cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5129368.v1
title: Supplementary Material for: Expression of AQP1 Was Associated with Apoptosis and Survival of Patients in Gastric Adenocarcinoma

description: <b><i>Rationale and Objective:</i></b> Recently, interest in the role of aquaporin 1 (AQP1) in human gastrointestinal carcinogenesis has developed. However, to date no studies have examined relationships between AQP1 expression and specific characteristics of gastric adenocarcinoma. <b><i>Methods:</i></b> We investigated 109 specimens of primary gastric adenocarcinoma and their corresponding normal gastric mucosa using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine AQP1 expression. We then evaluated disease free survival (DFS) and overall survival (OS) in these patients in association with AQP1 expression. <b><i>Results:</i></b> Both immunohistochemical and RT-PCR analyses identified increased AQP1 expression in tumors from patients with gastric adenocarcinoma (p &lt; 0.001). The 3-year DFS and OS rates were higher in the AQP1-negative group than in the positive group (DFS: 77.2 vs. 52.8%, p &lt; 0.001; OS: 85.1 vs. 70.7%, p &lt; 0.001). The 5-year DFS and OS rates exhibited a similar trend (p &lt; 0.001). Subgroup analysis of patients with early gastric adenocarcinoma (stages I and II) revealed a total 5-year OS of 90.0%, with 5-year OS being higher in the AQP1-negative group than in the positive group (95.2 vs. 84.2%). Furthermore, incidence of tumor recurrence following surgical treatment was significantly higher in the AQP1-positive group (4/19, 21.1%) compared with the negative group (0/21, 0%). <b><i>Conclusions:</i></b> Our study demonstrates that AQP1 plays an important role in gastric adenocarcinoma and may therefore represent a novel therapeutic target and prognostic marker in this disease.
DOI: 10.6084/m9.figshare.5129350
title: Supplementary Material for: Blood-Cerebrospinal Fluid Barrier Integrity in Delirium Determined by Q-Albumin

description: <b><i>Background/Aims:</i></b> Delirium is a common and serious complication in hospitalised patients and its pathophysiology is incompletely understood. We aimed to examine whether blood-cerebrospinal fluid barrier dysfunction, as measured by Q-albumin (the ratio of cerebrospinal fluid albumin to serum albumin), was associated with delirium. <b><i>Methods:</i></b> In this prospective cohort study of hip fracture patients from Oslo University Hospital, Norway, serum was collected preoperatively and cerebrospinal fluid just before the onset of spinal anaesthesia. Albumin levels in serum and cerebrospinal fluid were analysed consecutively, and Q-albumin was calculated using the formula [cerebrospinal fluid albumin (mg/dl) × 1,000]/[serum albumin (mg/dl)]. Q-albumin &gt;10.2 was used as the cut-off for blood-cerebrospinal fluid barrier dysfunction. Patients were assessed daily for delirium using the Confusion Assessment Method. <b><i>Results:</i></b> Out of 120 patients, 69 had delirium, 22 had subsyndromal delirium, and 29 were free from delirium. The majority of patients, i.e. 106 (88%), had intact blood-cerebrospinal fluid barrier integrity, but all 14 patients with blood-cerebrospinal barrier dysfunction had delirium (n = 11) or subsyndromal delirium (n = 3). <b><i>Conclusions:</i></b> The results suggest that blood-cerebrospinal fluid barrier dysfunction may be relevant for delirium pathophysiology when it occurs. However, the low prevalence (16% of delirium patients) indicates that this is not a prerequisite for the development of delirium.
DOI: 10.6084/m9.figshare.5129353
title: Supplementary Material for: Neurocognitive Deficits and Effects of Cognitive Reserve in Mild Cognitive Impairment

