bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiscale Computer Model of the Spinal Dorsal Horn Reveals Changes in Network Processing Associated with Chronic Pain
Authors: Medlock Laura , Sekiguchi Kazutaka , Hong Sungho , Dura-Bernal Salvador , Lytton William W. , Prescott Steven A. 
Published: March 2022

Pain-related sensory input is processed in the spinal dorsal horn (SDH) before being relayed to the brain. That processing profoundly influences whether stimuli are correctly or incorrectly perceived as painful. Significant advances have been made in identifying the types of excitatory and inhibitory neurons that comprise the SDH, and there is some information about how neuron types are connected, but it remains unclear how the overall circuit processes sensory input or how that processing is disrupted under chronic pain conditions. To explore SDH function, we developed a computational model of the circuit that is tightly constrained by experimental data. Our model comprises conductance-based neuron models that reproduce the characteristic firing patterns of spinal neurons. Excitatory and inhibitory neuron populations, defined by their expression of genetic markers, spiking pattern, or morphology, were synaptically connected according to available qualitative data. Using a genetic algorithm, synaptic weights were tuned to reproduce projection neuron firing rates (model output) based on primary afferent firing rates (model input) across a range of mechanical stimulus intensities. Disparate synaptic weight combinations could produce equivalent circuit function, revealing degeneracy that may underlie heterogeneous responses of different circuits to perturbations or pathologic insults. To validate our model, we verified that it responded to the reduction of inhibition (i.e., disinhibition) and ablation of specific neuron types in a manner consistent with experiments. Thus validated, our model offers a valuable resource for interpreting experimental results and testing hypothesesin silicoto plan experiments for examining normal and pathologic SDH circuit function.SIGNIFICANCE STATEMENTWe developed a multiscale computer model of the posterior part of spinal cord gray matter (spinal dorsal horn), which is involved in perceiving touch and pain. The model reproduces several experimental observations and makes predictions about how specific types of spinal neurons and synapses influence projection neurons that send information to the brain. Misfiring of these projection neurons can produce anomalous sensations associated with chronic pain. Our computer model will not only assist in planning future experiments, but will also be useful for developing new pharmacotherapy for chronic pain disorders, connecting the effect of drugs acting at the molecular scale with emergent properties of neurons and circuits that shape the pain experience.
Disrupted Choline Clearance and Sustained Acetylcholine ReleaseIn Vivoby a Common Choline Transporter Coding Variant Associated with Poor Attentional Control in Humans
Authors: Donovan Eryn , Avila Cassandra , Klausner Sarah , Parikh Vinay , Fenollar-Ferrer Cristina , Blakely Randy D. , Sarter Martin 
Published: March 2022

Transport of choline via the neuronal high-affinity choline transporter (CHT;SLC5A7) is essential for cholinergic terminals to synthesize and release acetylcholine (ACh). In humans, we previously demonstrated an association between a common CHT coding substitution (rs1013940; Ile89Val) and reduced attentional control as well as attenuated frontal cortex activation. Here, we used a CRISPR/Cas9 approach to generate mice expressing the I89V substitution and assessed,in vivo, CHT-mediated choline transport, and ACh release. Relative to wild-type (WT) mice, CHT-mediated clearance of choline in male and female mice expressing one or two Val89 alleles was reduced by over 80% in cortex and over 50% in striatum. Choline clearance in CHT Val89 mice was further reduced by neuronal inactivation. Deficits in ACh release, 5 and 10 min after repeated depolarization at a low, behaviorally relevant frequency, support an attenuated reloading capacity of cholinergic neurons in mutant mice. The density of CHTs in total synaptosomal lysates and neuronal plasma-membrane-enriched fractions was not impacted by the Val89 variant, indicating a selective impact on CHT function. When challenged with a visual disruptor to reveal attentional control mechanisms, Val89 mice failed to adopt a more conservative response bias. Structural modeling revealed that Val89 may attenuate choline transport by altering conformational changes of CHT that support normal transport rates. Our findings support the view that diminished sustained cholinergic signaling capacity underlies perturbed attentional performance in individuals expressing CHT Val89. The CHT Val89 mouse serves as a valuable model to study heritable risk for cognitive disorders arising from cholinergic dysfunction.SIGNIFICANCE STATEMENTAcetylcholine (ACh) signaling depends on the functional capacity of the neuronal choline transporter (CHT). Previous research demonstrated that humans expressing the common CHT coding variant Val89 exhibit attentional vulnerabilities and attenuated fronto-cortical activation during attention. Here, we find that mice engineered to express the Val89 variant exhibit reduced CHT-mediated choline clearance and a diminished capacity to sustain ACh release. Additionally, Val89 mice lack cognitive flexibility in response to an attentional challenge. These findings provide a mechanistic and cognitive framework for interpreting the attentional phenotype associated with the human Val89 variant and establish a model that permits a more invasive interrogation of CNS effects as well as the development of therapeutic strategies for those, including Val89 carriers, with presynaptic cholinergic perturbations.
Thalamocortical Mechanisms for Nostalgia-Induced Analgesia
Authors: Zhang Ming , Yang Ziyan , Zhong Jiahui , Zhang Yuqi , Lin Xiaomin , Cai Huajian , Kong Yazhuo 
Published: March 2022

