bluuebunny/crossref_metadata_2025 huggingface dataset:
Delay and Speed of Visual Feedback of a Keystroke Cause Illusory Heaviness and Stiffness
Authors: Yokosaka Takumi , Kawabe Takahiro
Published: March 2022

Imposing a delay between an action (e.g., a limb movement) and its related visual feedback (e.g., a cursor movement on the display) induces a peculiar sensation of heaviness or stiffness. Earlier studies have examined this delay-induced heaviness or stiffness sensation in relation to the non-arbitrary causal relationship between an action and its effect. Here, “non-arbitrary causal relationship” means that an action produces a specific and deterministic pattern of visual feedback; for example, a leftward limb movement consistently and deterministically causes a leftward visual motion. In modern graphical user interfaces, on the other hand, users often control visual information by pressing keys, wherein the relationship between the keystroke and the change in visual information is arbitrary. The present study examined whether the sensation of heaviness, stiffness and bumpiness could be caused when participants' keystroke produced a delayed arbitrary visual feedback. Participants were asked to press and hold down an assigned key to cause temporal luminance changes in a square centered on the display, an arbitrary visual feedback of their keystroke. Not only the onset delay of the temporal luminance change from the participant's keystroke but also the speed of the temporal luminance change were examined as a visual cue to heaviness, stiffness, or bumpiness. In Experiment 1, the participants' task was to give a rating for the strength of the heaviness, stiffness, or bumpiness perceived when they pressed the key. Our results showed that the heaviness and stiffness ratings increased as the delay increased and decreased as the speed increased. To check whether the manipulation of the delay and speed of the visual feedback caused changes in the subjective evaluation of sensorimotor incongruence, in Experiment 2, we asked the participants to give a rating for the sense of agency. The rating scores decreased as the delay increased and increased as the speed increased. The delay and speed influenced the rating scores for the sense of agency in the opposite direction to those for heaviness/stiffness. We discuss that the brain determines the heaviness and stiffness during a keystroke based on internalized statistics relating to the delay and speed of the action feedback.
Safety and Tolerability of Accelerated Low-Frequency Repetitive Transcranial Magnetic Stimulation Over the Primary Motor Cortex–A Pilot Study
Authors: Engelhardt Melina , Kimmel Jana , Raffa Giovanni , Conti Alfredo , Picht Thomas
Published: March 2022

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is capable of inducing changes in the functional organization of underlying brain regions, however, often at the cost of long stimulation protocols over several weeks. As these protocols can be difficult to implement in clinical settings, the aim of the present pilot study was to show the feasibility and safety of an accelerated low-frequency rTMS protocol applying multiple sessions daily. To this purpose, nine healthy subjects received 14 sessions of rTMS (1 Hz, 30 min, 110% RMT) to the hand motor hotspot. Subjects received stimulation for either 14 days once daily [classical rTMS (c-rTMS)], 7 days twice daily (accelerated rTMS; a-rTMS), or sham stimulation for 14 days once daily (s-rTMS). Daily stimulation sessions in the a-rTMS group were delivered with a 90-min break in between. In total, 74% of rTMS sessions in the c-rTMS group, 89% in the a-rTMS group, and 98% in the s-rTMS group were free of any side effects. Brief headaches and fatigue in stimulated muscle groups were the most frequent side effects. All side effects were reported to be at maximum mild and of short duration. Thus, accelerated low-frequency rTMS of the motor cortex seems to be a safe and feasible method, previously shown to induce a functional reorganization of the motor system. By shortening treatment duration in days, this approach can potentially make rTMS protocols more accessible to a wider range of patients.
Altered Brain Structural Reorganization and Hierarchical Integrated Processing in Obesity
Authors: Zhang Peng , Wu Guo-wei , Tang Li-rong , Yu Feng-xia , Li Meng-yi , Wang Zheng , Yang Zheng-han , Zhang Zhong-tao , Lv Han , Liu Yang , Wang Zhen-chang
Published: March 2022

The brain receives sensory information about food, evaluates its desirability and value, and responds with approach or withdrawal. The evaluation process of food in the brain with obesity may involve a variety of neurocircuit abnormalities in the integration of internal and external information processing. There is a lack of consistency of the results extant reported for aberrant changes in the brain with obesity that prohibits key brain alterations to be identified. Moreover, most studies focus on the observation of neural plasticity of function or structure, and the evidence for functional and structural correlations in the neuronal plasticity process of obesity is still insufficient. The aims of this article are to explore the key neural structural regions and the hierarchical activity pattern of key structural nodes and evaluate the correlation between changes in functional modulation and eating behavior. Forty-two participants with obesity and 33 normal-weight volunteers were recruited. Gray matter volume (GMV) and Granger causality analysis (GCA) were performed using the DPARSF, CAT12, and DynamicBC toolbox. Compared with the normal weight group, the obesity group exhibited significantly increased GMV in the left parahippocampal gyrus (PG). The obesity group showed decreased causal inflow to the left PG from the left orbitofrontal cortex (OFC), right calcarine, and bilateral supplementary motor area (SMA). Decreased causal outflow to the left OFC, right precuneus, and right SMA from the left PG, as well as increased causal outflow to the left middle occipital gyrus (MOG) were observed in the obesity group. Negative correlations were found between DEBQ-External scores and causal outflow from the left PG to the left OFC, and DEBQ-Restraint scores and causal inflow from the left OFC to the left PG in the obesity group. Positive correlation was found between DEBQ-External scores and causal outflow from the left PG to the left MOG. These results show that the increased GMV in the PG may play an important role in obesity, which may be related to devalued reward system, altered behavioral inhibition, and the disengagement of attentional and visual function for external signals. These findings have important implications for understanding neural mechanisms in obesity and developing individual-tailored strategies for obesity prevention.
CHIP Decline Is Associated With Isoflurane-Induced Neurodegeneration in Aged Mice
Authors: Xu Qiaoqiao , Xiong Juan , Xu Li , Wu Yuanyuan , Li Man , Li Qinqin , Jiang Tao , Luo Ailin , Zhang Yi
Published: March 2022

