bluuebunny/crossref_metadata_2025 huggingface dataset:
Credit Risk Modeling Using Interpreted XGBoost
Authors:   Wroclaw University of Economics and Business, Poland, Hernes Marcin , Adaszyński Jędrzej ,   Wroclaw University of Economics and Business, Poland, Tutak Piotr
Published: January 2024

Purpose: The aim of the paper is to develop a credit risk assessment model usingb the XGBoost classifier supported by interpretation issues. Design/methodology/approach: The risk modeling is based on Extreme Gradient Boosting (XGBoost) in the research. It is a method used for regression and classification problems. It is based on a sequence of decision trees using a gradient-based optimization method of the loss function to minimize the errors of weak estimators. We use also methods for performing local and global interpretability: ceteris paribus charts, SHAP and feature importance approach. Findings: Based on the research results, it can be concluded that XGBoost achieved higher values of performance metrics than logistic regression, except sensitivity. It means that XGBoost indicated a smaller percentage of all bad client. Results of local interpretability enable a conclusion that in the case of the client in question, the credit decision is positively influenced by credit scores from external suppliers, while it is negatively influenced by minimal external scoring and short seniority. The number of years in the car and higher education are also positive. Such information helps to justify a negative credit decision. Results of global interpretability enable a conclusion that higher values of the traits associated with the z-scores are accompanied by negative Shapley values, which can be interpreted as a negative effect on the explanatory variable. Research limitations/implications: XGBoost, A ceteris paribus plot, SHAP, and feature importance methods can be used to develop a credit risk assessment model including machine learning interpretability. The main limitation of research is to compare the results of XGBoost only to the logistic regression results. Future research should focus on comparing the results of XGBoost to other machine learning methods, including neural networks. Originality/value: One of the key processes in a bank is the credit decision process, which is the evaluation of a client’s repayment risk. In the consumer finance sector, the processes are usually largely automated, and increasingly the latest machine learning methods based on neural networks and ensemble learning methods are being used for the purpose. Although machine learning models allow for achieving higher accuracy of credit risk assessment compared to traditional statistical methods, the main problem is the low interpretability of machine learning models. The models often perform as the “black box”. However, the interpretation of the results of risk assessment models is very important due to the need to explain to the client the reasons for assessing their credit risk.
Comment rechercher l’intérêt supérieur de l’enfant lors d’une prise en charge palliative ? Analyse de 2 études de cas complexes
Authors: De Terwangne Brigitte , Tonon Corinne , Bellis Dominique , Freson Muriel , Watterman Noémie , Maelfeyt Julie
Published: January 2024

Cadre de la recherche : Dans le cadre de la mission d’une équipe de liaison pédiatrique spécialisée en soins palliatifs pédiatriques (SPP) en Belgique, cet article propose d’analyser les enjeux décisionnels face à l’intérêt supérieur de l’enfant dans une étude de deux cas cliniques complexes qui ont impacté cette équipe et ont questionné leur approche professionnelle.

Objectif : Cet article met en évidence la notion de l’intérêt supérieur de l’enfant se basant sur des enjeux décisionnels relatif à sa santé. Lorsque les avis des parents et de l’équipe soignante divergent quant au traitement à donner à un enfant en situation de soins palliatifs pédiatriques, nous analyserons les enjeux liés au processus décisionnel partagé (PDP) ainsi qu’aux facteurs éthiques pour identifier des pistes de compréhension et de solutions.

Méthodologie : Nous avons choisi pour méthode l’étude de deux cas cliniques complexes vécus à domicile par une équipe de liaison spécialisée en SPP. Cette méthode qualitative permet d’analyser la situation dans sa singularité et sa globalité. Il s’agit d’une étude de cas intrinsèque, basée sur un problème pratique rencontré, une confrontation personnelle à une situation professionnelle donnée complexe (Duport, 2020).

Résultats : Notre recherche expose la complexité de la trajectoire décisionnelle et la nécessité de prendre en compte les systèmes d’influence dans la prise de décision, ainsi que l’importance pour l’équipe de soins de prendre du recul et d’avoir une grille de lecture éthique adaptée à la situation donnée.

Conclusions : La prise en charge d’un enfant gravement malade suivi en SPP est évolutive et non linéaire. La prise de décision partagée (PDP) formalisée entre médecins, l’enfant et ses parents, et l’équipe soignante permet de prendre en compte toutes les composantes rentrant dans ce processus et vise à respecter l’intérêt supérieur de l’enfant. Les différents critères créent un climat de confiance indispensable à la bonne prise en charge de l’enfant.

Contributions : Le blocage dans la relation thérapeutique est un symptôme de perte du climat de confiance avec risque de repli, mais les systèmes peuvent parfois autogénérés leur propre solution, ce qui démontre l’importance de développer et de former les équipes à l’approche de la prise de décision partagée.
Le curatif, le palliatif… quelle importance ?

L’expérience de parents ayant accompagné leur enfant dans la grande
maladie et la fin de vie
Authors: Fortin Sylvie , Lessard Sabrina , Lajeunesse Alizée
Published: January 2024

Cadre de la recherche : Dans la grande maladie,
la prolifération des possibilités thérapeutiques retarde souvent le moment où la mort est
envisagée et où les soins palliatifs, trop souvent associés à la fin de vie et à la mort,
sont introduits dans les trajectoires des malades. Dans ce contexte, les soins palliatifs
pédiatriques tentent de jouer un rôle actif dans la relation de soins, au-delà de l’idée
de traitements pour la guérison.

