The UNITE database for molecular identification and taxonomic communication of fungi and other eukaryotes: sequences, taxa and classifications reconsidered.

UNITE (https://unite.ut.ee) is a web-based database and sequence management environment for molecular identification of eukaryotes. It targets the nuclear ribosomal internal transcribed spacer (ITS) region and offers nearly 10 million such sequences for reference. These are clustered into ∼2.4M species hypotheses (SHs), each assigned a unique digital object identifier (DOI) to promote unambiguous referencing across studies. UNITE users have contributed over 600 000 third-party sequence annotations, which are shared with a range of databases and other community resources. Recent improvements facilitate the detection of cross-kingdom biological associations and the integration of undescribed groups of organisms into everyday biological pursuits. Serving as a digital twin for eukaryotic biodiversity and communities worldwide, the latest release of UNITE offers improved avenues for biodiversity discovery, precise taxonomic communication and integration of biological knowledge across platforms.

Hodgkin Lymphoma after Disseminated Mycobacterium genavense Infection, Germany.

Mycobacterium genavense infection, a rare nontuberculous mycobacteria infection, occurs in heavily immunocompromised patients (i.e., those with advanced HIV disease, genetic disorders, or acquired immunologic disorders and those undergoing immunosuppressive therapy). We report a case of disseminated M. genavense infection preceding Hodgkin lymphoma in a patient without obvious risk factors for this infection.

Drug survival and reasons for drug discontinuation in palmoplantar pustulosis: a retrospective multicenter study.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease-related to psoriasis. Its treatment is challenging, and little is known about the sustainability of different medications. The aim of this study was to analyze drug survival rates and drug discontinuation in the treatment of PPP under real-world conditions. PATIENTS AND METHODS: Patients with PPP treated in the dermatology departments of five German university medical centers between 01/2005 and 08/2017 were included in our retrospective study. Drug survival of systemic therapies was assessed with Kaplan-Meier analysis and multivariate regression. RESULTS: Overall, 347 patients with 935 treatment courses were identified. Within the group of non-biologic systemic agents, apremilast showed the highest median drug survival (15 months), followed by cyclosporine (12 months), the combination of acitretin and topical PUVA (9 months), MTX (8 months), acitretin monotherapy (6 months), alitretinoin (5 months), and fumaric acid esters (3 months). Among biologicals, the highest maintenance rate was detected for certolizumab pegol (restricted mean: 47.4 months), followed by infliximab (median: 26 months), golimumab (22 months), ustekinumab (21 months), adalimumab (18 months), secukinumab (9 months), and etanercept (8 months). CONCLUSIONS: Biologicals and apremilast may serve as second-line options for treatment of PPP and should be further evaluated.

Hand-Held Photometer for Instant On-Spot Quantification of Nucleic Acids, Proteins, and Cells.

This paper presents a novel hand-held photometer, termed "Photopette", for on-spot absorbance measurements of biochemical analytes. The Photopette is a multicomponent, highly portable device with an overall weight of 160 g, which fits within 202 mm × 47 mm × 42 mm. Designed in the form factor of a micropipette, Photopette integrates a photodiode detector with light emitting diodes (LEDs) to form a highly customizable photometer which supports a wide variety of applications within the wavelengths between 260 and 1050 nm. A dual-purpose disposable reflective tip was designed to act as a sample holder and a light-reflecting system, which is in stark contrast to the operation of mainstream spectrophotometers and photometers. Small volume analytes may be measured with low sample loss using this proprietary CuveTip. A user-friendly software application running on smart devices was developed to control and read the values from Photopette via a low-energy Bluetooth link. This one-step strategy allows measurements on-spot without sample transfer, minimizing cross-contamination and human error. The results reported in this paper demonstrate Photopette's great potential to quantify DNA, direct protein, and cell density directly within the laminar flow hood. Results are compared with a Nanodrop 2000c spectrophotometer, a mainstream spectrophotometer for small-volume measurements.

"Drug-Survival"-Raten und Gründe für den Abbruch von Systemtherapien bei Psoriasis.

