abstract: @entity4 analogues are promising drugs for @entity3 , but because of their possible side effects such as increased risk of @entity1 , @entity4 which exert their estrogenic effects selectively on bone are desired. It has been shown that rhein inhibits osteoclast formation and bone resorption activity and has an antitumor role in several types of @entity1 . Having found that rhein had high affinity for the bone mineral, we synthesized @entity10 -rhein hybrid compounds and confirmed that one of these hybrid compounds, LC, exhibited a selective profile in the bone and prevented @entity5 but had no effect on endometrium growth in ovariectomized @entity2 . However, the mechanisms underlying its actions on @entity0 bone cells have not been well defined. Here we show that LC concurrently stimulates @entity11 ( @entity11 ) and inhibits @entity13 ( @entity13 ) and @entity6 ( @entity6 ) production by @entity0 osteoblastic MG-63 cells containing two @entity4 receptor (ER) isotypes. Treatment with the ER antagonist @entity7 abrogates the above actions of LC on osteoblast-derived cells. Using small interfering double-stranded RNAs (siRNA) technology, we further demonstrate that the effects of LC on @entity6 production are mediated by both @entity8 and @entity9 but those on @entity11 and @entity13 expression primarily by @entity8 . Furthermore, we also demonstrate that LC functions at least partially through activation of the classic @entity4 response element (ERE) pathway as well as Ras/ @entity14 / @entity12 and @entity15 /Akt signaling. The effect of LC on bone is due to not only its estrogenic activity but also action of its rhein moiety. Also, this compound shows much weaker effect on breast epithelial cell growth than that of @entity10 . Therefore, using rhein for conjugating compounds is a promising method of effectively targeting @entity4 to the bone.

title: LC, a novel XXXX -rhein hybrid compound, concurrently stimulates @entity11 and inhibits receptor activator of NF-kB ligand ( @entity13 ) and @entity6 production by @entity0 osteoblastic cells.

answer: @entity10


abstract: @entity4 analogues are promising drugs for @entity3 , but because of their possible side effects such as increased risk of @entity1 , @entity4 which exert their estrogenic effects selectively on bone are desired. It has been shown that rhein inhibits osteoclast formation and bone resorption activity and has an antitumor role in several types of @entity1 . Having found that rhein had high affinity for the bone mineral, we synthesized @entity10 -rhein hybrid compounds and confirmed that one of these hybrid compounds, LC, exhibited a selective profile in the bone and prevented @entity5 but had no effect on endometrium growth in ovariectomized @entity2 . However, the mechanisms underlying its actions on @entity0 bone cells have not been well defined. Here we show that LC concurrently stimulates @entity11 ( @entity11 ) and inhibits @entity13 ( @entity13 ) and @entity6 ( @entity6 ) production by @entity0 osteoblastic MG-63 cells containing two @entity4 receptor (ER) isotypes. Treatment with the ER antagonist @entity7 abrogates the above actions of LC on osteoblast-derived cells. Using small interfering double-stranded RNAs (siRNA) technology, we further demonstrate that the effects of LC on @entity6 production are mediated by both @entity8 and @entity9 but those on @entity11 and @entity13 expression primarily by @entity8 . Furthermore, we also demonstrate that LC functions at least partially through activation of the classic @entity4 response element (ERE) pathway as well as Ras/ @entity14 / @entity12 and @entity15 /Akt signaling. The effect of LC on bone is due to not only its estrogenic activity but also action of its rhein moiety. Also, this compound shows much weaker effect on breast epithelial cell growth than that of @entity10 . Therefore, using rhein for conjugating compounds is a promising method of effectively targeting @entity4 to the bone.

title: LC, a novel @entity10 -rhein hybrid compound, concurrently stimulates @entity11 and inhibits receptor activator of NF-kB ligand ( XXXX ) and @entity6 production by @entity0 osteoblastic cells.

answer: @entity13


abstract: @entity4 analogues are promising drugs for @entity3 , but because of their possible side effects such as increased risk of @entity1 , @entity4 which exert their estrogenic effects selectively on bone are desired. It has been shown that rhein inhibits osteoclast formation and bone resorption activity and has an antitumor role in several types of @entity1 . Having found that rhein had high affinity for the bone mineral, we synthesized @entity10 -rhein hybrid compounds and confirmed that one of these hybrid compounds, LC, exhibited a selective profile in the bone and prevented @entity5 but had no effect on endometrium growth in ovariectomized @entity2 . However, the mechanisms underlying its actions on @entity0 bone cells have not been well defined. Here we show that LC concurrently stimulates @entity11 ( @entity11 ) and inhibits @entity13 ( @entity13 ) and @entity6 ( @entity6 ) production by @entity0 osteoblastic MG-63 cells containing two @entity4 receptor (ER) isotypes. Treatment with the ER antagonist @entity7 abrogates the above actions of LC on osteoblast-derived cells. Using small interfering double-stranded RNAs (siRNA) technology, we further demonstrate that the effects of LC on @entity6 production are mediated by both @entity8 and @entity9 but those on @entity11 and @entity13 expression primarily by @entity8 . Furthermore, we also demonstrate that LC functions at least partially through activation of the classic @entity4 response element (ERE) pathway as well as Ras/ @entity14 / @entity12 and @entity15 /Akt signaling. The effect of LC on bone is due to not only its estrogenic activity but also action of its rhein moiety. Also, this compound shows much weaker effect on breast epithelial cell growth than that of @entity10 . Therefore, using rhein for conjugating compounds is a promising method of effectively targeting @entity4 to the bone.

title: LC, a novel @entity10 -rhein hybrid compound, concurrently stimulates @entity11 and inhibits receptor activator of NF-kB ligand ( @entity13 ) and XXXX production by @entity0 osteoblastic cells.

answer: @entity6


abstract: @entity4 analogues are promising drugs for @entity3 , but because of their possible side effects such as increased risk of @entity1 , @entity4 which exert their estrogenic effects selectively on bone are desired. It has been shown that rhein inhibits osteoclast formation and bone resorption activity and has an antitumor role in several types of @entity1 . Having found that rhein had high affinity for the bone mineral, we synthesized @entity10 -rhein hybrid compounds and confirmed that one of these hybrid compounds, LC, exhibited a selective profile in the bone and prevented @entity5 but had no effect on endometrium growth in ovariectomized @entity2 . However, the mechanisms underlying its actions on @entity0 bone cells have not been well defined. Here we show that LC concurrently stimulates @entity11 ( @entity11 ) and inhibits @entity13 ( @entity13 ) and @entity6 ( @entity6 ) production by @entity0 osteoblastic MG-63 cells containing two @entity4 receptor (ER) isotypes. Treatment with the ER antagonist @entity7 abrogates the above actions of LC on osteoblast-derived cells. Using small interfering double-stranded RNAs (siRNA) technology, we further demonstrate that the effects of LC on @entity6 production are mediated by both @entity8 and @entity9 but those on @entity11 and @entity13 expression primarily by @entity8 . Furthermore, we also demonstrate that LC functions at least partially through activation of the classic @entity4 response element (ERE) pathway as well as Ras/ @entity14 / @entity12 and @entity15 /Akt signaling. The effect of LC on bone is due to not only its estrogenic activity but also action of its rhein moiety. Also, this compound shows much weaker effect on breast epithelial cell growth than that of @entity10 . Therefore, using rhein for conjugating compounds is a promising method of effectively targeting @entity4 to the bone.

