bluuebunny/crossref_metadata_2025 huggingface dataset:
Smíšený mód a online dotazování: mezinárodní praxe a tuzemská připravenost na implementaci
Authors: Hubatková Barbora , Lakomý Martin
Published: October 2021

The cost of interviewer-administered data collection (CAPI, CATI) has been gradually rising, while response rates have been declining over time. This situation has led to the domination of online data collection (CAWI), which tends to suffer from poor population coverage and even lower response rates. This could be overcome by combining this method with another mode of data collection. This paper aims to summarise the main principles of mixed-mode design, its implementation in major international surveys, and the first results of a project testing the feasibility of the push-to-web mixed-mode design in the Czech context. The results illustrate that together, unequal distribution of technological skills and willingness to participate distort the recruitment of random samples for CAWI towards middle-aged and more educated respondents. The mixed-mode design – together with the described components – has the potential to better involve underrepresented groups, while it is essential to follow the rules for achieving comparable answers across modes and devices. Finally, we emphasize the need to disseminate findings to researchers and other users of survey data, as the use of mixed-mode design has been rapidly increasing.
Nový přístup v testování ekvivalence na příkladu měření subjektivního blahobytu
Authors: Raudenská Petra , Hanzlová Radka
Published: October 2021

Survey-based measures of subjective well-being are more and more often analyzed cross-culturally. However, international comparison of these measures requires measurement invariance. Therefore, the major goal of this study was to investigate the cross-country comparability of the five-item subjective well-being scales used in the International Social Survey Programme (2011, 2017). This study applied both the traditional exact and the more recent Bayesian approximate approach to assess whether the subjective well-being scales were measurement invariant. The Bayesian approach detected several non‑invariant items that were problematic for cross-national comparison and could be dropped from the scales. Consequently, measurement invariance was established in all countries for the reduced scales, allowing researchers to meaningfully compare their latent mean scores and the relationships with other theoretical constructs of interest. Thus, the study highlighted the advantages of using multiple indicators and the necessity of measurement invariance testing in subjective well-being research.
Theological Hermeneutics and Translation. Ernst Fuchs’s "Translation and Proclamation"
Authors: O’Keeffe Brian
Published: October 2021

The objective of this essay is to provide a commentary on an essay written by one of the chief representatives of the new-hermeneutical approach to Protestant theology, namely Ernst Fuchs. The essay, “Translation and Proclamation” (“Übersetzung und Verkündigung”), is, I hope to show, an extremely interesting engagement with translation in the context of theological hermeneutics. At issue is a certain ‘translation’ of the Scriptures which must occur so that the Word of God becomes available to the preacher – she who is tasked, among other things, to proclaim that Word. Insofar as preaching can be described as a performance, then translation is also asked to operate a certain ‘text performance’ as well. In examining what that operation is, we can gain useful purchase not only on the role of translation for theological hermeneutics but also for hermeneutics of the sort theorised by Hans-Georg Gadamer.
Lektüre und Performativität. Materialitäten fiktionaler Texte zwischen Semantik und Sinnlichkeit
Authors: Pfeiffer Jasmin
Published: October 2021

Over the past few years, the humanities has developed a strong interest in the material aspects of all domains of human life. In this context, researchers have started paying attention to the performative dimensions of reading: in order to interact with a text, the readers have to position their bodies in a certain way, they have to touch the cover of the book, turn the pages etc. Furthermore, texts are usually part of larger communicative and cultural contexts which frame our interactions with them. Based on this theoretical background, the present essay examines how those performative elements not only influence our reading experience, but can also take part in the constitution of meaning and thereby alter our interpretation of the text. At issue will firstly be a comparison between the manuscript of Victor Hugo’s Les Travailleurs de la mer and the printed version of the publishing house LGF and the exercise to demonstrate that the paper used for the manuscript possesses a high semantic and symbolic value. Secondly, by using the example of E. T. A. Hoffmann’s Lebens-Ansichten des Kater Murr, what is at stake is how fiction extending beyond the borders of the ‘original’ text, and including other artifacts, can offer new interpretive dimensions
Dental treatment of children with special needs under general anesthesia at the Clinic of dental medicine in Niš: A ten-year retrospective study
Authors: Čemerikić Ljiljana , Stojković Branislava , Tijanić Miloš , Popović Žana
Published: October 2021

Introduction: The oral health of children with special needs is most often impaired, with a high prevalence of caries and its complications. Due to the impossibility of establishing an adequate child-dentist contact and a large number of carious teeth, dental treatment under general anesthesia is often indicated in this population of children. Aim: To perform a comprehensive analysis of the dental treatment of children with special needs under general anesthesia at the Clinic of Dental Medicine in Niš over a period of ten years. Material and methods: A retrospective study analyzed the dental documentation of children with special needs in whom dental treatment was performed under general anesthesia at the Clinic of Dental Medicine in Niš in the period from January 1, 2010 to December 31, 2019. Results: 286 children with special needs (14.7%) out of a total number of 1943 admitted at the Department for Preventive and Pediatric Dentistry of the Clinic of Dental Medicne in Niš during the analyzed period, originally from Nišava, Jablanica, Pčinja, Toplica, Rasina, and other administrative districts of Serbia, were treated under general anesthesia. In the second half of the ten-year follow-up period, almost twice as many children were treated regarding the first five years. The records show that 1754 teeth were restored, 28 endodontically treated, and 1417 extracted. Conclusion: A high percentage of children with special needs treated under general anesthesia and a constant increase in the number of such children in Southeastern Serbia suggest the need for close cooperation between dentists of health care centers in Southeastern Serbia and dentists at the Clinic of Dental Medicine in Niš, a tertiary dental health care center towards which patients of this part of Serbia gravitate.
Management of recurrent aphthous stomatitis in HIV
Authors: Obradović Radmila , Kesić Ljiljana , Pejčić Ana , Bojović Marija , Petrović Milica , Stanković Ivana , Jovanović Marija , Popović Žana
Published: October 2021