description: <b><i>Background/Aims:</i></b> Mild cognitive impairment (MCI) is a frequent syndrome in the older population, which involves an increased risk to develop Alzheimer's disease (AD). The latter can be modified by the cognitive reserve, which can be operationalized by the length of school education. MCI can be differentiated into four subtypes according to the cognitive domains involved: amnestic MCI, multiple-domain amnestic MCI, non-amnestic MCI and multiple-domain non-amnestic MCI. While neurocognitive deficits are a constituent of the diagnosis of these subtypes, the question of how they refer to the cognitive reserve still needs to be clarified. <b><i>Methods:</i></b> We examined neuropsychological deficits in healthy controls, patients with MCI and patients with mild AD (n = 485) derived from a memory clinic. To reduce the number of neuropsychological variables, a factor analysis with varimax rotation was calculated. In a second step, diagnostic groups including MCI subtypes were compared with respect to their clinical and neuropsychological characteristics including cognitive reserve. <b><i>Results:</i></b> Most MCI patients showed the amnestic multiple-domain subtype followed by the pure amnestic subtype, while the non-amnestic subtypes were rare. The amnestic subtype displayed a significantly higher level of cognitive reserve and higher MMSE scores than the amnestic multiple-domain subtype, which was in most cases characterized by additional psychomotor and executive deficits. <b><i>Conclusions:</i></b> These findings confirm earlier reports revealing that the amnestic multiple-domain subtype is the most frequent one and indicating that a high cognitive reserve may primarily prevent psychomotor and executive deficits in MCI.
DOI: 10.6084/m9.figshare.5129347
title: Supplementary Material for: Novel Stratification of Mortality Risk by Kidney Disease Stage

description: <b><i>Background:</i></b> Chronic kidney disease (CKD) is a common disorder with a variable clinical course and it is associated with increased mortality. The Intermountain Risk Score (IMRS) is an electronic risk calculator that utilizes complete blood count (CBC) and basic metabolic panel (BMP) values to predict mortality in various healthcare populations. We hypothesized that IMRS would predict mortality in patients with CKD even with adjustment for serum phosphate and urinary albumin. <b><i>Methods:</i></b> Three thousand eight hundred seventy-two patients with CKD classes IIIA-V had IMRS calculated retrospectively and survival analysis was performed investigating 1- and 5-year mortality. Kaplan-Meier survival curves were generated for predefined IMRS groups of low, medium and high risk for CKD patients overall and by sex and CKD stage. Serum phosphate and urinary albumin/creatinine ratios were modeled in multivariate Cox-proportional hazard models. Receiver operator characteristic curves were used to determine c-statistics for mortality. <b><i>Results:</i></b> For all patients with CKD, mortality was significantly greater for those with medium- or high-risk compared to low-risk IMRS categories, among each CKD stage. Overall, IMRS was predictive of mortality at both 1 and 5 years, even when adjusted for CKD stage and predicted mortality more accurately than CKD stage alone. Albuminuria was not independently associated with mortality and serum phosphate weakly predicted mortality. <b><i>Conclusion:</i></b> IMRS is a strong predictor of mortality in patients with CKD and is robustly complementary to CKD stage in refining risk prediction. Given the universal availability and low cost of the CBC and BMP, IMRS may be of a substantial value in CKD risk assessment and management.
DOI: 10.6084/m9.figshare.5129350.v1
title: Supplementary Material for: Blood-Cerebrospinal Fluid Barrier Integrity in Delirium Determined by Q-Albumin

description: <b><i>Background/Aims:</i></b> Delirium is a common and serious complication in hospitalised patients and its pathophysiology is incompletely understood. We aimed to examine whether blood-cerebrospinal fluid barrier dysfunction, as measured by Q-albumin (the ratio of cerebrospinal fluid albumin to serum albumin), was associated with delirium. <b><i>Methods:</i></b> In this prospective cohort study of hip fracture patients from Oslo University Hospital, Norway, serum was collected preoperatively and cerebrospinal fluid just before the onset of spinal anaesthesia. Albumin levels in serum and cerebrospinal fluid were analysed consecutively, and Q-albumin was calculated using the formula [cerebrospinal fluid albumin (mg/dl) × 1,000]/[serum albumin (mg/dl)]. Q-albumin &gt;10.2 was used as the cut-off for blood-cerebrospinal fluid barrier dysfunction. Patients were assessed daily for delirium using the Confusion Assessment Method. <b><i>Results:</i></b> Out of 120 patients, 69 had delirium, 22 had subsyndromal delirium, and 29 were free from delirium. The majority of patients, i.e. 106 (88%), had intact blood-cerebrospinal fluid barrier integrity, but all 14 patients with blood-cerebrospinal barrier dysfunction had delirium (n = 11) or subsyndromal delirium (n = 3). <b><i>Conclusions:</i></b> The results suggest that blood-cerebrospinal fluid barrier dysfunction may be relevant for delirium pathophysiology when it occurs. However, the low prevalence (16% of delirium patients) indicates that this is not a prerequisite for the development of delirium.
DOI: 10.6084/m9.figshare.5129356.v1
title: Supplementary Material for: Programmed Cell Death Genes Are Linked to Elevated Creatine Kinase Levels in Unhealthy Male Nonagenarians

