Developing deep LSTMs with later temporal attention for predicting COVID-19 severity, clinical outcome, and antibody level by screening serological indicators over time.

OBJECTIVE: The clinical course of COVID-19, as well as the immunological reaction, is notable for its extreme variability. Identifying the main associated factors might help understand the disease progression and physiological status of COVID-19 patients. The dynamic changes of the antibody against Spike protein are crucial for understanding the immune response. This work explores a temporal attention (TA) mechanism of deep learning to predict COVID-19 disease severity, clinical outcomes, and Spike antibody levels by screening serological indicators over time. METHODS: We use feature selection techniques to filter feature subsets that are highly correlated with the target. The specific deep Long Short-Term Memory (LSTM) models are employed to capture the dynamic changes of disease severity, clinical outcome, and Spike antibody level. We also propose deep LSTMs with a TA mechanism to emphasize the later blood test records because later records often attract more attention from doctors. RESULTS: Risk factors highly correlated with COVID-19 are revealed. LSTM achieves the highest classification accuracy for disease severity prediction. Temporal Attention Long Short-Term Memory (TA-LSTM) achieves the best performance for clinical outcome prediction. For Spike antibody level prediction, LSTM achieves the best permanence. CONCLUSION: The experimental results demonstrate the effectiveness of the proposed models. The proposed models can provide a computer-aided medical diagnostics system by simply using time series of serological indicators.

Identification and preliminary validation of differently expressed genes as candidate biomarkers associated with atherosclerosis.

OBJECTIVE: Atherosclerosis (AS) is the primary cause of deadly cardio-cerebro vascular diseases globally. This study aims to explore the key differentially expressed genes (DEGs), potentially serving as predictive biomarkers for AS. METHODS: Microarray datasets were retrieved from the GEO database for DEGs and DE-miRNAs identification. Then biological function of DEGs were elucidated based on gene ontology (GO) and KEGG pathway enrichment analysis. The protein-protein interaction (PPI) network and DEGs-DE-miRNAs network were constructed, with emphasis on hub DEGs selection and their interconnections. Additionally, receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic precision of hub DEGs for AS. More importantly, an AS Syrian Golden hamster model was established to validate the expression levels of hub DEGs in AS. RESULTS: A total of 203 DEGs and 10 DE-miRNAs were screened, with six genes were chosen as hub DEGs. These DEGs were significantly enriched in AS-related biological processes and pathways, such as immune and inflammatory response, cellular response to IL-1 and TNF, positive regulation of angiogenesis, Type I diabetes mellitus, Cytokine-cytokine receptor interaction, TLR signaling pathway. Also, these DEGs and DE-miRNAs formed a closely-interacted DE-miRNAs - DEGs - KEGG pathway network. Besides, hub DEGs presented promising diagnostic potential for AS (AUC: 0.781 âˆ¼ 0.887). In addition, the protein expression levels of TNF-α, CXCL8, CCL4, IL-1ß, CCL3 and CCR8 were significantly increased in AS group Syrian Golden hamsters. CONCLUSION: The identified candidate genes TNF, CXCL8, CCL4, IL1B, CCL3 and CCR8 may have the potential to serve as prognostic biomarker in diagnosing AS.

α-synuclein regulates Cyclin D1 to promote abnormal initiation of the cell cycle and induce apoptosis in dopamine neurons.

The etiology of Parkinson's disease (PD) is characterized by the death of dopamine neurons in the substantia nigra pars compacta, while misfolding and abnormal aggregation of α-synuclein (α-syn) are core pathological features. Previous studies have suggested that damage to dopamine neurons may be related to cell cycle dysregulation, but the specific mechanisms remain unclear. In this study, a PD mouse model was induced by stereotactic injection of α-syn into the nucleus, and treated with the cell cycle inhibitor, roscovitine (Rosc). The results demonstrated that Rosc improved behavioral disorders caused by α-syn, increased TH protein expression, inhibited α-syn and p-α-syn protein expression, and reduced the expression levels of G1/S phase cell cycle genes Cyclin D1, Cyclin E, CDK2, CDK4, E2F and pRB. Additionally, Rosc decreased Bax and Caspase-3 expression caused by α-syn, while increasing Bcl-2 protein expression. Meanwhile, we observed that α-syn can influence neuronal cell autophagy by decreasing the expression level of Beclin 1 and increasing the expression level of P62. However, Rosc can improve this phenomenon. In a cell model induced by α-syn in dopamine neuron injury cells, knockdown of Cyclin D1 led to similar results as those observed in animal experiments: Knocking down Cyclin D1 improved the abnormal initiation of the cell cycle caused by α-syn and regulated cellular autophagy, resulting in a reduction of apoptosis in dopamine neurons. In summary, exogenous α-syn can lead to the accumulation of α-syn and phosphorylated α-syn in dopamine neurons, increase key factors of the G1/S phase cell cycle such as Cyclin D1, and regulate downstream related indicators, causing the cell cycle to restart and leading to apoptosis of dopamine neurons. This exacerbates PD symptoms. However, knockdown of Cyclin D1 inhibits the progression of the cell cycle and can reverse this situation. These findings suggest that a Cyclin D inhibitor may be a novel therapeutic target for treating PD.