Objectifs : Notre article cherche à mieux
comprendre le moment où les soins palliatifs deviennent une possibilité dans la
trajectoire de la grande maladie, et comment ils sont représentés. Nous nous intéressons à
la place que ces soins occupent dans le vécu des parents, ainsi que la manière dont
s’exprime leur expérience de la grande maladie, et plus précisément la dimension
relationnelle de la fin de vie.

Méthodologie : Nous nous appuyons sur les
témoignages de parents dont les enfants ont souffert de maladies graves et de décès. Par
le biais d’entretiens individuels semi-dirigés entre 2017 et 2019, nous avons recueilli
les histoires de 16 enfants et adolescents montréalais d’origine migrante ou non-migrante
(10 garçons et 6 filles âgés de quelques semaines à
19 ans),
atteints d’une maladie génétique ou rare, d’un cancer ou de plusieurs maladies
chroniques.

Résultats : Non seulement le type de maladie
est une composante importante dans le parcours des soins palliatifs, mais le care et le profil des familles sont également déterminants dans la
perception d’une expérience (néanmoins) positive de la fin de vie de leur enfant.

Conclusions : Les perspectives thérapeutiques
curatives/palliatives ont peu d’influence sur la satisfaction de nos participants quant
aux soins de fin de vie, tant qu’un lien de confiance thérapeutique est présent entre la
famille et l’équipe soignante. Que ce soit positif ou négatif, ce lien de confiance
influence les relations de soins pédiatriques et les trajectoires de maladies graves,
ainsi que les expériences de fin de vie vécues par les proches.

Contribution : À travers les expériences
d’enfants en fin de vie telles que partagées (principalement) par les mères, cet article
aborde les perspectives curatives et palliatives telles que choisies par les parents
d’enfants confrontés à un sombre pronostic. Au-delà des différentes philosophies qui
habitent ces approches, la qualité (et la continuité) des relations établies avec les
soignants est un facteur déterminant dans la qualité des expériences documentées par notre
étude.
L’accompagnement d’un enfant atteint de cancer :
une expérience aux multiples contextes pour les familles habitant loin des centres
spécialisés
Authors: Simard Chantale
Published: January 2024

Cadre de la recherche : Le cancer est la maladie
potentiellement mortelle la plus fréquente chez les enfants canadiens. Il s’agit d’une
expérience familiale traumatique. Des auteurs soulignent que les familles touchées sont
plus vulnérables si elles ne disposent pas de ressources suffisantes pour favoriser leur
processus de résilience. Or, celles habitant une localité éloignée des centres
hospitaliers spécialisés en oncologie pédiatrique (CHSOP) sont confrontées à des défis
additionnels en raison de leur accès limité à des ressources et services pouvant répondre
à leurs besoins immédiats. Alors que l’expérience familiale du cancer pédiatrique est
abondamment décrite dans les écrits scientifiques, celle liée à l’éloignement des CHSOP
demeure peu explorée. L’approche de soins fondée sur les forces de la personne et la
famille de Gottlieb et la théorie du renforcement de la résilience familiale de Walsh
(2012 ; 2016b) ont guidé cette étude. Cet article présente des résultats issus de la
première phase d’une plus vaste étude, conduite entre 2015 et 2021, soit ceux liés aux
différents contextes pouvant exacerber la vulnérabilité des familles.

Objectif : Explorer les facteurs liés au
processus de résilience de familles accompagnant un enfant atteint de cancer en contexte
d’éloignement (FAECCÉ).

Méthodologie : Une approche qualitative
descriptive a été adoptée à l’aide de 26 entrevues semi-structurées individuelles et de
groupe (n= 50 personnes : 39 membres de 11 familles, 11 infirmières).

Résultats : Parmi l’ensemble des résultats
obtenus lors de la plus vaste étude, deux principaux contextes d’éloignement ont été
dégagés et sont ici présentés : (1) lorsque les FAECCÉ sont dans leur localité, lors du
diagnostic de l’enfant, des retours du CHSOP et au quotidien, et (2) lorsqu’elles sont au
CHSOP, loin des personnes qui leur sont chères et de leurs repères habituels. Des
contextes aux facteurs de risque spécifiques, qui peuvent compromettre leur processus de
résilience.

Conclusions : L’éloignement est une expérience
multicontextuelle, persistante, qui touche tous les membres de la famille. Elle exige une
évaluation familiale particulière, et est favorisée par une meilleure communication et
collaboration entre les centres hospitaliers spécialisés et régionaux.

