bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Preconditioning Nerve Lesion Inhibits Mechanical Pain Hypersensitivity following Subsequent Neuropathic Injury
Authors: Moalem-Taylor Gila , Li Man , Allbutt Haydn N , Wu Ann , Tracey David J 
Published: January 2011

Background: A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury. Results: We found that a preconditioning crush injury to a terminal branch of the sciatic nerve seven days before partial ligation of the sciatic nerve (PSNL; a model of neuropathic pain) induced a significant attenuation of pain hypersensitivity, particularly mechanical allodynia. A preconditioning lesion of the tibial nerve induced a long-term significant increase in paw-withdrawal threshold to mechanical stimuli and paw-withdrawal latency to thermal stimuli, after PSNL. A preconditioning lesion of the common peroneal induced a smaller but significant short-term increase in paw-withdrawal threshold to mechanical stimuli, after PSNL. There was no difference between preconditioned and unconditioned animals in neuronal damage and macrophage and T-cell infiltration into the dorsal root ganglia (DRGs) or in astrocyte and microglia activation in the spinal dorsal and ventral horns. Conclusions: These results suggest that prior exposure to a mild nerve lesion protects against adverse effects of subsequent neuropathic injury, and that this conditioning-induced inhibition of pain hypersensitivity is not dependent on neuroinflammation in DRGs and spinal cord. Identifying the underlying mechanisms may have important implications for the understanding of neuropathic pain due to nerve injury.
A longitudinal study of chiropractic use among older adults in the United States
Authors: Weigel Paula , Hockenberry Jason M , Bentler Suzanne E , Obrizan Maksym , Kaskie Brian , Jones Michael P , Ohsfeldt Robert L , Rosenthal Gary E , Wallace Robert B , Wolinsky Fredric D 
Published: January 2011

Abstract

Background
Longitudinal patterns of chiropractic use in the United States, particularly among Medicare beneficiaries, are not well documented. Using a nationally representative sample of older Medicare beneficiaries we describe the use of chiropractic over fifteen years, and classify chiropractic users by annual visit volume. We assess the characteristics that are associated with chiropractic use versus nonuse, as well as between different levels of use.

Methods
We analyzed data from two linked sources: the baseline (1993-1994) interview responses of 5,510 self-respondents in the Survey on Assets and Health Dynamics Among the Oldest Old (AHEAD), and their Medicare claims from 1993 to 2007. Binomial logistic regression was used to identify factors associated with chiropractic use versus nonuse, and conditional upon use, to identify factors associated with high volume relative to lower volume use.

Results
There were 806 users of chiropractic in the AHEAD sample yielding a full period prevalence for 1993-2007 of 14.6%. Average annual prevalence between 1993 and 2007 was 4.8% with a range from 4.1% to 5.4%. Approximately 42% of the users consumed chiropractic services only in a single calendar year while 38% used chiropractic in three or more calendar years. Chiropractic users were more likely to be women, white, overweight, have pain, have multiple comorbid conditions, better self-rated health, access to transportation, higher physician utilization levels, live in the Midwest, and live in an area with fewer physicians per capita. Among chiropractic users, 16% had at least one year in which they exceeded Medicare's "soft cap" of 12 visits per calendar year. These over-the-cap users were more likely to have arthritis and mobility limitations, but were less likely to have a high school education. Additionally, these over-the-cap individuals accounted for 58% of total chiropractic claim volume. High volume users saw chiropractors the most among all types of providers, even more than family practice and internal medicine combined.

Conclusion
There is substantial heterogeneity in the patterns of use of chiropractic services among older adults. In spite of the variability of use patterns, however, there are not many characteristics that distinguish high volume users from lower volume users. While high volume users accounted for a significant portion of claims, the enforcement of a hard cap on annual visits by Medicare would not significantly decrease overall claim volume. Further research to understand the factors causing high volume chiropractic utilization among older Americans is warranted to discern between patterns of "need" and patterns of "health maintenance".
Dysphagia in head and neck cancer patients following intensity modulated radiotherapy (IMRT)
Authors: Peponi Evangelia , Glanzmann Christoph , Willi Bettina , Huber Gerhard , Studer Gabriela 
Published: January 2011

Abstract

Background
To evaluate the objective and subjective long term swallowing function, and to relate dysphagia to the radiation dose delivered to the critical anatomical structures in head and neck cancer patients treated with intensity modulated radiation therapy (IMRT, +/- chemotherapy), using a midline protection contour (below hyoid, ~level of vertebra 2/3).

