bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cystic fibrosis mutations for p.F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency
Authors: Sebro R , Levy H , Schneck K , Dimmock D , Raby BA , Cannon CL , Broeckel U , Risch NJ 
Published: October 2011

Sebro R, Levy H, Schneck K, Dimmock D, Raby BA, Cannon CL, Broeckel U, Risch NJ. Cystic fibrosis mutations for p.F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency.Cystic fibrosis (CF) is a monogenetic disease with a complex phenotype. Over 1500 mutations in the CFTR gene have been identified; however, the p.F508del mutation is most common. There has been limited correlation between the CFTR mutation genotype and the disease phenotypes. We evaluated the non‐p.F508del mutation of 108 p.F508del compound heterozygotes using the biological classification method, Grantham and Sorting Intolerant from Tolerant (SIFT) scores to assess whether these scoring systems correlated with sweat chloride levels, pancreatic sufficiency, predicted FEV1, and risk of infection with Pseudomonas aeruginosa in the last year. Mutations predicted to be ‘mild’ by the biological classification method are associated with more normal sweat chloride levels (p < 0.001), pancreatic sufficiency (p < 0.001) and decreased risk of infection with Pseudomonas in the last year (p = 0.014). Lower Grantham scores are associated with more normal sweat chloride levels (p < 0.001), and pancreatic sufficiency (p = 0.014). Higher SIFT scores are associated with more normal sweat chloride levels (p < 0.001) and pancreatic sufficiency (p = 0.011). There was no association between pulmonary function measured by predicted FEV1 and the biological classification (p = 0.98), Grantham (p = 0.28) or SIFT scores (p = 0.62), which suggests the pulmonary disease related to CF may involve other modifier genes and environmental factors.
Underutilization of A2 ABO incompatible kidney transplantation
Authors: Redfield Robert R. , Parsons Ronald F. , Rodriguez Eduardo , Mustafa Moiz , Cassuto James , Vivek Kumar , Noorchashm Hooman , Naji Ali , Levine Matthew H. , Abt Peter L. 
Published: October 2011

Redfield RR, Parsons RF, Rodriguez E, Mustafa M, Cassuto J, Vivek K, Noorchashm H, Naji A, Levine MH, Abt PL. Underutilization of A2 ABO incompatible kidney transplantation.  Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01543.x.  © 2011 John Wiley & Sons A/S.Abstract:  Background:  ABO compatibility creates a disadvantage for O and B renal allograft candidates. A2 ABO incompatible transplant may decrease waiting times and generate equivalent graft survival to an ABO compatible transplant.Methods:  Death‐censored graft survival was compared between A recipients and O, B, and AB recipients of an A2 allograft with multivariate Cox regression models utilizing data from the United Network of Organ Sharing (UNOS) between 1997 and 2007.Results:  Eighty‐five percent of A2 kidneys were transplanted into ABO compatible recipients vs. 15% into ABO incompatible recipients. Rates of A2 incompatible kidney transplants did not increase over the study period (14.8% to 14.6%). Mean wait time for A2→O kidneys was 337 vs. 684 d for O→O and for A2→B kidneys, 542 vs. 734 d for B→B. Adjusted relative risk of graft loss at five‐yr was similar between O, B, and AB recipients compared to A recipients of an A2 allograft, corresponding to a five‐yr graft survival of 84%, 86.2%, 86.1%, and 86.1%, respectively.Conclusion:  A2 incompatible kidney transplantation is underutilized. Graft outcomes are similar among A2 compatible and incompatible recipients. Shorter waiting time and improved access might be achieved if A2 kidneys are considered in all blood groups.
Castleman disease in a pediatric liver transplant recipient: A case report and literature review
Authors: Bonatti Hugo J. R. , Axt Jason , Hunter Ellen Bailey , Lott Sarah Louise , Frangoul Haydar , Gillis Lynette , Correa Hernan , Kelly Beau 
Published: October 2011