Introduction: Today, human immunodeficiency virus (HIV) infection is often health problem. People with HIV are living longer and more of them are seeking care for the oral complications of this disease. This is the reason why the management of HIV infection is regular in the dental and medical everyday practice. Although HIV-related recurrent aphthous stomatitis (RAS) constitute a small percentage of oral lesions they are one of the most painful conditions of the oral cavity. The aim: is to point out the therapeutic possibilities and health improvement in people with HIV. Conclusion: Once a diagnosis of RAS is reached, the choice of a specific treatment modality is individual and the potential side effects of drugs should always be taken into account. It is important to reduce pain and achieve a prolonged remission.
The protection of juveniles in a criminal proceedings
Authors: Kovačević Milica
Published: October 2021

In recent years a significant attention has been paid to the protection of juveniles in the context of a criminal procedure. It cannot be denied that the participation of juveniles in these proceedings could be the cause of secondary victimization and trauma. In addition, the specific position of the child established by the UN Convention on the Rights of the Child requires the minors to be allowed to actively participate in a criminal proceedings and to be adequately informed about various aspects and consequences of the procedure. The paper first gives a brief overview of the relevant international documents on the rights of juveniles in a criminal procedure, followed by the analysis of the domestic normative framework in the same field. A formal dogmatic approach has been applied. Afterwards, the author summarizes the state of the rights of minors in a criminal procedure in practice in Serbia. The aim of this paper is to point out the possible improvements of the position of juveniles in a criminal proceedings in Serbia.
The importance of Alpha-lipoic acid for the treatment of chronic wounds at the level of primary health care: A case report
Authors: Marinković Dragan
Published: October 2021

Although the term "wounds" and their treatment is mostly associated with surgical disciplines and higher levels of health care, chronic wounds are part of the pathological conditions that primary care physicians encounter in their daily practice and which, thanks to modern dressings and means for the treatment of chronic wounds, can be successfully treated at the primary level of health care if the localization and the degree of affected tissues allow (the best case is when only surface tissues are damaged). In addition to the use of modern means and dressings for the treatment of chronic wounds, the introduction of alphalipoic acid, in addition to the use of modern means and dressings for the treatment of chronic wounds, even in people with diabetes, accelerates and accelerates the healing process. Alpha-lipoic acid has a strong antioxidant and anti-inflammatory effect.
A Prospective Cohort Study of Stability in Preferred Place of Death Among Patients With Stage IV Cancer in Singapore
Authors: Malhotra Chetna , Koh Ling En , Teo Irene , Ozdemir Semra , Chaudhry Isha , Finkelstein Eric
Published: October 2021

Background: Advance care planning (ACP) involves documentation of patients’ preferred place of death (PoD). This assumes that patients’ preferred PoD will not change over time; yet, evidence for this is inconclusive. We aimed to assess the extent and correlates of change in patients’ preferred PoD over time. Materials and Methods: Using data from a cohort study of patients with advanced cancer in Singapore, we analyzed preferred PoD (home vs institution including hospital, hospice, and nursing home vs unclear) among 466 patients every 6 months for a period of 2 years. At each time point, we assessed the proportion of patients who changed their preferred PoD from the previous time point. Using a multinomial logistic regression model, we assessed patient factors (demographics, understanding of disease stage, ACP, recent hospitalization, quality of life, symptom burden, psychologic distress, financial difficulty, prognosis) associated with change in their preferred PoD. Results: More than 25% of patients changed their preferred PoD every 6 months, with no clear trend in change toward home or institution. Patients psychologically distressed at the time of the survey had increased likelihood of changing their preferred PoD to home (relative risk ratio [RRR], 1.02; 95% CI, 1.00–1.05) and to an institution (RRR, 1.06; 95% CI, 1.02–1.10) relative to no change in preference. Patients hospitalized in the past 6 months were more likely to change their preferred PoD to home (RRR, 1.56; 95% CI, 1.07–2.29) and less likely to change to an institution (RRR, 0.50; 95% CI, 0.28–0.88) relative to no change in preference. Conclusions: The present study provides evidence of instability in the preferred PoD of patients with advanced cancer. ACP documents need to be updated regularly to ensure they accurately reflect patients’ current preference.
Melanoma Metastases to the Adrenal Gland Are Highly Resistant to Immune Checkpoint Inhibitors
Authors: Borgers Jessica S.W. , Tobin Richard P. , Torphy Robert J. , Vorwald Victoria M. , Van Gulick Robert J. , Amato Carol M. , Cogswell Dasha T. , Chimed Tugs-Saikhan , Couts Kasey L. , Van Bokhoven Adrie , Raeburn Christopher D. , Lewis Karl D. , Wisell Joshua , McCarter Martin D. , Mushtaq Rao R. , Robinson William A.
Published: October 2021

