bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of the dose range for adverse neurological effects of amiodarone in patients from an in vitro toxicity test by in vitro–in vivo extrapolation
Authors: Algharably Engi Abd el-Hady , Di Consiglio Emma , Testai Emanuela , Kreutz Reinhold , Gundert-Remy Ursula 
Published: February 2021

AbstractAmiodarone is an antiarrhythmic agent inducing adverse effects on the nervous system, among others. We applied physiologically based pharmacokinetic (PBPK) modeling combined with benchmark dose modeling to predict, based on published in vitro data, the in vivo dose of amiodarone which may lead to adverse neurological effects in patients. We performed in vitro–in vivo extrapolation (IVIVE) from concentrations measured in the cell lysate of a rat brain 3D cell model using a validated human PBPK model. Among the observed in vitro effects, inhibition of choline acetyl transferase (ChAT) was selected as a marker for neurotoxicity. By reverse dosimetry, we transformed the in vitro concentration–effect relationship into in vivo effective human doses, using the calculated in vitro area under the curve (AUC) of amiodarone as the pharmacokinetic metric. The upper benchmark dose (BMDU) was calculated and compared with clinical doses eliciting neurological adverse effects in patients. The AUCs in the in vitro brain cell culture after 14-day repeated dosing of nominal concentration equal to 1.25 and 2.5 µM amiodarone were 1.00 and 1.99 µg*h/mL, respectively. The BMDU was 385.4 mg for intravenous converted to 593 mg for oral application using the bioavailability factor of 0.65 as reported in the literature. The predicted dose compares well with neurotoxic doses in patients supporting the hypothesis that impaired ChAT activity may be related to the molecular/cellular mechanisms of amiodarone neurotoxicity. Our study shows that predicting effects from in vitro data together with IVIVE can be used at the initial stage for the evaluation of potential adverse drug reactions and safety assessment in humans.
Khovanov homotopy type, periodic links and localizations
Authors: Borodzik Maciej , Politarczyk Wojciech , Silvero Marithania 
Published: February 2021

AbstractGiven an m-periodic link $$L\subset S^3$$

L
⊂

S
3

, we show that the Khovanov spectrum $$\mathcal {X}_L$$

X
L

constructed by Lipshitz and Sarkar admits a group action. We relate the Borel cohomology of $$\mathcal {X}_L$$

X
L

to the equivariant Khovanov homology of L constructed by the second author. The action of Steenrod algebra on the cohomology of $$\mathcal {X}_L$$

X
L

gives an extra structure of the periodic link. Another consequence of our construction is an alternative proof of the localization formula for Khovanov homology, obtained first by Stoffregen and Zhang. By applying the Dwyer–Wilkerson theorem we express Khovanov homology of the quotient link in terms of equivariant Khovanov homology of the original link.
Solution to a problem of FitzGerald
Authors: Hemelaer Jens , Rogers Morgan 
Published: February 2021

AbstractFitzGerald identified four conditions (RI), (UR), (RI*) and (UR*) that are necessarily satisfied by an algebra if its monoid of endomorphisms has commuting idempotents. We show that these conditions are not sufficient, by giving an example of an algebra satisfying the four properties, such that its monoid of endomorphisms does not have commuting idempotents. This settles a problem presented by FitzGerald at the Conference and Workshop on General Algebra and Its Applications in 2013 and more recently at the workshop NCS 2018. After giving the counterexample, we show that the properties (UR), (RI*) and (UR*) depend only on the monoid of endomorphisms of the algebra, and that the counterexample we gave is in some sense the easiest possible. Finally, we list some categories in which FitzGerald’s question has an affirmative answer.
Assessing Biotic and Abiotic Interactions of Microorganisms in Amazonia through Co-Occurrence Networks and DNA Metabarcoding
Authors: Ritter Camila Duarte , Forster Dominik , Azevedo Josue A. R. , Antonelli Alexandre , Nilsson R. Henrik , Trujillo Martha E. , Dunthorn Micah 
Published: February 2021