Diversity and spatiotemporal dynamics of fish communities in the Chongqing section of the upper Yangtze River based on eDNA metabarcoding.

Fish diversity plays a critical role in maintaining the balance of water ecosystems, especially in the Chongqing section of the National Nature Reserve for Rare and Endemic Fishes in the upper Yangtze River, which serves as an important habitat for rare and endemic fish, as well as an important channel for the replenishment of fishery resources in the Three Gorges Reservoir. Under a 10-year ban on fishing in the Yangtze River basin, we investigate fish diversity and seasonal variation in the Reserve by using environmental DNA (eDNA) metabarcoding. We found fishes belonging to 85 genera, 24 families, and 8 orders in the Reserve. A comparison of eDNA metabarcoding results with the diversity of a recent fish catch revealed that eDNA metabarcoding not only enables rapid and efficient fish monitoring but also has a high sensitivity. Furthermore, the study demonstrates that eDNA metabarcoding can be used as a tool for monitoring seasonal variations of fish composition in freshwater ecosystems. The alpha and beta diversity analysis both showed compositional differences in the fish community in accordance with seasonal variations. In addition, changes in eDNA relative sequence abundance and the detection of fish species at different sampling sites may reflect shifts in habitat use and distribution. Thus, we provide detailed seasonal data on fish diversity in the Chongqing section of the Reserve. This will contribute to conservation and to the understanding of fish diversity and community dynamics in the Chongqing section of the Reserve.

Mechanisms and treatments of chronic pain after traumatic brain injury.

While pain after trauma generally resolves, some trauma patients experience pain for months to years after injury. An example, relevant to both combat and civilian settings, is chronic pain after traumatic brain injury (TBI). Headache as well as pain in the back and extremities are common locations for TBI-related chronic pain to be experienced. TBI-related pain can exist alone or can exacerbate pain from other injuries long after healing has occurred. Consequences of chronic pain in these settings include increased suffering, higher levels of disability, serious emotional problems, and worsened cognitive deficits. The current review will examine recent evidence regarding dysfunction of endogenous pain modulatory mechanisms, neuroplastic changes in the trigeminal circuitry and alterations in spinal nociceptive processing as contributors to TBI-related chronic pain. Key pain modulatory centers including the locus coeruleus, periaqueductal grey matter, and rostroventromedial medulla are vulnerable to TBI. Both the rationales and existing evidence for the use of monoamine reuptake inhibitors, CGRP antagonists, CXCR2 chemokine receptor antagonists, and interventional therapies will be presented. While consensus guidelines for the management of chronic post-traumatic TBI-related pain are lacking, several approaches to this clinically challenging situation deserve focused evaluation and may prove to be viable therapeutic options.

Diagnostic performance of a novel automated CT-derived FFR technology in detecting hemodynamically significant coronary artery stenoses: A multicenter trial in China.

