Miracle-dz/UniFAR-FTUs huggingface dataset:
Porcine Endogenous Retroviruses Infect Cells Lacking Cognate Receptors by an Alternative Pathway: Implications for Retrovirus Evolution and Xenotransplantation

ABSTRACT A PHQ motif near the amino termini of gammaretroviral envelope glycoprotein surface (SU) subunits is important for infectivity but not for incorporation into virions or binding to cognate receptors. The H residue of this motif is most critical, with all substitutions we tested being inactive. Interestingly, porcine endogenous retroviruses (PERVs) of all three host-range groups, A, B, and C, lack full PHQ motifs, but most members have an H residue at position 10. H10A PERV mutants are noninfectious but were efficiently transactivated by adding to the assays a PHQ-containing SU or receptor-binding subdomain (RBD) derived from a gibbon ape leukemia virus (GALV). A requirement of this transactivation was a functional GALV receptor on the cells. In contrast to this heterologous transactivation, PERV RBDs and SUs were inactive in all tested cells, including porcine ST-IOWA cells. Surprisingly, transactivation by GALV RBD enabled wild-type or H10A mutant PERVs of all three host-range groups to efficiently infect cells from humans and rodents that lack functional PERV receptors and it substantially enhanced infectivities of wild-type PERVs, even for cells with PERV receptors. Thus, PERVs can suboptimally infect cells that contain cognate receptors or they can employ a transactivation pathway to more efficiently infect all cells. This ability to infect cells lacking cognate receptors was previously demonstrated only for nontransmissible variant gammaretroviruses with recombinant and mutant envelope glycoproteins. We conclude that some endogenously inherited mammalian retroviruses also have a receptor-independent means for overcoming host-range and interference barriers, implying a need for caution in xenotransplantation, especially of porcine tissues.
NA-Trees: A Dynamic Index for Spatial Data

In non-standard database applications, such as geographic information processing or CAD/CAM, methods of access are required that support efficient manipulation of multidimensional geometric objects on secondary storage. Spatial data consists of spatial objects made up of points, lines, regions, rectangles, surfaces, volumes, and even data of higher dimension. Being able to respond to spatial queries in a flexible manner places a premium on the appropriate representation of the spatial data. In order to be able to deal with proximity queries, an efficient spatial indexing strategy is needed. In this paper, we consider the problem of retrieving spatial data via exact match queries and range queries from a large, dynamic index, where an exact match query means finding the specific data object in a spatial database and a range query means reporting all data objects which are located in a specific range. By large, we mean that most of the index must be stored in secondary storage. By dynamic, we mean that insertions and deletions are intermixed with queries, so that the index cannot be built beforehand. A new data structure, a Nine-Areas tree (denoted NA-tree), is shown to be a solution to this problem. An NA-tree is designed for paged secondary storage to minimize the number of disk accesses during a tree search. From our simulation, we show that our NA-tree has a lower search cost (in terms of number of visited nodes) than the R-tree, R(superscript +)-tree, or R(superscript *)-tree.
Preeclampsia and Blood Pressure Trajectory during Pregnancy in Relation to Vitamin D Status

