bluuebunny/crossref_metadata_2025_split huggingface dataset:
National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD
Authors: Hasseli Rebecca , Mueller-Ladner Ulf , Schmeiser Tim , Hoyer Bimba F , Krause Andreas , Lorenz Hanns-Martin , Regierer Anne Constanze , Richter Jutta G , Strangfeld Anja , Voll Reinhard E , Pfeil Alexander , Schulze-Koops Hendrik , Specker Christof 
Published: September 2020

ObjectivesPatients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany.MethodsUsing an online questionnaire (www.COVID19-rheuma.de), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters—for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection—are documented.ResultsUntil 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males; 63 females; 1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course.ConclusionsIn a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic.
Dynamic Algorithms for Visibility Polygons in Simple Polygons
Authors: Inkulu R. , Sowmya K. , Thakur Nitish P. 
Published: September 2020

We devise the following dynamic algorithms for both maintaining as well as querying for the visibility and weak visibility polygons amid vertex insertions and deletions to the simple polygon. A fully-dynamic algorithm for maintaining the visibility polygon of a fixed point located interior to the simple polygon amid vertex insertions and deletions to the simple polygon. The time complexity to update the visibility polygon of a point [Formula: see text] due to the insertion (resp. deletion) of vertex [Formula: see text] to (resp. from) the current simple polygon is expressed in terms of the number of combinatorial changes needed to the visibility polygon of [Formula: see text] due to the insertion (resp. deletion) of [Formula: see text]. An output-sensitive query algorithm to answer the visibility polygon query corresponding to any point [Formula: see text] in [Formula: see text] amid vertex insertions and deletions to the simple polygon. If [Formula: see text] is not exterior to the current simple polygon, then the visibility polygon of [Formula: see text] is computed. Otherwise, our algorithm outputs the visibility polygon corresponding to the exterior visibility of [Formula: see text]. An incremental algorithm to maintain the weak visibility polygon of a fixed-line segment located interior to the simple polygon amid vertex insertions to the simple polygon. The time complexity to update the weak visibility polygon of a line segment [Formula: see text] due to the insertion of vertex [Formula: see text] to the current simple polygon is expressed in terms of the sum of the number of combinatorial updates needed to the geodesic shortest path trees rooted at [Formula: see text] and [Formula: see text] due to the insertion of [Formula: see text]. An output-sensitive algorithm to compute the weak visibility polygon corresponding to any query line segment located interior to the simple polygon amid both the vertex insertions and deletions to the simple polygon. Each of these algorithms requires preprocessing the initial simple polygon. And, the algorithms that maintain the visibility polygon (resp. weak visibility polygon) compute the visibility polygon (resp. weak visibility polygon) with respect to the initial simple polygon during the preprocessing phase.
Phase I and Biomarker Study of the Wnt Pathway Modulator DKN-01 in Combination with Gemcitabine/Cisplatin in Advanced Biliary Tract Cancer
Authors: Goyal Lipika , Sirard Cynthia , Schrag Michael , Kagey Michael H. , Eads Jennifer R. , Stein Stacey , El-Khoueiry Anthony B. , Manji Gulam A. , Abrams Thomas A. , Khorana Alok A. , Miksad Rebecca , Mahalingam Devalingam , Zhu Andrew X. , Duda Dan G. 
Published: September 2020

Abstract

Purpose:
Dickkopf-1 (DKK1) modulates Wnt signaling, promoting tumor growth, metastasis, and immunosuppression. High DKK1 expression has been detected in various tumor types—including biliary tract cancer (BTC)—and is associated with poor prognosis. DKN-01—a humanized mAb targeting DKK1—was evaluated in a phase I multicenter study in combination with gemcitabine and cisplatin in patients with unresectable or metastatic BTC with no prior systemic therapy for advanced disease.

Patients and Methods:
This study included a dose-escalation phase assessing DKN-01 at two dose levels (150 mg and 300 mg) combined with gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) followed by dose expansion. Primary endpoints evaluated safety and tolerability; secondary endpoints evaluated efficacy, pharmacokinetics, and circulating biomarkers.

