bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excitatory Projections from the Prefrontal Cortex to Nucleus Accumbens Core D1-MSNs and κ Opioid Receptor Modulate Itch-Related Scratching Behaviors
Authors: Wu Xiao-Bo , Zhu Qian , Gao Ming-Hui , Yan Sheng-Xiang , Gu Pan-Yang , Zhang Peng-Fei , Xu Meng-Lin , Gao Yong-Jing 
Published: January 2023

Itch is an uncomfortable and complex sensation that elicits the desire to scratch. The nucleus accumbens (NAc) activity is important in driving sensation, motivation, and emotion. Excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus are crucial in tuning the activity of dopamine receptor D1-expressing and D2-expressing medium spiny neurons (Drd1-MSN and Drd2-MSN) in the NAc. However, a cell-type and neural circuity-based mechanism of the NAc underlying acute itch remains unclear. We found that acute itch induced by compound 48/80 (C48/80) decreased the intrinsic membrane excitability in Drd1-MSNs, but not in Drd2-MSNs, in the NAc core of male mice. Chemogenetic activation of Drd1-MSNs alleviated C48/80-induced scratching behaviors but not itch-related anxiety-like behaviors. In addition, C48/80 enhanced the frequency of spontaneous EPSCs (sEPSCs) and reduced the paired-pulse ratio (PPR) of electrical stimulation-evoked EPSCs in Drd1-MSNs. Furthermore, C48/80 increased excitatory synaptic afferents to Drd1-MSNs from the mPFC, not from the basolateral amygdala (BLA) or ventral hippocampus (vHipp). Consistently, the intrinsic excitability of mPFC-NAc projecting pyramidal neurons was increased after C48/80 treatment. Chemogenetic inhibition of mPFC-NAc excitatory synaptic afferents relieved the scratching behaviors. Moreover, pharmacological activation of κ opioid receptor (KOR) in the NAc core suppressed C48/80-induced scratching behaviors, and the modulation of KOR activity in the NAc resulted in the changes of presynaptic excitatory inputs to Drd1-MSNs in C48/80-treated mice. Together, these results reveal the neural plasticity in synapses of NAc Drd1-MSNs from the mPFC underlying acute itch and indicate the modulatory role of the KOR in itch-related scratching behaviors.SIGNIFICANCE STATEMENTItch stimuli cause strongly scratching desire and anxiety in patients. However, the related neural mechanisms remain largely unclear. In the present study, we demonstrated that the pruritogen compound 48/80 (C48/80) shapes the excitability of dopamine receptor D1-expressing medium spiny neurons (Drd1-MSNs) in the nucleus accumbens (NAc) core and the glutamatergic synaptic afferents from medial prefrontal cortex (mPFC) to these neurons. Chemogenetic activation of Drd1-MSNs or inhibition of mPFC-NAc excitatory synaptic afferents relieves the scratching behaviors. In addition, pharmacological activation of κ opioid receptor (KOR) in the NAc core alleviates C48/80-induced itch. Thus, targeting mPFC-NAc Drd1-MSNs or KOR may provide effective treatments for itch.
Learning-Induced Odor Modulation of Neuronal Activity in Auditory Cortex
Authors: Gilday Omri David , Mizrahi Adi 
Published: January 2023

Sensory cortices, even of primary regions, are not purely unisensory. Rather, cortical neurons in sensory cortex show various forms of multisensory interactions. While some multisensory interactions naturally co-occur, the combination of others will co-occur through experience. In real life, learning and experience will result in conjunction with seemingly disparate sensory information that ultimately becomes behaviorally relevant, impacting perception, cognition, and action. Here we describe a novel auditory discrimination task in mice, designed to manipulate the expectation of upcoming trials using olfactory cues. We show that, after learning, female mice display a transient period of several days during which they exploit odor-mediated expectations for making correct decisions. Using two-photon calcium imaging of single neurons in auditory cortex (ACx) during behavior, we found that the behavioral effects of odor-mediated expectations are accompanied by an odor-induced modulation of neuronal activity. Further, we find that these effects are manifested differentially, based on the response preference of individual cells. A significant portion of effects, but not all, are consistent with a predictive coding framework. Our data show that learning novel odor–sound associations evoke changes in ACx. We suggest that behaviorally relevant multisensory environments mediate contextual effects as early as ACx.SIGNIFICANCE STATEMENTNatural environments are composed of multisensory objects. It remains unclear whether and how animals learn the regularities of congruent multisensory associations and how these may impact behavior and neural activity. We tested how learned odor–sound associations affected single-neuron responses in auditory cortex. We introduce a novel auditory discrimination task for mice in which odors set different contexts of expectation to upcoming trials. We show that, although the task can be solved purely by sounds, odor-mediated expectation impacts performance. We further show that odors cause a modulation of neuronal activity in auditory cortex, which is correlated with behavior. These results suggest that learning prompts an interaction of odor and sound information as early as sensory cortex.
Mechanisms That Underlie Expression of Estradiol-Induced Excitatory Synaptic Potentiation in the Hippocampus Differ between Males and Females
Authors: Jain Anant , Woolley Catherine S. 
Published: January 2023