Every tenth pregnancy is affected by hypertension, one of the most common complications and leading causes of maternal death worldwide. Hypertensive disorders in pregnancy include pregnancy-induced hypertension and preeclampsia. The pathophysiology of the development of hypertension in pregnancy is unknown, but studies suggest an association with vitamin D status, measured as 25-hydroxyvitamin D (25(OH)D). The aim of this study was to investigate the association between gestational 25(OH)D concentration and preeclampsia, pregnancy-induced hypertension and blood pressure trajectory. This cohort study included 2000 women. Blood was collected at the first (T1) and third (T3) trimester (mean gestational weeks 10.8 and 33.4). Blood pressure at gestational weeks 10, 25, 32 and 37 as well as symptoms of preeclampsia and pregnancy-induced hypertension were retrieved from medical records. Serum 25(OH)D concentrations (LC-MS/MS) in T1 was not significantly associated with preeclampsia. However, both 25(OH)D in T3 and change in 25(OH)D from T1 to T3 were significantly and negatively associated with preeclampsia. Women with a change in 25(OH)D concentration of ≥30 nmol/L had an odds ratio of 0.22 (p = 0.002) for preeclampsia. T1 25(OH)D was positively related to T1 systolic (β = 0.03, p = 0.022) and T1 diastolic blood pressure (β = 0.02, p = 0.016), and to systolic (β = 0.02, p = 0.02) blood pressure trajectory during pregnancy, in adjusted analyses. There was no association between 25(OH)D and pregnancy-induced hypertension in adjusted analysis. In conclusion, an increase in 25(OH)D concentration during pregnancy of at least 30 nmol/L, regardless of vitamin D status in T1, was associated with a lower odds ratio for preeclampsia. Vitamin D status was significantly and positively associated with T1 blood pressure and gestational systolic blood pressure trajectory but not with pregnancy-induced hypertension.
RPM2, independently of its mitochondrial RNase P function, suppresses an ISP42 mutant defective in mitochondrial import and is essential for normal growth

RPM2 is identified here as a high-copy suppressor of isp42-3, a temperature-sensitive mutant allele of the mitochondrial protein import channel component, Isp42p. RPM2 already has an established role as a protein component of yeast mitochondrial RNase P, a ribonucleoprotein enzyme required for the 5' processing of mitochondrial precursor tRNAs. A relationship between mitochondrial tRNA processing and protein import is not readily apparent, and, indeed, the two functions can be separated. Truncation mutants lacking detectable RNase P activity still suppress the isp42-3 growth defect. Moreover, RPM2 is required for normal fermentative yeast growth, even though mitochondrial RNase P activity is not. The portion of RPM2 required for normal growth and suppression of isp42-3 is the same. We conclude that RPM2 is a multifunctional gene. We find Rpm2p to be a soluble protein of the mitochondrial matrix and discuss models to explain its suppression of isp42-3.
Family grief.

As grief is both an individual and shared experience, adopting a systemic perspective is most appropriate for health-care professionals seeking to assist the bereaved. Within this framework, the family virtually always constitutes the most significant social group in which grief is experienced. In this paper we review the literature on family grief, covering clinical case reports, the observations of family therapists, systematic family bereavement research and family intervention studies. An understanding of patterns of family grief and vulnerability factors for morbid grief is pivotal to both preventive intervention and treatment of an established disorder.
Hyperprolactinemia and amenorrhea associated with olanzapine normalized after addition of aripiprazole

Hyperprolactinemia is a frequent side‐effect in the use of atypical antipsychotics. The propensity to induce hyperprolactinemia is highly substance dependent and hyperprolactinemia is not always associated with clinical side‐effects. We report a case in which hyperprolactinemia and amenorrhea under the treatment with olanzapine gets normalized after the addition of aripiprazole.
Diode laser treatment of posterior retinopathy of prematurity

AIMS To study the efficacy of infrared diode laser for the treatment of posterior retinopathy of prematurity (ROP). METHODS 48 eyes of 25 premature babies (mean birth weight 779 (SD 127.7) g; mean gestational age 25.5 (SD 1.47) weeks) with threshold ROP in zone I and posterior zone II were treated by the indirect infrared (810 nm) diode laser. Confluent burns were applied to the avascular retina. In 18 eyes, an additional row of laser burns was added posterior to the ridge. RESULTS Favourable anatomical results were noted in 41 eyes (85.4%). ROP stage 5 developed in two eyes, ROP stage 4A developed in four eyes, and ROP stage 4B in one eye. Three of the eyes with stage 4A eyes were successfully buckled; the fourth was not operated on and remained demarcated by laser scars. No complications were noted. CONCLUSION In this series, the diode laser was found to be a safe and effective treatment for posterior ROP.
[Association of HER-2/neu expression with prognosis of gastric cancer].