Methods
82 patients with stage III/IV squamous cell carcinoma of the larynx, oropharynx, or hypopharynx, who underwent successful definitive (n = 63, mean dose 68.9Gy) or postoperative (n = 19, mean dose 64.2Gy) simultaneous integrated boost (SIB) -IMRT either alone or in combination with chemotherapy (85%) with curative intent between January 2002 and November 2005, were evaluated retrospectively. 13/63 definitively irradiated patients (21%) presented with a total gross tumor volume (tGTV) >70cc (82-173cc; mean 106cc). In all patients, a laryngo-pharyngeal midline sparing contour outside of the PTV was drawn. Dysphagia was graded according subjective patient-reported and objective observer-assessed instruments. All patients were re-assessed 12 months later. Dose distribution to the swallowing structures was calculated.

Results
At the re-assessment, 32-month mean post treatment follow-up (range 16-60), grade 3/4 objective toxicity was assessed in 10%. At the 32-month evaluation as well as at the last follow up assessment mean 50 months (16-85) post-treatment, persisting swallowing dysfunction grade 3 was subjectively and objectively observed in 1 patient (1%). The 5-year local control rate of the cohort was 75%; no medial marginal failures were observed.

Conclusions
Our results show that sparing the swallowing structures by IMRT seems effective and relatively safe in terms of avoidance of persistent grade 3/4 late dysphagia and local disease control.
Guidelines in the management of obstructing cancer of the left colon: consensus conference of the world society of emergency surgery (WSES) and peritoneum and surgery (PnS) society
Authors: Ansaloni Luca , Andersson Roland E , Bazzoli Franco , Catena Fausto , Cennamo Vincenzo , Di Saverio Salomone , Fuccio Lorenzo , Jeekel Hans , Leppäniemi Ari , Moore Ernest , Pinna Antonio D , Pisano Michele , Repici Alessandro , Sugarbaker Paul H , Tuech Jean-Jaques 
Published: January 2011

Abstract

Background
Obstructive left colon carcinoma (OLCC) is a challenging matter in terms of obstruction release as well of oncological issues. Several options are available and no guidelines are established. The paper aims to generate evidenced based recommendations on management of OLCC.

Methods
The PubMed and Cochrane Library databases were queried for publications focusing on OLCC published prior to April 2010. A extensive retrieval, analyses, and grading of the literature was undertaken. The findings of the research were presented and largely discussed among panellist and audience at the Consensus Conference of the World Society of Emergency Surgery (WSES) and Peritoneum and Surgery (PnS) Society held in Bologna July 2010. Comparisons of techniques are presented and final committee recommendation are enounced.

Results
Hartmann's procedure should be preferred to loop colostomy (Grade 2B). Hartmann's procedure offers no survival benefit compared to segmental colonic resection with primary anastomosis (Grade 2C+); Hartmann's procedure should be considered in patients with high surgical risk (Grade 2C). Total colectomy and segmental colectomy with intraoperative colonic irrigation are associated with same mortality/morbidity, however total colectomy is associated with higher rates impaired bowel function (Grade 1A). Segmental resection and primary anastomosis either with manual decompression or intraoperative colonic irrigation are associated with same mortality/morbidity rate (Grade 1A). In palliation stent placement is associated with similar mortality/morbidity rates and shorter hospital stay (Grade 2B). Stents as a bridge to surgery seems associated with lower mortality rate, shorter hospital stay, and a lower colostomy formation rate (Grade 1B).

Conclusions
Loop colostomy and staged procedure should be adopted in case of dramatic scenario, when neoadjuvant therapy could be expected. Hartmann's procedure should be performed in case of high risk of anastomotic dehiscence. Subtotal and total colectomy should be attempted when cecal perforation or in case of synchronous colonic neoplasm. Primary resection and anastomosis with manual decompression seems the procedure of choice. Colonic stents represent the best option when skills are available. The literature power is relatively poor and the existing RCT are often not sufficiently robust in design thus, among 6 possible treatment modalities, only 2 reached the Grade A.
Two novel human NUMB isoforms provide a potential link between development and cancer
Authors: Karaczyn Aldona , Bani-Yaghoub Mahmud , Tremblay Roger , Kubu Chris , Cowling Rebecca , Adams Tamara L , Prudovsky Igor , Spicer Douglas , Friesel Robert , Vary Calvin , Verdi Joseph M 
Published: January 2011

