bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrin–ECM interactions and membrane-associated Catalase cooperate to promote resilience of the Drosophila intestinal epithelium
Authors: Mlih Mohamed , Karpac Jason
Published: May 2022

Balancing cellular demise and survival constitutes a key feature of resilience mechanisms that underlie the control of epithelial tissue damage. These resilience mechanisms often limit the burden of adaptive cellular stress responses to internal or external threats. We recently identified Diedel, a secreted protein/cytokine, as a potent antagonist of apoptosis-induced regulated cell death in the Drosophila intestinal midgut epithelium during aging. Here, we show that Diedel is a ligand for RGD-binding Integrins and is thus required for maintaining midgut epithelial cell attachment to the extracellular matrix (ECM)-derived basement membrane. Exploiting this function of Diedel, we uncovered a resilience mechanism of epithelial tissues, mediated by Integrin–ECM interactions, which shapes cell death spreading through the regulation of cell detachment and thus cell survival. Moreover, we found that resilient epithelial cells, enriched for Diedel–Integrin–ECM interactions, are characterized by membrane association of Catalase, thus preserving extracellular reactive oxygen species (ROS) balance to maintain epithelial integrity. Intracellular Catalase can relocalize to the extracellular membrane to limit cell death spreading and repair Integrin–ECM interactions induced by the amplification of extracellular ROS, which is a critical adaptive stress response. Membrane-associated Catalase, synergized with Integrin–ECM interactions, likely constitutes a resilience mechanism that helps balance cellular demise and survival within epithelial tissues.
A functional approach towards the design, development, and test of an affordable dynamic prosthetic foot
Authors: Falbriard Mathieu , Huot Grégory , Janier Mathieu , Chandran Rajasundar , Rechsteiner Michael , Michaud Véronique , Cugnoni Joël , Botsis John , Schönenberger Klaus , Aminian Kamiar
Published: May 2022

Humanitarian actors involved in physical rehabilitation, such as the International Committee of the Red Cross (ICRC), usually provide their beneficiaries with lower-limb prostheses comprising Solid Ankle Cushion Heel (SACH) feet as these are considered appropriate (price, durability, low profile to fit a majority of patients, appearance) and reliable for all ambulation levels. However, individuals in low-resource settings having higher ambulation abilities would greatly benefit from dynamic prosthetic feet with improved biomechanics and energy storage and release. Some attempts tried to address this increasing need (e.g. Niagara Foot) but most products proposed by large manufacturers often remain unaffordable and unsuitable to the context of low-resource settings. The design requirements and a price target were defined in partnership with the ICRC according to their initial assessment and used as a starting point for the development process and related technological choices. Numerical simulation and modeling were used to work on the design and to determine the required materials properties (mechanical, chemical, wear), and a cost modeling tool was used to select suitable materials and relevant processing routes (price vs. performance). A prosthetic foot comprising an internal keel made of composite materials, a filling foam, and a cosmetic shell with a foot shape was developed. Manufacturing processes meeting the cost criteria were identified and prototype feet were produced accordingly. These were successfully tested using a compression testing system before gait analyses were performed in the laboratory with non-amputees wearing testing boots. After validation in laboratory conditions, the prototype foot was tested in the field (Vietnam) with 11 trans-tibial unilateral amputees, who showed an increased mobility compared with the SACH foot. The collaboration of different research fields led to the development of a prosthetic foot which met the technical requirements determined by the ICRC’s specific needs in its field of operation. The materials and selected production processes led to a manufacturing cost of less than 100 USD per part.
Interoception is associated with anxiety and depression in pregnant women: A pilot study
Authors: Noda Minami , Sato Yoko , Suetsugu Yoshiko , Morokuma Seiichi
Published: May 2022

Pregnancy and postpartum are periods in which women develop psychosocially. However, becoming a mother is stressful, and mood disorders related to anxiety and depression often develop. In recent years, research on interoception—sensations related to the body’s internal physiological state—has attracted attention. Interoception has multifaceted characteristics. It involves directly perceiving information in the body while also inferring and evaluating it. In this study, we examined interoception, anxiety, and depression in Japanese pregnant women. Empirical examinations and questionnaire surveys were used to measure interoception in 32 pregnant women not at high risk of pregnancy. A Japanese adaption of the Multidimensional Assessment of Interoceptive Awareness was used to measure interoceptive sensibility, and a heartbeat counting task performance was used to measure interoceptive accuracy. Anxiety and depression were measured using the Japanese versions of the State-Trait Anxiety Inventory and the Edinburgh Postnatal Depression Scale, respectively. A correlation analysis was performed between interoception, anxiety and depression and between differences between sensibility and accuracy of interoception, anxiety and depression. We revealed that interoceptive sensibility and differences between sensibility and accuracy of interoception were associated with anxiety. Based on results of this pilot study, it is necessary to investigate using longitudinal studies whether interoception might be an effective predictor tool for early detection of anxiety during pregnancy and postpartum.
A research protocol on leap motion tracking device: A novel intervention method in distal radial fracture rehabilitation
Authors: Arora Sakshi P. , Naqvi Waqar M.
Published: May 2022

Introduction

Physiotherapeutic rehabilitation are used to optimize functional recovery following a distal radial fracture (DRF). Being most common upper limb fracture in all age groups, the DRF peaks in young men and in post-menopausal women with incidence ratio of 1:4. Leap motion control based rehabilitation of patients with DRF is limited. This research aims to assess the efficacy of leap motion control based rehabilitation in patients with DRF.

