bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Descriptor Learning with Auxiliary Classification Loss for Retrieving Images of Silk Fabrics in the Context of Preserving European Silk Heritage
Authors: Dorozynski Mareike , Rottensteiner Franz
Published: January 2022

With the growing number of digitally available collections consisting of images depicting relevant objects from the past in relation with descriptive annotations, the need for suitable information retrieval techniques is becoming increasingly important to support historians in their work. In this context, we address the problem of image retrieval for searching records in a database of silk fabrics. The descriptors, used as an index to the database, are learned by a convolutional neural network, exploiting the available annotations to automatically generate training data. Descriptor learning is combined with auxiliary classification loss with the aim of supporting the clustering in the descriptor space with respect to the properties of the depicted silk objects, such as the place or time of origin. We evaluate our approach on a dataset of fabric images in a kNN-classification, showing promising results with respect to the ability of the descriptors to represent semantic properties of silk fabrics; integrating the auxiliary loss improves the overall accuracy by 2.7% and the average F1 score by 5.6%. It can be observed that the largest improvements can be obtained for variables with imbalanced class distributions. An evaluation on the WikiArt dataset demonstrates the transferability of our approach to other digital collections.
The Signaling Pathway That cGAMP Riboswitches Found: Analysis and Application of Riboswitches to Study cGAMP Signaling in Geobacter sulfurreducens
Authors: Tan Zhesen , Chan Chi Ho , Maleska Michael , Banuelos Jara Bryan , Lohman Brian K. , Ricks Nathan J. , Bond Daniel R. , Hammond Ming C.
Published: January 2022

The Hypr cGAMP signaling pathway was discovered via the function of the riboswitch. In this study, we show the development of a method for affinity capture followed by sequencing to identify non-coding RNA regions that bind nucleotide signals such as cGAMP. The RNAseq of affinity-captured cGAMP riboswitches from the Geobacter sulfurreducens transcriptome highlights general challenges that remain for this technique. Furthermore, by applying riboswitch reporters in vivo, we identify new growth conditions and transposon mutations that affect cGAMP levels in G. sulfurreducens. This work reveals an extensive regulatory network and supports a second functional cGAMP synthase gene in G. sulfurreducens. The activity of the second synthase was validated using riboswitch-based fluorescent biosensors, and is the first known example of an active enzyme with a variant GGDDF motif.
Suitability of GRK Antibodies for Individual Detection and Quantification of GRK Isoforms in Western Blots
Authors: Reichel Mona , Weitzel Verena , Klement Laura , Hoffmann Carsten , Drube Julia
Published: January 2022

G protein-coupled receptors (GPCRs) are regulated by GPCR kinases (GRKs) which phosphorylate intracellular domains of the active receptor. This results in the recruitment of arrestins, leading to desensitization and internalization of the GPCR. Aside from acting on GPCRs, GRKs regulate a variety of membrane, cytosolic, and nuclear proteins not only via phosphorylation but also by acting as scaffolding partners. GRKs’ versatility is also reflected by their diverse roles in pathological conditions such as cancer, malaria, Parkinson’s-, cardiovascular-, and metabolic disease. Reliable tools to study GRKs are the key to specify their role in complex cellular signaling networks. Thus, we examined the specificity of eight commercially available antibodies targeting the four ubiquitously expressed GRKs (GRK2, GRK3, GRK5, and GRK6) in Western blot analysis. We identified one antibody that did not recognize its antigen, as well as antibodies that showed unspecific signals or cross-reactivity. Hence, we strongly recommend testing any antibody with exogenously expressed proteins to clearly confirm identity of the obtained Western blot results. Utilizing the most-suitable antibodies, we established the Western blot-based, cost-effective simple tag-guided analysis of relative protein abundance (STARPA). This method allows comparison of protein levels obtained by immunoblotting with different antibodies. Furthermore, we applied STARPA to determine GRK protein levels in nine commonly used cell lines, revealing differential isoform expression.
The Local Environment of Loop Switch 1 Modulates the Rate of ATP-Induced Dissociation of Human Cardiac Actomyosin
Authors: Gargey Akhil , Nesmelov Yuri E.
Published: January 2022

Two isoforms of human cardiac myosin, alpha and beta, share significant sequence similarities but show different kinetics. The alpha isoform is a faster motor; it spends less time being strongly bound to actin during the actomyosin cycle. With alpha isoform, actomyosin dissociates faster upon ATP binding, and the affinity of ADP to actomyosin is weaker. One can suggest that the isoform-specific actomyosin kinetics is regulated at the nucleotide binding site of human cardiac myosin. Myosin is a P-loop ATPase; the nucleotide-binding site consists of P-loop and loops switch 1 and 2. All three loops position MgATP for successful hydrolysis. Loops sequence is conserved in both myosin isoforms, and we hypothesize that the isoform-specific structural element near the active site regulates the rate of nucleotide binding and release. Previously we ran molecular dynamics simulations and found that loop S291-E317 near loop switch 1 is more compact and exhibits larger fluctuations of the position of amino acid residues in beta isoform than in alpha. In alpha isoform, the loop forms a salt bridge with loop switch 1, the bridge is not present in beta isoform. Two isoleucines I303 and I313 of loop S291-E317 are replaced with valines in alpha isoform. We introduced a double mutation I303V:I313V in beta isoform background and studied how the mutation affects the rate of ATP binding and ADP dissociation from actomyosin. We found that ATP-induced actomyosin dissociation occurs faster in the mutant, but the rate of ADP release remains the same as in the wild-type beta isoform. Due to the proximity of loop S291-E317 and loop switch 1, a faster rate of ATP-induced actomyosin dissociation indicates that loop S291-E317 affects structural dynamics of loop switch 1, and that loop switch 1 controls ATP binding to the active site. A similar rate of ADP dissociation from actomyosin in the mutant and wild-type myosin constructs indicates that loop switch 1 does not control ADP release from actomyosin.
Soluble Endoglin Stimulates Inflammatory and Angiogenic Responses in Microglia That Are Associated with Endothelial Dysfunction
Authors: Park Eun S. , Kim Sehee , Yao Derek C. , Savarraj Jude P. J. , Choi Huimahn Alex , Chen Peng Roc , Kim Eunhee
Published: January 2022

