bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani population
Authors: Jaworek Thomas J , Kausar Tasleem , Bell Shannon M , Tariq Nabeela , Maqsood Muhammad Imran , Sohail Asma , Ali Muhmmmad , Iqbal Furhan , Rasool Shafqat , Riazuddin Saima , Shaikh Rehan S , Ahmed Zubair M 
Published: June 2012

Abstract

Background
Oculocutaneous albinism (OCA) is caused by a group of genetically heterogeneous inherited defects that result in the loss of pigmentation in the eyes, skin and hair. Mutations in the TYR, OCA2, TYRP1 and SLC45A2 genes have been shown to cause isolated OCA. No comprehensive analysis has been conducted to study the spectrum of OCA alleles prevailing in Pakistani albino populations.

Methods
We enrolled 40 large Pakistani families and screened them for OCA genes and a candidate gene, SLC24A5. Protein function effects were evaluated using in silico prediction algorithms and ex vivo studies in human melanocytes. The effects of splice-site mutations were determined using an exon-trapping assay.

Results
Screening of the TYR gene revealed four known (p.Arg299His, p.Pro406Leu, p.Gly419Arg, p.Arg278*) and three novel mutations (p.Pro21Leu, p.Cys35Arg, p.Tyr411His) in ten families. Ex vivo studies revealed the retention of an EGFP-tagged mutant (p.Pro21Leu, p.Cys35Arg or p.Tyr411His) tyrosinase in the endoplasmic reticulum (ER) at 37°C, but a significant fraction of p.Cys35Arg and p.Tyr411His left the ER in cells grown at a permissive temperature (31°C). Three novel (p.Asp486Tyr, p.Leu527Arg, c.1045-15 T > G) and two known mutations (p.Pro743Leu, p.Ala787Thr) of OCA2 were found in fourteen families. Exon-trapping assays with a construct containing a novel c.1045-15 T > G mutation revealed an error in splicing. No mutation in TYRP1, SLC45A2, and SLC24A5 was found in the remaining 16 families. Clinical evaluation of the families segregating either TYR or OCA2 mutations showed nystagmus, photophobia, and loss of pigmentation in the skin or hair follicles. Most of the affected individuals had grayish-blue colored eyes.

Conclusions
Our results show that ten and fourteen families harbored mutations in the TYR and OCA2 genes, respectively. Our findings, along with the results of previous studies, indicate that the p.Cys35Arg, p.Arg278* and p.Gly419Arg alleles of TYR and the p.Asp486Tyr and c.1045-15 T > G alleles of OCA2 are the most common causes of OCA in Pakistani families. To the best of our knowledge, this study represents the first documentation of OCA2 alleles in the Pakistani population. A significant proportion of our cohort did not have mutations in known OCA genes. Overall, our study contributes to the development of genetic testing protocols and genetic counseling for OCA in Pakistani families.
Central syntropic effects elicited by trigeminal proprioceptive equilibrium in Alzheimer’s disease: a case report
Authors: De Cicco Vincenzo 
Published: June 2012

Abstract

Introduction
The presented patient, affected by Alzheimer’s disease, underwent neuropsychological evaluation and functional magnetic resonance imaging investigation under occlusal proprioceptive un-balance and re-balance conditions. Saccadic and pupillometric video-oculographic examinations were performed in order to detect connected trigeminal proprioceptive motor patterns able to interfere with reticular formation cerebellum functions linked to visual and procedural processes prematurely altered in Alzheimer’s disease.

Case presentation
A 66-year-old Caucasian man, affected by Alzheimer’s disease and with a neuropsychological evaluation issued by the Alzheimer’s Evaluation Unit, underwent an electromyographic investigation of the masseter muscles in order to assess their functional balance. The patient showed a bilateral lack of all inferior molars. The extreme myoelectric asymmetry in dental occlusion suggested the rebalancing of masseter muscular functions through concurrent transcutaneous stimulation of the trigeminal nerve supramandibular and submandibular motor branches. The above-mentioned method allows detection of symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch, called orthotic-syntropic bite. A few days later, the patient underwent a new neuropsychological investigation, together with a functional magnetic resonance imaging study, and saccadic, pupillometric video-oculographic examinations in occlusal un-balance and re-balance conditions.

