bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility and safety of nafamostat mesilate for anticoagulation in dogs
Authors: Isayama Noriko , Matsumura Goki , Uchimura Yusuke , Maeda Erika , Sasaki Kenta 
Published: November 2022

AbstractBackgroundSurgical interventions are recommended for cases of advanced mitral regurgitation, however, limited facilities are available. The most prominent complication in such procedures is heparin‐derived bleeding. An alternative anticoagulant to heparin, nafamostat mesilate (NM), can reduce the occurrence of complications associated with heparin such as bleeding or shock.ObjectivesThis study aimed to evaluate the utility and safety of using NM during anaesthesia in canines.MethodsSix healthy adult Beagle dogs were anaesthetised, and NM was administered intravenously as a 10 mg/kg bolus dose over 5 min, followed by a continuous infusion of 10 mg/kg/h over 20 min. Blood tests and blood pressure measurements were performed at 0, 5, 25 and 55 min after NM administration.ResultsActivated thromboplastin times at 0, 25 and 55 min were 13.0 ± 0.7 s, 106.7 ± 13.3 s and 28.2 ± 2.9 s, respectively, with a significant difference between 0 and 25 min (p < 0.01) only. No significant differences were observed in prothrombin time, antithrombin, fibrinogen and fibrin degradation product concentrations between timepoints. Activated clotting times (ACTs) at 0, 5, 25 and 55 min were 119.5 ± 9.6 s, 826.7 ± 78.6 s, 924.8 ± 42.4 s and 165.2 ± 13.5 s, respectively. Significant differences were observed between 0 and 5 min (p < 0.05) and between 0 and 25 min (p < 0.05). Blood pressure changes occurred in four dogs (66.7%). No other serious adverse effects were observed.ConclusionsACT results indicated that NM use in anaesthetised healthy dogs was sufficient to obtain procedural anticoagulation with minimal adverse effects. However, these preliminary data require validation in further studies on cardiopulmonary bypass surgery.
Integrating model simulation tools and cryo‐electron microscopy
Authors: Beton Joseph George , Cragnolini Tristan , Kaleel Manaz , Mulvaney Thomas , Sweeney Aaron , Topf Maya 
Published: November 2022

AbstractThe power of computer simulations, including machine‐learning, has become an inseparable part of scientific analysis of biological data. This has significantly impacted the field of cryogenic electron microscopy (cryo‐EM), which has grown dramatically since the “resolution‐revolution.” Many maps are now solved at 3–4 Å or better resolution, although a significant proportion of maps deposited in the Electron Microscopy Data Bank are still at lower resolution, where the positions of atoms cannot be determined unambiguously. Additionally, cryo‐EM maps are often characterized by a varying local resolution, partly due to conformational heterogeneity of the imaged molecule. To address such problems, many computational methods have been developed for cryo‐EM map reconstruction and atomistic model building. Here, we review the development in algorithms and tools for building models in cryo‐EM maps at different resolutions. We describe methods for model building, including rigid and flexible fitting of known models, model validation, small‐molecule fitting, and model visualization. We provide examples of how these methods have been used to elucidate the structure and function of dynamic macromolecular machines.This article is categorized under:
Structure and Mechanism > Molecular Structures
Structure and Mechanism > Computational Biochemistry and Biophysics
Software > Molecular Modeling
Synthesis, characterization and electrochemical properties of aminophosphine monodentate, ‐chelate, and ‐bridge diiron bis(monothiolate) carbonyls
Authors: Gao Xin‐Ping , Bai Shu‐Fen , Guo Ya‐Nan , Li Qian‐Li , Lü Shuang 
Published: November 2022