Increased soluble endoglin (sENG) has been observed in human brain arteriovenous malformations (bAVMs). In addition, the overexpression of sENG in concurrence with vascular endothelial growth factor (VEGF)-A has been shown to induce dysplastic vessel formation in mouse brains. However, the underlying mechanism of sENG-induced vascular malformations is not clear. The evidence suggests the role of sENG as a pro-inflammatory modulator, and increased microglial accumulation and inflammation have been observed in bAVMs. Therefore, we hypothesized that microglia mediate sENG-induced inflammation and endothelial cell (EC) dysfunction in bAVMs. In this study, we confirmed that the presence of sENG along with VEGF-A overexpression induced dysplastic vessel formation. Remarkably, we observed increased microglial activation around dysplastic vessels with the expression of NLRP3, an inflammasome marker. We found that sENG increased the gene expression of VEGF-A, pro-inflammatory cytokines/inflammasome mediators (TNF-α, IL-6, NLRP3, ASC, Caspase-1, and IL-1β), and proteolytic enzyme (MMP-9) in BV2 microglia. The conditioned media from sENG-treated BV2 (BV2-sENG-CM) significantly increased levels of angiogenic factors (Notch-1 and TGFβ) and pERK1/2 in ECs but it decreased the level of IL-17RD, an anti-angiogenic mediator. Finally, the BV2-sENG-CM significantly increased EC migration and tube formation. Together, our study demonstrates that sENG provokes microglia to express angiogenic/inflammatory molecules which may be involved in EC dysfunction. Our study corroborates the contribution of microglia to the pathology of sENG-associated vascular malformations.
A MicroRNA Next-Generation-Sequencing Discovery Assay (miND) for Genome-Scale Analysis and Absolute Quantitation of Circulating MicroRNA Biomarkers
Authors: Khamina Kseniya , Diendorfer Andreas B. , Skalicky Susanna , Weigl Moritz , Pultar Marianne , Krammer Teresa L. , Fournier Catharine Aquino , Schofield Amy L. , Otto Carolin , Smith Aaron Thomas , Buchtele Nina , Schoergenhofer Christian , Jilma Bernd , Frank Bernhard J. H. , Hofstaetter Jochen G. , Grillari Regina , Grillari Johannes , Ruprecht Klemens , Goldring Christopher E. , Rehrauer Hubert , Glaab Warren E. , Hackl Matthias
Published: January 2022

The plasma levels of tissue-specific microRNAs can be used as diagnostic, disease severity and prognostic biomarkers for chronic and acute diseases and drug-induced injury. Thereby, the combination of diverse microRNAs into biomarker signatures using multivariate statistics seems especially powerful from the perspective of tissue and condition specific microRNA shedding into the plasma. Although next-generation sequencing (NGS) technology enables one to analyse circulating microRNAs on a genome-scale level, it suffers from potential biases (e.g., adapter ligation bias) and lacks absolute transcript quantitation as well as tailor-made quality controls. In order to develop a robust NGS discovery assay for genome-scale quantitation of circulating microRNAs, we first evaluated the sensitivity, repeatability and ligation bias of four commercially available small RNA library preparation protocols. The protocol from RealSeq Biosciences was selected based on its performance and usability and coupled with a novel panel of exogenous small RNA spike-in controls to enable quality control and absolute quantitation, thus ensuring comparability of data across independent NGS experiments. The established microRNA Next-Generation-Sequencing Discovery Assay (miND) was validated for its relative accuracy, precision, analytical measurement range and sequencing bias and was considered fit-for-purpose for microRNA biomarker discovery. Summarized, all these criteria were met, and thus, our analytical platform is considered fit-for-purpose for microRNA biomarker discovery from biofluids in the setting of any diagnostic, prognostic or patient stratification need. The established miND assay was tested on serum, cerebrospinal fluid (CSF), synovial fluid (SF) and extracellular vesicles (EV) extracted from cell culture medium of primary cells and proved its potential to be used across different sample types.
The Influence of Intravaginal Gestagens Treatment on the Morphological Features and Endometrial Steroid Hormone Receptors Content during Anestrus Type II in Dairy Cattle
Authors: Trela Michał , Witkowska-Piłaszewicz Olga , Domańska Dominika , Kaczmarek Monika M. , Pawliński Bartosz , Gajewski Zdzisław , Domino Małgorzata
Published: January 2022

