tbuckley/cabot-search huggingface dataset:
Location, Location, Location: Geographic Clustering of Lower-Extremity Amputation Among Medicare Beneficiaries With Diabetes
Authors: David J. Margolis, Ole Hoffstad, Jeffrey Nafash, Charles E. Leonard, Cristin P. Freeman, Sean Hennessy, Douglas J. Wiebe
Journal: Diabetes Care (2011)

OBJECTIVE Lower-extremity amputation (LEA) is common among persons with diabetes. The goal of this study was to identify geographic variation and the influence of location on the incidence of LEA among U.S. Medicare beneficiaries with diabetes. RESEARCH DESIGN AND METHODS We conducted a cohort study of beneficiaries of Medicare. The geographic unit of analysis was hospital referral regions (HRRs). Tests of spatial autocorrelation and geographically weighted regression were used to evaluate the incidence of LEA by HRRs as a function of geographic location in the U.S. Evaluated covariates covered sociodemographic factors, risk factors for LEA, diabetes severity, provider access, and cost of care. RESULTS Among persons with diabetes, the annual incidence per 1,000 of LEA was 5.0 in 2006, 4.6 in 2007, and 4.5 in 2008 and varied by the HRR. The incidence of LEA was highly concentrated in neighboring HRRs. High rates of LEA clustered in contiguous portions of Texas, Oklahoma, Louisiana, Arkansas, and Mississippi. Accounting for geographic location greatly improved our ability to understand the variability in LEA. Additionally, covariates associated with LEA per HRR included socioeconomic status, prevalence of African Americans, age, diabetes, and mortality rate associated with having a foot ulcer. CONCLUSIONS There is profound "region-correlated" variation in the rate of LEA among Medicare beneficiaries with diabetes. In other words, location matters and whereas the likelihood of an amputation varies dramatically across the U.S. overall, neighboring locations have unexpectedly similar amputation rates, some being uniformly high and others uniformly low.
CD44 Proteolysis Increases CREB Phosphorylation and Sustains Proliferation of Thyroid Cancer Cells
Authors: Valentina De Falco, Anna Tamburrino, Simona Ventre, Maria Domenica Castellone, Mouhannad Malek, Serge N. Manié, Massimo Santoro
Journal: Cancer Research (2012)

CD44 is a marker of cancer stem-like cells and epithelial-mesenchymal transition that is overexpressed in many cancer types, including thyroid carcinoma. At extracellular and intramembranous domains, CD44 undergoes sequential metalloprotease- and γ-secretase-mediated proteolytic cleavage, releasing the intracellular protein fragment CD44-ICD, which translocates to the nucleus and activates gene transcription. Here, we show that CD44-ICD binds to the transcription factor CREB, increasing S133 phosphorylation and CREB-mediated gene transcription. CD44-ICD enhanced CREB recruitment to the cyclin D1 promoter, promoting cyclin D1 transcription and cell proliferation. Thyroid carcinoma cells harboring activated RET/PTC, RAS, or BRAF oncogenes exhibited CD44 cleavage and CD44-ICD accumulation. Chemical blockade of RET/PTC, BRAF, metalloprotease, or γ-secretase were each sufficient to blunt CD44 processing. Furthermore, thyroid cancer cell proliferation was obstructed by RNA interference-mediated knockdown of CD44 or inhibition of γ-secretase and adoptive CD44-ICD overexpression rescued cell proliferation. Together, these findings reveal a CD44-CREB signaling pathway that is needed to sustain cancer cell proliferation, potentially offering new molecular targets for therapeutic intervention in thyroid carcinoma.
Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial
Authors: Mirjam Steunebrink, Johannes Zwerver, Ruben Brandsema, Petra Groenenboom, Inge van den Akker-Scheek, Adam Weir
Journal: British Journal of Sports Medicine (2012)