Abstract
We previously identified four functionally distinct human NUMB isoforms. Here, we report the identification of two additional isoforms and propose a link between the expression of these isoforms and cancer. These novel isoforms, NUMB5 and NUMB6, lack exon 10 and are expressed in cells known for polarity and migratory behavior, such as human amniotic fluid cells, glioblastoma and metastatic tumor cells. RT-PCR and luciferase assays demonstrate that NUMB5 and NUMB6 are less antagonistic to NOTCH signaling than other NUMB isoforms. Immunocytochemistry analyses show that NUMB5 and NUMB6 interact and complex with CDC42, vimentin and the CDC42 regulator IQGAP1 (IQ (motif) GTPase activating protein 1). Furthermore, the ectopic expression of NUMB5 and NUMB6 induces the formation of lamellipodia (NUMB5) and filopodia (NUMB6) in a CDC42- and RAC1-dependent manner. These results are complemented by in vitro and in vivo studies, demonstrating that NUMB5 and NUMB6 alter the migratory behavior of cells. Together, these novel isoforms may play a role in further understanding the NUMB function in development and cancer.
DNA damage and cell cycle events implicate cerebellar dentate nucleus neurons as targets of Alzheimer's disease
Authors: Chen Jianmin , Cohen Mark L , Lerner Alan J , Yang Yan , Herrup Karl 
Published: January 2011

Abstract

Background
Although the cerebellum is considered to be predominantly involved in fine motor control, emerging evidence documents its participation in language, impulsive behavior and higher cognitive functions. While the specific connections of the cerebellar deep nuclei (CDN) that are responsible for these functions are still being worked out, their deficiency has been termed "cerebellar cognitive affective syndrome" - a syndrome that bears a striking similarity to many of the symptoms of Alzheimer's disease (AD). Using ectopic cell cycle events and DNA damage markers as indexes of cellular distress, we have explored the neuropathological involvement of the CDN in human AD.

Results
We examined the human cerebellar dentate nucleus in 22 AD cases and 19 controls for the presence of neuronal cell cycle events and DNA damage using immunohistochemistry and fluorescence in situ hybridization. Both techniques revealed several instances of highly significant correlations. By contrast, neither amyloid plaque nor neurofibrillary tangle pathology was detected in this region, consistent with previous reports of human cerebellar pathology. Five cases of early stage AD were examined and while cell cycle and DNA damage markers were well advanced in the hippocampus of all five, few indicators of either cell cycle events (1 case) or a DNA damage response (1 case) were found in CDN. This implies that CDN neurons are most likely affected later in the course of AD. Clinical-pathological correlations revealed that cases with moderate to high levels of cell cycle activity in their CDN are highly likely to show deficits in unorthodox cerebellar functions including speech, language and motor planning.

Conclusion
Our results reveal that the CDN neurons are under cellular stress in AD and suggest that some of the non-motor symptoms found in patients with AD may be partly cerebellar in origin.
Regulation patterns in signaling networks of cancer
Authors: Schramm Gunnar , Kannabiran Nandakumar , König Rainer 
Published: January 2011

Abstract

Background
Formation of cellular malignancy results from the disruption of fine tuned signaling homeostasis for proliferation, accompanied by mal-functional signals for differentiation, cell cycle and apoptosis. We wanted to observe central signaling characteristics on a global view of malignant cells which have evolved to selfishness and independence in comparison to their non-malignant counterparts that fulfill well defined tasks in their sample.

Results
We investigated the regulation of signaling networks with twenty microarray datasets from eleven different tumor types and their corresponding non-malignant tissue samples. Proteins were represented by their coding genes and regulatory distances were defined by correlating the gene-regulation between neighboring proteins in the network (high correlation = small distance). In cancer cells we observed shorter pathways, larger extension of the networks, a lower signaling frequency of central proteins and links and a higher information content of the network. Proteins of high signaling frequency were enriched with cancer mutations. These proteins showed motifs of regulatory integration in normal cells which was disrupted in tumor cells.

Conclusion
Our global analysis revealed a distinct formation of signaling-regulation in cancer cells when compared to cells of normal samples. From these cancer-specific regulation patterns novel signaling motifs are proposed.
Understanding protein evolutionary rate by integrating gene co-expression with protein interactions
Authors: Pang Kaifang , Cheng Chao , Xuan Zhenyu , Sheng Huanye , Ma Xiaotu 
Published: January 2011

AbstractBackgroundAmong the many factors determining protein evolutionary rate, protein-protein interaction degree (PPID) has been intensively investigated in recent years, but its precise effect on protein evolutionary rate is still heavily debated.ResultsWe first confirmed that the correlation between protein evolutionary rate and PPID varies considerably across different protein interaction datasets. Specifically, because of the maximal inconsistency between yeast two-hybrid and other datasets, we reasoned that the difference in experimental methods contributes to our inability to clearly define how PPID affects protein evolutionary rate. To address this, we integrated protein interaction and gene co-expression data to derive a co-expressed protein-protein interaction degree (ePPID) measure, which reflects the number of partners with which a protein can permanently interact. Thus, irrespective of the experimental method employed, we found that (1) ePPID is a better predictor of protein evolutionary rate than PPID, (2) ePPID is a more robust predictor of protein evolutionary rate than PPID, and (3) the contribution of ePPID to protein evolutionary rate is statistically independent of expression level. Analysis of hub proteins in the Structural Interaction Network further supported ePPID as a better predictor of protein evolutionary rate than the number of distinct binding interfaces and clarified the slower evolution of co-expressed multi-interface hub proteins over that of other hub proteins.ConclusionsOur study firmly established ePPID as a robust predictor of protein evolutionary rate, irrespective of experimental method, and underscored the importance of permanent interactions in shaping the evolutionary outcome.
Antithrombotic therapy and outcomes of cervical arterial dissection in the trauma patient: a case series
Authors: Hinson Holly E , Stallmeyer M JB , Furuno Jon P , Yarbrough Karen L , Cole John W 
Published: January 2011