BACKGROUND AND AIMS: Computed tomography-derived fractional flow reserve (CT-derived FFR) algorithms have emerged as promising noninvasive methods for identifying hemodynamically significant coronary artery disease (CAD). However, its broad adaption is limited by the complex workflow, slow processing, and supercomputer requirement. Therefore, CT-derived FFR solutions capable of producing fast and accurate results could help deliver time-sensitive results rapidly and potentially alter patient management. The current study aimed to determine the diagnostic performance of a novel CT-derived FFR algorithm, esFFR, on patients with CAD was evaluated. METHODS: 329 patients from 6 medical centers in China were included in this prospective study. CT-derived FFR calculations were performed on 350 vessels using the esFFR algorithm using patients' presenting coronary computed tomography angiography (CCTA) images, and results and processing speed were recorded. Using invasive FFR measurements from direct coronary angiography as the reference standard, the diagnostic performance of esFFR and CCTA in detecting hemodynamically significant lesions were compared. Post-hoc analyses were performed for patients with calcified lesions or stenoses within the CT-derived FFR diagnostic "gray zone." RESULTS: The esFFR values correlated well with invasive FFR. The sensitivity, specificity, accuracy, positive and negative predictive value for esFFR were all above 90%. The overall performance of esFFR was superior to CCTA. Coronary calcification had minimal effects on esFFR's diagnostic performance. It also maintained 85% of diagnostic accuracy for "gray zone" lesions, which historically was <50%. The average esFFR processing speed was 4.6 ± 1.3 minutes. CONCLUSIONS: The current study demonstrated esFFR had high diagnostic efficacy and fast processing speed in identifying hemodynamically significant CAD.

Mild Traumatic Brain Injury-Induced Augmented Postsurgical Pain Is Driven by Central Serotonergic Pain-Facilitatory Signaling.

BACKGROUND: Individuals recovering from mild traumatic brain injury (mTBI) have increased rates of acute and chronic pain. However, the mechanism through which mTBI triggers heightened pain responses and the link between mTBI and postsurgical pain remain elusive. Recent data suggest that dysregulated serotonergic pain-modulating circuits could be involved. We hypothesized that mTBI triggers dysfunction in descending serotonergic pain modulation, which exacerbates acute pain and delays pain-related recovery after surgery. METHODS: Using mouse models of mTBI and hindpaw incision for postsurgical pain in C57BL/6J mice, mechanical withdrawal thresholds were assessed throughout the postsurgical period. To determine whether mTBI leads to persistent alteration of endogenous opioid tone, mu-opioid receptors (MORs) were blocked with naloxone. Finally, the role of descending serotonergic signaling on postsurgical allodynia in animals with mTBI was examined using ondansetron (5-HT3 receptor antagonist) or a serotonin-specific neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), to ablate descending serotonergic fibers. The treatment effects on withdrawal thresholds were normalized to baseline (percentage of maximum possible effect, MPE%), and analyzed using paired t-test or 2-way repeated-measures ANOVA with post hoc multiple comparisons. RESULTS: Post-mTBI mice demonstrated transient allodynia in hindpaws contralateral to mTBI, while no nociceptive changes were observed in sham-mTBI animals (mean difference, MD, MPE%, post-mTBI day 3: -60.9; 95% CI, -88.7 to -35.0; P < .001). After hindpaw incision, animals without mTBI exhibited transient allodynia, while mice with prior mTBI demonstrated prolonged postsurgical allodynia (MD-MPE% postsurgical day 14: -65.0; 95% CI, -125.4 to -4.5; P = .04). Blockade of MORs using naloxone transiently reinstated allodynia in mTBI animals but not in sham-mTBI mice (MD-MPE% post-naloxone: -69.9; 95% CI, -94.8 to -45.1; P < .001). Intrathecal administration of ondansetron reversed the allodynia observed post-mTBI and postincision in mTBI mice (compared to vehicle-treated mTBI mice, MD-MPE% post-mTBI day 3: 82.7; 95% CI, 58.5-106.9; P < .001; postsurgical day 17: 62.5; 95% CI, 38.3-86.7; P < .001). Both the acute allodynia after TBI and the period of prolonged allodynia after incision in mTBI mice were blocked by pretreatment with 5,7-DHT (compared to sham-mTBI mice, MD-MPE% post-mTBI day 3: 0.5; 95% CI, -18.5 to 19.5; P = .99; postsurgical day 14: -14.6; 95% CI, -16.7 to 45.9; P = .48). Similar behavioral patterns were observed in hindpaw ipsilateral to mTBI. CONCLUSIONS: Collectively, our results show that descending serotoninergic pain-facilitating signaling is responsible for nociceptive sensitization after mTBI and that central endogenous opioid tone opposes serotonin's effects. Understanding brain injury-related changes in endogenous pain modulation may lead to improved pain control for those with TBI undergoing surgery.

