bluuebunny/crossref_metadata_2025 huggingface dataset:
Classificação geotecnológica de rochas. Apreciação sintética da questão (1 parte)
Authors: Franciss Fernando
Published: October 2022

O texto seguinte reune comentários relacionados com a idealização de metodologias de classificação de meios rochosos para uso em Mecânica das Rochas. Sua estruturação inclui uma apreciação das bases e princípios normativos da proposição de sistemas classificadores (Capítulo 2) algumas considerações referentes às propriedades físicas dos meios rochosos (Capítulo 3); conclusões mais importantes (Capítulo 4); um resumo das principais classificações existentes (anexo A).
“Queremos que esto llegue a mucha gente” o cómo la movilización del conocimiento sostiene la investigación social participativa
Authors: Susinos Teresa , Saiz-Linares Ángela , Ruiz-López Julia
Published: October 2022

Este trabajo se enmarca en un proyecto I+D+i financiado por el Ministerio de Economía y Competitividad de España cuyo propósito es el estudio de varios proyectos locales de investigación participativa. En este artículo examinamos cómo esta investigación participativa intersecciona con los fundamentos de la movilización del conocimiento y cómo ello se revela a lo largo del proyecto (no solo en la difusión final) a través de cuatro ejes interpretativos: relevancia; investigación participativa; comunicación y audiencia activa. Nos servimos de uno de los proyectos donde la creación colaborativa de un audiovisual nucleó un complejo proceso de investigación sobre la realidad carcelaria para ilustrar estos ejes en la práctica. Los participantes y co-creadores de esta obra han sido seis hombres jóvenes que han tenido o tenían una pena privativa de libertad, una trabajadora social y tres investigadoras de la universidad de Cantabria. Este trabajo muestra cómo estos resultados que brotan de un proyecto concreto pueden resultar inspiradores para otros proyectos de investigación guiados por el paradigma de la participación y de la acción social.
Ausländische Direktinvestitionen und lokale Wissensbasis: Die Einbettung von Niederlassungen in die deutsche duale Ausbildung
Authors: Fuchs Martina , Westermeyer Johannes , Finken Lena , Pilz Matthias
Published: October 2022

Dual vocational education and training systematically combines the learning of apprentices (in vocational schools) or students (in applied universities) with the ‘learning venue’ of the company. The dual vocational education and training exists in Germany, Austria and Switzerland and stands for regional competitiveness as well as for job opportunities of young people on the local labour market. Outside of these three countries, the dual system hardly exists, but dual practices are subject of international skill transfer policies. While this transfer is well researched, it is hardly known to what extent (in mirror image) subsidiaries of foreign companies take part in the dual system of German speaking countries. This question was examined, by focussing on subsidiaries of multinational companies in Germany. Theoretically, the contribution relates to research on local knowledge bases and the embeddedness of foreign subsidiaires. The study pursues a qualitative method. The results show that the local training managers have freedom for decision-making and use this in favour of getting involved in dual vocational education and training. However, the effort turns out to be high. Dual activities take place primarily as a strategy for adapting to the institutional environment, not as a way of shaping the environment. The local stakeholders are mostly reactive in this regard. This points to possible future fields of research on local knowledge bases and local embeddedness and, with regard to practice, to the relevance of mutual coordination.
Stadtregionen im Spannungsfeld zwischen Wohnungsfrage und Flächensparen. Trends, Strategien und Lösungsansätze in Kernstädten und ihrem Umland
Authors: Ehrhardt Denise , Eichhorn Sebastian , Behnisch Martin , Jehling Mathias , Münter Angelika , Schünemann Christoph , Siedentop Stefan
Published: October 2022

Growing city regions are in between the poles of high land and housing prices and national land-saving targets. The mobilization of building land to create living space and the reduction of new land take represent a conflict of goals that can only be resolved by taking an integrated look at the instruments for meeting both challenges. In order to address this conflict analytically, a regional causal loop diagram is used to map the complex mechanisms of action between housing markets and new land use for housing in core cities and their hinterland and to use it as a theoretical framework. Using a mixed-methods approach, trends in residential development as well as municipal solution strategies in German city regions are investigated. The results show increasing land use efficiency in core cities and the dense hinterland, with simultaneous high, price-induced migration gains in the less dense hinterland, where single-family housing still dominates. It becomes evident that the questions about land saving in the hinterland and housing in core cities have to be considered mutually. The regional land take can only be minimized if affordable and attractive housing is provided in the core cities, especially for families. For this, a more consistent use of existing land policy instruments in combination with a regional commitment to higher densities, especially in the hinterland, is necessary.
Optimization of fatigue life in laminated composite plates
Authors: Ahmed Bassam Ali
Published: October 2022

With the development of fiber technology on which the composite materials depend mainly was necessary to improve the rigidity, durability, and heat transfer in the areas of heating and cooling technologies. The effect of the fatigue phenomenon on composite materials using carbon fibers is studied. In this research paper, work was performed to study the improvement in the bearing capacity of the stress test sample with the addition of carbon fibers at different angles. The stresses affecting the test specimen are cylindrical with a length of 10 cm. The results proved that the best arrangement of the carbon fibers in the form of triple layers starting from the center of the cylinder circle to the outside was the share of the arrangement layer 45, 0, 0, where the lowest value was the number of fatigue life cycles, 2349 cycles in the bending test, as the amount of stress that this case reached was 6.1×108 Pa compared to the rest of the studied cases.
Alkali lignin as a pH response bifunctional material with both adsorption and flocculation for wastewater treatment
Authors: Qi Junjie , Hou Yahui , Liu Jiaying , Yuan Ze , Fang Jing , Fang Zhiqiang , Li Hao
Published: October 2022