Conclusions
Comparative data analysis has shown that a re-balanced occlusal condition can improve a patient’s cognitive-attentive functions. Moreover, the saccadic and pupillometric video-oculographic investigations have proven useful both in analyzing reticulo-cerebellar subcortical systems, prematurely altered in Alzheimer’s disease, and in implementing neurological evaluations.
A user-friendly software to easily count Anopheles egg batches
Authors: Mollahosseini Ali , Rossignol Marie , Pennetier Cédric , Cohuet Anna , Anjos António dos , Chandre Fabrice , Shahbazkia Hamid Reza 
Published: June 2012

Abstract

Background
Studies on malaria vector ecology and development/evaluation of vector control strategies often require measures of mosquito life history traits. Assessing the fecundity of malaria vectors can be carried out by counting eggs laid by Anopheles females. However, manually counting the eggs is time consuming, tedious, and error prone.

Methods
In this paper we present a newly developed software for high precision automatic egg counting. The software written in the Java programming language proposes a user-friendly interface and a complete online manual. It allows the inspection of results by the operator and includes proper tools for manual corrections. The user can in fact correct any details on the acquired results by a mouse click. Time saving is significant and errors due to loss of concentration are avoided.

Results
The software was tested over 16 randomly chosen images from 2 different experiments. The results show that the proposed automatic method produces results that are close to the ground truth.

Conclusions
The proposed approaches demonstrated a very high level of robustness. The adoption of the proposed software package will save many hours of labor to the bench scientist. The software needs no particular configuration and is freely available for download on: http://w3.ualg.pt/∼hshah/eggcounter/.
RETRACTED ARTICLE: Hypermethylation of the 5′ CpG island of the p14ARF flanking exon 1β in human colorectal cancer displaying a restricted pattern of p53 overexpression concomitant with increased MDM2 expression
Authors: Nyiraneza Christine , Sempoux Christine , Detry Roger , Kartheuser Alex , Dahan Karin 
Published: June 2012

Abstract
Background
It has been suggested that inactivation of p14ARF, a tumor suppressor central to regulating p53 protein stability through interaction with the MDM2 oncoprotein, abrogates p53 activity in human tumors retaining the wild-type TP53 gene. Differences in expression of tumor suppressor genes are frequently associated with cancer. We previously reported on a pattern of restricted p53 immunohistochemical overexpression significantly associated with microsatellite instability (MSI), low TP53 mutation frequency, and MDM2 overexpression in colorectal cancers (CRCs). In this study, we investigated whether p14ARF alterations could be a mechanism for disabling the p53 pathway in this subgroup of CRCs.

Results
Detailed maps of the alterations in the p14ARF gene were determined in a cohort of 98 CRCs to detect both nucleotide and copy-number changes. Methylation-specific PCR combined with bisulfite sequencing was used to evaluate the prevalence and distribution of p14ARF methylation. p14ARF alterations were then correlated with MSI status, TP53 mutations, and immunohistochemical expression of p53 and MDM2. The frequency of p14ARF mutations was extremely low (1/98; 1%), whereas coexistence of methylated and unmethylated alleles in both tumors and normal colon mucosa was common (91/98; 93%). Only seven of ninety-eight tumors (7%) had a distinct pattern of methylation compared with normal colon mucosa. Evaluation of the prevalence and distribution of p14ARF promoter methylation in a region containing 27 CpG sites in 35 patients showed a range of methylated CpG sites in tumors (0 to 25 (95% CI 1 to 13) versus 0 to 17 (95% CI 0 to 2)) in adjacent colon mucosa (P = 0.004). Hypermethylation of the p14ARF promoter was significantly correlated with the restricted p53 overexpression pattern (P = 0.03), and MDM2 overexpression (P = 0.02), independently of MSI phenotype. Although no significant correlation between p14ARF methylation and TP53 mutational status was seen (P = 0.23), methylation involving the proximal CpG sites within the 5′ CpG flanking exon 1β was present more frequently in tumors with restricted p53 overexpression than in those with diffuse p53 overexpression (range of methylated clones 17 to 36% (95% CI 24 to 36%) versus range 0 to 3% (95% CI 0 to 3%), P = 0. 0003).

