cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5124187.v1
title: Supplementary Material for: Brain-Site-Specific Proteome Changes Induced by Neuronal P60TRP Expression

description: p60 transcription regulator protein (p60TRP) facilitates the processing of the amyloid precursor protein towards the non-amyloidogenic pathway by inhibiting the β-secretase action. This protein was initially identified to be downregulated in the temporal lobe of brains from Alzheimer's disease patients. p60TRP is one of the G-protein-coupled receptor (GPCR)-associated proteins which directly influences the signalling capacity of GPCRs. In the present study, we investigated the brain-region-specific proteome profile of transgenic p60TRP mice to gain an insight into the molecular events mediated by the long-term effect of neuronal p60TRP overexpression on brain proteome changes and its potential implication for neuronal functions in the central nervous system. Using a proteomics research approach based on isobaric tags for relative and absolute quantitation, we identified 2,025 proteins, whereby 1,735 proteins were quantified, out of which 56 were found to be significantly altered in the cortex and/or hippocampus of neuronal transgenic neuronal p60TRP mice. Our data suggests that in vivo overexpression of neuronal p60TRP significantly affects cognitive and neuroprotective capacities.
DOI: 10.6084/m9.figshare.5124178
title: Supplementary Material for: Peptide Receptor Radionuclide Therapy (PRRT) in a Patient Affected by Metastatic Breast Cancer with Neuroendocrine Differentiation

description: <b><i>Background: </i></b>Breast cancer (BC) is the most frequent cancer in European women with nearly 30% of the patients eventually developing metastases. Neuroendocrine differentiation is a rare event, but overexpression of somatostatin receptors in BC has been reported in many studies. <b><i>Case Report: </i></b>A patient with liver metastases from BC was treated with peptide receptor radionuclide therapy (PRRT). Computed tomography scan and biochemical examinations showed a clear response to radionuclide therapy. <b><i>Conclusion: </i></b>PRRT may be useful in metastatic BC patients.
DOI: 10.6084/m9.figshare.5124181
title: Supplementary Material for: Gowers’ Queen Square Case Notes on Chorea: A 21st Century Re-Appraisal

description: <b><i>Objective:</i></b> To analyze the case notes of 127 patients with chorea admitted to the National Hospital at Queen Square, London, under the care of William Richard Gowers and review his contribution to the study of choreas. <b><i>Methods:</i></b> We consulted the case books available at the Queen Square Library, from 1878 to 1911, comprising 42 volumes. <b><i>Results:</i></b> 97 patients (76.3%) were female and the age of presentation ranged from 4 to 60 years (mean 14.3). 43 patients (33.8%) experienced recurrent attacks of chorea. 29 patients (22.8%) had a family history of chorea. Past history of rheumatic fever was observed in 46 patients (36.2%). 54 patients (42.5%) had speech impairment while a similar number had a cardiac murmur. Generalized chorea occurred in 87.4% and hemichorea in 11.8%. Gowers diagnosed different forms of chorea: Huntington’s disease, paralytic, persistent, recurrent, tetanoid, functional, maniacal, hemichorea and chorea gravidarum. <b><i>Conclusions:</i></b> Gowers was one of the pioneers in recognizing chorea as a physical sign found in a myriad of etiologies. He also provided a comprehensive description of the clinical features and natural history of Sydenham’s chorea in his work.
DOI: 10.6084/m9.figshare.5124190.v1
title: Supplementary Material for: Developmental Changes in Voltage-Gated Calcium Channel α<sub>2</sub>δ-Subunit Expression in the Canine Dorsal Root Ganglion