Alkali lignin (AL) has attracted great attention as a material for treating dye wastewater due to its low cost and environmental friendliness. However, the unique structure and aggregation characteristics of AL regarding the dye wastewater removal mechanism have not been systematically revealed. Here, the removal process of typical cationic dye contaminants (methylene blue, MB) from dye wastewater by AL at different pH was explored and the unique synergistic effect mechanism of adsorption and flocculation was revealed. With increasing pH, the removal rate initially increased and then decrease. With increasing MB concentration, the optimal pH value corresponding to the maximum adsorption rate increased regularly. Zeta potential and Fourier transform infrared spectroscopy (FTIR) showed that electrostatic and π–π interactions and hydrogen bonding consisted push-pull balance under the influence of pH. In addition, scanning electron microscopy (SEM), ultraviolet and visible spectrum (UV) and particle size analysis showed that the aggregate structure and synergistic mechanism changed with the solution pH and concentration. In the low concentration solution, adsorption dominated. While in the high concentration solution, flocculation dominated. The removal mechanism consisted of the synergy of adsorption and flocculation laying the foundation for the efficient and environmentally friendly treatment of dye wastewater by AL.
Assessment of the breadth of binding promiscuity of heme towards human proteins
Authors: Roumenina Lubka T. , Dimitrov Jordan D.
Published: October 2022

Heme regulates important biological processes by transient interactions with many human proteins. The goal of the present study was to assess extends of protein binding promiscuity of heme. To this end we evaluated interaction of heme with >9000 human proteins. Heme manifested high binding promiscuity by binding to most of the proteins in the array. Nevertheless, some proteins have outstanding heme binding capacity. Bioinformatics analyses revealed that apart from typical haemoproteins, these proteins are frequently involved in metal binding or have the potential to recognize DNA. This study can contribute for understanding the regulatory functions of labile heme.
Schwierigkeit und Trennschärfe von Aufgabentypen – evaluiert durch Ober- und Untergruppenanalysen in den DSH-Prüfungsteilen Leseverstehen und Hörverstehen
Authors: Friedland Alice , Sabo Milica
Published: October 2022

Die DSH-Prüfung (Deutsche Sprachprüfung für den Hochschulzugang) nimmt innerhalb der Prüfungen, welche in der Rahmenordnung für Deutsche Sprachprüfungen für den deutschen Hochschulzugang (kurz: RO-DT) gelistet sind, eine besondere Rolle ein. Sie stellt neben dem Prüfungsteil Deutsch der Feststellungsprüfung eines Studienkollegs die einzige Prüfung dar, die nicht grundsätzlich standardisiert ist und dementsprechend dezentral erstellt wird bzw. werden kann. Aus diesen Gründen ist eine ständige standortbezogene Evaluation der Prüfung notwendig. Am Beispiel des DSH-Standortes Friedrich-Schiller-Universität Jena soll aufgezeigt werden, wie die sogenannte Ober- und Untergruppenanalyse bzw. die vereinfachte Itemanalyse die Evaluation hinsichtlich der Gütekriterien Schwierigkeit und Trennschärfe unterstützen kann. Mithilfe der Ober- und Untergruppenanalyse ist auch eine Bestimmung des Schwierigkeitsgrads für jede Aufgabe möglich. Anhand von vier DSH-Prüfungssätzen soll dies für die Prüfungsteile der rezeptiven Fertigkeiten Leseverstehen und Hörverstehen aufgezeigt werden. Die zur Überprüfung der Fertigkeiten herangezogenen Aufgabentypen unterscheiden sich nicht wesentlich und sind deshalb für eine übergreifende Betrachtung der rezeptiven Prüfungsteile geeignet. Aus der Ober- und Untergruppenanalyse für die Prüfungsteile Lese- und Hörverstehen ergibt sich zum einen ein Vorschlag zur Testevaluation, welcher auch an anderen DSH-Standorten eingesetzt werden kann; zum anderen ergeben sich Hinweise für das Testerstellungsverfahren.
Lernverlaufsdiagnostik (LVD) der Schreibflüssigkeit bei Kindern mit Deutsch als Zweitsprache
Authors: Schaller Pascale , Winkes Julia
Published: October 2022

Der empirische Beitrag widmet sich der Lernverlaufsdiagnostik im Bereich Schreiben (LVD – Schreiben) und zeigt anhand einer Stichprobe von Kindern mit Deutsch als Erstsprache (DaE) und Deutsch als Zweitsprache (DaZ) der 3. bis 6. Klassenstufe auf, für welche Kennwerte sich die Kindergruppen in LVD – Schreiben unterscheiden. Der Fokus liegt bei der Reliabilität und der Validität des Verfahrens. Der Ansatz der Lernverlaufsdiagnostik wird vorgestellt und – basierend auf der Datenauswertung – in seinem Nutzen für die verschiedenen Kindergruppen eingeordnet.
The Participation of Marginal and Liminal Groups in Secondary State Formation under the Third Dynasty of Ur
Authors: Garfinkle Steven
Published: October 2022