Results:
Fifty-one patients with intrahepatic cholangiocarcinoma (63%), extrahepatic cholangiocarcinoma (8%), and gallbladder cancer (29%) were enrolled. No dose-limiting toxicities were seen, and the expansion phase proceeded with DKN-01 300 mg (N = 47). The most frequent grade 3/4 treatment-emergent adverse events included neutropenia (60%), thrombocytopenia (34%), and anemia (23%). The objective response rate was 21.3% and median progression-free survival was 8.7 months (95% confidence interval, 5.4–10.3 months). Better outcomes were associated with biomarkers of angiogenesis inhibition (increased sVEGFR1 and lower VEGF-C) and reduced inflammation (lower IL6 and decreased TNFα).

Conclusions:
DKN-01 300 mg was well tolerated in this combination but did not appear to have additional activity beyond historically reported efficacy with gemcitabine/cisplatin alone. Exploratory pharmacokinetic and biomarker data indicate potential antiangiogenic and immunomodulatory activity of DKN-01/chemotherapy and the need for increased dose/intensity. A study with DKN-01 600 mg in combination with a PD-1 inhibitor in BTC is ongoing.
LILRB4-targeting Antibody–Drug Conjugates for the Treatment of Acute Myeloid Leukemia
Authors: Anami Yasuaki , Deng Mi , Gui Xun , Yamaguchi Aiko , Yamazaki Chisato M. , Zhang Ningyan , Zhang Cheng Cheng , An Zhiqiang , Tsuchikama Kyoji 
Published: September 2020

Abstract
Acute myeloid leukemia (AML) is the most common and aggressive blood cancer in adults. In particular, significant unmet medical needs exist for effective treatment strategies for acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5) AML subtypes. Antibody–drug conjugates (ADC) are a promising drug class for AML therapy, as demonstrated by the FDA-approved anti-CD33 ADC, gemtuzumab ozogamicin (Mylotarg). However, CD33 is expressed in normal hematopoietic stem cells, highlighting the critical need to identify AML-specific targets to minimize the risk of potential adverse effects. We have demonstrated that the leukocyte immunoglobulin-like receptor subfamily B4 (LILRB4) is expressed at significantly higher levels on monocytic M4 and M5 AML cells than on normal counterparts. Here, we test whether LILRB4 is a promising ADC target to kill monocytic AML cells while sparing healthy counterparts. To this end, we generated ADCs from a humanized anti-LILRB4 mAb and the antimitotic payload, monomethyl auristatin F. The conjugates constructed were characterized and evaluated for LILRB4-specific cell killing potency, toxicity to progenitor cells, pharmacokinetics, and therapeutic efficacy. Our ADC linker technology platform efficiently generated homogeneous anti-LILRB4 ADCs with defined drug-to-antibody ratios. The homogeneous anti-LILRB4 ADCs demonstrated the capacity for LILRB4-mediated internalization, suitable physicochemical properties, and high cell killing potency against LILRB4-positive AML cells. Importantly, our data indicate that these ADCs spare normal progenitor cells. One of our homogeneous conjugates exerted a remarkable therapeutic effect and no significant toxicity in a xenograft mouse model of disseminated human AML. Our findings highlight the clinical potential of anti-LILRB4 ADCs in monocytic AML therapy.
Safety and Prognostic Value of Vasodilator Stress Cardiovascular Magnetic Resonance in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Pezel Théo , Sanguineti Francesca , Kinnel Marine , Landon Valentin , Bonnet Guillaume , Garot Philippe , Hovasse Thomas , Unterseeh Thierry , Champagne Stéphane , Louvard Yves , Claude Morice Marie , Garot Jérôme 
Published: September 2020

Background:
Patients with heart failure with reduced ejection fraction (HFrEF; heart failure with reduced left ventricular ejection fraction <40%) referred for stress cardiovascular magnetic resonance (CMR) may have a less optimal hemodynamic response to intravenous vasodilator. The aim was to assess the prognostic value of vasodilator stress perfusion CMR in patients with HFrEF.

