bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Variable Clock Underlies Internally Generated Hippocampal Sequences
Authors: Deng Xinyi , Chen Shizhe , Sosa Marielena , Karlsson Mattias P. , Wei Xue-Xin , Frank Loren M. 
Published: March 2022

Humans have the ability to store and retrieve memories with various degrees of specificity, and recent advances in reinforcement learning have identified benefits to learning when past experience is represented at different levels of temporal abstraction. How this flexibility might be implemented in the brain remains unclear. We analyzed the temporal organization of male rat hippocampal population spiking to identify potential substrates for temporally flexible representations. We examined activity both during locomotion and during memory-associated population events known as sharp-wave ripples (SWRs). We found that spiking during SWRs is rhythmically organized with higher event-to-event variability than spiking during locomotion-associated population events. Decoding analyses using clusterless methods further indicate that a similar spatial experience can be replayed in multiple SWRs, each time with a different rhythmic structure whose periodicity is sampled from a log-normal distribution. This variability increases with experience despite the decline in SWR rates that occurs as environments become more familiar. We hypothesize that the variability in temporal organization of hippocampal spiking provides a mechanism for storing experiences with various degrees of specificity.SIGNIFICANCE STATEMENTOne of the most remarkable properties of memory is its flexibility: the brain can retrieve stored representations at varying levels of detail where, for example, we can begin with a memory of an entire extended event and then zoom in on a particular episode. The neural mechanisms that support this flexibility are not understood. Here we show that hippocampal sharp-wave ripples, which mark the times of memory replay and are important for memory storage, have a highly variable temporal structure that is well suited to support the storage of memories at different levels of detail.
Mixed Selectivity in the Cerebellar Purkinje-Cell Response during Visuomotor Association Learning
Authors: Sendhilnathan Naveen , Goldberg Michael E. , Ipata Anna E. 
Published: March 2022

Although the cerebellum has been traditionally considered to be exclusively involved in motor control, recent anatomic and clinical studies show that it also has a role in reward-processing. However, the way in which the movement-related and the reward-related neural activity interact at the level of the cerebellar cortex and contribute toward learning is still unclear. Here, we studied the simple spike activity of Purkinje cells in the mid-lateral cerebellum when 2 male monkeys learned to associate a right or left-hand movement with one of two visual symbolic cues. These cells had distinctly different discharge patterns between an overtrained symbol–hand association and a novel symbol–hand association, responding in association with the movement of both hands, although the kinematics of the movement did not change between the two conditions. The activity change was not related to the pattern of the visual symbols, the movement kinematics, the monkeys' reaction times, or the novelty of the visual symbols. The simple spike activity changed throughout the learning process, but the concurrent complex spikes did not instruct that change. Although these neurons also have reward-related activity, the reward-related and movement-related signals were independent. We suggest that this mixed selectivity may facilitate the flexible learning of difficult reinforcement learning problems.SIGNIFICANCE STATEMENTThe cerebellum receives both motor-related and reward-related information. However, it is unclear how these two signals interact at the level of cerebellar cortex and contribute to learning nonmotor skills. Here we show that in the mid-lateral cerebellum, the reward information is encoded independently from the motor information such that during reward-based learning, only the reward information carried by the Purkinje cells inform learning while the motor information remains unchanged with learning.
Evolution Increases Primates Brain Complexity Extending RbFOX1 Splicing Activity to LSD1 Modulation
Authors: Forastieri Chiara , Italia Maria , Toffolo Emanuela , Romito Elena , Bonasoni Maria Paola , Ranzani Valeria , Bodega Beatrice , Rusconi Francesco , Battaglioli Elena 
Published: March 2022