Continuous Ketamine Infusion as a Treatment for Refractory Facial Pain.

Complex orofacial pain disorders, such as trigeminal neuralgia (TN) and atypical facial pain (AFP), can be excruciating and debilitating during attacks. Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, is a powerful analgesic that has been used to treat various chronic pain conditions, but its role in treating complex facial pain has only been recently explored. In this retrospective case series, we reviewed the efficacy of continuous ketamine infusion for 12 patients with facial pain refractory to medical treatment. Patients who presented with a diagnosis of TN were more likely to have significant and sustained pain relief after receiving ketamine infusion. By contrast, those who did not respond to the treatment were more likely to have a diagnosis of AFP. The current report suggests a fundamental difference between these two facial pain disorders in their respective underlying pathophysiology and supports the use of continuous ketamine infusion for refractory TN, but not AFP.

Short daylight photoperiod alleviated alarm substance-stimulated fear response of zebrafish.

Photoperiod has been well-documented to be involved in regulating many activities of animals. However, whether photoperiod takes part in mood control, such as fear response in fish and the underlying mode(s) of action remain unclear. In this study, adult zebrafish males and females (Danio rerio) were exposed to different photoperiods, Blank (12 h light: 12 h dark), Control (12 h light: 12 h dark), Short daylight (SD, 6 h light: 18 h dark) and Long daylight (LD, 18 h light: 6 h dark) for 28 days. After exposure, fear response of the fish was investigated using a novel tank diving test. After alarm substance administration, the onset to higher half, total duration in lower half and duration of freezing in SD-fish were significantly decreased, suggesting that short daylight photoperiod is capable of alleviating fear response in zebrafish. In contrast, comparing with the Control, LD didn't show significant effect on fear response of the fish. Further investigation revealed that SD increased the levels of melatonin (MT), serotonin (5-HT) and dopamine (DA) in the brain while decreased the plasma level of cortisol comparing to the Control. Moreover, the expressions of genes in MT, 5-HT and DA pathways and HPI axis were also altered consistently. Our data indicated that short daylight photoperiod might alleviate fear response of zebrafish probably through interfering with MT/5-HT/DA pathways and HPI axis.

Organosulfur Materials for Rechargeable Batteries: Structure, Mechanism, and Application.

Lithium-ion batteries have received significant attention over the last decades due to the wide application of portable electronics and increasing deployment of electric vehicles. In order to further enhance the performance of the batteries and overcome the capacity limitations of inorganic electrode materials, it is imperative to explore new cathode and functional materials for rechargeable lithium batteries. Organosulfur materials containing sulfur-sulfur bonds as a kind of promising organic electrode materials have the advantages of high capacities, abundant resources, tunable structures, and environmental benignity. In addition, organosulfur materials have been widely used in almost every aspect of rechargeable batteries because of their multiple functionalities. This review aims to provide a comprehensive overview on the development of organosulfur materials including the synthesis and application as cathode materials, electrolyte additives, electrolytes, binders, active materials in lithium redox flow batteries, and other metal battery systems. We also give an in-depth analysis of structure-property-performance relationship of organosulfur materials, and guidance for the future development of organosulfur materials for next generation rechargeable lithium batteries and beyond.

[Empirical analysis on lumbar disc herniation treated with "sinew-bone three needling technique" of Chinese medicine].

The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.

Chronic exposure to environmentally relevant concentrations of carbamazepine interferes with anxiety response of adult female zebrafish through GABA /5-HT pathway and HPI axis.

Carbamazepine (CBZ) is one of the widely distributed pharmaceutical residues in aquatic environments, yet few researches have addressed its chronic effect on the anxiety of fish, and the mechanisms possibly involved remained elusive. In this study, adult female zebrafish (Danio rerio) were exposed to environmental relevant concentrations of CBZ (CBZ-low, 10 µg/L; CBZ-high, 100 µg/L) for 28 days. After exposure, CBZ-high didn't affect the anxiety of fish. However, the onset time to the higher half of the tank was delayed and the total duration in the lower half of the tank was increased in CBZ-low fish, suggesting an increased anxiety. Further investigation indicated that CBZ-low significantly decreased the gamma-aminobutyric acid (GABA) level in the brain, while increased the serotonin (5-HT) level in the brain and cortisol level in plasma. Accordingly, the mRNA levels of genes in GABA (gad2, abat, gabrb2, gabrg2, gria1a and slc12a2) pathway and HPI (crha, actha, pc1 and pc2) axis were also altered. Despite the upregulation of tph2 was consistent with increased 5-HT level in the brain, significantly downregulated htr1aa and htr1b may indicate attenuated 5-HT potency. Although CBZ-high significantly reduced GABA level in the brain and increased cortisol level in plasma, the effects were dramatically alleviated than that of CBZ-low. Consistently, the expression of genes in HPI (crha, actha, pc1 and pc2) axis and GABA (gad2 and abat) pathway were also altered by CBZ-high, probably due to inconspicuous anxiety response of CBZ-high. Briefly, our data suggested that low concentration of CBZ disrupted zebrafish anxiety by interfering with neurotransmission and endocrine system, thereby bringing about adverse ecological consequences.

