Miracle-dz/UniFAR-FTUs huggingface dataset:
Grade-dependent Proteomics Characterization of Kidney Cancer*S

Kidney cancer is frequently metastatic on presentation at which point the disease is associated with a 95% mortality. Assessment of tumor grade on pathological examination is the most powerful means for prognostication as well as for stratification of patients into those who might respond to conventional or targeted therapy. Although there exist several grading systems in common use, all suffer from significant disparity among observers. In an attempt to objectify this process as well as to acquire grade-specific mechanistic information, we performed LC-MS/MS-based proteomics analysis on 50 clear cell kidney cancers equally distributed among normal tissues and Fuhrman grades 1–4. Initial experiments confirmed the utility of using archived formalin-fixed paraffin-embedded samples for LC-MS/MS-based proteomics analysis, and the LC-MS/MS findings were validated by extensive immunoblotting. We now show that changes among many biochemical processes and pathways are strongly grade-dependent with the glycolytic and amino acid synthetic pathways highly represented. In addition, proteins relating to acute phase and xenobiotic metabolism signaling are highly represented. Self-organized mapping of proteins with similar patterns of expression led to the creation of a heat map that will be useful in grade characterization as well as in future research relating to oncogenic mechanisms and targeted therapies for kidney cancer.
Patients with brain contusions: predictors of outcome and relationship between radiological and clinical evolution.

OBJECT Traumatic parenchymal mass lesions are common sequelae of traumatic brain injuries (TBIs). They occur in up to 8.2% of all TBI cases and 13%-35% of severe TBI cases, and they account for up to 20% of surgical intracranial lesions. Controversy exists concerning the association between radiological and clinical evolution of brain contusions. The aim of this study was to identify predictors of unfavorable outcome, analyze the evolution of brain contusions, and evaluate specific indications for surgery. METHODS In a retrospective, multicenter study, patients with brain contusions were identified in separate patient cohorts from 11 hospitals over a 4-year period (2008-2011). Data on clinical parameters and course of the contusion were collected. Radiological parameters were registered by using CT images taken at the time of hospital admission and at subsequent follow-up times. Patients who underwent surgical procedures were identified. Outcomes were evaluated 6 months after trauma by using the Glasgow Outcome Scale-Extended. RESULTS Multivariate analysis revealed the following reliable predictors of unfavorable outcome: 1) increased patient age, 2) lower Glasgow Coma Scale score at first evaluation, 3) clinical deterioration in the first hours after trauma, and 4) onset or increase of midline shift on follow-up CT images. Further multivariate analysis identified the following as statistically significant predictors of clinical deterioration during the first hours after trauma: 1) onset of or increase in midline shift on follow-up CT images (p < 0.001) and 2) increased effacement of basal cisterns on follow-up CT images (p < 0.001). CONCLUSIONS In TBI patients with cerebral contusion, the onset of clinical deterioration is predictably associated with the onset or increase of midline shift and worsened status of basal cisterns but not with hematoma or edema volume increase. A combination of clinical deterioration and increased midline shift/basal cistern compression is the most reasonable indicator for surgery.
The electronic structures of manganese oxide minerals

Molecular orbital calculations, using the Xa scattered wave method, were done for the clusters MnOl,0-, MnO? -, and MnOB- corresponding to Mn2*, Mn3*, and Mna* in octahedral coordination with O2-. Bond lengths representative of those observed in manganese oxides were chosen and 05 symmetry was used for each cluster. The calculated orbital energies and charge distributions are used to describe the nature of chemical bonding in manganese oxides. Spectroscopic transition energies are calculated and these are compared with experimental optical, X-ray emission and photoelectron (Esca) spectra of manganese oxides. The agreement between the calculated and experimental spectroscopic transition energies is fairly good and indicates that isolated clusters can be used to model the localized aspects of the electronic structure of manganese oxide minerals. The electronic structure ofthese clusters can also be related to the crystal chemistry of the manganese oxides. In spite of radius ratio considerations, Mna* is found to be considerably more stable in octahedral rather than tetrahedral coordination. This is demonstrated by comparing the electronic structure of MnOS- with that of a tetrahedral MnOX- cluster. A large degree of covalency in the MnOS- cluster is consistent with the strong Lewis acidity of Mna*. In contrast, the bonding in MnOl,O- is mostly ionic. The calculated exchange splittings of the crystal field orbitals show that low-spin Mn2* should not exist even under high-pressure, but that low spin Mn3* may substitute for Mna* in manganese (IV) oxides.
Risk Factors for Seizures in Children with Cerebral Palsy – A Descriptive Study