Background: Gestagens are the most widely used therapy in anestrus type II. The aim of this research is to evaluate the effectiveness of the vaginal progesterone inserts therapy in anestrus type II in cows. Methods: The study was conducted on 33 cows. Progesterone (PR) and estrogen (ER) receptors expression in endometrium was assessed on a molecular level based on mRNA tissue expression. Additionally, blood 17ß-estradiol and progesterone levels were evaluated. Results: A decrease in mRNA expression of A and B PR and ER α was noted in treated and untreated animals. In the treated group, an increase of ERß mRNA expression was observed, while a decreased was found in untreated animals. There was increased PR, ERα and ß expression in endometrial tissue in treated cows, and decreased expression of these factors in untreated cows. In the treated group, recurrence of ovarian cyclicity was noted in 52% of animals and pregnancy was obtained in 34.8% of them, while in the untreated group, recurrence did not occur. In the control group, spontaneous recurrence of ovarian cyclicity was not observed. An increase of PR expression was correlated with increased proliferation of endometrial cells. Conclusions: It seems likely that the endometrium is well developed and ready for placentation after removing the exogenous source of progesterone and preventing the recurrence of cyclicity of ovaries.
Estrogen Receptors-Mediated Apoptosis in Hormone-Dependent Cancers
Authors: Chimento Adele , De Luca Arianna , Avena Paola , De Amicis Francesca , Casaburi Ivan , Sirianni Rosa , Pezzi Vincenzo
Published: January 2022

It is known that estrogen stimulates growth and inhibits apoptosis through estrogen receptor(ER)-mediated mechanisms in many cancer cell types. Interestingly, there is strong evidence that estrogens can also induce apoptosis, activating different ER isoforms in cancer cells. It has been observed that E2/ERα complex activates multiple pathways involved in both cell cycle progression and apoptotic cascade prevention, while E2/ERβ complex in many cases directs the cells to apoptosis. However, the exact mechanism of estrogen-induced tumor regression is not completely known. Nevertheless, ERs expression levels of specific splice variants and their cellular localization differentially affect outcome of estrogen-dependent tumors. The goal of this review is to provide a general overview of current knowledge on ERs-mediated apoptosis that occurs in main hormone dependent-cancers. Understanding the molecular mechanisms underlying the induction of ER-mediated cell death will be useful for the development of specific ligands capable of triggering apoptosis to counteract estrogen-dependent tumor growth.
Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine
Authors: Timoshnikov Viktor A. , Selyutina Olga Yu. , Polyakov Nikolay E. , Didichenko Victoria , Kontoghiorghes George J.
Published: January 2022

The antioxidant/pro-oxidant activity of drugs and dietary molecules and their role in the maintenance of redox homeostasis, as well as the implications in health and different diseases, have not yet been fully evaluated. In particular, the redox activity and other interactions of drugs with essential redox metal ions, such as iron and copper, need further investigation. These metal ions are ubiquitous in human nutrition but also widely found in dietary supplements and appear to exert major effects on redox homeostasis in health, but also on many diseases of free radical pathology. In this context, the redox mechanistic insights of mainly three prototype groups of drugs, namely alpha-ketohydroxypyridines (alpha-hydroxypyridones), e.g., deferiprone, anthraquinones, e.g., doxorubicin and thiosemicarbazones, e.g., triapine and their metal complexes were examined; details of the mechanisms of their redox activity were reviewed, with emphasis on the biological implications and potential clinical applications, including anticancer activity. Furthermore, the redox properties of these three classes of chelators were compared to those of the iron chelating drugs and also to vitamin C, with an emphasis on their potential clinical interactions and future clinical application prospects in cancer, neurodegenerative and other diseases.
Protective Effect of Ethyl Rosmarinate against Ulcerative Colitis in Mice Based on Untargeted Metabolomics
Authors: Zhou Baisong , Liu Juntong , Wang Yaru , Wu Fulin , Wang Caixia , Wang Cuizhu , Liu Jinping , Li Pingya
Published: January 2022

Aiming at assessing the therapeutic effect of ethyl rosmarinate (ER) on ulcerative colitis (UC), the following activities were performed in vitro and in vivo in the present study. Firstly, a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to determine the level of inflammatory factors. Then, a UC mice model induced by dextran sodium sulfate (DSS) was established to further investigate the effects of ER on symptoms, inflammatory factors and colon histopathology. Finally, serum and colon metabolomics studies were performed to identify the biomarkers and metabolisms closely related to the protective effect of ER on UC. The results showed that after ER intervention, the levels of inflammatory factors (NO, TNF-α, IL-1β and IL-6) and key enzyme (MPO) in cell supernatant, serum or colon were significantly decreased, and the disease activity index and colon tissue damage in mice were also effectively improved or restored. In addition, 28 biomarkers and 6 metabolisms were found to be re-regulated by ER in the UC model mice. Therefore, it could be concluded that ER could effectively ameliorate the progression of UC and could be used as a new natural agent for the treatment of UC.
Evaluation of the Impact of Esterases and Lipases from the Circulatory System against Substrates of Different Lipophilicity
Authors: Lam Leslie , Ilies Marc A.
Published: January 2022