Background:Adrenal gland metastases (AGMs) are common in advanced-stage melanoma, occurring in up to 50% of patients. The introduction of immune checkpoint inhibitors (ICIs) has markedly altered the outcome of patients with melanoma. However, despite significant successes, anecdotal evidence has suggested that treatment responses in AGMs are significantly lower than in other metastatic sites. We sought to investigate whether having an AGM is associated with altered outcomes and whether ICI responses are dampened in the adrenal glands.Patients and Methods:We retrospectively compared ICI responses and overall survival (OS) in 68 patients with melanoma who were diagnosed with an AGM and a control group of 100 patients without AGMs at a single institution. Response was determined using RECIST 1.1. OS was calculated from time of ICI initiation, anti–PD-1 initiation, initial melanoma diagnosis, and stage IV disease diagnosis. Tumor-infiltrating immune cells were characterized in 9 resected AGMs using immunohistochemical analysis.Results:Response rates of AGMs were significantly lower compared with other metastatic sites in patients with AGMs (16% vs 22%) and compared with those without AGMs (55%). Patients with AGMs also had significantly lower median OS compared with those without AGMs (3.1 years vs not reached, respectively). We further observed that despite this, AGMs exhibited high levels of tumor-infiltrating immune cells.Conclusions:In this cohort of patients with melanoma, those diagnosed with an AGM had lower ICI response rates and OS. These results suggest that tissue-specific microenvironments of AGMs present unique challenges that may require novel, adrenal gland–directed therapies or surgical resection.
L’objet en question. Quelques réflexions sur le statut de l’objet dans les mises en scène muséales de la disparition
Authors: Jurgenson Luba
Published: October 2021

Dans certaines scénographies récentes, le contact avec l’objet est médié par la photographie, la vidéo ou l’installation artistique. Le rôle de ces nouveaux médias muséaux est de rendre présents des objets qui ne se trouvent pas physiquement dans les collections du musée mais également, et surtout, de faire réfléchir le spectateur sur la représentation en tant que telle et sur les limites de la reconstitution du passé. Nous proposons ici une réflexion sur deux fonctions muséales de l’objet : l’auto-représentation (l’apparaître/la présence) qui engage les outils de la phénoménologie et la transmission d’un message (fonction « médium ») qui fait appel, parmi d’autres, à ceux de la sémiotique.
Faire la navette : construire un objet-témoin de la mémoire collective de la ville postindustrielle belge de Verviers
Authors: Aubert Baptiste
Published: October 2021

Comment rendre compte de la mémoire d’une ville postindustrielle par le médium du cinéma ? Dans cet article, je présente un dispositif cinématographique construit autour de la collecte d’objets et de témoignages. En revisitant la notion d’« objet-témoin », je parcours les brocantes de la ville de Verviers afin d’acquérir d’anciennes navettes de métiers à tisser et de reconstruire leur histoire avec les vendeurs·euses qui s’en séparent. L’ensemble des récits collectés me permet de questionner, puis de représenter la « mémoire collective » de cette ville postindustrielle belge.
Entre les visages : l’image-témoin en glissement
Authors: Baronian Marie-Aude
Published: October 2021

Cet article se concentre sur un des tropes majeurs du témoignage audiovisuel : le visage. Il s’agit de réfléchir, dans le contexte de la violence de masse, à la façon dont le visage cristalliserait l’image-témoin elle-même. Pour ce faire, deux installations vidéo sont prises en compte : Entre l’écoute et la parole : derniers témoins. Auschwitz-Birkenau 1945–2005 (2010) de l’artiste Esther Shalev-Gerz et Chorus (2015) du cinéaste Atom Egoyan. Les deux artistes touchent, respectivement, à la Shoah et au génocide des Arméniens en multipliant les écrans par lesquels les visages des survivants (réels ou fictifs) apparaissent comme les seuls possibles loci du témoignage indicible. Parallèlement, l’article insiste sur la pertinence de la pensée du philosophe Emmanuel Levinas lorsqu’on invoque la relation entre image et témoignage au-delà des régimes représentationnels et spectatoriels. Au bout du compte, on tentera de désacraliser et de décaricaturer le visage comme figure démonstrative et dévoilante (souvent typique du témoignage audiovisuel), afin de révéler l’infini glissement qui singularise l’image-témoin.
Le commentaire de Jean Cayrol pour Nuit et Brouillard d’Alain Resnais : au confluent du témoignage et de l’intermédialité*
Authors: Santerre Ariane
Published: October 2021

Cet article se consacre à l’apport du poète et résistant déporté Jean Cayrol au documentaire Nuit et brouillard (1956) d’Alain Resnais en croisant les approches littéraire, testimoniale et intermédiale. S’inspirant de ce film classique comme étude de cas, l’enjeu principal de cette contribution consiste à examiner l’interaction entre texte et images de manière à interroger, à travers leur médium respectif ou par le fait de leur combinaison, les possibilités ainsi que les limites de l’expérience communicative de l’extrême.
Faire son temps. Boltanski/Benjamin, le conteur comme témoin
Authors: Klein Anne
Published: October 2021