AbstractTo develop the biomimetic chemistry of [FeFe]‐H2ases, three new aminophosphine substituted diiron bis(monothiolate) carbonyls were synthesized by reactions of [Fe2(μ‐SBn)2(CO)6] (Bn=CH2C6H5) with aryl‐substituted aminodiphosphine (PNP) ligand (Ph2P)2NC6H4‐4‐C≡CH under two different conditions. Treatment of them in the presence of Me3NO ⋅ 2H2O at room temperature gave PNP‐chelated complex [Fe2(μ‐SBn)2(CO)4{(κ2‐Ph2P)2N(C6H4‐4‐C≡CH)}] (2) together with unexpected aminophosphine monosubstituted complex [Fe2(μ‐SBn)2(CO)5{κ1‐Ph2PNH(NC6H4‐4‐C≡CH)}](1), while treatment of them in refluxing toluene gave PNP‐bridged complex [Fe2(μ‐SBn)2(CO)4{(μ‐Ph2P)2N(C6H4‐4‐C≡CH)}] (3) as the major product. Complex 1 has two isomers (1‐anti and 1‐syn), and chelate complex 2 is the isomer of bridge complex 3. The more interesting finding is that 1‐anti and 2 can be converted into 1‐syn and 3, respectively. Complexes 1–3 were well characterized by elemental analysis, FT‐IR, NMR spectroscopy, and X‐ray diffraction analyses. In addition, electrochemical and electrocatalytic properties of 1–3 were studied by cyclic voltammetry (CV).
Marine Geology of Kuwait
Authors: Karam Qusaie Ebrahim 
Published: November 2022

AbstractKuwait marine geology can be directly or indirectly influenced by various environmental, anthropogenic, industrial, and geomorphological factors continuously altering its nature and affecting its numerous compartments like fauna/flora, water chemistry, physical oceanography, etc. In this chapter, we attempted to describe salient characteristics about Kuwait onshore, and offshore marine geology from historical and modern perspectives. It highlights unique and dynamic ecological and geological factors that are continuously influencing its nature concerning local and transboundary environmental impacts in addition to the significantly booming oil industry that is persistently transforming Kuwait’s marine geology.
Geo- and Environmental Hazard Studies in Kuwait
Authors: Al-Awadhi Jasem Mohammed , Abd el-aal Abd el-aziz Khairy , Misak Raafat , Abdulhadi Ahmed 
Published: November 2022

AbstractLow magnitude Earthquakes are the most natural hazard facing Kuwait, while other environmental challenges such as flooding, dust fallout, land degradation, and aeolian sand movement often arise from human impact as well as natural factors. Because of the rapid socio-economic development in the last five decades in Kuwait, these issues cause environmental and social problems as well as economic disturbance; they are also considered natural disasters for country. The scale and intensity of the geological environment hazards are considerably increasing especially land degradation, and impacting on the harsh structure of desert ecosystem. Due to fragility of the desert environment, human activities exceeding the carrying capability of the geo-environment system can easily lead to geological and environmental hazards; such as runoff, sand and dunes movements and dust fallout causing serial environmental and health impacts. Geographic Information System (GIS) has been used to evaluate the degrees of geological hazard and risk by producing maps for each hazard; seismic, sand potentiality, hydrologic risk, land degradation, and sand drift severity maps are produced.
Ca2+ binding to synapsin I regulates resting Ca2+ and recovery from synaptic depression in nerve terminals
Authors: Moschetta Matteo , Ravasenga Tiziana , De Fusco Antonio , Maragliano Luca , Aprile Davide , Orlando Marta , Sacchetti Silvio , Casagrande Silvia , Lignani Gabriele , Fassio Anna , Baldelli Pietro , Benfenati Fabio 
Published: November 2022

