bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the COVID‐19 pandemic on urological cancers: The surgical experience of two cancer hubs in London and Milan
Authors: Monroy‐Iglesias Maria J. , Rai Sonpreet , Mistretta Francesco A. , Roberts Graham , Dickinson Harvey , Russell Beth , Moss Charlotte , De Berardinis Rita , Ferro Matteo , Musi Gennaro , Brown Christian , Nair Rajesh , Thurairaja Ramesh , Fernando Archana , Cathcart Paul , Khan Azhar , Dasgupta Prokar , Malde Sachin , Hadijpavlou Marios , Dolly Saoirse , Haire Kate , Tagliabue Marta , de Cobelli Ottavio , Challacombe Ben , Van Hemelrijck Mieke 
Published: January 2022

AbstractObjectiveTo report on the outcomes of urological cancer patients undergoing radical surgery between March–September 2020 (compared with 2019) in the European Institute of Oncology (IEO) in Milan and the South East London Cancer Alliance (SELCA).Materials and MethodsSince March 2020, both institutions implemented a COVID‐19 minimal ‘green’ pathway, whereby patients were required to isolate for 14 days prior to admission and report a negative COVID‐19 polymerase chain reaction (PCR) test within 3 days of surgery. COVID‐19 positive patients had surgery deferred until a negative swab. Surgical outcomes assessed were: American Society of Anaesthesiologists (ASA) grade; surgery time; theatre time; intensive care unit (ICU) stay >24 h; pneumonia; length of stay (LOS); re‐admission. Postoperative COVID‐19 infection rates and associated mortality were also recorded.ResultsAt IEO, uro‐oncological surgery increased by 4%, as compared with the same period in 2019 (n = 515 vs. 534). The main increase was observed for renal (16%, n = 98 vs. 114), bladder (24%, n = 45 vs. 56) and testicular (27%, n = 26 vs. 33). Patient demographics were all comparable between 2019 and 2020. Only one bladder cancer patient developed COVID‐19, reporting mild/moderate disease. There was no COVID‐19 associated mortality. In the SELCA cohort, uro‐oncological surgery declined by 23% (n = 403 vs. 312) compared with the previous year. The biggest decrease was seen for prostate (−42%, n = 156 vs. 91), penile (−100%, n = 4 vs. 0) and testicular cancers (−46%, n = 35 vs. 24). Various patient demographic characteristics were notably different when comparing 2020 versus 2019. This likely reflects the clinical decision of deferring COVID‐19 vulnerable patients. One patient developed COVID‐19, with no COVID‐19 related mortality.ConclusionThe COVID‐19 minimal ‘green’ pathways that were put in place have shown to be safe for uro‐oncological patients requiring radical surgery. There were limited complications, almost no peri‐operative COVID‐19 infection and no COVID‐19‐related mortality in either cohort.
Direct capture and selective elution of a secreted polyglutamate‐tagged nanobody using bare magnetic nanoparticles
Authors: Zanker Alexander A. , Stargardt Patrick , Kurzbach Sophie C. , Turrina Chiara , Mairhofer Juergen , Schwaminger Sebastian P. , Berensmeier Sonja 
Published: January 2022

AbstractBackgroundThe secretion and direct capture of proteins from the extracellular medium is a promising approach for purification, thus enabling integrated bioprocesses.Major ResultsWe demonstrate the secretion of a nanobody (VHH) to the extracellular medium (EM) and its direct capture by bare, non‐functionalized magnetic nanoparticles (MNPs). An ompA signal peptide for periplasmic localization, a polyglutamate‐tag (E8) for selective MNP binding, and a factor Xa protease cleavage site were fused N‐terminally to the nanobody. The extracellular production of the E8‐VHH (36 mg L–1) was enabled using a growth‐decoupled Escherichia coli‐based expression system. The direct binding of E8‐VHH to the bare magnetic nanoparticles was possible and could be drastically improved up to a yield of 88% by adding polyethylene glycol (PEG). The selectivity of the polyglutamate‐tag enabled a selective elution of the E8‐VHH from the bare MNPs while raising the concentration factor (5x) and purification factor (4x) significantly.ConclusionOur studies clearly show that the unique combination of a growth‐decoupled E. coli secretion system, the polyglutamate affinity tag, non‐functionalized magnetic nanoparticles, and affinity magnetic precipitation is an innovative and novel way to capture and concentrate nanobodies.
Titer improvement of milbemycins via coordinating metabolic competition and transcriptional co‐activation controlled by Streptomyces antibiotic regulatory protein family regulator in Streptomyces bingchenggensis
Authors: Wang Haiyan , Liu Yuqing , Cheng Xu , Zhang Yanyan , Li Shanshan , Wang Xiangjing , Xiang Wensheng 
Published: January 2022