Contribution : La proposition de précieuses
pistes pour des soins plus adaptés à la réalité des FAECCÉ.
Celestina en la ficción contemporánea: El ritual de las doncellas (2006) de José Calvo Poyato y En la orilla (2016) de Rafael Chirbes
Authors: Montero Moreno Ana Mónica
Published: January 2024

La Tragicomedia de Calisto y Melibea (ca. 1502) –inicialmente concebida como una comedia y hoy en día más conocida como (La) Celestina– ha gozado de un éxito notable desde el momento de su creación poco antes de 1499 hasta hoy. La bibliografía sobre Celestina es inabarcable y su influencia en la dramaturgia y el cine es considerable. Recientemente, algunos críticos han comenzado a analizar su influencia en la novelística contemporánea. Este ensayo complementa este esfuerzo al observar cómo dos escritores, que trabajan con categorías literarias dispares, interpretan y adaptan aspectos de Celestina de manera radicalmente diferente. Así, por un lado, Celestina ha influido en el argumento, el desarrollo de los personajes y la reconstrucción histórica en El ritual de las doncellas (2006), una novela del género policíaco, ambientada en el barroco, escrita por el historiador José Calvo Poyato. Por otro lado, para el novelista Rafael Chirbes, Celestina no es solo una “caja de herramientas” con técnicas, escenas y citas útiles para los escritores, sino que constituye una revolución literaria en sí. Según Chirbes esta obra es modelo de una concepción ética de la literatura de acuerdo con la cual el lenguaje es el instrumento que puede revelar la manipulación ideológica, la corrupción social y el maltrato de los vencidos en los procesos históricos. En conclusión, la comparación de dos reescrituras de Celestina en las plumas de José Calvo Poyato y Rafael Chirbes –adaptaciones que, a primera vista, pueden pasar desapercibidas– revela dos fenómenos de intertextualidad que afectan la literatura tanto popular como culta y permite indagar en los valores literarios y el poder creativo de esta obra maestra del siglo XV.
Surface curvature and basal hydraulic stress induce spatial bias in cell extrusion
Authors: Huang Cheng-Kuang , Yong Xianbin , She David T. , Lim Chwee Teck
Published: January 2024

Epithelial cell extrusion is employed in maintaining a healthy epithelium. It remains unclear how environmental conditions specific to various epithelial tissues, such as geometry and fluid osmolarity, affect cell extrusions. We found that, over curved surfaces, epithelial monolayers exhibited higher extrusion rates in concave regions than convex ones. This difference, and overall extrusions, decreased when osmotically induced basal hydraulic stress was reduced by increasing media osmolarity or by culturing monolayers on hydrogels. Mechanistically, basal fluid accumulation antagonized cell-substrate adhesions and the subsequent FAK-Akt survival pathway, leading to apoptotic cell death. Convex surfaces induced cellular forces that acted against osmosis, thereby promoting adhesions and lowering apoptosis. This effect was reversed in concave regions, and together, resulted in a curvature induced spatial bias in cell extrusions.
A generative model of electrophysiological brain responses to stimulation
Authors: Vidaurre Diego
Published: January 2024

Each brain response to a stimulus is, to a large extent, unique. However this variability, our perceptual experience feels stable. Standard decoding models, which utilise information across several areas to tap into stimuli representation and processing, are fundamentally based on averages. Therefore, they can focus precisely on the features that are most stable across stimulus presentations. But which are these features exactly is difficult to address in the absence of a generative model of the signal. Here, I introduce genephys, a generative model of brain responses to stimulation publicly available as a Python package that, when confronted with a decoding algorithm, can reproduce the structured patterns of decoding accuracy that we observe in real data. Using this approach, I characterise how these patterns may be brought about by the different aspects of the signal, which in turn may translate into distinct putative neural mechanisms. In particular, the model shows that the features in the data that support successful decoding—and, therefore, likely reflect stable mechanisms of stimulus representation—have an oscillatory component that spans multiple channels, frequencies, and latencies of response; and an additive, slower response with a specific (cross-frequency) relation to the phase of the oscillatory component. At the individual trial level, still, responses are found to be highly variable, which can be due to various factors including phase noise and probabilistic activations.
Evolution of the gene regulatory network of body axis by enhancer hijacking in amphioxus
Authors: Shi Chenggang , Chen Shuang , Liu Huimin , Pan Rongrong , Li Shiqi , Wang Yanhui , Wu Xiaotong , Li Jingjing , Li Xuewen , Xing Chaofan , Liu Xian , Wang Yiquan , Qu Qingming , Li Guang
Published: January 2024

A central goal of evolutionary developmental biology is to decipher the evolutionary pattern of gene regulatory networks (GRNs) that control embryonic development, and the mechanism underlying GRNs evolution. The Nodal signaling that governs the body axes of deuterostomes exhibits a conserved GRN orchestrated principally by Nodal, Gdf1/3, and Lefty. Here we show that this GRN has been rewired in cephalochordate amphioxus. We found that while the amphioxus Gdf1/3 ortholog exhibited nearly no embryonic expression, its duplicate Gdf1/3-like, linked to Lefty, was zygotically expressed in a similar pattern as Lefty. Consistent with this, while Gdf1/3-like mutants showed defects in axial development, Gdf1/3 mutants did not. Further transgenic analyses showed that the intergenic region between Gdf1/3-like and Lefty could drive reporter gene expression as that of the two genes. These results indicated that Gdf1/3-like has taken over the axial development role of Gdf1/3 in amphioxus, possibly through hijacking Lefty enhancers. We finally demonstrated that, to compensate for the loss of maternal Gdf1/3 expression, Nodal has become an indispensable maternal factor in amphioxus and its maternal mutants caused axial defects as Gdf1/3-like mutants. We therefore demonstrated a case that the evolution of GRNs could be triggered by enhancer hijacking events. This pivotal event has allowed the emergence of a new GRN in extant amphioxus, presumably through a stepwise process. In addition, the co-expression of Gdf1/3-like and Lefty achieved by a shared regulatory region may have provided robustness during body axis formation, which provides a selection-based hypothesis for the phenomena called developmental system drift.
Projection neurons are necessary for the maintenance of the mouse olfactory circuit
Authors: Sánchez-Guardado Luis , Razavi Peyman , Wang Bo , Callejas-Marín Antuca , Lois Carlos
Published: January 2024