Perioperative neurocognitive disorders (PND) commonly occur in elderly patients, and isoflurane could be a risk factor. During the pathogenesis of neurodegeneration, the ubiquitin–proteasome system (UPS) participates in the process of aging, which affects synaptic plasticity and synaptic function. However, whether UPS is involved in the etiology of PND is unclear. In this study, we examined the expression change of ubiquitin E3 ligase protein carboxyl-terminus of Hsc70-interacting protein (CHIP) and the function turbulence of UPS in isoflurane-exposed aged mouse to illustrate the role of UPS in PND. Neurodegenerative behavioral changes were shown in isoflurane-exposed aged mice and correlated with neuropathological changes manifested with reduced number of intersections and spine density in the cortex. Ubiquitin function was decreased while the apoptosis was activated, and CHIP protein expression decline altered synapsin expression and phosphorylation associated with the neurodegeneration in isoflurane-induced PND. Aging was the big important factor. And it remained consistent with the synapsin phosphorylation/dephosphorylation level changes in CHIP knock-down N2a cells. Per our observation, the decline in CHIP protein expression and synaptic degeneration might reveal the reason for synaptic degeneration in the underlying pathogenesis of PND caused by isoflurane.
Effects of High-Definition Transcranial Direct Current Stimulation Over the Primary Motor Cortex on Cold Pain Sensitivity Among Healthy Adults
Authors: Li Xiaoyun , Lin Xinxin , Yao Junjie , Chen Shengxiong , Hu Yu , Liu Jiang , Jin Richu
Published: March 2022

Some clinical studies have shown promising effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on pain relief. Nevertheless, a few studies reported no significant analgesic effects of tDCS, likely due to the complexity of clinical pain conditions. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds that are present in the clinical data. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) stimulation over M1 on sensitivity to experimental pain and assess whether these effects could be influenced by the pain-related cognitions and emotions. A randomized, double-blinded, crossover, and sham-controlled design was adopted. A total of 28 healthy participants received anodal, cathodal, or sham HD-tDCS over M1 (1 mA for 20 min) in different sessions, in which montage has the advantage of producing more focal stimulation. Using a cold pressor test, several indices reflecting the sensitivity to cold pain were measured immediately after HD-tDCS stimulation, such as cold pain threshold and tolerance and cold pain intensity and unpleasantness ratings. Results showed that only anodal HD-tDCS significantly increased cold pain threshold when compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain tolerance, pain intensity, and unpleasantness ratings. Correlation analysis revealed that individuals that a had lower level of attentional bias to negative information benefited more from attenuating pain intensity rating induced by anodal HD-tDCS. Therefore, single-session anodal HD-tDCS modulates the sensory-discriminative aspect of pain perception as indexed by the increased pain threshold. In addition, the modulating effects of HD-tDCS on attenuating pain intensity to suprathreshold pain could be influenced by the participant’s negative attentional bias, which deserves to be taken into consideration in the clinical applications.
Secular Trends in the Prevalence of and Disability-Adjusted Life Years Due to Common Micronutrient Deficiencies in China From 1990 to 2019: An Age-Period-Cohort Study and Joinpoint Analysis
Authors: Chen Haiying , Lu Jinxin , Li Yongze
Published: March 2022

Background

Understanding the national burdens and trends of micronutrient deficiencies can help guide effective intervention strategies. However, there is a lack of evidence of secular trends and age and sex differences in China. This study aims to elucidate trends in common micronutrient deficiencies, in particular, dietary iron, iodine and vitamin A deficiencies in China, from 1990 to 2019 using Global Burden of Disease (GBD) 2019 study data.

Methods

Prevalence and DALYs trends of common micronutrient deficiencies from 1990 to 2019 were assessed by joinpoint regression analysis. Age, period and cohort effects on the prevalence of common micronutrient deficiencies were estimated by an age-period-cohort model.

Results

From 1990 to 2019, the age-standardized prevalence rates of iodine, vitamin A and dietary iron deficiencies changed by −0.6% (95% CI: −0.7% to −0.5%), −6.3% (−6.6% to −6.0%), and −3.5% (−3.6% to −3.4%) in males and + 0.8% (+ 0.6% to + 1.0%), −4.5% (−4.8% to −4.2%), and −3.3% (−3.4% to −3.2%) in females, respectively. The average annual percent change (AAPC) in the iodine deficiency prevalence increased in females aged 20 years and older. The relative risk (RR) of iodine deficiency associated with the age effect peaked at 30–34 years of age and then decreased with increasing age. The RR of vitamin A deficiency decreased with age. The age distribution of the RR of iron deficiency differed significantly between sexes. The RRs of vitamin A deficiency and dietary iron deficiency decreased over time, whereas the RR of iodine deficiency substantially increased starting in 2004. The RRs of iodine deficiency and dietary iron deficiency associated with the cohort effect decreased, but the vitamin A deficiency prevalence increased in successive birth cohorts.