AbstractSynapsin I (SynI) is a synaptic vesicle (SV)-associated phosphoprotein that modulates neurotransmission by controlling SV trafficking. The SynI C-domain contains a highly conserved ATP binding site mediating SynI oligomerization and SV clustering and an adjacent main Ca2+ binding site, whose physiological role is unexplored. Molecular dynamics simulations revealed that the E373K point mutation irreversibly deletes Ca2+ binding to SynI, still allowing ATP binding, but inducing a destabilization of the SynI oligomerization interface. Here, we analyzed the effects of this mutation on neurotransmitter release and short-term plasticity in excitatory and inhibitory synapses from primary hippocampal neurons. Patch-clamp recordings showed an increase in the frequency of miniature excitatory postsynaptic currents (EPSCs) that was totally occluded by exogenous Ca2+ chelators and associated with a constitutive increase in resting terminal Ca2+ concentrations. Evoked EPSC amplitude was also reduced, due to a decreased readily releasable pool (RRP) size. Moreover, in both excitatory and inhibitory synapses, we observed a marked impaired recovery from synaptic depression, associated with impaired RRP refilling and depletion of the recycling pool of SVs. Our study identifies SynI as a novel Ca2+ buffer in excitatory terminals. Blocking Ca2+ binding to SynI results in higher constitutive Ca2+ levels that increase the probability of spontaneous release and disperse SVs. This causes a decreased size of the RRP and an impaired recovery from depression due to the failure of SV reclustering after sustained high-frequency stimulation. The results indicate a physiological role of Ca2+ binding to SynI in the regulation of SV clustering and trafficking in nerve terminals.
Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis
Authors: Morton Jedidiah I. , Marquina Clara , Shaw Jonathan E. , Liew Danny , Polkinghorne Kevan R. , Ademi Zanfina , Magliano Dianna J. 
Published: November 2022

Abstract
Aims/hypothesis
Whether sodium–glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs.

Methods
We designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained.

Results
The numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs.

Conclusions/interpretation
At current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.

Graphical abstract
The Coven–Meyerowitz tiling conditions for 3 odd prime factors
Authors: Łaba Izabella , Londner Itay 
Published: November 2022

AbstractIt is well known that if a finite set $$A\subset \mathbb {Z}$$

A
⊂
Z

tiles the integers by translations, then the translation set must be periodic, so that the tiling is equivalent to a factorization $$A\oplus B=\mathbb {Z}_M$$

A
⊕
B
=

Z
M

of a finite cyclic group. We are interested in characterizing all finite sets $$A\subset \mathbb {Z}$$

A
⊂
Z

that have this property. Coven and Meyerowitz (J Algebra 212:161–174, 1999) proposed conditions (T1), (T2) that are sufficient for A to tile, and necessary when the cardinality of A has at most two distinct prime factors. They also proved that (T1) holds for all finite tiles, regardless of size. It is not known whether (T2) must hold for all tilings with no restrictions on the number of prime factors of |A|. We prove that the Coven–Meyerowitz tiling condition (T2) holds for all integer tilings of period $$M=(p_ip_jp_k)^2$$

M
=

(

p
i

p
j

p
k

)

2

, where $$p_i,p_j,p_k$$

p
i

,

p
j

,

p
k

are distinct odd primes. The proof also provides a classification of all such tilings.
Predicting clinically significant prostate cancer with a deep learning approach: a multicentre retrospective study
Authors: Zhao Litao , Bao Jie , Qiao Xiaomeng , Jin Pengfei , Ji Yanting , Li Zhenkai , Zhang Ji , Su Yueting , Ji Libiao , Shen Junkang , Zhang Yueyue , Niu Lei , Xie Wanfang , Hu Chunhong , Shen Hailin , Wang Ximing , Liu Jiangang , Tian Jie 
Published: November 2022

Abstract

Purpose
This study aimed to develop deep learning (DL) models based on multicentre biparametric magnetic resonance imaging (bpMRI) for the diagnosis of clinically significant prostate cancer (csPCa) and compare the performance of these models with that of the Prostate Imaging and Reporting and Data System (PI-RADS) assessment by expert radiologists based on multiparametric MRI (mpMRI).

Methods
We included 1861 consecutive male patients who underwent radical prostatectomy or biopsy at seven hospitals with mpMRI. These patients were divided into the training (1216 patients in three hospitals) and external validation cohorts (645 patients in four hospitals). PI-RADS assessment was performed by expert radiologists. We developed DL models for the classification between benign and malignant lesions (DL-BM) and that between csPCa and non-csPCa (DL-CS). An integrated model combining PI-RADS and the DL-CS model, abbreviated as PIDL-CS, was developed. The performances of the DL models and PIDL-CS were compared with that of PI-RADS.