description: The voltage-gated calcium channel subunit α<sub>2</sub>δ plays a fundamental role in propagation of excitatory signals associated with release of glutamate and neuropeptides substance P (SP) and calcitonin gene-related protein (CGRP). It can be selectively inhibited by gabapentinoids. Hence, investigation of the α<sub>2</sub>δ subunit may predict the efficacy of gabapentinoid therapy in neuropathic pain. Since sensory processing underlies significant age-related changes, this study was conducted in order to elucidate the role of the α<sub>2</sub>δ subunit in the sensory transmission during canine development. Dorsal root ganglia (DRG) were harvested from four spinal segments of 16 puppies and 10 adult dogs without a history of neurological signs, pain, spinal disease or orthopedic disorders. α<sub>2</sub>δ-Subunit expression and coexpression with SP and CGRP was evaluated immunohistochemically regarding the number of immunopositive ganglion cells, staining intensity and subcellular distribution. All tested ganglia were immunopositive for α<sub>2</sub>δ. Cell counts and expression levels were significantly lower in pups than in adult dogs (p &lt; 0.05). In the cervical segments of both groups, the number and percentage of immunopositive neurons was significantly higher than in lumbar DRG (p &lt; 0.05). Multilabeling studies in all tested animals confirmed the coexpression of α<sub>2</sub>δ and pain peptides SP and CGRP. This anatomical study for the first time documents the involvement of α<sub>2</sub>δ subunits in sensory signal processing in dogs. The proportion of positive neurons and the intracellular expression levels show a net increase from early postnatal life to adulthood. A significant portion of α<sub>2</sub>δ-positive cells in the dogs exhibited C- and Aδ-phenotypes compatible with nociceptive neurons. The coexpression of α<sub>2</sub>δ, SP and CGRP imply that these neurons are involved with peptidergic nociception. The cervicolumbar gradient of α<sub>2</sub>δ expression in adults reflects functional differences in between forelimbs and hind limbs. These data will facilitate translational studies on neuropathic pain states in this species such as common canine nerve entrapment syndromes.
DOI: 10.6084/m9.figshare.5124172
title: Supplementary Material for: No Evidence for Effects of a High-Frequency Repetitive Transcranial Magnetic Stimulation Series on Verbal and Figural Fluency and TAP Task Performance in Healthy Male Volunteers

description: <b><i>Background:</i></b> Study results on cognitive effects of repetitive transcranial magnetic stimulation (rTMS) in healthy people are inconsistent. Moreover, former trials performed exclusively single-session stimulations. This sham-controlled study analyzed the influence of 9 serial high-frequency rTMS on cognition. <b><i>Methods:</i></b> 44 young healthy male volunteers received active or sham rTMS. We evaluated verbal fluency tasks, the Ruff Figural Fluency Test and different Test for Attentional Performance tasks (alertness, go/no-go, divided attention, working memory, flexibility) prior to the first stimulation, immediately (within 5–30 min) after stimulation on day 5 and on day 10 (1 day after the last stimulation). <b><i>Results:</i></b> Overall, our statistical analyses revealed no significant cognitive effects of serial rTMS. <b><i>Conclusion:</i></b> In this sham-controlled study design, 9 serial rTMS over the left dorsolateral prefrontal cortex (targeted by the 5-cm rule) did neither enhance nor impair the assessed cognitive functions in healthy male volunteers.
DOI: 10.6084/m9.figshare.5124175
title: Supplementary Material for: Risk Score for Predicting Recurrence in Patients with Ischemic Stroke: The Fukuoka Stroke Risk Score for Japanese

description: <b><i>Background:</i></b> Currently, there are only a few risk scores to predict long-term recurrence of ischemic stroke and no risk score has been developed for the Asian population. The aim of the present study was to develop a new risk score to predict 1-year recurrence in Japanese patients with ischemic stroke and compare it with the other ones. <b><i>Methods:</i></b> Data used in this analysis were extracted from the Fukuoka stroke registry (FSR) database, including 3,067 Japanese patients who experienced ischemic stroke. FSR is a multicenter, hospital-based, prospective registry of Japanese patients with acute stroke. Associations between potential clinical variables that could be involved in the increase of risk and recurrence of ischemic stroke within 1 year after initial stroke onset were evaluated using univariate and multivariate analyses. To calculate risk scores, weighted points proportionally based on standardized coefficient values were assigned to variables that were identified to be significant risks for recurrence by multivariate analysis. The Hosmer-Lemeshow goodness-of-fit test was used to test agreement between a predicted outcome using a model and an actual observed outcome. Kaplan-Meier analysis was used to estimate average cumulative recurrence rates within three risk groups. Intergroup comparisons in recurrence rate among the risk groups were performed using a log-rank test. <b><i>Results:</i></b> Univariate and multivariate analyses identified nine significant predictors for 1-year recurrence, to which we assigned the following points: age (65–74 years, 1 point; ≥75 years, 2 points), hypertension (1 point), diabetes mellitus (1 point), smoker (1 point), atrial fibrillation (1 point), cardiac diseases (1 point), chronic kidney disease (1 point), nonlacunar stroke (1 point), and previous ischemic stroke (2 points). The Hosmer-Lemeshow goodness-of-fit test demonstrated good agreement between the observed and predicted recurrence rate (χ<sup>2</sup> = 2.30, p = 0.97). The ROC curve for the risk score models showed acceptable discriminant power with a C-statistic of 0.636 (95% confidence interval: 0.573–0.698). Trends toward increased risk of recurrence with higher scores were observed. The 1-year recurrence rates were 2.93, 5.83 and 7.96% in low- (≤3 points), intermediate (4–5 points), and high-risk groups (≥6 points), respectively. Kaplan-Meier curves with log-rank test showed a significant difference in recurrence among the three risk groups (p &lt; 0.0001). <b><i>Conclusions:</i></b> A new risk score was developed and successfully validated. Our results suggest that this simple risk score enables clinicians to assess 1-year recurrence risk in Japanese patients with ischemic stroke.
DOI: 10.6084/m9.figshare.5124181.v1
title: Supplementary Material for: Gowers’ Queen Square Case Notes on Chorea: A 21st Century Re-Appraisal