Recent branching (100 MYA) of the mammalian evolutionary tree has enhanced brain complexity and functions at the putative cost of increased emotional circuitry vulnerability. Thus, to better understand psychopathology, a burden for the modern society, novel approaches should exploit evolutionary aspects of psychiatric-relevant molecular pathways. A handful of genes is nowadays tightly associated to psychiatric disorders. Among them, neuronal-enriched RbFOX1 modifies the activity of synaptic regulators in response to neuronal activity, keeping excitability within healthy domains. We here dissect a higher primates-restricted interaction between RbFOX1 and the transcriptional corepressor Lysine Specific Demethylase 1 (LSD1/KDM1A). A single nucleotide variation (AA to AG) inLSD1gene appeared in higher primates and humans, endowing RbFOX1 with the ability to promote the alternative usage of a novel 3′ AG splice site, which extends LSD1 exon E9 in the upstream intron (E9-long). Exon E9-long regulates LSD1 levels by Nonsense-Mediated mRNA Decay. As reintroduction of the archaicLSD1variant (AA) abolishes E9-long splicing, the novel 3′ AG splice site is necessary for RbFOX1 to control LSD1 levels. LSD1 is a homeostatic immediate early genes (IEGs) regulator playing a relevant part in environmental stress-response. In primates and humans, inclusion of LSD1 as RbFOX1 target provides RbFOX1 with the additional ability to regulate the IEGs. These data, together with extensive RbFOX1 involvement in psychiatric disorders and its stress-dependent regulation in male mice, suggest the RbFOX1-LSD1-IEGs axis as an evolutionary recent psychiatric-relevant pathway. Notably, outside the nervous system, RbFOX2-dependent LSD1 modulation could be a candidate deregulated mechanism in cancer.SIGNIFICANCE STATEMENTTo be better understood, anxiety and depression need large human genetics studies aimed at further resolving the often ambiguous, aberrant neuronal pathomechanisms that impact corticolimbic circuitry physiology. Several genetic associations of the alternative splicing regulator RbFOX1 with psychiatric conditions suggest homeostatic unbalance as a neuronal signature of psychopathology. Here we move a step forward, characterizing a disease-relevant higher primates-specific pathway by which RbFOX1 acquires the ability to regulate neuronal levels of Lysine Specific Demethylase 1, an epigenetic modulator of environmental stress response. Thus, two brain-enriched enzymes, independently shown to homeostatically protect neurons with a clear readout in terms of emotional behavior in lower mammals, establish in higher primates and humans a new functional cooperation enhancing the complexity of environmental adaptation and stress vulnerability.
Magnitude of Resistance and Metabolism of Acaricides in Two-spotted Spider Mite, Tetranychus urticae Koch on Vegetables in Southern Districts of Tamil Nadu
Authors: Naveena K. , Shanthi M. , Chinniah C. , Jayaraj J. , Ramasubramanian T. , Mini M.L. , Renuka R. 
Published: March 2022

Background: Two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae) is a destructive, polyphagous and cosmopolitan pest infesting a wide range of vegetables. Farmers frequently use acaricides in the vegetable ecosystem for mite management leading to increased probability for the development of resistance against acaricides in mite species. Literature about resistance in T. urticae to novel acaricides is scanty from this region. Hence, this study was aimed to evaluate the magnitude of acaricide resistance in T. urticae populations on vegetable crops from Southern districts of Tamil Nadu against seven acaricides. The role of detoxification enzymes in conferring bio-chemical resistance in the mite species was also studied. Methods: The laboratory experiments were conducted at completely randomized design (CRD) during 2019-2021 in central instrumentation laboratory, Department of Agricultural Entomology, Agricultural College and Research Institute, Tamil Nadu Agricultural University, Madurai. The level of resistance in T. urticae populations to fenazaquin, propargite, spiromesifen, buprofezin, fenpropathrin, diafenthiuron and chlorfenapyr was evaluated following the leaf dip bioassay technique. The activity of the detoxifying enzymes viz., Glutathione S Transferase (GST), Mixed Function Oxidase (MFO) and Carboxylesterase (CarE) were estimated. Result: Fenazaquin was highly toxic to T. urticae, which recorded a low level of resistance (2.00 to 8.62-fold). T. urticae exhibited a low to moderate level of resistance to fenpropathrin (1.86 to 37.28-fold), moderate to a high level of resistance to diafenthiuron (15.81 to 50.53-fold), high level of resistance to propargite (45.16 to 65.10-fold) and chlorfenapyr (54.67 to 100.14-fold) and extremely high level of resistance to spiromesifen (193.04 to 452.61-fold) and buprofezin (377.97 to 514.44-fold). Among all the test populations, the highly resistant DAmRg population exhibited the highest specific activity of the detoxifying enzymes, viz., GST (26.98 nmoles ml-1 min-1 mg of protein-1), MFO (5.07 nmoles ml-1 min-1 mg of protein-1) and CarE (827.90 nmoles ml-1 min-1 mg of protein-1). The CarE activity was found to be positively correlated with highly resistant acaricide, propargite (r = 0.995) and MFO activity with buprofezin having an extremely high level of resistance (r = 0.997). This preliminary knowledge would be instrumental in framing the acaricide resistant management (ARM) strategies.
Understanding Racial Inequities in the Implementation of Harm Reduction Initiatives
Authors: Lopez Andrea M. , Thomann Matthew , Dhatt Zena , Ferrera Julieta , Al-Nassir Marwa , Ambrose Maggie , Sullivan Shane 
Published: March 2022