Le témoignage considéré comme la transmission de quelque chose du passé est ici appréhendé à travers la démarche de Christian Boltanski. La proposition s’appuie sur une remémoration de Faire son temps, la plus récente des oeuvres-expositions de l’artiste. En croisant une lecture du Conteur de Walter Benjamin et de l’oeuvre de Boltanski, dont on postule qu’elle se compose des installations et de la parole de l’artiste, on cherche à comprendre les ressorts du témoignage comme modalité de transmission de et par l’expérience. Boltanski semble finalement contredire l’affirmation de Benjamin, selon qui l’art de conter était, en 1936, voué à disparaître.
Le « recyclage » dans l’acquisition des clitiques obliques en catalan : la sous-spécification et la complexité
Authors: Heap David , Soto-Corominas Adriana
Published: October 2021

Le but de la présente étude est d’examiner les remplacements des clitiques par les enfants de langue catalane, quelle que soit leur dominance linguistique, qui acquièrent variablement les clitiques obliques hi et en. Nous analysons la plupart de ces cas de substitution à l’aide de la sous-spécification et de la géométrie des traits, mais pour un des cas, nous avons recours à des effets des contraintes à la complexité pour comprendre la substitution attestée.
Une recette pour des arguments nuls
Authors: Paul Ileana , Massam Diane
Published: October 2021

Cet article présente une étude de cas d’ellipses d’argument dans le contexte des recettes de cuisine. En anglais et en français, les patients définis peuvent être nuls dans les recettes, même si cette ellipse n’est pas possible en dehors de ce contexte (Trancher et servir chaud). Des mécanismes spécifiques à ce registre ont été proposés pour rendre compte de ces arguments nuls. On parle moins du fait que les recettes permettent aussi les agents nuls, qui sont légitimés par l’impératif ou l’infinitif. Dans cet article, il s’agit d’exemples de recettes dans deux langues austronésiennes, le niuéen et le malgache. On propose que bien que les arguments nuls soient un aspect pragmatique du registre des recettes dans toutes les langues, ils sont légitimés par des moyens différents, selon les caractéristiques syntaxiques de la langue. En niuéen, les agents nuls sont le résultat de l’impératif, comme en anglais, mais les patients nuls surviennent grâce au paradigme pronominal régulier. Aucune règle spécifique au registre n’est, alors, nécessaire. Le malgache, par contre, profite de sa morphologie verbale pour réaliser les agents nuls dans les recettes, et l’omission des patients est le résultat de l’effacement des topiques (topic-drop). Cet article élargit donc l’étude interlinguistique de la syntaxe du registre des recettes.
UTICAJ I ZNAČAJ REGULATORNOG KAPITALA NA BANKARSKI SEKTOR REPUBLIKE SRPSKE
Authors: Slijepčević Vitomir
Published: October 2021

Bankarski sektor Republike Srpske predstavlja ključni faktor makroekonomske stabilnosti privrednog sistema zemlje. Zato sve promjene koje se dešavaju u ovom sektoru značajno utiču na ukupnost odnosa na finansijskom tržištu i u nacionalnoj ekonomiji zemlje. Cilj ovog istraživanja je prikazati pouzdanost i validnost propisnih parametara adekvatnosti regulatornog kapitala, finansijske poluge i drugih na ocjenu stabilnosti i sigurnosti bankarskog sektora, odnosno pojedinačno bilo koje banke. Zadatak ovog istraživanja je dobii odgovor na pitanje: „Da li su minimalno propisane stope adekvatnosti regulatornog kapitala i finansijske poluge dovoljne da obezbijede stabilan bankarski sektor Republike Srpske?“ U radu su korišćene osnovne statističke metode istraživanja, grafičkog predstavljanja, analize, sinteze, komparacije i apstrahovanja dobijenih rezultata. Provedeno istraživanje je pokazalo da postoji konstantan rast parametara adekvatnosti kapitala i finansijske poluge, ali da njihova visina i raspon nije pouzdan pokazatelj stabilnosti i opstanka banaka.
MEĐUNARODNOPRAVNI SUBJEKTIVITET U USLOVIMA GLOBALIZACIJE
Authors: Petrović Željko
Published: October 2021

Ovaj rad se bavi aktuelnim pitanjima međunarodnopravnog subjektiviteta u uslovima globalizacije. Vrši se analiza teorija i suvremenih shvatanja međunarodnopravnog subjektiviteta. Danas je sve teže odrediti da li određeni subjekt ima međunarodnopravni subjektivitet. Države i dalje su najbitniji subjekti međunarodnog prava, ali nisu jedini, te same države nastupaju u međunarodnoj zajednici koja se u mnogo čemu promjenila. Sve je veći broj međunarodnih organizacija kao subjekata međunarodnog prava koje imaju sve veću ulogu. Najnoviji tokovi međunarodnih političkih, ekonomskih, kulturnih, socioloških i drugih odnosa današnjice uvjetuju progresivni razvoj međunarodnog prava, te aktualiziraju državu kao subjekta međunarodnog prava.
Research On Real-time Monitoring of HIFU Focal Damage Based On Transducer Driving Signal
Authors: 钱骏  , 李雁浩
Published: October 2021