HINTERGRUND UND ZIELE: Mittelschwere bis schwere Psoriasis erfordert häufig eine langfristige systemische Behandlung. Die Therapietreue bezüglich eines Medika-ments (Überlebensrate, "Drug Survival") reflektiert dessen Wirksamkeit, Sicherheit sowie die Zufriedenheit mit der Behandlung und ist ein Indikator für den Therapieerfolg. Das Ziel der vorliegenden Studie was die Ermittlung der "Drug-Survival"-Raten sowie der Gründe für den Abbruch einer Behandlung mit Fumarsäureestern (fumaric acid esters, FAE), Methotrexat (MTX), Acitretin (ACI), Cyclosporin A (CyA), Adalimumab (ADA), Etanercept (ETA), Infliximab (INF) und Ustekinumab (UST) bei Patienten mit mittelschwerer bis schwerer Psoriasis. PATIENTEN UND METHODEN: Wir führten eine retrospektive Analyse an 373 Patienten durch, die im Zeitraum 1/2003-5/2014 insgesamt 696 Behandlungen an einem deutschen Universitätsklinikum erhalten hatten. ERGEBNISSE: Die unbereinigte Überlebenswahrscheinlichkeit war für UST am höchsten, gefolgt von ADA, ETA, INF, FAE, MTX, ACI und CyA. In der multivariaten Regressionsanalyse mit FAE als Referenz betrug die Hazard Ratio (HR) für einen Abbruch 0,14 (95 % Konfidenzintervall: 0,06-0,35) bei UST, 0,43 (0,26-0,73) bei ADA, 2,11 (1,14-3,91) bei ACI und 3,26 (1,44-7,39) bei CyA. Das "Drug Survival" von INF war länger, wenn es in Kombination mit MTX eingesetzt wurde (HR 2,87; 1,21-6,81). Traditionelle systemische Antipsoriatika sowie INF wurden am häufigsten aufgrund von Nebenwirkungen abgesetzt; alle anderen Biologika aufgrund ihrer Unwirksamkeit für kutane Psoriasis-Läsionen. SCHLUSSFOLGERUNGEN: "Drug-Survival"-Raten sollten bei der Therapieentscheidung berücksichtigt werden, um den Patienten eine bestmögliche Langzeitstrategie zu bieten.

Drug survival rates and reasons for drug discontinuation in psoriasis.

BACKGROUND AND OBJECTIVES: Moderate-to-severe psoriasis frequently requires long-term systemic therapy. Reflecting efficacy, safety, and treatment satisfaction, drug survival is an indicator of therapeutic success. The objective of the present study was to assess drug survival rates and reasons for discontinuation of fumaric acid esters (FAE), methotrexate (MTX), acitretin (ACI), cyclosporine A (CyA), adalimumab (ADA), etanercept (ETA), infliximab (INF), and ustekinumab (UST) in patients with moderate-to-severe psoriasis. PATIENTS AND METHODS: We performed a retrospective analysis of 373 patients who had received a total of 696 treatment courses at a German university hospital in the period 1/2003-5/2014. RESULTS: The crude probability of survival was highest for UST, followed by ADA, ETA, INF, FAE, MTX, ACI, and CyA. In multivariate regression analysis using FAE as reference, hazard ratios (HR) for discontinuation were 0.14 (95 % confidence interval: 0.06-0.35) for UST, 0.43 (0.26-0.73) for ADA, 2.11 (1.14-3.91) for ACI, and 3.26 (1.44-7.39) for CyA. INF showed longer survival when combined with MTX (HR 2.87, 1.21-6.81). Traditional systemic antipsoriatic agents as well as INF were most frequently discontinued due to adverse events; all other biologics, due to inefficacy with respect to cutaneous lesions. CONCLUSIONS: Drug survival rates should be integrated into therapeutic decisions in order to provide patients with an optimal long-term strategy.

Plasma HMGB-1 after the initial dose of epirubicin/docetaxel in cancer.