AbstractStreptomyces bingchenggensis is a promising producer of milbemycins (MILs), the macrolide pesticide used widely in agriculture. The relationship between different biosynthetic gene clusters (BGCs) and the MIL BGC remains unclear, which hinders the precise metabolic engineering of S. bingchenggensis for titer improvement. To address this issue, this study discovered the regulatory function of a previously unidentified regulator KelR on a type‐II polyketide BGC, MIL BGC, and two other BGCs, and caused titer improvement. First, a type II polyketide synthase (PKS) gene cluster kel with a bidirectional effect on MIL biosynthesis was found using transcriptome analysis. A Streptomyces antibiotic regulatory protein (SARP) family regulator KelR from the kel cluster was then characterized as an activator of several BGCs including mil and kel clusters. Metabolic competition between mil and kel clusters at the late fermentation stage was confirmed. Finally, KelR and those BGCs were manipulated in S. bingchenggensis, which led to a 71.7% titer improvement of MIL A3/A4 to 4058.2 ± 71.0 mg/L. This study deciphered the regulatory function of a previously unidentified regulatory protein KelR on several BGCs including mil in S. bingchenggensis and provided an example of coordinating metabolic competition and coregulation for titer improvement of secondary metabolites.
The pH‐Dependence of the Hydration of 5‐Formylcytosine: an Experimental and Theoretical Study
Authors: Zott Fabian L. , Korotenko Vasily , Zipse Hendrik 
Published: January 2022

Abstract5‐Formylcytosine is an important nucleobase in epigenetic regulation, whose hydrate form has been implicated in the formation of 5‐carboxycytosine as well as oligonucleotide binding events. The hydrate content of 5‐formylcytosine and its uracil derivative has now been quantified using a combination of NMR and mass spectroscopic measurements as well as theoretical studies. Small amounts of hydrate can be identified for the protonated form of 5‐formylcytosine and for neutral 5‐formyluracil. For neutral 5‐formylcytosine, however, direct detection of the hydrate was not possible due to its very low abundance. This is in full agreement with theoretical estimates.
Furfural Adsorption and Hydrogenation at the Oxide‐Metal Interface: Evidence of the Support Influence on the Selectivity of Iridium‐Based Catalysts
Authors: Campisi Sebastiano , Motta Davide , Barlocco Ilaria , Stones Rebecca , Chamberlain Thomas W. , Chutia Arunabhiram , Dimitratos Nikolaos , Villa Alberto 
Published: January 2022

AbstractHere, tetrakis(hydroxymethyl)phosphonium chloride‐protected colloidal iridium nanoparticles were deposited by sol‐immobilisation on three different supports (CeO2, NiO and TiO2) and were investigated for the liquid‐phase direct hydrogenation (H2 atmosphere) and catalytic transfer hydrogenation – CTH (N2 atmosphere) of furfural to study the effect of the H donor. The occurrence of strong‐metal support interactions in 1 wt % Ir/CeO2 catalyst, as disclosed by XPS, was revealed to be responsible for the high activity observed in the direct hydrogenation (81 % conversion after 6 h) and for the unusual selectivity to 2‐methylfuran (70 %) under CTH conditions. On the other hand, Ir/NiO showed peculiar selectivity to tetrahydrofurfuryl alcohol in both H2 and N2 atmospheres (71 % and 70 %, respectively). The density functional theory calculations further showed that the unique selectivity of Ir/NiO may be ascribed to the adsorption properties of furfural on the support, which activates a dual‐site hydrogenation mechanism.
Exploring the Association of Electron‐Donating Corroles with Phthalocyanines as Electron Acceptors
Authors: Platzer Benedikt , Berionni Berna Beatrice , Bischetti Martina , Cicero Daniel O. , Paolesse Roberto , Nardis Sara , Torres Tomás , Guldi Dirk M. 
Published: January 2022

AbstractElectron‐donating corroles (Cor) were integrated with electron‐accepting phthalocyanines (Pc) to afford two different non‐covalent Cor ⋅ Pc systems. At the forefront was the coordination between a 10‐meso‐pyridine Cor and a ZnPc. The complexation was corroborated in a combination of NMR, absorption, and fluorescence assays, and revealed association with binding constants as high as 106 m−1. Steady‐state and time‐resolved spectroscopies evidenced that regardless of exciting Cor or Pc, the charge‐separated state evolved efficiently in both cases, followed by a slow charge‐recombination to reinstate the ground state. The introduction of non‐covalent linkages between Cor and Pc induces sizeable differences in the context of light harvesting and transfer of charges when compared with covalently linked Cor‐Pc conjugates.
Analysis of a novel immune checkpoint, Siglec‐15, in pancreatic ductal adenocarcinoma
Authors: Chen Xianlong , Mo Shengwei , Zhang Yue , Ma Heng , Lu Zhaohui , Yu Shuangni , Chen Jie 
Published: January 2022

