieved in 16/37 (43%). Patients who achieved remission had a higher pre-IL5/5R FeNO level (85ppb [39-198] vs 75ppb [42-96], p=0.03). CONCLUSION: Significant improvements in clinical outcomes are possible following a switch to dupilumab in patients experiencing a suboptimal response to anti-IL5/5R therapies. A higher FeNO in poor responders to anti-IL5/5R who achieve remission with dupilumab is suggestive of an IL-13 driven sub-phenotype of T2-high asthma in which the eosinophil appears unlikely to play a key role in the disease pathogenesis.

Projected development in Borneo and Sumatra will greatly reduce connectivity for an apex carnivore.

The islands of Borneo and Sumatra are strongholds for biodiversity and home for many endemic species. They also have experienced amongst the highest deforestation rates globally. Both islands are undergoing massive, rapid infrastructure development, leading to further deforestation and habitat fragmentation. Here, we identify priority areas for continued functional forest connectivity across Borneo and Sumatra, using spatial models of clouded leopard (Neofelis diardi, a forest indicator species) movement, and impacts thereto from existing and future infrastructure development. We specifically measure and map the anticipated impacts on forest functional connectivity of three major infrastructure development projects (Pan Borneo Highway, Trans-Sumatran Toll Road, and the new Indonesian capital city of Nusantara). We found that core clouded leopard habitats are already highly fragmented in Sumatra, constituting only ∼13 % of the island, with potential dispersal corridors still linking some habitat fragments. In Borneo, clouded leopard core habitats cover 34 % of the island, with one large central core area and several much smaller satellite cores, which are largely unprotected (15 % protected, compared to 42 % in Sumatra). The largest negative effect on habitat connectivity was predicted for Nusantara (66 % of the total connectivity loss predicted for all three infrastructure projects), reverberating across the entirety of Borneo with the strongest effects in East Kalimantan. The Pan Borneo Highway accounted for 28 % of the total connectivity loss, affecting every province in Borneo and Brunei, with 6 % of this decrease located within protected areas. The Trans-Sumatran Toll Road had the smallest negative effect on connectivity (6 %) but only when excluding the already built segments, which, when included, produce a total negative impact similar to that of the Pan Borneo Highway.

Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown. OBJECTIVE: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA. METHODS: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed. RESULTS: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups. CONCLUSIONS: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.

Sensitive MRD detection from lymphatic fluid after surgery in HPV-associated oropharyngeal cancer.

PURPOSE: To demonstrate lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) compared to plasma, which can be leveraged for patient risk stratification. EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 HPV (+) OPSCC patients, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared to TMN stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathological features, to compare with progression-free survival (PFS). RESULTS: Postoperative lymph was enriched with cf-HPV compared to plasma (P < 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P < 0.0001), and trial-defined pathological risk criteria (mean AUC = 0.78). Additionally, the lymph mutation number and variant allele frequency (VAF) were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (-) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P < 0.0001). CONCLUSIONS: Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflect single- and multi-feature high-risk pathological criteria. Incorporating lymphatic MRD and clinicopathological feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer.

Real-World Effectiveness of Anti-IL-5/5R Therapy in Severe Atopic Eosinophilic Asthma with Fungal Sensitization.