Methods

In an randomized parallel group trial, subjects (n = 40) with DRF will be recruited. The participants will be enrolled into either experimental or control group with 1:1 allocation ratio. Following the primary assessment and allocation, the participants in experimental group will receive both leap motion control and conventional therapy over a period of six weeks. Participants in conventional group would undergo only conventional therapy. The primary outcome measures will be Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and Universal goniometer however the grip strength and Visual Analog Scale (VAS) will be used as secondary outcome measures.

Purpose of the study

The findings of this trial will examine the impact of leap motion control in DRF patients with conventional therapy on improving the functional activity, range of motion (ROM), grip strength and pain.

Expected clinical implications

To conclude, this research seeks to examine the rapid and long term effects of leap motion control in DRF patients. The study findings would help prospective patients with DRF, which may include a newly designed approach of rehabilitation.
The efficacy of T790M mutation testing in liquid biopsy—Real clinic data
Authors: Krawczyk Paweł , Grzycka-Kowalczyk Luiza , Błach Justyna , Reszka Katarzyna , Chmielewska Izabela , Kieszko Robert , Wójcik-Superczyńska Magdalena , Szczyrek Michał , Jankowski Tomasz , Milanowski Janusz
Published: May 2022

Osimertnib is still widely used in the treatment of NSCLC patients who have previously received erlotinib, gefitinib or afatinib and have developed resistance to these drugs mediated by the T790M mutation in exon 20 of EGFR gene. We assessed the results of T790M mutation testing in liquid biopsy by Entrogen test and real-time PCR technique in routine clinical practice. Analysis was conducted in 73 plasma samples from 41 patients with locally advanced or metastatic lung adenocarcinoma treated with first- or second-generation of EGFR TKIs. We detected T790M mutation in 18 patients (43.9% of patients, 24.6% positive tests in 73 samples). The incidence of T790M mutation in liquid biopsy was significantly higher in patients with T3-T4 tumors compared to patients with T0-T2 tumors (p = 0.0368, χ2 = 4.36). Median PFS at the time of progression according to RECIST was significantly (p = 0.0444) higher in patients with T790M mutation than in patients without this mutation (22.5 vs. 15 months). Our results confirmed that T790M mutation is more often detected in patients with a large tumor spreading in the chest and with the long duration of response to first- or second generation of EGFR TKIs. The low sensitivity of the real-time PCR technique in T790M mutation detection could be partially compensated by repeating the tests.
Thalamic activations in rat brain by fMRI during tactile (forepaw, whisker) and non-tactile (visual, olfactory) sensory stimulations
Authors: Sanganahalli Basavaraju G. , Thompson Garth J. , Parent Maxime , Verhagen Justus V. , Blumenfeld Hal , Herman Peter , Hyder Fahmeed
Published: May 2022

The thalamus is a crucial subcortical hub that impacts cortical activity. Tracing experiments in animals and post-mortem humans suggest rich morphological specificity of the thalamus. Very few studies reported rodent thalamic activations by functional MRI (fMRI) as compared to cortical activations for different sensory stimuli. Here, we show different portions of the rat thalamus in response to tactile (forepaw, whisker) and non-tactile (visual, olfactory) sensory stimuli with high field fMRI (11.7T) using a custom-build quadrature surface coil to capture high sensitivity signals from superficial and deep brain regions simultaneously. Results demonstrate reproducible thalamic activations during both tactile and non-tactile stimuli. Forepaw and whisker stimuli activated broader regions within the thalamus: ventral posterior lateral (VPL), ventral posterior medial (VPM), lateral posterior mediorostral (LPMR) and posterior medial (POm) thalamic nuclei. Visual stimuli activated dorsal lateral geniculate nucleus (DLG) of the thalamus but also parts of the superior/inferior colliculus, whereas olfactory stimuli activated specifically the mediodorsal nucleus of the thalamus (MDT). BOLD activations in LGN and MDT were much stronger than in VPL, VPM, LPMR and POm. These fMRI-based thalamic activations suggest that forepaw and whisker (i.e., tactile) stimuli engage VPL, VPM, LPMR and POm whereas visual and olfactory (i.e., non-tactile) stimuli, respectively, recruit DLG and MDT exclusively.
Is oxytocin a trust hormone? Salivary oxytocin is associated with caution but not with general trust
Authors: Shou Qiulu , Yamada Junko , Nishina Kuniyuki , Matsunaga Masahiro , Kiyonari Toko , Takagishi Haruto
Published: May 2022