AbstractSpecies may co-occur due to responses to similar environmental conditions, biological associations, or simply because of coincident geographical distributions. Disentangling patterns of co-occurrence and potential biotic and abiotic interactions is crucial to understand ecosystem function. Here, we used DNA metabarcoding data from litter and mineral soils collected from a longitudinal transect in Amazonia to explore patterns of co-occurrence. We compared data from different Amazonian habitat types, each with a characteristic biota and environmental conditions. These included non-flooded rainforests (terra-firme), forests seasonally flooded by fertile white waters (várzeas) or by unfertile black waters (igapós), and open areas associated with white sand soil (campinas). We ran co-occurrence network analyses based on null models and Spearman correlation for all samples and for each habitat separately. We found that one third of all operational taxonomic units (OTUs) were bacteria and two thirds were eukaryotes. The resulting networks were nevertheless mostly composed of bacteria, with fewer fungi, protists, and metazoans. Considering the functional traits of the OTUs, there is a combination of metabolism modes including respiration and fermentation for bacteria, and a high frequency of saprotrophic fungi (those that feed on dead organic matter), indicating a high turnover of organic material. The organic carbon and base saturation indices were important in the co-occurrences in Amazonian networks, whereas several other soil properties were important for the co-exclusion. Different habitats had similar network properties with some variation in terms of modularity, probably associated with flooding pulse. We show that Amazonian microorganism communities form highly interconnected co-occurrence and co-exclusion networks, which highlights the importance of complex biotic and abiotic interactions in explaining the outstanding biodiversity of the region.
Outcomes of clinical utility in amyloid-PET studies: state of art and future perspectives
Authors: Cotta Ramusino Matteo , Perini Giulia , Altomare Daniele , Barbarino Paola , Weidner Wendy , Salvini Porro Gabriella , Barkhof Frederik , Rabinovici Gil D. , van der Flier Wiesje M. , Frisoni Giovanni B. , Garibotto Valentina , Teipel Stefan , Boccardi Marina 
Published: February 2021

Abstract
Purpose
To review how outcomes of clinical utility are operationalized in current amyloid-PET validation studies, to prepare for formal assessment of clinical utility of amyloid-PET-based diagnosis.

Methods
Systematic review of amyloid-PET research studies published up to April 2020 that included outcomes of clinical utility. We extracted and analyzed (a) outcome categories, (b) their definition, and (c) their methods of assessment.

Results
Thirty-two studies were eligible. (a) Outcome categories were clinician-centered (found in 25/32 studies, 78%), patient-/caregiver-centered (in 9/32 studies, 28%), and health economics-centered (5/32, 16%). (b) Definition: Outcomes were mainly defined by clinical researchers; only the ABIDE study expressly included stakeholders in group discussions. Clinician-centered outcomes mainly consisted of incremental diagnostic value (25/32, 78%) and change in patient management (17/32, 53%); patient-/caregiver-centered outcomes considered distress after amyloid-pet-based diagnosis disclosure (8/32, 25%), including quantified burden of procedure for patients’ outcomes (n = 8) (1/8, 12.5%), impact of disclosure of results (6/8, 75%), and psychological implications of biomarker-based diagnosis (75%); and health economics outcomes focused on costs to achieve a high-confidence etiological diagnosis (5/32, 16%) and impact on quality of life (1/32, 3%). (c) Assessment: all outcome categories were operationalized inconsistently across studies, employing 26 different tools without formal rationale for selection.

Conclusion
Current studies validating amyloid-PET already assessed outcomes for clinical utility, although non-clinician-based outcomes were inconsistent. A wider participation of stakeholders may help produce a more thorough and systematic definition and assessment of outcomes of clinical utility and help collect evidence informing decisions on reimbursement of amyloid-PET.
Multi-scale optoacoustic molecular imaging of brain diseases
Authors: Razansky Daniel , Klohs Jan , Ni Ruiqing 
Published: February 2021