title: LC, a novel @entity10 -rhein hybrid compound, concurrently stimulates @entity11 and inhibits receptor activator of NF-kB ligand ( @entity13 ) and @entity6 production by XXXX osteoblastic cells.

answer: @entity0


abstract: AIM: The clinical and radiological diagnosis of @entity4 ( @entity4 ) can be difficult. When radiological evidence is present, severity and complications, such as perforation and full-thickness @entity1 , often may not be obvious. This study aims to establish early signs of full-thickness @entity1 or perforation by using standard and @entity3 laparoscopy before clinical deterioration of @entity0 occurs. @entity0 AND METHODS: Thirteen @entity0 with preoperative presumed clinical and/or radiological diagnosis of @entity4 underwent laparoscopy. A 4.7-mm umbilical or left upper quadrant camera port was inserted by using the open method. The abdominal cavity was inspected for @entity2 , fibrin, adhesion formation, and presence of free intestinal contents. If necessary, one or two 3-mm working ports were inserted for manipulation of bowel. RESULTS: Median age of 13 @entity0 was 17 (3-38) days. Their median weight was 1160 (910-2415) g. The first 5 @entity0 had standard laparoscopy only, with the next 8 having @entity3 -aided assessment added to the laparoscopy. Standard laparoscopy identified perforation in 5 @entity0 and gangrenous bowel in 2. One @entity0 was found to have chyle ascites, and 1 @entity0 had no abnormal findings on laparoscopy. @entity3 identified gangrenous bowel in 3 additional @entity0 . Laparotomy and necessary surgical intervention were performed in all 10 @entity0 with positive laparoscopy findings. Eleven @entity0 survived and were doing well at a median of 9 (range, 6-39) months of follow-up. CONCLUSION: Laparoscopy helps to improve assessment of @entity0 with a diagnosis of @entity4 . It allows for early identification of perforation and @entity1 . Where @entity2 is suspected, @entity3 laparoscopy may have an added benefit in identifying @entity1 segments.

title: XXXX : early conventional and @entity3 laparoscopic assessment.

answer: @entity4


abstract: AIM: The clinical and radiological diagnosis of @entity4 ( @entity4 ) can be difficult. When radiological evidence is present, severity and complications, such as perforation and full-thickness @entity1 , often may not be obvious. This study aims to establish early signs of full-thickness @entity1 or perforation by using standard and @entity3 laparoscopy before clinical deterioration of @entity0 occurs. @entity0 AND METHODS: Thirteen @entity0 with preoperative presumed clinical and/or radiological diagnosis of @entity4 underwent laparoscopy. A 4.7-mm umbilical or left upper quadrant camera port was inserted by using the open method. The abdominal cavity was inspected for @entity2 , fibrin, adhesion formation, and presence of free intestinal contents. If necessary, one or two 3-mm working ports were inserted for manipulation of bowel. RESULTS: Median age of 13 @entity0 was 17 (3-38) days. Their median weight was 1160 (910-2415) g. The first 5 @entity0 had standard laparoscopy only, with the next 8 having @entity3 -aided assessment added to the laparoscopy. Standard laparoscopy identified perforation in 5 @entity0 and gangrenous bowel in 2. One @entity0 was found to have chyle ascites, and 1 @entity0 had no abnormal findings on laparoscopy. @entity3 identified gangrenous bowel in 3 additional @entity0 . Laparotomy and necessary surgical intervention were performed in all 10 @entity0 with positive laparoscopy findings. Eleven @entity0 survived and were doing well at a median of 9 (range, 6-39) months of follow-up. CONCLUSION: Laparoscopy helps to improve assessment of @entity0 with a diagnosis of @entity4 . It allows for early identification of perforation and @entity1 . Where @entity2 is suspected, @entity3 laparoscopy may have an added benefit in identifying @entity1 segments.

title: @entity4 : early conventional and XXXX laparoscopic assessment.

answer: @entity3


abstract: BACKGROUND/PURPOSE: The aim of the present pilot study was to evaluate the safety and clinical application of intraperitoneal microdialysis (MD) in preterm @entity0 operated on for @entity7 ( @entity7 ). METHODS: Fourteen @entity0 underwent MD. Two were excluded from analysis: 1 because of catheter malfunction and 1 because of fatal outcome immediately after surgery. The median MD time was 122 hours. Samples were collected every 4 hours, and the concentration of @entity2 , @entity5 , @entity6 , and @entity3 was measured. RESULTS: Three @entity0 were reoperated on: 2 because of recurrent @entity7 and 1 because of @entity4 . In the 2 cases with recurrent @entity7 , changes in MD variables were found. Another had a prolonged postoperative period owing to @entity1 . The values of MD normalized along with the return of bowel function. In 8 @entity0 , the postoperative course was uncomplicated. The results of peritoneal MD in @entity0 with complications were significantly different from those with an uncomplicated course ( @entity5 /pyruvate ratio and @entity2 concentration). CONCLUSION: Peritoneal MD is a safe procedure and an applicable method in surveillance of the metabolic and inflammatory changes in the peritoneal cavity after surgery for @entity7 . Larger series are needed to evaluate the clinical significance and use of this method.

title: Intraperitoneal microdialysis in the postoperative surveillance after surgery for XXXX : a preliminary report.