The assembly and maintenance of neural circuits is crucial for proper brain function. Although the assembly of brain circuits has been extensively studied, much less is understood about the mechanisms controlling their maintenance as animals mature. In the olfactory system, the axons of olfactory sensory neurons (OSNs) expressing the same odor receptor converge into discrete synaptic structures of the olfactory bulb (OB) called glomeruli, forming a stereotypic odor map. The OB projection neurons, called mitral and tufted cells (M/Ts), have a single dendrite that branches into a single glomerulus, where they make synapses with OSNs. We used a genetic method to progressively eliminate the vast majority of M/T cells in early postnatal mice, and observed that the assembly of the OB bulb circuits proceeded normally. However, as the animals became adults the apical dendrite of remaining M/Ts grew multiple branches that innervated several glomeruli, and OSNs expressing single odor receptors projected their axons into multiple glomeruli, disrupting the olfactory sensory map. Moreover, ablating the M/Ts in adult animals also resulted in similar structural changes in the projections of remaining M/Ts and axons from OSNs. Interestingly, the ability of these mice to detect odors was relatively preserved despite only having 1–5% of projection neurons transmitting odorant information to the brain, and having highly disrupted circuits in the OB. These results indicate that a reduced number of projection neurons does not affect the normal assembly of the olfactory circuit, but induces structural instability of the olfactory circuitry of adult animals.
Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain
Authors: Lin Ya-Hui , Wang Li-Wen , Chen Yen-Hui , Chan Yi-Chieh , Hu Shang-Hsiu , Wu Sheng-Yan , Chiang Chi-Shiun , Huang Guan-Jie , Yang Shang-Da , Chu Shi-Wei , Wang Kuo-Chuan , Lin Chin-Hsien , Huang Pei-Hsin , Cheng Hwai-Jong , Chen Bi-Chang , Chu Li-An
Published: January 2024

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.
Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons
Authors: Raudales Ricardo , Kim Gukhan , Kelly Sean M , Hatfield Joshua , Guan Wuqiang , Zhao Shengli , Paul Anirban , Qian Yongjun , Li Bo , Huang Z Josh
Published: January 2024

Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remain poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage (Nkx2.1) and molecular (Unc5b, Pthlh) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum–insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta, and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal, and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species.
The Spatial Frequency Representation Predicts Category Coding in the Inferior Temporal Cortex
Authors: Toosi Ramin , Karami Behnam , Koushki Roxana , Shakerian Farideh , Noroozi Jalaledin , Rezayat Ehsan , Vahabie Abdol-Hossein , Akhaee Mohammad Ali , Dehaqani Mohammad-Reza A
Published: January 2024

Understanding the neural representation of spatial frequency (SF) in the primate cortex is vital for unraveling visual processing mechanisms in object recognition. While numerous studies concentrate on the representation of SF in the primary visual cortex, the characteristics of SF representation and its interaction with category representation remain inadequately understood. To explore SF representation in the inferior temporal (IT) cortex of macaque monkeys, we conducted extracellular recordings with complex stimuli systematically filtered by SF. Our findings disclose an explicit SF coding at single-neuron and population levels in the IT cortex. Moreover, the coding of SF content exhibits a coarse-to-fine pattern, declining as the SF increases. Temporal dynamics analysis of SF representation reveals that low SF (LSF) is decoded faster than high SF (HSF), and the SF preference dynamically shifts from LSF to HSF over time. Additionally, the SF representation for each neuron forms a profile that predicts category selectivity at the population level. IT neurons can be clustered into four groups based on SF preference, each exhibiting different category coding behaviors. Particularly, HSF-preferred neurons demonstrate the highest category decoding performance for face stimuli. Despite the existing connection between SF and category coding, we have identified uncorrelated representations of SF and category. In contrast to the category coding, SF is more sparse and places greater reliance on the representations of individual neurons. Comparing SF representation in the IT cortex to deep neural networks, we observed no relationship between SF representation and category coding. However, SF coding, as a category-orthogonal property, is evident across various ventral stream models. These results dissociate the separate representations of SF and object category, underscoring the pivotal role of SF in object recognition.
The Spatial Frequency Representation Predicts Category Coding in the Inferior Temporal Cortex
Authors: Toosi Ramin , Karami Behnam , Koushki Roxana , Shakerian Farideh , Noroozi Jalaledin , Rezayat Ehsan , Vahabie Abdol-Hossein , Akhaee Mohammad Ali , Dehaqani Mohammad-Reza A.
Published: January 2024