description: Declining health in the oldest-old takes an energy toll for the simple maintenance of body functions. The underlying mechanisms, however, differ in males and females. In females, the declines are explained by loss of muscle mass; but this is not the case in males, in whom they are associated with increased levels of circulating creatine kinase. This relationship raises the possibility that muscle damage rather than muscle loss is the cause of the increased energy demands of unhealthy aging in males. We have now examined factors that contribute to the increase in creatine kinase. Much of it (60%) can be explained by a history of cardiac problems and lower kidney function, while being mitigated by moderate physical activity, reinforcing the notion that tissue damage is a likely source. In a search for genetic risk factors associated with elevated creatine kinase, the Ku70 gene <i>XRCC6</i> and the ceramide synthase gene <i>LASS1</i> were investigated because of their roles in telomere length and longevity and healthy aging, respectively. Single nucleotide polymorphisms in these two genes were independently associated with creatine kinase levels. The <i>XRCC6</i> variant was epistatic to one of the <i>LASS1</i> variants but not to the other. These gene variants have potential regulatory activity. Ku70 is an inhibitor of the proapoptotic Bax, while the product of Lass1, ceramide, operates in both caspase-dependent and -independent pathways of programmed cell death, providing a potential cellular mechanism for the effects of these genes on tissue damage and circulating creatine kinase.
DOI: 10.6084/m9.figshare.5129341
title: Supplementary Material for: Early Vasospasm after Aneurysmal Subarachnoid Hemorrhage Predicts the Occurrence and Severity of Symptomatic Vasospasm and Delayed Cerebral Ischemia

description: <b><i>Background:</i></b> Cerebral vasospasm usually develops several days after subarachnoid hemorrhage (SAH) and is generally acknowledged as a strong outcome predictor. In contrast, much less is known about the nature and eventual consequences of early angiographic vasospasm (EAVS) seen on admission digital subtraction angiography (DSA). Therefore, we aimed at identifying the risk factors and clinical impact of EAVS after SAH. <b><i>Methods:</i></b> Five hundred and thirty-one SAH patients with admission DSA performed within 72 h after the bleeding event were selected from a comprehensive database containing all consecutive SAH patients treated at our institution between January 2005 and December 2012. Predictors of EAVS, as well as associations between EAVS and delayed vasospasm-related complications, and unfavorable outcome (defined as modified Rankin scale &gt;3) were evaluated in univariate and multivariate analyses. <b><i>Results:</i></b> EAVS was seen on 60 DSAs (11.3%) and was independently correlated with delayed symptomatic vasospasm requiring intra-arterial spasmolysis (OR 5.24, p &lt; 0.0001), angioplasty (OR 2.56, p = 0.015) and repetitive endovascular treatment (OR 4.71, p &lt; 0.0001). EAVS also increased the risk for multiple versus single territorial infarction on the follow-up CT scan(s) (OR 2.04, p = 0.047) and independently predicted unfavorable outcome (OR 2.93, p = 0.008). The presence of radiographic signs suspicious for fibromuscular dysplasia were independently associated with the occurrence of EAVS (OR 2.98, p = 0.026) and the need for repetitive endovascular vasospasm treatment (OR 3.95, p = 0.019). <b><i>Conclusions:</i></b> In view of the strong correlation with delayed symptomatic vasospasm and its ischemic complications, EAVS can be considered an alerting signal for severe symptomatic vasospasm. Therefore, more attention should be paid to the presence of EAVS on admission DSA.
DOI: 10.6084/m9.figshare.5129344
title: Supplementary Material for: Estradiol Rapidly Attenuates ORL-1 Receptor-Mediated Inhibition of Proopiomelanocortin Neurons via G<sub>q</sub>-Coupled, Membrane-Initiated Signaling

