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In April 2012, a group of nephrologists organized a consensus conference in Cambridge (UK) on type II membranoproliferative glomerulonephritis and decided to use a new terminology, “C3 glomerulopathy” (C3 GP). Further knowledge on the complement system and on kidney biopsy contributed toward distinguishing this disease into three subgroups: dense deposit disease (DDD), C3 glomerulonephritis (C3 GN), and the CFHR5 nephropathy. The persistent presence of microhematuria with or without light or heavy proteinuria after an infection episode suggests the potential onset of C3 GP. These nephritides are characterized by abnormal activation of the complement alternative pathway, abnormal deposition of C3 in the glomeruli, and progression of renal damage to end-stage kidney disease. The diagnosis is based on studying the complement system, relative genetics, and kidney biopsies. The treatment gap derives from the absence of a robust understanding of their natural outcome. Therefore, a specific treatment for the different types of C3 GP has not been established. Recommendations have been obtained from case series and observational studies because no randomized clinical trials have been conducted. Current treatment is based on corticosteroids and antiproliferative drugs (cyclophosphamide, mycophenolate mofetil), monoclonal antibodies (rituximab) or complement inhibitors (eculizumab). In some cases, it is suggested to include sessions of plasma exchange.

Although several methods exist for extracting and sequencing historical DNA originating from dry-preserved insect specimens deposited in natural history museums, no consensus exists as to what is the optimal approach. We demonstrate that a customized, low-cost archival DNA extraction protocol (∼€10 per sample), in combination with Ultraconserved Elements (UCEs), is an effective tool for insect phylogenomic studies. We successfully tested our approach by sequencing DNA from scarab dung beetles preserved in both wet and dry collections, including unique primary type and rare historical specimens from internationally important natural history museums in London, Paris and Helsinki. The focal specimens comprised of enigmatic dung beetle genera (Nesosisyphus, Onychothecus and Helictopleurus) and varied in age and preservation. The oldest specimen, the holotype of the now possibly extinct Mauritian endemic Nesosisyphus rotundatus, was collected in 1944. We obtained high-quality DNA from all studied specimens to enable the generation of a UCE-based dataset that revealed an insightful and well-supported phylogenetic tree of dung beetles. The resulting phylogeny propounded the reclassification of Onychothecus (previously incertae sedis) within the tribe Coprini. Our approach demonstrates the feasibility and effectiveness of combining DNA data from historic and recent museum specimens to provide novel insights. The proposed archival DNA protocol is available at DOI 10.17504/protocols.io.81wgbybqyvpk/v3.

Subclinical acute rejection (SCAR) in kidney transplantation, defined by histologic lesions without clinical dysfunction, remains a major cause of allograft injury and is currently detectable only by invasive protocol biopsies. We conducted a multicenter study in which transcriptomic profiling of Formalin-Fixed, Paraffin-Embedded biopsies from SCAR and control patients revealed a distinct signature with upregulation of NFKBIZ, TNFSF14, SLAMF8 , and CD247 , validated by qRT-PCR and immunohistochemistry but not detectable in urine. Focusing on secreted cytokines, CXCL10 and FasL emerged as candidate urinary biomarkers and were first measured in 12 SCAR patients and 12 controls, showing a significant increase in SCAR. Validation in an independent cohort of 86 kidney transplant recipients, after excluding patients with confounders, confirmed higher CXCL10 and FasL levels in SCAR. When combined as a composite biomarker signature (CXCL10 + FasL), ROC analysis yielded an AUC of 0.711 (95% CI, 0.549–0.874), with 50% sensitivity and 84% specificity at the optimal cutoff. In the still poorly studied context of SCAR, this work is a proof-of-concept approach linking intragraft transcriptomics to urinary cytokine levels. Our findings support the utility of urinary CXCL10 and FasL in assisting clinicians in identifying patients who may benefit from further evaluation, including consideration of a graft biopsy, thereby contributing to improved long-term allograft outcomes.