BACKGROUND: Severe asthma with fungal sensitization (SAFS) is a complex clinical phenotype associated with poorly controlled type 2 inflammation and significant morbidity from both the disease itself and a high steroid burden. OBJECTIVE: To assess the effectiveness of biologic therapies targeting eosinophilic inflammation in SAFS. METHODS: We assessed the effectiveness of treatment with mepolizumab or benralizumab in patients with SAFS, and compared outcomes with patients with severe atopic asthma without fungal sensitization and patients with severe nonatopic asthma. Baseline clinical characteristics and clinical outcomes at 48 weeks were evaluated. A subgroup analysis was performed of patients who met the criteria for allergic bronchopulmonary aspergillosis (ABPA) rather than SAFS. RESULTS: A total of 193 patients treated with mepolizumab (n = 63) or benralizumab (n = 130) were included. Patients with SAFS had higher baseline IgE level compared with patients with severe atopic asthma without fungal sensitization and severe nonatopic asthma (733 ± 837 IU/mL vs 338 ± 494 and 142 ± 171, respectively; both P < .001). There were no other significant baseline differences in clinical characteristics between groups. At 48 weeks, there were significant improvements in 6-item asthma control questionnaire score and exacerbation frequency, and reduction in maintenance oral corticosteroid dose across all groups (all P < .05). No significant between-group differences in outcomes were observed at 48 weeks. Patients with ABPA (n = 9) had a significant reduction in exacerbation frequency (P = .013) with treatment. CONCLUSIONS: Treatment with eosinophil-targeting biologics led to improvements in exacerbation frequency, oral corticosteroid requirements, and patient-reported outcomes in patients with SAFS, with a reduction in exacerbations in the subgroup of patients with ABPA. These data highlight the potential clinical utility of targeting eosinophilic inflammation in SAFS and ABPA.

The impact of the first COVID-19 surge on severe asthma patients in the UK. Which is worse: the virus or the lockdown?

Asthma therapy, including monoclonal antibodies, was not associated with #COVID19 infection or hospitalisation in a UK severe asthma population. Shielding led to a reported worsening of mental health in nearly half of patients contacted (47%). https://bit.ly/3jImUsG.

A pragmatic guide to choosing biologic therapies in severe asthma.

There are now several monoclonal antibody (mAb) therapies ("biologics") available to treat severe asthma. Omalizumab is an anti-IgE mAb and is licensed in severe allergic asthma. Current evidence suggests it may decrease exacerbations by augmenting deficient antiviral immune responses in asthma. Like all other biologics, clinical efficacy is greatest in those with elevated T2 biomarkers. Three biologics target the interleukin (IL)-5-eosinophil pathway, including mepolizumab and reslizumab that target IL-5 itself, and benralizumab that targets the IL-5 receptor (IL-5R-α). These drugs all reduce the exacerbation rate in those with raised blood eosinophil counts. Mepolizumab and benralizumab have also demonstrated steroid-sparing efficacy. Reslizumab is the only biologic that is given intravenously rather than by the subcutaneous route. Dupilumab targets the IL-4 receptor and like mepolizumab and benralizumab is effective at reducing exacerbation rate as well as oral corticosteroid requirements. It is also effective for the treatment of nasal polyposis and atopic dermatitis. Tezepelumab is an anti-TSLP (thymic stromal lymphopoietin) mAb that has recently completed phase 3 trials demonstrating significant reductions in exacerbation rate even at lower T2 biomarker thresholds. Many patients with severe asthma qualify for more than one biologic. To date, there are no head-to-head trials to aid physicians in this choice. However, post-hoc analyses have identified certain clinical characteristics that are associated with superior responses to some therapies. The presence of allergic and/or eosinophilic comorbidities, such as atopic dermatitis, nasal polyposis or eosinophilic granulomatosis with polyangiitis, that may additionally benefit by the choice of biologic should also be taken into consideration, as should patient preferences which may include dosing frequency. To date, all biologics have been shown to have excellent safety profiles.

Real-World Effectiveness of Benralizumab in Severe Eosinophilic Asthma.

