bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new hope: novel therapeutic approaches to treatment of chronic lymphocytic leukaemia with defects inTP53
Authors: Shindiapina Polina , Brown Jennifer R. , Danilov Alexey V. 
Published: July 2014

SummaryChronic lymphocytic leukaemia (CLL) is an indolent B‐cell malignancy with heterogeneous outcomes. Chromosomal abnormalities inCLLare predictive of the natural disease course; del(11q) and del(17p) are recognized as high risk genetic lesions. Del(17p) is associated with an impaired function ofTP53, a key tumour suppressor, and is particularly problematic. Such patients respond poorly to chemo‐immunotherapy and have significantly shorter survival compared to patients with standard and low‐risk cytogenetics. WhileTP53 pathway defects are rare at initial diagnosis, their frequency increases in relapsedCLL. Until very recently, this group of patients represented an unmet clinical need with few therapeutic options. However, the advent of targeted therapies has expanded the drug armamentarium and introduced new hope for these highly refractory patients. Agents that target B‐cell receptor signalling,BH3‐mimetics and others induce apoptosis of the neoplastic B‐cells in aTP53‐independent manner. Their use in the clinic is associated with remarkable activity in patients with del(17p). In this review we discuss the frequency and clinical significance of del(17p) and genetic mutations leading to disruptedTP53, the putative role of otherTP53 homologues, and the results of key clinical trials involving both conventional chemotherapy and novel agents.
Comparison of magnetic resonance imaging and ultrasound (MRI‐US) fusion‐guided prostate biopsies obtained from axial and sagittal approaches
Authors: Hong Cheng W. , Rais‐Bahrami Soroush , Walton‐Diaz Annerleim , Shakir Nabeel , Su Daniel , George Arvin K. , Merino Maria J. , Turkbey Baris , Choyke Peter L. , Wood Bradford J. , Pinto Peter A. 
Published: July 2014

ObjectiveTo compare cancer detection rates and concordance between magnetic resonance imaging and ultrasound (MRI‐US) fusion‐guided prostate biopsy cores obtained from axial and sagittal approaches.Patients and MethodsInstitutional records of MRI‐US fusion‐guided biopsy were reviewed. Detection rates for all cancers, Gleason ≥3 + 4 cancers, and Gleason ≥4 + 3 cancers were computed. Agreement between axial and sagittal cores for cancer detection, and frequency where one was upgraded the other was computed on a per‐target and per‐patient basis.ResultsIn all, 893 encounters from 791 patients that underwent MRI‐US fusion‐guided biopsy in 2007–2013 were reviewed, yielding 4688 biopsy cores from 2344 targets for analysis. The mean age and PSA level at each encounter was 61.8 years and 9.7 ng/mL (median 6.45 ng/mL). Detection rates for all cancers, ≥3 + 4 cancers, and ≥4 + 3 cancers were 25.9%, 17.2%, and 8.1% for axial cores, and 26.1%, 17.6%, and 8.6% for sagittal cores. Per‐target agreement was 88.6%, 93.0%, and 96.5%, respectively. On a per‐target basis, the rates at which one core upgraded or detected a cancer missed on the other were 8.3% and 8.6% for axial and sagittal cores, respectively. Even with the inclusion of systematic biopsies, omission of axial or sagittal cores would have resulted in missed detection or under‐characterisation of cancer in 4.7% or 5.2% of patients, respectively.ConclusionCancer detection rates, Gleason scores, and core involvement from axial and sagittal cores are similar, but significant cancer may be missed if only one core is obtained for each target. Discordance between axial and sagittal cores is greatest in intermediate‐risk scenarios, where obtaining multiple cores may improve tissue characterisation.
Transrectal ultrasonography (TRUS)‐guided pelvic plexus block to reduce pain during prostate biopsy: a randomised controlled trial
Authors: Jindal Tarun , Mukherjee Subhabrata , Sinha Rajan K. , Kamal Mir R. , Ghosh Nabankur , Saha Barun , Mitra Nilanjan , Sharma Pramod K. , Mandal Soumendra N. , Karmakar Dilip 
Published: July 2014

