bluuebunny/crossref_metadata_2025 huggingface dataset:
O IMPOSTO SELETIVO E SUAS SEMELHANÇAS COM AS EXCISE TAXES NA TRIBUTAÇÃO DE BENS E SERVIÇOS NA PROPOSTA DA REFORMA TRIBUTÁRIA BRASILEIRA
Authors: Mello Costa de Carvalho Raquel
Published: May 2024

O presente trabalho tem como objetivo analisar a proposta da reforma tributária aprovada pela Câmara dos Deputados, com foco na proposição de introduzir um imposto seletivo do tipo excise tax no contexto brasileiro. A proposta de reforma tributária visa reestruturar o sistema de tributos para simplificar, tornar mais eficiente e equitativo o panorama fiscal do país. Ela reflete as decisões políticas e ajustes realizados, visando aprimorar o sistema tributário brasileiro. Já o imposto de consumo, chamado imposto seletivo, conhecido como excise tax, nos países de língua inglesa, é uma potencial ferramenta para direcionar padrões de consumo e alocar recursos em áreas prioritárias, demandando análises cuidadosas para a sua implementação justa e eficaz. Para tanto, foi feita uma análise bibliográfica e doutrinária de todos os aspectos relevantes que cercam o tema, em especial sobre os elementos jurídicos a serem tutelados pela norma tributária acerca do imposto seletivo. A hipótese é de que o sistema tributário, com a introdução do imposto seletivo, mediante a reforma tributária em tramitação, contribuiria para uma modificação mais abrangente das dinâmicas tributárias extrafiscais e suas implicações para a realidade brasileira.
SCREEN TIME AND AGGRESSION IN ADOLESCENTS: A MODERATING ROLE OF CONTENT-BASED MEDIA EXPOSURE
Authors: Majeed Saima
Published: May 2024

Objectives: This study was designed to explore the relationship between excessive screen time, content-based media exposure, and aggression in adolescents. Another important aim was to examine the moderating role of content-based media exposure between screen time and aggression.
Study Design: A correlational cross-sectional research design was followed.
Place and Duration of Study: Forman Christian College (A chartered University). March 2022-July 2022). Subjects and Methods:  A convenient sample of 250 adolescents with an age range of 13 to 17 years was drawn from two public and two private schools and colleges in Lahore. The measures for data collection were the Screen-Time Addiction Questionnaire Content-Based Media Exposure Scale and The Aggression Scale are used to understand the strategic elements of how screen time shapes the world around adolescents that may lead to aggressive behaviors.
Results: The results of the Pearson product-moment correlation indicated that screen time has a positive relationship with both anti-social (.32* p<.05) and neutral content (.37* p<.05) of media exposure. Similarly, anti-social media exposure has a significant positive relationship (56** p<.01) with aggression. Violent and neutral content exposure has an inverse relationship (-.40** p<.01) with each other. Anti-social media exposure proved a significant positive (β=4.32, p<.05) predictor of aggression. Furthermore, media exposure significantly moderates the relationship 1.98*** p<.001).
Conclusion: Mean scores indicated that the present population spent more time on screens watching violent, anti-social content and scored high on aggression. Adolescents who spent more time watching anti-social /violent content scored high on aggression.  Educators, parents, and content designers should keep this thing in mind for designing online content for the public, especially for children and adolescents.
Analysis of a Honeypot Intrusion Detection System for Medical and Healthcare Services
Authors:   School of Computer Science & Engineering, Vellore Institute of Technology University, Vellore, Tamil Nadu, India, Yadav Aastha , Raisurana Sarthak ,   School of Computer Science & Engineering, Vellore Institute of Technology University, Vellore, Tamil Nadu, India, Iyengar N.Ch. Sriman Narayana ,   Sreenidhi Institute of Science and Technology, Yamnampet, Ghatkesar, Hyderabad, India
Published: May 2024

Cyber-attacks have been increasingly becoming alarming in recent years specifically for medical and healthcare systems. One of the cyber-attackers aims is to break into the medical or healthcare networks and gain access to the patient’s medical records. This paper deals with the honeypot-based intrusion detection system to provide information security for medical and healthcare systems. The proposed system utilizes the Dionaea and Kippo SSH (Kippo Secure Shell) honeypots to secure the medical and healthcare network infrastructure and analyze the activities of cyber-attackers. A possible Metasploit and Brute force attacks logged by the Dionaea and Kippo SSH will be analyzed to prepare the malware analysis report of the suspicious file download.
Bible Readings or News Articles in Undergraduate Corporate Finance: A Teaching Methodology Comparison
Authors: Saunders Kent T.
Published: May 2024