AbstractSiglec‐15, a novel immune checkpoint, is an emerging target for next‐generation cancer immunotherapy. However, the role of Siglec‐15 in pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We investigated the expression of Siglec‐15 and its association with clinicopathological characteristics, programmed cell death‐ligand 1 (PD‐L1), immune cells, and DNA damage repair (DDR) molecules in a cohort of 291 patients with PDAC. Positive tumour cell expression of Siglec‐15 and PD‐L1 was observed in 18.6 and 30.3% of the samples, respectively. We also detected Siglec‐15 positivity in macrophages in 3.4% of patients. Co‐expression of Siglec‐15 with PD‐L1 was observed in 6.1% of the patients. A total of 33 PD‐L1‐negative samples (18.0%) were Siglec‐15‐positive. Siglec‐15 was observed more frequently in moderate‐to‐well‐differentiated tumours. Siglec‐15 was associated with a low density of Tregs and CD45RO T cells, high BRCA1 expression, and improved survival. Both Siglec‐15 and PD‐L1 are independent factors of patient outcomes. The prognostic significance of Siglec‐15 for survival was more discriminative in lymph node‐negative, high BRCA1 expression, or low BRCA2 expression tumours than in lymph node‐positive, low BRCA1 expression, or high BRCA2 expression tumours. In conclusion, we identified Siglec‐15 as a promising predictor for prognosis combined with different DDR molecular statuses and complex tumour‐infiltrating cells in PDAC. Targeting Siglec‐15 may be a novel therapeutic option for patients who are unresponsive to anti‐PD‐1 therapy. Future studies are needed to validate the prognostic significance of Siglec‐15 and to investigate its regulatory mechanisms in this disease.
Growth and Genetic Manipulation of Entamoeba histolytica
Authors: Suleiman Rene L. , Ralston Katherine S. 
Published: January 2022

AbstractEntamoeba histolytica is a parasitic protozoan and the causative agent of amoebiasis in humans. Amoebiasis has a high incidence of disease, resulting in ∼67,900 deaths per year, and it poses a tremendous burden of morbidity and mortality in children. Despite its importance, E. histolytica is an understudied parasite. These protocols describe the in vitro growth, maintenance, cryopreservation, genetic manipulation, and cloning of axenic E. histolytica trophozoites. There has been significant progress in genetic manipulation of this organism over the past decade, and these protocols outline the ways in which these advances can be implemented. © 2022 Wiley Periodicals LLC.Basic Protocol 1: Culturing E. histolytica trophozoitesSupport Protocol 1: Preparation of TYI‐S‐33 mediumSupport Protocol 2: Lot testing of Biosate peptone and adult bovine serum for TYI‐S‐33 mediumBasic Protocol 2: Cryopreservation of E. histolytica trophozoitesSupport Protocol 3: Preparation of cryoprotectant solutionsBasic Protocol 3: Transfection of E. histolytica trophozoites with Attractene reagentBasic Protocol 4: Creating clonal lines using limiting dilutionBasic Protocol 5: Knockdown of one to two genes with trigger‐induced RNA interferenceSupport Protocol 4: Evaluation of RNA interference knockdown with reverse transcriptase PCRBasic Protocol 6: E. histolytica growth curves
High step‐up buck–boost DC–DC converter with coupled inductor and low component count for distributed PV generation systems
Authors: Toebe Ademir , Miguel Klein Faistel Tiago , Manuel Santos Spencer Andrade António 
Published: January 2022