ObjectiveTo assess the role of pelvic plexus block (PPB) in reducing pain during transrectal ultrasonography(TRUS)‐guided prostate biopsy, compared with the conventional periprostatic nerve block (PNB).Patients and MethodsA prospective, double‐blind observational study was conducted with patients being randomised into three groups. Group‐1 (47 patients) received intrarectal local anaesthesia (IRLA) with 10 mL 2% lignocaine jelly along with pelvic plexus block (PPB) with 2.5 mL 2% lignocaine injection bilaterally. Group‐2 (46 patients) received IRLA with periprostatic nerve block (PNB). Group‐3 (46 patients) received only IRLA without any type of nerve block. The patients were requested to rate the level of pain from 0 to 10 on a visual analogue scale (VAS) at two time points: VAS‐1: during biopsy procedure and VAS‐2: 30 min after the procedure.ResultsThe mean age of the patients, mean volume of the prostates and mean serum PSA values were comparable among the three groups. The mean pain score during biopsy was significantly less in the PPB group [mean (range) sore of 2.91 (2–4)] compared with the PNB group [mean (range) score of 4 (3–5)], and both these groups were superior to the no nerve block group [mean score of 5.4 (3–7)]. There was no significant difference between the mean pain scores, 30 min after the procedure among the three groups with the mean (range) scores being 2.75 (2–4), 2.83 (2–4) and 2.85 (2–4), respectively.ConclusionPPB is superior to conventional periprostatic nerve block (PNB) for pain control during TRUS‐guided biopsy and both are in turn superior to no nerve block.
Design, Synthesis, Antibacterial Evaluation and Docking Study of Novel 2‐Hydroxy‐3‐(nitroimidazolyl)‐propyl‐derived Quinolone
Authors: Li Qing , Xing Junhao , Cheng Haibo , Wang Hui , Wang Jing , Wang Shuai , Zhou Jinpei , Zhang Huibin 
Published: July 2014

A novel series of 2‐hydroxy‐3‐(nitroimidazolyl)‐propyl‐derived quinolones 6a–o were synthesized and evaluated for their in vitro antibacterial activity. Most of the target compounds exhibited potent activity against Gram‐positive strains. Among them, moxifloxacin analog 6n displayed the most potent activity against Gram‐positive strains including S. epidermidis (MIC = 0.06 μg/mL), MSSE (MIC = 0.125 μg/mL), MRSE (MIC = 0.03 μg/mL), S. aureus (MIC = 0.125 μg/mL), MSSA (MIC = 0.125 μg/mL), (MIC = 2 μg/mL). Its activity against MRSA was eightfold more potent than reference drug gatifloxacin. Finally, docking study of the target compound 6n revealed that the binding model of quinolone nucleus was similar to that of gatifloxacin and the 2‐hydroxy‐3‐(nitroimidazolyl)‐propyl group formed two additional hydrogen bonds.
The functional polymorphisms of VDR, GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases
Authors: Inoue N , Watanabe M , Ishido N , Katsumata Y , Kagawa T , Hidaka Y , Iwatani Y 
Published: July 2014

Summary
Vitamin D is a multi-functional immune regulator, and a low serum concentration of vitamin D promotes autoimmune inflammation. In this study, we evaluate the association between the prognosis of autoimmune thyroid disease (AITD) and the functional polymorphisms of genes that regulate vitamin D metabolism. For 139 Graves’ disease (GD) patients, 116 Hashimoto's disease (HD) patients and 76 control subjects, we genotyped the following polymorphisms using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP): vitamin D receptor (VDR): rs731236, rs7975232, rs2228570 and rs1544410; group-specific component (GC): rs7041 and rs4588; and CYP2R1: rs10741657. The frequency of the TT genotype for the rs731236 polymorphism was higher in GD patients than in HD patients (P = 0·0147). The frequency of the C allele for the rs7975232 polymorphism was higher in GD patients than in control subjects (P = 0·0349). The proportion of GD patients whose anti-thyrotrophin receptor antibody (TRAb) level was &gt;51% was higher in those with the CC genotype than in those with the CA+AA genotypes (P = 0·0065). The frequency of the CC genotype for the rs2228570 polymorphism was higher in HD patients than in control subjects (P = 0·0174) and GD patients (P = 0·0149). The frequency of the Gc1Gc1 genotype for the GC polymorphism and the AG genotype for the CYP2R1 polymorphism were lower in intractable GD than in GD in remission (P = 0·0093 and 0·0268, respectively). In conclusion, genetic differences in the VDR gene may be involved in the development of AITD and the activity of GD, whereas the genetic differences in the GC and CYP2R1 genes may be involved with the intractability of GD.
Detection rate of FNA cytology in medullary thyroid carcinoma: a meta‐analysis
Authors: Trimboli Pierpaolo , Treglia Giorgio , Guidobaldi Leo , Romanelli Francesco , Nigri Giuseppe , Valabrega Stefano , Sadeghi Ramin , Crescenzi Anna , Faquin William C. , Bongiovanni Massimo , Giovanella Luca 
Published: July 2014