As a predominately positive emotion, nostalgia serves various adaptive functions, including a recently revealed analgesic effect. The current fMRI study aimed to explore the neural mechanisms underlying the nostalgia-induced analgesic effect on noxious thermal stimuli of different intensities. Human participants' (males and females) behavior results showed that the nostalgia paradigm significantly reduced participants' perception of pain, particularly at low pain intensities. fMRI analysis revealed that analgesia was related to decreased brain activity in pain-related brain regions, including the lingual and parahippocampal gyrus. Notably, anterior thalamic activation during the nostalgia stage predicted posterior parietal thalamus activation during the pain stage, suggesting that the thalamus might play a key role as a central functional linkage in the analgesic effect. Moreover, while thalamus-PAG functional connectivity was found to be related to nostalgic strength, periaqueductal gray-dorsolateral prefrontal cortex (PAG-dlPFC) functional connectivity was found to be associated with pain perception, suggesting possible analgesic modulatory pathways. These findings demonstrate the analgesic effect of nostalgia and, more importantly, shed light on its neural mechanism.SIGNIFICANCE STATEMENTNostalgia is known to reduce individuals' perception of physical pain. The underlying brain mechanisms, however, are unclear. Our study found that the thalamus plays a key role as a functional linkage between nostalgia and pain, suggesting a possible analgesic modulatory mechanism of nostalgia. These findings have implications for the underlying brain mechanisms of psychological analgesia.
Cocaine-Induced Changes in SpermCdkn1aMethylation Are Associated with Cocaine Resistance in Male Offspring
Authors: Swinford-Jackson Sarah E. , Fant Bruno , Wimmer Mathieu E. , Chan Donovan , Knouse Melissa C. , Sarmiento Mateo , Thomas Arthur S. , Huffman Phillip J. , Mankame Sharvari , Worobey Samantha J. , Pierce R. Christopher 
Published: March 2022

Paternal environmental perturbations can influence the physiology and behavior of offspring. For example, our previous work showed reduced cocaine reinforcement in male, but not female, progeny of rat sires that self-administered cocaine. The information transfer from sire to progeny may occur through epigenetic marks in sperm, encompassing alterations in small noncoding RNAs, including microRNAs (miRNAs) and/or DNA methylation. Here, no reliable changes in miRNAs in the sperm of cocaine- relative to saline-experienced sires were identified. In contrast, 272 differentially methylated regions were observed in sperm between these groups. Two hypomethylated promoter regions in the sperm of cocaine-experienced rats were upstream of cyclin-dependent kinase inhibitor 1a (Cdkn1a).Cdkn1amRNA also was selectively increased in the NAc of cocaine-sired male (but not female) offspring. Cocaine self-administration also enhancedCdkn1aexpression in the accumbens of cocaine-sired rats. These results suggest that changes inCdkn1amay play a role in the reduced cocaine reinforcing efficacy observed in cocaine-sired male rats. Introducing a 90 d delay between sire self-administration and breeding reversed both cocaine resistance and the increase in accumbensCdkn1amRNA in male offspring, indicating that cocaine-induced epigenetic modifications are eliminated with sperm turnover. Collectively, our results indicate that cocaine self-administration produces hypomethylation ofCdkn1ain sperm and a selective increase in the expression of this gene in the NAc of male offspring, which is associated with blunted cocaine reinforcement.SIGNIFICANCE STATEMENTThe relatively new field of transgenerational epigenetics explores the effects of environmental perturbations on offspring behavior and physiology. Our prior work in rats indicated that male, but not female, progeny of sires that self-administered cocaine displayed reduced cocaine reinforcement. The information transfer from sire to progeny may occur through heritable epigenetic marks in sperm, including DNA methylation. The present findings revealed two hypomethylated promoter regions upstream of theCdkn1agene in sire sperm. Remarkably,Cdkn1aexpression was selectively decreased in offspring NAc, a brain region that regulates cocaine reinforcement.
Fines, Fees, and Fundamental Rights
Authors: Albin-Lackey Chris 
Published: March 2022