This paper compares two sections of undergraduate financial management. The classes were virtually identical with the exception of how each class session started. The news article class began with student news article presentations. The Bible reading class began with student Bible readings. The classes are compared with respect to grades, student attitudes of the Bible’s relationship to finance, and student awareness of current events in finance. Statistical analysis was conducted using t-tests, Mann-Whitney tests, ordinary least squares, and ordinal regression. How class sessions started did not affect students’ overall course grades. However, the Bible reading class responded significantly higher to the statement “to what extent do you feel that the Bible is related to finance?” Additionally, the news article class responded significantly higher to the statement “to what extent are you aware of current events in finance?”
Value Functions, Fostering and Kingdom Gains
Authors: Wick Katherine
Published: May 2024

Behavioral economics is rising in popularity in American classrooms, and its discussion is relevant to students across business, public health, social sciences, and the humanities. As professors teach about loss aversion and risk, we introduce students to the kinked value function as an important part of prospect theory. In this paper, I will show a Kingdom-based approach to teaching about value functions in the context of the foster care system where there exists a crisis of capacity. It is only when Christians place their reference point in the Kingdom that risky endeavors show returns that outweigh losses.
Blending Customer-Orientated Sales, Servant Leadership, and Biblical Principles of Servanthood into a New Sales Framework: The Serving Salesperson
Authors: McQuiston Daniel H.
Published: May 2024

This paper blends the philosophical concepts of customer-oriented sales and servant leadership together and combines that blend with biblical principles of servanthood to propose a “serving salesperson” framework for sales. After examining the literature on customer-oriented sales and servant leadership, the paper employs the results of a qualitative survey of a sample of Christian salespeople to identify the characteristics of a “serving salesperson.” The paper then goes on to offer a set of seven practices of the serving salesperson. Biblical illustrations of each of the seven practices are then offered.
The Development of an Integrated Experiential Model for Student Transformation
Authors: Bovee Steven L. , O'Brien Marcia
Published: May 2024

This paper presents a model for student transformation: spiritually, intellectually, and professionally. The implementation of this model has been supported by a paradigm shift in business faculty and staff who have embraced the challenge of developing servant leaders through an integrated process of curricular, co-curricular, and experiential learning and transformational teaching. The authors share the evolution in thinking that generated this model and the related approach to teaching and learning, along with some concrete examples of its implementation and lessons learned along the way. They also discuss anticipated next steps to further integrate the model into teaching and learning efforts and to assess its effectiveness in achieving intended learning and growth outcomes.
Case Study: James Jewelers
Authors: Redmer Timothy A. O.
Published: May 2024

James Jewelers is a critical decision case involving Bob and Bonnie James, owners of James Jewelers in Spartanburg, South Carolina. This case accurately reflects dilemmas frequently faced by entrepreneurs in the highly competitive retail markets. The very survival of James Jewelers and the financial stability of Bob and Bonnie are dependent on a correct decision regarding the future of James Jewelers. Bob and Bonnie have been working in the jewelry business for 20 years and are in the midst of experiencing their second failure. With debt concerns, shrinking inventory, and a lost lease, Bob has to decide whether to throw in the towel and look for other forms of employment, or try to start over. Bob’s values and beliefs enter into the decision as he feels a strong obligation to repay his debt and continue to provide a quality product and service to devoted customers. Some suppliers and many customers have stuck with James Jewelers for a number of years, and Bob feels that quitting would be a disservice to those who had faith in him. However, the financial condition of his operation continues to deteriorate. Sometimes staying in business could change a condition from bad to worse and even more people could be negatively impacted by an unsuccessful operation. Then again, if he can turn the business around, there is a greater probability that Bob can make good on his obligations. Bob and Bonnie need to decide quickly if they want to try to save or discontinue the operation of James Jewelry.
Southern Discomfort: A Second Response to Richard Martinez
Authors: VanderVeen Steve
Published: May 2024

Dr. Richard Martinez (2004, pp. 14-17), in his gracious response to my rejoinder to his article (2004, pp. 7-13), gives us insight into the importantrelationship between the content of what we teach as well as the method we use to teach it. First, I comment on specific points related to content. Then I comment on the issue of pedagogy.
Teaching Ayn Rand’s Atlas Shrugged at the Christian University
Authors: McCormick Blaine
Published: May 2024

McCormick seeks to help the reader understand “Atlas Shrugged” in a Christian cultural context, contrast the novel’s objectivistic philosophy with that of Christianity, and contrast the business activities seen in the novel with Christian business prescriptions.
Middle Management as a Calling
Authors: Klay Robin , Lunn John , TenHaken Vicki
Published: May 2024

After discussing the doctrine of calling and the history and importance of the middle management profession, the authors challenge business professors to present management as an exciting calling for students.
What the Best College Teachers Do by Ken Bain
Authors: Johnson Sharon G.
Published: May 2024