AbstractThe ability to non-invasively visualize endogenous chromophores and exogenous probes and sensors across the entire rodent brain with the high spatial and temporal resolution has empowered optoacoustic imaging modalities with unprecedented capacities for interrogating the brain under physiological and diseased conditions. This has rapidly transformed optoacoustic microscopy (OAM) and multi-spectral optoacoustic tomography (MSOT) into emerging research tools to study animal models of brain diseases. In this review, we describe the principles of optoacoustic imaging and showcase recent technical advances that enable high-resolution real-time brain observations in preclinical models. In addition, advanced molecular probe designs allow for efficient visualization of pathophysiological processes playing a central role in a variety of neurodegenerative diseases, brain tumors, and stroke. We describe outstanding challenges in optoacoustic imaging methodologies and propose a future outlook.
Surgical Outcome of Pancreaticoduodenectomy in Patients with a History of Roux‐en‐Y Reconstruction after Tumor Removal
Authors: Marukawa Daiki , Tomimaru Yoshito , Kobayashi Shogo , Iwagami Yoshifumi , Yamada Daisaku , Akita Hirofumi , Noda Takehiro , Gotoh Kunihito , Doki Yuichiro , Eguchi Hidetoshi 
Published: February 2021

AbstractBackgroundThe need for pancreaticoduodenectomy (PD) after Roux‐en‐Y (RY) reconstruction after tumor removal is expected to increase in future, but current studies on outcome are sparse. This surgery is challenging, due to intraabdominal adhesions and/or anatomical changes introduced by the previous abdominal surgery. Here, we investigated the surgical outcomes of PD after RY reconstruction following tumor removal.MethodsWe enrolled 283 patients that underwent PD. Surgical outcomes for PD were compared between patients with or without a history of RY reconstruction after tumor removal. Outcomes were also compared between two different surgical procedures for the post‐PD reconstruction.ResultsAmong 283 patients, 11 had a history of RY reconstruction after tumor removal (3.9%). Among these, RY reconstructions had been performed where the small intestine was anastomosed to a remnant stomach after distal gastrectomy (n = 2), to remnant stomach after proximal gastrectomy (n = 1), to the esophagus after total gastrectomy (n = 6), or to the hepatic duct after extrahepatic bile duct resection (n = 2). Surgical outcomes were not significantly different between cases with and without RY reconstructions. We identified two different reconstruction procedures after removing the periampullary tumor during PD. The surgical outcomes were not significantly different between these two reconstruction groups.ConclusionsThe surgical outcome of PD was not significantly affected by a history of RY reconstruction. Similarly, the type of reconstruction performed during PD did not significantly affect the outcome. These results could be useful when planning PD in patients with a history of RY reconstruction after tumor removal.
Validation of the Surgical Outcome Risk Tool (SORT) for Predicting Postoperative Mortality in Colorectal Cancer Patients Undergoing Surgery and Subgroup Analysis
Authors: Magouliotis Dimitrios E. , Walker David , Baloyiannis Ioannis , Fergadi Maria P. , Mamaloudis Ioannis , Chasiotis Georgios , Tzovaras George A. 
Published: February 2021

AbstractBackgroundThe accurate evaluation of perioperative risk is crucial to facilitate the shared decision‐making process. Surgical outcome risk tool (SORT) has been developed to provide enhanced and more feasible identification of high‐risk surgical patients. Nonetheless, SORT has not been validated for patients with colorectal cancer undergoing surgery. Our aim was to determine whether SORT can accurately predict mortality after surgery for colorectal cancer and to compare it with traditional risk models.Method526 patients undergoing surgery performed by a colorectal surgical team in a single Greek tertiary hospital (2011–2019) were included. Five risk models were evaluated: (1) SORT, (2) Physiology and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM), (3) Portsmouth POSSUM (P‐POSSUM), (4) Colorectal POSSUM (CR‐POSSUM), and (5) the Association of Great Britain and Ireland (ACPGBI) score. Model accuracy was assessed by observed to expected (O:E) ratios, and area under Receiver Operating Characteristic curve (AUC).ResultsTen patients (1.9%) died within 30 days of surgery. SORT was associated with an excellent level of discrimination [AUC:0.81 (95% CI:0.68–0.94); p = 0.001] and provided the best performing calibration of all models in the entire dataset analysis (H–L:2.82; p = 0.83). Nonetheless, SORT underestimated mortality. SORT model demonstrated excellent discrimination and calibration predicting perioperative mortality in patients undergoing (1) open surgery, (2) emergency/acute surgery, and (3) in cases with colon‐located cancer.ConclusionSORT is an easily adopted risk‐assessment tool, associated with enhanced accuracy, that could be implemented in the perioperative pathway of patients undergoing surgery for colorectal cancer.
Mono- and multispecies biofilms from a crustose coralline alga induce settlement in the scleractinian coral Leptastrea purpurea
Authors: Petersen Lars-Erik , Moeller Mareen , Versluis Dennis , Nietzer Samuel , Kellermann Matthias Y. , Schupp Peter J. 
Published: February 2021