The US Department of Justice’s investigation into the Ferguson, MO police department blew the lid off of a hidden, nationwide scandal. Too many police departments and courts all over the country were using predatory fines and fees to extract wealth from their communities’ poorest citizens. In many states, these abuses were inextricably bound up with deeply entrenched patterns of racist law enforcement. After Ferguson, it felt like a long overdue reckoning was near at hand.
Seven years after the DoJ published its Ferguson report, have we made any progress? Did the reckoning ever happen? This paper draws upon nationwide research by the National Center for Access to Justice (NCAJ) at Fordham Law School to provide some insight into this question. NCAJ’s Fines and Fees index ranks all 50 states based on whether they have adopted policies that are essential to any rights-respecting approach to monetary sanctions. Overall, the results are grim—not nearly enough has changed and some states are trending in the wrong direction. On the other hand, there has been widespread progress on some issues. There are reasons for optimism, and there are lessons in the data for activists who want to think pragmatically about how to realize change.
Efektivitas Penggunaan Aplikasi Wordwall dalam Pembelajaran Daring (Online) Matematika pada Materi Bilangan Cacah Kelas 1 di MIN 2 Kota Tangerang Selatan
Authors: Wafiqni Nafia , Putri Fanny Mestyana 
Published: March 2022

The purpose of this study was to determine the effectiveness of the use of the Wordwall application in online mathematics learning on counting number 1 in MIN 2 South Tangerang and the effectiveness of using Wordwall media in the closing activity which was reviewed throgh test results (final test of all materials). The research used is a combination research by combining quantitative and qualitative techniques. With the subject of this research are 56 studens of class 1 MIN 2 South Tangerang. In this study, various instruments were used to collect data such as: (1) interviews to support the result of student response questionnaires (2) interviews to support the results of student response questionnaires (3) questions throgh the Wordwall media and test questions to see the effectiveness of using Wordwall media in online mathematict learning activities. The results of this study were (1) in the student response questionnaire using Wordwall media in the closing activities of online mathematics learning, counting numbers were very effective with an average questionnaire value of 32,3 (2) the results of the tests carried out by the students resulted in a percentage completeness of 88,04 and 75% of the number of students so that it has been declared effective.
Phytochemical component, and antioxidant and vasculo-protective activities of Taiwan cocoa polyphenols by different processing methods
Authors: Chu Heuy-Ling , Fu Hong-Xuan , Chou En-Kuang , Lin Ying-Chun 
Published: March 2022

Cocoa tree (Theobroma cacao L.) is a recently planted crop in Taiwan, a country located in East Asia. Taiwanese cocoa beans are appreciated globally because of their distinctive flavor and aroma. The effects of the water extracts of unfermented Taiwan cocoa beans (WUFCB) and fermented and roasted Taiwan cocoa beans (WFRCB) on the anti-oxidation, vascular protection, and variation in phytochemical components were investigated. Variations in the catechins components of WUFCB and WFRCB were examined by high performance liquid chromatography. The values of catechin compounds in WUFCB (epicatechin [EC]: 52.32 ± 0.56 mg/g, and catechin (C): 15.14 ± 0.26 mg/g) were approximately two times higher than those found in WFRCB (EC: 26.22 ± 0.48 mg/g, and C: 4.56 ± 0.10 mg/g), indicating that the fermentation and roasting steps caused decline in catechins compounds of WFRCB. In the range of 50–300 µg mL-1, both WUFCB and WFRCB depict noncytotoxicity in endothelial cells; they protect cells from H2O2-induced cytotoxicity as established by MTT assay. Meanwhile, nitric oxide (NO) levels in endothelial cells were elevated by WUFCB. In addition, WUFCB displayed radical scavenging in the acellular model and inhibited increase in reactive oxygen species (ROS) noted in endothelial cell induced by H2O2. Overall, the significant vascular protection of WUFCB is associated with increased NO formation. The decreased ROS generation against oxidative damage was attributed to abundant catechin compounds. This study establishes Taiwan cocoa polyphenol as an effective and complementary tool for preventing endothelial dysfunction and cardiovascular disease.
The effect of adding rubber crumbs on the cyclic permanent deformation of waste mixtures containing coal wash and steel furnace slag
Authors: Qi Yujie , Indraratna Buddhima 
Published: March 2022