Esterases and lipases can process amphiphilic esters used as drugs and prodrugs and impact their pharmacokinetics and biodistribution. These hydrolases can also process ester components of drug delivery systems (DDSs), thus triggering DDSs destabilization with premature cargo release. In this study we tested and optimized assays that allowed us to quantify and compare individual esterase contributions to the degradation of substrates of increased lipophilicity and to establish limitations in terms of substrates that can be processed by a specific esterase/lipase. We have studied the impact of carbonic anhydrase; phospholipases A1, A2, C and D; lipoprotein lipase; and standard lipase on the hydrolysis of 4-nitrophenyl acetate, 4-nitrophenyl palmitate, DGGR and POPC liposomes, drawing structure–property relationships. We found that the enzymatic activity of these proteins was highly dependent on the lipophilicity of the substrate used to assess them, as expected. The activity observed for classical esterases was diminished when lipophilicity of the substrate increased, while activity observed for lipases generally increased, following the interfacial activation model, and was highly dependent on the type of lipase and its structure. The assays developed allowed us to determine the most sensitive methods for quantifying enzymatic activity against substrates of particular types and lipophilicity.
Identification and Characterization of WRKY41, a Gene Conferring Resistance to Powdery Mildew in Wild Tomato (Solanum habrochaites) LA1777
Authors: Lian Qinggui , He Xinyi , Zhang Bingbing , Wang Yang , Ma Qing
Published: January 2022

WRKYs, a large family of transcription factors, are involved in plant response to biotic and abiotic stresses, but the role of them in tomato resistance to Oidium neolycopersici is still unclear. In this study, we evaluate the role of WRKYs in powdery mildew-resistant wild tomato (Solanum habrochaites) LA1777 defense against O. neolycopersici strain lz (On-lz) using a combination of omics, classical plant pathology- and cell biology-based approaches. A total of 27 WRKYs, belonging to group I, II, and III, were identified as differentially expressed genes in LA1777 against On-lz. It was found that expression of ShWRKY41 was increased after Pseudomonas syringae pv. tomato (Pst) DC3000, On-lz and Botrytiscinerea B05 inoculation or ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) treatment. GUS staining of ShWRKY41 promoter indicated that the expression of ShWRKY41 could be induced by SA and ethylene. Furthermore, ShWRKY41 gene silencing reduced the resistance to On-lz infection by decreasing the generation of H2O2 and HR in LA1777 seedlings. Overall, our research suggests that ShWRKY41 plays a positive role in defense activation and host resistance to O. neolycopersici in wild tomato (S. habrochaites) LA1777.
Using Knowledge Graph Structures for Semantic Interoperability in Electronic Health Records Data Exchanges
Authors: Sachdeva Shelly , Bhalla Subhash
Published: January 2022

Information sharing across medical institutions is restricted to information exchange between specific partners. The lifelong electronic health records (EHR) structure and content require standardization efforts. The existing standards such as openEHR, HL7, and CEN TC251 EN 13606 (Technical committee on Health Informatics of the European Committee for Standardization) aim to achieve data independence along with semantic interoperability. This study aims to discover knowledge representation to achieve semantic health data exchange. OpenEHR and CEN TC251 EN 13606 use archetype-based technology for semantic interoperability. The HL7 Clinical Document Architecture is on its way to adopting this through HL7 templates. Archetypes are the basis for knowledge-based systems as these are means to define clinical knowledge. The paper examines a set of formalisms for the suitability of describing, representing, and reasoning about archetypes. Each of the information exchange technologies such as XML, Web Ontology Language, Object Constraint Language, and Knowledge Interchange Format is evaluated as a part of the knowledge representation experiment. These examine the representation of Archetypes as described by Archetype Definition Language. The evaluation maintains a clear focus on the syntactic and semantic transformations among different EHR standards.
Exploring Life in Concentration Camps through a Visual Analysis of Prisoners’ Diaries
Authors: Khulusi Richard , Billib Stephanie , Jänicke Stefan
Published: January 2022

Diaries are private documentations of people’s lives. They contain descriptions of events, thoughts, fears, and desires. While diaries are usually kept in private, published ones, such as the diary of Anne Frank, show that they bear the potential to give personal insight into events and into the emotional impact on their authors. We present a visualization tool that provides insight into the Bergen-Belsen memorial’s diary corpus, which consists of dozens of diaries written by concentration camp prisoners. We designed a calendar view that documents when authors wrote about concentration camp life. Different modes support quantitative and sentiment analyses, and we provide a solution for historians to create thematic concepts that can be used for searching and filtering for specific diary entries. The usage scenarios illustrate the importance of the tool for researchers and memorial visitors as well as for commemorating the Holocaust.
Electroantennographic and Behavioural Responses of European Cherry Fruit Fly, Rhagoletis cerasi, to the Volatile Organic Compounds from Sour Cherry, Prunus cerasus, Fruit
Authors: Būda Vincas , Radžiutė Sandra , Apšegaitė Violeta , Blažytė-Čereškienė Laima , Čepulytė Rasa , Bumbulytė Gabrielė , Mozūraitis Raimondas
Published: January 2022