According to Ken Bain, director of the Center for Teaching Excellence at New York University, teaching is both an intellectual creation and a performing art (p. 174). It is best done by those eager to seek real answers to such questions as:1. What do I need to know and understand to engage my students in the great questions of my discipline?2. How do I need to prepare myself and my students to attain significant learning objectives?3. What should I expect of myself and my students?4. What approaches should I take in the classroom to foster excitement about and engagement with the ideas, issues, and controversies of my discipline?5. How might I assess my real impact on student learning so that I can continue to challenge myself to grow as an individual?
The 25 Most Common Problems in Business (and How Jesus Solved Them) by Jim Zabloski
Authors: Johnson Sharon G.
Published: May 2024

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The Corrosion of Character: The Personal Consequences of Work in the New Capitalism by Richard Sennett
Authors: Smith Yvonne S.
Published: May 2024

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Total intravenous anesthesia using remimazolam for patients with heart failure with reduced ejection fraction: a case series
Authors: Lee Jimin , Yoon Ji-Uk , Byeon Gyeong-Jo , Shon Hong-Sik , Yi Ahhyeon , Kim Hee Young
Published: May 2024

Patients with heart failure undergoing surgery that requires general anesthesia face substantial perioperative risks; however, clear guidelines are not available for anesthesia management in patients with a reduced left ventricular ejection fraction. Traditional intravenous and volatile anesthetics require careful administration to prevent severe hypotension and bradycardia in patients with heart failure. Remimazolam has emerged as a promising alternative to conventional anesthetics because of its reduced cardiovascular depressive effects. We present three cases illustrating the successful use of remimazolam to induce and maintain general anesthesia in patients with heart failure and reduced cardiac function. Our cases demonstrate the safe use of remimazolam for general anesthesia in patients with heart failure and a reduced ejection fraction.
Frequent outbreaks of cholera in Zimbabwe: Urgent need for strengthened public health interventions
Authors: Dzinamarira T , Murewanhema G , Mapingure M , Chingombe I , Musuka G N
Published: May 2024

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Heart groups in South Africa advocate for tighter LDL-C control and lipoprotein(a) testing to curb atherosclerotic cardiovascular disease
Authors: Klug E Q , Raal F J
Published: May 2024

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Improving access to suicide prevention services through the National Suicide Prevention Framework implementation: The community level evidence-based recommendations
Authors: Nyasulu J C Y , Siddiqi D A , Seedat S , Bantjies J , Udedi M , Gondwe S , Kambale S , Mkandawire M , Silungwe N , Hendricks L A , Maposa I , Vumu J , Skinner D
Published: May 2024

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Cystic echinococcosis: The parasitic tale of a sinister cystic disease
Authors: John J
Published: May 2024

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The South African Prostate Cancer Screening Guidelines
Authors: John J , Adam A , Kaestner L , Spies P , Mutambirwa S , Lazarus J
Published: May 2024

Prostate cancer (PCa) is the most widespread solid organ malignancy in males and ranks as the fifth leading cause of death globally. Identifying and treating men with clinically significant disease while avoiding the over-diagnosis and over-treatment of indolent disease remains a significant challenge. Several professional associations have developed guidelines on screening and early diagnosis of asymptomatic men with prostate-specific antigen testing. With recent updates from several large randomised prospective trials, the South African Urological Association and the Prostate Cancer Foundation of South Africa have developed these evidence-based recommendations to guide clinicians on PCa screening and early diagnosis for South African men.
Liver cystic echinococcosis: A retrospective study on the demographics and clinical profile of patients managed at a single tertiary institution in central Eastern Cape Province, South Africa
Authors: Govindasamy A , Bhattarai P R , Van Niekerk J , John J
Published: May 2024

Background. Cystic echinococcosis (CE) is a zoonotic disease with an Africa-wide prevalence of 1.7%. CE is caused by the tapeworm Echinococcus granulosus sensu lato, with the liver being the most commonly affected organ. In South Africa (SA), there is a paucity of data on liver CE demographics and management.
Objectives. To describe the demographics and clinical profile of patients with liver CE in a single tertiary hospital in Eastern Cape Province, SA.
Methods. A 4-year (2019 - 2022) retrospective clinical record review study was conducted on patients presenting with liver CE to the Department of Surgery at Frere Hospital. The demographics, clinical characteristics and management of patients with liver CE are reported.
Results. A total of 56 patients diagnosed with and managed for liver CE were included in the study. The mean age of the patients was 37.5 years. Abdominal pain (n=39; 69.6%) was the most common presenting symptom, and a palpable abdominal mass (n=36; 64.3%) was the predominant presenting sign. Most patients had disease confined to the liver (n=35; 62.5%). The right lobe of the liver was most commonly affected (n=38; 67.9%), and most patients had a single liver cyst on imaging (n=32; 57.1%). The majority of the patients (n=36; 64.3%) were managed with surgical partial cystectomy, with a perioperative bile leak being the most common complication.
Conclusion. In our setting, liver CE contributes to a significant local burden of the disease. The disease often has a nonspecific clinical presentation, necessitating imaging for the diagnosis. We observed good short-term outcomes in patients managed with combined partial cystectomy and medical therapy, although there is a risk of perioperative bile leak.
Digital Asset Register Toolkit
Authors:   Digital Preservation Coalition, McMeekin Sharon , Currie Amy
Published: May 2024