SummaryBackgroundThe early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine‐needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta‐analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates.Research Design and MethodsA comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms ‘medullary thyroid’ AND ‘cytology’, ‘FNA’, ‘FNAB’, ‘FNAC’, ‘fine needle’ or ‘fine‐needle’. The search was updated until 21 March 2014, and no language restrictions were used.ResultsFifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as ‘MTC’ or ‘suspicious for MTC’) on a per lesion‐based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6–60·1%). The included studies were statistically heterogeneous in their estimates of DR (I‐square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: −3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta‐analysis.ConclusionsThe presented meta‐analysis demonstrates that FNAC is able to detect approximately one‐half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results.
Combined immunomodulatory therapies resulted in stepwise recovery in autoimmune autonomic ganglionopathy
Authors: Nishihara Hideaki , Koga Michiaki , Higuchi Osamu , Tasaki Ayako , Ogasawara Jun‐ichi , Kawai Motoharu , Nakane Shunya , Kanda Takashi 
Published: July 2014

AbstractSome intractable cases of autoimmune autonomic ganglionopathy are treated with diverse combinations of immunomodulatory therapies. However, it is unclear which of the immunotherapies directly contributed to the relief of dysautonomia when several immunotherapies have been utilized. To evaluate which of the immunomodulatory therapies are effective, we describe a 60‐year‐old man with autoimmune autonomic ganglionopathy who was successfully treated by combined immunomodulatory therapies. The patient showed subacute pure autonomic failure without antecedent infectious symptoms, and was admitted to Yamaguchi University Hospital, Yamaguchi, Japan. He demonstrated involvement of cardiovascular, pupillary, sudomotor, gastrointestinal and bladder functions. Serum ganglionic acetylcholine receptor autoantibody titer was highly elevated. The diagnosis of autoimmune autonomic ganglionopathy was made. Plasma exchange was repeated nine times, resulting in minimal improvement. Subsequently, intravenous immunoglobulin therapy followed by steroid administration was initiated, after which his symptoms gradually improved. Plasma noradrenaline levels showed a stepwise elevation after each treatment, including plasma exchange. Our case adds to the evidence that combining several immunomodulatory therapies is beneficial for some intractable cases of autoimmune autonomic ganglionopathy that do not adequately respond to a single immunomodulatory therapy. Each immunomodulatory therapy should be effective even though they are not enough to show clinical improvement.
Predictive genetic testing for adult‐onset disorders in minors: a critical analysis of the arguments for and against the 2013 ACMG guidelines
Authors: Anderson J.A. , Hayeems R.Z. , Shuman C. , Szego M.J. , Monfared N. , Bowdin S. , Zlotnik Shaul R. , Meyn M.S. 
Published: July 2014

AbstractThe publication of the ACMG recommendations has reignited the debate over predictive testing for adult‐onset disorders in minors. Response has been polarized. With this in mind, we review and critically analyze this debate. First, we identify long‐standing inconsistencies between consensus guidelines and clinical practice regarding risk assessment for adult‐onset genetic disorders in children using family history and molecular analysis. Second, we discuss the disparate assumptions regarding the nature of whole genome and exome sequencing underlying arguments of both supporters and critics, and the role these assumptions play in the arguments for and against reporting. Third, we suggest that implicit differences regarding the definition of best interests of the child underlie disparate conclusions as to the best interests of children in this context. We conclude by calling for clarity and consensus concerning the central foci of this debate.
CHIPS for genetic testing to improve a regional clinical genetic service
Authors: Niida Y. , Ozaki M. , Inoue M. , Takase E. , Kuroda M. , Mitani Y. , Okumura A. , Yokoi A. , Fujita S. , Yamada K. 
Published: July 2014