17β-estradiol (E2) is synthesized in the hippocampus of both sexes and acutely potentiates excitatory synapses in each sex. Previously, we found that the mechanisms for initiation of E2-induced synaptic potentiation differ between males and females, including in the molecular signaling involved. Here, we used electrical stimulation and two-photon glutamate uncaging in hippocampal slices from adult male and female rats to investigate whether the downstream consequences of distinct molecular signaling remain different between the sexes or converge to the same mechanism(s) of expression of potentiation. This showed that synaptic activity is necessary for expression of E2-induced potentiation in females but not males, which paralleled a sex-specific requirement in females for calcium-permeable AMPARs (cpAMPARs) to stabilize potentiation. Nonstationary fluctuation analysis of two-photon evoked unitary synaptic currents showed that the postsynaptic component of E2-induced potentiation occurs either through an increase in AMPAR conductance or in nonconductive properties of AMPARs (number of channels × open probability) and never both at the same synapse. In females, most synapses (76%) were potentiated via increased AMPAR conductance, whereas in males, more synapses (60%) were potentiated via an increase in nonconductive AMPAR properties. Inhibition of cpAMPARs eliminated E2-induced synaptic potentiation in females, whereas some synapses in males were unaffected by cpAMPAR inhibition; these synapses in males potentiated exclusively via increased AMPAR nonconductive properties. This sex bias in expression mechanisms of E2-induced synaptic potentiation underscores the concept of latent sex differences in mechanisms of synaptic plasticity in which the same outcome in each sex is achieved through distinct underlying mechanisms.SIGNIFICANCE STATEMENTEstrogens are synthesized in the brains of both sexes and potentiate excitatory synapses to the same degree in each sex. Despite this apparent similarity, the molecular signaling that initiates estrogen-induced synaptic potentiation differs between the sexes. Here we show that these differences extend to the mechanisms of expression of synaptic potentiation and result in distinct patterns of postsynaptic neurotransmitter receptor modulation in each sex. Such latent sex differences, in which the same outcome is achieved through distinct underlying mechanisms in males versus females, indicate that molecular mechanisms targeted for drug development may differ between the sexes even in the absence of an overt sex difference in behavior or disease.
¿El BREAKOUT o Escape Room un recurso viable para la Educación Infantil?
Authors: Arimon-Nuevo Judit , Freixa-Toha Judit , Sabido-Codina Judit 
Published: January 2023

Los nuevos paradigmas de la didáctica de las ciencias sociales apuestan, por un lado, por la introducción de metodologías basadas en el juego ya desde edades muy tempranas como la educación infantil, y, por otro lado, por realizar un cambio de mirada hacia el desarrollo de habilidades relacionadas con las ciencias sociales en relación con los contenidos. Es por todo ello, que en el presente estudio se busca analizar la viabilidad de aplicar recursos didácticos ludificados del área de ciencias sociales en una secuencia didáctica de El Principito para el segundo ciclo de Educación Infantil, concretamente de 4 a 6 años. Para alcanzar dicho objetivo, se han realizado varias observaciones no participativas de la aplicación del Breakout EDU o juego de escape (escape room) en dos centros educativos de la comunidad autónoma de Cataluña (n=56). Como resultado de dichas observaciones y el posterior análisis con el programa Iramuteq se ha constatado que el Breakout EDU o juego de escape puede ser un recurso didáctico óptimo para Educación Infantil, siempre y cuando tenga unas pautas didácticas muy marcadas y estructuradas por el docente y se haya realizado un ejemplo resuelto previo.
Podocyte Geranylgeranyl Transferase Type-I Is Essential for Maintenance of the Glomerular Filtration Barrier
Authors: Boi Roberto , Bergwall Lovisa , Ebefors Kerstin , Bergö Martin O. , Nyström Jenny , Buvall Lisa 
Published: January 2023