Among the numerous studies into the dynamic loading behaviour of rubber crumbs–soil/waste mixtures, the main focus is on how the content of rubber crumbs ([Formula: see text]) affects the damping ratio, shear modulus and total deformation. However, research into the influence of [Formula: see text] on the permanent strain rate ([Formula: see text]) and the deformation mechanism under repeated loading is very limited. In the current study, the cyclic deformation response for waste mixtures of steel furnace slag (SFS), coal wash (CW) and rubber crumbs (RC) is analysed and the test results reveal that [Formula: see text] has a significant influence on the initial [Formula: see text] and the slope of the permanent axial strain rate line, whereas cyclic deviator stress ([Formula: see text]) mainly affects the initial [Formula: see text]. The influence of [Formula: see text] and [Formula: see text] on the [Formula: see text] value of the waste mixture is incorporated in an empirical model, which enables prediction of the permanent deformation mechanism of SFS + CW + RC mixtures with wider-ranging amounts of RC and higher cyclic deviator stresses.
A comparative study of serum electrolytes, calcium and phosphorus levels in end stage renal disease patients undergoing hemodialysis
Authors: Pratibha K  , Soumya N  
Published: March 2022

End stage Renal Disease (ESRD) represents the terminal stage of Chronic Kidney Disease (CKD) stage 5 where in there is accumulation of toxins, fluid and electrolytes which are normally excreted by the kidneys resulting in the uremic syndrome which leads to death unless the toxins are removed by renal replacement therapy, using dialysis or kidney transplantation. To estimate and compare the serum levels of electrolytes, calcium and phosphorus in ESRD patients before and after hemodialysis sessions.Cross sectional study conducted on 70 ESRD diagnosed patients, aged 30-75years of either gender on maintenance Hemodialysis. Blood samples were collected before and after Hemodialysis, analysed for Serum Electrolytes by semi autoanalyser from Roche. Serum Calcium and Phosphorus using Cobas Integra 400 plus from Roche for which Internal and External Quality Assurance Programmes are maintained. The data obtained was analysed using statistical package SPSS 20 version. The parameters are compared using paired‘t’ test, the test of probability less than 0.05 (P &#60; 0.05) considered as statistically significant. There is significant decrease in mean serum Potassium, Chloride and Phosphorus, significant increase in serum Calcium and no change in serum Sodium after hemodialysis.Thus from our study we conclude that monitoring serum electrolytes, calcium and phosphorus have prognostic significance in ESRD patients undergoing hemodialysis.
Estimation of glycemic control in patients with type 2 diabetes mellites with various forms of tuberculosis with dots
Authors: Krishna T Sharmila , Devi C Suvarna , Sreedhar U , Viswa Kumar R , Naidu M Prasad 
Published: March 2022