This Toolkit aims to offer practical guidance on how to build, maintain, and use a Digital Asset Register (DAR). It starts by taking you through what a DAR is, why you may wish to build one, and who this toolkit is aimed at. Subsequent sections detail what makes a good DAR, a step-by-step guide to developing one, an example template, further details about information gathering, and using and updating your DAR.
Periodismo e inteligencia artificial generativa 2024: nuevos datos de investigación
Authors: Ollé Candela
Published: May 2024

El uso, el impacto y la evolución de la inteligencia artificial generativa (IAG) en la profesión periodística plantea limitaciones, dudas, preocupaciones y retos como, por ejemplo, seguir la rápida evolución de esta tecnología disruptiva. Para saber cuál es la situación actual de la industria mediática, a mediados del 2024, y poder entender mejor qué representa y podría representar la IAG para los periodistas, seleccionamos algunos de los datos y destacamos parte de las conclusiones de dos interesantes informes internacionales recién publicados.
In silico screening and identification of lead molecules from Garcinia gummi-gutta with multitarget activity against SARS-CoV-2
Authors: Sugathan Keerthi J. , Sreekumar Sivanandan , Kamalan Biju Charuvila
Published: May 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has affected the human population, resulting in multiple waves of pandemics around the world. One of the main threats is hyper-evolved viral variants with high transmissibility and virulence, and the best solution is the application of multitargeted drugs of plant origin. In this perspective, the anti-SARS-CoV-2 activity of Garcinia gummi-gutta was evaluated through an in silico approach. A total of 97 phytochemicals from G. gummi-gutta were tested against three therapeutic targets of SARS-CoV-2, namely spike protein, main protease (Mpro), RNA-dependent RNA polymerase, and two human host targets such as angiotensin-converting enzyme-2 and nuclear factor-κB through molecular docking. Out of 97 phytochemicals screened, 18 of them showed significant binding free energy with all the five selected targets. The compound amentoflavone was chosen as the best lead molecule based on binding energy, molecular interactions, and absorption distribution metabolism and excretion profile. The interaction of amentoflavone with Mpro was further verified using molecular dynamic simulation. The overall results revealed that the compound amentoflavone can be recommended as the best lead compound with multitargeting potential against SARS-CoV-2, and can be recommended for further experimental studies leading to drug discovery.
Dipeptidyl peptidase-4 inhibition of Peronema canescens Jack leaves and stems: Bioassay-guided fractionation, compound profiling by LC-MS/MS, and interaction mechanism
Authors: Elya Berna , Cahyan Forestrania Roshamur , Hashim Najihah Mohd , Triadisti Nita
Published: May 2024

Sungkai (Peronema canescens Jack) has been used for generations as a traditional antidiabetic drug for the Borneo people, but scientific data as a dipeptidyl peptidase-4 (DPP-4) inhibitor has never been reported. This study aims to obtain the most active chromatographic fraction as a DPP-4 inhibitor and the profile of the compounds contained. Bioassay-guided fractionation was used in this study and bioassays using spectrofluorometric principles. Compound profiling is carried out using ultra-performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry (UPLC-ESI-QToF-MS/MS), and molecular docking is used to investigate interactions between compounds and DPP-4. The study found that the most effective extracts were ethyl acetate and methanol extracts from the leaves, which showed inhibitory percentages of 70.0% ± 0.7233% and 59.69% ± 1.9394%, respectively, at a concentration of 100 μg/ml. The fractionation produces the most active fraction, the second fraction from P. canescens methanol extract (FPSM2 fraction), with a percent inhibition of 88.28% ± 2.1204%. The compounds contained in FPSM2 were identified through UPLC-ESI-QToF-MS/MS, including pectolinarigenin, glycitein, formononetin, latifoline, 3-oxo-alpha-ionol, moracin M, and loliolide. Assay results showed that P. canescens has been shown to have inhibitory activity against DPP-4, suggesting that this plant has excellent potential to be developed as a DPP-4 inhibitor.
Characterization and safety assessment of Hydroxypropyl Musa paradisiaca starch for pharmaceutical applications
Authors: Metta Samyuktha , Sahoo Suvendu Kumar
Published: May 2024