OBJECTIVE To investigate the association between the expression of human epidermal growth factor receptor (HER)-2/neu gene and prognosis of gastric cancer. METHODS The expression of HER-2/neu in gastric cancer was detected by immunohistochemical technique and analyzed in relation with the follow-up and clinicopathologic data of the patients. RESULTS Thirty-two of the 103 gastric cancer specimens (31.1%) were positive for HER-2/neu, but whose expression was not found in benign gastric lesion and normal gastric mucosa. HER-2/neu expression was not correlated with the patients' sex, age, tumor size and location or the degree of differentiation (P>0.05), but with the depth of invasion, clinical stage, lymph node and distant metastasis of the tumor and survival of the patients (P<0.05). CONCLUSION HER-2/neu expression is closely related to invasion, metastasis and prognosis of gastric cancer and can be used to evaluate the biological behavior and prognosis of gastric cancer.
A Critical Evaluation of the Endocervical Curettage

A prospective study was undertaken to critically evaluate the endocervical curettage. The study group consisted of 261 patients with colposcopically identifiable cervical lesions that had not been previously biopsied and were not macroscopically suspicious for invasive cancer. In 210 patients, the entire lesion, transformation zone, and squamocolumnar junction were visible (satisfactory colposcopy), and in 51 patients, the full extent of the lesion was not visualized colposcopically (unsatisfactory colposcopy). We used a method of examination not previously described. Colposcopy was performed before and after the endocervical curettage, but before the ectocervical biopsy. This method of examination allowed us to identify potentially contaminated endocervical curettages and to test the null hypothesis that a positive endocervical curettage in patients with satisfactory colposcopy is not the result of contamination. Twenty of 210 endocervical curettages in patients with satisfactory colposcopy were potentially contaminated, as suggested by an ectocervical lesion disrupted by the endocervical curettage. No patient with a positive endocervical curettage had an intact ectocervical lesion. Therefore, the null hypothesis was rejected ( P < .005). Of the 51 patients with unsatisfactory colposcopy, 39 (76%) underwent cone biopsy. Invasive cancer was diagnosed by cone biopsy in two patients when both ectocervical biopsy and endoccrvical curettage demonstrated only dysplasia. We also confirmed that patients with unsatisfactory colposcopy occasionally benefit from having a n endocervical curettage. However, basing the treatment plan for any lesion short of invasive cancer solely on thc results of colposcopy, tctocervical biopsy, and/or endocervical curettage could lead to significant undertreatment of some patients.
Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma.

OBJECTIVE Transsphenoidal surgery is the treatment of choice for nonfunctioning pituitary macroadenomas (NFMA). In this study we evaluated the long-term effects of a treatment strategy in which postoperative radiotherapy was not routinely applied to patients with NFMA. DESIGN This was a retrospective follow-up study. PATIENTS We included 109 consecutive patients (age 56 +/- 13 yr) operated for NFMA between 1992 and 2004. RESULTS Radiological imaging revealed a macroadenoma in all patients, with suprasellar extension in 96% and parasellar/infrasellar extension in 36% of cases. Visual field defects were present in 87% of the patients and improved in 84% of these patients after surgery. Only six patients received postoperative radiotherapy. Ten patients died during the follow-up period. Ninety-seven patients could be assessed for tumor regrowth or tumor recurrence after a mean follow-up period of 6.0 +/- 3.7 yr. In nine patients there was evidence for tumor regrowth, and in one patient tumor recurrence was observed. The mean time to tumor growth/recurrence after initial therapy was 6.9 (range 3-12) yr. Follow-up duration was found to be an independent predictor for tumor regrowth. CONCLUSION Transsphenoidal surgery without postoperative radiotherapy is an effective and safe treatment strategy for NFMA, without evidence for tumor regrowth in 90% of all patients, at least for the duration of follow-up presented in this study. Additional studies are required to exclude higher regrowth and recurrence rates during prolongation of the duration of follow-up.
Prevalence of drooling in children with cerebral palsy attending special schools.