description: Estradiol rapidly regulates the activity of arcuate nucleus (ARH) proopiomelanocortin (POMC) neurons that project to the medial preoptic nucleus (MPN) to regulate lordosis. Orphanin FQ/nociceptin (OFQ/N) acts via opioid receptor-like (ORL)-1 receptors to inhibit these POMC neurons. Therefore, we tested the hypothesis that estradiol excites POMC neurons by rapidly attenuating inhibitory ORL-1 signaling in these cells. Hypothalamic slices through the ARH were prepared from ovariectomized rats injected with Fluorogold into the MPN. Electrophysiological recordings were generated in ARH neurons held at or near -60 mV, and neuronal phenotype was determined post hoc by immunohistofluorescence. OFQ/N application induced robust outward currents and hyperpolarizations via G protein-gated, inwardly rectifying K<sup>+</sup> (GIRK) channels that were attenuated by pretreatment with either 17-β estradiol (E<sub>2</sub>) or E<sub>2</sub> conjugated to bovine serum albumin. This was blocked by the estrogen receptor (ER) antagonist ICI 182,780 and mimicked by the G<sub>q</sub>-coupled membrane ER (G<sub>q</sub>-mER) ligand STX and the ERα agonist PPT. Inhibiting phosphatidylinositol-3-kinase (PI3K) blocked the estrogenic attenuation of ORL-1/GIRK currents. Antagonizing either phospholipase C (PLC), protein kinase C (PKC), protein kinase A (PKA) or neuronal nitric oxide synthase (nNOS) also abrogated E<sub>2</sub> inhibition of ORL-1/GIRK currents, whereas activation of PKC, PKA, protein kinase B (Akt) and nNOS substrate L-arginine all attenuated the OFQ/N response. This was observed in 92 MPN-projecting, POMC-positive ARH neurons. Thus, ORL-1 receptor-mediated inhibition of POMC neurons is rapidly and negatively modulated by E<sub>2</sub>, an effect which is stereoselective and membrane initiated via G<sub>q</sub>-mER and ERα activation that signals through PLC, PKC, PKA, PI3K and nNOS.
DOI: 10.6084/m9.figshare.5129335
title: Supplementary Material for: The Prevalence of Huntington's Disease

description: <b><i>Background:</i></b> Reviews of the epidemiology of Huntington's disease (HD) suggest that its worldwide prevalence varies widely. This review was undertaken to confirm these observations, to assess the extent to which differences in case-ascertainment and/or diagnosis might be responsible, and to investigate whether the prevalence pattern has changed over the past 50 years. <b><i>Methods:</i></b> Eighty two relevant studies were identified from Medline and Embase, previous reviews, scrutiny of references from included and excluded studies and enquiry among those interested in the field. <b><i>Results:</i></b> The lowest rates were among the Asians and the highest among the Caucasians. The differences are not fully explained by varying approaches to case-ascertainment or diagnosis. There was evidence of an increasing prevalence of between 15 and 20% per decade in studies from Australia, North America and Western Europe. <b><i>Conclusions:</i></b> The prevalence of HD varies more than tenfold between different geographical regions. This variation can in part be attributed to differences in case-ascertainment and/or diagnostic criteria, but there is consistent evidence of a lower incidence in Asian populations. There is also evidence that in Australia, North America and in Western Europe (including the United Kingdom), prevalence has increased over the past 50 plus years.
DOI: 10.6084/m9.figshare.5129323
title: Supplementary Material for: FP-CIT- and IBZM-SPECT in Corticobasal Syndrome: Results from a Clinical Follow-Up Study

description: <b><i>Objective:</i></b> To evaluate the striatal presynaptic dopamine transporter (FP-CIT-SPECT) and postsynaptic D<sub>2</sub> receptor (IBZM-SPECT) binding in patients with corticobasal syndrome (CBS). <b><i>Background:</i></b> FP-CIT and IBZM are commercially available and approved SPECT tracers for in vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration, but only few data for CBS are available. <b><i>Methods:</i></b> 23 patients meeting clinical criteria for early- to mid-stage CBS (disease duration ≤4 years) were examined with SPECT radiotracers FP-CIT and IBZM. All suspected CBS patients underwent a clinical follow-up examination and were re-evaluated after 19.7 ± 15.2 months (mean ± SD). Postmortem diagnosis was available for 2 patients. In patients who met research criteria for probable CBS at the final follow-up visit (n = 19; disease duration: 1.95 ± 0.91 years), SPECT binding values were compared to those of age- and gender-matched Parkinson's disease (PD) patients (n = 18, disease duration: 1.92 ± 0.91 years; clinical follow-up: 32 ± 29.6 months) and neurologically normal control subjects (n = 19). <b><i>Results:</i></b> In comparison to the healthy control subjects, both patient groups showed significant and asymmetric reduction of the striatal presynaptic dopamine transporter binding, but PD patients had significantly lower FP-CIT binding ratios than probable-CBS patients. FP-CIT binding values of probable-CBS patients and healthy controls demonstrated marked overlaps, and in 7 patients (39%) scans revealed no dopaminergic deficit. IBZM uptake did not show significant between-group differences. <b><i>Conclusion:</i></b> Our data indicate that in the early- to mid-stage CBS the degree of nigrostriatal impairment is only mild with a significant proportion of preserved dopamine transporter binding.
DOI: 10.6084/m9.figshare.5129332
title: Supplementary Material for: Muscle Strength and Fitness in Pediatric Obesity: a Systematic Review from the European Childhood Obesity Group