AbstractIn current practice of clinical genetics, molecular diagnosis has become more widely used than ever before. DNA diagnosis is important for appropriate medical care of the patient, and proper genetic counseling to the family. However, genetic testing of orphan disease cannot always be performed easily. In multiple congenital anomalies (MCA) syndromes by monogenic cause, the broad mutational spectrum and large size of responsible genes often make molecular diagnosis expensive and cumbersome. We solve this problem with on‐demand genetic testing by CHIPS (CEL nuclease mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining) technology, which is the ultimately conventional and economical mutation screening system. In this article, we show eight patients with MCA syndromes who were recently treated at our hospital, and demonstrate that CHIPS successfully offers efficient and inexpensive genetic testing and facilitates clinical genetic service in our local region.
Available web‐based dental implants information for patients. How good is it?
Authors: Leira‐Feijoo Yago , Ledesma‐Ludi Yanina , Seoane‐Romero Juan M. , Blanco‐Carrión Juan , Seoane Juan , Varela‐Centelles Pablo 
Published: July 2014

AbstractBackgroundMassive use of the Internet for health issues has raised concerns about the quality of the information available and about consumers' ability to tell “good” from “bad” information.PurposeTo assess the quality of patient‐addressed, dental implants‐related websites in terms of reliability, accessibility, usability and readability.Materials and MethodsTwo search engines (Google and Yahoo) were used in this study. The first 100 sites, as listed by each engine, were considered for the study. Each site was categorised and analysed for quality using the DISCERN and the LIDA instruments. The Flesch‐Kinkaid Reading Grade Level (FKRGL) and the Flesh Reading Ease Score (FRES) were used to assess legibility.ResultsAfter applying the inclusion and exclusion criteria, 32 single websites entered the study. The median score for the DISCERN instrument (3 [2–3]) indicated serious or potentially important shortcoming in the quality of the information obtained. LIDA scores showed modest percentages for accessibility (79.36 [74.60–85.31]) and intermediate for usability (59.20 (50.46‐68.51)) and reliability (55.55 [45.37–66.66]). Legibility indices reached scores within the range of difficult to read (FRES = 51.72 [38.70–55.27]); FKRGL = 12.76 [10.07–14.87]).ConclusionsAvailable e‐health information on dental implants in English language is difficult to read for the average patient and poor in terms of quality.
Cost estimation of single‐implant treatment in the periodontally healthy patient after 16–22 years of follow‐up
Authors: Dierens M. , Vandeweghe S. , Kisch J. , Nilner K. , Cosyn J. , De Bruyn H. 
Published: July 2014

AbstractBackgroundCosts for single‐implant treatment are mostly described for the initial treatment. Information on the additional cost related to aftercare is scarce.ObjectiveTo make an estimation of complication costs of single implants in periodontally healthy patients after 16–22 years and to compare costs for various prosthetic designs.Materials and methodsPatients with a single implant were recalled for a clinical examination and file investigation. Prosthetic designs included single‐tooth (ST) and CeraOne (CO) abutments supporting a porcelain‐fused‐to‐metal (PFM), all‐ceramic (CER), or gold‐acrylic (ACR) crown. Costs related to failures or technical, biologic, and aesthetic complications were retrieved from patient's records. Total and yearly additional complication costs were calculated as a percentage relative to the initial cost. Chair time needed to solve the complication was recorded and prosthetic designs were compared by Kruskal–Wallis tests.ResultsFifty patients with 59 surviving implants were clinically investigated. Additional complication costs after a mean follow‐up of 18.5 years amounted to 23% (range 0–110%) of the initial treatment cost. In total, 39% of implants presented with no costs, whereas 22% and 8% encountered additional costs over 50% and 75%, respectively. In 2%, the complication costs exceeded the initial cost. The mean yearly additional cost was 1.2% (range 0–6%) and mean complication time per implant was 67 min (range 0–345 min). Differences between prosthetic designs (CO, ST‐PFM, ST‐ACR) were statistically significant for total cost (P = 0.011), yearly cost (P = 0.023), and time (P = 0.023). Pairwise comparison revealed significant lower costs for CO compared with ST‐ACR reconstructions.ConclusionPatients should be informed about additional costs related to complications with single implants. The mean additional cost spent on complications was almost one‐quarter of the initial treatment price. A majority of implants presented with lower additional costs, whereas the highest complication costs were related to a smaller group with 22% of the implants needing more than half of the initial cost for complication management. Expenses were significantly different for various prosthetic designs.
The potential for biodiversity offsetting to fund effective invasive species control
Authors: Norton David A. , Warburton Bruce 
Published: July 2014