Exploring a novel therapeutic strategy: the interplay between gut microbiota and high-fat diet in the pathogenesis of metabolic disorders.

In the past two decades, the rapid increase in the incidence of metabolic diseases, including obesity, diabetes, dyslipidemia, non-alcoholic fatty liver disease, hypertension, and hyperuricemia, has been attributed to high-fat diets (HFD) and decreased physical activity levels. Although the phenotypes and pathologies of these metabolic diseases vary, patients with these diseases exhibit disease-specific alterations in the composition and function of their gut microbiota. Studies in germ-free mice have shown that both HFD and gut microbiota can promote the development of metabolic diseases, and HFD can disrupt the balance of gut microbiota. Therefore, investigating the interaction between gut microbiota and HFD in the pathogenesis of metabolic diseases is crucial for identifying novel therapeutic strategies for these diseases. This review takes HFD as the starting point, providing a detailed analysis of the pivotal role of HFD in the development of metabolic disorders. It comprehensively elucidates the impact of HFD on the balance of intestinal microbiota, analyzes the mechanisms underlying gut microbiota dysbiosis leading to metabolic disruptions, and explores the associated genetic factors. Finally, the potential of targeting the gut microbiota as a means to address metabolic disturbances induced by HFD is discussed. In summary, this review offers theoretical support and proposes new research avenues for investigating the role of nutrition-related factors in the pathogenesis of metabolic disorders in the organism.

Multidirectional associations between the gut microbiota and Parkinson's disease, updated information from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway.

The human gastrointestinal tract is inhabited by a diverse range of microorganisms, collectively known as the gut microbiota, which form a vast and complex ecosystem. It has been reported that the microbiota-gut-brain axis plays a crucial role in regulating host neuroprotective function. Studies have shown that patients with Parkinson's disease (PD) have dysbiosis of the gut microbiota, and experiments involving germ-free mice and fecal microbiota transplantation from PD patients have revealed the pathogenic role of the gut microbiota in PD. Interventions targeting the gut microbiota in PD, including the use of prebiotics, probiotics, and fecal microbiota transplantation, have also shown efficacy in treating PD. However, the causal relationship between the gut microbiota and Parkinson's disease remains intricate. This study reviewed the association between the microbiota-gut-brain axis and PD from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway. We found that the interactions among gut microbiota and PD are very complex, which should be "multidirectional", rather than conventionally regarded "bidirectional". To realize application of the gut microbiota-related mechanisms in the clinical setting, we propose several problems which should be addressed in the future study.

Complete mitochondrial genome of Acrossocheilus yunnanensis (Cypriniformes: Cyprinidae: Acrossocheilus) and its phylogenetic analysis.

Acrossocheilus yunnanensis is an endemic species in China. In this study, the complete mitochondrial genome of A. yunnanensis was determined. It was 16,587 bp in length, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a putative control region. Phylogenetic analysis showed that A. yunnanensis was clustered with A. monticola.

Thiuram Monosulfide with Ultrahigh Redox Activity Triggered by Electrochemical Oxidation.