AbstractThis paper presents a non‐isolated high step‐up buck–boost with a coupled inductor DC–DC converter relevant for distributed photovoltaic (PV) generation systems. The proposed topology can reach high voltage gain through the combination of a buck–boost converter with a coupled inductor. The configuration of the proposed converter allows to achieve a natural voltage clamp circuit for the switch, recovering the energy stored in the leakage inductance of the coupled inductor. Moreover, the converter allows soft‐switching conditions, that is, Zero Current Switching (ZCS) for the diodes and nearly ZCS for the active switch. Also, the proposed converter presents a low component count and common ground connection of the input and output. The proposed converter is evaluated theoretically by the principle of operation in continuous‐conduction mode (CCM) and discontinuous‐conduction mode (DCM), voltage gain derivation, external characteristics, semiconductor voltage stress, current stress, and design guidelines. Finally, a 650‐W, 36/380‐V, 50‐kHz prototype was built in the laboratory to experimentally evaluate the proposed converter, which reached a maximum efficiency rate of 96.58%.
Ranging patterns and factors associated with movement in free‐roaming domestic dogs in urban Malawi
Authors: De la Puente‐Arévalo María , Motta Paolo , Dürr Salome , Warembourg Charlotte , Nikola Christopher , Burdon‐Bailey Jordana , Mayer Dagmar , Lohr Frederic , Gibson Andy D. , Chikungwa Patrick , Chulu Julius , Gamble Luke , Anderson Neil E. , Bronsvoort Barend M deC. , Mellanby Richard J. , Mazeri Stella 
Published: January 2022

AbstractRabies is a neglected zoonotic disease that causes around 59,000 deaths per year globally. In Africa, rabies virus is mostly maintained in populations of free‐roaming domestic dogs (FRDD) that are predominantly owned. Characterizing the roaming behavior of FRDD can provide relevant information to understand disease spread and inform prevention and control interventions. To estimate the home range (HR) of FRDD and identify predictors of HR size, we studied 168 dogs in seven different areas of Blantyre city, Malawi, tracking them with GPS collars for 1–4 days. The median core HR (HR50) of FRDD in Blantyre city was 0.2 ha (range: 0.08–3.95), while the median extended HR (HR95) was 2.14 ha (range: 0.52–23.19). Multivariable linear regression models were built to identify predictors of HR size. Males presented larger HR95 than females. Dogs living in houses with a higher number of adults had smaller HR95, while those living in houses with higher number of children had larger HR95. Animals that received products of animal origin in their diets had larger HR95, and only in the case of females, animals living in low‐income areas had larger HR50 and HR95. In contrast, whether male dogs were castrated or not was not found to be associated with HR size. The results of this study may help inform rabies control and prevention interventions in Blantyre city, such as designing risk‐based surveillance activities or rabies vaccination campaigns targeting certain FRDD subpopulations. Our findings can also be used in rabies awareness campaigns, particularly to illustrate the close relationship between children and their dogs.
Comparative biogeography of volant and nonvolant mammals in a temperate island archipelago
Authors: Pichler Taylor R. , Mallinger Elyse C. , Farmer Morgan J. , Morrison Megan J. , Khadka Bijit , Matzinger Parker J. , Kirschbaum Alan , Goodwin Katy R. , Route William T. , Van Stappen Julie , Van Deelen Timothy R. , Olson Erik R. 
Published: January 2022

AbstractIsland biogeography theory is a foundational ecological concept that describes how island or habitat patch size and isolation predict biodiversity, but few have studied how the effects of island biogeography vary with life history characteristics of temperate mammal communities. From 2014 to 2020, we surveyed volant and nonvolant mammals within the Apostle Islands archipelago (Wisconsin, USA) using camera trapping, live trapping, and acoustic monitoring. We used linear regression and information‐theoretic model selection to evaluate the effects of island size and isolation on indices of biodiversity. We also examined the effects of life history characteristics (i.e., body mass, winter inactivity) on the relative abundance and distribution of each species on the islands and the mainland. For volant mammals, island size and isolation were not associated with any metrics of diversity. We found island size was positively associated with nonvolant mammal species richness and diversity, but not species evenness. Island isolation was not a significant predictor for small nonvolant mammal diversity, although both size and isolation appeared to influence island biogeography of medium‐large nonvolant mammals. We also found that the interaction between winter inactivity and body mass influenced the vagility of nonvolant mammals in the archipelago. Our results suggest that life history characteristics are important in mediating species responses to biogeography, supporting the dispersal‐limitation nonequilibrium view of island biogeography theory, particularly for nonvolant mammals.
Large herbivores in a partially migratory population search for the ideal free home
Authors: Martin Hans W. , Hebblewhite Mark , Merrill Evelyn H. 
Published: January 2022