BACKGROUND: Benralizumab is an IL5-receptor monoclonal antibody licensed for the treatment of severe eosinophilic asthma (SEA). It has demonstrated efficacy in clinical trials in reducing asthma exacerbation rates and maintenance oral corticosteroids (mOCSs). RESEARCH QUESTION: What is the real-world effectiveness of benralizumab and what baseline characteristics are associated with response to therapy? STUDY DESIGN AND METHODS: We assessed outcomes in all SEA patients who began benralizumab treatment at our specialist center. At each dosing visit, exacerbation history, mOCS dose, spirometry, and Asthma Control Questionnaire (ACQ6) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) scores were recorded. Response to treatment was defined as a reduction of ≥ 50% in annualized exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super response was defined as zero exacerbations and no mOCSs for asthma. RESULTS: One hundred thirty patients were included in the analysis. At 48 weeks, a 72.8% reduction in AER was noted, from 4.92 ± 3.35 per year in the year preceding biologic treatment to 1.34 ± 1.71 per year (P < .001), including 57 patients (43.8%) who were exacerbation-free with benralizumab. In those receiving mOCSs (n = 74 [56.9%]), the median daily prednisolone dose fell from 10 mg (interquartile range, 5-20 mg) to 0 mg (interquartile range, 0-5 mg; P < .001), and 38 of 74 patients (51.4%) were able to discontinue mOCS therapy. Clinically and statistically significant improvements were found in ACQ6 scores, mAQLQ scores, and FEV1. Overall, 51 patients (39%) met the super responder definition and 112 patients (86%) met the responder definition. The optimal regression model of super responders vs other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen patients (13.8%) were nonresponders to benralizumab. Evidence of chronic airway infection was observed in 6 of 18 patients, and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies was observed in 5 of 18 patients. INTERPRETATION: In a large real-world SEA cohort, benralizumab led to significant improvements in all clinical outcome measures. A lack of response was seen in a minority of patients and should be a focus for future investigation.

Steroid-sparing effects of benralizumab in patients with eosinophilic granulomatosis with polyangiitis.

Benralizumab reduces oral corticosteroid requirements in patients with EGPA and leads to improved patient-reported outcome measures https://bit.ly/2GI0vhf.

Biologic treatment options for severe asthma.

Asthma is a common condition that causes episodic expiratory airflow limitation due to bronchial smooth muscle constriction and airways inflammation resulting in increased respiratory symptoms and acute asthma exacerbations. Patients with severe asthma have relied on either recurrent courses or daily use of oral corticosteroids (OCS) to control their disease. However a high level of OCS exposure is associated with significant morbidity and mortality. In recent years the elucidation of the role of T2 inflammation underpinning asthma pathogenesis has led to the development of monoclonal antibody (mAb) therapies targeting this pathway. Established therapies now include omalizumab targeting IgE, mepolizumab and reslizumab targeting IL-5, benralizumab targeting the IL-5R and dupilumab targeting IL-4R. For many patients these therapies have been transformative and their use has additionally advanced our understanding of the immunology that underpins the disease. This article reviews the biologic therapies currently available for the treatment of severe asthma.

Simulating impacts of rapid forest loss on population size, connectivity and genetic diversity of Sunda clouded leopards (Neofelis diardi) in Borneo.

Habitat loss is the greatest threat to biodiversity in Borneo, and to anticipate and combat its effects it is important to predict the pattern of loss and its consequences. Borneo is a region of extremely high biodiversity from which forest is being lost faster than in any other. The little-known Sunda clouded leopard (Neofelis diardi) is the top predator in Borneo and is likely to depend critically on habitat connectivity that is currently being rapidly lost to deforestation. We modeled the effects of landscape fragmentation on population size, genetic diversity and population connectivity for the Sunda clouded leopard across the entirety of Borneo. We modelled the impacts of land use change between the years 2000, 2010 and projected forwards to 2020. We found substantial reductions across all metrics between 2000 and 2010: the proportion of landscape connected by dispersal fell by approximately 12.5% and the largest patch size declined by around 15.1%, leading to a predicted 11.4% decline in clouded leopard numbers. We also predict that these trends will accelerate greatly towards 2020, with the percentage of the landscape being connected by dispersal falling by about 57.8%, the largest patch size falling by around 62.8% and the predicted clouded leopard population falling by 62.5% between 2010 and 2020. We predicted that these large declines in clouded leopard population size and connectivity will also substantially reduce the genetic diversity of the remaining clouded leopard population.