Conclusion
p14ARF epigenetic silencing may represent an important deregulating mechanism of the p53-MDM2-p14ARF pathway in CRCs exhibiting a restricted p53 overexpression pattern.
Long-Term Disease-Specific Functioning Among Prostate Cancer Survivors and Noncancer Controls in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Taylor Kathryn L. , Luta George , Miller Anthony B. , Church Timothy R. , Kelly Scott P. , Muenz Larry R. , Davis Kimberly M. , Dawson David L. , Edmond Sara , Reding Douglas , Mabie Jerome E. , Riley Thomas L. 
Published: June 2012

Purpose Within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), we assessed the long-term disease-specific functioning among prostate cancer (PCa) survivors versus noncancer controls, the impact of trial arm (screening/usual care) on functioning, and the effect of treatment modality on functioning. Patients and Methods PCa survivors (n = 529), 5 to 10 years postdiagnosis, were frequency-matched to noncancer controls (n = 514) for race, screening center, year of enrollment, and trial arm. Participants completed a telephone interview regarding PCa-specific symptomatology. Weights accounted for patient selection from the five PLCO screening centers. Propensity-score methods were used to balance groups of interest with respect to demographic and medical characteristics. Results Weighted linear regression analyses revealed poorer sexual and urinary function among PCa survivors compared with noncancer controls (P < .001). Trial arm was not significantly related to any outcome (P > .31). Compared with radical prostatectomy patients (n = 201), radiation-therapy patients (n = 110) reported better sexual (P < .05) and urinary (P < .001) functioning but poorer bowel outcomes (P < .05). Survivors who received treatment combinations including androgen deprivation (n = 207) reported significantly poorer hormone-related symptoms compared with radical prostatectomy patients (P < .05). Conclusion This study demonstrated the persistence of clinically significant, long-term PCa treatment-related sexual and urinary adverse effects up to 10 years postdiagnosis. To our knowledge, this was the first comparison of prostate-related dysfunction among screened survivors versus screened noncancer controls and indicated that these long-term problems were attributable to PCa treatment and not to aging or comorbidities. Finally, differences in long-term adverse effects between treatment modalities are particularly relevant for patients and clinicians when making treatment decisions.
Which Hospice Patients With Cancer Are Able to Die in the Setting of Their Choice? Results of a Retrospective Cohort Study
Authors: Jeurkar Neha , Farrington Sue , Craig Teresa R. , Slattery Julie , Harrold Joan K. , Oldanie Betty , Teno Joan M. , Casarett David J. 
Published: June 2012

Purpose To determine which hospice patients with cancer prefer to die at home and to define factors associated with an increased likelihood of dying at home. Methods An electronic health record–based retrospective cohort study was conducted in three hospice programs in Florida, Pennsylvania, and Wisconsin. Main measures included preferred versus actual site of death. Results Of 7,391 patients, preferences regarding place of death were determined at admission for 5,837 (79%). After adjusting for other characteristics, patients who preferred to die at home were more likely to die at home (adjusted proportions, 56.5% v 37.0%; odds ratio [OR], 2.21; 95% CI, 1.77 to 2.76). Among those patients (n = 3,152) who preferred to die at home, in a multivariable logistic regression model, patients were more likely to die at home if they had at least one visit per day in the first 4 days of hospice care (adjusted proportions, 61% v 54%; OR, 1.23; 95% CI, 1.07 to 1.41), if they were married (63% v 54%; OR, 1.35; 95% CI, 1.10 to 1.44), and if they had an advance directive (65% v 50%; OR, 2.11; 95% CI, 1.54 to 2.65). Patients with moderate or severe pain were less likely to die at home (OR, 0.56; 95% CI, 0.45 to 0.64), as were patients with better functional status (higher Palliative Performance Scale score: < 40, 64.8%; 40 to 70, 50.2%; OR, 0.79; 95% CI, 0.67 to 0.93; > 70, 40.5%; OR, 0.53; 95% CI, 0.35 to 0.82). Conclusion Increased hospice visit frequency may increase the likelihood of patients being able to die in the setting of their choice.
Characterization of a canine model of glycogen storage disease type IIIa
Authors: Yi Haiqing , Thurberg Beth L. , Curtis Sarah , Austin Stephanie , Fyfe John , Koeberl Dwight D. , Kishnani Priya S. , Sun Baodong 
Published: June 2012