The Ur III period (2112–2004 BC) provides rich opportunities to evaluate the contributions of marginal and liminal groups to the political economy of the era, and to re-assess our understanding of what constituted such groups in an era of early state formation. These opportunities arise in part from the well preserved and detailed administrative corpora at major provincial centers like Umma and Ĝirsu, as well as from significant centers of royal activity like Puzriš-Dagan and Iri-sagrig. These archives document many of the activities of the two groups on which this article focuses: the large body of marginalized dependent laborers (Sumerian ĝuruš) who performed a great deal of the agricultural work in Mesopotamia, and the liminal figures who frequent our records, often associated with pastoralism, and who are identified as Amorites (Sumerian Mar-tu). The former group I identify as “insiders” who were socio-economically marginalized, and the latter group I identify as “outsiders” who occasionally had the opportunity to become privileged insiders. Our tendency in the study of early agrarian societies to regard pastoralists as “outsiders” allows for a critique of how we identify and describe liminal groups; and this has added significance for how we understand the state building projects of the Third Dynasty of Ur.
Historical development of SIRGAS
Authors: Drewes Hermann
Published: October 2022

The Geodetic Reference System for the Americas (Sistema de Referencia Geodésico para las Américas, SIRGAS) was initiated in 1993 for South America at an international conference organised by the International Association of Geodesy (IAG), the Pan-American Institute for Geography and History (PAIGH), the Deutsches Geodätisches Forschungsinstitut (DGFI), and the U.S. Defense Mapping Agency (DMA) in Asunción, Paraguay. The corresponding South American reference network was observed in 1995 by a ten-day GPS campaign at 58 stations. The network was extended to Central and North America in 2000 and immediately afterwards converted to a frame of continuously observing GNSS stations instead of short-term campaigns. The linear station position changes (velocities) were estimated by a multi-year least squares adjustment of weekly solutions, the first being published in 2002. The total set of station velocities served for the computation of continuous surface deformation models, the first over South America was published in 2005. Today, SIRGAS is accepted by most of the American states as the official geodetic reference frame. Besides the product generation (station positions, velocities, and surface deformation), SIRGAS is active in education and training offering schools and workshops for students, surveyors, and other stakeholders.
Improving of electric network feeding nuclear facility based on multiple types DGs placement
Authors: Saleh Alaa A. , Adail Ahmed S.
Published: October 2022

Nuclear Facility (NF), during shutdown and startup, are in the essential need for reliable electric power that should be delivered by electric power grid to NF. Safe operation of NF needs a limited variation in both frequency and voltage.The reduction of power losses, improving voltage profile, and frequency in electric grid connected with NF can be achieved by optimally distributed generators (DGs) placement. This paper presents a mathematical model for multible types of DGs placement in electric grid feeding NF. Also, it proposes artificial intelligence solution methodology for active and reactive power DGs placement problem. The trained Adaptive Neuro-Fuzzy Inference System (ANFIS) with Cat Swarm Optimization algorithm (CSO) is used for optimal solution. The optimization technique is tested and validated by using different sizes of electric grid. Test results showed a more reliable and efficient approach compared with other approachs.
SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
Authors: Deng Yan , Li Xin , Jiang Wenlei , Tang Jindan
Published: October 2022

Papillary thyroid carcinoma (PTC) accounts for more than 80% of all thyroid carcinoma cases. Small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) has been indicated to be carcinogenic in several cancers; however, its function and mechanism in PTC are unclarified. Real time quantitative polymerase chain reaction and western blotting revealed the upregulation of SNRPB and downregulation of tumor protein p53 in PTC tissues compared with the normal tissues. Flow cytometry and western blotting displayed that SNRPB silencing induced cell cycle arrest at G1 phase and suppressed the expression levels of Cyclin family proteins in PTC cells. In vivo experiments suggested that SNRPB silencing inhibited PTC tumor growth in mice. Bioinformatics analysis revealed that the expression of SNRPB and cell cycle-associated genes in thyroid carcinoma tissues is positively correlated. Immunofluorescence staining and co-immunoprecipitation demonstrated that SNRPB directly interacted with p53 and suppressed its expression in PTC cells. In conclusion, SNRPB facilitates cell cycle progression in PTC by inhibiting p53 expression.
lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
Authors: Xie Zhi , Wang Chen , Li Li , Chen Xianfeng , Wei Guanjing , Chi Yan , Liang Yanping , Lan Lizhen , Hong Jiqiong , Li Lili
Published: October 2022

Invasion and metastasis of melanoma are a series of complicated biological events regulated by multiple factors. The coregulation of many molecules involved in the development and progression of melanoma contributes to invasion and migration. mGluR1 is a metabotropic glutamate receptor that is overexpressed in melanocytes and is sufficient to induce melanoma. In our study, we found that mGluR1 was obviously increased in melanoma. Furthermore, we found that miR-129-5p could directly target and regulate mGluR1 mRNA, which was significantly reduced in A375 cells. Overexpression of miR-129-5p inhibited cell migration, invasion and clonal formation. lncRNA-AC130710 directly targeted and suppressed miR-129-5p in A375 cells. Downregulation of lncRNA-AC130710 suppressed the levels of mGluR1 mRNA by promoting miR-129-5p expression and further inhibiting migration, invasion and colony formation in A375 cells, which was associated with the activation of the PKCα-MAPK signaling pathway. Taken together, our study showed that the lncRNA-AC130710/miR-129-5p/mGluR1 axis plays an important role in the invasion and metastasis of melanoma.
A Defense on the Usefulness of ‘Big-G’ Grounding
Authors: Kortabarria Markel
Published: October 2022