description: <b><i>Objective:</i></b> To analyze the case notes of 127 patients with chorea admitted to the National Hospital at Queen Square, London, under the care of William Richard Gowers and review his contribution to the study of choreas. <b><i>Methods:</i></b> We consulted the case books available at the Queen Square Library, from 1878 to 1911, comprising 42 volumes. <b><i>Results:</i></b> 97 patients (76.3%) were female and the age of presentation ranged from 4 to 60 years (mean 14.3). 43 patients (33.8%) experienced recurrent attacks of chorea. 29 patients (22.8%) had a family history of chorea. Past history of rheumatic fever was observed in 46 patients (36.2%). 54 patients (42.5%) had speech impairment while a similar number had a cardiac murmur. Generalized chorea occurred in 87.4% and hemichorea in 11.8%. Gowers diagnosed different forms of chorea: Huntington’s disease, paralytic, persistent, recurrent, tetanoid, functional, maniacal, hemichorea and chorea gravidarum. <b><i>Conclusions:</i></b> Gowers was one of the pioneers in recognizing chorea as a physical sign found in a myriad of etiologies. He also provided a comprehensive description of the clinical features and natural history of Sydenham’s chorea in his work.
DOI: 10.6084/m9.figshare.5124184.v1
title: Supplementary Material for: Specific Collaborative Group Intervention for Patients with Medically Unexplained Symptoms in General Practice: A Cluster Randomized Controlled Trial

description: <b><i>Background:</i></b> Patients with medically unexplained symptoms (MUS) are frequent in primary care and substantially impaired in their quality of life (QoL). Specific training of general practitioners (GPs) alone did not demonstrate sustained improvement at later follow-up in current reviews. We evaluated a collaborative group intervention. <b><i>Methods:</i></b> We conducted a cluster randomized controlled trial. Thirty-five GPs recruited 304 MUS patients (intervention group: 170; control group: 134). All GPs were trained in diagnosis and management of MUS (control condition). Eighteen randomly selected intervention GPs participated in training for a specific collaborative group intervention. They conducted 10 weekly group sessions and 2 booster meetings in their practices, together with a psychosomatic specialist. Six and 12 months after baseline, QoL was assessed with the Short-Form 36. The primary outcome was the physical composite score (PCS), and the secondary outcome was the mental composite score (MCS). <b><i>Results:</i></b> At 12 months, intention-to-treat analyses showed a significant between-group effect for the MCS (p = 0.023) but not for the PCS (p = 0.674). This effect was preceded by a significant reduction of somatic symptom severity (15-item somatic symptom severity scale of the Patient Health Questionnaire, PHQ-15) at 6 months (p = 0.008) that lacked significance at 12 months (p = 0.078). As additional between-group effects at 12 months, per-protocol analyses showed less health anxiety (Whiteley-7; p = 0.038) and less psychosocial distress (PHQ; p = 0.024); GP visits were significantly (p = 0.042) reduced in the intervention group. <b><i>Conclusions:</i></b> Compared to pure GP training, collaborative group intervention achieved a progressive, clinically meaningful improvement in mental but not physical QoL. It could bridge gaps between general practice and mental health care.
DOI: 10.6084/m9.figshare.5124169
title: Supplementary Material for: Renoprotection by Continuous Erythropoietin Receptor Activator in Puromycin Aminonucleoside-Induced Nephrotic Syndrome