Prevalence of drooling in children with cerebral palsy (CP) and its severity across dental age (i.e. children with primary, mixed, and permanent dentitions) was investigated. One hundred and sixty children and adolescents (91 males, 69 females; mean age 10 years 10 months, SD 4 years 2 months; range 4 to 18 years) with CP who attended special schools were involved in this study. Sixty eight per cent of participants had spastic CP with the majority (45%) diagnosed as having quadriplegia. Presence or absence of drooling was determined by direct observation of the participants. Other data, such as age, sex, learning disability, and type of CP were collected using questionnaires. Results showed 93 of 160 children (58%) with CP had a drooling condition and of these 53 (33%) had severe drooling. It was found that the degree of drooling decreased as the child's dental age increased. Prevalence of drooling in children with primary dentition was found to be 75% as compared with 43% of those with permanent dentition, although this difference was not statistically significant. It was concluded that any invasive treatment to reduce drooling should, perhaps, be postponed until the child's oromusculature has matured.
The signal transducer and activator of transcription 1alpha and interferon regulatory factor 1 are not essential for the induction of indoleamine 2,3-dioxygenase by lipopolysaccharide: involvement of p38 mitogen-activated protein kinase and nuclear factor-kappaB pathways, and synergistic effect of s

Indoleamine 2,3-dioxygenase (IDO) is induced by interferon (IFN)-gamma-mediated effects of the signal transducer and activator of transcription 1alpha (STAT1alpha) and interferon regulatory factor (IRF)-1. The induction of IDO can also be mediated through an IFN-gamma-independent mechanism, although the mechanism of induction has not been identified. In this study, we explored whether lipopolysaccharide (LPS) or several proinflammatory cytokines can induce IDO via an IFN-gamma-independent mechanism, and whether IDO induction by LPS requires the STAT1alpha and IRF-1 signaling pathways. IDO was induced by LPS or IFN-gamma in peripheral blood mononuclear cells and THP-1 cells, and a synergistic IDO induction occurred when THP-1 cells were cultured in the presence of a combination of tumor necrosis factor-alpha, interleukin-6 or interleukin-1beta. An electrophoretic mobility shift assay using STAT1alpha and IRF-1 consensus oligonucleotide probes showed no STAT1alpha or IRF-1 binding activities in LPS-stimulated THP-1 cells. Further, the LPS-induced IDO activity was inhibited by both p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) inhibitors. These findings suggest that the induction of IDO by LPS in THP-1 cells is not regulated by IFN-gamma via recruitment of STAT1alpha or IRF-1 to the intracellular signaling pathway, and may be related to the activity of the p38 MAPK pathway and NF-kappaB.
The use of general anesthesia in pediatric dental care of children at multi-dental centers in Saudi Arabia.

OBJECTIVE High caries reports in young Saudi children strongly suggest the need occasionally for general anesthesia to provide quality dental work. The purpose of this study was to investigate the characteristics of patients, dental procedures and hospital protocols for Pediatric Dental General Anesthesia (PDGA) procedure at multi-dental centers in Jeddah, Saudi Arabia. STUDY DESIGN Study sample included 90 children attending PDGA treatment at three governmental hospitals in Jeddah. Collected data included patient's demographics, medical condition, admission type, intra-operative protocols, and dental procedures. RESULTS Results showed the mean age of treated children was 5 +/- 2 years and the majority of them (93%) were treated for the first time under general anesthesia (GA). Long waiting duration for PDGA procedure was reported regardless of the patient age and medical status. Being very young with extensive caries was the major indication for GA (58%). Children mean preoperative fasting times were 10 +/- 2 hours. Hospitals were significantly different in some protocols for PDGA procedures. Child behavior during GA induction was significantly related to child's age, premedication use, and hospital admission type. The mean number of treated teeth per child was 14 +/- 3.8 and the treatment mostly included restorations. Age was found to significantly affect the type of dental treatment, while gender and medical status did not. CONCLUSIONS PDGA procedure is used mostly for young children with extensive dental caries. Children treated under GA received a comprehensive dental care in Saudi hospitals. Efforts should be directed to improve some of the existing hospitals protocols with PDGA procedure. The long waiting period for PDGA operation indicated the need to improve available facilities in the three hospitals.
Immune-Mediated Pore-Forming Pathways Induce Cellular Hypercitrullination and Generate Citrullinated Autoantigens in Rheumatoid Arthritis