Understanding the neural representation of spatial frequency (SF) in the primate cortex is vital for unraveling visual processing mechanisms in object recognition. While numerous studies concentrate on the representation of SF in the primary visual cortex, the characteristics of SF representation and its interaction with category representation remain inadequately understood. To explore SF representation in the inferior temporal (IT) cortex of macaque monkeys, we conducted extracellular recordings with complex stimuli systematically filtered by SF. Our findings disclose an explicit SF coding at single-neuron and population levels in the IT cortex. Moreover, the coding of SF content exhibits a coarse-to-fine pattern, declining as the SF increases. Temporal dynamics analysis of SF representation reveals that low SF (LSF) is decoded faster than high SF (HSF), and the SF preference dynamically shifts from LSF to HSF over time. Additionally, the SF representation for each neuron forms a profile that predicts category selectivity at the population level. IT neurons can be clustered into four groups based on SF preference, each exhibiting different category coding behaviors. Particularly, HSF-preferred neurons demonstrate the highest category decoding performance for face stimuli. Despite the existing connection between SF and category coding, we have identified uncorrelated representations of SF and category. In contrast to the category coding, SF is more sparse and places greater reliance on the representations of individual neurons. Comparing SF representation in the IT cortex to deep neural networks, we observed no relationship between SF representation and category coding. However, SF coding, as a category-orthogonal property, is evident across various ventral stream models. These results dissociate the separate representations of SF and object category, underscoring the pivotal role of SF in object recognition.
CaBP1 and 2 enable sustained CaV1.3 calcium currents and synaptic transmission in inner hair cells
Authors: Oestreicher David , Chepurwar Shashank , Kusch Kathrin , Rankovic Vladan , Jung Sangyong , Strenzke Nicola , Pangrsic Tina
Published: January 2024

To encode continuous sound stimuli, the inner hair cell (IHC) ribbon synapses utilize calcium-binding proteins (CaBPs), which reduce the inactivation of their CaV1.3 calcium channels. Mutations in the CABP2 gene underlie non-syndromic autosomal recessive hearing loss DFNB93. Besides CaBP2, the structurally related CaBP1 is highly abundant in the IHCs. Here, we investigated how the two CaBPs cooperatively regulate IHC synaptic function. In Cabp1/2 double-knockout mice, we find strongly enhanced CaV1.3 inactivation, slowed recovery from inactivation and impaired sustained exocytosis. Already mild IHC activation further reduces the availability of channels to trigger synaptic transmission and may effectively silence synapses. Spontaneous and sound-evoked responses of spiral ganglion neurons in vivo are strikingly reduced and strongly depend on stimulation rates. Transgenic expression of CaBP2 leads to substantial recovery of IHC synaptic function and hearing sensitivity. We conclude that CaBP1 and 2 act together to suppress voltage- and calcium-dependent inactivation of IHC CaV1.3 channels in order to support sufficient rate of exocytosis and enable fast, temporally precise and indefatigable sound encoding.
Caenorhabditis elegans Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA
Authors: Consalvo Claudia D , Aderounmu Adedeji M , Donelick Helen M , Aruscavage P Joseph , Eckert Debra M , Shen Peter S , Bass Brenda L
Published: January 2024

Invertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon response. While some invertebrate Dicers act alone during antiviral defense, Caenorhabditis elegans Dicer acts in a complex with a dsRNA binding protein called RDE-4, and an RLR ortholog called DRH-1. We used biochemical and structural techniques to provide mechanistic insight into how these proteins function together. We found RDE-4 is important for ATP-independent and ATP-dependent cleavage reactions, while helicase domains of both DCR-1 and DRH-1 contribute to ATP-dependent cleavage. DRH-1 plays the dominant role in ATP hydrolysis, and like mammalian RLRs, has an N-terminal domain that functions in autoinhibition. A cryo-EM structure indicates DRH-1 interacts with DCR-1’s helicase domain, suggesting this interaction relieves autoinhibition. Our study unravels the mechanistic basis of the collaboration between two helicases from typically distinct innate immune defense pathways.
Tgif1-deficiency impairs cytoskeletal architecture in osteoblasts by activating PAK3 signaling
Authors: Bolamperti Simona , Saito Hiroaki , Heerdmann Sarah , Hesse Eric , Taipaleenmäki Hanna
Published: January 2024

Osteoblast adherence to bone surfaces is important for remodeling bone tissue. This study demonstrates that deficiency of TG-interacting factor 1 (Tgif1) in osteoblasts results in altered cell morphology, reduced adherence to collagen type I-coated surfaces, and impaired migration capacity. Tgif1 is essential for osteoblasts to adapt a regular cell morphology and to efficiently adhere and migrate on collagen type I-rich matrices in vitro. Furthermore, Tgif1 acts as a transcriptional repressor of p21-activated kinase 3 (Pak3), an important regulator of focal adhesion formation and osteoblast spreading. Absence of Tgif1 leads to increased Pak3 expression, which impairs osteoblast spreading. Additionally, Tgif1 is implicated in osteoblast recruitment and activation of bone surfaces in the context of bone regeneration and in response to parathyroid hormone 1–34 (PTH 1–34) treatment in vivo in mice. These findings provide important novel insights in the regulation of the cytoskeletal architecture of osteoblasts.
Relationship between perceptual and mechanical markers of fatigue during bench press and bench pull exercises: impact of inter-set rest period length
Authors: Janicijevic Danica , Miras-Moreno Sergio , Morenas-Aguilar Maria Dolores , Jiménez-Martínez Pablo , Alix-Fages Carlos , García-Ramos Amador
Published: January 2024