Objectives. To elucidate a structurally oriented theoretical framework that considers legacies of racism, trauma, and social exclusion and to interrogate the “unmet obligations” of the institutionalization of the harm reduction infrastructure to provide equitable protections to Black and Latinx people who use drugs (PWUD) in Maryland. Methods. In 2019, we conducted a rapid ethnographic assessment of and qualitative interviews with PWUD (n = 72) and stakeholders (n = 85) in 5 Maryland counties. We assessed PWUD’s experiences, service gaps in as well as barriers and facilitators to accessing services, and the potential to expand harm reduction programs. Results. The unmet obligations we found included enforcement and punitive governance of syringes, naloxone, and other drug use equipment; racism and racialization, social exclusion, and legacies of trauma; and differential implications of harm reduction for populations experiencing racialized criminalization. Conclusions. The implementation of harm reduction policies are a first step, but assessment of structural dynamics are needed for diverse communities with unique histories. This research illuminates a key paradox: progressive policy is implemented, yet the overdose crisis escalates in communities where various forms of racialized exclusions are firmly entrenched. (Am J Public Health. 2022;112(S2):S173–S181. https://doi.org/10.2105/AJPH.2022.306767 )
Mothers Who Use Drugs: Closing the Gaps in Harm Reduction Response Amidst the Dual Epidemics of Overdose and Violence in a Canadian Urban Setting
Authors: Boyd Jade , Maher Lisa , Austin Tamar , Lavalley Jennifer , Kerr Thomas , McNeil Ryan 
Published: March 2022

Objectives. To identify key gaps in overdose prevention interventions for mothers who use drugs and the paradoxical impact of institutional practices that can increase overdose risk in the context of punitive drug policies and a toxic drug supply. Methods. Semistructured interviews were conducted with 40 women accessing 2 women-only, low-barrier supervised consumption sites in Greater Vancouver, British Columbia, Canada, between 2017 and 2019. Our analysis drew on intersectional understandings of structural, everyday, and symbolic violence. Results. Participants’ substance use and overdose risk (e.g., injecting alone) was shaped by fear of institutional and partner scrutiny and loss (or feared loss) of child custody or reunification. Findings indicate that punitive policies and institutional practices that frame women who use drugs as unfit parents continue to negatively shape the lives of women, most significantly among Indigenous participants. Conclusions. Nonpunitive policies, including access to safe, nontoxic drug supplies, are critical first steps to decreasing women’s overdose risk alongside gender-specific and culturally informed harm-reduction responses, including community-based, peer-led initiatives to maintain parent–child relationships. (Am J Public Health. 2022;112(S2):S191–S198. https://doi.org/10.2105/AJPH.2022.306776 )
Integrating Community-Based HIV and Non-Communicable Disease Care with Microfinance Groups: A Formative Study in Western Kenya
Authors: Kafu Catherine , Wachira Juddy , Omodi Victor , Said Jamil , Pastakia Sonak D , Tran Dan , Onyango Jael Adongo , Aburi Dan , Wilson-Barthes Marta , Galárraga Omar , Genberg Becky Lynn 
Published: March 2022