RA-associated hypercitrullination is specifically induced by immune-mediated membrane pore-forming pathways. Costumed Targets in Rheumatoid Arthritis Just as kids (and many adults) don their costumes for Halloween, proteins frequently change their appearance with posttranslational modifications. One such modification is citrullination, turning the amino acid arginine in a protein into the amino acid citrulline. However, citrullination can be either a trick or a treat: It helps control the expression of genes, but also makes the costumed proteins targets for the immune system, resulting in autoimmune diseases such as rheumatoid arthritis (RA). Now, Romero et al. find that RA-associated hypercitrullination may be induced by immune-mediated membrane pore-forming pathways. Although antibodies to citrullinated protein antigens have been reported to be markers of RA, the mechanisms behind the production of citrullinated autoantigens have remained unclear. Here, the authors examined the citrullination pattern in RA-associated synovial fluid cells and found a cellular hypercitrullination not observed in either activated or dying neutrophils, another source of citrullinated proteins. They then found that this cellular hypercitrullination was induced by two immune-mediated changes in cell membrane: perforin and the complement membrane attack complex. This insight could lead to new approaches to treating RA. Autoantibodies to citrullinated protein antigens are specific markers of rheumatoid arthritis (RA). Although protein citrullination can be activated by numerous stimuli in cells, it remains unclear which of these produce the prominent citrullinated autoantigens targeted in RA. In these studies, we show that RA synovial fluid cells have an unusual pattern of citrullination with marked citrullination of proteins across the broad range of molecular weights, which we term cellular hypercitrullination. Although histone citrullination is a common event during neutrophil activation and death induced by different pathways including apoptosis, NETosis, and necroptosis/autophagy, hypercitrullination is not induced by these stimuli. However, marked hypercitrullination is induced by two immune-mediated membranolytic pathways, mediated by perforin and the membrane attack complex (MAC), which are active in the RA joint and of importance in RA pathogenesis. We further demonstrate that perforin and MAC activity on neutrophils generate the profile of citrullinated autoantigens characteristic of RA. These data suggest that activation of peptidylarginine deiminases during complement and perforin activity may be at the core of citrullinated autoantigen production in RA. These pathways may be amenable to monitoring and therapeutic modulation.
Micrometastatic tumor detection in patients with head and neck cancer: a preliminary report.

OBJECTIVE To apply a new immunocytochemistry (ICC) assay to peripheral blood samples for micrometastatic circulating tumor cell detection in patients with head and neck squamous cell cancer (HNSCC). DESIGN The ICC assay uses established monoclonal antibodies that bind to tumor-associated antigens combined with an enrichment system that uses positive selection with anti-human epithelial antigen (EpCAM antibody) to detect circulating tumor cells. SUBJECTS Eighteen consecutive patients newly diagnosed as having HNSCC are described. RESULTS Of the 18 patients, 8 (44%) demonstrated circulating tumor cells using the ICC assay. The numbers of patients positive for circulating tumor cells per stage are as follows: stage I, 1 of 1; stage II, 0 of 2; stage III, 2 of 5; stage IV, 5 of 6; and unknown stage, 0 of 4. The numbers of patients positive for circulating tumor cells per location are as follows: oral cavity, 1 of 2; oropharynx, 3 of 4; glottic area, 3 of 5; supraglottic area, 1 of 3; and unknown primary 0 of 4. CONCLUSIONS Circulating tumor cells were identified in almost half of the patients using the ICC assay. In a literature review, we were not able to identify previous reports of circulating tumor cell detection in patients with HNSCC from peripheral blood samples using ICC or identify any study that has attempted to quantify circulating tumor cell levels. Although the clinical implications of circulating tumor cells in micrometastatic tumor detection in patients with HNSCC are still unknown, they may be significant. Long-term follow-up may help elucidate the patients in whom conventional treatment may fail and, thus, those who may benefit from different treatment; it may also assist with the detection of recurrence with a simple blood collection.