This study aimed to explore whether the relationship between perceptual (rating of perceived exertion; RPE) and mechanical (maximal number of repetitions completed [MNR], fastest set velocity, and mean velocity decline) variables is affected by the length of inter-set rest periods during resistance training sets not leading to failure. Twenty-three physically active individuals (15 men and eight women) randomly completed 12 testing sessions resulting from the combination of two exercises (bench press and bench pull), three inter-set rest protocols (1, 3, and 5 min), and two minimal velocity thresholds (farther from muscular failure [MVT0.45 for bench press and MVT0.65 for bench pull] and closer to muscular failure [MVT0.35 for bench press and MVT0.55 for bench pull]). The duration of inter-set rest periods did not have a significant impact on RPE values (p ranged from 0.061 to 0.951). Higher proximities to failure, indicated by lower MVTs, were associated with increased RPE values (p < 0.05 in 19 out of 24 comparisons). Moreover, as the number of sets increased, an upward trend in RPE values was observed (p < 0.05 in seven out of 12 comparisons). Finally, while acknowledging some inconsistencies, it was generally observed that higher magnitudes of the mechanical variables, especially MNR (rs < −0.55 in three out of four comparisons), were associated with lower RPE values. These results, which were comparable for the bench press and bench pull exercises, suggest that post-set RPE values are affected by the fatigue experienced at both the beginning and end of the set.
Implementación de un modelo de evaluación formativa de la docencia: cambios que genera en las estrategias didácticas para el desarrollo de habilidades científicas dentro del aula
Authors:   , Fuentes Pavéz Alejandro Andrés
Published: January 2024

Este trabajo adopta una perspectiva metodológica cualitativa mediante el diseño de investigación acción técnica para implementar un modelo colaborativo y reflexivo de evaluación formativa de la docencia en el departamento de ciencias de un establecimiento particular subvencionado, con la finalidad de analizar los cambios que genera en las estrategias didácticas llevadas a cabo por los docentes para el desarrollo de habilidades científicas. Este modelo se implementó con tres docentes, los cuales se observaron y retroalimentaron de forma cruzada durante dos ciclos evaluativos en los cuales se implementaron reflexiones guiadas. Los datos se recopilaron principalmente a través de reflexiones escritas y grabaciones de las reuniones grupales de los docentes. Tras la implementación, se puede afirmar que el modelo propicia una mejora incipiente por parte de las estrategias implementadas por dos de los tres docentes. Además, las características de colaboración y reflexión del modelo potenciaron las retroalimentaciones y a su vez la mejora de sus prácticas. Finalmente, el modelo permitió resignificar la percepción sobre la evaluación de la docencia de uno de los docentes.
Perceived Organizational Support as Mediation of Work Engagement and Self-efficacy on Employee Performance
Authors: Nugraha Desta , Kharismasyah Alfato Yusnar
Published: January 2024

Objective: Employee performance in the context of the government agency sector is a significant concern, considering their vital role in providing public services and achieving development goals. The understanding of how perceived organizational support (POS) functions as mediation in the context of an agency still needs to be improved. Therefore, this research aims to fill the gap in previous research and explain the role of POS as a mediator that facilitates the influence of work engagement and self-efficacy on employee performance in the agency environment.

Study Design: In this research, perceived organizational support (POS) is considered a mediating mechanism that can explain the relationship between work engagement, self-efficacy, and employee performance.

Place and Duration of Study: Water Resources Management Center of Serayu Citanduy, Indonesia, between November 2023 and January 2024.

Methodology: This research involved 105 respondents who were employees at the Serayu Citanduy Water Resources Management Center. Data was collected through questionnaires, and data analysis was carried out using SmartPLS 4.0 software.

Results: There is a significant positive effect of work engagement on employee performance (β= .228, P value= .011), self-efficacy on employee performance (β= .238, P value= .017), POS on employee performance (β= .366, P value= .001), work engagement on employee performance through POS (β= .154, P value= .016), and self-efficacy on employee performance through POS (β= .122, P value= .004).

Conclusion: Partially, work engagement, self-efficacy, and POS have a positive and significant relationship with employee performance. Employees who feel involved in work will easily be used as capital by the organization or company to increase productivity. Employee who feels confident in their abilities will find it easier to develop themselves and later perform well. In addition, this research found that POS acts as a mediator, connecting work engagement and self-efficacy with employee performance indirectly.
Studies on Fresh and Cryopreserved Seminal Attributes in Beetal Bucks Outside their Breeding Tract
Authors: Keshav . , Dutta Mitali , Rongmei Soihem Diana , Yadav Anand Kumar , Jadav Ravindra
Published: January 2024