Wood-boring beetles and, in particular, Scolytinae (Coleoptera: Curculionidae) are one of the most successful groups of invasive species worldwide. They can be easily transported across continents at the larval stage as their development takes place inside the tissues of live plants, timber, wood products and wood-packaging materials. This grants them protection from adverse travel conditions and allows them to often go unnoticed by phytosanitary inspections at ports of entry. In this context, knowledge of biological traits of these species, particularly the recorded host plants, is essential for planning effective monitoring strategies. This kind of information is scattered through a large amount of papers, catalogs and books. Thus, the purpose of this paper is to provide a comprehensive list of host plants and their economic categorization for five scolytine tribes. This fourth contribution presents the list of host plants for 829 species belonging to five tribes that mainly, but not exclusively, infest conifers: Hylastini LeConte, Hylurgini Gistel, Ipini Bedel, Phloeosinini Nusslin, and Polygraphini Chapuis.

The evaluation of kidney biopsies performed by expert pathologists is a crucial process for assessing if a kidney is eligible for transplantation. In this evaluation process, an important step consists of the quantification of global glomerulosclerosis, which is the ratio between sclerotic glomeruli and the overall number of glomeruli. Since there is a shortage of organs available for transplantation, a quick and accurate assessment of global glomerulosclerosis is essential for retaining the largest number of eligible kidneys. In the present paper, the authors introduce a Computer-Aided Diagnosis (CAD) system to assess global glomerulosclerosis. The proposed tool is based on Convolutional Neural Networks (CNNs). In particular, the authors considered approaches based on Semantic Segmentation networks, such as SegNet and DeepLab v3+. The dataset has been provided by the Department of Emergency and Organ Transplantations (DETO) of Bari University Hospital, and it is composed of 26 kidney biopsies coming from 19 donors. The dataset contains 2344 non-sclerotic glomeruli and 428 sclerotic glomeruli. The proposed model consents to achieve promising results in the task of automatically detecting and classifying glomeruli, thus easing the burden of pathologists. We get high performance both at pixel-level, achieving mean F-score higher than 0.81, and Weighted Intersection over Union (IoU) higher than 0.97 for both SegNet and Deeplab v3+ approaches, and at object detection level, achieving 0.924 as best F-score for non-sclerotic glomeruli and 0.730 as best F-score for sclerotic glomeruli.

Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by high immunogenicity which makes it particularly suitable for immune checkpoint inhibitors (ICIs) treatment. We report the case of a 53-year-old man with metastatic DM successfully treated with the combination of anti-CTLA-4 and anti-PD-1 antibodies, who developed serious immune-related adverse events (irAEs). The primary tumor was characterized by absent PD-L1 expression and no-brisk lymphocytes infiltration. NGS showed absence of BRAF mutation, a high tumor mutational burden, and an UV-induced DNA damage signature. Metastatic lesions regressed rapidly after few cycles of ICIs until complete response, however the patient developed serious irAEs including hypothyroidism, adrenal deficiency, and acute interstitial nephritis which led to the definitive suspension of treatment. Currently, the patient has normal renal functionality and no disease relapse after 26 months from starting immunotherapy, and after 9 months from its definitive suspension. Efficacy and toxicity are two sides of the same coin of high sensitivity to ICIs in DM. For this reason, these patients should be closely monitored during ICIs therapy to promptly identify serious side effects and to correctly manage them.

Numerous taxonomic studies have focused on the dung beetle genus Helictopleurus d’Orbigny, 1915, endemic to Madagascar. However, this genus stilll needs a thorough revision. Semantic technologies, such as nanopublications, hold the potential to enhance taxonomy by transforming how data are published and analysed. This paper evaluates the effectiveness of nanopublications in establishing synonyms within the genus Helictopleurus . In this study, we identify four new synonyms within Helictopleurus : H. rudicollis (Fairmaire, 1898) = H. hypocrita Balthasar, 1941 syn. nov. ; H. vadoni Lebis, 1960 = H. perpunctatus Balthasar, 1963 syn. nov. ; H. halffteri Balthasar, 1964 = H. dorbignyi Montreuil, 2005 syn. nov. ; H. clouei (Harold, 1869) = H. gibbicollis (Fairmaire, 1895) syn. nov. Helictopleurus may have a significantly larger number of synonyms than currently known, indicating potentially inaccurate estimates about its recent extinction. We also publish the newly-established synonyms as nanopublications, which are machine-readable data snippets accessible online. Additionally, we explore the utility of nanopublications in taxonomy and demonstrate their practical use with an example query for data extraction.