Contemporary metaphysics has undergone a change of perspective due to the irruption of Grounding in discussions of metaphysical dependence. Proponents argue that Grounding is the primitive relationship of determination underlying many of the traditionally posited idioms of metaphysical dependence. In a recent line of scepticism Jessica Wilson has argued that the inability of the notion to be informatively effective regarding substantial matters of metaphysical determination renders it useless in the face of theoretical work. To supply this lack of informativeness proponents must resort to the already available set of specific ‘small-g’ relations, which renders the formulation of ‘big-G’ Grounding pre-theoretically unmotivated. In response two motivations are said to remain: The priority and unity arguments. Wilson insists that neither of these motivations succeeds in establishing ‘big-G’ Grounding as theoretically useful. I argue that none of Wilson’s critiques succeeds in establishing eliminative scepticism.
Forgiveness and flourishing
Authors: Toussaint Loren
Published: October 2022

This article reviews work that my colleagues and I have conducted over the past 20 years examining connections of forgiveness of others and self-forgiveness with flourishing. I also highlight our work investigating psychoeducational approaches to forgiveness education. Definitions of forgiveness of others, self-forgiveness, divine forgiveness, and flourishing are offered at the outset. Then I turn to considering conceptual models of the forgiveness and flourishing connection. I review both the stress-and-coping models of forgiveness of others and self-forgiveness, and suggest that these models offer a lens on how and why forgiveness might be connected to flourishing. Examples of research testing different aspects of these models are then offered with an eye toward understanding both the direct and mediating/moderating influence of forgiveness and self-forgiveness on flourishing. Forgiveness education is discussed next. Here I review leading methods of forgiveness education (i. e., REACH Forgiveness and Forgive for Good) and review both the steps of each model and provide examples of the efficacy trials that have been done to demonstrate that forgiveness is a teachable skill when appropriate methods are used. I conclude by summarizing what I have learned about forgiveness and suggest some areas of science and society in need of future forgiveness work.
„Und Gott hatte das Fleisch brennend lieb!“
Authors: Gosebrink Hildegard
Published: October 2022

Der Beitrag skizziert Leben und gegenwärtige Rezeption Hildegards von Bingen (1098–1179). Er informiert über die authentischen Quellen, die ihre Werke überliefern, und gibt auf dieser Basis Orientierungshilfen, wo Hildegard heute vereinnahmt und vermarktet wird. Er wagt eine Spurensuche zum Thema „Schöpfung“, angefangen von ihrem Erstlingswerk Scivias bis zum Singspiel Ordo virtutum.

Hildegard geht von einem kommunikationsfreudigen Gott aus, der sich in der Schöpfung mitteilt. Sie sieht den Menschen als Mittelpunkt der Schöpfung. Ihr Anthropozentrismus bedeutet jedoch keinen Freibrief, die Schöpfung auszubeuten. Der Mensch ist großartig und abhängig zugleich, er ist von Gott mit Kräften bzw. Ressourcen zur Aktivität und Verantwortung ausgestattet. Dabei kommt der Mensch sowohl im heilen Urzustand der Schöpfung als auch nach ihrem Fall in den Blick. Hildegard versteht Erlösung bzw. Heilung als Wandlung, bei der sie dem Menschen aktive Mitwirkung zuschreibt. Die Edelsteine sind hier wichtige Metaphern.

Schließlich werden sieben „Ankerpunkte“ für einen heutigen Dialog mit Hildegard benannt, die das Anliegen von „Spiritual Care“ inspirieren können.
The design method of the V-shaped groove piston ring
Authors: Zhang Le , He Lidong , Wang Xiaodong , Huang Xinwei , Jia Xingyun , Liu Chunrui
Published: October 2022

Aiming at the problems of large leakage and high friction heat generation of the piston ring under high pressure and high speed, based on the previous research on the V-shaped groove piston ring, the research on the design method of the V-shaped groove piston ring is carried out in depth. The numerical analysis is carried out focusing on the number of V-shaped grooves and the depth of the V-shaped grooves of the piston ring. The influence law is verified and analyzed by using a high-pressure and high-speed rotating test bench. The simulation and experimental results show that the leakage of 4 grooves and 8 grooves piston ring is reduced by 14.9 and 28.5%, and the temperature is reduced by 10.9 and 4.7%; When there are 8 V-shaped grooves on the piston ring, the leakage is reduced by 28.5 and 21.7%; when the V-shaped groove depth is 0.04 and 0.08 mm, the temperature is reduced by 4.1%. However, when the V-shaped groove depth is 0.12 mm, the leakage is increased by 2.7% compared with the traditional piston ring. Appropriate groove number and groove depth can realize the coordinated design of low leakage and low friction temperature rise.
Motorcycle Tourism
Authors: Gronau Werner , Große Hokamp Jana
Published: October 2022