description: <b><i>Background/Aims:</i></b> Recent studies have demonstrated that erythropoiesis-stimulating agents (ESAs) induce a tissue-protective effect in the kidney. In this study, we examined whether continuous erythropoietin receptor activator (CERA), a long-acting ESA, could prevent kidney injury, especially podocyte damage, in a rat model of nephrotic syndrome induced by puromycin aminonucleoside (PAN). <b><i>Methods:</i></b> Rats were injected with CERA (30 µg/kg) or vehicle 4 h before the injection of PAN (50 mg/kg). Renal function, kidney injury, and podocyte damage were assessed at 7 days. <b><i>Results:</i></b> The levels of proteinuria, BUN, and plasma creatinine significantly increased in rats with PAN-induced nephrosis. Treatment with CERA significantly prevented these deteriorations induced by PAN. Glomerular lesions, especially vacuolation of podocytes, and the increase of desmin expression in PAN-treated rats were significantly ameliorated by treatment with CERA. Treatment with CERA also significantly prevented the decrease in the protein productions of nephrin and podocin in the kidneys of PAN-treated rats. We found persistent activation of the Akt signaling pathway in the kidneys of CERA-treated rats. <b><i>Conclusion:</i></b> CERA could ameliorate renal dysfunction in PAN-induced nephrosis, which might be due to the amelioration of podocyte injury. CERA inhibited the depletion of nephrin and podocin, key components of the glomerular filtration barrier, and alleviated proteinuria. Activation of the Akt signaling pathway might be involved in the renoprotective effect of CERA
DOI: 10.6084/m9.figshare.5124163
title: Supplementary Material for: Glycolytic and Mitochondrial Metabolism in Pancreatic Islets from MSG-Treated Obese Rats Subjected to Swimming Training

description: <b><i>Backgrounds/Aims: </i></b>Obese rats obtained by neonatal monosodium glutamate (MSG) administration present insulin hypersecretion. The metabolic mechanism by which glucose catabolism is coupled to insulin secretion in the pancreatic β-cells from MSG-treated rats is understood. The purpose of this study was to evaluate glucose metabolism in pancreatic islets from MSG-treated rats subjected to swimming training. <b><i>Methods: </i></b>MSG-treated and control (CON) rats swam for 30 minutes (3 times/week) over a period of 10 weeks. Pancreatic islets were isolated and incubated with glucose in the presence of glycolytic or mitochondrial inhibitors. <b><i>Results: </i></b>Swimming training attenuated fat pad accumulation, avoiding changes in the plasma levels of lipids, glucose and insulin in MSG-treated rats. Adipocyte and islet hypertrophy observed in MSG-treated rats were attenuated by exercise. Pancreatic islets from MSG-treated obese rats also showed insulin hypersecretion, greater glucose transporter 2 (GLUT2) expression, increased glycolytic flux and reduced mitochondrial complex III activity. <b><i>Conclusion: </i></b>Swimming training attenuated islet hypertrophy and normalised GLUT2 expression, contributing to a reduction in the glucose responsiveness of pancreatic islets from MSG-treated rats without altering glycolytic flux. However, physical training increased the activity of mitochondrial complex III in pancreatic islets from MSG-treated rats without a subsequent increase in glucose-induced insulin secretion.
DOI: 10.6084/m9.figshare.5124175.v1
title: Supplementary Material for: Risk Score for Predicting Recurrence in Patients with Ischemic Stroke: The Fukuoka Stroke Risk Score for Japanese

description: <b><i>Background:</i></b> Currently, there are only a few risk scores to predict long-term recurrence of ischemic stroke and no risk score has been developed for the Asian population. The aim of the present study was to develop a new risk score to predict 1-year recurrence in Japanese patients with ischemic stroke and compare it with the other ones. <b><i>Methods:</i></b> Data used in this analysis were extracted from the Fukuoka stroke registry (FSR) database, including 3,067 Japanese patients who experienced ischemic stroke. FSR is a multicenter, hospital-based, prospective registry of Japanese patients with acute stroke. Associations between potential clinical variables that could be involved in the increase of risk and recurrence of ischemic stroke within 1 year after initial stroke onset were evaluated using univariate and multivariate analyses. To calculate risk scores, weighted points proportionally based on standardized coefficient values were assigned to variables that were identified to be significant risks for recurrence by multivariate analysis. The Hosmer-Lemeshow goodness-of-fit test was used to test agreement between a predicted outcome using a model and an actual observed outcome. Kaplan-Meier analysis was used to estimate average cumulative recurrence rates within three risk groups. Intergroup comparisons in recurrence rate among the risk groups were performed using a log-rank test. <b><i>Results:</i></b> Univariate and multivariate analyses identified nine significant predictors for 1-year recurrence, to which we assigned the following points: age (65–74 years, 1 point; ≥75 years, 2 points), hypertension (1 point), diabetes mellitus (1 point), smoker (1 point), atrial fibrillation (1 point), cardiac diseases (1 point), chronic kidney disease (1 point), nonlacunar stroke (1 point), and previous ischemic stroke (2 points). The Hosmer-Lemeshow goodness-of-fit test demonstrated good agreement between the observed and predicted recurrence rate (χ<sup>2</sup> = 2.30, p = 0.97). The ROC curve for the risk score models showed acceptable discriminant power with a C-statistic of 0.636 (95% confidence interval: 0.573–0.698). Trends toward increased risk of recurrence with higher scores were observed. The 1-year recurrence rates were 2.93, 5.83 and 7.96% in low- (≤3 points), intermediate (4–5 points), and high-risk groups (≥6 points), respectively. Kaplan-Meier curves with log-rank test showed a significant difference in recurrence among the three risk groups (p &lt; 0.0001). <b><i>Conclusions:</i></b> A new risk score was developed and successfully validated. Our results suggest that this simple risk score enables clinicians to assess 1-year recurrence risk in Japanese patients with ischemic stroke.
DOI: 10.6084/m9.figshare.5124178.v1
title: Supplementary Material for: Peptide Receptor Radionuclide Therapy (PRRT) in a Patient Affected by Metastatic Breast Cancer with Neuroendocrine Differentiation