BACKGROUND: The response of breast cancer patients to neoadjuvant chemotherapy (NCT) is highly heterogeneous, and reliable predictive instruments remain to be defined. High-mobility group box-1 (HMGB-1) protein is a cell death marker, which is easily detectable in plasma. We hypothesized that the initial dose of NCT with epirubicin/docetaxel induces changes in plasma HMGB-1 which could allow for an early prediction of response to therapy. MATERIALS AND METHODS: First, we analysed whether epirubicin/docetaxel releases HMGB-1 from HCC1143 breast cancer cells in vitro. Thereafter, plasma HMGB-1 levels before and 1-4 days after the first dose of epirubicin/docetaxel-based NCT were determined in 41 breast cancer patients and correlated with pathological response to treatment. RESULTS: Treatment of HCC1143 cells with epirubicin/docetaxel resulted in a significant HMGB-1 release in vitro. In vivo, HMGB-1 levels increased significantly only in responders (pathological complete response or partial remission, n = 22) but not in nonresponders (stable or progressive disease, n = 19). CONCLUSION: Our data suggest that early dynamic changes of plasma HMGB1 could be a promising biomarker to predict the final response to NCT in breast cancer patients.

Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer.

Diabetic foot ulcer (DFU) is a severe complication of diabetes and a challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges the need for additional treatment. Stem cell-based therapy for DFU has been investigated over the past years. Its therapeutic effect is through promoting angiogenesis, secreting paracrine factors, stimulating vascular differentiation, suppressing inflammation, improving collagen deposition, and immunomodulation. It is controversial which type and origin of stem cells, and which administration route would be the most optimal for therapy. We reviewed the different types and origins of stem cells and routes of administration used for the treatment of DFU in clinical and preclinical studies. Diabetes leads to the impairment of the stem cells in the diseased patients, which makes it less ideal to use autologous stem cells, and requires looking for a matching donor. Moreover, angioplasty could be complementary to stem cell therapy, and scaffolds have a positive impact on the healing process of DFU by stem cell-based therapy. In short, stem cell-based therapy is promising in the field of regenerative medicine, but more studies are still needed to determine the ideal type of stem cells required in therapy, their safety, proper dosing, and optimal administration route.

Targeting an Oncolytic Influenza A Virus to Tumor Tissue by Elastase.

Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs) containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA), which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site. We chose this cleavage site because elastase is expressed in the tumor microenvironment. Moreover, the exchange of the cleavage site previously has been shown to attenuate viral growth in lungs. Newly generated elastase-activated influenza viruses (AE viruses) grew to similar titers in tumor cells as the trypsin-activated counterparts (AT viruses). Intratumoral injection of AE viruses into syngeneic B16f1 melanoma-derived tumors in mice reduced tumor growth similar to AT viruses and had a better therapeutic effect in heterologous human PANC-1-derived tumors. Therefore, the introduction of the attenuation marker "elastase cleavage site" in viral HA allows for safe, effective oncolytic virus therapy.

Prognostic value of HMGB1 in early breast cancer patients under neoadjuvant chemotherapy.

The response to neoadjuvant chemotherapy in breast cancer patients is usually assessed by pCR and RCB score. However, the prognostic value of these parameters is still in discussion. We showed recently that an epirubicin/docetaxel therapy is associated with an increase in the cell death marker high-mobility group box 1 protein (HMGB1) in the circulation. Here, we investigate whether this increase correlates with the long-term outcome. Thirty-six early breast cancer patients under neoadjuvant epirubicin/docetaxel combination chemotherapy were included in this study. To determine the immediate effect of this treatment on HMGB1, we collected blood samples before and 24-96 h after the initial dose. This time course was then compared to the 5-year follow-up of the patients. HMGB1 levels varied before chemotherapy between 4.1 and 11.3 ng/mL and reacted differently in response to therapy. Some patients showed an increase while others did not show any changes. Therefore, we subdivided the patient collective into two groups: patients with an at least 1.1 ng/mL increase in HMGB1 and patients with smaller changes. The disease-free survival was longer in the HMGB1 increase group (56.2 months vs. 46.6 months), but this difference did not reach significance. The overall survival (OS) was significantly better in patients with an increase in HMGB1 (log rank P = 0.021). These data suggest that an immediate increase in HMGB1 levels correlates with improved outcome in early breast cancer patients receiving neoadjuvant chemotherapy, and may be a valuable complementary biomarker for early estimation of prognosis.