Studies on the association between trust and oxytocin, a neuropeptide of the central nervous system, have not reached a consensus, thereby challenging the possibility of a direct association between the two. However, previous studies have not examined how oxytocin is correlated with trust, based on its categorization into different factors in the field of social science. For instance, based on Yamagishi’s trust theory, trust can be categorized into two factors: general trust and caution. General trust refers to beliefs about the trustworthiness of others, whereas caution refers to the belief that caution is needed when dealing with high social uncertainty. In this study, to examine the relationship between these two factors and oxytocin, we analyzed data of 197 adults (men = 98, women = 99; mean age = 41.7 years; standard deviation for age = 10.4 years) and examined the relationships between these two factors of trust and endogenous salivary oxytocin levels. We found that oxytocin was positively correlated with caution rather than with general trust thereby suggesting that oxytocin plays a role in regulating caution rather than general trust among the components of trust. The present study demonstrated that salivary oxytocin level can act as a biomarker that partially predicts one’s trust, especially as reflected by caution.
An adaptive, asymptomatic SARS-CoV-2 workforce screening program providing real-time, actionable monitoring of the COVID-19 pandemic
Authors: Hijano Diego R. , Hoffman James M. , Tang Li , Schultz-Cherry Stacey L. , Thomas Paul G. , Hakim Hana , Webby Richard J. , Hayden Randall T. , Gaur Aditya H. ,   St. Jude COVID-19 Employee Screening Program Team
Published: May 2022

COVID-19 remains a challenge worldwide, and testing of asymptomatic individuals remains critical to pandemic control measures. Starting March 2020, a total of 7497 hospital employees were tested at least weekly for SARS CoV-2; the cumulative incidence of asymptomatic infections was 5.64%. Consistently over a 14-month period half of COVID-19 infections (414 of 820, total) were detected through the asymptomatic screening program, a third of whom never developed any symptoms during follow-up. Prompt detection and isolation of these cases substantially reduced the risk of potential workplace and outside of workplace transmission. COVID-19 vaccinations of the workforce were initiated in December 2020. Twenty-one individuals tested positive after being fully vaccinated (3.9 per 1000 vaccinated). Most (61.9%) remained asymptomatic and in majority (75%) the virus could not be sequenced due to low template RNA levels in swab samples. Further routine testing of vaccinated asymptomatic employees was stopped and will be redeployed if needed; routine testing for those not vaccinated continues. Asymptomatic SARS-CoV-2 testing, as a part of enhanced screening, monitors local dynamics of the COVID-19 pandemic and can provide valuable data to assess the ongoing impact of COVID-19 vaccination and SARS-CoV-2 variants, inform risk mitigation, and guide adaptive, operational planning including titration of screening strategies over time, based on infection risk modifiers such as vaccination.
Regulation of CLB6 expression by the cytoplasmic deadenylase Ccr4 through its coding and 3’ UTR regions
Authors: Revilleza Jastin Edrian Cocuangco , Sato Megumi , Irie Kaoru , Suda Yasuyuki , Mizuno Tomoaki , Irie Kenji
Published: May 2022

RNA stability control contributes to the proper expression of gene products. Messenger RNAs (mRNAs) in eukaryotic cells possess a 5’ cap structure and the 3’ poly(A) tail which are important for mRNA stability and efficient translation. The Ccr4-Not complex is a major cytoplasmic deadenylase and functions in mRNA degradation. The CLB1-6 genes in Saccharomyces cerevisiae encode B-type cyclins which are involved in the cell cycle progression together with the cyclin-dependent kinase Cdc28. The CLB genes consist of CLB1/2, CLB3/4, and CLB5/6 whose gene products accumulate at the G2-M, S-G2, and late G1 phase, respectively. These Clb protein levels are thought to be mainly regulated by the transcriptional control and the protein stability control. Here we investigated regulation of CLB1-6 expression by Ccr4. Our results show that all CLB1-6 mRNA levels were significantly increased in the ccr4Δ mutant compared to those in wild-type cells. Clb1, Clb4, and Clb6 protein levels were slightly increased in the ccr4Δ mutant, but the Clb2, Clb3, and Clb5 protein levels were similar to those in wild-type cells. Since both CLB6 mRNA and Clb6 protein levels were most significantly increased in the ccr4Δ mutant, we further analyzed the cis-elements for the Ccr4-mediated regulation within CLB6 mRNA. We found that there were destabilizing sequences in both coding sequence and 3’ untranslated region (3’ UTR). The destabilizing sequences in the coding region were found to be both within and outside the sequences corresponding the cyclin domain. The CLB6 3’ UTR was sufficient for mRNA destabilization and decrease of the reporter GFP gene and this destabilization involved Ccr4. Our results suggest that CLB6 expression is regulated by Ccr4 through the coding sequence and 3’ UTR of CLB6 mRNA.
Weighted

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Authors: Yao Fengping
Published: May 2022

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Load carrying capacity of masonry arch railway bridges at the serviceability limit state
Authors: Vokál Marek , Drahorád Michal
Published: May 2022

This article focuses on masonry arch railway bridges. The main topic is the algorithm, which was developed for the purpose of a non-linear arch bridge analysis. The sensitivity analysis of the input parameters of the calculation was carried out. Subsequently, the study was carried out for the comparison of four calculation methods. For this comparison, a set of arch bridges were chosen. Two methods used commercial software, and the other two methods were developed. One of the developed algorithms uses a simple linear calculation. The second developed algorithm uses an iterative approach to handle material and geometrical non-linearity. The first commercial software method uses 2D non-linear models, the second method is a limit collapse analysis using the software LimitState:RING. These three methods were developed to handle the SLS (serviceability limit state) criteria, and their results were compared to the result of LCC at the ULS (ultimate LS) using LimitState:RING.
Estrategia de aprendizaje de la programación apoyado en aprendizaje significativo, brain-based learning y disposición estética
Authors: Trejos Buriticá Omar Ivan , Muñoz Guerrero Luis Eduardo
Published: May 2022