The aim of the current investigation was to produce native banana starch (NBS) and hydroxypropyl banana starch (HPBS) , assess physicochemical properties, and evaluate toxicity. NBS was modified to its propyl form with a propylene oxide solution and characterized. The physicochemical properties of NBS and HPBS met the required specifications. The amylose content of NBS was found to be 25.41% ± 0.08%. The degree of substitution and hydroxyl propyl group % were found to be 0.028 and 2.894, respectively, which were within the Food and Drug Administration’s (FDA’s) acceptable limits of 0.2% and 7%, respectively. The NBS possesses superior swelling power (26.68 ± 1.06) compared to the HPBS swelling power (15.66 ± 0.61). In terms of soluble starch content (%), HPBS displayed a higher soluble starch content percentage (69.21 ± 2.04) compared to the NBS (17.01 ± 1.06). The HPBS yielded high viscosity relative to the NBS in all the concentrations of starch solutions. The increase in the soluble starch content and viscosity of propyl starch may be attributed to the increased number of hydroxy propyl group substitutions in the HPBS. For up to 14 days of the experimental period in the acute toxicity studies, the rats showed no symptoms of toxicity or fatalities. According to the findings of the subacute toxicity studies, neither the hematological nor the biochemical analyses showed any apparent abnormalities. The study’s overall results show that HPBS were safe up to doses of 1,000 mg/kg body weight, which may be regarded as a safe dosage. The modified starch’s enhanced physicochemical properties make it suitable for industrial use, and it meets FDA-approved limits, affirming its safety as a pharmaceutical excipient.
Numerical simulation study on microdischarge via a unified fluid model
Authors: Wang Zhen , Zhao Zhi-Hang , Fu Yang-Yang ,   Department of Electrical Engineering, Tsinghua University, Beijing 100084, China
Published: May 2024

Numerical simulation has become an indispensable tool in the study of gas discharge. However, it is typically used to reveal microscopic properties in a discharge under specific conditions. In this work, a unified fluid model for discharge simulation is introduced in detail. The model includes the continuity equation, the energy conservation equation of the species (electrons and heavy particles), and Poisson’s equation. The model takes into account some processes such as cathode electron emission (secondary electron emission and thermionic emission), reaction enthalpy change, gas heating, and cathode heat conduction. The full current-voltage characteristic (CVC) curve covers a range of discharge regimes, such as the Geiger-Müller discharge regime, Townsend discharge regime, subnormal glow discharge regime, normal glow discharge regime, abnormal glow discharge regime, and arc discharge regime. The obtained CVC curve is consistent with the results in the literature, confirming the validity of the unified fluid model. On this basis, the CVC curves are obtained in a wide pressure range of 50–3000 Torr. Simulation studies are carried out focusing on the discharge characteristics for microgap of 400 µm at pressures of 50 Torr and 500 Torr, respectively. The distributions of typical discharge parameters under different pressure conditions are analyzed by comparison. The results indicate that the electric field in the discharge gap is uniform, and that the space charge effect can be ignored in Townsend discharge regime. The cathode fall region and the quasi-neutral region both appear in glow discharge regime, and the space charge effect is significant. In particular, the electric field reversal occurs in abnormal discharge regime due to the heightened particle density gradient. The electron density reaches about 1022 m–3 in arc discharge regime dominated by thermionic emission and thermal ionization, with the current density increasing. The gas temperature peak is 11850 K when the pressure is 500 Torr, and the cathode surface is heated to nearly 4000 K due to heat conduction. The present model can be used to simulate gas discharge across a wide range of condition parameters, promoting and expanding fluid model applications, and assisting in a more comprehensive investigation of discharge parameter properties.
Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes
Authors: Chang Yuan , Lusk Savannah , Chang Andersen , Ward Christopher S , Ray Russell S
Published: May 2024

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS) and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. Therefore, we fully characterized the cumulative fate maps and acute adult expression patterns of all three Vesicular Glutamate Transporters (
Slc17a7
(Vglut1),
Slc17a6
(Vglut2), and
Slc17a8
(Vglut3)) in NA neurons, identifying a novel, dynamic expression pattern for Vglut2 and an undescribed co-expression domain for Vglut3 in the NA system. In contrast to our initial hypothesis that NA derived glutamate is required to breathing, our functional studies showed that loss of Vglut2 throughout the NA system failed to alter breathing or metabolism under room air, hypercapnia, or hypoxia in unrestrained and unanesthetized mice. These data demonstrate that Vglut2-based glutamatergic signaling within the central NA system is not required for normal baseline breathing and hypercapnic, hypoxic chemosensory reflexes. These outcomes challenge the current understanding of central NA neurons in the control of breathing and suggests that glutamate may not be a critical target to understand NA neuron dysfunction in respiratory diseases.
Theta cycle dynamics of spatial representations in the lateral septum
Authors: Bzymek Katarzyna , Kloosterman Fabian
Published: May 2024