To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone.Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN or placebo patch in combination with eccentric squats on a decline board. Measurements were performed at baseline, 6, 12 and 24 weeks. Primary outcome measure was the Victorian Institute of Sports Assessment-Patella (VISA-P) questionnaire. Secondary outcome measures were patient satisfaction and pain scores during sports. Generalised estimated equation was used to analyse the treatment, time and treatment×time effect. Analyses were performed following the intention-to-treat principle.VISA-P scores for both groups improved over the study period to 75.0±16.2 and 80.7±22.1 at 24 weeks. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.80). Mean Visual Analogue Scores pain scores during sports for both groups increased over the study period to 6.6±3 and 7.8±3.1. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.38). Patient satisfaction showed no difference between GTN and placebo groups (p=0.25) after 24 weeks, but did show a significant difference over time (p=0.01). Three patients in the GTN group reported some rash.It seems that continuous topical GTN treatment in addition to an eccentric exercise programme does not improve clinical outcome compared to placebo patches and an eccentric exercise programme in patients with chronic patellar tendinopathy.
Temporarily Deferred Therapy (watchful waiting) for Men Younger Than 70 Years and With Low-Risk Localized Prostate Cancer in the Prostate-Specific Antigen Era
Authors: Corey A. Carter, Timothy Donahue, Leon Sun, Hongyu Wu, David G. McLeod, Christopher Amling, Raymond Lance, John Foley, Wade Sexton, Leo Kusuda, Andrew Chung, Douglas Soderdahl, Stephen Jackman, Judd W. Moul
Journal: Journal of Clinical Oncology (2003)

Watchful waiting (WW) is an acceptable strategy for managing prostate cancer (PC) in older men. Prostate-specific antigen (PSA) testing has resulted in a stage migration, with diagnoses made in younger men. An analysis of the Department of Defense Center for Prostate Disease Research Database was undertaken to document younger men with low- or intermediate-grade PC who initially chose WW.We identified men choosing WW who were diagnosed between January 1991 and January 2002, were 70 years or younger, had a Gleason score < or = 6 with no Gleason pattern 4, had no more than three positive cores on biopsy, and whose clinical stage was < or = T2 and PSA level was < or = 20. We analyzed their likelihood of remaining on WW, the factors associated with secondary treatment, and the influence of comorbidities.Three hundred thirteen men were identified. Median follow-up time was 3.8 years. Median age was 65.4 years (range, 41 to 70 years). Ninety-eight patients remained on WW; 215 proceeded to treatment. A total of 57.3% and 73.2% chose treatment within the first 2 and 4 years, respectively. Median PSA doubling time (DT) was 2.5 years for those who underwent therapy; those remaining on WW had a median DT of 25.8 years. The type of secondary treatment was associated with the number of patient's comorbidities (P =.012).Younger patients who choose WW seemed more likely to receive secondary treatment than older patients. PSA DTs often predict the use of secondary treatment. The number of comorbidities a patient has influences the type of secondary therapy chosen. The WW strategy may better be termed temporarily deferred therapy.
The Lazarus phenomenon
Authors: Vedamurthy Adhiyaman, Sonja Adhiyaman, Radha Sundaram
Journal: Journal of the Royal Society of Medicine (2007)

Even though Lazarus phenomenon is rare, it is probably under reported. There is no doubt that Lazarus phenomenon is a reality but so far the scientific explanations have been inadequate. So far the only plausible explanation at least in some cases is auto-PEEP and impaired venous return. In patients with PEA or asystole, dynamic hyperinflation should considered as a cause and a short period of apnoea (30–60 seconds) should be tried before stopping resuscitation. Since ROSC occurred within 10 minutes in most cases, patients should be passively monitored for at least 10 minutes after the cessation of CPR before confirming death.
Cisplatin induces N-acetyl cysteine suppressible F2-isoprostane production and injury in renal tubular epithelial cells.
Authors: A Salahudeen, V Poovala, W Parry, R Pande, V Kanji, N Ansari, J Morrow, J Roberts
Journal: Journal of the American Society of Nephrology (1998)