Abstract
Background: The Harambee Study is a cluster randomized trial in western Kenya that tests the effect, mechanisms, and cost-effectiveness of integrating community-based HIV and non-communicable disease (NCD) care with group microfinance (MF) on HIV treatment outcomes. This paper documents the formative work to: (1) identify, enumerate, and characterize existing community-based microfinance groups to refine the study’s eligibility criteria, and (2) elicit support from multi-sectoral stakeholders in preparation for trial start. Methods: This mixed methods formative research took place between November 2019 and February 2020 in western Kenya. Surveys were administered to 115 group leaders of community-based MF groups. Field notes and GPS coordinates of group meeting locations and HIV healthcare facilities were also taken. A further 28 in-person meetings and two workshops involving stakeholders from multiple sectors of the health system took place throughout the formative phase. Quantitative survey data was analyzed using STATA IC/13. Longitude and latitude coordinates were mapped to County boundaries using Esri ArcMap. Qualitative data obtained from the meetings and field notes were analyzed thematically.Results: A total of 105 community-based microfinance groups were reached and 77 were eligible for the study. Of the eligible groups, we found differences in terms of definition of active membership, microfinance models, meeting location, and meeting frequency. Despite these differences, all the groups had an annual cycle period. Predominant themes emerging from the minutes and field notes revealed enthusiasm and support for the intervention among key stakeholders. Key stakeholders expressed a desire to have interventions integrated into the AMPATH care model for sustainability after the study period. Continuous engagement of various stakeholders, collaboration on various aspects of the study, identification of areas that could potentially lead to conflict, and overall increased transparency were identified as crucial to this integration.Conclusions: For randomized controlled trials (RCTs) conducted in rural communities, formative research is essential for pre-determining eligibility, mapping implementation sites and eliciting buy-in from community leaders. Adaptations identified from formative work should be addressed prior to study start.Trial registration: NCT04417127. Registered 4 June 2020 - Retrospectively registered, https:// www.clinicaltrials.gov/ct2/show/NCT04417127
Labelling of subpleural deposited pulmonary foci of blue dye and contrast agent substances under CT-guided control and their subsequent video thoracoscopic wedge resection: The BLUEPAT prospective randomized study
Authors: Červeňák Vladimír , Chovanec Zdeněk , Čundrle Ivan , Šitina Michal , Berková Alena , Hanslík Tomáš , Penka Igor , Vaníček Jiří , Součková Lenka 
Published: March 2022

Abstract
Background: Colour marking of indicated deposits is an innovative, accurate and gentle method that allows subsequent wedge resection of the marked tissue using a mini-invasive, video-assisted thoracoscopic (VATS) method with all its benefits. One of the expected benefits of this clinical trial is the introduction and optimization of the evaluated method into routine management in the diagnosis and treatment of focal lung diseases. The BLUEPAT clinical trial aims to evaluate the method of colour marking of subpleural deposited small lung deposits with the subsequent performance of VATS wedge resection in surgical practice.Methods: The BLUEPAT clinical trial is a prospective, monocentric, open-label, randomized study that will include 72 subjects with subpleural deposited lesions with the need for additional histological diagnostics to optimize subsequent treatment. These patients will be randomized into 2 groups in a 1:1 ratio. The first group will undergo VATS wedge resection of lung deposits marked with patent blue and contrast agent iohexol under CT-guided control. The second group will undergo VATS resection without prior colour coding of the lung deposits. The feasibility and safety of both methods will be assessed based on the evaluation of the parameters of the primary and secondary objectives of the study. The safety of the methods will be monitored by recording all related adverse events. The patients will participate in the clinical trial for 30 days.Discussion: The BLUEPAT clinical trial provides a unique evaluation of this innovative approach in the diagnosis and treatment of focal lung diseases. Clinical trials support the patent blue dyeing diagnostic procedures for the detection of breast cancer.Trial registration: EudraCT Number 2021-001122-22, Registered on 20.04.2021, https://www.sukl.eu/modules/evaluation/detail.php?id=51957&lang=2
ISSI 2021: Terahertz Spectroscopic Characterization and Thickness Evaluation of Internal Delamination Defects in GFRP Composites
Authors: Nsengiyumva Walter , ZHONG Shuncong , Luo Manting , Wang Bing 
Published: March 2022