European cherry fruit fly, Rhagoletis cerasi (Diptera: Tephritidae), is the most important pest of sweet and sour cherry fruit. This fly is difficult to control by insecticide application since most of the conventional insecticides used have been banned in Europe. Traps are used for both the pest’s mass trapping and the detection of the beginning of the flight period. Data on flies’ reactions to host-plant volatile organic compounds (VOCs) can be used to search for new attractants. VOCs were collected from the headspace of sour cherry, P. cerasus, fruit. Gas chromatography–mass spectrometry (GC–MS) resulted in the identification of 51 compounds. Terpenes and esters predominated in two aspects: in the highest diversity of the compounds, and the amount of the total VOC emissions (62.3%). Among the single VOCs, ethyl octanoate prevails, followed by (E)-4,8-dimethyl-1,3,7-nonatriene. GC–electroantennographic detection (GC–EAD) revealed 14 EAG-active compounds and those were identified. In Y-tube olfactometer tests, EAG-active compounds ((E)-β-ocimene, linalool, and (Z)-3-hexenyl 3-methylbutanoate) attracted R. cerasi females in a similar way to the odour of sour cherry fruit.
First Report on Mitochondrial Gene Rearrangement in Non-Biting Midges, Revealing a Synapomorphy in Stenochironomus Kieffer (Diptera: Chironomidae)
Authors: Zheng Chen-Guang , Liu Zheng , Zhao Yan-Min , Wang Yang , Bu Wen-Jun , Wang Xin-Hua , Lin Xiao-Long
Published: January 2022

(1) Background: Gene rearrangement of mitochondrial genome, especially those with phylogenetic signals, has long fascinated evolutionary biologists. The synapomorphic gene rearrangements have been identified across multiple orders and at many different taxonomic levels, supporting the monophyletic or systematic relationships of related lineages. However, mitochondrial gene rearrangement has never been observed in the non-biting midges (Diptera: Chironomidae); (2) methods: in this study, the complete mitogenomes of seven Stenochironomus species were sequenced and analyzed for the first time; (3) results: each mitogenome of Stenochironomus contains 37 typical genes and a control region. The whole mitogenomes of Stenochironomus species exhibit a higher A+T bias than other published chironomid species. The gene order rearranges from trnI-trnQ-trnM to trnI-trnM-trnQ in all the seven mitogenomes of Stenochironomus, which might be act as a synapomorphy of the genus, supporting the monophyletic of Stenochironomus species. In addition, another derived gene cluster: trnA-trnG-ND3-trnR exists in Stenochironomus tobaduodecimus. The derived gene orders described above are the first case of mitochondrial gene rearrangement in Chironomidae. Coupled with published data, phylogenetic relationships were reconstructed within Chironominae, and strongly supported the monophyly of Stenochironomus; (4) conclusions: our study provides new insights into the mitochondrial gene order of Chironomidae, and provides a valuable resource for understanding the synapomorphic gene rearrangements.
Why Do Insects Close Their Spiracles? A Meta-Analytic Evaluation of the Adaptive Hypothesis of Discontinuous Gas Exchange in Insects
Authors: Oladipupo Seun O. , Wilson Alan E. , Hu Xing Ping , Appel Arthur G.
Published: January 2022

The earliest description of the discontinuous gas exchange cycle (DGC) in lepidopterous insects supported the hypothesis that the DGC serves to reduce water loss (hygric hypothesis) and facilitate gaseous exchange in hyperoxia/hypoxia (chthonic hypothesis). With technological advances, other insect orders were investigated, and both hypotheses were questioned. Thus, we conducted a meta-analysis to evaluate the merit of both hypotheses. This included 46 insect species in 24 families across nine orders. We also quantified the percent change in metabolic rates per °C change of temperature during the DGC. The DGC reduced water loss (−3.27 ± 0.88; estimate ± 95% confidence limits [95% CI]; p < 0.0001) in insects. However, the DGC does not favor gaseous exchange in hyperoxia (0.21 ± 0.25 [estimate ± 95% CI]; p = 0.12) nor hypoxia, but did favor gaseous exchange in normoxia (0.27 ± 0.26 [estimate ± 95% CI]; p = 0.04). After accounting for variation associated with order, family, and species, a phylogenetic model reflected that metabolic rate exhibited a significant, non-zero increase of 8.13% (± 3.48 95% CI; p < 0.0001) per °C increase in temperature. These data represent the first meta-analytic attempt to resolve the controversies surrounding the merit of adaptive hypotheses in insects.
Amniotic Fluid microRNA in Severe Twin-Twin Transfusion Syndrome Cardiomyopathy—Identification of Differences and Predicting Demise
Authors: Schuchardt Eleanor L. , Miyamoto Shelley D. , Crombleholme Timothy , Karimpour-Fard Anis , Korst Armin , Neltner Bonnie , Howley Lisa W. , Cuneo Bettina , Sucharov Carmen C.
Published: January 2022

Twin-twin transfusion syndrome (TTTS) is a rare but serious cause of fetal cardiomyopathy with poorly understood pathophysiology and challenging prognostication. This study sought a nonbiased, comprehensive assessment of amniotic fluid (AF) microRNAs from TTTS pregnancies and associations of these miRNAs with clinical characteristics. For the discovery cohort, AF from ten fetuses with severe TTTS cardiomyopathy were selected and compared to ten normal singleton AF. Array panels assessing 384 microRNAs were performed on the discovery cohort and controls. Using a stringent q < 0.0025, arrays identified 32 miRNAs with differential expression. Top three microRNAs were miR-99b, miR-370 and miR-375. Forty distinct TTTS subjects were selected for a validation cohort. RT-PCR targeted six differentially-expressed microRNAs in the discovery and validation cohorts. Expression differences by array were confirmed by RT-PCR with high fidelity. The ability of these miRNAs to predict clinical differences, such as cardiac findings and later demise, was evaluated on TTTS subjects. Down-regulation of miRNA-127-3p, miRNA-375-3p and miRNA-886 were associated with demise. Our results indicate AF microRNAs have potential as a diagnostic and prognostic biomarker in TTTS. The top microRNAs have previously demonstrated roles in angiogenesis, cardiomyocyte stress response and hypertrophy. Further studies of the mechanism of actions and potential targets is warranted.
Body Mass Index Specifiers in Anorexia Nervosa: Anything below the “Extreme”?
Authors: Toppino Federica , Longo Paola , Martini Matteo , Abbate-Daga Giovanni , Marzola Enrica
Published: January 2022