The contribution at hands aims on providing a rough overview on almost 20 years of academic research emerging in the field of so-called motorcycle tourism. From the early beginning of academic contributions when motorcycling was perceived as a “gangs-thing”, as a field of ethnographic studies. To the days when motorcycling was accepted as a general leisure activity and consequently became a part of drive tourism research. The focus of motorcycling as a drive tourism form also contributed to a growing interest in the field of business and tourism studies, as it defined a new paradigm for the field, which still prevails today. “The major change in the global self-drive markets is a shift from the car as a form of least-cost transport towards the use of a variety of self-driven vehicles that add value to the tourism experience” (Carson & Schmallegger, 2011, p. 364). Following the historical perspective, the second section of the article outlines the ongoing diversification of research fields around motorcycling tourism in recent years including studies on interest and motivations of motorcycle tourists, target group segmentations, or impact studies on destinations, which might indicate motorcycle tourism becoming an emerging field of tourism research. The final section provides an outlook of possible topics of the near future.
Engaging with students as partners in education-space design
Authors: Streule Mike , McCrone Luke , Andrew Yasmin , Walker Craig
Published: October 2022

Engaging with Students as Partners (SaP) in areas of curriculum design and pedagogic consultancy is relatively well established. Here we present a case study of two recent projects at Imperial College London, a research-intensive science, technology, engineering, mathematics, and medicine (STEMM) university, that have extended the SaP model to the design and delivery of modifications to education spaces. Using a research-informed approach and tested method ensured that the students remained active throughout the “twists and turns” of the project, rather than the more traditional snapshot student-consultation approach often taken early in the design process. Students experienced authentic partnership with staff, the space, and their department/institution more broadly whilst staff acknowledged that the quality of outputs significantly exceeded expectations at a fraction of the cost of engaging external design consultants. More broadly, projects such as these establish precedents for a more ambitious institutional approach to working with students as partners.
HDAC2 in Primary Sensory Neurons Constitutively Restrains Chronic Pain by Repressing α2δ-1 Expression and Associated NMDA Receptor Activity
Authors: Zhang Jixiang , Chen Shao-Rui , Zhou Meng-Hua , Jin Daozhong , Chen Hong , Wang Li , DePinho Ronald A. , Pan Hui-Lin
Published: October 2022

α2δ-1 (encoded by theCacna2d1gene) is a newly discovered NMDA receptor-interacting protein and is the therapeutic target of gabapentinoids (e.g., gabapentin and pregabalin) frequently used for treating patients with neuropathic pain. Nerve injury causes sustained α2δ-1 upregulation in the dorsal root ganglion (DRG), which promotes NMDA receptor synaptic trafficking and activation in the spinal dorsal horn, a hallmark of chronic neuropathic pain. However, little is known about how nerve injury initiates and maintains the high expression level of α2δ-1 to sustain chronic pain. Here, we show that nerve injury caused histone hyperacetylation and diminished enrichment of histone deacetylase-2 (HDAC2), but not HDAC3, at theCacna2d1promoter in the DRG. Strikingly,Hdac2knockdown or conditional knockout in DRG neurons in male and female mice consistently induced long-lasting mechanical pain hypersensitivity, which was readily reversed by blocking NMDA receptors, inhibiting α2δ-1 with gabapentin or disrupting the α2δ-1–NMDA receptor interaction at the spinal cord level.Hdac2deletion in DRG neurons increased histone acetylation levels at theCacna2d1promoter, upregulated α2δ-1 in the DRG, and potentiated α2δ-1–dependent NMDA receptor activity at primary afferent central terminals in the spinal dorsal horn. Correspondingly,Hdac2knockdown-induced pain hypersensitivity was blunted inCacna2d1knockout mice. Thus, our findings reveal that HDAC2 functions as a pivotal transcriptional repressor of neuropathic pain via constitutively suppressing α2δ-1 expression and ensuing presynaptic NMDA receptor activity in the spinal cord. HDAC2 enrichment levels at theCacna2d1promoter in DRG neurons constitute a unique epigenetic mechanism that governs acute-to-chronic pain transition.

SIGNIFICANCE STATEMENTExcess α2δ-1 proteins produced after nerve injury directly interact with glutamate NMDA receptors to potentiate synaptic NMDA receptor activity in the spinal cord, a prominent mechanism of nerve pain. Because α2δ-1 upregulation after nerve injury is long lasting, gabapentinoids relieve pain symptoms only temporarily. Our study demonstrates for the first time the unexpected role of intrinsic HDAC2 activity at the α2δ-1 gene promoter in limiting α2δ-1 gene transcription, NMDA receptor-dependent synaptic plasticity, and chronic pain development after nerve injury. These findings challenge the prevailing view about the role of general HDAC activity in promoting chronic pain. Restoring the repressive HDAC2 function and/or reducing histone acetylation at the α2δ-1 gene promoter in primary sensory neurons could lead to long-lasting relief of nerve pain.
Maladaptive Laterality in Cortical Networks Related to Social Communication in Autism Spectrum Disorder
Authors: Persichetti Andrew S. , Shao Jiayu , Gotts Stephen J. , Martin Alex
Published: October 2022

Neuroimaging studies of individuals with autism spectrum disorders (ASDs) consistently find an aberrant pattern of reduced laterality in brain networks that support functions related to social communication and language. However, it is unclear how the underlying functional organization of these brain networks is altered in ASD individuals. We tested four models of reduced laterality in a social communication network in 70 ASD individuals (14 females) and a control group of the same number of tightly matched typically developing (TD) individuals (19 females) using high-quality resting-state fMRI data and a method of measuring patterns of functional laterality across the brain. We found that a functionally defined social communication network exhibited the typical pattern of left laterality in both groups, whereas there was a significant increase in within- relative to across-hemisphere connectivity of homotopic regions in the right hemisphere in ASD individuals. Furthermore, greater within- relative to across-hemisphere connectivity in the left hemisphere was positively correlated with a measure of verbal ability in both groups, whereas greater within- relative to across-hemisphere connectivity in the right hemisphere in ASD, but not TD, individuals was negatively correlated with the same verbal measure. Crucially, these differences in patterns of laterality were not found in two other functional networks and were specifically correlated to a measure of verbal ability but not metrics of other core components of the ASD phenotype. These results suggest that previous reports of reduced laterality in social communication regions in ASD is because of the two hemispheres functioning more independently than seen in TD individuals, with the atypical right-hemisphere network component being maladaptive.