Objetivo: Analizar y establecer si existe relación entre la disposición estética de elementos en el tablero y su impacto en el aprendizaje de la programación de computadores.
Metodología: Este estudio se realizó en paralelo entre dos grupos por semestre del año 2015 al 2018. Los elementos estéticos referidos en esta investigación se aplicaron en un grupo, y dichos elementos fueron removidos en el otro. La investigación es de carácter cualitativo, con un componente final cuantitativo.
Resultados: Los resultados evidencian una relación directa entre el aprendizaje de la programación de computadores por parte de los estudiantes y la disposición estética a la que se refiere este artículo.
Conclusiones: Se concluye que el conocimiento es más comprensible y significativo para el estudiante cuando está estéticamente distribuido con los recursos del aula, lo cual facilita la ubicación del conocimiento en la memoria a largo plazo.
Financiamiento: Universidad Tecnológica de Pereira
Taxonomía de las alternativas de outsourcing mediante revisión sistemática de literatura
Authors: López Ramírez Cesar Augusto , García Cáceres Rafael Guillermo , Herrera Rodríguez Jenny Mairena
Published: May 2022

Objetivo: Facilitar la gestión de la cadena de suministro y los procesos de toma de decisiones. Se analiza el caso de América Latina como opción de outsourcing para ilustrar su aplicación.
Metodología: Se presenta una taxonomía soportada en Systematic Literature Review para determinar la estrategia de outsourcing logístico que debe desarrollar una empresa o cadena de suministro, entre las alternativas de deslocalización y nearshoring. Para determinar los criterios de decisión, se realiza una revisión de la literatura y se proporciona una caracterización de los criterios centrales de las dos estrategias.
Resultados: La alternativa de offshoring suelen brindar beneficios relacionados con mayores capacidades productivas que inciden en menores costos de fabricación, lo que la hace idónea para la producción de productos masivos. Las ventajas de nearshoring se centran en una mayor flexibilidad, lo que lo hace idóneo para la producción de productos con mayor margen de utilidad a mercados exclusivos.
Conclusiones: Latinoamérica aparece en el momento como una gran opción tanto para offshoring como para nearshoring, especialmente para EE.UU., Canadá y los países Europeos. Para esto, los estados y las compañías deben reformular sus estrategias de crecimiento político-privado centrado en estrategias claras que promuevan el desarrollo de capacidades productivas, logísticas, tecnológicas y de innovación, el fomento a la inversión extranjera, el desarrollo educativo y científico, y el crecimiento de las demandas regionales.
Financiación: Universidad Pedagógica y Tecnológica de Colombia (UPTC).
Palabras clave: Nearshore, Offshore, Onshore, Outsourcing.
Notes on Quasicrystals and the Origin of Life
Authors: Gardiner John , - -
Published: May 2022

We still do not understand the origins of life. Here I suggest that it may have arisen as a fractal quasicrystal of organic molecules on a metallic quasicrystalline template. It may have arisen at least twice, once with pentagonal symmetry and once with octagonal symmetry. In both instances these protolife forms are part of an imperfect fractal continuum from the subatomic to the galactic.
Structure of analytical ion-acoustic solitary wave solutions for the dynamical system of nonlinear wave propagation
Authors: Zahed Hanadi , Seadawy Aly R. , Iqbal Mujahid
Published: May 2022

In the present study, the ion-acoustic solitary wave solutions for Kadomtsev–Petviashvili (KP) equation, potential KP equation, and Gardner KP equation are constructed. The nonlinear KP equations are studying the nonlinear process of waves without collisions plasma and having non-isothermal electrons and cold ions. Two-dimensional ion-acoustic solitary waves (IASWs) in magnetized plasma are consisting of electrons and ions. We obtained the ion-acoustic solitary wave solutions same as dark and bright, kink and anti-kink wave solitons. The physical phenomena of various structures for IASWs are represented graphically with symbolic computations. These results are more helpful in the development of soliton dynamics, quantum plasma, dynamic of adiabatic parameters, fluid dynamics, and industrial phenomena.
Copper nanoparticles catalyzed carbon–heteroatom bond formation and synthesis of related heterocycles by greener procedures
Authors: Ahammed Sabir , Ranu Brindaban C.
Published: May 2022

A variety of procedures for the carbon–nitrogen, carbon–oxygen, carbon–sulfur and carbon–selenium bond formation using copper nanoparticles in greener conditions have been highlighted. The synthesis of several heterocyclic compounds of biological importance has also been reported using these protocols.
The geographical dispersion of inventor networks in peripheral economies
Authors: Cano-Kollmann Marcelo , Mudambi Ram , Tavares-Lehmann Ana Teresa
Published: May 2022