Background: Children between the age group of 1 to 12 years suffering from cerebral palsy with and without seizures have a higher risk of mortality and morbidity. Few interventions likely to be beneficial like maternal risk factors, antenatal, natal, postnatal growth and development, neonatal seizures and its related complications 1 . Aims and objectives: To find out the risk factors for Seizures in children with Cerebral Palsy. To study maternal physical and socio-economic risk factors responsible for cerebral palsy and seizures in cerebral palsy also to identify significant modifiable risk factors for cerebral palsy in the locality, if any, and point out strategic measures to favourably modify those. Materials and methods: It is a descriptive, Matched pair, case-control study. The study was done on Cerebral palsy babies in Karpaga Vinayaga Institute of Medical Science & Research Centre, Kanchipuram, Tamilnadu during the period of January 2011-April 2016. This was a retrospective descriptive study of children with cerebral palsy (with and without seizures) were admitted. Obstetrical and maternal risk factors,natal and neonatal, growth and development upto the age of 12 years were collected. Overall 400 children were included in this study, Cerebral palsy children with and without seizures. Results: Out of total 400children during 4years and 3 months (January 2011 – April 2016), there were 200 children had cerebral palsy without seizures and remaining children had cerebral palsy with seizures. The male population were 62.3% & female were37.7%. Conclusions: Maternal factors like Age, socio-economic status (SES), parity, height, pre-pregnancy weight, gestational weight gain , hypertension, anaemia, Previous history of IUGR, and adequacy of Anti-natal Checkup, maternal education , place of delivery, birth asphyxia, neonatal seizures, pattern of seizures, duration of seizures, number of episodes of seizures, family history of seizures , neonatal jaundice, were significant and to pinpoint modifiable ones & suggest strategies to favourably modify cerebral palsy and seizures in cerebral palsy children.
Effects of Linagliptin on Pancreatic α Cells of Type 1 Diabetic Mice

The dipeptidyl peptidase-4 inhibitor linagliptin promotes β-cell survival and insulin secretion by prolonging endogenous glucagon-like peptide 1 (GLP-1) action and therefore helps to maintain normoglycemia in diabetic patients. The effect of linagliptin on glucagon-producing α cells, however, was not clear. In this study, we investigated whether linagliptin had any effects on α cells with regard to their proliferation and hormonal production using type 1 diabetes mouse models, including streptozotocin-induced and nonobese diabetes mice. After diabetes development, the mice were either untreated or treated with linagliptin or insulin for up to 6 weeks. Our results showed that linagliptin significantly increased circulating GLP-1 levels in both type 1 diabetes models, but therapeutic benefit was detected in nonobese diabetes mice only. Circulating C-peptide and glucagon levels (nonfasting) were not significantly altered by linagliptin treatment in either model. In addition, we found that linagliptin did not increase α-cell proliferation compared with the untreated or insulin-treated controls as assessed by in vivo 5-bromo-2′-deoxyuridine labeling assay. Finally, we examined whether linagliptin treatment altered GLP-1 vs glucagon expression in pancreatic α cells. Immunohistochemistry assays showed that linagliptin treatment resulted in detection of GLP-1 in more α cells than in control groups, suggesting linagliptin was able to increase intraislet GLP-1 presence, presumably by inhibiting GLP-1 degradation. In summary, this study indicates that linagliptin would not confer adverse effect on α cells, such as causing α cell hyperplasia, and instead may facilitate a blood glucose–lowering effect by increasing GLP-1 presence in α cells.
Resonant-Switched Capacitor Converters for Chip-Scale Power Delivery: Design and Implementation