SIGNIFICANCE STATEMENTA consistent neuroimaging finding in individuals with ASD is an aberrant pattern of reduced laterality of the brain networks that support functions related to social communication and language. We tested four models of reduced laterality in a social communication network in ASD individuals and a TD control group using high-quality resting-state fMRI data. Our results suggest that reduced laterality of social communication regions in ASD may be because of the two hemispheres functioning more independently than seen in TD individuals, with atypically greater within- than across-hemisphere connectivity in the right hemisphere being maladaptive.
Russia’s Invasion of Ukraine and China–North Korea Relations
Authors: Pacheco Pardo Ramon , Kim Yeong Ik
Published: October 2022

Russia’s invasion of Ukraine has had repercussions in regions beyond Europe. One of these regions is Asia, including Northeast Asia. This region is home to China and North Korea, two authoritarian countries often lumped together with Russia as potential threats to the liberal international order. The relationship between China and North Korea has thus been affected by Russia’s aggression toward Ukraine. Beijing and Pyongyang share a decades-old alliance. Despite its ups and downs, the alliance survives as of 2022. Russia’s actions in Ukraine have only reinforced it, bringing China and North Korea closer to each other. Both of them have sided with Moscow, and for similar reasons, including their opposition to what they see as the US’s and NATO’s aggressive stance. And both have taken the same actions to support Russia, further strengthening their connection.
Status of a Child Born as a Result of IVF Procedure
Authors: Bączyk-Rozwadowska Kinga
Published: October 2022

Due to the constant development of medicine and biotechnology, including the in vitro procedure, more and more infertile couples can fulfil their desire to have a child. Traditional rules of family law concerning the determination of status familiae of such children have then turned out to be insufficient. The situation is even more complicated when IVF procedure assumes the use of donated genetic material or the involvement of a surrogate mother. Therefore in the field of family law the intention to “create” a child starts to play quite an important role. Family law is then undergoing far-reaching transformations, especially in those countries where same-sex couples are eligible to start IVF procedures (Great Britain, USA, Germany, Austria).
Limits of Parental Interference in a Child’s Personal Rights – Selected Issues
Authors: Michałowska Kinga
Published: October 2022

The article discusses the issues of the limits of parental interference in children’s personal rights. The conducted research covers the subject broadly. It starts with the general issues of legal capacity as the basis for the protection of subjective rights and then proceeds to demonstrating the lack of limitations in the protection of a child’s personal rights. A child growing up in a family remains under parental authority, which gives rise to certain obligations and rights of parents towards the child. Parents look after, educate and guide the child, carrying out their duties in the best interests of the child and guided by their good. It happens, however, that by caring for children, parents violate their personal rights. Therefore, the determinants of exercising parental authority were examined. Particular attention was paid to the scope of rights resulting from parental authority, the assessment of the manner of exercising it, the right of the child to express his or her own position and the principle of the best interests of the child. These determinants made it possible to indicate the limit of parental interference in the child’s personal rights. The practical side of the implementation of the right to the protection of a child’s personal rights was also indicated, as well as a proposal to amend the content of the family and guardianship code.
Private Autonomy and Family Public Policy in Italy
Authors: Buccianti Giovanni Liberati
Published: October 2022

The article deals with the general clause of public policy in Italian family law. It analyses the recent case-law application of both international and internal public policy in the Italian legal system. Nowadays, public policy is used for protecting and developing the fundamental rights of individuals in the EU space. However, the content of this general clause is debated, and there are several theses (e.g. constitutional, discretionary, globalized public policy). Adhering to one concept rather than another has different consequences. Think, for example, of the recognition of double paternity acquired abroad through a surrogacy contract. Moreover, family public policy can be viewed both as public policy of the family (a general clause that protects the family rather than its members) and public policy in the family (a general clause that protects the fundamental rights of the individuals rather than the family). Subsequently, the article analyses prenuptial and postnuptial agreements in Italy. Italian jurisprudence considers both agreements invalid because they are in contradiction to public policy. The article suggests that families can use the contractual instrument. However, personal and patrimonial clauses in domestic family agreements need to be compatible both with the public policy of the family and public policy in the family. Ultimately, public policy becomes a tool attributed to ordinary judges for guaranteeing widespread constitutional legality.
The effect of thyroid dysfunction on breast cancer risk: an updated meta-analysis
Authors: Tran Thi-Van-Trinh , Kitahara Cari Meinhold , Leenhardt Laurence , de Vathaire Florent , Boutron-Ruault Marie-Christine , Journy Neige
Published: October 2022