The objectives of the present research were to assess fresh and cryopreserved. seminal characteristics of breeding Beetal buck semen outside of its breeding tract. Semen was collected twice in a week from twelve Beetal bucks for 6 weeks. The mean value of  ejaculate volume(ml), mass motility(o-5 scale), progressive motility(%), sperm viability (%), intact acrosome(%), sperm abnormality(%) and plasma membrane integrity(%) were ranged from 0.73 ± 0.08 ml to 1.17 ± 0.27 ml; 4.17+ to 4.67+, 80.83 ± 1.54 to 87.50 ± 2.14; 83.83 ± 0.95 to 90.33 ± 0.80; 87.00 ± 0.86 to 94.67 ± 0.33; 6.83 ± 0.31 to 10.33 ± 0.67 and 59.33 ± 1.52 to 66.67 ± 1.17, respectively. The mean value of post thaw sperm motility, post thaw sperm viability, post thaw acrosome integrity, post thaw sperm abnormalities and post thaw plasma membrane integrity were ranged from 52.50± 1.12 to 66.67 ± 1.67; 60.00 ± 1.24 to 69.67 ± 1.05; 66.00 ± 0.77 to 78.83 ± 2.15; 9.00 ± 0.45 to 12.83 ± 0.60 and 41.50 ± 1.18 to 53.50 ± 1.23, respectively. It was determined that, even outside of the breeding tract, the foundational characteristics of Beetal bucks are within the range defined for other Indian breeds of goat.
Mixture‐based adaptive probabilistic control
Authors: Kárný Miroslav , Böhm Josef , Guy Tatiana V. , Nedoma Petr
Published: March 2003

Quasi‐Bayes algorithm, combined with stabilized forgetting, provides a tool for efficient recursive estimation of dynamic probabilistic mixture models. They can be interpreted either as models of closed‐loop with switching modes and controllers or as a universal approximation of a wide class of non‐linear control loops.

Fully probabilistic control design extended to mixture models makes basis of a powerful class of adaptive controllers based on the receding‐horizon certainty equivalence strategy.

Paper summarizes the basic elements mentioned above, classifies possible types of control problems and provides solution of the key one referred to as ‘simultaneous’ design. Results are illustrated on mixtures with components formed by normal auto‐regression models with external variable (ARX). Copyright © 2003 John Wiley & Sons, Ltd.
Rapid platelet inhibition after a single capsule of Aggrenox®: Challenging a conventional full‐dose aspirin antiplatelet advantage?
Authors: Serebruany Victor L. , Malinin Alex I. , Sane David C.
Published: March 2003

Aggrenox® is a novel combination of 25 mg of aspirin with 200 mg of sustained release dipyridamole. In a recent large trial (ESPS‐2), Aggrenox® was twice as effective for secondary stroke prevention as either aspirin or dipyridamole alone, suggesting superior platelet inhibition for combination therapy. We sought to compare the time course of platelet inhibition with Aggrenox® compared with escalating doses of non‐enteric coated aspirin. Data from 10 healthy volunteers were analyzed. Fasting subjects sequentially ingested aspirin in the following order: 325 mg, 81 mg, 25 mg, and then one pill of Aggrenox® after a 3‐week interval for aspirin washout. Platelet function was assessed at baseline, 15, 30, 60, and 120 min post‐medication with 5 μM epinephrine and 5 μM ADP using conventional aggregometry. Aspirin provided significant (P < 0.01) reduction of platelet aggregation at 15 min post 325 mg, 30 min post 81 mg, and unexpectedly within 60 min after taking 25 mg of aspirin. A single pill of Aggrenox® also inhibited platelet aggregation within 1 hr after administration. Aspirin inhibits platelets remarkably fast. Both Aggrenox® and a matching dose of aspirin (25 mg) exhibit significant antiplatelet properties within 60 min after ingestion. These findings could be relevant for the optimal balance between the reduction of vascular events via sufficient and rapid platelet inhibition and low risk of bleeding complications associated with the Aggrenox® therapy. Am. J. Hematol. 72:280–281, 2003. © 2003 Wiley‐Liss, Inc.
A novel mechanism underlying drug resistance in chronic epilepsy
Authors: Remy Stefan , Gabriel Siegrun , Urban Bernd W. , Dietrich Dirk , Lehmann Thomas N. , Elger Christian E. , Heinemann Uwe , Beck Heinz
Published: March 2003

The development of resistance to pharmacological treatment is common to many human diseases. In chronic epilepsy, many patients develop resistance to anticonvulsant drug treatment during the course of their disease, with the underlying mechanisms remaining unclear. We have studied cellular mechanisms underlying drug resistance in resected hippocampal tissue from patients with temporal lobe epilepsy by comparing two groups of patients, the first displaying a clinical response to the anticonvulsant carbamazepine and a second group with therapy‐resistant seizures. Using patch‐clamp recordings, we show that the mechanism of action of carbamazepine, use‐dependent block of voltage‐dependent Na+ channels, is completely lost in carbamazepine‐resistant patients. Likewise, seizure activity elicited in human hippocampal slices is insensitive to carbamazepine. In marked contrast, carbamazepine‐induced use‐dependent block of Na+ channels and blocked seizure activity in vitro in patients clinically responsive to this drug. Consistent with these results in human patients, we also show that use‐dependent block of Na+ channels by carbamazepine is absent in chronic experimental epilepsy. Taken together, these data suggest that a loss of Na+ channel drug sensitivity may constitute a novel mechanism underlying the development of drug‐resistant epilepsy. Ann Neurol 2003
[123I]‐FP‐CIT‐SPECT demonstrates dopaminergic deficit in orthostatic tremor
Authors: Katzenschlager Regina , Costa Durval , Gerschlager Willibald , O'Sullivan John , Zijlmans Jan , Gacinovic Svetoslav , Pirker Walter , Wills Adrian , Bhatia Kailash , Lees Andrew J. , Brown Peter
Published: March 2003