Abstract

Background
The use of antithrombotic therapy (anticoagulants and/or antiplatelets) in the setting of traumatic cervical arterial dissection (CAD) for the prevention of stroke remains controversial. This issue is further complicated by the frequent co-existence of intracranial hemorrhage (ICH) and other intracranial injuries, and also the wide variability in treatment due to a lack of evidence-based guidance. To address these controversies, a registry in a major Level I trauma center was created. The purpose of this investigation was to compare the safety of antithrombotic therapy in post-traumatic CAD. Analysis from the first year is presented.

Methods
All cervical dissections from the year 2005 were identified in patients at least 18 years of age by diagnosis code from radiology and trauma databases. Presence of arterial injury and grade, and other intracranial disease or injury such as stroke was diagnosed by a trauma radiologist and adjudicated by a neuroradiologist.

Results
Fifty-five patients with cervical artery dissection were identified. Fourteen patients presented with a total of 20 acute, post-traumatic intracranial hemorrhages (ICH). Seven of the 14 patients with ICH were treated with antithrombotic therapy, and none extended their intracranial hemorrhages. Of the 41 patients without pre-existing ICH, 28 were treated with antithrombotic therapy and only one developed an interval hematoma. Among all 55 cases, two patients developed an acute ischemic stroke in the territory of the dissected artery after admission; both patients were in the untreated group.

Conclusion
In so far as antithrombotic therapy may offer benefit in preventing early ischemic stroke following cervical artery dissection, these data suggest withholding antiplatelet or other antithrombotics following trauma may not be warranted, even in the setting of intracranial hemorrhage. From a safety perspective, this registry-based case series indicates antithrombotic management of arterial injury did not contribute to development or progression of ICH, even in patients with pre-existing ICH. This data suggest that instituting early antithrombotic therapy presents a low risk of ICH or hemorrhage extension among traumatic cervical dissection patients.
Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression
Authors: Klomp Jeff A , Petillo David , Niemi Natalie M , Dykema Karl J , Chen Jindong , Yang Ximing J , Sääf Annika , Zickert Peter , Aly Markus , Bergerheim Ulf , Nordenskjöld Magnus , Gad Sophie , Giraud Sophie , Denoux Yves , Yonneau Laurent , Méjean Arnaud , Vasiliu Viorel , Richard Stéphane , MacKeigan Jeffrey P , Teh Bin T , Furge Kyle A 
Published: January 2011

Abstract

Background
Germline mutations in the folliculin (FLCN) gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS), a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affected individuals are histologically similar to sporadic chromophobe renal cell carcinoma (RCC) and sporadic renal oncocytoma. However, most sporadic tumors lack FLCN mutations and the extent to which the BHDS-derived renal tumors share genetic defects associated with the sporadic tumors has not been well studied.

Methods
BHDS individuals were identified symptomatically and FLCN mutations were confirmed by DNA sequencing. Comparative gene expression profiling analyses were carried out on renal tumors isolated from individuals afflicted with BHDS and a panel of sporadic renal tumors of different subtypes using discriminate and clustering approaches. qRT-PCR was used to confirm selected results of the gene expression analyses. We further analyzed differentially expressed genes using gene set enrichment analysis and pathway analysis approaches. Pathway analysis results were confirmed by generation of independent pathway signatures and application to additional datasets.

Results
Renal tumors isolated from individuals with BHDS showed distinct gene expression and cytogenetic characteristics from sporadic renal oncocytoma and chromophobe RCC. The most prominent molecular feature of BHDS-derived kidney tumors was high expression of mitochondria-and oxidative phosphorylation (OXPHOS)-associated genes. This mitochondria expression phenotype was associated with deregulation of the PGC-1α-TFAM signaling axis. Loss of FLCN expression across various tumor types is also associated with increased nuclear mitochondrial gene expression.

Conclusions
Our results support a genetic distinction between BHDS-associated tumors and other renal neoplasias. In addition, deregulation of the PGC-1α-TFAM signaling axis is most pronounced in renal tumors that harbor FLCN mutations and in tumors from other organs that have relatively low expression of FLCN. These results are consistent with the recently discovered interaction between FLCN and AMPK and support a model in which FLCN is a regulator of mitochondrial function.