The validity of body mass index (BMI) specifiers for anorexia nervosa (AN) has been questioned, but their applicability to inpatients with extremely low BMIs and their prognostic validity are currently unknown. Therefore, we designed this study: (a) to test current BMI specifiers in severe inpatients; (b) to explore a “very extreme” specifier (VE-AN; BMI ≤ 13.5); and (c) to verify inpatients’ hospitalization outcome according to BMI severity. We enrolled 168 inpatients with AN completing the following: Eating disorder Examination-Questionnaire, Eating Disorder Inventory-2, State-Trait Anxiety Inventory, Beck Depression Inventory, Body Shape Questionnaire, and EQ-5D-VAS. According to the current BMI classification, those with a BMI < 15 versus those with non-extreme AN (NE-AN, BMI ≥ 15) differed on all measures but the quality of life with those with NE-AN reporting more impaired scores on all measures. Adopting an exploratory classification comparing VE-AN, extreme AN (E-AN, BMI = 13.6–14.99), and NE-AN, no differences emerged between VE-AN and E-AN, while those with NE-AN reported significantly more impaired scores on all variables while the quality of life again did not differ across groups. Hospitalization outcome improved for all groups, independently of BMI. Groups differed concerning the length of stay that mirrored BMI severity and impacted also hospitalization outcomes. Taken together, our data support the lack of validity of current BMI specifiers in AN, even in the acute setting. Moreover, the exploratory subgroup of patients with BMI ≤ 13.5 did not delineate a clinically different group.
3D Stereophotogrammetric Quantitative Evaluation of Posture and Spine Proprioception in Subacute and Chronic Nonspecific Low Back Pain
Authors: Kinel Edyta , Roncoletta Piero , Pietrangelo Tiziana , D’Amico Moreno
Published: January 2022

The literature shows that low back pain causes a reduced lumbar range of movement, affecting patients’ proprioception and motor control. Nevertheless, studies have found that proprioception and motor control of the spine and posture are vague and individually expressed even in healthy young adults. This study aimed to investigate the standing posture and its modifications induced by an instinctive self-correction manoeuvre in subacute and chronic nonspecific low back pain (NSLBP) patients to clarify how NSLBP relates to body upright posture, proprioception, and motor control and how these are modified in patients compared to healthy young adults (121 healthy young adults: 57 females and 64 males). A cohort of 83 NSLBP patients (43 females, 40 males) were recruited in a cross-sectional observational study. Patients’ entire body posture, including 3D spine shape reconstruction, was measured using a non-ionising 3D optoelectronic stereophotogrammetric approach. Thirteen quantitative biomechanical parameters describing the nature of body posture were computed. The statistical analysis was performed using multivariate methods. NSLBP patients did not present an altered proprioception and motor control ability compared to healthy young adults. Furthermore, as for healthy subjects, NSLBP patients could not focus and control their posture globally. Proprioception and motor control in natural erect standing are vague for most people regardless of gender and concurrent nonspecific low back pain. Self-correction manoeuvres improving body posture and spine shape must be learned with specific postural training focusing on the lumbar spine.
Minimally Invasive versus Full Sternotomy SAVR in the Era of TAVR: An Institutional Review
Authors: Wilson Tyler W. , Horns Joshua J. , Sharma Vikas , Goodwin Matthew L. , Kagawa Hiroshi , Pereira Sara J. , McKellar Stephen H. , Selzman Craig H. , Glotzbach Jason P.
Published: January 2022

In the era of advancing transcatheter aortic valve replacement (TAVR) technology, traditional open surgery remains a valuable intervention for patients who are not TAVR candidates. We sought to compare perioperative variables and postoperative outcomes of minimally invasive and full sternotomy surgical aortic valve replacement (SAVR) at a single institution. A retrospective analysis of 113 patients who underwent isolated SAVR via full sternotomy or upper hemi-sternotomy between January 2015 and December 2019 at the University of Utah Hospital was performed. Preoperative comorbidities and demographic information were not different among groups, with the exception of diabetes, which was significantly more common in the full sternotomy group (p = 0.01). Median procedure length was numerically shorter in the minimally invasive group but was not significant following the Bonferroni correction (p = 0.047). Other perioperative variables were not significantly different. The two groups showed no difference in the incidence of postoperative adverse events (p = 0.879). As such, minimally invasive SAVR via hemi-sternotomy remains a safe and effective alternative to full sternotomy for patients who meet the criteria for aortic valve replacement.
An Expert-Supervised Registration Method for Multiparameter Description of the Knee Joint Using Serial Imaging
Authors: Babel Hugo , Omoumi Patrick , Cosendey Killian , Stanovici Julien , Cadas Hugues , Jolles Brigitte M. , Favre Julien
Published: January 2022