answer: @entity7


abstract: AIM: To study the protective effect of tea @entity5 (TPs) on submandibular glands affected by @entity1 . METHODS: Sixty @entity0 were randomly divided into radiation group (R-group, N = 30) and TP-pre-treated-radiation group (TPR-group, N = 30). The @entity0 were intragastrically administered with TP or normal @entity2 from 14 days before radiation, continuously daily, until the experiment. All the @entity0 in both groups were irradiated with a single exposure dose of 15 Gy gamma rays that were delivered to the head and neck areas. Ten @entity0 of each group were anatomised on the 3rd, 6th and 30th day after irradiation, respectively. The submandibular glands of the @entity0 were removed for the study. The morphologic changes of the submandibular glands were observed by transmission electron microscopy (TEM). The @entity7 ( @entity7 )-mediated @entity6 ( @entity4 )- @entity3 nick-end labelling (TUNEL) method was used to detect apoptosis of the submandibular glands' cells. RESULTS: Electron microscope observation of the submandibular glands showed that the lesions of the TPR-group were mild. Change in apoptosis of the cells was not obvious compared with the R-group. The cell apotosis was typical after irradiation in the R-group. Apoptosis index that was detected in the cells of submandibular glands of the TPR-group was statistically significantly decreased compared with the R-group (P < 0.01) on the 3rd, 6th and 30th day after irradiation. CONCLUSION: TP could protect submandibular glands from @entity1 , and the protection mechanism may be realised by anti-apoptosis.

title: Tea XXXX protect against irradiation-induced injury in submandibular glands' cells: a preliminary study.

answer: @entity5


abstract: INTRODUCTION: Although the natural history and management of infected open @entity4 ( @entity4 ) repair is well described, only sporadic case reports have described the fate of @entity0 with infected endografts placed in the abdominal aorta. The present study describes a tertiary referral center's experience with @entity7 repairs (EVARs). METHODS: The medical records of 1302 open and endovascular aortic procedures were queried from January 2000 to January 2010. The cases were reviewed for prior aortic procedures, prosthetic implants, and etiology of current open procedure. Demographics, operative details, and perioperative courses were documented. RESULTS: Nine @entity0 (1 @entity0 ) with a mean age of 71 years had an EVAR that later required an open procedure for explantation and surgical revision for suspected @entity1 . All grafts were explanted through a midline transperitoneal approach, with a mean time to explant of 33 months. The explanted endografts included 4 Zenith (Cook, Bloomington, Ind), 2 Ancure (Endovascular Technologies, Menlo Park, @entity6 ), 2 Excluders (Gore, Flagstaff, Ariz), and 1 AneuRx (Medtronic, Minneapolis, Minn). Eight of the nine original EVARs were performed at other hospitals; 1 @entity0 had EVAR and open explant at the University of Michigan. All @entity0 had preoperative computed tomography scans, except one who was transferred in extremis with a @entity2 . Three @entity0 also had a tagged leukocyte scan, and two had magnetic resonance imaging to further reinforce the suspicion of @entity1 before explantation and bypass planning. Rifampin-soaked Hemashield (Boston Scientific) in situ grafts were used in four @entity0 , with extra-anatomic (axillary-bifemoral) bypass used in the other five. The in situ group had no positive preoperative or postoperative cultures, with the exception of the unstable @entity0 who died the day of surgery. For the other five @entity0 , positive tissue cultures were found for Bacteroides, @entity3 , coagulase-negative Staphylococcus, Streptococcus, and Candida. Three @entity0 were found to have @entity5 , two of whom died before discharge from the hospital. The remaining seven survived to discharge. Average length of stay was 22 days, with a median follow-up of 11 months. CONCLUSION: This series of infected EVARs is the largest group of infected @entity4 endografts reported to date. Because EVAR of AAAs is presently the most common method of repair, development of endograft @entity1 , while rare, can be managed with acceptable mortality rates. @entity0 presenting with @entity5 after EVAR appear to have a more virulent course.

title: Graft @entity1 after XXXX repair.

answer: @entity4


abstract: INTRODUCTION: Although the natural history and management of infected open @entity4 ( @entity4 ) repair is well described, only sporadic case reports have described the fate of @entity0 with infected endografts placed in the abdominal aorta. The present study describes a tertiary referral center's experience with @entity7 repairs (EVARs). METHODS: The medical records of 1302 open and endovascular aortic procedures were queried from January 2000 to January 2010. The cases were reviewed for prior aortic procedures, prosthetic implants, and etiology of current open procedure. Demographics, operative details, and perioperative courses were documented. RESULTS: Nine @entity0 (1 @entity0 ) with a mean age of 71 years had an EVAR that later required an open procedure for explantation and surgical revision for suspected @entity1 . All grafts were explanted through a midline transperitoneal approach, with a mean time to explant of 33 months. The explanted endografts included 4 Zenith (Cook, Bloomington, Ind), 2 Ancure (Endovascular Technologies, Menlo Park, @entity6 ), 2 Excluders (Gore, Flagstaff, Ariz), and 1 AneuRx (Medtronic, Minneapolis, Minn). Eight of the nine original EVARs were performed at other hospitals; 1 @entity0 had EVAR and open explant at the University of Michigan. All @entity0 had preoperative computed tomography scans, except one who was transferred in extremis with a @entity2 . Three @entity0 also had a tagged leukocyte scan, and two had magnetic resonance imaging to further reinforce the suspicion of @entity1 before explantation and bypass planning. Rifampin-soaked Hemashield (Boston Scientific) in situ grafts were used in four @entity0 , with extra-anatomic (axillary-bifemoral) bypass used in the other five. The in situ group had no positive preoperative or postoperative cultures, with the exception of the unstable @entity0 who died the day of surgery. For the other five @entity0 , positive tissue cultures were found for Bacteroides, @entity3 , coagulase-negative Staphylococcus, Streptococcus, and Candida. Three @entity0 were found to have @entity5 , two of whom died before discharge from the hospital. The remaining seven survived to discharge. Average length of stay was 22 days, with a median follow-up of 11 months. CONCLUSION: This series of infected EVARs is the largest group of infected @entity4 endografts reported to date. Because EVAR of AAAs is presently the most common method of repair, development of endograft @entity1 , while rare, can be managed with acceptable mortality rates. @entity0 presenting with @entity5 after EVAR appear to have a more virulent course.

title: Graft XXXX after @entity4 repair.