Conclusion

Micronutrient deficiency prevalence rates and associated DALYs decreased from 1990 to 2019 in China. Young adults, children aged less than 5 years, and older individuals were disproportionately affected by iodine, vitamin A, and dietary iron deficiencies, respectively. The results of this study may help identify individuals who would benefit from interventions to improve micronutrient deficiency.
Potential Role of Ginger (Zingiber officinale Roscoe) in the Prevention of Neurodegenerative Diseases
Authors: Arcusa Raúl , Villaño Débora , Marhuenda Javier , Cano Miguel , Cerdà Begoña , Zafrilla Pilar
Published: March 2022

Ginger is composed of multiple bioactive compounds, including 6-gingerol, 6-shogaol, 10-gingerol, gingerdiones, gingerdiols, paradols, 6-dehydrogingerols, 5-acetoxy-6-gingerol, 3,5-diacetoxy-6-gingerdiol, and 12-gingerol, that contribute to its recognized biological activities. Among them, the major active compounds are 6-shogaol and 6-gingerol. Scientific evidence supports the beneficial properties of ginger, including antioxidant and anti-inflammatory capacities and in contrast, a specific and less studied bioactivity is the possible neuroprotective effect. The increase in life expectancy has raised the incidence of neurodegenerative diseases (NDs), which present common neuropathological features as increased oxidative stress, neuroinflammation and protein misfolding. The structure-activity relationships of ginger phytochemicals show that ginger can be a candidate to treat NDs by targeting different ligand sites. Its bioactive compounds may improve neurological symptoms and pathological conditions by modulating cell death or cell survival signaling molecules. The cognitive enhancing effects of ginger might be partly explained via alteration of both the monoamine and the cholinergic systems in various brain areas. Moreover, ginger decreases the production of inflammatory related factors. The aim of the present review is to summarize the effects of ginger in the prevention of major neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis.
Metataxonomic Analysis of Milk Samples From SARS-CoV-2-Positive and SARS-CoV-2-Negative Women
Authors: Gómez-Torres Natalia , Sánchez-García Laura , Castro Irma , Arroyo Rebeca , Cabañas Fernando , González-Sánchez Raquel , López-Azorín Manuela , Moral-Pumarega M. Teresa , Escuder-Vieco Diana , Cabañes-Alonso Esther , Rodríguez Juan Miguel , Alba Claudio , Pellicer Adelina
Published: March 2022

Objective

To assess the impact of SARS-CoV-2 viral infection on the metataxonomic profile and its evolution during the first month of lactation.

Methods

Milk samples from 37 women with full-term pregnancies and mild SARS-CoV-2 infection and from 63 controls, collected in the first and fifth postpartum weeks, have been analyzed. SARS-CoV-2 RNA was assessed by reverse transcription polymerase chain reaction (RT-PCR) both in cases and controls. After DNA extraction, the V3-V4 hypervariable region of the gene 16S rRNA was amplified and sequenced using the MiSeq system of Illumina. Data were submitted for statistical and bioinformatics analyses after quality control.

Results

All the 1st week and 5th week postpartum milk samples were negative for SARS-CoV-2 RNA. Alpha diversity showed no differences between milk samples from the study and control group, and this condition was maintained along the observation time. Analysis of the beta-diversity also indicated that the study and control groups did not show distinct bacterial profiles. Staphyloccus and Streptococcus were the most abundant genera and the only ones that were detected in all the milk samples provided. Disease state (symptomatic or asymptomatic infection) did not affect the metataxonomic profile in breast milk.

Conclusion

These results support that in the non-severe SARS-CoV-2 pregnant woman infection the structure of the bacterial population is preserved and does not negatively impact on the human milk microbiota.
Based on SEER Database: Population Distribution, Survival Analysis, and Prognostic Factors of Organ Metastasis of Lung Large Cell Neuroendocrine Carcinoma
Authors: Liu Chang-fu , Tao Yu-jian
Published: March 2022

Background

The incidence rate of lung large cell neuroendocrine carcinoma (LCNEC) in lung cancer is low, but the malignancy is high and the prognosis is poor. We used the Surveillance, Epidemiology, and End Results (SEER) database to determine the population distribution of organ metastasis in LCNEC, conduct survival analysis, judge prognostic factors, and provide direction for follow-up diagnosis and treatment.

Materials and methods

By logging into the SEER database, the data of lung LCNEC were retrieved and the target population was selected. According to the presence or absence of organ metastasis (bone, brain, liver, and lung), we divided the target population into the no organ metastasis group (n = 1,202) and the organ metastasis group (n = 870). By analyzing the clinicopathological data of patients and using the survival function, the corresponding median survival time was obtained, and the influencing factors of each group were analyzed. Then, the significant influencing factors were analyzed by multivariate Cox regression analysis to screen out the independent influencing factors.