There is increasing evidence of a potential role of the dopaminergic system in orthostatic tremor (OT): Association with parkinsonism and treatment effects of L‐dopa and dopamine agonists have been reported. Eleven patients with isolated OT had single‐photon emission computed tomography (SPECT) using 123I‐FP‐CIT ([123I]‐2β‐carbomethoxy‐3β‐(‐4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane) as dopamine transporter tracer. Results were compared with 12 age‐matched normal controls and 12 patients with Parkinson's disease (PD). A marked reduction in striatal tracer binding was found in OT compared to normal controls (p < 0.001). Tracer uptake was significantly higher and more symmetrical than in PD, and caudate and putamen were equally affected. L‐dopa challenges, performed in seven patients, showed a small but non‐significant improvement on EMG and a small but significant improvement in clinical parameters on blinded video rating. Two‐month open‐label L‐dopa treatment (600 mg/day) led to a small improvement in two of five patients but no significant overall change. Olfactory function on University of Pennsylvania Smell Identification Test was normal. Our finding of a marked tracer uptake reduction on dopamine transporter SPECT supports a role of the dopaminergic system in OT. Lack of evidence of a clinically relevant therapeutic response to L‐dopa suggests that other mechanisms must also be involved in the pathogenesis. Ann Neurol 2003
Phenotype modulators in myophosphorylase deficiency
Authors: Martinuzzi Andrea , Sartori Elena , Fanin Marina , Nascimbeni Annachiara , Valente Lucia , Angelini Corrado , Siciliano Gabriele , Mongini Tiziana , Tonin Paola , Tomelleri Giuliano , Toscano Antonio , Merlini Luciano , Bindoff Laurence A. , Bertelli Stefano
Published: March 2003

Myophosphorylase deficiency is characterized by exercise intolerance, muscle cramps, and recurrent myoglobinuria. Some patients are severely affected, whereas others are minimally affected or asymptomatic. The molecular basis of the disease has been elucidated but does not provide an explanation for the clinical variability. In a large cohort of patients with myophosphorylase deficiency, we tested the hypothesis that polymorphic variants in either myoadenylate deaminase (MADA) or angiotensin‐converting enzyme (ACE) could act as modulators of phenotype expression. Forty‐seven patients were evaluated. Clinical severity was assessed according to a severity scale of four grades. MADA activity was studied by histochemical and biochemical analysis of muscle, and the Q12X mutation in the adenine monophosphate deaminase 1 gene (AMPD1) and the insertion/deletion polymorphism in the ACE gene were assessed genetically. A complete MADA defect together with the Q12X mutation was detected in one severely affected patient. Eleven patients were heterozygous for the Q12X mutation. There was no association between clinical grading and MADA status. In contrast, we found a highly significant (p < 0.01) association between ACE genotype and clinical severity, with strong correlation between severe phenotype and number of D alleles. We show that ACE insertion/deletion polymorphism may play a significant role as phenotype modulator in McArdle's disease. Ann Neurol 2003
Efficient three‐drug cocktail for disease induced by mutant superoxide dismutase
Authors: Kriz Jasna , Gowing Geneviève , Julien Jean‐Pierre
Published: March 2003

There is currently no effective pharmacological treatment for amyotrophic lateral sclerosis (ALS). Because evidence suggests that multiple pathways may contribute to ALS pathogenesis, we tested in a mouse model of ALS (SOD1G37R mice) a combination approach consisting of three drugs for distinct targets in the complex pathway to neuronal death: minocycline, an antimicrobial agent that inhibits microglial activation, riluzole, a glutamate antagonist, and nimodipine, a voltage‐gated calcium channel blocker. The efficacy of this three‐drug cocktail was remarkable when administered in the diet from late presymptomatic stage (8–9 months). It delayed the onset of disease, slowed the loss of muscle strength, and increased the average longevity of SOD1G37R mice by 6 weeks. The protective effect of the treatment was corroborated by the reduced immunodetection signals for markers of gliosis and neurodegeneration in the spinal cord of SOD1G37R mice. These results indicate that such three‐drug combination may represent an effective strategy for ALS treatment. Ann Neurol 2003
Diminished striatal [123I]iodobenzovesamicol binding in idiopathic cervical dystonia
Authors: Albin Roger L. , Cross Donna , Cornblath Wayne T. , Wald John A. , Wernette Kristine , Frey Kirk A. , Minoshima Satoshi
Published: March 2003

Striatal dysfunction is thought to underlie many dystonias. We used [123I]iodobenzovesamicol single‐photon emission computed tomography imaging to determine the density of cholinergic terminals in the striatum and other brain regions in 13 subjects with idiopathic cervical dystonia. Striatal [131I]iodobenzovesamicol binding was reduced. These results support a role for striatal dysfunction in idiopathic dystonias and suggest diminished striatal cholinergic interneuron density in cervical dystonia. Ann Neurol 2003;53:528–532