In a previous systematic review and meta-analysis of studies reporting associations between hyper-/hypothyroidism and breast cancer incidence published through 29 January 2019, we identified a higher risk with diagnosed hyperthyroidism compared to euthyroidism, but no association with diagnosed hypothyroidism. This 2-year updated meta-analysis aims to investigate the role of menopause in this association and the dose–response relationship with blood levels of thyroid-stimulating hormone (TSH) and thyroid hormones. After the exclusion of studies with only mortality follow-up, with thyroid dysfunction evaluated as a cancer biomarker or after prior breast cancer diagnosis, we reviewed 25 studies that were published up to 01 December 2021 and identified in MEDLINE, the COCHRANE library, Embase, or Web of Science; of these, 9 were included in the previous meta-analysis. Risk estimates from 22 of the 25 studies were included in the meta-analysis and pooled using random-effects models. Compared to euthyroidism, hyperthyroidism and hypothyroidism diagnoses were associated with higher (pooled risk ratio (RR): 1.12, 95% CI: 1.06–1.18, 3829 exposed cases) and lower risks (RR = 0.93, 95% CI: 0.86–1.00, 5632 exposed cases) of breast cancer, respectively. The increased risk after hyperthyroidism was greater among postmenopausal women (RR = 1.19, 95% CI 1.09–1.30) and the decreased risk after hypothyroidism was more pronounced among premenopausal women (RR = 0.69, 95% CI 0.53–0.89). Among women with no prior history of thyroid disease, every 1 mIU/L increase in TSH level was associated with a 0.8% (95% CI > 0–1.5%) lower risk of breast cancer. In conclusion, this meta-analysis supports an association between thyroid hormone levels and breast cancer risk, which could be modified by menopausal status.
Germline CDKN1B variant type and site are associated with phenotype in MEN4
Authors: Halperin Reut , Arnon Liat , Nasirov Sapir , Friedensohn Limor , Gershinsky Michal , Telerman Alona , Friedman Eitan , Bernstein-Molho Rinat , Tirosh Amit
Published: October 2022

Multiple endocrine neoplasia 4 (MEN4) is a rare multiglandular endocrine neoplasia syndrome clinically hallmarked by primary hyperparathyroidism (PHPT), pituitary adenoma (PitAd), and neuroendocrine tumors (NET), clinically overlapping MEN1. The underlying mutated gene – CDKN1B, encodes for the cell-cycle regulator p27. Possible genotype–phenotype correlations in MEN4 have not been thoroughly assessed. Prompted by the findings in three Israeli MEN4 kindreds, we performed a literature review on published and unpublished data from previously reported MEN4/CDKN1B cases. Univariate analysis analyzed time-dependent risks for developing PHPT, PitAd, or NET by variant type and position along the gene. Overall, 74 MEN4 cases were analyzed. PHPT risk was 53.4% by age 60 years (mean age at diagnosis age 50.6 ± 13.9 years), risk for PitAd was 23.2% and risk for NET was 16.2% (34.4 ± 21.4 and 52.9 ± 13.9 years, respectively). The frameshift variant p.Q107fs was the most common variant identified (4/41 (9.7%) kindreds). Patients with indels had higher risk for PHPT vs point mutations (log-rank, P = 0.029). Variants in codons 94–96 were associated with higher risk for PHPT (P < 0.001) and PitAd (P = 0.031). To conclude, MEN4 is clinically distinct from MEN1, with lower risk and older age for PHPT diagnosis. We report recurrent CDKN1B frameshift variants and possible genotype–phenotype correlations.
Maternal glucocorticoids do not directly mediate the effects of maternal social stress on the fetus
Authors: Sze Ying , Fernandes Joana , Kołodziejczyk Zofia M , Brunton Paula J
Published: October 2022

Stress during pregnancy negatively affects the fetus and increases the risk for affective disorders in adulthood. Excess maternal glucocorticoids are thought to mediate fetal programming; however, whether they exert their effects directly or indirectly remains unclear. During pregnancy, protective mechanisms including maternal hypothalamic–pituitary–adrenal (HPA) axis hyporesponsiveness and placental 11β-hydroxysteroid dehydrogenase (11βHSD) type 2, which inactivates glucocorticoids, limit mother-to-fetus glucocorticoid transfer. However, whether repeated stress negatively impacts these mechanisms is not known. Pregnant rats were exposed to repeated social stress on gestational days (GD) 16–20 and several aspects of HPA axis and glucocorticoid regulation, including concentrations of glucocorticoids, gene expression for their receptors (Nr3c1, Nr3c2), receptor chaperones (Fkbp51, Fkbp52) and enzymes that control local glucocorticoid availability (Hsd11b1, Hsd11b2), were investigated in the maternal, placental and fetal compartments on GD20. The maternal HPA axis was activated following stress, though the primary driver was vasopressin, rather than corticotropin-releasing hormone. Despite the stress-induced increase in circulating corticosterone in the dams, only a modest increase was detected in the circulation of female fetuses, with no change in the fetal brain of either sex. Moreover, there was no change in the expression of genes that mediate glucocorticoid actions or modulate local concentrations in the fetal brain. In the placenta labyrinth zone, stress increased Hsd11b2 expression only in males and Fkbp51 expression only in females. Our results indicate that any role glucocorticoids play in fetal programming is likely indirect, perhaps through sex-dependent alterations in placental gene expression, rather than exerting effects via direct crossover into the fetal brain.
Nuevas realidades y desafíos en ambientes virtuales de aprendizaje: una política educativa de la Fundación Universitaria Konrad Lorenz
Authors: Rodríguez Bernal Yoshira
Published: October 2022