AbstractMicroorganisms have been reported to induce settlement in various marine invertebrate larvae but their specificity of inductive capacities for the settlement of coral larvae remains poorly understood. In this study, we isolated 56 microbial strains from the crustose coralline alga (CCA) Hydrolithon reinboldii using five different media either with or without additional antibiotics and/or spiked CCA extract. We tested the isolates for their potential to induce settlement behavior in larvae of the brooding scleractinian coral Leptastrea purpurea. From these 56 CCA-associated microbial strains, we identified six bacterial classes and 18 families. The culturable bacterial community associated with H. reinboldii was dominated by Gammaproteobacteria, Actinobacteria, and Alphaproteobacteria while the Illumina MiSeq analysis showed that the culture-independent bacterial community was dominated by Gammaproteobacteria, Alphaproteobacteria, and Flavobacteria. Furthermore, we found no correlation between inductive settlement capacities and phylogenetic relationships. Instead, settlement behavior of L. purpurea larvae was induced by specific isolated species. Strains #1792 (Pseudovibrio denitrificans), #1678 (Acinetobacter pittii), #1633 (Pseudoalteromonas phenolica), #1772 (Marine bacterium LMG1), #1721 (Microbulbifer variabilis), and #1783 (Pseudoalteromonas rubra) induced settlement behavior in coral larvae at mostly high and significant levels (≥ 40%) but the remaining isolates strongly varied in their activity. Multispecies biofilms consisting of four strains (#1792, #1678, #1633, and #1721) were observed to synergistically increase settlement behavior levels (> 90%); however, the addition of #1772 to the multispecies biofilms negatively affected coral larvae and resulted in a total loss of inducing activity. The findings provide new insights into the role of bacteria in the settlement process of scleractinian corals and may help to identify the true nature of bacteria-derived morphogenic cues.
Effect of the air–sea coupled system change on the ENSO evolution from boreal spring
Authors: Fang Xiang-Hui , Zheng Fei 
Published: February 2021

AbstractRealistic simulation and accurate prediction of El Niño-Southern Oscillation (ENSO) is still a challenge. One fundamental obstacle is the so-called spring predictability barrier (SPB), which features a low predictive skill of the ENSO with prediction across boreal spring. Our observational analysis shows that the leading empirical orthogonal function mode of the seasonal Niño3.4 index evolution (i.e., from May to the following April) explains nearly 90% of its total variance, and the principle component is almost identical to the Niño3.4 index in the mature phase. This means a good ENSO prediction for a year ranging May-next April can be achieved if the Niño3.4 index in the mature phase is accurately obtained in advance. In this work, by extracting physically oriented variables in the spring, a linear regression approach that can reproduce the mature ENSO phases in observation is firstly proposed. Further investigation indicates that the specific equation, however, is significantly modulated by an interdecadal regime shift in the air–sea coupled system in the tropical Pacific. During 1980–1999, ocean adjustment and vertical processes were dominant, and the recharge oscillator theory was effective to capture the ENSO evolutions. While, during 2000–2018, zonal advection and thermodynamics became important, and successful prediction essentially relies on the wind stress information and their controlled processes, both zonally and meridionally. These results imply that accounting for the interdecadal regime shift of the tropical Pacific coupled system and the dominant processes in spring in modulating the ENSO evolution could reduce the impact of SPB and improve ENSO prediction.
Molecular clocks in ancient proteins: Do they reflect the age at death even after millennia?
Authors: Mahlke Nina Sophia , Renhart Silvia , Talaa Dorothea , Reckert Alexandra , Ritz-Timme Stefanie 
Published: February 2021