In this paper we explore patenting activity in two peripheral economies (Portugal and Greece), to analyze the dispersion of inventor networks. Inventor networks are key conduits through which knowledge flows. Therefore, they can be critical in the catch-up process of peripheral economies – economies that belong to the group of rich countries but have weaker innovation systems. As global value chains fragment into geographically dispersed activities, opportunities arise for peripheral economies to participate in global innovation processes. However, different types of innovation activities have distinct network properties. More codifiable innovative activities can be carried out through collaboration by internationally dispersed teams. On the other hand, activities that are more dependent on tacit knowledge are likely to require the co-location of knowledge workers. This implies that innovation that relies mostly on tacit knowledge will provide limited connectivity benefits for peripheral economies’ innovation systems. We hypothesize that, while this is generally true, “leading” innovative multinational enterprises may possess more sophisticated capabilities for transnational collaboration than less innovative firms. Therefore, innovation in activities involving tacit knowledge may show different network characteristics depending on who performs them: leading firms or “laggards”. Our results, based on data from Portugal and Greece are consistent with our hypotheses.
Üben, Üben, Üben. Ein Dreiergespräch über die religions- und philosophiedidaktische Grundfrage nach der Ambiguität der Praxis als Ort der Wahrheit
Authors: Berner-Zumpf Daniela , Kamcili-Yildiz Naciye , Schroeter-Wittke Harald
Published: May 2022

Üben ist eine philosophisch und religiös weit verbreitete und fundamentale Praxis, die die Ambiguität von Wahrheit performt. In Anlehnung an Bollnows Erörterungen „Vom Geist des Übens“ (1978) werden evangelische, islamische und philosophische Einsichten und Erfahrungen zur Didaktik auf die schulische Wirklichkeit und darüber hinaus reflektiert.
„Alle zusammen“ – ein neues Buch für den Religionsunterricht oder: Das Buch für einen neuen Religionsunterricht
Authors: Steinkühler Martina
Published: May 2022

Dieser Artikel ist ein Beitrag zur Debatte um den konfessionellen Religionsunterricht unter den Bedingungen weltanschaulicher Pluralität. Den Anlass bildet ein neues Unterrichtswerk. Es erhebt den Anspruch, ein wahrhaft offenes Angebot für heterogene Gruppen bereitzustellen – bedingungslos und ohne eine andere Absicht, als zum Nachdenken über das Leben herauszufordern. In einer vergleichenden Analyse des neuen Buches mit eingeführten Lehrwerken kann gezeigt werden, dass bei jeweils ähnlicher Profilierung dennoch verschiedene Vorstellungen von religiösem Lernen umgesetzt werden. Den entscheidenden Unterschied macht die ‚Stimme des Buches‘: Setzt sie einen Rahmen oder setzt sie frei? Die Beobachtungen führen zu der Frage, wie viel Freiheit nötig oder möglich ist, wenn die Konfessionalität ihren Sinn behalten soll.
Glutamate Transporters EAAT2 and EAAT5 Differentially Shape Synaptic Transmission from Rod Bipolar Cell Terminals
Authors: Tang Fu-Sheng , Yuan He-Lan , Liu Jun-Bin , Zhang Gong , Chen Si-Yun , Ke Jiang-Bin
Published: May 2022

Excitatory amino acid transporters (EAATs) control visual signal transmission in the retina by rapidly removing glutamate released from photoreceptors and bipolar cells (BCs). Although it has been reported that EAAT2 and EAAT5 are expressed at presynaptic terminals of photoreceptors and some BCs in mammals, the distinct functions of these two glutamate transporters in retinal synaptic transmission, especially at a single synapse, remain elusive. In this study, we found that EAAT2 was expressed in all BC types while coexisting with EAAT5 in rod bipolar (RB) cells and several types of cone BCs from mice of either sex. Our immunohistochemical study, together with a recently published literature (Gehlen et al., 2021), showed that EAAT2 and EAAT5 were both located in RB axon terminals near release sites. Optogenetic, electrophysiological and pharmacological analyses, however, demonstrated that EAAT2 and EAAT5 regulated neurotransmission at RB→AII amacrine cell synapses in significantly different ways: EAAT5 dramatically affected both the peak amplitude and kinetics of postsynaptic responses in AIIs, whereas EAAT2 had either relatively small or opposite effects. By contrast, blockade of EAAT1/GLAST, which was exclusively expressed in Müller cells, showed no obvious effect on AII responses, indicating that glutamate uptake by Müller cells did not influence synaptic transmission from RB terminals. Furthermore, we found that temporal resolution at RB→AII synapses was reduced substantially by blockade of EAAT5 but not EAAT2. Taken together, our work reveals the distinct functions of EAAT2 and EAAT5 in signal transmission at RB ribbon synapses.
Synaptic Integration in CA1 Pyramidal Neurons Is Intact despite Deficits in GABAergic Transmission in theScn1aHaploinsufficiency Mouse Model of Dravet Syndrome
Authors: Chancey Jessica Hotard , Howard MacKenzie Allen
Published: May 2022