Result

In the overall sample group, multivariate Cox regression analysis showed that sex, age, primary site surgery, bone metastasis, brain metastasis, liver metastasis, radiotherapy, and chemotherapy were independent prognostic factors. The 1-year survival rate was 13.8% in the bone metastasis group, 19.1% in the brain metastasis group, 13.8% in the liver metastasis group, and 20.3% in the intrapulmonary metastasis group. In the organ metastasis group, multivariate Cox regression analysis showed that sex, chemotherapy, radiotherapy sequence with surgery, primary site surgery, liver metastasis, and age at diagnosis were independent factors affecting the prognosis.

Conclusion

In the overall sample of LCNEC, bone metastasis, brain metastasis, and liver metastasis all reduced the overall survival time, while the effect of intrapulmonary metastasis on the overall survival time was not statistically significant. Sex, chemotherapy, radiotherapy sequence with surgery, primary site surgery, liver metastasis, and age were independent factors affecting the prognosis of the LCNEC organ metastasis group. Women, chemotherapy, and radiotherapy sequence with surgery were favorable factors, while old age, liver metastasis, and male were unfavorable factors.
Prognostic and Predictive Value of Liquid Biopsy-Derived Androgen Receptor Variant 7 (AR-V7) in Prostate Cancer: A Systematic Review and Meta-Analysis
Authors: Khan Tanzila , Becker Therese M. , Scott Kieran F. , Descallar Joseph , de Souza Paul , Chua Wei , Ma Yafeng
Published: March 2022

In advanced prostate cancer, access to recent diagnostic tissue samples is restricted and this affects the analysis of the association of evolving biomarkers such as AR-V7 with metastatic castrate resistance. Liquid biopsies are emerging as alternative analytes. To clarify clinical value of AR-V7 detection from liquid biopsies, here we performed a meta-analysis on the prognostic and predictive value of androgen receptor variant 7 (AR-V7) detected from liquid biopsy for patients with prostate cancer (PC), three databases, the Embase, Medline, and Scopus were searched up to September 2021. A total of 37 studies were included. The effects of liquid biopsy AR-V7 status on overall survival (OS), radiographic progression-free survival (PFS), and prostate-specific antigen (PSA)-PFS were calculated with RevMan 5.3 software. AR-V7 positivity detected in liquid biopsy significantly associates with worse OS, PFS, and PSA-PFS (P <0.00001). A subgroup analysis of patients treated with androgen receptor signaling inhibitors (ARSi such as abiraterone and enzalutamide) showed a significant association of AR-V7 positivity with poorer OS, PFS, and PSA-PFS. A statistically significant association with OS was also found in taxane-treated patients (P = 0.04), but not for PFS (P = 0.21) or PSA-PFS (P = 0.93). For AR-V7 positive patients, taxane treatment has better OS outcomes than ARSi (P = 0.01). Study quality, publication bias and sensitivity analysis were integrated in the assessment. Our data show that liquid biopsy AR-V7 is a clinically useful biomarker that is associated with poor outcomes of ARSi-treated castrate resistant PC (CRPC) patients and thus has the potential to guide patient management and also to stratify patients for clinical trials. More studies on chemotherapy-treated patients are warranted.

Systematic Review Registration

PROSPERO, CRD42021239353.
Action of Hyaluronic Acid as a Damage-Associated Molecular Pattern Molecule and Its Function on the Treatment of Temporomandibular Disorders
Authors: Ferreira Natália dos Reis , Sanz Carolina Kaminski , Raybolt Aline , Pereira Cláudia Maria , DosSantos Marcos Fabio
Published: March 2022

The temporomandibular joint is responsible for fundamental functions. However, mechanical overload or microtraumas can cause temporomandibular disorders (TMD). In addition to external factors, it is known that these conditions are involved in complex biological mechanisms, such as activation of the immune system, activation of the inflammatory process, and degradation of extracellular matrix (ECM) components. The ECM is a non-cellular three-dimensional macromolecular network; its most studied components is hyaluronic acid (HA). HA is naturally found in many tissues, and most of it has a high molecular weight. HA has attributed an essential role in the viscoelastic properties of the synovial fluid and other tissues. Additionally, it has been shown that HA molecules can contribute to other mechanisms in the processes of injury and healing. It has been speculated that the degradation product of high molecular weight HA in healthy tissues during injury, a low molecular weight HA, may act as damage-associated molecular patterns (DAMPs). DAMPs are multifunctional and structurally diverse molecules that play critical intracellular roles in the absence of injury or infection. However, after cellular damage or stress, these molecules promote the activation of the immune response. Fragments from the degradation of HA can also act as immune response activators. Low molecular weight HA would have the ability to act as a pro-inflammatory marker, promoting the activation and maturation of dendritic cells, the release of pro-inflammatory cytokines such as interleukin 1 beta (IL-1β), and tumor necrosis factor α (TNF-α). It also increases the expression of chemokines and cell proliferation. Many of the pro-inflammatory effects of low molecular weight HA are attributed to its interactions with the activation of toll-like receptors (TLRs 2 and 4). In contrast, the high molecular weight HA found in healthy tissues would act as an anti-inflammatory, inhibiting cell growth and differentiation, decreasing the production of inflammatory cytokines, and reducing phagocytosis by macrophages. These anti-inflammatory effects are mainly attributed to the interaction of high-weight HA with the CD44 receptor. In this study, we review the action of the HA as a DAMP and its functions on pain control, more specifically in orofacial origin (e.g., TMD).
Carbon Monoxide (CO), Nitric Oxide, and Hydrogen Sulfide Signaling During Acute CO Poisoning
Authors: Coburn Ronald F.
Published: March 2022