In the low intracellular chloride milieu, chloride ions of cisplatin may exchange for cellular SH moieties resulting in glutathione depletion, H2O2 accumulation, and lipid peroxidation. Cisplatin-induced lipid peroxidation, in addition to causing direct cellular injury, may further contribute to cisplatin-induced renal dysfunction by generating vasoconstrictive E2- and F2-isoprostanes. The aim of this study was to determine whether cisplatin-induced renal epithelial (LLC-PK1 and primary human proximal tubular) cell injury is associated with increased production of isoprostanes, and whether this can be suppressed with a thiol donor, N-acetyl cysteine. It was confirmed that incubation of renal epithelial cells with cisplatin resulted in N-acetyl cysteine-inhibitable glutathione depletion, H2O2 accumulation, lipid degradation, and lactate dehydrogenase release. In additional experiments, incubation of cells with cisplatin for 48 h was accompanied by a dose-related increase in total (free plus esterified) F2-isoprostanes. An increase in F2-isoprostanes was discernible at 16.5 microM cisplatin and doubled at 66.0 microM. N-Acetyl cysteine at 50 microM concentration effectively suppressed 66.0 microM cisplatin-induced increase in isoprostanes. Similar findings were also obtained in human cells. Thus, cisplatin-induced tubular cell injury is accompanied by increased isoprostane production through a mechanism involving thiol depletion. On the basis of this new finding, it is hypothesized that these arachidonic acid peroxidation products may be partially responsible for the cisplatin-induced renal vasoconstriction demonstrable in the in vivo models.
Natural Progression of Diabetic Peripheral Neuropathy in the Zenarestat Study Population
Authors: Mark J. Brown, Shawn J. Bird, Sharon Watling, Hong Kaleta, Lee Hayes, Stephen Eckert, Howard L. Foyt
Journal: Diabetes Care (2004)

The aim of this study was to report the baseline and natural progression of diabetic peripheral neuropathy over 12 months in a large mild-to-moderate neuropathy population.Patients from a multicentered trial of zenarestat, an aldose reductase inhibitor, had serial measures of neurologic function, including nerve conduction studies (NCSs), quantitative sensory testing (QST), and clinical neuropathy rating scores at baseline and at 12 months. Baseline population descriptors and changes in neurologic function in placebo-treated patients were analyzed.Sural sensory velocity (P = 0.0008 [95% CI -1.04 to -0.27]), median sensory amplitude (P = 0.0021 [-1.3 to -0.29]), median distal motor latency (P = 0.002 [0.09-0.28]), cool thermal QST (P = 0.0005 [0.27-0.94]), and Michigan Neuropathy Screening Instrument results (P = 0.0087 [0.04-0.30]) declined significantly from baseline in the placebo population. NCS changes from baseline were independent of baseline HbA1c stratification.The neurologic decline over 12 months is evident when measured by NCS and cool thermal QST. Other measures (vibration QST, neuropathy rating scores, monofilament examination) are insensitive to changes over 12 months in a mild-to-moderate affected population of this size.
Original Gleason System Versus 2005 ISUP Modified Gleason System: The Importance of Indicating Which System Is Used in the Patient’s Pathology and Clinical Reports
Authors: Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Roberta Mazzucchelli, Gregor Mikuz, Ziya Kirkali, Francesco Montorsi
Journal: European Urology (2010)
The continuing challenge of air pollution
Authors: B. Brunekreef
Journal: European Respiratory Journal (2010)

Empirical evidence in the finance literature clearly demonstrates that institutional investors do not add value from selecting managers. Yet plan sponsors are highly confident in their manager selection abilities, as shown by results from three surveys reported in this article. The author proposes that the apparent inconsistency between performance and perception is due to investors using inappropriate benchmarks—specifically, they do not evaluate terminated managers. As evidence, the author presents regression results that show a near-zero statistical relationship between surveyed pension officers’ self-confidence and their belief in the importance of evaluating performance of investment decisions.
Metastatic spinal cord compression
Authors: N. A. Quraishi, C. Esler
Journal: BMJ (2011)