Mutations ofSCN1A, which encodes the voltage-gated sodium channel Nav1.1, can cause epilepsy disorders such as Dravet syndrome (DS) that are comorbid with wide-ranging neurologic dysfunction. Many studies suggest that Nav1.1 haploinsufficiency causes forebrain GABAergic interneuron hypoexcitability, while pyramidal neuron physiology is mostly unaltered, and that this serves as a primary cell physiology phenotype linking mutation to disease. We hypothesized that deficits in inhibition would alter synaptic integration during activation of the hippocampal microcircuit, thus disrupting cellular information processing and leading to seizures and cognitive deficits. We tested this hypothesis usingex vivowhole-cell recordings from CA1 pyramidal neurons in a heterozygousScn1aknock-out mouse model and wild-type (WT) littermates, measuring responses to single and patterned synaptic stimulation and spontaneous synaptic activity. Overall, our experiments reveal a surprising normalcy of excitatory and inhibitory synaptic temporal integration in the hippocampus ofScn1ahaploinsufficient mice. While miniature IPSCs and feedforward inhibition and were decreased, we did not identify a pattern or frequency of input that caused a failure of synaptic inhibition. We further show that reduced GABA release probability and subsequent reduced short-term depression may act to overcome deficits in inhibition normalizing input/output functions in theScn1ahaploinsufficient hippocampus. These experiments show that CA1 pyramidal neuron synaptic processing is surprisingly robust, even during decreased interneuron function, and more complex circuit activity is likely required to reveal altered function in the hippocampal microcircuit.
Rapid Alternate Monocular Deprivation Does Not Affect Binocular Balance and Correlation in Human Adults
Authors: Lin (林温曼) Wenman , Wei (魏君涵) Junhan , Wang (王文静) Wenjing , Zou (邹李颖) Liying , Zhou (周诗旗) Shiqi , Jiang (江楠) Nan , Reynaud Alexandre , Zhou (周佳玮) Jiawei , Yu (于旭东) Xudong , Hess Robert F.
Published: May 2022

Recent studies show that the human adult visual system exhibits neural plasticity. For instance, short-term monocular deprivation shifts the eye dominance in favor of the deprived eye. This phenomenon is believed to occur in the primary visual cortex by reinstating neural plasticity. However, it is unknown whether the changes in eye dominance after monocularly depriving the visual input can also be induced by alternately depriving both eyes. In this study, we found no changes in binocular balance and interocular correlation sensitivity after a rapid (7 Hz), alternate, and monocular deprivation for 1 h in adults. Therefore, the effect of short-term monocular deprivation cannot seem to be emulated by alternately and rapidly depriving both eyes.
Predictors of metformin monotherapy failure in gestational diabetes mellitus
Authors: Benido Silva Vânia , Fonseca Liliana , Pereira Maria Teresa , Vilaverde Joana , Pinto Clara , Pichel Fernando , Almeida Maria do Céu , Dores Jorge
Published: May 2022

Objective

Metformin has emerged as a safe and effective pharmacological alternative to insulin in gestational diabetes mellitus (GDM), being associated with lower maternal weight gain and hypoglycemia risk. Nevertheless, glycemic control is unaccomplished in a considerable proportion of women only treated with metformin. We aim to determine the metformin monotherapy failure rate in GDM and to identify predictors of its occurrence.

Design and methods

This was a retrospective multicenter study including pregnant women with GDM patients who started metformin as a first-line pharmacological treatment (n  = 2891). A comparative analysis of clinical and analytical data between the group of women treated with metformin monotherapy and those needing combined therapy with insulin was performed.

Results

In 685 (23.7%) women with GDM, combined therapy to achieve adequate glycemic control was required. Higher pregestational BMI (OR 1.039; CI 95% 1.008–1.071; P-value = 0.013), higher fasting plasma glucose (PG) levels in oral glucose tolerance test (OGTT) (OR 1.047; CI 95% 1.028–1.066; P-value <0.001) and an earlier gestational age (GA) at metformin introduction (0.839; CI 95% 0.796–0.885, P-value < 0.001) were independent predictive factors for metformin monotherapy failure. The best predictive cutoff values were a fasting PG in OGTT ≥87 mg/dL and GA at metformin introduction ≤29 weeks.

Conclusions

In 685 (23.7%) women, combined therapy with insulin to reach glycemic control was required. Higher pre-gestational BMI, fasting PG levels in OGTT ≥87 mg/dL and introduction of metformin ≤29 weeks of GA were independent predictive factors for metformin monotherapy failure. The early recognition of these characteristics can contribute to the establishment of individualized therapeutic strategies and attain better metabolic control during pregnancy.
Analysis of a pitfall in congenital adrenal hyperplasia newborn screening: evidence of maternal use of corticoids detected on dried blood spot
Authors: Houang Muriel , Nguyen-Khoa Thao , Eguether Thibaut , Ribault Bettina , Brabant Séverine , Polak Michel , Netchine Irène , Lamazière Antonin
Published: May 2022

Neonatal screening for congenital adrenal hyperplasia (CAH) faces many specific challenges. It must be done using a performant analytical approach that combines sensitivity and specificity to capture the potential causes of mortality during the first week of life, such as salt wasting and glucocorticoid deficiency. Here, we confirm that maternal inhaled corticosteroid intake during pregnancy is a possible cause of missed CAH diagnosis. Thanks to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis, we were able to quantify endogenous steroid metabolites and also detect the presence of exogenous steroids in the dried blood spot of a newborn. Adding LC-MS/MS analysis as second-tier test, especially one that includes both 17-hydroxyprogesterone and 21-deoxycortisol measurements, would probably improve CAH diagnosis. In familial neonatal screening one could also look for maternal corticosteroid therapies that are hidden to prevent false-negative tests.
Hypertriglyceridemia in young adults with a 22q11.2 microdeletion
Authors: Blagojevic Christina , Heung Tracy , Malecki Sarah , Ying Shengjie , Cancelliere Sabrina , Hegele Robert A , Bassett Anne S
Published: May 2022

Objective

Mild to moderate hypertriglyceridemia is a condition often associated with obesity and diabetes, with as yet incomplete knowledge of underlying genetic architecture. The 22q11.2 microdeletion is associated with multimorbidity, including increased risk of obesity and diabetes. In this study, we sought to investigate whether the 22q11.2 microdeletion was associated with mild to moderate hypertriglyceridemia (1.7–10 mmol/L).