An internal representation of the environment – or map – allows animals to evaluate multiple routes and adapt their navigation strategy to current needs and future goals. The hippocampal formation plays a crucial role in learning a spatial map and using the map for goal-directed navigation. The lateral septum forms a major node for connections between the hippocampus and subcortical brain regions that could link the spatial map to motivation and reward processing centers such as the ventral tegmental area and hypothalamus. It is not known, however, how the lateral septum contributes to the processing of spatial information and route planning.In this study, we investigated the temporal dynamics of spatial representations in the lateral septum. Neuropixels probes were used to record cellular activity along the dorsal-ventral extent of the lateral septum while rats performed one of two spatial navigation tasks in a Y-maze. The activity of a large fraction of cells was theta rhythmic and a subset of cells showed evidence of being active on alternate theta cycles (theta cycle skipping). Both theta rhythmicity and cycle skipping were strongest in the dorsal lateral septum. Similarly, spatially selective firing was most prominent in the dorsal lateral septum. Using neural decoding, we show that the lateral septum cell population encodes both the current location and alternatingly the possible future paths within single theta cycles when rats approach the choice point in the maze.Our data further shows that the alternating expression of spatial representations in the lateral septum is task-dependent, such that it is strongest when the task also requires the animals to alternate between rewarded goal arms. These data suggest that task demands and experience shape which representations are activated near a choice point. The lateral septum receives strong input from hippocampal place cells, and while there may be integration and transformation of incoming spatial signals, our findings support the idea that hippocampal spatial representations and their temporal dynamics are conveyed to subcortical projection areas through the lateral septum.
Reactivation strength during cued recall is modulated by graph distance within cognitive maps
Authors: Kern Simon , Nagel Juliane , Gerchen Martin F. , Guersoy Cagatay , Meyer-Lin-denberg Andreas , Kirsch Peter , Dolan Raymond J. , Gais Steffen , Feld Gordon B.
Published: May 2024

Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8-minute consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic (MEG) recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.
Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans women
Authors: Delgouffe Emily , Silva Samuel Madureira , Chalmel Frédéric , Cools Wilfried , Raets Camille , Tilleman Kelly , T'Sjoen Guy , Baert Yoni , Goossens Ellen
Published: May 2024

Although the impact of gender-affirming hormone therapy (GAHT) on spermatogenesis in trans women has already been studied, data on its precise effects on the testicular environment is poor. Therefore, this study aimed to characterize, through histological and transcriptomic analysis, the spermatogonial stem cell niche of 106 trans women who underwent standardized GAHT, comprising estrogens and cyproterone acetate. A partial dedifferentiation of Sertoli cells was observed, marked by the co-expression of androgen receptor and anti-Müllerian hormone which mirrors the situation in peripubertal boys. The Leydig cells also exhibited a distribution analogous to peripubertal tissue, accompanied by a reduced insulin-like factor 3 expression. Although most peritubular myoid cells expressed alpha-smooth muscle actin 2, the expression pattern was disturbed. Besides this, fibrosis was particularly evident in the tubular wall and the lumen was collapsing in most participants. A spermatogenic arrest was also observed in all participants. The transcriptomic profile of transgender tissue confirmed a loss of mature characteristics - a partial rejuvenation - of the spermatogonial stem cell niche and, in addition, detected inflammation processes occurring in the samples. The present study shows that GAHT changes the spermatogonial stem cell niche by partially rejuvenating the somatic cells and inducing fibrotic processes. These findings are important to further understand how estrogens and testosterone suppression affect the testis environment, and in the case of orchidectomized testes as medical waste material, their potential use in research.
High-density sampling reveals volume growth in human tumours
Authors: Angaji Arman , Owusu Michel , Velling Christoph , Dick Nicola , Weghorn Donate , Berg Johannes
Published: May 2024

In growing cell populations such as cancer, mutations can serve as markers that allow tracking the past evolution from current samples. The genomic analysis of bulk samples and samples from multiple regions have shed light on the evolutionary forces acting on tumours. However, little is known empirically on the spatio-temporal dynamics of tumour evolution. Here, we leverage published data from resected hepatocellular carcinomas, each with several hundred samples taken in two and three dimensions. Using spatial metrics of evolution, we find that tumour cells grow predominantly uniformly within the tumour volume instead of at the surface. We determine how mutations and cells are dispersed throughout the tumour and how cell death contributes to the overall tumour growth. Our methods shed light on the early evolution of tumours in vivo and can be applied to high-resolution data in the emerging field of spatial biology.
Axon arrival times and physical occupancy establish visual projection neuron integration on developing dendrites in the Drosophila optic glomeruli
Authors: McFarland Brennan W. , Jang HyoJong , Smolin Natalie , Hina Bryce W. , Parisi Michael J. , Davis Kristen C. , Mosca Timothy J. , Godenschwege Tanja A. , Nern Aljoscha , Kurmangaliyev Yerbol Z. , von Reyn Catherine R.
Published: May 2024