Summary
Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE) in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR). The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) activities; serum creatine phosphokinase (CPK) activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12, and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.
Deletion of a conserved regulatory element required for Hmx1 expression in craniofacial mesenchyme in the dumbo rat: a novel cause of congenital ear malformation
Authors: Quina Lely , Kuramoto Takashi , Luquetti Daniela V. , Cox Timothy C. , Serikawa Tadao , Turner Eric E. 
Published: June 2012

SummaryHmx1 is a homeodomain transcription factor expressed in the developing eye, peripheral ganglia, and branchial arches of avian and mammalian embryos. Recent studies have identified a loss-of-function allele at the HMX1 locus as the causative mutation in the oculo-auricular syndrome (OAS) in humans, characterized by ear and eye malformations. The mouse dumbo (dmbo) mutation, with similar effects on ear and eye development, also results from a loss-of-function mutation in the Hmx1 gene. A recessive dmbo mutation causing ear malformation in rats has been mapped to the chromosomal region containing the Hmx1 gene, but the nature of the causative allele is unknown. Here we show that dumbo rats and mice exhibit similar neonatal ear and eye phenotypes. In midgestation embryos, dumbo rats show a specific loss of Hmx1 expression in neural crest-derived craniofacial mesenchyme (CM), while Hmx1 is expressed normally in retinal progenitors, sensory ganglia, and in CM which is derived from mesoderm. High throughput resequencing of 1Mb of rat chromosome 14 from dmbo/dmbo rats, encompassing the Hmx1 locus, reveals numerous divergences from the rat genomic reference sequence, but no coding changes in Hmx1. Fine genetic mapping narrows the dmbo critical region to an interval of ~410Kb immediately downstream of the Hmx1 transcription unit, and further sequence analysis of this region reveals a 5,777bp deletion located ~80Kb downstream in dmbo/dmbo rats which is not apparent in 137 other rat strains. The dmbo deletion region contains a highly conserved domain of ~500bp which is a candidate distal enhancer, and which exhibits a similar relationship to Hmx genes in all vertebrate species for which data are available. We conclude that the rat dumbo phenotype is likely to result from loss of function of an ultraconserved enhancer specifically regulating Hmx1 expression in neural crest-derived CM. Dysregulation of Hmx1 expression is thus a candidate mechanism for congenital ear malformation, most cases of which remain unexplained.
Open transversus abdominis plane block and analgesic requirements in patients following right hemicolectomy
Authors: Brady RR , Ventham NT , Roberts DM , Graham C , Daniel T 
Published: June 2012