Real-time monitoring of HIFU focal region is a key problem in clinical treatment of focused ultrasound. At present, the change of strong echo in B-ultrasound images is often used in clinical practice to monitor tissue damage in the focal area. However, the strong echo in B-ultrasound images is mostly related to cavitation and boiling bubbles in the focal area, which cannt to monitor the treatment status accurately and in real time. In HIFU treatment, the focal area tissue will be accompanied by changes in temperature, cavitation, boiling, and tissue characteristics. The acoustic load on the surface of the transducer is also constantly changing. To solve this problem, a real-time detection platform of transducer voltage and current is built in this paper, which can sense the state change of focal area tissue by measuring the electrical parameters of the transducer. The experimental results show that the stability of the phase difference of the transducer driving signal will be different (the fluctuation amplitude will be different) when different media are placed on the surface of the transducer to change the acoustic load on the surface of the transducer. The fluctuation amplitude of the phase difference of the driving signal will be larger than that in the water when the iron plate is placed in in the focal plane. However, the phase fluctuation amplitude will be much smaller than that in the water when the beef liver is placed. This shows that different acoustic loads can cause the change of the electrical parameters of the transducer. The isolated bovine liver tissue was used as the HIFU irradiation object, and the results of the phase difference change were compared with the results of the isolated bovine liver tissue damage. The experimental results show that the phase of the transducer voltage and current will change from relatively stable to large fluctuations during the HIFU irradiation. At this time, obvious damage can be seen in the focal region when the irradiation is stopped, and the grayscale of B ultrasound image has no significant change. In addition, when the cavitation occurs in the focal region, the fluctuation amplitude and range will be larger than that. The damage area of the lower focal area under the monitoring method is smaller than that under b-ultrasonic monitoring, and the overinput of radiation dose can be avoided. This method can provide a new research scheme and means for HIFU focal area tissue damage monitoring.
A single synonymous nucleotide change impacts the male-killing phenotype of prophage WO gene wmk
Authors: Perlmutter Jessamyn I , Meyers Jane E , Bordenstein Seth R
Published: October 2021

Wolbachia are the most widespread bacterial endosymbionts in animals. Within arthropods, these maternally transmitted bacteria can selfishly hijack host reproductive processes to increase the relative fitness of their transmitting females. One such form of reproductive parasitism called male killing, or the selective killing of infected males, is recapitulated to degrees by transgenic expression of the prophage WO-mediated killing (wmk) gene. Here, we characterize the genotype-phenotype landscape of wmk-induced male killing in D. melanogaster using transgenic expression. While phylogenetically distant wmk homologs induce no sex-ratio bias, closely-related homologs exhibit complex phenotypes spanning no death, male death, or death of all hosts. We demonstrate that alternative start codons, synonymous codons, and notably a single synonymous nucleotide in wmk can ablate killing. These findings reveal previously unrecognized features of transgenic wmk-induced killing and establish new hypotheses for the impacts of post-transcriptional processes in male killing variation. We conclude that synonymous sequence changes are not necessarily silent in nested endosymbiotic interactions with life-or-death consequences.
Physical observables to determine the nature of membrane-less cellular sub-compartments
Authors: Heltberg Mathias L , Miné-Hattab Judith , Taddei Angela , Walczak Aleksandra M , Mora Thierry
Published: October 2021

The spatial organization of complex biochemical reactions is essential for the regulation of cellular processes. Membrane-less structures called foci containing high concentrations of specific proteins have been reported in a variety of contexts, but the mechanism of their formation is not fully understood. Several competing mechanisms exist that are difficult to distinguish empirically, including liquid-liquid phase separation, and the trapping of molecules by multiple binding sites. Here, we propose a theoretical framework and outline observables to differentiate between these scenarios from single molecule tracking experiments. In the binding site model, we derive relations between the distribution of proteins, their diffusion properties, and their radial displacement. We predict that protein search times can be reduced for targets inside a liquid droplet, but not in an aggregate of slowly moving binding sites. We use our results to reject the multiple binding site model for Rad52 foci, and find a picture consistent with a liquid-liquid phase separation. These results are applicable to future experiments and suggest different biological roles for liquid droplet and binding site foci.
Molecular reconstruction of recurrent evolutionary switching in olfactory receptor specificity
Authors: Prieto-Godino Lucia L , Schmidt Hayden R , Benton Richard
Published: October 2021

Olfactory receptor repertoires exhibit remarkable functional diversity, but how these proteins have evolved is poorly understood. Through analysis of extant and ancestrally reconstructed drosophilid olfactory receptors from the Ionotropic receptor (Ir) family, we investigated evolution of two organic acid-sensing receptors, Ir75a and Ir75b. Despite their low amino acid identity, we identify a common ‘hotspot’ in their ligand-binding pocket that has a major effect on changing the specificity of both Irs, as well as at least two distinct functional transitions in Ir75a during evolution. Moreover, we show that odor specificity is refined by changes in additional, receptor-specific sites, including those outside the ligand-binding pocket. Our work reveals how a core, common determinant of ligand-tuning acts within epistatic and allosteric networks of substitutions to lead to functional evolution of olfactory receptors.
mTORC1-induced retinal progenitor cell overproliferation leads to accelerated mitotic aging and degeneration of descendent Müller glia
Authors: Lim Soyeon , Kim You-Joung , Park Sooyeon , Choi Ji-heon , Sung Young Hoon , Nishimori Katsuhiko , Kozmik Zbynek , Lee Han-Woong , Kim Jin Woo
Published: October 2021