Abstract
In recent years, terahertz time-domain spectroscopy (THz-TDS) has attracted significant attention due to its superior time and spatial resolution as well as its capabilities of localizing and characterizing internal defects in glass-fiber-reinforced polymer-matrix (GFRP) composite materials. In this study, the THz-TDS system is used to detect and evaluate hidden multi-delamination in plastic multilayered GFRP composite laminates. To remove the noise from the time-of-flight (TOF) signals, a wavelet shrinkage de-noising algorithm was used, leading to enhanced THz signals and further enabling an easy localization and evaluation of overlapping multi-delamination defects in GFRP composite laminates. In particular, both the thicknesses and locations of these delamination defects in the z-direction (i.e., through-the-thickness direction) were analyzed and measured considering the interaction between pulsed THz waves and the GFRP composite laminate. THz wave power and absorbance levels at every interface with different refractive indices in the GFRP composite samples were discussed based on analytical and experimental results. The present study shows the capabilities of the THz-TDS for the spectroscopic characterization of composite materials and helps users to know how they can theoretically estimate the thickness of the composite material that can be nondestructively evaluated by the THz-TDS.
The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis
Authors: Almulla Abbas F. , Supasitthumrong Thitiporn , Tunvirachaisakul Chavit , Algon Ali Abbas Abo , Al-Hakeim Hussein K. , Maes Michael 
Published: March 2022

Abstract
Background: Coronavirus disease 2019 (COVID-19) is accompanied by activated immune-inflammatory pathways and oxidative stress, which both may induce indoleamine-2,3-dioxygenase (IDO), a key enzyme of the tryptophan (TRP) catabolite (TRYCAT) pathway. The aim of the current study was to systematically review and meta-analyze the TRYCAT pathway status including levels of TRP and kynurenine (KYN) and IDO activity, as assessed using the KYN/TRP ratio. Methods: This systematic review was performed in December 2021 and searched data in PubMed, Google Scholar, and Web of sciences. In our meta-analysis we included 14 articles which examine TRP and TRYCATs in COVID-19 patients versus non-COVID-19 controls, and severe/critical versus mild/moderate COVID-19. Overall, the analysis was performed on 1269 individuals, namely 794 COVID-19 patients and 475 controls. Results: The results show a significant (p <0.0001) increase in the KYN/TRP ratio (standardized mean difference, SMD=1.099, 95% confidence interval, CI: 0.714; 1.484) and KYN (SMD= 1.123, 95% CI: 0.730;1.516) and significantly lower TRP ((SMD= -1.002, 95%CI: -1.738; -0.266) in COVID-19 versus controls. The KYN/TRP ratio (SMD= 0.945, 95%CI: 0.629; 1.262) and KYN (SMD= 0.806, 95%CI: 0.462; 1.149) were also significantly (p <0.001) higher and TRP lower (SMD= -0.909, 95% CI: -1.569; -0.249) in severe/critical versus mild/moderate COVID-19. No significant difference was detected in the kynurenic acid (KA)/KYN ratio and KA between COVID-19 patients and controls. Conclusions: Our results indicate increased activity of the IDO enzyme in COVID-19 and in severe/critical patients. The TRYCAT pathway is probably implicated in the pathophysiology and progression of COVID-19 and may signal a worse outcome of the disease.
Quantitative electroencephalographic biomarker of pharmacological treatment response in anxiety disorder: A retrospective study
Authors: Byeon Jun , Moon Jung Yeon , Je Se Ryoung , Kim Jun Won 
Published: March 2022

Abstract
Objectives: This study investigated the effectiveness of a quantitative electroencephalography(qEEG) biomarker in predicting the response to pharmacological treatment in patients with anxiety disorder.Methods: A total of 86 patients were diagnosed with anxiety disorder by using the Diagnostic and Statistical Manual of Mental Disorders 5th edition and treated with antidepressants. After 8-12weeks, the participants were divided into treatment-resistant(TRS) and treatment-response(TRP) groups on the basis of the Clinical Global Impressions-Severity(CGI-S) score. We obtained the absolute-EEG measurements for 19-channels and analyzed qEEG findings according to the Hz range: delta, theta, alpha, and beta. The beta-wave was subdivided into low-beta, beta, and high-beta. The theta-beta ratio(TBR) was calculated, and an analysis of covariance was performed.Results: Among the 86 patients with anxiety disorder, 65% were classified in the TRS group. The TRS and TRP groups did not differ regarding age, sex, and medication-dosage. However, the baseline CGI-S was higher in the TRP. After calibration by covariates, the TRP showed a higher beta-wave and high-beta-waves in T3 and T4. The TRP showed a lower TBR, especially in T3 and T4. Conclusion: These results indicate that patients with a lower TBR and higher beta and high-beta waves in T3 and T4 are more likely to respond to medication.