Bonatti HJR, Axt J, Hunter EB, Lott SL, Frangoul H, Gillis L, Correa H, Kelly B. Castleman disease in a pediatric liver transplant recipient: A case report and literature review.  Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S.Abstract:  Castleman disease is a rare hematologic disorder, closely linked to the HHV‐8, and most commonly observed in immunocompromised individuals. Thirteen months following a liver transplant for CPS‐1 defect, a 15‐month‐old boy presented with fevers, anemia, and growth retardation. Abdominal CT scan showed splenomegaly and generalized lymphadenopathy. Histology of chest wall lymph nodes revealed a mixed CD3+ T‐cell and CD20+ B‐cell population with atretic germinal centers consistent with multicentric Castleman disease. Qualitative DNA PCR detected HHV‐8 in the resected lymph node and in the blood, supporting the diagnosis. Immunosuppression was tapered, and he was transitioned from tacrolimus to sirolimus. His graft function remained stable, and repeat imaging showed regression of the lymphadenopathy. The child is living one yr after Castleman disease diagnosis with a well‐functioning graft. Castleman disease is a potential complication of solid organ transplant and HHV‐8 infection. Reduction in immunosuppression and switch to sirolimus may be an effective strategy to treat this condition.
Growth discontinuity in males of the deep‐water giant red shrimpAristaeomorpha foliaceain the Mediterranean Sea
Authors: Ragonese Sergio , Vitale Sergio , Dimech Mark , De Santi Alberto 
Published: October 2011

AbstractThe deep‐water giant red shrimp,Aristaeomorpha foliacea(Risso, 1827) (Decapoda, Aristeidae), represents a highly valuable resource for bottom trawling in the Mediterranean Sea. Recent assessments have described both a worsening of the status of the traditionally exploited stocks and low levels of annual‐based instantaneous natural mortality (M 0.4–0.7 year−1) in the unexploited stocks. The mortality (M) figures, however, are in contrast with the longevity (Tmax) of 3–4‐year males and 4–5‐year females, estimated from classical length frequency distribution analysis. Reduced growth (after the onset of sexual maturity) and pile‐up of older individuals in the larger size classes have been considered to be reasonable explanations for the contrast between M and Tmax. We propose that a discontinuity of the growth models could address this contrast. Because a clear discontinuity in sexual maturity is evident only in males, length frequency distribution data for different sets of males collected from the South of Sicily and the Maltese Islands deep bottoms (400–800 m) were fitted with both the classic (c) and double‐phased (d) von Bertalanffy growth formula (VBGF). According to the dVBGF, adult males sharply reduce their growth rate after reaching an age between 1.2 and 1.5 year, which corresponds to the estimates of age at sexual maturity (tmbetween 1 and 1.5 years). The reduction in growth determines a higher Tmax(7.3–9.5 year) and lower M (0.4–0.6 year−1) than previously derived on the basis of cVBGF estimates (Tmax3–4 years and M 1.2 year−1). The dVBGF results suggest that sexual dimorphism and length–sex segregation in giant red shrimps reflect an alternative life history strategy that is based mainly on growth reduction in adult males and it might be adopted for implementing more conservative assessments.
Concomitant presence of endothelial nitric oxide 894T and angiotensin II‐converting enzyme D alleles are associated with diabetic nephropathy in a Kurdish population from Western Iran
Authors: RAHIMI ZOHREH , VAISI‐RAYGANI ASAD , RAHIMI ZIBA , PARSIAN ABBAS 
Published: October 2011

ABSTRACT:Aim:  The present study investigated the influence of insertion (I)/deletion (D) polymorphism of the angiotensin II‐converting enzyme (ACE) gene in combination with endothelial nitric oxide (eNOS) G894T polymorphism on the predisposition to diabetic nephropathy (DN).Methods:  Using polymerase chain reaction (PCR) and PCR‐restriction fragment length polymorphism (PCR‐RFLP) method, the ACE and eNOS polymorphisms were genotyped in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric type 2 diabetes mellitus (T2DM) patients from Western Iran.Results:  The presence of eNOS T or ACE D allele was not associated with increased risk of macroalbuminuria (odds ratio (OR) = 1.36, P = 0.27 and OR = 1.6, P = 0.062, respectively). However, in the presence of both alleles there was a trend towards increased risk of macroalbuminuria (fivefold, P = 0.05).Conclusion:  Our study indicates that the concomitant presence of both ACE D and eNOS T alleles tends to be associated with an elevation risk of macroalbuminuria compared with the presence of each polymorphism alone. This risk could be attributed to the increasing activity of ACE and angiotensin II level in the presence of D allele and decreasing NO production in the presence of T allele accelerating diabetic nephropathy.
Evolution of the biosynthesis of di‐myo‐inositol phosphate, a marker of adaptation to hot marine environments
Authors: Gonçalves Luís G. , Borges Nuno , Serra François , Fernandes Pedro L. , Dopazo Hernán , Santos Helena 
Published: October 2011