Major toxic effects of acute carbon monoxide (CO) poisoning result from increases in reactive oxygen species (ROS) and reactive nitrogen species (RNS) producing oxidative stress. The importance of altered nitric oxide (NO) signaling in evoking increases in RNS during CO poisoning has been established. Although there is extensive literature describing NO and hydrogen sulfide (H2S) signaling in different types of cells under normal conditions, how CO poisoning-evoked deregulation of additional NO signaling pathways and H2S signaling pathways could result in cell injury has not been previously considered in detail. The goal of this article was to do this. The approach was to use published data to describe signaling pathways driven by CO bonding to different ferroproteins and then to collate data that describe NO and H2S signaling pathways that could interact with CO signaling pathways and be important during CO poisoning. Arteriolar smooth muscle cells—endothelial cells located in the coronary and some cerebral circulations—were used as a model to illustrate major signaling pathways driven by CO bonding to different ferroproteins. The results were consistent with the concept that multiple deregulated and interacting NO and H2S signaling pathways can be involved in producing cell injury evoked during acute CO poisoning and that these pathways interact with CO signaling pathways.
Medication Use and Costs Among Older Adults Aged 90 Years and Older in Italy
Authors: Zazzara Maria Beatrice , Cangini Agnese , Da Cas Roberto , Ippoliti Ilaria , Marengoni Alessandra , Pierantozzi Andrea , Poluzzi Elisabetta , Zito Simona , Onder Graziano , the Italian Working Group on Medication Use in the Elderly
Published: March 2022

Older adults are often affected by multiple chronic conditions and experience geriatric syndromes that may affect the risk/benefit profile of medications. Little is known about the use of such medications in the older population. This article describes medication use and costs in Italian adults aged ≥90 years. Data from the 2019 Pharmaceutical Prescriptions database, concerning data on medications reimbursed by the Italian National Health Service, were analyzed in terms of prevalence and amount of use expressed as defined daily dose/1,000 users (DDD/1,000 users/day), accounting for different age-groups and sex. All individuals aged ≥90 years used at least one medication, with a mean number of 3128 DDD/1,000 users/day corresponding to an annual cost of 683 euros per user. Both use and costs linearly decreased with increasing age, with men accounting for a higher amount of DDD/1,000 users and costs than women across all age-groups. Antihypertensives (1330 DDD/1,000 inhabitants), antiplatelet agents (337 DDD/1,000 inhabitants), medications for peptic ulcer and gastroesophageal reflux (328 DDD/1,000 inhabitants), and lipid-lowering agents (166 DDD/1,000 inhabitants) were the most frequently used medications. We observed a progressive decrease in the usage of the majority of medications with increasing age, with the exception of antibiotics and antipsychotics. Individuals aged ≥90 years used a lower DDD/1,000 users, with an associated decrease in annual costs. The persistent use of preventive medications highlights the potential lack of awareness regarding medication rationalization and guidance for optimizing prescriptions. Our findings highlight the need for further initiatives to improve medications’ appropriateness in these older age-groups.
In Vivo Dopamine Neuron Imaging-Based Small Molecule Screen Identifies Novel Neuroprotective Compounds and Targets
Authors: Kim Gha-hyun J. , Mo Han , Liu Harrison , Okorie Meri , Chen Steven , Zheng Jiashun , Li Hao , Arkin Michelle , Huang Bo , Guo Su
Published: March 2022

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with prominent dopamine (DA) neuron degeneration. PD affects millions of people worldwide, but currently available therapies are limited to temporary relief of symptoms. As an effort to discover disease-modifying therapeutics, we have conducted a screen of 1,403 bioactive small molecule compounds using an in vivo whole organism screening assay in transgenic larval zebrafish. The transgenic model expresses the bacterial enzyme nitroreductase (NTR) driven by the tyrosine hydroxylase (th) promotor. NTR converts the commonly used antibiotic pro-drug metronidazole (MTZ) to the toxic nitroso radical form to induce DA neuronal loss. 57 compounds were identified with a brain health score (BHS) that was significantly improved compared to the MTZ treatment alone after FDR adjustment (padj<0.05). Independently, we curated the high throughput screening (HTS) data by annotating each compound with pharmaceutical classification, known mechanism of action, indication, IC50, and target. Using the Reactome database, we performed pathway analysis, which uncovered previously unknown pathways in addition to validating previously known pathways associated with PD. Non-topology-based pathway analysis of the screening data further identified apoptosis, estrogen hormone, dipeptidyl-peptidase 4, and opioid receptor Mu1 to be potentially significant pathways and targets involved in neuroprotection. A total of 12 compounds were examined with a secondary assay that imaged DA neurons before and after compound treatment. The z’-factor of this secondary assay was determined to be 0.58, suggesting it is an excellent assay for screening. Etodolac, nepafenac, aloperine, protionamide, and olmesartan showed significant neuroprotection and was also validated by blinded manual DA neuronal counting. To determine whether these compounds are broadly relevant for neuroprotection, we tested them on a conduritol-b-epoxide (CBE)-induced Gaucher disease (GD) model, in which the activity of glucocerebrosidase (GBA), a commonly known genetic risk factor for PD, was inhibited. Aloperine, olmesartan, and nepafenac showed significant protection of DA neurons in this assay. Together, this work, which combines high content whole organism in vivo imaging-based screen and bioinformatic pathway analysis of the screening dataset, delineates a previously uncharted approach for identifying hit-to-lead candidates and for implicating previously unknown pathways and targets involved in DA neuron protection.
Autophagy and Skin Diseases
Authors: Klapan Kim , Simon Dagmar , Karaulov Alexander , Gomzikova Marina , Rizvanov Albert , Yousefi Shida , Simon Hans-Uwe
Published: March 2022