There is an increasing need for power management systems that can be fully integrated in silicon to reduce cost and form factor in mobile applications, and provide point-of-load voltage regulation for high-performance digital systems. Switched-capacitor (SC) converters have shown promise in this regard due to relatively high energy-density of capacitors and favorable device utilization figures of merit. Resonant switched-capacitor (ReSC) converters show similar promise as they benefit from many of the same architectures and scaling trends, but also from ongoing improvements in mm-scale magnetic devices. In this study, we explore the design and optimization of 2:1 step-down topologies, based on representative capacitor technologies, CMOS device parameters, and air-core inductor models. We compare the SC approach to the ReSC approach in terms of efficiency and power density. Finally, a chip-scale ReSC converter is presented that can deliver over 4 W at 0.6 W/mm2 with 85% efficiency. The two-phase, nominally 2:1 converter supports input voltages from 3.6-6.0 V, and is implemented in 180-nm bulk CMOS with die-attached air-core solenoid inductors.
The Role of Structural Factors in HIV Transmission in Uganda: a Multi-Level Analysis

Since the early 1980s, Uganda has been in the spotlight of global concerns about the HIV/AIDS epidemic that has almost brought the country to its knees. Consequently, a number of social epidemiologists and researchers from different social science fields have, over the past two and half decades, focused their attention on Uganda, attempting to identify the risk factors that expose people to HIV infection in order to inform intervention policy. Although studies coming out of this effort have provided important insights into risks of HIV infection, they have been criticized for almost entirely focusing on individual behavioral factors, such as prostitution and inconsistent condom use, as the primary causal factors of HIV infection, without comprehending the contextual background in which HIV infection takes place. Using the 2000/01 Uganda Demographic and Health Survey and employing multilevel logistic regression methods, I address this concern by investigating the influence of contextual factors on three behaviors related to the risk of HIV infection (HIV testing, multiple sexual partnering, and inconsistent condom use). Analyses reveal that educational attainment, socioeconomic status, and
The Relationship of CCR5 Antagonists to CD4+ T-Cell Gain: A Meta-Regression of Recent Clinical Trials in Treatment-Experienced HIV-Infected Patients

Abstract Purpose: Lower CD4+ T-cell counts are related to increased morbidity and mortality despite virologic suppression. CCR5 antagonists are associated with robust CD4+ T-cell responses. We examined the relationship of CCR5 antagonists to CD4+ T-cell gains. Design: Meta-regression of recent phase 2–3 trials evaluating new antiretroviral agents in treatment-experienced subjects. Methods: We analyzed the relationship of CCR5 antagonists to CD4+ T-cell count increase 24 weeks after initiating the new regimen using a linear model with generalized estimating equations controlling for differing rates of virologic suppression. Each treatment group was treated as a data point weighted by sample size. Results: We included 46 treatment groups from 17 trials (11 groups from 5 trials used CCR5 antagonists). Controlling for average baseline HIV-1 RNA and proportion of subjects achieving HIV-1 RNA <50 copies/mL, use of a CCR5 antagonist was associated with an additional significant CD4+ T-cell gain of +30/μL (95% CI, 19–42) at 24 weeks compared to treatment groups not using a CCR5 antagonist. Conclusions: Use of a CCR5 antagonist was associated with an enhanced CD4+ T-cell count response independent of virologic suppression. This observation supports further evaluation of CCR5 antagonists in patients with discordant immunologic and virologic responses to ART.
Startle modulation by heat pain with varying threat levels in chronic pain patients and pain-free controls