<h3>Objective</h3> The purpose of this study was to investigate barriers to surge capacity of an overcrowded emergency department (ED) for a foodborne disease outbreak (FBDO) and to identify solutions to the problems. <h3>Design</h3> The emergency response of an overcrowded ED to a serious FBDO with histamine fish poisoning was reviewed. <h3>Setting</h3> The ED of a tertiary academic medical centre (study hospital) with 1600 acute beds in southern Taiwan. <h3>Results</h3> Among the 346 patients in the outbreak, 333 (96.2%) were transferred to the study hospital without prehospital management within about 2 h. The most common symptoms were dizziness (58.9%), nausea and vomiting (36.3%). 181 patients (54.4%) received intravenous fluid infusion and blood tests were ordered for 82 (24.6%). All patients were discharged except one who required admission. The prominent problems with surge capacity of the study hospital were shortage of spare space in the ED, lack of biological incident response plan, poor command system, inadequate knowledge and experience of medical personnel to manage the FBDO. <h3>Conclusions</h3> Patients with FBDO could arrive at the hospital shortly after exposure without field triage and management. The incident command system and emergency operation plan of the study hospital did not address the clinical characteristics of the FBDO and the problem of ED overcrowding. Further planning and training of foodborne disease and surge capacity would be beneficial for hospital preparedness for an FBDO.
Heterogeneous nature of renal lesions in type II diabetes.
Authors: V Gambara, G Mecca, G Remuzzi, T Bertani
Journal: Journal of the American Society of Nephrology (1993)

The nature of renal damage in patients with type II diabetes remains unclear. This study was directed to evaluate pathologic changes in 52 patients affected by type II diabetes with overt clinical nephropathy by conventional and morphometric techniques. The duration of diabetes ranged from 6 to 384 months, urinary protein excretion ranged from 0.9 to 9.2 g/24 h, and serum creatinine ranged from 0.9 to 9 mg/dL. Specimens were examined semiquantitatively by light microscopy, immunofluorescence, and electron microscopy. Glomerular tuft cross-sectional area was measured by a versatile computer system. Pathologic examination revealed three distinct patterns arbitrarily defined as Classes 1, 2, and 3. Class 1 included 19 patients with typical changes of diabetic nephropathy characterized by a high score of glomerulosclerosis (mean score, 2.1), marked glomerular hypertrophy (23,632 microns2), and arteriolar hyalinosis (mean score, 2). There was a positive correlation between glomerulosclerosis and arteriolar hyalinosis scores (P < 0.05). Class 2 included 16 patients showing chronic and aspecific changes. As compared with Class 1 patients, these patients had less glomerulosclerosis (mean score, 1.3) and less arteriolar hyalinosis (mean score, 0.8) but more severe ischemic glomerular lesions (mean score, 1.4) and arteriosclerosis (mean score, 2). Class 3 included 17 patients showing glomerular disease superimposed on diabetic glomerulosclerosis. There were no differences in age, mean duration of diabetes, renal function, urinary protein excretion, and mean arterial pressure among the three classes of patients. This study indicates that renal lesions in patients with type II diabetes manifest in a quite heterogeneous fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
The Columbia–Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings From Three Multisite Studies With Adolescents and Adults
Authors: Kelly Posner, Gregory K. Brown, Barbara Stanley, David A. Brent, Kseniya V. Yershova, Maria A. Oquendo, Glenn W. Currier, Glenn A. Melvin, Laurence Greenhill, Sa Shen, J. John Mann
Journal: American Journal of Psychiatry (2011)

The Columbia–Suicide Severity Rating Scale was initially designed to assess suicidal ideation and behavior in clinical trials. Psychometric analysis of data on adolescents indicated that a lifetime history of worst-point suicidal ideation including either suicidal intent or intent with a plan predicts a future risk of an actual attempt that is four times as great as the risk associated with a history of current suicidal ideation—including a desire to be dead—or increased general ratings of depression.
Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer
Authors: Li-Ying Sung, Shaorong Gao, Hongmei Shen, Hui Yu, Yifang Song, Sadie L Smith, Ching-Chien Chang, Kimiko Inoue, Lynn Kuo, Jin Lian, Ao Li, X Cindy Tian, David P Tuck, Sherman M Weissman, Xiangzhong Yang, Tao Cheng
Journal: Nature Genetics (2006)
Vindesine–ifosfamide–platinum (VIP) induction chemotherapy in surgically staged IIIA-N2 non-small-cell lung cancer: A prospective study
Authors: J.F. Vansteenkiste, P.R. De Leyn, G.J. Deneffe, Y.N. Lievens, K.L. Nackaerts, D.E. Van Raemdonck, E. van der Schueren, T.E. Lerut, M.G. Demedts
Journal: Annals of Oncology (1998)
Evidence of the Oncologic Superiority of Cylindrical Abdominoperineal Excision for Low Rectal Cancer
Authors: Nicholas P. West, Paul J. Finan, Claes Anderin, Johan Lindholm, Torbjorn Holm, Philip Quirke
Journal: Journal of Clinical Oncology (2008)