AbstractCompensating for biodiversity losses in 1 location by conserving or restoring biodiversity elsewhere (i.e., biodiversity offsetting) is being used increasingly to compensate for biodiversity losses resulting from development. We considered whether a form of biodiversity offsetting, enhancement offsetting (i.e., enhancing the quality of degraded natural habitats through intensive ecological management), can realistically secure additional funding to control biological invaders at a scale and duration that results in enhanced biodiversity outcomes. We suggest that biodiversity offsetting has the potential to enhance biodiversity values through funding of invasive species control, but it needs to meet 7 key conditions: be technically possible to reduce invasive species to levels that enhance native biodiversity; be affordable; be sufficiently large to compensate for the impact; be adaptable to accommodate new strategic and tactical developments while not compromising biodiversity outcomes; acknowledge uncertainties associated with managing pests; be based on an explicit risk assessment that identifies the cost of not achieving target outcomes; and include financial mechanisms to provide for in‐perpetuity funding. The challenge then for conservation practitioners, advocates, and policy makers is to develop frameworks that allow for durable and effective partnerships with developers to realize the full potential of enhancement offsets, which will require a shift away from traditional preservation‐focused approaches to biodiversity management.El Potencial de la Compensación de la Biodiversidad para Financiar Controles Efectivos de Especies Invasoras
Xyleborus glabratus attacks and systemic colonization by Raffaelea lauricola associated with dieback of Cinnamomum camphora in the southeastern United States
Authors: Fraedrich S. W. , Harrington T. C. , Best G. S. 
Published: July 2014

SummaryLaurel wilt, caused by Raffaelea lauricola, is responsible for extensive mortality of redbay and other American members of the Lauraceae in the southeastern United States. Raffaelea lauricola is a mycangial symbiont of the redbay ambrosia beetle (Xyleborus glabratus), and the beetle and fungus were accidentally introduced from Asia. Branch dieback of camphortree (Cinnamomum camphora), an Asian member of the Lauraceae, has been occasionally observed in areas where laurel wilt has decimated redbay populations, and R. lauricola was isolated from such camphortrees. However, the role of X. glabratus and R. lauricola in this branch dieback remains unclear. Examination of camphortrees on Jekyll Island, Georgia showed that healthy‐appearing trees and those with branch dieback had been attacked by X. glabratus, but the trees with branch dieback had four times as many beetle attacks. Raffaelea lauricola was routinely isolated from discoloured xylem near beetle tunnels in healthy trees and those with dieback. Single‐point inoculations with R. lauricola on stems of mature, healthy camphortree trees failed to induce wilt‐like symptoms or branch dieback, although areas of discoloration were scattered throughout the xylem, and R. lauricola was reisolated irregularly at various heights in some inoculated trees. In growth chamber experiments, single‐point inoculations with R. lauricola resulted in systemic colonization but no wilt symptoms or branch dieback in camphortree saplings. In contrast, inoculations at multiple points along the stem (simulating multiple attacks by the vector) caused branch dieback and wilt‐like symptoms, including a brownish, diffuse discoloration of the xylem. Camphortree appears to be more resistant than American species of Lauraceae to the vascular wilt caused by R. lauricola. The fungus does colonize camphortrees systemically, however, and can apparently cause branch dieback. This suggests that the fungus may provide brood material for X. glabratus in Asia as it does in the southeastern United States.