INTRODUCTION Reducing exogenously administered opioids in the post-operative period is associated with early return of bowel function and decreased post-operative complication rates. We evaluated the effectiveness of a surgeon-delivered open transversus abdominis plane (TAP) block as a method to reduce post-operative opioid requirements, sedation and inpatient stay. METHODS The patient cohort was identified from those who had undergone a right hemicolectomy for colonic cancer. Patients received either an open TAP block and post-operative patient controlled anaesthesia (PCA) (n=20) or were part of a control group who received subcutaneous local anaesthetic infiltration and PCA (n=16). RESULTS PCA morphine use was reduced within the first 24 hours post-operatively in the TAP block group compared with controls (42.1mg vs 72.3mg, p=0.002). Sedation was also reduced significantly in the early post-operative period (p<0.04). There was a non-significant trend towards reduced length of stay in the intervention group (8.2 vs 8.73 days). There were no recorded complications attributable to the open TAP block. CONCLUSIONS Open TAP blocks are safe and reduce post-operative opioid requirements and sedation after right hemicolectomies. They should be considered as part of a multimodal enhanced recovery approach to patients undergoing abdominal surgery via a transverse incision.
Human body projectiles implantation in victims of suicide bombings and implications for health and emergency care providers: the 7/7 experience
Authors: Patel HDL , Dryden S , Gupta A , Stewart N 
Published: June 2012

INTRODUCTION On 7 July 2005 four suicide bombings occurred on the London transport systems. In some of the injured survivors, bone fragments were embedded as biological foreign bodies. The aim of this study was to revisit those individuals who had sustained human projectile implantation injuries as a result of the bomb blasts at all scenes, review the process of body parts mapping and DNA identification at the scene, detail the management of such injuries and highlight the protocols that have been put in place for protection against blood borne pathogens. METHODS We retrospectively reviewed 12 instances of victims who sustained human body projectile implantation injuries. The Metropolitan Police and forensic scientists identified the human projectiles using DNA profiling and mapped these on the involved carriages and those found outside. All human projectiles included were greater than 3cm2. RESULTS Twelve cases had human projectile implantation injuries. Of these, two died at the scene and ten were treated in hospital. Projectiles were mapped at three of the four bomb blast sites. Our findings show that victims within a 2m radius of the blast had human projectile injuries. Eight of the allogenic bony fragments that were identified in the survivors originated from the suicide bomber. All the victims with an open wound should have prophylaxis against hepatitis B and serum stored for appropriate action against HIV and hepatitis C infection. CONCLUSIONS All victims following a suicide bombing should be assumed to have human body projectile implantation injuries with blood products or bony fragments. All immediate care providers should receive prophylaxis against hepatitis B virus and appropriate action should be taken against HIV and hepatitis C infection.
Association of PBEF gene polymorphisms with acute lung injury, sepsis, and pneumonia in a northeastern Chinese population
Authors: Liu Yaxin , Shao Yuxia , Yu Baiquan , Sun Liyan , Lv Fuzhen 
Published: June 2012

Abstract

Background: Several studies have suggested that pre-B-cell colony-enhancing factor (PBEF) gene polymorphisms are associated with susceptibility to and prognosis of acute lung injury (ALI) in several populations of Caucasians. The aim of this study was to detect the distribution of PBEF alleles and to evaluate any potential relationship between PBEF polymorphisms and ALI, sepsis, and pneumonia in the Han population of Northeast China.

Methods: Genotyping of two PBEF promoter single-nucleotide polymorphisms (SNPs), rs61330082 (C–1535T) and rs9770242 (T–1001G), were performed in patients with ALI (n=130), sepsis alone (n=107), bacterial pneumonia (n=195) and 150 healthy volunteers using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: We found no variation in the T-1001G allele of PBEF. The homozygous TT genotype was the only genotype. This result is different from that observed in Caucasians. The frequency of the -1543T allele was lower in patients with ALI and sepsis than that in healthy subjects ALI vs. healthy controls: OR=0.60, 95% CI 0.43–0.84, p=0.003; and sepsis vs. healthy controls: OR=0.69, 95% CI 0.49–0.99, p=0.04, respectively). The frequency of TT genotype of -1543T was significantly lower in patients with ALI and sepsis than in healthy subjects (ALI vs. healthy controls: OR=0.23, 95% CI 0.10–0.54, p=0.001; and sepsis vs. healthy controls: OR=0.36, 95% CI 0.15–0.83, p=0.02, respectively).

Conclusions: This study suggested that -1543T allele might be a protective factor for ALI and sepsis, but it apparently had no connection with pneumonia in northeastern Chinese Han patients.