Retinal progenitor cells (RPCs) divide in limited numbers to generate the cells comprising vertebrate retina. The molecular mechanism that leads RPC to the division limit, however, remains elusive. Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Müller glia (MG) that degenerate from senescence-associated cell death. We further show the hyperproliferation of Tsc1-deficient RPCs and the degeneration of MG in the mouse retina disappear by concomitant deletion of hypoxia-induced factor 1-alpha (Hif1a), which induces glycolytic gene expression to support mTORC1-induced RPC proliferation. Collectively, our results suggest that, by having mTORC1 constitutively active, an RPC divides and exhausts mitotic capacity faster than neighboring RPCs, and thus produces retinal cells that degenerate with aging-related changes.
The Lon protease temporally restricts polar cell differentiation events during the Caulobacter cell cycle
Authors: Omnus Deike J , Fink Matthias J , Szwedo Klaudia , Jonas Kristina
Published: October 2021

The highly conserved protease Lon has important regulatory and protein quality control functions in cells from the three domains of life. Despite many years of research on Lon, only a few specific protein substrates are known in most organisms. Here, we used a quantitative proteomics approach to identify novel substrates of Lon in the dimorphic bacterium Caulobacter crescentus. We focused our study on proteins involved in polar cell differentiation and investigated the developmental regulator StaR and the flagella hook length regulator FliK as specific Lon substrates in detail. We show that Lon recognizes these proteins at their C-termini, and that Lon-dependent degradation ensures their temporally restricted accumulation in the cell cycle phase when their function is needed. Disruption of this precise temporal regulation of StaR and FliK levels in a Δlon mutant contributes to defects in stalk biogenesis and motility, respectively, revealing a critical role of Lon in coordinating developmental processes with cell cycle progression. Our work underscores the importance of Lon in the regulation of complex temporally controlled processes by adjusting the concentrations of critical regulatory proteins. Furthermore, this study includes the first characterization of FliK in C. crescentus and uncovers a dual role of the C-terminal amino acids of FliK in protein function and degradation.
Interplay between epigallocatechin-3-gallate and ionic strength during amyloid aggregation
Authors: Ziaunys Mantas , Mikalauskaite Kamile , Sakalauskas Andrius , Smirnovas Vytautas
Published: October 2021

The formation and accumulation of protein amyloid aggregates is linked with multiple amyloidoses, including neurodegenerative Alzheimer’s or Parkinson’s disease. The mechanism of such fibril formation is impacted by various environmental conditions, which greatly complicates the search for potential anti-amyloid compounds. One of these factors is solution ionic strength, which varies between different aggregation protocols during in vitro drug screenings. In this work, we examine the interplay between ionic strength and a well-known protein aggregation inhibitor—epigallocatechin-3-gallate. We show that changes in solution ionic strength have a major impact on the compound’s inhibitory effect, reflected in both aggregation times and final fibril structure. We also observe that this effect is unique to different amyloid-forming proteins, such as insulin, alpha-synuclein and amyloid-beta.
Role of Point of Care Ultra Sound (POCUS) in Assessment of Fluid Resuscitation in Septic Patients
Authors: Fouad Sohier , Elshamaa Nagat , El-Baradey Ghada , Elgendy Hala
Published: October 2021

Background: Initial fluid resuscitation in sepsis must be guided by clinical judgment based on ongoing reevaluation of the hemodynamic status (heart rate, blood pressure, arterial oxygen saturation, respiratory rate, temperature, urine output) and ultrasound measurements (stroke volume, cardiac output, lung ultrasound and inferior vena cava diameter) as positive fluid balance is harmful.

Methods: Adults Patients (≥ 18 years old) with symptoms or signs of tissue hypoperfusion (Sequential organ failure assessment score SOFA≥ 2) are included. Patients with elevated intra-abdominal pressure (as, ascites, pregnancy), Recent abdominal operation, cannot lie flat, Patient on mechanical ventilation and patients with valvular heart disease were excluded. IVC CI, SV, COP and B mean score were measured on patient arrival and after every 10 ml/kg isotonic saline over the first hour of patient arrival. Thereafter, patients were divided into two groups high caval index and low caval index according to inferior vena cava collapsibility index.

Results: Among our 50 patients,38% of patients were with high caval index and 62% have low caval index.

Conclusion: POCUS has additive value in guiding of fluid resuscitation in sepsis in order to avoid fluid overload and to identify proper timing of vasopressor use.
Effect of Intravenous Acetaminophen and Flurbiprofen on Postoperative Pain after Lumbar Disc Surgery
Authors: Ono Maki , Terao Yoshiaki , Komatsu Yuya , Shimazaki Ayako , Oji Natsuko , Oji Makito
Published: October 2021

Aims: Lumbar disc surgery is often associated with moderate to severe postoperative pain. Whether non-steroidal anti-inflammatory drugs or acetaminophen provides effective analgesia following lumbar disc surgery remains controversial. This study aimed to determine whether flurbiprofen produces analgesic effects equivalent to those of acetaminophen after lumbar disc surgery.

Study Design: Prospective, randomized, open-label, placebo-controlled trial

Place and Duration of Study: Department of Anesthesia, Nagasaki Rosai Hospital, Sasebo, Japan, between April 2018 and March 2019.