Significance Statement
A tightly regulated actin cytoskeleton attained through balanced activity of RhoGTPases is crucial to maintaining podocyte function. However, how RhoGTPases are regulated by geranylgeranylation, a post-translational modification, has been unexplored. The authors found that loss of the geranylgeranylation enzyme geranylgeranyl transferase type-I (GGTase-I) in podocytes led to progressive albuminuria and foot process effacement in podocyte-specific GGTase-I knockout mice. In cultured podocytes, the absence of geranylgeranylation resulted in altered activity of its downstream substrates Rac1, RhoA, Cdc42, and Rap1, leading to alterations of β1-integrins and actin cytoskeleton structural changes. These findings highlight the importance of geranylgeranylation in the dynamic management of RhoGTPases and Rap1 to control podocyte function, providing new knowledge about podocyte biology and glomerular filtration barrier function.

Background
Impairment of the glomerular filtration barrier is in part attributed to podocyte foot process effacement (FPE), entailing disruption of the actin cytoskeleton and the slit diaphragm. Maintenance of the actin cytoskeleton, which contains a complex signaling network through its connections to slit diaphragm and focal adhesion proteins, is thus considered crucial to preserving podocyte structure and function. A dynamic yet tightly regulated cytoskeleton is attained through balanced activity of RhoGTPases. Most RhoGTPases are post-translationally modified by the enzyme geranylgeranyl transferase type-I (GGTase-I). Although geranylgeranylation has been shown to regulate activities of RhoGTPases and RasGTPase Rap1, its significance in podocytes is unknown.

Methods
We used immunofluorescence to localize GGTase-I, which was expressed mainly by podocytes in the glomeruli. To define geranylgeranylation's role in podocytes, we generated podocyte-specific GGTase-I knockout mice. We used transmission electron microscopy to evaluate FPE and measurements of urinary albumin excretion to analyze filtration barrier function. Geranylgeranylation's effects on RhoGTPases and Rap1 function were studied in vitro by knockdown or inhibition of GGTase-I. We used immunocytochemistry to study structural modifications of the actin cytoskeleton and β1 integrins.

Results
Depletion of GGTase-I in podocytes in vivo resulted in FPE and concomitant early-onset progressive albuminuria. A reduction of GGTase-I activity in cultured podocytes disrupted RhoGTPase balance by markedly increasing activity of RhoA, Rac1, and Cdc42 together with Rap1, resulting in dysregulation of the actin cytoskeleton and altered distribution of β1 integrins.

Conclusions
These findings indicate that geranylgeranylation is of crucial importance for the maintenance of the delicate equilibrium of RhoGTPases and Rap1 in podocytes and consequently for the maintenance of glomerular integrity and function.
Libro. Democratización del Deporte, la Educación Física y la Recreación
Authors: Tavosnanska Pedro Hugo 
Published: January 2023

Cuarenta y siete autores de 12 países de América Latina y España, reúnen en esta obra aspectos sobre la Democratización, la Integración Regional y la Cooperación Internacional en el Deporte, la Educación Física y la Recreación. En este trabajo de 17 capítulos -que no fue realizado de modo independiente por cada uno de los autores- participan representantes oficiales de 45 instituciones del Mercosur, Latinoamérica y España que trabajaron articuladamente en pos de un mismo objetivo: la Democratización. Es la primera vez en nuestro continente que tan diversas instituciones abordan esta temática. Han construido, no sólo declamado, puentes de integración y cooperación, puentes de convivencia democrática y unidad latinoamericana. Es interesante poder leer las diversas miradas, los matices, las diferencias, conocer las experiencias vividas en los más variados rincones de la región. Sin duda este libro en conjunto demuestra un deseo importante de participar, como así también una trayectoria y una experiencia institucional que hicieron posible concretarlo. De este modo, creemos que nuestro movimiento político-institucional –que es el ForoMercosur Latinoamericano– se ha consolidado como el único espacio de este tipo en América Latina, que articula y lucha en pos de la Democratización del Deporte y la Integración Regional.
Performance and Next-Generation Development of the Finite-Fault Rupture Detector (FinDer) within the United States West Coast ShakeAlert Warning System
Authors: Böse Maren , Andrews Jennifer , Hartog Renate , Felizardo Claude 
Published: January 2023