answer: @entity1


abstract: BACKGROUND: While @entity2 ( @entity2 ) is established in the management of small unifocal @entity0 its role in management of @entity4 ( @entity4 ), multicentric (MC) and @entity1 is still evolving. METHODS: Medline was searched; studies meeting pre-determined criteria were included. Data were extracted and entered into evidence tables. RESULTS: Twenty six studies met inclusion criteria and reported data on accuracy; no randomized trials were identified. For @entity1 (n = 314 cases), success rate for identification of an @entity3 was 86-94%, @entity3 positivity rate 42-59%, false negative rate (FNR) 0-33% and overall accuracy 78-100%. For MC (n = 294 cases): success rate 92-100%, @entity3 positivity rate 25-61%, FNR 4-8% and accuracy 96-100%. For 'multiple @entity0 ' (studies combining @entity4 /MC cases; n = 996 cases): success rate 92-100%, @entity3 positivity rate 12-63%, FNR 0-25%, and accuracy 82-100%. For @entity1 (n = 1912 cases): success rate 86-100%, @entity3 positivity rate 49-77%, FNR 3-18% and accuracy 85-98%. For MC/ @entity4 and larger @entity1 overall non- @entity3 positivity rates were up to 82%; axillary recurrence rates were low but seldom reported. CONCLUSION: There are no randomized trials evaluating the safety of @entity2 in @entity0 . Based on limited evidence, success rate and FNR appear to be similar to those for small unifocal @entity1 , however node positivity rates are higher and rates of non- @entity3 positivity are very high. Awareness of these issues is essential when recommending @entity2 based axillary management for these higher-risk @entity1 .

title: Accuracy of @entity2 in large and XXXX /multicentric @entity0 --a systematic review.

answer: @entity4


abstract: BACKGROUND: While @entity2 ( @entity2 ) is established in the management of small unifocal @entity0 its role in management of @entity4 ( @entity4 ), multicentric (MC) and @entity1 is still evolving. METHODS: Medline was searched; studies meeting pre-determined criteria were included. Data were extracted and entered into evidence tables. RESULTS: Twenty six studies met inclusion criteria and reported data on accuracy; no randomized trials were identified. For @entity1 (n = 314 cases), success rate for identification of an @entity3 was 86-94%, @entity3 positivity rate 42-59%, false negative rate (FNR) 0-33% and overall accuracy 78-100%. For MC (n = 294 cases): success rate 92-100%, @entity3 positivity rate 25-61%, FNR 4-8% and accuracy 96-100%. For 'multiple @entity0 ' (studies combining @entity4 /MC cases; n = 996 cases): success rate 92-100%, @entity3 positivity rate 12-63%, FNR 0-25%, and accuracy 82-100%. For @entity1 (n = 1912 cases): success rate 86-100%, @entity3 positivity rate 49-77%, FNR 3-18% and accuracy 85-98%. For MC/ @entity4 and larger @entity1 overall non- @entity3 positivity rates were up to 82%; axillary recurrence rates were low but seldom reported. CONCLUSION: There are no randomized trials evaluating the safety of @entity2 in @entity0 . Based on limited evidence, success rate and FNR appear to be similar to those for small unifocal @entity1 , however node positivity rates are higher and rates of non- @entity3 positivity are very high. Awareness of these issues is essential when recommending @entity2 based axillary management for these higher-risk @entity1 .

title: Accuracy of @entity2 in large and @entity4 /multicentric XXXX --a systematic review.

answer: @entity0


abstract: BACKGROUND: While @entity2 ( @entity2 ) is established in the management of small unifocal @entity0 its role in management of @entity4 ( @entity4 ), multicentric (MC) and @entity1 is still evolving. METHODS: Medline was searched; studies meeting pre-determined criteria were included. Data were extracted and entered into evidence tables. RESULTS: Twenty six studies met inclusion criteria and reported data on accuracy; no randomized trials were identified. For @entity1 (n = 314 cases), success rate for identification of an @entity3 was 86-94%, @entity3 positivity rate 42-59%, false negative rate (FNR) 0-33% and overall accuracy 78-100%. For MC (n = 294 cases): success rate 92-100%, @entity3 positivity rate 25-61%, FNR 4-8% and accuracy 96-100%. For 'multiple @entity0 ' (studies combining @entity4 /MC cases; n = 996 cases): success rate 92-100%, @entity3 positivity rate 12-63%, FNR 0-25%, and accuracy 82-100%. For @entity1 (n = 1912 cases): success rate 86-100%, @entity3 positivity rate 49-77%, FNR 3-18% and accuracy 85-98%. For MC/ @entity4 and larger @entity1 overall non- @entity3 positivity rates were up to 82%; axillary recurrence rates were low but seldom reported. CONCLUSION: There are no randomized trials evaluating the safety of @entity2 in @entity0 . Based on limited evidence, success rate and FNR appear to be similar to those for small unifocal @entity1 , however node positivity rates are higher and rates of non- @entity3 positivity are very high. Awareness of these issues is essential when recommending @entity2 based axillary management for these higher-risk @entity1 .

title: Accuracy of XXXX in large and @entity4 /multicentric @entity0 --a systematic review.

answer: @entity2


abstract: Trypanosomatids present unusual organelles, such as the kinetoplast that contains the mitochondrial DNA arranged in catenated circles. The nucleus of these protozoa presents distinct domains during interphase as well as a closed mitosis. DNA topoisomerases modulate the topological state of DNA by regulating supercoiling of the double-stranded DNA during replication, transcription, recombination and repair. Because topoisomerases play essential roles in cellular processes, they constitute a potential target for antitumour and antimicrobial drugs. In this study, the effects of various topoisomerase inhibitors and DNA-binding drugs were tested on the cellular proliferation and ultrastructure of the @entity0 epimastigote form Blastocrithidia culicis was used as a comparative model, which has a more relaxed kinetoplast DNA (kDNA) organization. The results showed that the eukaryotic topoisomerase I inhibitors @entity5 and @entity6 were the most effective compounds in the arrest of @entity0 proliferation. Of the eukaryotic topoisomerase II inhibitors, @entity1 , but not @entity4 , was effective against cell proliferation. The prokaryotic topoisomerase II inhibitors @entity3 and @entity2 targeted the kinetoplast specifically, thus promoting ultrastructural kDNA rearrangement in B. culicis. Of the DNA-binding drugs, berenil caused remarkable kDNA disorganization. With the exception of @entity5 , there have been no previous evaluations of the compounds tested here on trypanosomatid ultrastructure. In conclusion, inhibitors of the same class may have different effects on trypanosomatid proliferation and ultrastructure. The results obtained in this work may help to reveal the mechanism of action of different topoisomerase inhibitors in trypanosomatids.

title: Effect of topoisomerase inhibitors and DNA-binding drugs on the cell proliferation and ultrastructure of XXXX .