Methodology: We studied 76 patients who underwent elective lumbar disc surgery under general anesthesia. The patients were randomly allocated to one of three groups. Group A (n=25) received 1000 mg of acetaminophen intravenously every 6 h. Group F (n=25) received 50 mg of flurbiprofen intravenously every 6 h. Group C (n=26) received saline intravenously every 6 h as a placebo. Each drug was started before skin closure 18 h after surgery. All patients were anesthetized under total intravenous anesthesia with propofol and remifentanil and received fentanyl before skin closure. Postoperative pain was evaluated using a numerical rating scale (NRS) at 0, 1, 3, 6, 12, 18, and 24 h postoperatively. The patients were administered diclofenac sodium or loxoprofen, as rescue analgesics, as needed.

Results: There were no significant differences in patient characteristics among the three groups. There were no significant differences in NRS scores among the three groups during the study period. However, rescue analgesics were administered significantly less frequently in group F than in groups A and C over 12 h and 24 h, respectively.

Conclusion: The results of this study showed that flurbiprofen might provide more effective analgesia than acetaminophen following lumbar disc surgery.
Flexible Metal‐Organic Framework for Mechanical Sub Tbyte inch−2 Data Recording under Ambient Condition
Authors: Alekseevskiy P. V. , Rzhevskiy S. , Gilemkhanova V. , Kulachenkov N. K. , Sapianik A. , Barsukova M. , Fedin V. P. , Milichko V. A.
Published: October 2021

Metal‐organic frameworks (MOFs), demonstrating structural response on external stimuli, represent a promising family of crystalline materials for microelectronic and data storage devices. Herein, manipulation with MOF structure at the nanometer scale for the device miniaturization is still a challenge. Here, mechanical recording and reading the nanometer scale patterns onto flexible 2D MOF at ambient conditions are reported. Treatment of the MOF surface with a hot solvent decreases the roughness up to 1/7 of the layer thickness. Therefore, an atomic force microscope probe is allowed to cause the deformations with the spatial resolution up to 25 nm (≈0.1 Tbyte inch−2 storage density) and the depth from 0.4 nm. Selective chemical etching by the solvent can further develop the pattern, while the integrity of the MOF structure maintains. The realization of the "read‐only‐memory" concept on flexible MOF at ambient conditions paves the way for next‐generation sustainable data storage materials.
Elucidating Extracellular Matrix and Stiffness Control of Primary Human Hepatocyte Phenotype via Cell Microarrays
Authors: Monckton Chase P. , Brougham‐Cook Aidan , Kaylan Kerim B. , Underhill Gregory H. , Khetani Salman R.
Published: October 2021

How the liver's extracellular matrix (ECM) protein composition and stiffness cooperatively regulate primary human hepatocyte (PHH) phenotype is unelucidated. Here, protein microarrays and high‐content imaging with single‐cell resolution are utilized to assess PHH attachment/functions on 10 major liver ECM proteins in single‐ and two‐way combinations robotically spotted onto polyacrylamide gels of 1  or 25 kPa stiffness. Albumin, cytochrome‐P450 3A4 (CYP3A4), and hepatocyte nuclear factor alpha (HNF4α) positively correlate with each other and cell density on both stiffnesses. The 25 kPa stiffness supports higher average albumin and HNF4α expression after 14 d, while ECM protein composition significantly modulates PHH functions across both stiffnesses. Unlike previous rodent data, PHH functions are highest only when collagen‐IV or fibronectin are mixed with specific proteins, whereas noncollagenous proteins without mixed collagens downregulate functions. Combination of collagen‐IV and hyaluronic acid retains high CYP3A4 on 1 kPa, whereas collagens‐IV and ‐V better retain HNF4α on 25 kPa over 14 d. Adapting ECM conditions to 96‐well plates containing conjugated hydrogels reveals novel regulation of other functions (urea, CYP1A2/2A6/2C9) and drug‐mediated CYP induction by the ECM protein composition/stiffness. This high‐throughput pipeline can be adapted to elucidate ECM's role in liver diseases and facilitate optimization of engineered tissues.
Metal nanocluster‐based devices: Challenges and opportunities
Authors: Chen Lizhen , Black Andres , Parak Wolfgang J. , Klinke Christian , Chakraborty Indranath
Published: October 2021

Atomically precise nanoclusters (NCs) with fascinating physicochemical characteristics different from their nanoparticles (NPs) counterparts have gained increasing attention in diverse fields of applications. The foremost outcome of such NC‐based applications is leading to transform them into devices. In fact, there are already some reports on the development of NC‐based devices. For instance, NCs exhibit their potential in solar cells, showing high light‐harvesting efficiency comparable to traditional semiconductor solar cells. Further, recent progress in characterizing Au NCs films and micro‐crystals shows semiconductor‐like properties such as field effect and photoresponse. These successes indicate that metal NCs possess a high potential for application in multidisciplinary areas for advancing the development in fundamental and practical purposes. However, no such comprehensive review is available to highlight recent advances and new applicable devices based on noble metal NCs. Herein, we reviewed the recent development in this area, including synthesis challenges of metal NCs and related applications of NC‐sensitized solar cells, strain sensors, chemo‐/biosensors, transistors, floating memory, and other devices. Furthermore, the future opportunities such as modifying synthetic methods to make other metal NCs, enhancing the efficiency of solar cells, and exploring more NC‐based devices alternative to semiconductors are pointed out. We hope that rapidly increasing interest in NC‐based devices will stimulate the research in this area and inspire the advances in combined devices accordingly.
Enhanced electrochemical performance of neural electrodes based on PEDOT:PSS hydrogel
Authors: Zeng Qi , Wu Tianzhun
Published: October 2021

Poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has attracted much attention on applications of neural interfaces and other biomedical fields due to its excellent electrical performances and good biocompatibility. However, its stability still remains challenge. Here, a conductive polymer hydrogel (CPH) made from PEDOT:PSS is modified on platinum (Pt) substrate successfully through electrochemical gelation, employing copper (Cu) as the sacrificial layer. The as‐prepared CPH electrode provides extensive large surface area with good adhesion after dried in the air. The uniform flower‐like structure helps the electrode achieve a significantly low square impedance down to 10.09 Ω cm2 (reduction of 54.89%) at 1 kHz, compared with that of bare Pt. It exhibits a high cathodic charge storage capacity (CSCc) up to 82.36 mC cm−2, about 27 and 16.18 times higher than that of bare Pt and PEDOT:PSS coating respectively. Besides, no obviously variation of CSCc occurs after 5 CV cycles in phosphate buffered saline (PBS), and superior charge injection capacity (CIC) was also observed. Such CPH material presents great potential for preparing functionalized flexible electrode, implying promising applications on neural implants and other flexible electronics.
Synthesis of a Negative Photochrome with High Switching Quantum Yields and Capable of Singlet‐Oxygen Production and Storage
Authors: Ziani Zakaria , Loiseau Frédérique , Lognon Elise , Boggio‐Pasqua Martial , Philouze Christian , Cobo Saioa , Royal Guy
Published: October 2021

A dimethyldihydropyrene (DHP) photochromic unit has been functionalized by donor (triphenylamine group) and acceptor (methylpyridinium) substituents. This compound was characterized by NMR, absorption and emission spectroscopies as well as cyclic voltammetry, and its properties were rationalized by theoretical calculations. The incorporation of both electron‐donor and ‐withdrawing groups at the photochromic center allows i) an efficient photo‐isomerization of the system when illuminated at low energy (quantum yield: Φc‐o=13.3 % at λex=660 nm), ii) the reversible and quantitative formation of two endoperoxyde isomers when illuminated under aerobic conditions at room temperature, and iii) the storage and production of singlet oxygen. The photo‐isomerization mechanism was also investigated by spin‐flip TD‐DFT (SF‐TD‐DFT) calculations.
Family‐based treatment for adolescent anorexia nervosa: Outcomes of a stepped‐care model
Authors: Le Grange Daniel , Pradel Martin , Pogos Danielle , Yeo Michele , Hughes Elizabeth K. , Tompson Alicia , Court Andrew , Crosby Ross D. , Sawyer Susan M.
Published: October 2021

Objective

Stepped‐care models of treatment are underexplored in eating disorders. To enhance treatment outcomes, and informed by literature about adaptations to family‐based treatment (FBT), we developed an FBT‐based stepped‐care model for adolescents with anorexia nervosa (AN) that was consistent with family preference (i.e., tailored) and responsive to adolescent needs (i.e., intensity). The aim of this study was to evaluate the effectiveness of this model in terms of remission at end‐of‐treatment.

Method

Adolescents (N = 82), aged 12–18 years (M = 15.1, SD = 1.8) and meeting Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria for AN, were assessed at baseline, Weeks 24 and 48. FBT was tailored to family preference and clinical need, with 16–18 sessions by Week 24. This was followed by three FBT booster sessions or an extension of FBT plus booster sessions (Week 48). The primary outcome was defined as weight > 95% of %median body mass index plus within 1 SD of the Eating Disorder Examination (EDE) global score community norms.

Results

Remission rates were 45.1% and 52.4% at Weeks 24 and 48, respectively. Commensurable improvements were evident across secondary outcomes (e.g., EDE subscale scores). As a reference point, remission rates compared positively with results from a recent randomized clinical trial from the same center and at the same time points (Week 24:45.1% vs. 32.1% and Week 48:52.4% vs. 30.2%). Controlling for propensity score, no statistically significant differences were observed.

Discussion

This stepped‐care model, designed to be responsive to the individual needs of adolescents and their families, achieved encouraging rates of remission. This study provides an important signal that supports future clinical trials of stepped‐care models for adolescents with AN.
Voltammetric Sensing of Soybean Agglutinin Using an Electrode Modified with Electron‐transfer, Carbohydrate‐mimetic/Cross‐linker‐peptide‐collagen Film
Authors: Ishizaki Sora , Kuramitz Hideki , Sugawara Kazuharu
Published: October 2021

We constructed an electrochemical sensor based on an electrode modified with electron‐transfer, carbohydrate‐mimetic peptides on collagen film. The peptide consisted of Ac‐Y4C combined with soybean agglutinin (SBA). To evaluate the binding between SBA and the peptide, we prepared Ac‐Y4CAn (3‐6) containing oligoalanine as a cross‐linker. When SBA and Y4C on the electrode were incubated, the peak was decreased by the SBA uptake of the peptide. The change in the peak current using Ac‐Y4CA6 was the greatest of the four peptides. The calibration curve was linear and ranged from 4.0×10−14 to 1.2×10−12 M with a detection limit of 1.3×10−14 M.