AbstractMigration is a tactic used across taxa to access resources in temporally heterogenous landscapes. Populations that migrate can attain higher abundances because such movements allow access to higher quality resources, or reduction in predation risk resulting in increased fitness. However, most migratory species occur in partially migratory populations, a mix of migratory and non‐migratory individuals. It is thought that the portion of migrants in a partial migration population is maintained either through (1) a population‐level evolutionary stable state where counteracting density‐dependent vital rates act on migrants and residents to balance fitness or (2) conditional migration, where the propensity to migrate is influenced by the individual's state. However, in many respects, migration is also a form of habitat selection and the proportion of migrants and residents may be the result of density‐dependent habitat selection. Here, we test whether the theory of Ideal Free Distribution (IFD) can explain the coexistence of different migratory tactics in a partially migratory population. IFD predicts individuals exhibit density‐dependent vital rates and select different migratory tactics to maximize individual fitness resulting in equal fitness (λ) between tactics. We tested the predictions of IFD in a partially migratory elk population that declined by 70% with 19 years of demographic data and migratory tactic switching rates from >300 individuals. We found evidence of density dependence for resident pregnancy and adult female survival providing a fitness incentive to switch tactics. Despite differences in vital rates between migratory tactics, mean λ (fitness) was equal. However, as predicted by the IFD, individuals switched tactics toward those of higher fitness. Our analysis reveals that partial migration may be driven by tactic selection that follows the ideal free distribution. These findings reinforce that migration across taxa may be a polymorphic behavior in large herbivores where migratory tactic selection is determined by differential costs and benefits, mediated by density dependence.
Intermittent inotropic therapy with levosimendan vs. milrinone in advanced heart failure patients
Authors: Milwidsky Assi , Frydman Shir , Laufer‐Perl Michal , Sadeh Ben , Sapir Orly , Granot Yoav , Hochstadt Aviram , Korotetski Liuba , Ketchker Liora , Topilsky Yan , Banai Shmuel , Havakuk Ofer 
Published: January 2022

AbstractAimsRoutine, intermittent inotropic therapy (IIT) is still applied in advanced heart failure (HF) patients either as a bridge to definitive treatment or as a mean to improve quality of life (QOL), despite limited evidence to support its' use. Given recent reports of improved QOL and reduced HF hospitalization, with levosimendan compared with placebo in advanced HF patients, we aimed to assess the effects of switching a small group of milrinone‐treated patients to levosimendan. This was performed as part of a protocol for changing our ambulatory HF clinic milrinone‐based IIT to levosimendan.Methods and resultsSingle‐centre study of consecutive ambulatory advanced HF patients that received ≥4 cycles of once‐weekly milrinone IIT at our HF outpatient clinic, who were switched to levosimendan IIT. All patients had left ventricular ejection fraction ≤35%, elevated B‐natriuretic peptide (BNP), and were in New York Heart Association Classes III–IV despite maximally tolerated guideline directed medical therapy. Patients were evaluated using BNP levels, echocardiography, cardio‐pulmonary exercise test, and HF QOL questionnaire before and after 4 weeks of levosimendan IIT. The cohort included 11 patients, 10 (91%) were male and the mean age was 76 ± 12 years. After 4 weeks of levosimendan therapy, maximal O2 consumption improved in 8/9 (89%) by a mean of 2.28 mL/kg [95% CI −0.22–3.38, P = 0.05]. BNP levels decreased in 9/11 (82%) levosimendan treated patients, from a median of 1015 ng/L [261–1035] to 719 ng/L [294–739], (P < 0.01). QOL as measure by the EQ‐5D‐5L questionnaire improved in 8/11 (82%) patients after levosimendan IIT, by a median of two points [95% CO −4.14–0.37, P = 0.09]. On echocardiography, peak systolic annular velocity (S') increased after levosimendan IIT by an average of 3 cm/s [95% CI 0.16–2.10, P = 0.03].ConclusionsIn this small‐scale study of ambulatory advanced HF patients, we observed improvements in right ventricular systolic function, maximal O2 consumption, and BNP after switching from milrinone to levosimendan based IIT.
Application of a Ferrocene‐Based Palladacycle Precatalyst to Enantioselective Aryl‐Aryl Kumada Coupling
Authors: Arthurs Ross A. , Hughes David L. , Richards Christopher J. 
Published: January 2022

AbstractThe palladium catalysed reaction of 1‐iodo‐2‐methylnaphthalene and 2‐methyl‐1‐naphthylmagnesium bromide gave quantitatively an (Sa)‐configured cross‐coupled product in 80 % e.e. using (R,Sp)‐PPFA as a ligand. N,N‐Dimethylaminomethylferrocene was cyclopalladated (Na2PdCl4, (S)−Ac−Phe−OH, 93 % e.e., as determined by 1H NMR as a result of self‐induced non‐equivalence), and the resulting (Sp)‐configured dimeric palladacycle was employed as a precatalyst for this cross‐coupling reaction (5 mol%). Addition to the palladacycle of diphenylphosphine and subsequent base‐promoted bidentate ligand synthesis and palladium capture gave an in situ generated catalyst resulting in an (Sp)‐configured product in up to 71 % e.e.