Design

This was a cohort study comparing 6793 population-based adults and 267 with a 22q11.2 microdeletion aged 17–69 years, excluding those with diabetes or on statins.

Methods

We used binomial logistic regression modeling to identify predictors of hypertriglyceridemia, accounting for the 22q11.2 microdeletion, male sex, BMI, ethnicity, age, and antipsychotic medications.

Results

The 22q11.2 microdeletion was a significant independent predictor of mild to moderate hypertriglyceridemia (odds ratio (OR): 2.35, 95% CI: 1.70–3.26). All other factors examined were also significant predictors (OR: 1.23–2.10), except for antipsychotic medication use. Within the 22q11.2 microdeletion subgroup, only male sex (OR: 3.10, 95% CI: 1.77–5.44) and BMI (OR: 1.63, 95% CI: 1.14–1.98) were significant predictors of hypertriglyceridemia, evident at mean age 31.2 years.

Conclusions

The 22q11.2 microdeletion is associated with hypertriglyceridemia even when accounting for other known risk factors for elevated triglycerides. This effect is seen in young adulthood (76.6% were <40 years), in the absence of diabetes, and irrespective of antipsychotics, suggesting that the 22q11.2 microdeletion may represent an unrecognized genetic risk factor for hypertriglyceridemia, providing novel opportunities for animal and cellular models. Early dyslipidemia screening and management strategies would appear prudent for individuals with 22q11.2 microdeletions.
Role of endogenous incretins in the regulation of postprandial lipoprotein metabolism
Authors: Taskinen Marja-Riitta , Matikainen Niina , Björnson Elias , Söderlund Sanni , Ainola Mari , Hakkarainen Antti , Lundbom Nina , Sihlbom Carina , Thorsell Annika , Andersson Linda , Adiels Martin , Hartmann Bolette , Deacon Carolyn F , Holst Jens J , Packard Chris J , Borén Jan
Published: May 2022

Objective

Incretins are known to influence lipid metabolism in the intestine when administered as pharmacologic agents. The aggregate influence of endogenous incretins on chylomicron production and clearance is less clear, particularly in light of opposing effects of co-secreted hormones. Here, we tested the hypothesis that physiological levels of incretins may impact on production or clearances rates of chylomicrons and VLDL.

Design and methods

A group of 22 overweight/obese men was studied to determine associations between plasma levels of glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) after a fat-rich meal and the production and clearance rates of apoB48- and apoB100-containing triglyceride-rich lipoproteins. Subjects were stratified by above- and below-median incretin response (area under the curve).

Results

Stratification yielded subgroups that differed about two-fold in incretin response. There were neither differences in apoB48 production rates in chylomicrons or VLDL fractions nor in apoB100 or triglyceride kinetics in VLDL between men with above- vs below-median incretin responses. The men with above-median GLP-1 and GLP-2 responses exhibited higher postprandial plasma and chylomicron triglyceride levels, but this could not be related to altered kinetic parameters. No differences were found between incretin response subgroups and particle clearance rates.

Conclusion

We found no evidence for a regulatory effect of endogenous incretins on contemporaneous chylomicron or VLDL metabolism following a standardised fat-rich meal. The actions of incretins at pharmacological doses may not be reflected at physiological levels of these hormones.
Glucagon-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a double-blind, randomized, placebo-controlled study
Authors: Atila Cihan , Gaisl Odile , Vogt Deborah R , Werlen Laura , Szinnai Gabor , Christ-Crain Mirjam
Published: May 2022

Background

The differential diagnosis of diabetes insipidus is challenging. The most reliable approaches are copeptin measurements after hypertonic saline infusion or arginine, which is a known growth hormone secretagogue but has recently also been shown to stimulate the neurohypophysis. Similar to arginine, glucagon stimulates growth hormone release, but its effect on the neurohypophysis is poorly studied.

Design

Double-blind, randomized, placebo-controlled trial including 22 healthy participants, 10 patients with central diabetes insipidus, and 10 patients with primary polydipsia at the University Hospital Basel, Switzerland.

Methods

Each participant underwent the glucagon test (s.c. injection of 1 mg glucagon) and placebo test. The primary objective was to determine whether glucagon stimulates copeptin and to explore whether the copeptin response differentiates between diabetes insipidus and primary polydipsia. Copeptin levels were measured at baseline, 30, 60, 90, 120, 150, and 180 min after injection.

Results

In healthy participants, glucagon stimulated copeptin with a median increase of 7.56 (2.38; 28.03) pmol/L, while placebo had no effect (0.10 pmol/L (−0.70; 0.68); P < 0.001). In patients with diabetes insipidus, copeptin showed no relevant increase upon glucagon, with an increase of 0.55 (0.21; 1.65) pmol/L, whereas copeptin was stimulated in patients with primary polydipsia with an increase of 15.70 (5.99; 24.39) pmol/L. Using a copeptin cut-off level of 4.6pmol/L had a sensitivity of 100% (95% CI: 100–100) and a specificity of 90% (95% CI: 70–100) to discriminate between diabetes insipidus and primary polydipsia.