As knee osteoarthritis is a disease of the entire joint, our pathophysiological understanding could be improved by the characterization of the relationships among the knee components. Diverse quantitative parameters can be characterized using magnetic resonance imaging (MRI) and computed tomography (CT). However, a lack of methods for the coordinated measurement of multiple parameters hinders global analyses. This study aimed to design an expert-supervised registration method to facilitate multiparameter description using complementary image sets obtained by serial imaging. The method is based on three-dimensional tissue models positioned in the image sets of interest using manually placed attraction points. Two datasets, with 10 knees CT-scanned twice and 10 knees imaged by CT and MRI were used to assess the method when registering the distal femur and proximal tibia. The median interoperator registration errors, quantified using the mean absolute distance and Dice index, were ≤0.45 mm and ≥0.96 unit, respectively. These values differed by less than 0.1 mm and 0.005 units compared to the errors obtained with gold standard methods. In conclusion, an expert-supervised registration method was introduced. Its capacity to register the distal femur and proximal tibia supports further developments for multiparameter description of healthy and osteoarthritic knee joints, among other applications.
The Accuracy of Transurethral Bladder Resection in Detecting Bladder Cancer Histological Variants and Their Prognostic Value at Radical Cystectomy
Authors: La Croce Giovanni , Naspro Richard , Finati Marco , Pellucchi Federico , Sodano Mario , Manica Michele , Catellani Michele , Gianatti Andrea , Roscigno Marco , Da Pozzo Luigi Filippo
Published: January 2022

Objectives: to investigate the accuracy of transurethral resection of bladder tumours (TURBT) in detecting histological variants (BHV) at radical cystectomy (RC) and to evaluate the impact of TURBT before cystectomy on oncological outcomes. Methods: Data of 410 consecutive RCs were assessed. Positive and negative predictive values were used to assess the accuracy of TURBT in detecting BHV. Cohen’s Kappa coefficient was used to calculate the agreement grade. Logistic regression analysis predicted features based on the presence of BHV at TURBT. Multivariable backward conditional Cox regression analysis was used to estimate oncological outcomes. Results: A total of 73 patients (17.8%) showed BHV at TURBT as compared to 108 (26.3%) at RC. A moderate agreement in histological diagnosis was found between TURBT and RC (0.58). However, sensitivity and specificity in detecting BHV were 56% and 96%, respectively. Furthermore, positive predictive value (PPV) was 84.7% and negative predictive value (NPV) was 84.6%. Presence of BHV at TURBT was an independent predictor for pathologic upstage, albeit not a predictor for positive nodes or positive surgical margins. However, at multivariable analysis adjusted for all confounders, presence of BHV at TURBT was an independent predictor for recurrence after RC, but not for survival. Conversely, the presence of BHV at RC was an independent predictor for both recurrence and survival. Conclusion: There was a moderate agreement between TURBT and RC histopathological findings. TURBT, alone, could not provide an accurate and definitive histological diagnosis. Detection of BHV in TURBT specimens is not an independent predictor of oncological outcomes; indeed, only pathological features at RC are associated with worse survival. However, BHV presence in cystectomy specimens resulted as an independent predictor of both cancer-specific and overall mortality.
Morphological Relation of Peripheral Nerve Sheath Tumors and Nerve Fascicles: Prospective Study and Classification
Authors: Holzbauer Matthias , Aufschnaiter-Hießböck Kathrin , Zaussinger Maximilian , Aszmann Oskar , Schmidt Manfred
Published: January 2022

Removal of benign peripheral nerve sheath tumors (bPNST) represents a surgical challenge. The morphological relation of bPNST and healthy nerve fascicles are of utmost importance for achieving both removal of the entire tumor and preservation of functional integrity of the peripheral nerve. Thus, we intraoperatively assessed the morphological patterns between bPNST and nerve fascicles using photo documentation obtained between January 2009 and September 2021. In 31 patients (20 women and 11 men) with a mean age of 48 ± 18 years a total of 34 bPNST were removed. Four constant morphological patterns between bPNST relatively to nerve fascicles were detected: (1) bPNST is located peripherally (n = 16), (2) it splits the nerve into two main fascicles (n = 5), (3) it totally splits up the nerve out of the nerve’s center (n = 8) und (4) it encloses the nerve and its fascicles (n = 5) without any detectable boundary layer. Histology revealed 28 schwannomas, five neurofibromas, and one perineurioma. The proposed classification reflects the increasing complexity of tumor removal with a higher type number. This might be beneficial for preoperative diagnostics, i.e., high-resolution ultrasound or MRI-tractography, as well as for planning the bPNST’s surgical resection and the possible need for nerve reconstruction.
Freshwater Clam Extract Mitigates Neuroinflammation and Amplifies Neurotrophic Activity of Glia: Insights from In Vitro Model of Neurodegenerative Pathomechanism
Authors: Lin Muh-Shi , Chen Shu-Mei , Hua Kuo-Feng , Chen Wei-Jung , Hsieh Cho-Chen , Lin Chai-Ching
Published: January 2022