ABSTRACTRapid fault rupture information is important to estimate seismic ground motions and damage in large earthquakes, and is, therefore, of great value for earthquake early warning (EEW) and rapid response. The Finite-Fault Rupture Detector (FinDer) algorithm computes earthquake line-source models by comparing spatial distributions of high-frequency seismic amplitudes with precomputed template maps. FinDer is one of two seismic EEW algorithms currently adopted by the United States West Coast ShakeAlert EEW system. Between March 2018 and October 2022, FinDer detected 1048 earthquakes (2.3 ≤ M ≤ 7.1) inside the FinDer-reporting region in California, Oregon, and Washington with a median detection time of 8.5 s (75th and 95th percentile: 11.5 s, 38.9 s) after event origin and median errors (first report) of 6.7 km (75th and 95th percentile: 10.5 km, 25.5 km) in location, −0.45 s (mean ± st. dev.: 0.1 ± 5.9 s) in origin time, and 0.33 units (mean ± st. dev.: 0.33 ± 0.31 m.u.) in magnitude. Ground motions estimated using FinDer source parameters are in excellent agreement with observed peak ground accelerations, and residuals are, on average, 30% smaller than if predicted from catalog source parameters. This suggests that FinDer’s simple source parameter terms are accounting for more complex high-frequency source characteristics. This article summarizes the performance of FinDer in ShakeAlert and describes the recent improvements to the algorithm addressing issues encountered during real-time operation. This includes the handling of latent seismic data, robust event detection in regions with sparse instrumentation, enabling faster magnitude convergence in large earthquakes, use of fault- and scenario-specific earthquakes (e.g., along the Cascadia subduction zone or San Andreas fault), as well as increased robustness of FinDer in complex earthquake sequences. We demonstrate the performance of the new FinDer version 3 algorithm using waveform playbacks of selected events along the U.S. West Coast, Japan, and China, including both historic and synthetic earthquakes.
Women’s Views on Factors that Influence Utilisation of Postnatal Follow-Up in Oman
Authors: Al Hadi Amal , Dawson Jennifer , Paliwoda Michelle , Walker Karen , New Karen 
Published: January 2023

Objective: Postnatal follow-up care (PNFC) is important to promote maternal and newborn health and wellbeing. In Oman, women’s utilisation of postnatal follow-up services has declined with rates as low as 0.29 (mean visits) in some Governorates; well below the recommended postnatal follow up visits at two- and six-weeks for assessment of mother and newborn. The reasons for low utilisation are not well understood. The aim of this study is to explore women’s views and identify factors that influence their utilisation of postnatal follow-up services. Methods: Purposive sampling and semi-structured telephone interviews with 15 women aged 20 to 39 years at six to eight weeks post childbirth between May 2021 to August 2022. Data were analysed using Erlingsson and Brysiewicz content analysis approach. Results: Six categories were identified as influencing PNFC utilisation: 1) need for information; 2) experiences and expectations; 3) family support, expectations and customs; 4) sociocultural beliefs and practice; 5) impact of Covid-19 and 6) the healthcare environment. Influencing factors within each category include the need to: empower women, provide individualised care, address family and community expectations, offer alternatives to face-to-face clinic visits, provide organised, scheduled appointments. Conclusion: Women in Oman identified the need for consistent information from health care providers (HCPs), a more organised postnatal follow-up service including scheduled appointments and a woman-centred approach to PNFC.
Keywords: Postnatal care; postpartum period; qualitative research.
Rural–Urban Disparities in Adverse Maternal Outcomes in the United States, 2016–2019
Authors: Harrington Katharine A. , Cameron Natalie A. , Culler Kasen , Grobman William A. , Khan Sadiya S. 
Published: January 2023