Autophagy is a highly conserved lysosomal degradation system that involves the creation of autophagosomes, which eventually fuse with lysosomes and breakdown misfolded proteins and damaged organelles with their enzymes. Autophagy is widely known for its function in cellular homeostasis under physiological and pathological settings. Defects in autophagy have been implicated in the pathophysiology of a variety of human diseases. The new line of evidence suggests that autophagy is inextricably linked to skin disorders. This review summarizes the principles behind autophagy and highlights current findings of autophagy’s role in skin disorders and strategies for therapeutic modulation.
Ergothioneine as a Natural Antioxidant Against Oxidative Stress-Related Diseases
Authors: Fu Tong-Tong , Shen Liang
Published: March 2022

L-Ergothioneine (EGT) is a natural antioxidant derived from microorganisms, especially in edible mushrooms. EGT is found to be highly accumulated in tissues that are susceptible to oxidative damage, and it has attracted extensive attention due to its powerful antioxidant activity and the tight relationships of this natural product with various oxidative stress-related diseases. Herein, we 1) introduce the biological source and in vivo distribution of EGT; 2) review the currently available evidence concerning the relationships of EGT with diabetes, ischemia-reperfusion injury-related diseases like cardiovascular diseases and liver diseases, neurodegenerative diseases, and other diseases pathogenically associated with oxidative stress; 3) summarize the potential action mechanisms of EGT against these diseases; 4) discuss the advantages of EGT over other antioxidants; and 5) also propose several future research perspectives for EGT. These may help to promote the future application of this attractive natural antioxidant.
Set Size and Donation Behavior
Authors: Lindkvist Amanda M. , Luke Timothy J.
Published: March 2022

Choice overload is the phenomenon that increasing the number of options in an assortment makes choosing between options more difficult, sometimes leading to avoidance of making a choice. In this pre-registered online experiment (N = 501), choice overload was tested in a charitable behavior context, where participants faced a monetary donation choice. Charity organization assortment size was varied between groups, ranging between 2 and 80 options. The results indicate that there were no meaningful differences in donation likelihood between the 16 organization assortment sizes, neither for individuals with high preference certainty nor for individuals with uncertain preferences among charitable causes. Having more charitable organizations to choose from did not affect donation behavior.
Perceived Organizational Support and Proactive Innovation Behavior: The Mediating Role of Basic Psychological Needs
Authors: Fan Chuanhao , Tang Sijie , Chen Long , Sun Tingting
Published: March 2022

Drawing upon self-determination theory, this study aimed to explore the mechanisms underlying the impact of perceived organizational support on proactive innovation behavior and reveal the serial mediation effects of basic psychological needs. We collected time-lagged data of 481 employees from research institutions in China, and structural equation modeling analyses were carried out to test the hypotheses. The results indicate that perceived organizational support is significantly and positively related to proactive innovation behavior, and this relationship was mediated by the need for autonomy, competence, and relatedness. These findings contribute new knowledge to proactive innovation behavior by providing a new perspective of the satisfaction of psychological needs. Theoretical and practical implications are discussed.
Detecting Patient Safety Errors by Characterizing Incidents Reported by Medical Imaging Staff
Authors: Tarkiainen Tarja , Sneck Sami , Haapea Marianne , Turpeinen Miia , Niinimäki Jaakko
Published: March 2022

The objectives of the study were to characterize events related to patient safety reported by medical imaging personnel in Finland in 2007–2017, the number and quality of reported injuries, the risk assessment, and the planned improvement of operations. The information was collected from a healthcare patient safety incident register system. The data contained information on the nature of the patient safety errors, harms and near-misses in medical imaging, the factors that lead to the events, the consequences for the patient, the level of risks, and future measures. The number of patient safety incident reports included in the study was 7,287. Of the incident reports, 75% concerned injuries to patients and 25% were near-misses. The most common consequence of adverse events and near-misses were minor harm (37.2%) related to contrast agent, or no harm (27.9%) related to equipment malfunction. Supervisors estimated the risks as low (47.7%) e.g., data management, insignificant (35%) e.g., verbal communication or moderate (15.7%) e.g., the use of contrast agent. The most common suggestion for learning from the incident was discussing it with the staff (58.1%), improving operations (5.7%) and submitting it to a higher authority (5.4%). Improving patient safety requires timely, accurate and clear reporting of various patient safety incidents. Based on incident reports, supervisors can provide feedback to staff, develop plans to prevent accidents, and monitor the impact of measures taken. Information on the development of occupational safety should be disseminated to all healthcare professionals so that the same mistakes are not repeated.
Factors Associated With Oral Cancer Adverse Outcome at the Rwanda Military Hospital, a Retrospective Cross-Sectional Study
Authors: Ndayisabye Halifa , Ndagijimana Albert , Biracyaza Emmanuel , Umubyeyi Aline
Published: March 2022