Results
In each external validation cohort, the area under the receiver operating characteristic curve (AUC) values of the DL-BM and DL-CS models were not significantly different from that of PI-RADS (P > 0.05), whereas the AUC of PIDL-CS was superior to that of PI-RADS (P < 0.05), except for one external validation cohort (P > 0.05). The specificity of PIDL-CS for the detection of csPCa was much higher than that of PI-RADS (P < 0.05).

Conclusion
Our proposed DL models can be a potential non-invasive auxiliary tool for predicting csPCa. Furthermore, PIDL-CS greatly increased the specificity of csPCa detection compared with PI-RADS assessment by expert radiologists, greatly reducing unnecessary biopsies and helping radiologists achieve a precise diagnosis of csPCa.
Der Nationale Kompetenzbasierte Lernzielkatalog Medizin NKLM 2.0 – Auswirkungen auf die Lehre in der Augenheilkunde
Authors: Plange Niklas , Feltgen Nicolas ,   Arbeitsgemeinschaft Lehre, Feltgen Nicolas , Bartz-Schmidt Karl Ulrich , Beyer Tabea , Hedergott Andrea , Holz Frank , Käsmann-Kellner Barbara , Lauermann Jost Lennart , Maier Philip , Mercieca Karl , Pitz Susanne , Plange Niklas , Salchow Daniel J. , Schmack Ingo , Stahl Andreas , Stasik Isabel 
Published: November 2022

Zusammenfassung
Hintergrund
Der „Masterplan Medizin 2020“ umfasst eine 2017 verabschiedete politische Agenda von grundlegenden Veränderungen der medizinischen Ausbildung. Der Nationale Kompetenzbasierte Lernkatalog Medizin (NKLM) soll die inhaltliche Grundlage für diese Neustrukturierungen darstellen und wird in einer neuen Approbationsordnung rechtsverbindlich werden.

Methode
Der NKLM 2.0 wurde Ende 2021 verabschiedet. Die Grundlage ist ein kompetenzbasiertes Lernzielkonzept, welches die Arzt-Patienten-Kommunikation in das Zentrum des ärztlichen Handelns stellt. Die Struktur des NKLM soll dargestellt und die für die Lehre in der Augenheilkunde relevanten Inhalte sollen als Übersicht aufgearbeitet werden.

Ergebnisse
Spezifische Inhalte für die Lehre der Augenheilkunde finden sich in den Kapiteln V „Konsultationsanlässe“, Kapitel VI „Erkrankungen“, Kapitel VII „Übergeordnete und krankheitsbezogene Lernziele“ und Kapitel VIII „Übergeordnete Kompetenzen“. Die Kapitel werden stichpunktartig dargestellt.

Schlussfolgerung
Der NKLM 2.0 hat eine komplexe Struktur, die auf den ersten Blick nicht einfach zu durchdringen ist. Für die inhaltliche Neustrukturierung der Lehre der Augenheilkunde ist es notwendig, dass die Inhalte des NKLM 2.0 in der entsprechenden Tiefe vermittelt werden, da dieser in Zukunft rechtsverbindlich sein wird. Er bietet dennoch genug inhaltlichen Freiraum, um die Lerntiefe und die Lehre im Detail nicht einzuengen.
Endothelial dysfunction as a factor leading to arterial hypertension
Authors: Drożdż Dorota , Drożdż Monika , Wójcik Małgorzata 
Published: November 2022

Abstract
Hypertension remains the main cause of cardiovascular complications leading to increased mortality. The discoveries of recent years underline the important role of endothelial dysfunction (ED) in initiating the development of arterial hypertension. The endothelium lines the interior of the entire vascular system in the body and acts as a physical barrier between blood and tissues. Substances and mediators produced by the endothelium exhibit antithrombotic and anti-inflammatory properties. Oxidative stress and inflammation are conditions that damage the endothelium and shift endothelial function from vasoprotective to vasoconstrictive, prothrombotic, and pro-apoptotic functions. A dysfunctional endothelium contributes to the development of hypertension and further cardiovascular complications. Reduced nitric oxide (NO) bioavailability plays an essential role in the pathophysiology of ED-associated hypertension. New technologies provide tools to identify pathological changes in the structure and function of the endothelium. Endothelial dysfunction (ED) contributes to the development of arterial hypertension and should be considered in therapeutic strategies for children with hypertension.
Humoral immune response and live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant after COVID-19 mRNA vaccination in children and young adults with chronic kidney disease
Authors: Stich Maximilian , Di Cristanziano Veronica , Tönshoff Burkhard , Weber Lutz Thorsten , Dötsch Jörg , Rammer Marian Theodor , Rieger Susanne , Heger Eva , Garbade Sven F. , Burgmaier Kathrin , Benning Louise , Speer Claudius , Habbig Sandra , Haumann Sophie 
Published: November 2022