SummaryThe synthesis of di‐myo‐inositol phosphate (DIP), a common compatible solute in hyperthermophiles, involves the consecutive actions of inositol‐1‐phosphate cytidylyltransferase (IPCT) and di‐myo‐inositol phosphate phosphate synthase (DIPPS). In most cases, both activities are present in a single gene product, but separate genes are also found in a few organisms. Genes for IPCT and DIPPS were found in the genomes of 33 organisms, all with thermophilic/hyperthermophilic lifestyles. Phylogeny of IPCT/DIPPS revealed an incongruent topology with 16S RNA phylogeny, thus suggesting horizontal gene transfer. The phylogenetic tree of the DIPPS domain was rooted by using phosphatidylinositol phosphate synthase sequences as out‐group. The root locates at the separation of genomes with fused and split genes. We propose that the gene encoding DIPPS was recruited from the biosynthesis of phosphatidylinositol. The last DIP‐synthesizing ancestor harboured separated genes for IPCT and DIPPS and this architecture was maintained in a crenarchaeal lineage, and transferred by horizontal gene transfer to hyperthermophilic marineThermotogaspecies. It is plausible that the driving force for the assembly of those two genes in the early ancestor is related to the acquired advantage of DIP producers to cope with high temperature. This work corroborates the view that Archaea were the first hyperthermophilic organisms.
Novel therapeutics for the management of castration‐resistant prostate cancer (CRPC)
Authors: Lee Daniel J. , Cha Eugene K. , Dubin Justin M. , Beltran Himisha , Chromecki Thomas F. , Fajkovic Harun , Scherr Douglas S. , Tagawa Scott T. , Shariat Shahrokh F. 
Published: October 2011

What's known on the subject? and What does the study add?Historically, therapies for CRPC have primarily been chemotherapy‐based. A variety of novel therapeutics for CRPC have recently been developed and tested. When evaluating novel therapies for CRPC, there are various different endpoints that can be assessed.Novel treatments for CRPC to be discussed include docetaxel‐based combinations, new cytotoxic agents, immunotherapeutics, and targeted therapies. We evaluate prostate‐specific antigen, circulating tumour cells, progression‐free survival, overall survival, and other endpoints used in clinical trials.
Androgen‐deprivation therapy is the initial treatment for metastatic prostate cancer. Although highly effective, all men who live long enough will eventually experience disease progression and develop castration resistance. Patients who have castration‐resistant prostate cancer (CRPC) have a median survival of ≈1–3 years.
When evaluating novel therapies for CRPC, one must consider the endpoints measured for determination of response. We will discuss PSA, circulating tumour cells, progression‐free survival, overall survival, and other endpoints used in clinical trials.
Docetaxel and sipuleucel‐T are currently the preferred first‐line treatment options for patients with CRPC; cabazitaxel is a new option for patients after docetaxel failure.
Patients with CRPC historically have very poor survival, underscoring the unmet need for novel therapeutics. Although many agents appear promising, well‐designed randomized phase III trials are necessary to establish their impact on survival and health‐related quality of life.
Promising new therapies include hormonal agents, such as abiraterone and MDV3100, as well as other novel immunotherapeutics and anti‐prostate‐specific membrane antigen therapies. In the future, we anticipate therapies tailored to individual patients' malignancies using various molecular analyses.
The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)
Authors: Gudjónsson Sigurdur , Bläckberg Mats , Chebil Gunilla , Jahnson Staffan , Olsson Hans , Bendahl Pär‐Ola , Månsson Wiking , Liedberg Fredrik 
Published: October 2011