Oral cancer (OC) is one of the most common cancers that remain global public health concerns in low- and middle-income countries. The epidemiology of OC in Africa endures uncertain. Earlier reports suggested a relatively low incidence of OC among Africans. Acting on behavioral factors and setting early diagnosis and treatments of OC can tremendously reduce morbidity and mortality related to it. This study determined factors associated with the OC adverse outcome and death in the Rwanda Military Hospital. A cross-sectional study was conducted among 311 medical records of patients who consulted in the Oral and Maxilla Facial Department between January 1, 2007 and December 31, 2019. Associated factors were estimated by use of odds ratios (OR) with their 95% confidence intervals (CI) in bivariate and multivariate logistic regression analyses to estimate predictors of an OC adverse outcome and death. Almost three quarters of the participants were from rural areas (n = 229, 73.6%) and alcohol users (n = 247, 79.1%). Concerning primary site infection, 54.02% of the participants had the intra-oral cavity within the past 5 years. Muslims had greater odds to experience an OC adverse outcome and death [aOR = 6.7; 95% CI (3.8–11.9), p < 0.001] than the Catholics. Those with no formal education significantly had greater likelihoods to have an OC adverse outcome and death [aOR = 2.6; 95% CI (1.3–5.3), p = 0.005] than those with higher education or university. Those with primary education had greater likelihoods [aOR = 1.8; 95% CI (1.1–3.1), p = 0.03] to have an OC adverse outcome than those with higher or university education. Those with oral hygiene had less risk to have an OC adverse outcome and death [aOR = 0.2; 95% CI (0.0–0.9), p = 0.039] than their counterparts. Using multi-sectorial approaches, including policy makers, clinicians, and researchers from public and private institutions, may be of an added value to promote clinical research on OC for earning knowledge, contributing to combat risk behaviors and improve the population's information and education on OC prevention.
Tinjauan Yuridis Pencabutan Hak Kewarganegaraan Mantan Anggota Organisasi Militan Ekstremis (ISIS) Perspektif Hukum Internasional dan Aturan Kewarganegaraan
Authors: Haqqi Abdullah Raden Aji , Yulianto Rohmad Adi , Mamang Damrah
Published: March 2022

Citizenship is a legal bond between a person and a country. Citizenship gives people an identity. According to the Universal Declaration of Human Rights affirms that "everyone has the right to a nationality", thus this declaration recognizes the importance of citizenship legally and practically for the fulfillment of human rights. Therefore, governments must work to ensure that everyone has a nationality. Former members of extremist militant organizations themselves can be interpreted as military groups (Army, Navy and Air Force), and militias and volunteer corps that meet these four requirements, are called “Former members”. They are justified in actively participating in hostilities. Also included in the ex-member group are: residents of an area that has not been occupied by the enemy, who spontaneously took up arms when organizing themselves, and carried weapons openly. Extremism is not really new. There has been a lot of extremist behavior that is usually associated with terrorist behavior and attacks against a group, both in Indonesia and abroad. Extremist behavior is slightly different from criminal behavior in general. The crimes committed by extremists are crimes based on the path they have chosen regarding their way of seeing the world. Law number 12 of 2006 concerning citizenship, it is stated in article 23 that Indonesian citizens will lose their citizenship in several ways, starting from the person concerned obtaining another citizenship, entering the service of a foreign army, entering the service of a foreign country, swearing allegiance to a foreign country. , participating in the elections of foreign countries, and several other matters mentioned in Chapter IV of the law. So even though it is true that ISIS itself is not a country as described in the writing of this thesis, this cannot be used as a basis for guiding that an Indonesian citizen who is a member of ISIS cannot lose his citizenship because it is clearly regulated in both laws and regulations. The government is what causes the Indonesian citizen to lose his citizenship automatically, not because of certain individuals who can decide whether or not a person's citizenship is lost or not.
atuação da medicina e da polícia sobre os loucos sergipanos (1907)
Authors: Emmanoel Menezes Santos Wagner
Published: March 2022

O início da república brasileira foi marcado por novas concepções sobre a loucura e os loucos na sociedade. Nesse momento, os médicos começaram a ganhar ainda mais expressão e se aliaram ao governo para tentar conter os grupos considerados degenerados, fazendo um controle sobre a saúde da população. Os loucos se tornaram um problema social e passaram a sofrer um controle da medicina e da polícia, que os retiraram das ruas e passaram a colocá-los em hospícios. O artigo tem o objetivo de discutir a atuação dos médicos e dos policiais sergipanos sobre os loucos que ficavam perambulando pelas ruas, bem como notar qual a solução encontrada para tal fato social. A fonte consultada foi o relatório do presidente do Estado de Sergipe, Guilherme de Sousa Campos, referente ao ano de 1907.
A infância e a adoção no Brasil:
Authors: Mergár Stella Scantamburlo de
Published: March 2022

A infância e a adoção são assuntos praticamente indissociáveis. No Brasil, a legislação referente à adoção somente surgiu efetivamente com o Código Civil de 1916, sendo que, durante quase três séculos, o instituto esteve situado em um limbo jurídico. Era comum, durante o período colonial brasileiro, a prática do costume pelas famílias de se acolher os “filhos de criação”, tendo inexistido uma preocupação efetiva em regular tais relações e os efeitos advindos delas. Diante desses fatos, é preciso reconstruir as práticas que antecederam à formatação do instituto da adoção, bem como analisar, ainda que rapidamente, a história da infância abandonada no Brasil até a promulgação do ECA.
Limpando o excesso de cinzas do passado para viver no presente:
Authors: Barrero Junior Roger Camacho , Costa Júnior José dos Santos
Published: March 2022