AbstractAge at death estimation in cases of human skeletal finds is an important task in forensic medicine as well as in anthropology. In forensic medicine, methods based on “molecular clocks” in dental tissues and bone play an increasing role. The question, whether these methods are applicable also in cases with post-depositional intervals far beyond the forensically relevant period, was investigated for two “protein clocks”, the accumulation of D-aspartic acid (D-Asp) and the accumulation of pentosidine (Pen) in dentine. Eight teeth of skeletons from different burial sites in Austria and with post-depositional intervals between c. 1216 and c. 8775 years were analysed. The results of age at death estimation based on D-Asp and Pen in dentine were compared to that derived from a classical morphological examination. Age at death estimation based on D-Asp resulted consistently in false high values. This finding can be explained by a post-mortem accumulation of D-Asp that may be enhanced by protein degradation. In contrast, the Pen-based age estimates fitted well with the morphological age diagnoses. The described effect of post-mortem protein degradation is negligible in forensically relevant time horizons, but not for post-depositional intervals of thousands of years. That means that the “D-Asp clock” loses its functionality with increasing post-depositional intervals, whereas Pen seems to be very stable. The “Pen-clock” may have the potential to become an interesting supplement to the existing repertoire of methods even in cases with extremely long post-depositional intervals. Further investigations have to test this hypothesis.
Modulation of intracortical inhibition during physically performed and mentally simulated balance tasks
Authors: Mouthon A. , Ruffieux J. , Taube W. 
Published: February 2021

Abstract
Purpose
Action observation (AO) during motor imagery (MI), so-called AO + MI, has been proposed as a new form of non-physical training, but the neural mechanisms involved remains largely unknown. Therefore, this study aimed to explore whether there were similarities in the modulation of short-interval intracortical inhibition (SICI) during execution and mental simulation of postural tasks, and if there was a difference in modulation of SICI between AO + MI and AO alone.

Method
21 young adults (mean ± SD = 24 ± 6.3 years) were asked to either passively observe (AO) or imagine while observing (AO + MI) or physically perform a stable and an unstable standing task, while motor evoked potentials and SICI were assessed in the soleus muscle.

Result
SICI results showed a modulation by condition (F2,40 = 6.42, p = 0.009) with less SICI in the execution condition compared to the AO + MI (p = 0.009) and AO (p = 0.002) condition. Moreover, switching from the stable to the unstable stance condition reduced significantly SICI (F1,20 = 8.34, p = 0.009) during both, physically performed (− 38.5%; p = 0.03) and mentally simulated balance (− 10%, p < 0.001, AO + MI and AO taken together).

Conclusion
The data demonstrate that SICI is reduced when switching from a stable to a more unstable standing task during both real task execution and mental simulation. Therefore, our results strengthen and further support the existence of similarities between executed and mentally simulated actions by showing that not only corticospinal excitability is similarly modulated but also SICI. This proposes that the activity of the inhibitory cortical network during mental simulation of balance tasks resembles the one during physical postural task execution.
Canine DVL2 variant contributes to brachycephalic phenotype and caudal vertebral anomalies
Authors: Niskanen Julia E. , Reunanen Vilma , Salonen Milla , Bannasch Danika , Lappalainen Anu K. , Lohi Hannes , Hytönen Marjo K. 
Published: February 2021

AbstractA frameshift deletion variant in the Wnt pathway gene dishevelled 2 (DVL2) is associated with a truncated, kinked tail (“screw tail”) in English Bulldogs, French Bulldogs and Boston Terriers. These breeds are also characterized by distinctive morphological traits, including a wide head, flat face and short-limbed dwarfism, which are characteristic of Robinow syndrome in humans, caused by defects in genes such as DVL1 and DVL3. Based on these phenotypic and genetic similarities, it has previously been hypothesized that the canine DVL2 variant results in a syndromic phenotype called the Robinow-like syndrome. In our study, we investigated the distribution of the DVL2 variant in 1954 dogs from 15 breeds, identifying breeds with allele variation and enabling the dissection of the genotype–phenotype correlation for the first time. With CT examinations in American Staffordshire Terriers, we confirmed that the DVL2 allele is associated with caudal vertebral malformations and a brachycephalic phenotype. We also hypothesize that the variant may be linked to additional health conditions, including brachycephalic obstructive airway syndrome and congenital heart defects. Altogether, our study strengthens the role of DVL2 as one of the contributors to the “bulldog type” morphology and features on the spectrum of human Robinow syndrome.