Since ancient times people are aware of the association between tuberculosis and diabetes mellitus. Patients with tuberculosis and diabetes experience worse clinical manifestations, increased risk of treatment failure, recurrence, and death. The present study was conducted to evaluate glycosylated hemoglobin (HbA1c) and blood glucose levels, in patients with Type - 2 diabetes mellitus with various forms of tuberculosis who are on RNTCP DOTS and antidiabetic regimens. The study subjects included Type-2 diabetes mellitus with tuberculosis who are registered under RNTCP DOTS, in Dept of Pulmonology, PESIMSR, Kuppam, Chittoor district. Study groups comprises, 20 cases of type 2 DM WITH TB who are on oral hypo glycemic agents (OHA), 20 cases of Type 2DM WITH TB who are on oral hypoglycemic agents (OHA) with insulin, 20 cases of Type 2 DM WITH TB who are on insulin. HbAc is measured by fully automatic Bio-Rad D10 - HbA1c Analyzer. Blood glucose levels are estimated by auto analyser VITROS 250 in PESIMSR, Kuppam. The mean HbA1c levels showed good control in those patients kept on insulin alone compared to OHA and OHA with insulin groups (P &#60;0.001). The mean HbAC levels were high in OHA alone group compared to other groups (P&#60;0.001). The study revealed that increased levels of Glycosylated haemoglobin (HbA1C) are observed in those patients kept on OHA alone with DOTS as compared with other two groups. There is strong interaction between anti tubercular drugs and OHA which in turn leads to poor glycemic control. Poor glycemic state in diabetic patients is having strong impact on TB treatment outcome.
A survey on: Tobacco awareness in urban region of Maharashtra
Authors: Sayyed Anjum A K , Lanjewar Soumya , Agarwal Namrata , Pratinidhi Shilpa A 
Published: March 2022

Tobacco has been a prevalent cause of disease burden over India since decades. Gap in awareness among the population leads to use of tobacco, causing a number of deaths across India.The study aimed at assessing prevalence, attitude, knowledge gap harbouring in the urban population of Maharashtra. Effect of mass media was gauged along with the ability of people to avoid their addiction.A quantitative, online Google form based Questionnaire survey was conducted in a convenient sample of urban population across Maharashtra. 344 people participated following, the data was analysed using Microsoft Excel.29.1% (n=100) of the urban population were Tobacco users, most of which having Undergraduate/Postgraduate Educational qualification. 25% (n=61) of Non users didn’t know about the tobacco content in various products. Majority of Tobacco users were aware of the risk of Tobacco use causing heart attacks and also hold an opinion that smoking should be banned in public places. 38% (n=91) Tobacco users felt that there was a lack of impact of Tobacco use on social behaviour. People with different education levels consumed cigarettes/bidis the most.Higher educated class was found to have a higher conscious decision in Tobacco Usage. The need for Mass media enhancement was felt due to low impact on quitting behaviour. Tobacco was found to have a low impact on socializing, and it's true effects can be studied in future.
Study of serum electrolytes, calcium and magnesium in preeclampsia at a tertiary hospital in central Karnataka
Authors: Savadi Basavaraj V , Nalwarkar Bhagyajyoti , Rashmi B M  
Published: March 2022

Preeclampsia(PE) is a hypertensive disorder affecting about 5-14% of pregnancies worldwide and around 20% of high-risk pregnancies, resulting in maternal and perinatal morbidity and mortality. Imbalances in milieu of serum sodium and potassium, that are involved in functioning of vascular smooth muscles, leads to vasoconstriction and hypertension in PE. Calcium deficiency stimulates parathyroid hormone, leading to vasoconstriction. Magnesium regulates blood pressure by monitoring vascular tone and structure. There is scarcity of studies on these factors in PE in central Karnataka. To estimate levels of serum calcium, magnesium, sodium and potassium in preeclampsia. Hospital based cross-sectional study conducted from September, 2020 to February, 2021 at a Tertiary Teaching Hospital in Chitradurga. 60 diagnosed cases of preeclampsia and equal number of age, parity and gestational age matched women with singleton normal pregnancies, attending antenatal clinic or admitted and treated in obstetrics wards of the hospital were included in the study. Clinical examination and laboratory investigations to estimate biochemical parameters were conducted. Data was analyzed in SPSS V:20. Statistical tests like chi-square and One-way ANOVA test were applied to find the significance of associations. Hypernatremia, hypokalemia, hypomagnesemia and hypocalcemia were significant in preeclampsia compared to normal pregnancy group. In severe preeclamptia, highest levels of serum sodium and lowest levels of serum potassium, magnesium and calcium were found compared to the mild PE group. Timely estimation of serum electrolytes, calcium and magnesium through the course of pregnancy could help in early detection and prompt treatment of preeclampsia and also can prevent the adverse outcomes of pregnancies. Also, dietary restriction of sodium and dietary supplementation of calcium, magnesium and potassium rich foods to the pregnant women and calcium supplementation could reduce the risk of preeclampsia.