Background Empirical evidence suggests that affective responses to pain are changed in chronic pain. The investigation of startle responses to pain might contribute to clarifying whether such alterations also expand to motivational defensive reactions. We aimed at comparing startle responses to tonic heat pain with high threat (HT) or low threat (LT) in patients with chronic musculoskeletal pain and controls. As pain-related anxiety and catastrophizing are typically elevated in chronic pain, we expected to find stronger startle responses in patients specifically under experimental HT. Methods Patients with chronic musculoskeletal, preferentially, back pain (N = 19) and matched pain-free controls (N = 19) underwent two pain-related threat conditions (high and low) in balanced order. Only, in the HT condition, 50% of the trials were announced to include a short further noxious temperature increase at the end. Startle responses to loud tones were always assessed prior to a potential temperature increase in the phase of anticipation and were recorded by surface electromyogram. Results Surprisingly, we observed no differences in startle responses and ratings of emotional and pain responses between patients and controls despite significantly higher pain-related anxiety and catastrophizing in the patients. Overall, startle was potentiated in the HT condition, but only in participants who started with this condition. Conclusion Our results suggest that, in general, patients with pain are not more responsive emotionally to experimental threat manipulations despite elevated pain anxiety and catastrophizing. Instead, exaggerated responses in patients might be triggered only by individual concerns relating to pain, which are not sufficiently mirrored by our threat paradigm.
Impact of Torticollis Associated With Plagiocephaly on Infants’ Motor Development

ObjectiveThis study investigated whether torticollis (congenital or acquired) in infants with plagiocephaly affects the achievement of specific gross motor milestones. MethodsA total of 175 infants affected by plagiocephaly with or without torticollis were recruited and included in this prospective trial. Anthropometric and clinical variables were recorded at baseline. The infants were included in a physiotherapy treatment program, and they were monthly assessed until hospital discharge. ResultsSignificant differences (P < 0.05) were observed in the achievement of rolling over, crawling, and standing skills depending on the specific profile (plagiocephaly and plagiocephaly with congenital or acquired torticollis). After adjusting for the severity of the plagiocephaly and the age at referral, the torticollis was significantly (P < 0.05) associated with crawling and standing skills. ConclusionsThe findings suggest that the presence or absence of congenital or acquired torticollis is an important factor that affects gross motor development in infants with plagiocephaly.
Chronic wounds: why some heal and others don't? Psychosocial determinants of wound healing in older people

Chronic wounds are health problems that affect elderly patients as well as health care professionals. Its chronicity, together with its high recurrence rate, creates not only a big challenge to nurses' workload and health cost, but also has a direct impact on elderly patients' physiological and psychosocial well-being. This study explores the psychosocial well-being of elderly patients with chronic wounds and investigates the role of psychosocial factors, if any, in predicting the likelihood of chronic wound healing. The key findings of this study indicated poor psychosocial well-being of elderly patients with chronic wounds and better emotional status had a significant effect in predicting a higher proportion of complete wound healing.
Differential Displacement of Classical Cadherins by VE-Cadherin

VE-cadherin is an endothelial cell-specific, type II classical cadherin that plays an important role in permeability, vasculogenesis, and vascular remodeling. Endothelial cells express equal levels of VE- and N-cadherin; VE-cadherin is present in junctions while N-cadherin is diffusely expressed over the surface of the cell. The present study was designed first to determine if the ability of VE-cadherin to displace N-cadherin from junctions was endothelial-cell specific, and second to determine if VE-cadherin could displace other classical cadherins from cell junctions. Our data suggest that VE-cadherin specifically influences the cellular localization of N-cadherin, independent of cell type, and does not effect the localization of other classical cadherins.
Diacylglycerol kinase zeta rescues G alpha q-induced heart failure in transgenic mice.

BACKGROUND The G alpha q protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG) and protein kinase C (PKC), plays a critical role in the development of cardiac hypertrophy and heart failure (HF). It has been reported that the expression of a constitutively active mutant of the G protein alpha q subunit in the hearts of transgenic mice (G alpha q-TG) induces cardiac hypertrophy and lethal HF. DAG kinase (DGK) catalyzes DAG and controls its cellular levels, thus acting as a regulator of GPCR signaling. It has been found that transgenic mice with cardiac-specific overexpression of DGK zeta (DGK zeta-TG) inhibit GPCR agonist-induced activation of the DAG-PKC signaling and subsequent cardiac hypertrophy, so this study tested the hypothesis that DGK zeta could rescue G alpha q-TG mice from developing HF. METHODS AND RESULTS Double transgenic mice (G alpha q/DGK zeta-TG) with cardiac-specific overexpression of both DGK zeta and G alpha q were generated by crossing G alpha q-TG with DGK zeta-TG mice, and the pathophysiological consequences were analyzed. DGK zeta prevented cardiac dysfunction, determined by dilatation of left ventricular (LV) dimensions, reduction of LV fractional shortening, and marked increases in LV end-diastolic pressure in G alpha q-TG mice. Translocation of PKC isoforms, phosphorylation activity of c-jun N-terminal kinase and p38 mitogen-activated protein kinase in G alpha q-TG mice were attenuated by DGK zeta. DGK zeta improved the survival rate of G alpha q-TG mice. CONCLUSIONS These results demonstrate the first evidence that DGK zeta blocks cardiac dysfunction and progression to lethal HF by activated G alpha q protein without detectable adverse effects in the in-vivo heart and suggest that DGK zeta is a novel therapeutic target for HF.
Monumental architecture in mountain landscapes: the diy-geδ-bay sites of northern Cameroon