Scolytinae (Coleoptera: Curculionidae) are one of the most successful groups of invasive species. They are generally moved among continents transported within live plants, timber and wood-packaging materials. The damages caused by these insects, of economic and ecological relevance, can be caused both by the direct action of burrowing within host plant tissues and by the pathogens carried by some species. In order to prevent the introduction of new and potentially harmful species by planning effective monitoring strategies, the knowledge of recorded host plants is essential. This third contribution provides a complete list of host plants, with economic categorization, for 2,193 scolytine species, belonging to 16 tribes: Amphiscolytini, Bothrosternini, Carphodicticini, Chaetophloeini, Crypturgini, Diamerini, Dryocoetini, Hexacolini, Hylesinini, Hyorrhynchini, Hypoborini, Micracidini, Phloeotribini, Phrixosomatini, Scolytini, and Scolytoplatypodini.

Treatment with immune checkpoint inhibitors (ICIs) has improved the prognosis of patients with a number of types of cancer, but the frequent development of immune-related adverse effects (irAEs) can worsen the outcome. The most common irAEs involve the gastrointestinal, cutaneous, and endocrine systems, but nephrotoxicity, resulting from damage to the tubule-interstitial compartment, may occur in some patients. The early phases of acute interstitial nephritis (AIN) are characterized by systemic symptoms that indicate a poor clinical state as well as a mild deterioration of renal function. Tubular injury is due to a direct effect mediated by cytotoxic CD8+ T cells, which sustain the local production of pro-inflammatory cytokines that progressively impair renal function. The treatment of AIN is mainly based on high-dose steroids, which in most instances leads to the recovery of renal function. However, the premature discontinuation of ICI therapy may prevent the impact of treatment on the clinical progression of the malignancy. Adequately addressing irAEs requires a standardized therapy that is based on the results of large clinical trials.

Acute kidney injury (AKI) is increasingly emerging as a global emergency. Sepsis, major surgery, and nephrotoxic drugs are the main causes of AKI in hospitalized patients. However, glomerulonephritis accounts for about 10% of AKI episodes in adults, mainly related to rapidly progressive glomerulonephritis resulting from granulomatous polyangiitis (GPA, Wegener granulomatosis), microscopic polyangiitis (MPA), and anti-glomerular basement membrane (GBM) disease. Also, diffuse proliferative lupus nephritis, immunoglobulin A nephropathy, post-streptococcal glomerulonephritis, mixed cryoglobulinemia, mesangiocapillary glomerulonephritis, membranous nephropathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and scleroderma can induce acute renal failure. Early diagnosis of AKI due to glomerulonephritis is crucial for prompt, effective management to improve short- and long-term outcomes. Kidney biopsy is the gold standard for the diagnosis of glomerular disease, but it is not frequently performed in critically ill patients because of their clinical conditions. In this setting, a growing number of diagnostic assays can support the working hypothesis, including antineutrophil cytoplasmic antibodies (ANCAs), anti-double-stranded DNA antibodies, anti-GBM antibodies, antistreptolysin O and anti-DNase B antibodies, cryoglobulins, antiphospholipid antibodies, and complement levels. Therapeutic strategies in AKI patients with glomerulonephritis include high-dose corticosteroids, cyclophosphamide, and plasma exchange. This article reviews the wide spectrum of glomerulopathies associated with AKI, describing the immunological mechanisms underlying glomerular diseases and presenting an overview of the therapeutic options.