Longe de ser uma produção que recupera um passado histórico, a memória consiste em todo um trabalho de produção com intenso investimento social de sentidos sobre as experiências passadas. Como as historiadoras e historiadores podem ler a memória como objeto da História? Por meio do diálogo com dois importantes estudiosos da relação história/memória, Alessandro Portelli e Ulpiano Bezerra de Meneses, o texto constrói uma reflexão de caráter teórico-conceitual sobre o lugar da memória na operação historiográfica. A memória pode ser tratada como objeto da história. Tal estatuto impõe a tarefa de situar temporalmente sua produção e a rede de relações em que ela se dá, além dos atores, fins e recursos materiais e simbólicos envolvidos em sua elaboração e gestão social. Fazer a História enquanto trabalho intelectual metodologicamente embasado requer o exercício heurístico, e eminentemente ético, de não naturalizar a memória, mas compreendê-la enquanto produção fisiológica, cultural e politicamente situada. Desnaturalizar a memória para elaborar a história permite multiplicar as leituras do passado e abrir novos olhares sobre o presente.
Entre costumes e tipos
Authors: Santana Mirna Brito
Published: March 2022

O objetivo desse artigo é pensar nas últimas décadas do século XIX brasileiro e os discursos sobre razão, ordenamento social, modernização e progresso que começavam a ganhar fôlego sob a ótica científica. Para essa reflexão é utilizado como fonte o conto O Alienista de Machado de Assis, como crítica do literato sobre a cientificidade de seu tempo. Espera-se que o diálogo entre realidade e ficção crie compatibilidades, mas também dissonâncias que possam evidenciar a complexidade e contradições na definição de Brasil para os indivíduos desse tempo histórico.
Cinelândia Bauruense
Authors: Sales Barbosa Vinicius , Paride Pallotta Fabio
Published: March 2022

A cidade de Bauru possuiu no século XX seu crescimento exponencial devido à ferrovia, que possibilitou o comércio cafeeiro com outras regiões. A elitização dos espaços, causada por uma elite cafeeira, ocasionou a criação da Cinelândia Bauruense, complexo de cinemas de rua compreendidos no centro da cidade, semelhante ao construído nas cidades de São Paulo e Rio de Janeiro. O presente artigo buscou trabalhar a importância da História para a preservação da memória enquanto fundamento para a construção da identidade das sociabilidades urbanas. O esquecimento da memória coletiva da Cinelândia, marcado pelo declínio dos cinemas de rua devido ao nascimento dos cinemas no Shopping, ocasionou a transformação da identidade bauruense criada ao longo do século XX e remodelada no século XXI.
caso de família:
Authors: Moura Souza Priscila de
Published: March 2022

O estudo apresenta a conflituosa relação do saber médico com as práticas de cura e a intervenção no cotidiano dos citadinos, a partir da análise de dois processos-crime da década de 1940 na cidade de Parnaíba-PI. Pretende-se analisar os processos-crime e o desvelar de historicidades distintas, dando visibilidade a atores sociais diversos, as contradições e as tramas nos quais eles estão envolvidos.
Sanatório Domingos Freire (Belém-PA):
Authors: Costa Livia Gaby , Salvador Miranda Cybelle
Published: March 2022

Este artigo analisa a relação entre a higienização de Belém, e a construção do primeiro sanatório da capital, Sanatório Domingos Freire, inaugurado em 1900. Este equipamento congrega as ações de setorização da cidade modernizada em função da dinâmica proporcionada pela exportação da borracha. Do ponto de vista arquitetônico, a construção situa-se afastada do acesso principal; setorizada rigidamente entre espaços do limpo e do sujo, bem como entre os sexos, princípios compartilhados com outros sanatórios coetâneos no Brasil e em Portugal. Ao percorrer periódicos da época, depreende-se que, a despeito do discurso terapêutico que alude aos avanços da ciência moderna, o sanatório é visto de modo recorrente como local que condena à morte aqueles que para lá são conduzidos.
Da colher de pau ao fio da navalha
Authors: Corvello Cynthia
Published: March 2022

Este artigo propõe uma reflexão a partir de uma perspectiva de gênero sobre as relações de poder entre sujeitos criminalizados e instituições (re)produtoras de saber. A análise proposta tem como mote o laudo psiquiátrico que faz parte do acervo documental de uma das primeiras mulheres custodiadas no Instituto Penal Feminino Desembargadora Auri Moura Costa (IPFDAMC), inaugurado em agosto de 1974, na capital do estado do Ceará. Entende-se que a documentação produzida na instituição de confinamento se apresenta como fonte histórica privilegiada para a compreensão das tessituras entre o Direito e a Psiquiatria no esforço de patologização de mulheres cuja conduta rompia com ideias de feminilidade existentes do período. Utiliza-se ainda discursos presentes em outras fontes históricas como revistas médicas, leis, decretos e publicações oficiais, entre outras, no intuito de refletir sobre parte da historicidade dos saberes criminológicos e da produção de sujeitos e condutas criminalizáveis.