Study Type – Diagnostic (case series)Level of Evidence 4What's known on the subject? and What does the study add?It is well known that CIS is a major risk factor for muscle‐invasive bladder cancer and that this entity can be difficult to diagnose. Taking cold‐cup mapping biopsies from different areas of the bladder (BMAP) is commonly used in patients at risk of harbouring CIS. The diagnostic accuracy of this approach has not been assessed until now.By using the CIS found in the cystoprostatectomy specimen as an indicator of the true occurrence of CIS and comparing that with the findings of BMAP, it is clear that the sensitivity of BMAP to detect CIS when present is low and that negative findings should be considered unreliable.OBJECTIVES
To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS).
CIS of the urinary bladder is a flat high‐grade lesion of the mucosa associated with a significant risk of progression to muscle‐invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold‐cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known.
PATIENTS AND METHODS
Male patients with bladder cancer scheduled for cystectomy underwent cold‐cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra.
After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS.
RESULTS
The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (≥2) CIS lesions were found in 30%.
BMAP (cold‐cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold‐cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively.
CONCLUSION
Traditional cold‐cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.
Genetic pathways involved in carcinogenesis of clear cell renal cell carcinoma: genomics towards personalized medicine
Authors: Audenet François , Yates David R. , Cancel‐Tassin Géraldine , Cussenot Olivier , Rouprêt Morgan 
Published: October 2011

What's known on the subject? and What does the study add?Sporadic clear cell Renal Cell Carcinoma (ccRCC) is dominated by nutations of the VHL gene located on chromosome 3p in up to 90% of cases. This gene plays a critical role in hypoxia response, including stimulation of neoangiogenesis. Since 2006, anti‐angiogenci therapies targeting this pathway are used in metastatic patients with objective response rate as high as 45%. However, these treatments don't target directly the tumour cell, allowing the potential for disease progession despite treatment.Large scale analysis recently showed that substantial genetic heterogeneity exists in ccRCC. Associated alterations include genes implicated in methylation regulation in 15% of cases, underlying the importance of epigenetic modifications, and truncating mutations in chromatin remodelling complex PRMB1 in 41% of cases. Systematic screening of these tumours is a way to fully determine the somatic genetic architecture of RCC in order to improve tumour classification, to develop prognostic and predictive markers and to target new molecular pathways involved in carcinogenesis.• A critical review is provided of the recent progress in oncogenetics applied to renal cell carcinoma (RCC) by highlighting our current understanding of the genetic pathways involved in carcinogenesis and its current and future clinical application.• RCC comprises a model of translational research because an improved understanding of molecular pathways has led to several targeted therapy options for patients with metastatic RCC.• Alteration of the product of the Von Hippel–Lindau gene/hypoxia inductible factor/vascular endothelial growth factor pathway is well characterized in carcinogenesis and is the target of the current therapies for metastatic RCC.• However, substantial genetic heterogeneity exists in this cancer and current treatments do not target directly the tumour cell.• Improving overall survival still remains a challenging objective but, currently, there is a lack of prognostic and predictive biomarkers for response to treatment.• Further information is awaited from the genomic approach to tumour classification, prognostic markers and predictive indicators of response to the treatment, as well as the personal susceptibility of developing RCC when exposed to risk factors.• Recent technological developments, such as large‐scale analysis and high‐speed sequencing, will allow the systematic screening of tumours to fully determine the somatic genetic architecture of RCC.
MRI and its role in the evaluation and surgical decision making in patients with challenging IPP presentations: descriptions of MRI findings and algorithm for patient management
Authors: McPhail E. Fred , Nehra Ajay , Bruner Bryan C. , Kawashima Akira , King Bernard F. , Kim Bohyun 
Published: October 2011