description: The increasing prevalence of paediatric obesity and related metabolic complications has been mainly associated with lower aerobic fitness while less is known regarding potential musculoskeletal impairments. The purpose of the present systematic review was to report the evidence regarding muscular fitness in children and adolescents with obesity. A systematic article search was conducted between November 2014 and June 2015 using MEDLINE, EMBASE, CINAHL psycINFO, SPORTDiscus and SocINDEX. Articles published in English and reporting results on muscle strength and muscular fitness in children and adolescents aged 6 to 18 years were eligible. Of 548 identified titles, 36 studies were included for analyses. While laboratory-based studies described higher absolute muscular fitness in youth with obesity compared with their lean peers, these differences are negated when corrected for body weight and lean mass, then supporting field-based investigations. All interventional studies reviewed led to improved muscular fitness in youth with obesity. Children and adolescents with obesity display impaired muscular fitness compared to healthy-weight peers, which seems mainly due to factors such as excessive body weight and increased inertia of the body. Our analysis also points out the lack of information regarding the role of age, maturation or sex in the current literature and reveals that routinely used field tests analysing overall daily muscular fitness in children with obesity provide satisfactory results when compared to laboratory-based data.
DOI: 10.6084/m9.figshare.5129326
title: Supplementary Material for: Pharmacological or Genetic Activation of Hsp70 Protects against Loss of Parkin Function

description: Mutations of parkin are a prevalent genetic contributor to familial Parkinson's disease (PD). As a key regulator of protein and mitochondrial homeostasis, parkin plays a pivotal role in maintaining dopaminergic neuronal survival. However, whereas <i>Drosophila</i> parkin null mutants exhibit prominent parkinsonian features, parkin-deficient mice generally lack an overt phenotype. Here, we found that the expression of Hsp70 along with several other members of the chaperone family is elevated in parkin null mice, suggesting a possible compensatory mechanism for the loss of parkin function in these mice that could have masked their phenotype. Supporting this, we demonstrate that the enhancement of chaperone function induced either pharmacologically via 17-AAG treatment or genetically via Hsp70 overexpression can protect cells against proteolytic and mitochondrial stress in a manner that is similar to that brought about by parkin overexpression. Importantly, we further showed that enhanced chaperone activity can ameliorate the pathological phenotypes in <i>Drosophila</i> parkin null mutants, which suggests the ability of chaperones to phenocopy parkin function. Taken together, our results suggest that Hsp members may act as compensatory factors for parkin loss of function and that the exploitation of these factors may be of potential therapeutic value.
DOI: 10.6084/m9.figshare.5129329
title: Supplementary Material for: Severe Short Stature in Two Siblings as the Presenting Sign of <b><i>ACP5</i></b> Deficiency

description: <b><i>Background:</i></b><i>ACP5</i> deficiency is known to cause spondyloenchondrodysplasia (SPENCD), which is characterized by various autoimmune and neurological symptoms in addition to short stature. <b><i>Methods:</i></b> Two siblings from a consanguineous Turkish family, a girl aged 13 years (P1) and a boy aged 8 years (P2), presented to their endocrinologist with progressive growth failure and severe short stature (-5 SDS). They had no comorbid conditions and, on physical examination, there were no signs of an overt skeletal dysplasia with normal appearance of extremities. Other than a low baseline IGF-1, extensive laboratory workup, including growth hormone stimulation and IGF-1 generation tests, was normal. Exome sequencing was performed. <b><i>Results:</i></b> Exome sequencing identified the presence of a homozygous frameshift mutation (p.Ser258Trpfs*39) in <i>ACP5</i> in both siblings, which was confirmed by Sanger sequencing. This specific mutation has previously been described in patients with SPENCD. Additional workup in the two siblings showed distinct features of skeletal dysplasia on X-rays consistent with SPENCD, but none of the common autoimmune or neurological abnormalities associated with this condition. <b><i>Conclusion:</i></b> Severe short stature can be the only presenting sign of <i>ACP5</i> deficiency and the latter could therefore be considered as a rare cause in the differential diagnosis of severe, proportionate growth failure.