Behaviorally relevant, higher order representations of an animal’s environment are built from the convergence of visual features encoded in the early stages of visual processing. Although developmental mechanisms that generate feature encoding channels in early visual circuits have been uncovered, relatively little is known about the mechanisms that direct feature convergence to enable appropriate integration into downstream circuits. Here we explore the development of a collision detection sensorimotor circuit in
Drosophila melanogaster
, the convergence of visual projection neurons (VPNs) onto the dendrites of a large descending neuron, the giant fiber (GF). We find VPNs encoding different visual features establish their respective territories on GF dendrites through sequential axon arrival during development. Physical occupancy, but not developmental activity, is important to maintain territories. Ablation of one VPN results in the expansion of remaining VPN territories and functional compensation that enables the GF to retain responses to ethologically relevant visual stimuli. GF developmental activity, observed using a pupal electrophysiology preparation, appears after VPN territories are established, and likely contributes to later stages of synapse assembly and refinement. Our data highlight temporal mechanisms for visual feature convergence and promote the GF circuit and the
Drosophila
optic glomeruli, where VPN to GF connectivity resides, as a powerful developmental model for investigating complex wiring programs and developmental plasticity.
Geometry and dynamics of representations in a precisely balanced memory network related to olfactory cortex
Authors: Meissner-Bernard Claire , Zenke Friedemann , Friedrich Rainer W.
Published: May 2024

Biological memory networks are thought to store information in the synaptic connectivity between assemblies of neurons. Recent models suggest that these assemblies contain both excitatory and inhibitory neurons (E/I assemblies), resulting in co-tuning and precise balance of excitation and inhibition. To understand computational consequences of E/I assemblies under biologically realistic constraints we created a spiking network model based on experimental data from telencephalic area Dp of adult zebrafish, a precisely balanced recurrent network homologous to piriform cortex. We found that E/I assemblies stabilized firing rate distributions compared to networks with excitatory assemblies and global inhibition. Unlike classical memory models, networks with E/I assemblies did not show discrete attractor dynamics. Rather, responses to learned inputs were locally constrained onto manifolds that “focused” activity into neuronal subspaces. The covariance structure of these manifolds supported pattern classification when information was retrieved from selected neuronal subsets. Networks with E/I assemblies therefore transformed the geometry of neuronal coding space, resulting in continuous representations that reflected both relatedness of inputs and an individual’s experience. Such continuous internal representations enable fast pattern classification, can support continual learning, and may provide a basis for higher-order learning and cognitive computations.
Blood metabolomic profiling reveals new targets in the management of psychological symptoms associated with alcohol use disorder
Authors: Leclercq Sophie , Ahmed Hany , Amadieu Camille , Petit Géraldine , Koistinen Ville , Leyrolle Quentin , Poncin Marie , Stärkel Peter , Kok Eloise , Karhunen Pekka J. , De Timary Philippe , Layé Sophie , Neyrinck Audrey M. , Kärkkäinen Olli , Hanhineva Kati , Delzenne Nathalie M.
Published: May 2024

Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to alcohol addiction are not yet fully understood, and in this respect, metabolomics represents a promising approach to decipher metabolic events related to AUD. The plasma metabolome contains a plethora of bioactive molecules that reflects the functional changes in host metabolism but also the impact of the gut microbiome and nutritional habits. In this study, we investigated the impact of chronic alcohol abuse, and of a three-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 patients diagnosed with severe alcohol use disorder (AUD). We found that the plasma levels of different lipids ((lyso)phosphatidylcholines, long-chain fatty acids), short-chain fatty acids (i.e. 3-hydroxyvaleric acid) and bile acids were altered in AUD patients. In addition, several microbial metabolites, including indole-3-propionic acid, p-cresol sulfate, hippuric acid, pyrocatechol sulfate, and metabolites belonging to xanthine class (paraxanthine, theobromine and theophylline) were sensitive to alcohol abuse and alcohol withdrawal. 3-Hydroxyvaleric acid, caffeine metabolites (theobromine, paraxanthine and theophylline) and microbial metabolites (hippuric acid and pyrocatechol sulfate) were correlated with anxiety, depression and alcohol craving. Metabolomics analysis in post-mortem samples of frontal cortex and cerebrospinal fluid of those consuming a high level of alcohol revealed that those metabolites can be found also in brain tissue. Our data allow to for the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets in the management of neuropsychiatric diseases such as AUD.The study was registered at clinicaltrial.gov under the identification number NCT03803709.
The decoding of extensive samples of motor units in human muscles reveals the rate coding of entire motoneuron pools
Authors: Avrillon Simon , Hug François , Enoka Roger , Caillet Arnault H. , Farina Dario
Published: May 2024