Study Type – Diagnostic (case series)Level of Evidence 4What's known on the subject? and What does the study add?It is known that magnetic resonance imaging (MRI) is safe and effective for imaging patients with inflatable penile prostheses (IPPs). Previous series have reported results of MRI for imaging series of patients with IPPs. The impact on management in particular with regard to salvage procedures is not well defined.This study represents the largest known experience with MRI evaluation of IPPs. This also provides an algorithm that assists with decisions regarding utilization of MRI and treatment planning based on results.OBJECTIVE
In some patients who undergo placement of an inflatable penile prosthesis (IPP) the device may function inadequately. We describe the use of magnetic resonance imaging (MRI) for anatomical localization and detection of prosthesis malrotation, angulation, displacement and erosion in IPPs with equivocal clinical examination.
PATIENTS AND METHODS
We prospectively performed MRI by a defined protocol including T1‐weighted imaging, and transaxial, sagittal and coronal fat‐saturated fast spin‐echo T2‐weighted imaging in both deflated and inflated states to evaluate patients seen at our referral centre for IPP‐related complaints.
We retrospectively reviewed 32 such MRI studies performed as a supplement to clinical examination between 2000 and 2008.
RESULTS
Of 32 cases, 75% (24/32) underwent surgical intervention. Of these, 45% (11/24) underwent device salvage procedures including cylinder revision in 33% (8/24), cylinder replacement in 8% (2/24) and pump replacement in 4% (1/24).
MRI was most useful for determination of surgical approach in those with abnormal physical examination, and for justification of either surgical or expectant management in those with indeterminate physical examination.
CONCLUSIONS
MRI is safe and effective for imaging genitourinary prostheses.
We found MRI to be a valuable adjunct for evaluation of IPP‐related complaints when clinical examination is equivocal as it detected a variety of prosthetic and corporal abnormalities and impacted management decisions regarding observation, replacement or device salvage procedures.
We provide technique, results and an algorithm that can be beneficial in this complex subset of patients.
Affective prosody labeling in youths with bipolar disorder or severe mood dysregulation
Authors: Deveney Christen M. , Brotman Melissa A. , Decker Ann Marie , Pine Daniel S. , Leibenluft Ellen 
Published: October 2011

Background:  Accurate identification of nonverbal emotional cues is essential to successful social interactions, yet most research is limited to emotional face expression labeling. Little research focuses on the processing of emotional prosody, or tone of verbal speech, in clinical populations.Methods:  Using the Diagnostic Analysis of Nonverbal Accuracy, the current study examined whether youths with pediatric‐onset bipolar disorder (BD) and/or those with chronic and severe irritability (i.e. the severe mood dysregulation phenotype) are impaired in their ability to identify the emotional prosody of a spoken sentence with neutral content.Results:  Youths with severe mood dysregulation (n = 67) performed more poorly than healthy comparison children (n = 57), even when the sample was limited to unmedicated patients. Medicated BD youths (n = 52) exhibited impairment relative to healthy comparison children. No interactions between group and emotion were observed, suggesting that emotional prosody labeling problems may represent a general deficit in chronically irritable youths and in medicated youths with BD.Conclusion:  In concert with previously documented facial emotion labeling deficits, difficulties ascertaining the correct emotional tone of a spoken sentence may contribute to emotion dysregulation in chronically irritable children, and possibly also in youths with BD.
Grouping mechanisms in response preparation investigated with event‐related brain potentials
Authors: Sangals Jörg , Dippel Gabriel , Sommer Werner 
Published: October 2011

AbstractPreliminary information about responses facilitates performance, especially when the information can be grouped into stimulus‐response sets, for example, into fingers belonging to the same hand. Here, we studied the mechanisms of supposedly fast and automatic exogenous as compared to slow and controlled endogenous grouping of same‐hand fingers. As compared to endogenous cuing, exogenous cuing facilitated reaction times and induced larger amplitudes of the contingent negative variation, but did not show any advantage in amplitude or latency of the lateralized readiness potential or in the magnitude of current source density over the motor cortices. Similarly, the stimulus preceding negativity did not seem to be a plausible explanation for the observed effect. Therefore, at least one functional mechanism underlying exogenous stimulus‐response grouping appears to be the facilitation of central response programming.