answer: @entity0


abstract: Oral (p.o.) administration of a single dose of kalmegh leaf extract (KE; 0.5 g/kg and 1.0 g/kg) or @entity3 (A; 5 mg/kg and 10 mg/kg) to adult male albino @entity0 (100-120 g) produced a dose-related and time-dependent characteristic activation of brush-border membrane-bound hydrolases, viz. @entity2 , maltase and sucrase in three regions of small intestine (viz. duodenum, jejunum and ileum). The maximum stimulation of these disaccharidases was obtained at 6 hr of either KE or A administration. Further, it was also noted that the extent of activation of the disaccharidases with KE or A, both at higher and lower doses, followed the order: (a) Maltase greater than sucrase greater than @entity2 in duodenum and (b) Maltase greater than @entity2 greater than sucrase in jejunum and ileum. Long term administration (for 7, 15 and 30 consecutive days) of either KE (500 p.o.) or A (5 mg/kg/day; p.o.) stimulated @entity2 , maltase and sucrase in all parts of the small intestine. Maximum stimulation of @entity2 and maltase was noted after 30 consecutive days of treatment while sucrase exhibited maximum activation after 15 consecutive of treatment with either KE or A. These results suggest that both KE and A accelerate intestinal digestion and absorption of @entity1 by activating these intestinal disaccharidases.

title: XXXX and kalmegh (Andrographis paniculata) extract: effect on intestinal brush-border membrane-bound hydrolases.

answer: @entity3


abstract: PURPOSE: @entity2 (PSA) test has become a widely used screening test in @entity1 ( @entity3 ). However, low specificity of serum PSA leads to many false-positive and false-negative results and clinical uncertainty. Development of @entity3 -specific diagnostic and prognostic markers is needed. Detection of circulating PSA-expressing cells (CPECs) in blood and bone marrow of @entity3 @entity0 has potential in molecular diagnosis and prognosis. Our novel observations of the frequent presence of CPECs in @entity3 @entity0 with organ-confined disease by reverse transcription (RT)-PCR-PSA assay in epithelial cells enriched from peripheral blood (ERT-PCR/PSA) have led us to test the hypothesis that CPECs have diagnostic potential for @entity3 . EXPERIMENTAL DESIGN: Epithelial cells from peripheral blood of radical prostatectomy @entity0 or prostate biopsy @entity0 were isolated using antiepithelial cell antibody, Ber-EP4-coated magnetic beads, and total RNA specimens from these cells were analyzed for PSA expression by RT-PCR. RESULTS: Peripheral blood specimens of 108 of 135 (80.0%) @entity3 @entity0 were positive in ERT-PCR/PSA assay. Peripheral blood specimens from 45 control @entity0 were virtually negative (97.8%). In the blinded investigation, 84 @entity0 who had biopsy for suspicion of @entity3 were evaluated by ERT-PCR/PSA assay. Eighteen of 22 (81.8%) @entity0 with biopsy-proven @entity3 were positive, and 54 of 62 (87.1%) @entity0 with biopsy negative for @entity3 were negative in this assay (P < 0.001). CONCLUSIONS: Our study provides intriguing novel results showing that the majority of @entity0 with clinically organ-confined @entity3 contain CPECs. Strong concordance between the biopsy results and ERT-PCR/PSA assay (sensitivity 81.8%; specificity 87.1%) suggests a potentially new diagnostic application of this type of assay in @entity3 diagnosis.

title: Diagnostic potential of XXXX expressing epithelial cells in blood of @entity1 @entity0 .

answer: @entity2


abstract: PURPOSE: @entity2 (PSA) test has become a widely used screening test in @entity1 ( @entity3 ). However, low specificity of serum PSA leads to many false-positive and false-negative results and clinical uncertainty. Development of @entity3 -specific diagnostic and prognostic markers is needed. Detection of circulating PSA-expressing cells (CPECs) in blood and bone marrow of @entity3 @entity0 has potential in molecular diagnosis and prognosis. Our novel observations of the frequent presence of CPECs in @entity3 @entity0 with organ-confined disease by reverse transcription (RT)-PCR-PSA assay in epithelial cells enriched from peripheral blood (ERT-PCR/PSA) have led us to test the hypothesis that CPECs have diagnostic potential for @entity3 . EXPERIMENTAL DESIGN: Epithelial cells from peripheral blood of radical prostatectomy @entity0 or prostate biopsy @entity0 were isolated using antiepithelial cell antibody, Ber-EP4-coated magnetic beads, and total RNA specimens from these cells were analyzed for PSA expression by RT-PCR. RESULTS: Peripheral blood specimens of 108 of 135 (80.0%) @entity3 @entity0 were positive in ERT-PCR/PSA assay. Peripheral blood specimens from 45 control @entity0 were virtually negative (97.8%). In the blinded investigation, 84 @entity0 who had biopsy for suspicion of @entity3 were evaluated by ERT-PCR/PSA assay. Eighteen of 22 (81.8%) @entity0 with biopsy-proven @entity3 were positive, and 54 of 62 (87.1%) @entity0 with biopsy negative for @entity3 were negative in this assay (P < 0.001). CONCLUSIONS: Our study provides intriguing novel results showing that the majority of @entity0 with clinically organ-confined @entity3 contain CPECs. Strong concordance between the biopsy results and ERT-PCR/PSA assay (sensitivity 81.8%; specificity 87.1%) suggests a potentially new diagnostic application of this type of assay in @entity3 diagnosis.

title: Diagnostic potential of @entity2 expressing epithelial cells in blood of XXXX @entity0 .

answer: @entity1


abstract: PURPOSE: @entity2 (PSA) test has become a widely used screening test in @entity1 ( @entity3 ). However, low specificity of serum PSA leads to many false-positive and false-negative results and clinical uncertainty. Development of @entity3 -specific diagnostic and prognostic markers is needed. Detection of circulating PSA-expressing cells (CPECs) in blood and bone marrow of @entity3 @entity0 has potential in molecular diagnosis and prognosis. Our novel observations of the frequent presence of CPECs in @entity3 @entity0 with organ-confined disease by reverse transcription (RT)-PCR-PSA assay in epithelial cells enriched from peripheral blood (ERT-PCR/PSA) have led us to test the hypothesis that CPECs have diagnostic potential for @entity3 . EXPERIMENTAL DESIGN: Epithelial cells from peripheral blood of radical prostatectomy @entity0 or prostate biopsy @entity0 were isolated using antiepithelial cell antibody, Ber-EP4-coated magnetic beads, and total RNA specimens from these cells were analyzed for PSA expression by RT-PCR. RESULTS: Peripheral blood specimens of 108 of 135 (80.0%) @entity3 @entity0 were positive in ERT-PCR/PSA assay. Peripheral blood specimens from 45 control @entity0 were virtually negative (97.8%). In the blinded investigation, 84 @entity0 who had biopsy for suspicion of @entity3 were evaluated by ERT-PCR/PSA assay. Eighteen of 22 (81.8%) @entity0 with biopsy-proven @entity3 were positive, and 54 of 62 (87.1%) @entity0 with biopsy negative for @entity3 were negative in this assay (P < 0.001). CONCLUSIONS: Our study provides intriguing novel results showing that the majority of @entity0 with clinically organ-confined @entity3 contain CPECs. Strong concordance between the biopsy results and ERT-PCR/PSA assay (sensitivity 81.8%; specificity 87.1%) suggests a potentially new diagnostic application of this type of assay in @entity3 diagnosis.