Background. An extensive body of research suggests that brain inflammation and oxidative stress are the underlying causes of Parkinson’s disease (PD), for which no potent therapeutic approach exists to mitigate the degradation of dopamine neurons. Freshwater clams, an ancient health food of Chinese origin, have been documented to exhibit anti-inflammatory and antioxidant effects. We previously reported that freshwater clam extract (FCE) can attenuate astrocytic activation and subsequent proinflammatory cytokine production from substantia nigra in an MPTP-induced PD mouse model. This article provides insight into the potential mechanisms through which FCE regulates neuroinflammation in a glia model of injury. Materials and methods. In total, 1 μg/mL lipopolysaccharide (LPS) and 200 μM rotenone were conducted in primary glial cell cultures to mimic the respective neuroinflammation and oxidative stress during injury-induced glial cell reactivation, which is relevant to the pathological process of PD. Results. FCE markedly reduced LPS-induced neuroinflammation by suppressing NO and TNF-α production and the expression of pro-inflammatory cytokines. In addition, FCE was effective at reducing rotenone-induced toxicity by diminishing ROS production, promoting antioxidant enzymes (SOD, catalase, and GPx) and minimizing the decline in glial-cell-secreted neurotrophic factors (GDNF, BDNF). These impacts ultimately led to a decrease in glial apoptosis. Conclusions. Evidence reveals that FCE is capable of stabilizing reactive glia, as demonstrated by reduced neuroinflammation, oxidative stress, the increased release of neurotrophic factors and the inhibition of apoptosis, which provides therapeutic insight into neurodegenerative diseases, including PD.
Ventilation-Induced Lung Injury (VILI) in Neonates: Evidence-Based Concepts and Lung-Protective Strategies
Authors: Kalikkot Thekkeveedu Renjithkumar , El-Saie Ahmed , Prakash Varsha , Katakam Lakshmi , Shivanna Binoy
Published: January 2022

Supportive care with mechanical ventilation continues to be an essential strategy for managing severe neonatal respiratory failure; however, it is well known to cause and accentuate neonatal lung injury. The pathogenesis of ventilator-induced lung injury (VILI) is multifactorial and complex, resulting predominantly from interactions between ventilator-related factors and patient-related factors. Importantly, VILI is a significant risk factor for developing bronchopulmonary dysplasia (BPD), the most common chronic respiratory morbidity of preterm infants that lacks specific therapies, causes life-long morbidities, and imposes psychosocial and economic burdens. Studies of older children and adults suggest that understanding how and why VILI occurs is essential to developing strategies for mitigating VILI and its consequences. This article reviews the preclinical and clinical evidence on the pathogenesis and pathophysiology of VILI in neonates. We also highlight the evidence behind various lung-protective strategies to guide clinicians in preventing and attenuating VILI and, by extension, BPD in neonates. Further, we provide a snapshot of future directions that may help minimize neonatal VILI.
Perioperative Acetaminophen and Dexmedetomidine Eliminate Post-Operative Opioid Requirement following Pediatric Tonsillectomy
Authors: Rudikoff Andrew G. , Tieu David D. , Banzali Franklin M. , Nguyen Carolyn V. , Rettig Robert L. , Nashed Marlene M. , Mora-Marquez Janet , Chen Qiaoling , Conte Antonio Hernandez , Mason Keira P.
Published: January 2022

Administration of post-operative opioids following pediatric tonsillectomy can elicit respiratory events in this patient population that often arise as central and obstructive sleep apnea. The primary objective of this study was to determine whether a perioperative combination of dexmedetomidine and acetaminophen could eliminate post-operative (in recovery and at home) opioid requirements. Following IRB approval and a waiver for informed consent, the medical records of 681 patients who underwent tonsillectomy between 1 January 2013 and 31 December 2018 were evaluated. Between 1 January 2013 and 31 December 2015, all patients received a fentanyl-sevoflurane-based anesthetic, without acetaminophen or dexmedetomidine, and received opioids in recovery and for discharge home. On 1 January 2016, an institution-wide practice change replaced this protocol with a multimodal perioperative regimen of acetaminophen (intravenous or enteral) and dexmedetomidine and eliminated post-operative opioids. This is the first time that the effect of an acetaminophen and dexmedetomidine combination on the perioperative and home opioid requirement has been reported. Primarily, we compared the need for rescue opioids in the post-anesthesia care period and after discharge. The multi-modal protocol eliminated the need for post-tonsillectomy opioid administration. Dexmedetomidine in combination with acetaminophen eliminated the need for post-operative opioids in the recovery period.
Patterns and Predictors of Medication Change after Discharge from Hospital: An Observational Study in Older Adults with Neurological Disorders
Authors: Schwarzkopf Anna , Schönenberg Aline , Prell Tino
Published: January 2022

Background: Medication is often changed after inpatient treatment, which affects the course of the disease, health behavior and adherence. Thus, it is important to understand patterns of medication changes after discharge from hospital. Methods: Inpatients at the Department of Neurology received a comprehensive assessment during their stay, including adherence, depression, cognition, health and sociodemographic variables. A month after being discharged, patients were contacted to enquire about post-discharge medication changes. Results: 910 older adults aged 70 ± 8.6 years participated, of which 204 (22.4%) reported medication changes. The majority of changes were initiated by physicians (n = 112, 56.3%) and only 25 (12.6%) patients reported adjusting medication themselves. Reasons for medication changes differed between patients and doctors (p < 0.001), with side effects or missing effects cited frequently. Sociodemographic and patient-related factors did not significantly predict medication changes. Conclusion: Patients reported less post-discharge medication changes than expected, and contrary to previous literature on nonadherence, only a fraction of those changes were performed by patients themselves. Socioeconomic and clinical parameters regarding personality, mood and cognition were poorly associated with post-discharge medication changes. Instead, individual health-related factors play a role, with patient factors only indirectly influencing physicians’ decisions.