Abstract
Background
Data on humoral immune response to standard COVID-19 vaccination are scarce in adolescent patients and lacking for children below 12 years of age with chronic kidney disease including kidney transplant recipients.

Methods
We therefore investigated in this retrospective two-center study (DRKS00024668; registered 23.03.2021) the humoral immune response to a standard two-dose mRNA vaccine regimen in 123 CKD patients aged 5–30 years. A live-virus assay was used to assess the serum neutralizing activity against the SARS-CoV-2 omicron (BA.1) variant.

Results
Children aged 5–11 years had a comparable rate and degree of immune response to adolescents despite lower vaccine doses (10 µg vs. 30 µg BNT162b2). Treatment with two (odds ratio 9.24) or three or more (odds ratio 17.07) immunosuppressants was an independent risk factor for nonresponse. The immune response differed significantly among three patient cohorts: 48 of 77 (62.3%) kidney transplant recipients, 21 of 26 (80.8%) patients on immunosuppressive therapy, and 19 of 20 (95.0%) patients with chronic kidney disease without immunosuppressive therapy responded. In the kidney transplant recipients, immunosuppressive regimens comprising mycophenolate mofetil, an eGFR of < 60 mL/min/1.73 m2, and female sex were independent risk factors for nonresponse. Two of 18 (11.1%) and 8 of 16 (50.0%) patients with an anti-S1-RBD IgG of 100–1411 and > 1411 BAU/mL, respectively, showed a neutralization activity against the omicron variant.

Conclusion
A standard mRNA vaccine regimen in immunosuppressed children and adolescents with kidney disease elicits an attenuated humoral immune response with effective live virus neutralization against the omicron variant in approximately 10% of the patients, underlying the need for omicron-adapted vaccination.

Graphical abstract
Normative values of renin and aldosterone in clinically stable preterm neonates
Authors: Xu James Haiyang , Bariciak Erika , Harrison Mary-Ann , Broom Margaret , Lemyre Brigitte , Webster Richard J. , Weiler Gabrielle , Dahlstrom Jane E. , Kent Alison 
Published: November 2022

Abstract
Background
There is a paucity of literature on the normative levels of plasma renin concentration (PRC) and serum aldosterone (SA) in premature neonates. This study aims to provide normative data on PRC and SA levels in preterm neonates in the first 2 weeks after birth and explore associations with maternal, perinatal, or postnatal factors.

Methods
Neonates born at 26- to 34-week gestation were recruited from two neonatal intensive care units in Canada and Australia. The direct renin assay PRC and SA were analyzed on day 1 and days 14–21 after birth to compare across categorical variables and to produce normative values.

Results
A total of 262 subjects were enrolled from the Canadian (29%) and Australian (71%) sites. The mean gestational age was 30 weeks, with a mean birth weight of 1457 g. The normative values of PRC and SA for neonates born between 26 + 0 and 29 + 6 weeks and 30 + 0 and 34 + 0 weeks of gestation were produced for day 1 and day 14–21 after birth. Both PRC and SA increased from day 1 to day 14–21. The more premature neonates reached a higher PRC on days 14–21 after birth but exhibited lower SA levels on day 1 after birth. When comparing gender, birth weight, and maternal risk factor categories, no statistical differences in PRC or SA were found. A small but significant decrease in PRC, but not SA, was noted for neonates with placental pathology.

Conclusions
This study produced normative values of PRA and SA in clinically stable preterm neonates that can be referenced for use in clinical practice.

Graphical Abstract