title: Diagnostic potential of @entity2 expressing epithelial cells in blood of @entity1 XXXX .

answer: @entity0


abstract: PURPOSE: The small GTP-binding protein Rho and its best-characterized downstream effector Rho-associated @entity4 - @entity5 protein kinase, ROCK, participate in actin cytoskeleton organization, and are linked to pathogenesis and progression of several @entity0 @entity2 . We investigated the roles of Rho and ROCK in @entity3 . EXPERIMENTAL DESIGN: Using Western blotting, we quantitated Rho and ROCK protein expression in paired @entity2 and nontumor surgical samples from 107 consecutive Japanese @entity0 with @entity3 . RESULTS: @entity6 , @entity8 , and ROCK were more abundant in @entity2 and metastatic lymph nodes than in nontumor bladder and uninvolved lymph nodes (P < 0.0001). Amounts of @entity6 and @entity8 protein, and ROCK protein expression correlated positively with one another (P < 0.0001). High @entity6 , @entity8 , and ROCK expression were related to poor @entity2 differentiation (P < 0.05, P < 0.01, and P < 0.01, respectively), muscle invasion (P < 0.001), and lymph node @entity1 (P < 0.05). Kaplan-Meier plots linked high @entity6 , @entity8 , and ROCK protein expression to shortened disease-free and overall survival (P < 0.0001). By univariate analysis, high @entity6 , @entity8 , and ROCK protein expression predicted shortened disease-free and overall survival (P < 0.0001). By multivariate analysis, only @entity8 was independently influenced in disease-free survival (P < 0.05), and @entity6 and @entity8 in overall survival (P < 0.001). In contrast, @entity7 expression was inversely related to the grade and stage (P < 0.05), and its higher expression is associated with better overall survival (P < 0.05). In superficial @entity2 (Ta or T1; 63 @entity0 ), @entity6 , @entity8 , and ROCK were unrelated with recurrence-free survival. Overall survival in @entity2 invading muscle (T2 to T4; 44 @entity0 ) was significantly influenced by @entity6 , @entity8 , and ROCK in a Kaplan-Meier analysis (P < 0.0001, P < 0.0001, and P < 0.01, respectively). Whereas @entity6 , @entity8 , and ROCK independently predicted shortened overall survival in @entity0 with invasive @entity2 by univariate analysis (P < 0.0001, P < 0.0001, and P < 0.01, respectively), only @entity8 did so by multivariate analysis (P < 0.05). CONCLUSION: Rho/ROCK pathway apparently involved in occurrence and progression of @entity3 may be valuable prognostic markers.

title: Significant association of Rho/ROCK pathway with invasion and @entity1 of XXXX .

answer: @entity3


abstract: PURPOSE: The small GTP-binding protein Rho and its best-characterized downstream effector Rho-associated @entity4 - @entity5 protein kinase, ROCK, participate in actin cytoskeleton organization, and are linked to pathogenesis and progression of several @entity0 @entity2 . We investigated the roles of Rho and ROCK in @entity3 . EXPERIMENTAL DESIGN: Using Western blotting, we quantitated Rho and ROCK protein expression in paired @entity2 and nontumor surgical samples from 107 consecutive Japanese @entity0 with @entity3 . RESULTS: @entity6 , @entity8 , and ROCK were more abundant in @entity2 and metastatic lymph nodes than in nontumor bladder and uninvolved lymph nodes (P < 0.0001). Amounts of @entity6 and @entity8 protein, and ROCK protein expression correlated positively with one another (P < 0.0001). High @entity6 , @entity8 , and ROCK expression were related to poor @entity2 differentiation (P < 0.05, P < 0.01, and P < 0.01, respectively), muscle invasion (P < 0.001), and lymph node @entity1 (P < 0.05). Kaplan-Meier plots linked high @entity6 , @entity8 , and ROCK protein expression to shortened disease-free and overall survival (P < 0.0001). By univariate analysis, high @entity6 , @entity8 , and ROCK protein expression predicted shortened disease-free and overall survival (P < 0.0001). By multivariate analysis, only @entity8 was independently influenced in disease-free survival (P < 0.05), and @entity6 and @entity8 in overall survival (P < 0.001). In contrast, @entity7 expression was inversely related to the grade and stage (P < 0.05), and its higher expression is associated with better overall survival (P < 0.05). In superficial @entity2 (Ta or T1; 63 @entity0 ), @entity6 , @entity8 , and ROCK were unrelated with recurrence-free survival. Overall survival in @entity2 invading muscle (T2 to T4; 44 @entity0 ) was significantly influenced by @entity6 , @entity8 , and ROCK in a Kaplan-Meier analysis (P < 0.0001, P < 0.0001, and P < 0.01, respectively). Whereas @entity6 , @entity8 , and ROCK independently predicted shortened overall survival in @entity0 with invasive @entity2 by univariate analysis (P < 0.0001, P < 0.0001, and P < 0.01, respectively), only @entity8 did so by multivariate analysis (P < 0.05). CONCLUSION: Rho/ROCK pathway apparently involved in occurrence and progression of @entity3 may be valuable prognostic markers.

title: Significant association of Rho/ROCK pathway with invasion and XXXX of @entity3 .

answer: @entity1


abstract: BACKGROUND: @entity4 ( @entity4 ), an inherited @entity2 , is a severe @entity3 of infancy which is clinically characterized by absence of @entity1 and presence of intestinal villous atrophy. Mutations in the @entity5 gene were identified to cause @entity4 . Recent cases of @entity4 harboring the @entity7 (19q13.2) mutation were described. METHODS: Four @entity4 Italian @entity0 were clinically and immunohistochemically characterized. Direct DNA sequencing of @entity5 and @entity7 genes was performed. RESULTS: All @entity0 were of Italian origin. Three different mutations were detected (p.Asp219Metfs*15, @entity8 *6 and @entity9 ) in the @entity5 gene; one of them is novel ( @entity9 ). Two @entity0 (P1 and P2) showed compound heterozygosity revealing two mutations in separate alleles. A third @entity0 (P3) was heterozygous for only one novel @entity5 missense mutation ( @entity9 ). In a syndromic @entity0 (P4), no deleterious @entity5 mutation was found. Additional @entity7 mutational analysis was performed. P4 showed a homozygous @entity7 mutation ( @entity10 ). No @entity7 mutation was found in P3. @entity6 was also evaluated as a candidate gene by mutational screening in P3 but no mutation was identified. CONCLUSION: This study presented a molecular characterization of @entity4 Italian @entity0 , and identified three mutations in the @entity5 gene and one in the @entity7 gene. One of @entity5 mutations was novel, therefore increasing the mutational spectrum of allelic variants of the @entity5 gene. Molecular analysis of the @entity7 gene also allowed us to identify a @entity7 substitution mutation ( @entity11 ) recently found to be associated with syndromic @entity4 subjects.