Methods:
Between 2008 and 2018, consecutive patients with HFrEF defined by left ventricular ejection fraction <40% prospectively referred for vasodilator stress perfusion CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement by CMR.

Results:

Of 1053 patients with HFrEF (65±11 years, median [interquartile range] left ventricular ejection fraction 38.7% [37.2–39.0]), 1018 (97%) completed the CMR protocol and 950 (93%) completed the follow-up (median [interquartile range], 5.6 [3.6–7.3] years); 117 experienced a MACE (12.3%). Stress CMR was well tolerated without any adverse events. Patients without ischemia or late gadolinium enhancement experienced a lower annual event rate of MACE (1.8%) than those with both ischemia and late gadolinium enhancement (12.0%;
P
<0.001). Using Kaplan-Meier analysis, inducible ischemia and late gadolinium enhancement were significantly associated with the occurrence of MACE (hazard ratio, 2.46 [95% CI, 1.69–3.60]; and hazard ratio, 2.92 [95% CI, 1.77–4.83], respectively, both
P
<0.001). In multivariable Cox regression, inducible ischemia was an independent predictor of a higher incidence of MACE (hazard ratio, 2.26 [95% CI, 1.52–3.35];
P
<0.001).

Conclusions:
Stress CMR is safe and has a good discriminative prognostic value to predict the occurrence of MACE in patients with HFrEF.
Biological attributes of Salibro™, a novel sulfonamide nematicide. Part 2: Impact on the fitness of various non-target nematodes
Authors: Thoden Tim C. , Alkader Mariam A. , Wiles John A. 
Published: September 2020

Summary
Currently a renaissance in chemical nematicides is taking place with novel products like Nimitz® (a.s. fluensulfone), Velum Prime® (a.s. fluopyram) and Salibro™ (a.s. fluazaindolizine – Reklemel™ active) entering the marketplace. Although a considerable amount of published data is already available on their laboratory and field impact on plant-parasitic nematodes, little is understood of their compatibility with the beneficial or free-living nematodes that are part of the soil health network. In a range of laboratory studies, the effects of these nematicides on the vitality and reproduction of several species was tested, including both cosmopolitan free-living nematodes (Acrobeloides, Cruznema, Panagrobelus) as well as commercially applied entomopathogenic nematodes (Steinernema, Heterorhabditis). Within aqueous exposure and agar plate in vitro assays, species sensitivity to those nematicides differed significantly but their fitness (vitality and reproduction; infectivity to insect hosts) was generally not adversely impacted by concentrations of 5-50 ppm (a.s.) of Salibro. Even at 250 ppm (a.s.) of Salibro only some species of the bacterial-feeding species showed some negative impact. By contrast, both Nimitz at 50 ppm (a.s.) and Velum at 5 ppm (a.s.) consistently demonstrated stronger adverse impacts. In second level soil drenching assays, either no, or occasionally slight, adverse effects on the natural community of free-living nematodes were observed if soils were drenched with different volumes of Salibro at 5-50 ppm (a.s.), while relatively stronger reductions were measured within the plant-parasitic species (especially root-knot nematodes). Both Nimitz and Vydate (a.s. oxamyl) showed some degree of compatibility at 5 and 25 ppm (a.s.), respectively, which was generally higher than for Velum Prime at 5 ppm (a.s.). Overall, these data indicate that, when used at common field rates, Salibro will be one of the best options as part of integrated nematode management programmes where the use of chemical nematicides is required.
Molecular and morphological characterisation of Trichodorus species (Nematoda: Trichodoridae), with description of T. pseudoaequalis n. sp. from California and other states of the USA
Authors: Decraemer Wilfrida , Subbotin Sergei A. 
Published: September 2020