Abdominoperineal excision (APE) of the rectum and anus for rectal cancer continues to have greater local recurrence and poorer survival than that seen following anterior resection. Changing to an extended prone perineal dissection results in a more cylindrical specimen and should improve outcomes.One hundred twenty-eight specimens from patients who underwent APE that was performed for potentially curable primary rectal adenocarcinoma were dissected according to standard protocol in Leeds and Stockholm between 1997 and 2007 and were studied. Tissue morphometry was performed on the cross sectional photographs of 93 patient cases.The cylindrical technique removed more tissue in the distal rectum and in all slices that contained tumor compared with the standard operation (both P < .0001). Greater distance was observed from the muscularis propria or internal sphincter to the anterior, posterior, and lateral resection margins (all P < .0001). This was associated with lower circumferential resection margin (CRM) involvement (14.8% v 40.6%; P = .013) and intraoperative perforations (3.7% v 22.8%; P = .0255). An increase in the amount of tissue removed in the distal rectum (P < .0001) was demonstrated by a single surgeon who changed from the standard to the cylindrical technique during the study period; the change was associated with a reduction in CRM positivity (from 36.2% to 12.5%) and in perforations (from 12.8% to 0.0%).Cylindrical APE performed in the prone position for low rectal cancer removes more tissue around the tumor that leads to a reduction in CRM involvement and intraoperative perforations, which should reduce local disease recurrence. The cylindrical technique has the potential to improve patient outcomes substantially if appropriate surgical education programs are developed.
PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial
Authors: W Voskuijl
Journal: Gut (2004)

<b>Background:</b> Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. <b>Aims:</b> To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. <b>Patients:</b> One hundred patients (aged 6 months–15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. <b>Methods:</b> After faecal disimpaction, patients &lt;6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children ⩾6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency ⩾3/week and encopresis ⩽1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. <b>Results:</b> A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre <i>v</i> 7 post treatment/week; lactulose: 3 pre <i>v</i> 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre <i>v</i> 3 post/week; lactulose: 8 pre <i>v</i> 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. <b>Conclusions:</b> PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.
Patterns of expansion and expression divergence in the plant polygalacturonase gene family.
Authors: Joonyup Kim, Shin-Han Shiu, Sharon Thoma, Wen-Hsiung Li, Sara E Patterson
Journal: Genome biology (2006)

Abstract Background Polygalacturonases (PGs) belong to a large gene family in plants and are believed to be responsible for various cell separation processes. PG activities have been shown to be associated with a wide range of plant developmental programs such as seed germination, organ abscission, pod and anther dehiscence, pollen grain maturation, fruit softening and decay, xylem cell formation, and pollen tube growth, thus illustrating divergent roles for members of this gene family. A close look at phylogenetic relationships among Arabidopsis and rice PGs accompanied by analysis of expression data provides an opportunity to address key questions on the evolution and functions of duplicate genes. Results We found that both tandem and whole-genome duplications contribute significantly to the expansion of this gene family but are associated with substantial gene losses. In addition, there are at least 21 PGs in the common ancestor of Arabidopsis and rice. We have also determined the relationships between Arabidopsis and rice PGs and their expression patterns in Arabidopsis to provide insights into the functional divergence between members of this gene family. By evaluating expression in five Arabidopsis tissues and during five stages of abscission, we found overlapping but distinct expression patterns for most of the different PGs. Conclusion Expression data suggest specialized roles or subfunctionalization for each PG gene member. PGs derived from whole genome duplication tend to have more similar expression patterns than those derived from tandem duplications. Our findings suggest that PG duplicates underwent rapid expression divergence and that the mechanisms of duplication affect the divergence rate.