The DGB sites are complexes of dry-stone terraces and platforms in the Mandara Mountains of northern Cameroon. They constitute the earliest well-established evidence for human occupation of this region and raise important questions about the nature of monumentality, relationships with social complexity and areal culture history. The present state of knowledge of the DGB sites and questions arising are summarised and reviewed. While it appears that the sites represent indigenous responses to major areal droughts in the fifteenth and sixteenth centuries, this is neither a complete explanation nor does it address the relationship between the montagnards and the state societies at that time developing in the surrounding plains. Deeper understanding of the DGB sites requires research into their variation and their roles within inhabited landscapes, as well as a reformulation of largely implicit models of historical process and agency corresponding to a topographical dichotomisation of mountain and plains.
Residual impairments and work status 15 years after penetrating head injury

We investigated the relationship of neurologic, neuropsychological, and social interaction impairments to the work status of a large sample of penetrating head-injured patients wounded some 15 years earlier during combat in Vietnam. Extensive standardized testing of neurologic, neuropsychological, and social functioning was done at follow-up on each head-injured patient (N = 520), as well as on a sample of uninjured controls (N = 85). Fifty-six percent of the head-injured patients were working at follow-up compared with 82% of the uninjured controls. Seven systematically defined impairments proved to be most correlated with work status. These were post-traumatic epilepsy, paresis, visual field loss, verbal memory loss, visual memory loss, psychological problems, and violent behavior. These disabilities had a cumulative and nearly equipotent effect upon the likelihood of work. We suggest that a simple summed score of the number of these seven disabilities can yield a residual “disability score” which may prove to be a practical tool for assessing the likelihood of return to work for patients in this population and perhaps in other brain-injured populations. These findings may also help to focus rehabilitation efforts on those disabilities most likely to affect return to work.
Clinical recognition of allodynia in migraine

Background: Allodynia, a manifestation of central sensitization, is not routinely evaluated during clinical interviews even though its therapeutic implications are known. Objective: To assess the frequency and manifestations of allodynia in a clinic-based migraine population. Methods: A total of 295 consecutive International Headache Society migraine patients were evaluated using a semistructured questionnaire. Results: A total of 157 (53.3%) reported allodynia. A total of 133 (84.7% of those with allodynia) had cephalic, 54 (18%) had both cephalic and extracephalic, and 24 (8.5%) exhibited pure extracephalic allodynia. Prominent scalp symptoms were sensitivity to touch; soreness or tenderness; difficulty brushing, combing, or washing hair; difficulty lying with head resting on the side of allodynia; and circumscribed area of hypersensitivity and tenderness. Scalp allodynia was ipsilateral to predominant headache side in the majority and occurred at the height of headache. Extracephalic allodynia of the upper extremities occurred in 72, toes in 6. Truncal allodynia occurred in some. Age range and age at onset of migraine were identical in allodynic and non-allodynic patients. Patients with allodynia were on an average 8 years older than non-allodynic patients (p < 0.05). Correlation was found between the duration of illness as well as frequency of migraine attacks and allodynia. Frequent migraineurs exhibited prolonged allodynia. Conclusions: Clinically detectable allodynia, which occurs with high frequency in migraineurs, should become part of the clinical evaluation because of its implications in early treatment with triptans, recurrence of headache, consistency of response to triptans, and development of chronicity of migraine.