Summary
During surveys for stubby root nematodes in the natural vegetation of California, Oregon and Washington, USA, three known species, viz., Trichodorus californicus, T. intermedius and T. obscurus were recovered together with ten unidentified Trichodorus species. The three known and one new species were studied using an integrated approach. Trichodorus pseudoaequalis n. sp. is characterised by a medium-sized body about 800 μm long on average, male with two ventromedian cervical papillae anterior to secretory-excretory pore and three precloacal supplements all located anterior to the retracted spicules; spicules 39 μm long (average), slightly ventrally curved, more so in head region and blade with slight indentation mid-way and striation more pronounced in posterior half. Females possess a rather short (average 33% of corresponding body diam.) pear-shaped vagina with small vaginal sclerotised pieces (ca 1.5 μm long), rounded triangular in shape, obliquely orientated and close together; one pair of sublateral body pores anterior (about four vulval body diam.) to vulva and one pair of post-advulvar sublateral body pores. Trichodorus pseudoaequalis n. sp. differs from the most similar species, T. aequalis, in male characters like general spicule shape and ornamentation and in the position of the dorsal pharyngeal gland nucleus in both sexes (at same level of posterior ventrosublateral pair vs clearly separated). The phylogenetic relationships of the recovered species were reconstructed using the ITS2 rRNA and the D2-D3 expansion segments of 28S rRNA gene sequences.
A synoptic review of the family Dendronotidae (Mollusca: Nudibranchia): a multilevel organismal diversity approach
Authors: Korshunova Tatiana , Bakken Torkild , Grøtan Viktor V. , Johnson Kjetil B. , Lundin Kennet , Martynov Alexander 
Published: September 2020

Abstract
A synoptic review of the family Dendronotidae is presented based on morphological and molecular data. Three genera are recognized: Dendronotus, Pseudobornella, and Cabangus gen. nov. Two new Dendronotus species are described, D. yrjargul sp. nov. and D. nordenskioeldi sp. nov., which reveal fine-scale differences. Dendronotus yrjargul sp. nov. from mid-Norway and the Arctic regions is a sister species to the North Pacific D. kalikal. These two species are showing clear morphological and ontogenetic differences but are close in genetic distance. In contrast, Dendronotus nordenskioeldi sp. nov. from the Laptev Sea is externally similar to the white morphs of D. lacteus or D. frondosus, but according to the molecular data and radular morphology it is distinct from any of its congenerics. Comparison of molecular and morphological data of D. niveus from the type locality (White Sea) and material from other localities with those from the American North Atlantic coast (type locality of D. elegans) reveals their substantial similarity. Therefore, D. niveus is considered a junior synonym of D. elegans. The present review of the family Dendronotidae contributes to a general discussion on the species concepts and on a recent proposal of multilevel organismal diversity.
The Importance of Organizational Considerations for the Implementation of Information Technology
Authors: Lunt P. J. , Barclay I. 
Published: September 2020

Many companies introducing information technology, in any form, can experience problems because the organizational aspects of introducing such technology have not received their due consideration. The paper will firstly review the various aspects to be considered, and then discusses the results of research work undertaken in companies in the UK and Japan, to compare and contrast the differing approaches of these two countries to technology implementation.
Characteristics and Outcomes of Mechanically Ventilated COVID-19 Patients—An Observational Cohort Study
Authors: Krause Martin , Douin David J. , Kim Kevin K. , Fernandez-Bustamante Ana , Bartels Karsten 
Published: September 2020