title: Genetic analysis of Italian @entity0 with XXXX .

answer: @entity4


abstract: BACKGROUND: @entity4 ( @entity4 ), an inherited @entity2 , is a severe @entity3 of infancy which is clinically characterized by absence of @entity1 and presence of intestinal villous atrophy. Mutations in the @entity5 gene were identified to cause @entity4 . Recent cases of @entity4 harboring the @entity7 (19q13.2) mutation were described. METHODS: Four @entity4 Italian @entity0 were clinically and immunohistochemically characterized. Direct DNA sequencing of @entity5 and @entity7 genes was performed. RESULTS: All @entity0 were of Italian origin. Three different mutations were detected (p.Asp219Metfs*15, @entity8 *6 and @entity9 ) in the @entity5 gene; one of them is novel ( @entity9 ). Two @entity0 (P1 and P2) showed compound heterozygosity revealing two mutations in separate alleles. A third @entity0 (P3) was heterozygous for only one novel @entity5 missense mutation ( @entity9 ). In a syndromic @entity0 (P4), no deleterious @entity5 mutation was found. Additional @entity7 mutational analysis was performed. P4 showed a homozygous @entity7 mutation ( @entity10 ). No @entity7 mutation was found in P3. @entity6 was also evaluated as a candidate gene by mutational screening in P3 but no mutation was identified. CONCLUSION: This study presented a molecular characterization of @entity4 Italian @entity0 , and identified three mutations in the @entity5 gene and one in the @entity7 gene. One of @entity5 mutations was novel, therefore increasing the mutational spectrum of allelic variants of the @entity5 gene. Molecular analysis of the @entity7 gene also allowed us to identify a @entity7 substitution mutation ( @entity11 ) recently found to be associated with syndromic @entity4 subjects.

title: Genetic analysis of Italian XXXX with @entity4 .

answer: @entity0


abstract: Increased plasma levels of @entity9 , a platelet activation marker, are observed in @entity6 . Urinary albumin excretion, a marker of endothelial cell perturbation, is related to @entity3 in @entity2 . To test the value of these markers in predicting forthcoming @entity5 , the relations between urinary excretions of high molecular weight @entity9 (HMW-beta TGf) and albumin and subsequent @entity5 in a cohort of 15,484 middle-aged @entity1 were investigated in a nested case-control study. Baseline questionnaire data and urine samples were available from a @entity0 screening program in Utrecht during 1982-1985. Cases were Utrecht hospital admissions for @entity7 (n = 50) or angiographically confirmed @entity5 (n = 28) from 1982-1985 to 1990-1991. Classifying events occurred a median of 5.1 years after baseline. Controls were a random sample from the cohort, individually case matched for baseline examination date and age, at a 1:2 ratio. HMW-beta TG/ @entity8 ratios (ng/mmol, mean +/- standard error) were 5.3 +/- 0.3 in cases and 4.7 +/- 0.3 in controls; albumin/ @entity8 ratios (mg/mmol, median) were, respectively, 0.37 and 0.22. Crude odds ratios for classification in the highest compared with the lowest tertiles of HMW-beta TG/ @entity8 and albumin/ @entity8 distributions were elevated for cases compared with controls: HMW-beta TG/ @entity8 odds ratio = 2.4, 95% confidence interval 1.1-5.0; albumin/ @entity8 odds ratio = 2.1, 95% confidence interval 1.0-4.1. These relations persisted after adjustment for smoking, @entity4 , Quetelet index, and menopausal status. Both urinary HMW-beta TG and albumin excretion are markers of @entity5 risk in middle-aged @entity1 , indicating that increased platelet activation and endothelial cell perturbation precede @entity5 events in @entity1 .

title: Urinary excretions of high molecular weight @entity9 and albumin are independently associated with XXXX in @entity1 , a nested case-control study of middle-aged @entity1 in the Diagnostisch Onderzoek Mammacarcinoom (DOM) Cohort, Utrecht, Netherlands.

answer: @entity5


abstract: Increased plasma levels of @entity9 , a platelet activation marker, are observed in @entity6 . Urinary albumin excretion, a marker of endothelial cell perturbation, is related to @entity3 in @entity2 . To test the value of these markers in predicting forthcoming @entity5 , the relations between urinary excretions of high molecular weight @entity9 (HMW-beta TGf) and albumin and subsequent @entity5 in a cohort of 15,484 middle-aged @entity1 were investigated in a nested case-control study. Baseline questionnaire data and urine samples were available from a @entity0 screening program in Utrecht during 1982-1985. Cases were Utrecht hospital admissions for @entity7 (n = 50) or angiographically confirmed @entity5 (n = 28) from 1982-1985 to 1990-1991. Classifying events occurred a median of 5.1 years after baseline. Controls were a random sample from the cohort, individually case matched for baseline examination date and age, at a 1:2 ratio. HMW-beta TG/ @entity8 ratios (ng/mmol, mean +/- standard error) were 5.3 +/- 0.3 in cases and 4.7 +/- 0.3 in controls; albumin/ @entity8 ratios (mg/mmol, median) were, respectively, 0.37 and 0.22. Crude odds ratios for classification in the highest compared with the lowest tertiles of HMW-beta TG/ @entity8 and albumin/ @entity8 distributions were elevated for cases compared with controls: HMW-beta TG/ @entity8 odds ratio = 2.4, 95% confidence interval 1.1-5.0; albumin/ @entity8 odds ratio = 2.1, 95% confidence interval 1.0-4.1. These relations persisted after adjustment for smoking, @entity4 , Quetelet index, and menopausal status. Both urinary HMW-beta TG and albumin excretion are markers of @entity5 risk in middle-aged @entity1 , indicating that increased platelet activation and endothelial cell perturbation precede @entity5 events in @entity1 .

title: Urinary excretions of high molecular weight XXXX and albumin are independently associated with @entity5 in @entity1 , a nested case-control study of middle-aged @entity1 in the Diagnostisch Onderzoek Mammacarcinoom (DOM) Cohort, Utrecht, Netherlands.