description: <b><i>Background: </i></b>Breast cancer (BC) is the most frequent cancer in European women with nearly 30% of the patients eventually developing metastases. Neuroendocrine differentiation is a rare event, but overexpression of somatostatin receptors in BC has been reported in many studies. <b><i>Case Report: </i></b>A patient with liver metastases from BC was treated with peptide receptor radionuclide therapy (PRRT). Computed tomography scan and biochemical examinations showed a clear response to radionuclide therapy. <b><i>Conclusion: </i></b>PRRT may be useful in metastatic BC patients.
DOI: 10.6084/m9.figshare.5124166
title: Supplementary Material for: Canonical Bcl-2 Motifs of the Na<sup>+</sup>/K<sup>+</sup> Pump Revealed by the BH3 Mimetic Chelerythrine: Early Signal Transducers of Apoptosis?

description: <b><i>Background/Aims: </i></b>Chelerythrine [CET], a protein kinase C [PKC] inhibitor, is a prop-apoptotic BH3-mimetic binding to BH1-like motifs of Bcl-2 proteins. CET action was examined on PKC phosphorylation-dependent membrane transporters (Na<sup>+</sup>/K<sup>+</sup> pump/ATPase [NKP, NKA], Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>+</sup> [NKCC] and K<sup>+</sup>-Cl<sup>-</sup> [KCC] cotransporters, and channel-supported K<sup>+</sup> loss) in human lens epithelial cells [LECs]. <b><i>Methods: </i></b>K<sup>+</sup> loss and K<sup>+</sup> uptake, using Rb<sup>+</sup> as congener, were measured by atomic absorption/emission spectrophotometry with NKP and NKCC inhibitors, and Cl<sup>-</sup> replacement by NO<sub>3</sub><sup>ˉ</sup> to determine KCC. <sup>3</sup>H-Ouabain binding was performed on a pig renal NKA in the presence and absence of CET. Bcl-2 protein and NKA sequences were aligned and motifs identified and mapped using PROSITE in conjunction with BLAST alignments and analysis of conservation and structural similarity based on prediction of secondary and crystal structures. <b><i>Results: </i></b>CET inhibited NKP and NKCC by &gt;90% (IC<sub>50</sub> values ∼35 and ∼15 µM, respectively) without significant KCC activity change, and stimulated K<sup>+</sup> loss by ∼35% at 10-30 µM. Neither ATP levels nor phosphorylation of the NKA α1 subunit changed. <sup>3</sup>H-ouabain was displaced from pig renal NKA only at 100 fold higher CET concentrations than the ligand. Sequence alignments of NKA with BH1- and BH3-like motifs containing pro-survival Bcl-2 and BclXl proteins showed more than one BH1-like motif within NKA for interaction with CET or with BH3 motifs. One NKA BH1-like motif (ARAAEILARDGPN) was also found in all P-type ATPases. Also, NKA possessed a second motif similar to that near the BH3 region of Bcl-2. <b><i>Conclusion: </i></b>Findings support the hypothesis that CET inhibits NKP by binding to BH1-like motifs and disrupting the α<sub>1</sub> subunit catalytic activity through conformational changes. By interacting with Bcl-2 proteins through their complementary BH1- or BH3-like-motifs, NKP proteins may be sensors of normal and pathological cell functions, becoming important yet unrecognized signal transducers in the initial phases of apoptosis. CET action on NKCC1 and K<sup>+</sup> channels may involve PKC-regulated mechanisms; however, limited sequence homologies to BH1-like motifs cannot exclude direct effects.