To advance our understanding of the neural control of muscle, we decoded the firing activity of extensive samples of motor units in the Tibialis Anterior (129±44 per participant; n=8) and the Vastus Lateralis (130±63 per participant; n=8) during isometric contractions of up to 80% of maximal force. From this unique dataset, we characterised the rate coding of each motor unit as the relation between its instantaneous firing rate and the muscle force, with the assumption that the linear increase in isometric force reflects a proportional increase in the net synaptic excitatory inputs received by the motoneuron. This relation was characterised with a natural logarithm function that comprised two phases. The initial phase was marked by a steep acceleration of firing rate, which was greater for low-than medium- and high-threshold motor units. The second phase comprised a linear increase in firing rate, which was greater for high-than medium- and low-threshold motor units. Changes in firing rate were largely non-linear during the ramp-up and ramp-down phases of the task, but with significant prolonged firing activity only evident for medium-threshold motor units. Contrary to what is usually assumed, our results demonstrate that the firing rate of each motor unit can follow a large variety of trends with force across the pool. From a neural control perspective, these findings indicate how motor unit pools use gain control to transform inputs with limited bandwidths into an intended muscle force.
Two long-axis dimensions of hippocampal-cortical integration support memory function across the adult lifespan
Authors: Nordin Kristin , Pedersen Robin , Falahati Farshad , Johansson Jarkko , Grill Filip , Andersson Micael , Korkki Saana M , Bäckman Lars , Zalesky Andrew , Rieckmann Anna , Nyberg Lars , Salami Alireza
Published: May 2024

The hippocampus is a complex structure critically involved in numerous behavior-regulating systems. In young adults, multiple overlapping spatial modes along its longitudinal and transverse axes describe the organization of its functional integration with neocortex, extending the traditional framework emphasizing functional differences between sharply segregated hippocampal subregions. Yet, it remains unknown whether these modes (i.e., gradients) persist across the adult human lifespan, and relate to memory and molecular markers associated with brain function and cognition. In two independent samples, we demonstrate that the principal anteroposterior and second-order, mid-to-anterior/posterior hippocampal modes of neocortical functional connectivity, representing distinct dimensions of macroscale cortical organization, manifest across the adult lifespan. Specifically, individual differences in topography of the second-order gradient predicted episodic memory and mirrored dopamine D1 receptor distribution, capturing shared functional and molecular organization. Older age was associated with less distinct transitions along gradients (i.e., increased functional homogeneity). Importantly, a youth-like gradient profile predicted preserved episodic memory – emphasizing age-related gradient dedifferentiation as a marker of cognitive decline. Our results underscore a critical role of mapping multidimensional hippocampal organization in understanding the neural circuits that support memory across the adult lifespan.
Successful treatment of diplopia using prism correction combined with vision therapy/orthoptics improves health-related quality of life
Authors: Portela-Camino Juan Antonio , Sanchez Irene , Gutierrez Cristina , Martín-González Santiago
Published: May 2024

Background

To track improvement in diplopia symptoms with strabismus-specific health-related quality of life (HRQOL) questionnaire across a treatment consisting of prism correction followed by vision therapy/orthoptics when prism treatment alone has not succeeded.

Methods

Forty-eight participants with diplopia and a mean age of 62.45 were asked to complete an Adult Strabismus-20 (AS-20) questionnaire and a Diplopia Questionnaire (DQ) before and after prism correction. Inclusion criteria were diplopia reported on the DQ as “sometimes”, “often” or “always” at reading or straight-ahead distance. The prism correction was classified as successful if the participant reported “never” or “rarely” on the DQ for reading and straight-ahead distance; and unsuccessful if the perceived diplopia worsened or remained the same. For all participants, mean initial AS-20 scores were compared with mean post-prism correction scores, taking into account AS-20 subscales (reading and general functions, and self-perception and interaction). Participants in the failed prism treatment subgroup subsequently underwent a programme of vision therapy wearing their prism correction, the results of which were again determined by participants’ responses on the AS-20 questionnaire, completed before and after the vision therapy.

Results

Five of the 48 participants dropped out of the study. Prism correction was classified as successful in 22 of 43 participants (51%), and unsuccessful in 21 (49%). Those participants for whom the prism correction was classified as a success showed a statistically significant improvement (p = 0.01) in both reading and general functions. In the failed treatment subgroup, no significant change in AS-20 score was recorded for any of the domains (p = 0.1). After treatment with vision therapy/orthoptics, however, 13 of the 20 participants in the unsuccessful prism correction subgroup (one of them dropped out the study) achieved binocular vision and statistically significant improvement in reading and general functions (p = 0.01).

Conclusions

Although effective prism correction of diplopia is correlated with enhanced HRQOL, prism correction alone is frequently not sufficient to achieve this objective. In these cases, vision therapy/orthoptics treatment as a coadjutant to prism correction is shown to improve HRQOL.