Conclusion

Glucagon stimulates the neurohypophysis, and glucagon-stimulated copeptin has the potential for a safe, novel, and precise test in the differential diagnosis of diabetes insipidus.
FDG PET/CT in differentiated thyroid cancer patients with low thyroglobulin levels
Authors: Lebbink Chantal A , de Vries Lisa H , Borel Rinkes Inne H M , Braat Arthur J A T , van Leeuwaarde Rachel S , Lodewijk Lutske , van Treijen Mark J C , Vriens Menno R , Valk Gerlof D , van Santen Hanneke M , de Keizer Bart
Published: May 2022

Objective

To evaluate the usefulness of [18F]fluorodeoxyglucose (FDG) positron emissive tomography (PET)/CT in patients with low detectable thyroglobulin levels suspicious for persistent or recurrent differentiated thyroid cancer (DTC).

Methods

A retrospective case series study evaluating FDG PET/CT in patients with detectable thyroglobulin (Tg) levels (≥0.20 and <10.00 ng/mL) after initial treatment with total thyroidectomy and I-131 thyroid remnant ablation for pT1-3aN0-1bM0 DTC. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of FDG PET/CT were calculated.

Results

Twenty-seven patients underwent FDG PET/CT. Median Tg level at FDG PET/CT was 2.00 ng/mL (range 0.30–9.00). FDG PET/CT was positive in 14 patients (51.9%): lesions suspicious for lymph node metastases were depicted in 12 patients, and lung metastases in 2. DTC was confirmed in 13/14 FDG PET/CT-positive patients. In 9/13 patients with a negative FDG PET/CT, DTC was confirmed ≤3 months after FDG PET/CT. The sensitivity, PPV, specificity and NPV were 59.1, 92.9, 80.0 and 30.8%, respectively.

Conclusions

This case series shows that FDG PET/CT might be useful to detect persistent or recurrent DTC in patients with low detectable Tg. However, when FDG PET/CT is negative, this does not rule out DTC and further investigations are necessary.
Dopamine agonist therapy for prolactinomas: do we need to rethink the place of surgery in prolactinoma management?
Authors: De Sousa Sunita M C
Published: May 2022

The current treatment paradigm for prolactinomas involves dopamine agonist (DA) therapy as the first-line treatment, with surgical resection reserved for cases where there is DA failure due to resistance or intolerance. This review highlights how DA therapy can be optimised to overcome its increasingly recognised pitfalls, whilst also addressing the potential for expanding the use of surgery in the management of prolactinomas. The first part of the review discusses the limitations of DA therapy, namely: DA resistance; common DA side effects; and the rare but serious DA-induced risks of cardiac valvulopathy, impulse control disorders, psychosis, CSF rhinorrhoea and tumour fibrosis. The second part of the review explores the role of surgery in prolactinoma management with reference to its current second-line position and recent calls for surgery to be considered as an alternative first-line treatment alongside DA therapy. Randomised trials comparing medical vs surgical therapy for prolactinomas are currently underway. Pending these results, a low surgical threshold approach is herein proposed, whereby DA therapy remains the default treatment for prolactinomas unless there are specific triggers to consider surgery, including concern regarding DA side effects or risks in vulnerable patients, persistent and bothersome DA side effects, emergence of any serious risks of DA therapy, expected need for long-term DA therapy, as well as the traditional indications for surgery. This approach should optimise the use of DA therapy for those who will most benefit from it, whilst instituting surgery early in others in order to minimise the cumulative burden of prolonged DA therapy.
Bioinformation Systems with Detectors and Signal Coding Capabilities
Authors: Klyuchko Olena , Beletsky Anatoliy , Gonchar Olga , Melezhyk Olga
Published: May 2022

Introduction. The integration of computer technologies into various fields of science allows the development of new methodologies, hybrid information systems with advanced capabilities, such as EcoIS bioinformation system for monitoring the environment with the use of biological data detectors.Problem Statement. The development of innovation bioinformation systems with biological data detectors is a very important task, as they have numerous advantages: allow rapid diagnostics and testing of chemicals in thefirst moments of their action, may be incorporated easily into electronic registration systems, may serve as elementary analytical units with data coding capabilities, etc.Purpose. The purpose of this research is to make a comprehensive analysis of different types of biological data detectors to develop a physical model of a biosensor capable of encoding signals and a bioinformation system with such detectors.Materials and Methods. The comparative analysis of information systems with functions of ecomonitoring and different types of biosensors have been used; the data are taken from electrophysiological experiments on registration of chemosensitive transmembrane electric currents in voltage clamp and patch clamp modes.Results. The physical model of biosensor has been developed and tested. The integration of the developed biosensors into the electronic bioinformation system by the example of EcoIS authors’ system has been demonstrated. Neuron-like biosensor has been considered an abstraction in the unity of its functions: signal receiver — filter — analyzer — encoder/decoder, where the input information is obtained in the form of chemical structures or electrical signals, after the conversion (recoding) of information it is registered as electrical signals with changed characteristics. The prospects for developing the cutting-edge methods for information protection in systems with biosensors have been shown.
Conclusions. This development may be used for creating a bioinformation system for environmental moni toring with integrated biosensor system and data protection based on the principles and achievements of contemporary biophysics.