Objectives. To describe differences in maternal admissions to the intensive care unit (ICU) and mortality in rural versus urban areas in the United States. Methods. We performed a nationwide analysis and calculated age-standardized rates and rate ratios (RRs) of maternal ICU admission and mortality per 100 000 live births between 2016 and 2019 in rural versus urban areas. Results. From 2016 to 2019, there was no significant increase in age-standardized rates of maternal ICU admissions in rural (170.6–192.3) or urban (161.7–172.4) areas, with a significantly higher rate, albeit a relatively small difference, in rural versus urban areas (2019 RR = 1.14; 95% confidence interval [CI] = 1.04, 1.20). Maternal mortality increased in both rural (66.9–81.7 deaths per 100 000 live births) and urban (38.1–42.3) areas and was nearly 2 times higher in rural areas (2019 RR = 1.93; 95% CI = 1.71, 2.17). Conclusions. Pregnant individuals in rural areas are at higher risk for ICU admission and mortality than are their urban counterparts. Significant increases in maternal mortality occurred in rural and urban areas. Public Health Implications. Public health efforts need to focus on resource-limited rural areas to mitigate geographic disparities in maternal morbidity and mortality. (Am J Public Health. 2023;113(2): 224–227. https://doi.org/10.2105/AJPH.2022.307134 )
Medication Abortion “Reversal” Laws: How Unsound Science Paved the Way for Dangerous Abortion Policy
Authors: Redd Sara K. , AbiSamra Roula , Blake Sarah C. , Komro Kelli A. , Neal Rachel , Rice Whitney S. , Hall Kelli S. 
Published: January 2023

Objectives. To longitudinally examine the legal landscape of laws requiring abortion patients be informed about the possibility of medication abortion (MAB) “reversal” (in quotes as it does not refer to an evidence-based medical procedure). Methods. We collected legal data on enacted state MAB-reversal laws across all 50 US states and Washington, DC, (collectively, states) from 2012 through 2021. We descriptively analyzed these laws to identify legal variation over time and geography, and conducted a content analysis to identify qualitative themes and patterns in MAB-reversal laws. Results. As of 2021, 14 states (27%)—mostly in the midwestern and southern United States—have enacted MAB-reversal laws. States largely use explicit language to describe reversal, require patients receive information during preabortion counseling, require physicians or physicians' agents to inform patients, instruct patients to contact a health care provider or visit “abortion pill reversal” resources for more information, and require reversal information be posted on state-managed Web sites. Conclusions. Reversal laws continue a dangerous precedent of using unsound science to justify laws regulating abortion access, intrude upon the patient‒provider relationship, and may negatively affect the emotional and physical health of patients seeking an MAB. (Am J Public Health. 2023;113(2):202–212. https://doi.org/10.2105/AJPH.2022.307140 )
Mechanical Failures in Magnetic Intramedullary Lengthening Nails
Authors: Hlukha Larysa P. , Alrabai Hamza M. , Sax Oliver C. , Hammouda Ahmed I. , McClure Philip K. , Herzenberg John E. 
Published: January 2023

Background:
Magnetic intramedullary lengthening nails (MILNs) have gained popularity in recent years for the treatment of limb-lengthening discrepancies. We sought to catalog mechanical failures and their prevention and management in a large, single-institution series. We specifically assessed the rate of mechanical failures, the types of failures observed, and management strategies.

Methods:
We retrospectively reviewed 377 patients (420 limbs) who underwent limb lengthening with early (P1) or later (P2) MILN iterations with ≥12-month follow-up. Mechanical failure was defined as mechanical breakage of the instrumentation or nail and/or failure of the internal lengthening mechanism. Failure assessment was arranged by lengthening phases and was sorted with a complication classification system. All lengthening and alignment parameters were assessed radiographically.

Results:
Mechanical failure was observed in 40 nails (9.5%), most of which (63%) were corrected with an additional surgical procedure. The mechanical failure rate was 11.3% in P1 nails and 9% in P2 nails. Two nails failed the intraoperative distraction test, and 1 nail was found to have a broken washer during the insertion phase. Sixteen nails had mechanical failures in the lengthening phase. Some nails (8 of 16) required nail replacement surgery. Thirteen nails failed during the consolidation phase; 7 of these cases were managed by replacement with either a functional MILN or a conventional intramedullary nail. Eight failures happened during the extraction phase and were managed intraoperatively.

Conclusions:
A 9.5% overall rate of mechanical failure of MILNs was observed in this large series. Resolution was achieved with an additional surgery in most cases. Nail distraction and weight-bearing compliance should be closely monitored during the lengthening and consolidation phases. Nail removal can be difficult and requires a careful study of radiographs for locking-screw bone overgrowth and backup removal equipment.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.