Background: The United States currently has more confirmed cases of COVID-19 than any other country in the world. Given the variability in COVID-19 testing and prevention capability, identifying factors associated with mortality in patients requiring mechanical ventilation is critical. This study aimed to identify which demographics, comorbidities, markers of disease progression, and interventions are associated with 30-day mortality in COVID-19 patients requiring mechanical ventilation. Methods: Adult patients with a confirmed diagnosis of COVID-19 admitted to one of the health system’s intensive care units and requiring mechanical ventilation between March 9, 2020 and April 1, 2020, were included in this observational cohort study. We used Chi-Square and Mann-Whitney U tests to compare patient characteristics between deceased and living patients and multiple logistic regression to assess the association between independent variables and the likelihood of 30-day mortality. Results: We included 85 patients, of which 20 died (23.5%) within 30 days of the first hospital admission. In the univariate analysis, deceased patients were more likely ≥60 years of age (p < 0.001), non-Hispanic (p = 0.026), and diagnosed with a solid malignant tumor (p = 0.003). Insurance status also differed between survivors and non-survivors (p = 0.019). Age ≥60 and malignancy had a 9.5-fold (95% confidence interval 1.4-62.3, p = 0.020) and 5.8-fold higher odds ratio (95% confidence interval 1.2-28.4, p = 0.032) for 30-day mortality after adjusted analysis using multivariable logistic regression, while other independent variables were no longer significant. Conclusions: In our observational cohort study of 85 mechanically ventilated COVID-19 patients, age, and a diagnosis of a solid malignant tumor were associated with 30-day mortality. Our findings validate concerns for the survival of elderly and cancer patients in the face of the COVID-19 pandemic in the United States, where testing capabilities and preventative measures have been inconsistent. Preventative efforts geared to patients at risk for intensive care unit mortality from COVID-19 should be explored.
One-Year Single-Center Results of the Multilayer Flow Modulator Stents for the Treatment of Type B Aortic Dissection
Authors: Costache Victor S. , Meekel Jorn P. , Costache Andreea , Melnic Tatiana , Bucurenciu Cristian , Chitic Anca , Candea Gabriela , Solomon Crina , Yeung Kak K. 
Published: September 2020

Purpose To report a single-center series of patients with type B aortic dissection treated with the Multilayer Flow Modulator (MFM). Materials and Methods Over a 36-month period, 23 patients (median age 53 years; 20 men) with complicated type B aortic dissections (2 acute, 5 subacute, and 16 chronic) were treated with the MFM. Primary endpoints of rupture or dissection-related death, overall mortality, and reintervention were evaluated using the Kaplan-Meier method; estimates for freedom from the endpoints are reported with the 95% confidence interval (CI). Secondary outcomes included technical success, adverse events, and aortic remodeling. Clinical and imaging data were collected preoperatively, directly postoperatively, and annually to 36 months for analysis using computational fluid dynamics (CFD). Results Initial technical success was 91.3%. The estimates of the endpoints at 12 months were 100% for freedom from rupture or aortic-related death, 95.7% for freedom from overall mortality, and 91.3% for freedom from reintervention. No device-related neurological or systemic complications occurred, and no additional reinterventions were needed during follow-up. A total of 144 branches overstented by the MFM remained patent. Morphologic analysis of the aortic dissection showed progressive true lumen volume increase (75.9%, p<0.001) with concomitant false lumen volume decrease (42.8%, p<0.001); the CFD analyses showed increased laminar flow. Conclusion In the current series, the MFM provided a safe and feasible treatment option for complicated acute, subacute, and chronic type B aortic dissections, with high technical success, low mortality, and active aortic remodeling. Further studies should elucidate the long-term safety of the MFM and its effectiveness in a larger patient cohort.
DropSafe safety pen needle helps to prevent accidental needlesticks after injections: results of a simulated clinical study
Authors: Malinowski Mariusz , Serafin Anna , Prazmowska-Wilanowska Aleksandra 
Published: September 2020

Background: Most needlestick injuries (NSIs) result from unsafe needle devices. DropSafe safety pen needle (SPN) was designed to help prevent such injuries before, during and after use through a built-in sharps injury prevention feature (SIPF). Methods: A two-phase study was undertaken. For the pilot study, five non-healthcare users (NHCUs) performed evaluations. For the validation study, 30 evaluators comprising 10 healthcare professionals (HCPs) and 20 NHCUs performed evaluations. The aim of the study was to validate the performance of the SIPF of the SPN and to collect feedback from the evaluators on several aspects of the safety device. Participants performed simulated injections into an orange. Results: The results show that no device failures were observed, and all manipulations were performed without a needlestick or without contact with the needle after injection. The safety feature of the SPN was activated successfully. It was shown that: the label on the seal was legible; the SPNs were easy to attach to the pen injector; injections were easy to perform; it was clear when safety feature was activated; removing the SPN from the injection pen was easy; and the written instructions were easy to understand. Conclusion: The performance of the safety feature of SPN was successfully evaluated in terms of the prevention of NSIs. User feedback demonstrate that the device’s ease of use, handling and instructions for use ensure safety and effectiveness of the SPN when used as intended.