Organosulfides are promising cathodes for lithium batteries but often suffer from sluggish kinetics and low cycle stability. Herein, we report an electron-deficient organosulfide (ED-OS), which is formed via electrochemical oxidation of thiuram monosulfide, a low-cost sustainable material. The ED structure of (dimethylcarbamothioyl)thio can stretch the electron cloud of the adjacent C═S bond forming an S radical and lead to the cleavage of the S-C bond on the other side forming another S radical. The two (dimethylcarbamothioyl)thio radicals can form S-S bonds individually with low energy barriers, which thus are easy to break and could accommodate lithium ions with ultrafast reaction kinetics. It exhibits an ultralong cyclability of over 8000 cycles with a low capacity-fade rate of 0.0038% per cycle at a high rate of 10C in a lithium cell. In addition, we demonstrate that the same electrochemical oxidation can be applied to other thiuram compounds. This work provides new opportunities in developing ultrahigh-redox-activity organic electrode materials which can be started as needed.

Treatment Efficacy and Technical Advantages of Temporary Spinal Nerve Root Stimulation Compared to Traditional Spinal Cord Stimulation for Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is a common complication after herpes zoster infection. While conventional dorsal column temporary spinal cord stimulation (tSCS) has been shown as an effective treatment option for this pain condition, recent data suggests ipsilateral temporary spinal nerve root stimulation (tSNRS) as a safe alternative for treating PHN. However, there is no direct clinical comparison between the newer tSNRS and the traditional tSCS. OBJECTIVES: The current retrospective study aimed to describe the technical factors and the therapeutic efficacy of tSNR for patients with unilateral PHN and to compare these parameters with those treated with tSCS. STUDY DESIGN: Retrospective cohort study. SETTING: Single-center study in a large academic hospital. METHODS: One hundred sixty patients with unilateral PHN who underwent 7-14 days of tSCS (n = 109) or tSNRS (n = 51) treatment were included. Technical factors between the 2 groups, such as procedure time, radiation dosage, number of electrodes used, number of stimulation parameter adjustments, and average cost, were compared. Treatment efficacy, measured by analgesic coverage, pain visual analog scale (VAS), total analgesic agent consumption, Pittsburgh sleep quality index (PSQI), and physical and mental quality of life, were also compared between the 2 groups at baseline, post-procedure, and 3 months after stimulation treatment. RESULTS: Patients who underwent tSNRS reported significant improvement in pain level, sleep quality, and overall quality of life immediately postprocedure and during the follow-up period. This therapeutic effect was comparable to the tSCS group. Moreover, tSNRS achieved this therapeutic effect with a fewer number of implanted electrodes and stimulation adjustments than tSCS. The precision and consistency of the tSNRS technique were associated with a significant overall lower cost, a shorter procedure time, and less intraoperative radiation exposure in the tSNRS group than in those who received tSCS. LIMITATIONS: The current retrospective cohort study was limited by its relatively short follow-up period. Also, the selection of stimulation techniques was not randomized. CONCLUSIONS: While tSNRS provides similar therapeutic efficacy compared to tSCS for patients with unilateral PHN; it offers several technical advantages. These advantages include shorter procedure time, less radiation exposure, fewer implanted electrodes, more effective stimulation, and lower overall cost.

Shifting the Balance: How Top-Down and Bottom-Up Input Modulate Pain via the Rostral Ventromedial Medulla.

The sensory experience of pain depends not only on the transmission of noxious information (nociception), but on the state of the body in a biological, psychological, and social milieu. A brainstem pain-modulating system with its output node in the rostral ventromedial medulla (RVM) can regulate the threshold and gain for nociceptive transmission. This review considers the current understanding of how RVM pain-modulating neurons, namely ON-cells and OFF-cells, are engaged by "top-down" cognitive and emotional factors, as well as by "bottom-up" sensory inputs, to enhance or suppress pain.

A multisource database tracking the impact of the COVID-19 pandemic on the communities of Boston, MA, USA.

A pandemic, like other disasters, changes how systems work. In order to support research on how the COVID-19 pandemic impacted the dynamics of a single metropolitan area and the communities therein, we developed and made publicly available a "data-support system" for the city of Boston. We actively gathered data from multiple administrative (e.g., 911 and 311 dispatches, building permits) and internet sources (e.g., Yelp, Craigslist), capturing aspects of housing and land use, crime and disorder, and commercial activity and institutions. All the data were linked spatially through BARI's Geographical Infrastructure, enabling conjoint analysis. We curated the base records and aggregated them to construct ecometric measures (i.e., descriptors of a place) at various geographic scales, all of which were also published as part of the database. The datasets were published in an open repository, each accompanied by a detailed documentation of methods and variables. We anticipate updating the database annually to maintain the tracking of the records and associated measures.