El panorama social, económico, político y cultural en el que nos situamos advierte inevitables transformaciones, entre otras actividades, de los procesos educativos tal como los conocemos, especialmente ante el reto de la continuidad académica en el marco del aislamiento colectivo por causa de la emergencia sanitaria en el 2020. Al respecto, las instituciones de educación superior se vieron obligadas a asumir un papel preceptor en la reconstrucción de una nueva realidad, lo cual implica “potenciar la capacidad tecnológica combinando formas tradicionales y modernas que estimulen la formación y hagan viable el desarrollo humano sostenible” (Unesco, 1999). Este es el caso de la Fundación Universitaria Konrad Lorenz, que concentra, además, actividades investigativas para la promoción del conocimiento científico y tecnológico, ante lo cual fue un desafío afrontar las nuevas realidades. A continuación, se presenta un resumen de la experiencia obtenida y las estrategias implementadas con rigor y toda la responsabilidad en la prestación del servicio educativo.
Identification of factors affecting outcomes in patients with Guillain Barre syndrome
Authors: Bhatia Vaidehi Dipesh , Khant Poonam Batuk , Vyshnavee Inguva , Shiyaf Mohammed , Thunga Girish , Gorthi Sankar Prasad , Kunhikatta Vijayanarayana
Published: October 2022

Background. Guillain Barre syndrome (GBS) is a rare autoimmune neurological disorder resulting in variable clinical course and outcome. Various factors such as age, symptoms and disease form that influence the outcome of GBS have been previously studied.

Aim. This study aimed at identifying factors affecting the outcomes in patients with GBS.

Methods. A retrospective observational study was conducted on GBS (ICD-G61.0) patients admitted to the hospital between 2014 and 2019. Patient information on demographics, medical and medication history, laboratory parameters, electrophysiological data, type of GBS and therapy received were retrieved from medical records. Univariate and multivariate analysis were conducted to identify factors associated with outcome (improved and not improved) and calculate odds ratio (OR).

Results. A total of 212 GBS patients were included in the study, of which 67% were males and the mean age was 39.9±20.1 years. 168 (79%) patients showed improvement whereas the remaining 44(21%) did not show improvement. Patients with hypertension (OR=4.512; CI=1.309-15.556, p=0.017), alcoholics (OR=5.148; CI=1.234-21.472, p=0.025), sepsis (OR= 9.139; CI=1.102-75.760, p=0.040) and cardiac arrest (OR=17.495; CI=1.249-245.027, p=0.034) were associated with risk of no improvement. Whereas those treated with IVIgG plus Physiotherapy/Occupational therapy (OR=0.062; CI=0.016-0.242, p=0.001) and Plasmapheresis plus Physiotherapy/Occupational therapy (OR=0.007; CI=0.000- 0.147, p=0.001) were associated with improvement.

Conclusion. Understanding these factors help to further give a more directed and focused management to improve the condition in patients who are at risk of poor outcome. Further follow-up studies could be done to determine and manage the residual disabilities associated with GBS to improve patient’s quality of life.
Proton pump inhibitors use and risk of inflammatory bowel diseases: a meta-analysis of observational studies
Authors: Shastri Sanjana Aditya , Kantamneni Raveena , Rashid Muhammed , Chandran Viji Pulikkel , Suhita Ramadugula , Begum Izwath , Nair Sreedharan , Thunga Girish
Published: October 2022

Background and objective. Proton Pump Inhibitors (PPIs) reduce gastric acid production and they are indicated for myriad gastrointestinal conditions. Prolonged use of PPI has been linked to the risk of inflammatory bowel disease (IBD) though this fact is not well established. We aimed to conduct a systematic review and meta-analysis to estimate the risk of IBD occurrence with PPI use.

Methodology. The databases such as PubMed, Scopus, and Cochrane Library were accessed from inception to December 2020. Additionally, the bibliographic search and a random search in Google, Google Scholar, and ResearchGate were performed to find additional sources. The observational studies estimating the risk of IBD following the use of PPI, published in the English language were considered for this review. The methodological quality of included studies was assessed using the Modified Downs and Black checklist.

Results. Eight out of 2038 studies with 157,758 participants were included in this meta-analysis. A significantly higher risk of IBD (adjusted odds ratio [aOR] 2.43; 95% Confidence Interval [CI] 1.18-5.02; P=0.02; n=6) was observed in participants taking PPIs for any indication. Moreover, a significant association was observed between PPI exposure on the different types of IBD such as ulcerative colitis and Crohn’s disease together (aOR: 3.60; 95% CI: 1.10-11.74), collagenous colitis (OR: 4.73; 95% CI: 1.99-11.22) and lymphocytic Colitis (OR: 3.77; 95% CI: 2.91- 4.87), but not with ulcerative colitis (P=0.47) and microscopic colitis (P=0.07) alone. Similarly, a significant association was observed among Europeans (aOR: 3.98; 95% CI: 2.36-6.71), but not with North American (aOR: 0.48; 95% CI: 0.01- 26.71) studies. Overall the study quality was good.

Conclusion. The current evidence indicates that exposure to PPI is significantly associated with increased risk of IBD. Further, adequately powered studies from various parts of the world are needed for better quantification and generalizability of our findings.

PROSPERO Protocol Registration Number: CRD42020209674