answer: @entity9


abstract: Increased plasma levels of @entity9 , a platelet activation marker, are observed in @entity6 . Urinary albumin excretion, a marker of endothelial cell perturbation, is related to @entity3 in @entity2 . To test the value of these markers in predicting forthcoming @entity5 , the relations between urinary excretions of high molecular weight @entity9 (HMW-beta TGf) and albumin and subsequent @entity5 in a cohort of 15,484 middle-aged @entity1 were investigated in a nested case-control study. Baseline questionnaire data and urine samples were available from a @entity0 screening program in Utrecht during 1982-1985. Cases were Utrecht hospital admissions for @entity7 (n = 50) or angiographically confirmed @entity5 (n = 28) from 1982-1985 to 1990-1991. Classifying events occurred a median of 5.1 years after baseline. Controls were a random sample from the cohort, individually case matched for baseline examination date and age, at a 1:2 ratio. HMW-beta TG/ @entity8 ratios (ng/mmol, mean +/- standard error) were 5.3 +/- 0.3 in cases and 4.7 +/- 0.3 in controls; albumin/ @entity8 ratios (mg/mmol, median) were, respectively, 0.37 and 0.22. Crude odds ratios for classification in the highest compared with the lowest tertiles of HMW-beta TG/ @entity8 and albumin/ @entity8 distributions were elevated for cases compared with controls: HMW-beta TG/ @entity8 odds ratio = 2.4, 95% confidence interval 1.1-5.0; albumin/ @entity8 odds ratio = 2.1, 95% confidence interval 1.0-4.1. These relations persisted after adjustment for smoking, @entity4 , Quetelet index, and menopausal status. Both urinary HMW-beta TG and albumin excretion are markers of @entity5 risk in middle-aged @entity1 , indicating that increased platelet activation and endothelial cell perturbation precede @entity5 events in @entity1 .

title: Urinary excretions of high molecular weight @entity9 and albumin are independently associated with @entity5 in XXXX , a nested case-control study of middle-aged @entity1 in the Diagnostisch Onderzoek Mammacarcinoom (DOM) Cohort, Utrecht, Netherlands.

answer: @entity1


abstract: Increased plasma levels of @entity9 , a platelet activation marker, are observed in @entity6 . Urinary albumin excretion, a marker of endothelial cell perturbation, is related to @entity3 in @entity2 . To test the value of these markers in predicting forthcoming @entity5 , the relations between urinary excretions of high molecular weight @entity9 (HMW-beta TGf) and albumin and subsequent @entity5 in a cohort of 15,484 middle-aged @entity1 were investigated in a nested case-control study. Baseline questionnaire data and urine samples were available from a @entity0 screening program in Utrecht during 1982-1985. Cases were Utrecht hospital admissions for @entity7 (n = 50) or angiographically confirmed @entity5 (n = 28) from 1982-1985 to 1990-1991. Classifying events occurred a median of 5.1 years after baseline. Controls were a random sample from the cohort, individually case matched for baseline examination date and age, at a 1:2 ratio. HMW-beta TG/ @entity8 ratios (ng/mmol, mean +/- standard error) were 5.3 +/- 0.3 in cases and 4.7 +/- 0.3 in controls; albumin/ @entity8 ratios (mg/mmol, median) were, respectively, 0.37 and 0.22. Crude odds ratios for classification in the highest compared with the lowest tertiles of HMW-beta TG/ @entity8 and albumin/ @entity8 distributions were elevated for cases compared with controls: HMW-beta TG/ @entity8 odds ratio = 2.4, 95% confidence interval 1.1-5.0; albumin/ @entity8 odds ratio = 2.1, 95% confidence interval 1.0-4.1. These relations persisted after adjustment for smoking, @entity4 , Quetelet index, and menopausal status. Both urinary HMW-beta TG and albumin excretion are markers of @entity5 risk in middle-aged @entity1 , indicating that increased platelet activation and endothelial cell perturbation precede @entity5 events in @entity1 .

title: Urinary excretions of high molecular weight @entity9 and albumin are independently associated with @entity5 in @entity1 , a nested case-control study of middle-aged XXXX in the Diagnostisch Onderzoek Mammacarcinoom (DOM) Cohort, Utrecht, Netherlands.

answer: @entity1


abstract: BACKGROUND: @entity7 is a novel @entity8 with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of @entity7 versus @entity9 in @entity0 with @entity1 . METHODS: This was a phase 3, double-blind, global multicentre, comparative-group study. @entity0 with suspected @entity1 were randomised in a 1:1 ratio using an interactive voice-web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active @entity2 at baseline, to receive @entity7 372 mg (prodrug; equivalent to 200 mg @entity7 ; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or @entity9 (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in @entity0 who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in @entity0 who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893. FINDINGS: 527 adult @entity0 were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with @entity7 (48 @entity0 ) and 20% with @entity9 (52 @entity0 ), with an adjusted treatment difference of -1  0% (95% CI -7  8 to 5  7). Because the upper bound of the 95% CI (5  7%) did not exceed 10%, non-inferiority was shown. Most @entity0 (247 [96%] receiving @entity7 and 255 [98%] receiving @entity9 ) had treatment-emergent adverse events (p=0  122); the most common were @entity5 (174 [68%] vs 180 [69%]) and @entity4 (152 [59%] vs 158 [61%]). Proportions of @entity0 with treatment-emergent adverse events by system organ class were similar overall. However, @entity7 -treated @entity0 had a lower frequency of @entity3 (23 [9%] vs 42 [16%]; p=0  016), @entity6 (39 [15%] vs 69 [27%]; p=0  002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0  037). Drug-related adverse events were reported in 109 (42%) @entity0 receiving @entity7 and 155 (60%) receiving @entity9 (p<0  001). INTERPRETATION: @entity7 was non-inferior to @entity9 for the primary treatment of suspected @entity1 . @entity7 was well tolerated compared with @entity9 , with fewer study-drug-related adverse events. Our results support the use of @entity7 for the primary treatment of @entity0 with @entity1 . FUNDING: Astellas Pharma Global Development, Basilea Pharmaceutica International.

title: XXXX versus @entity9 for primary treatment of @entity1 caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial.

answer: @entity7


abstract: BACKGROUND: @entity7 is a novel @entity8 with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of @entity7 versus @entity9 in @entity0 with @entity1 . METHODS: This was a phase 3, double-blind, global multicentre, comparative-group study. @entity0 with suspected @entity1 were randomised in a 1:1 ratio using an interactive voice-web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active @entity2 at baseline, to receive @entity7 372 mg (prodrug; equivalent to 200 mg @entity7 ; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or @entity9 (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in @entity0 who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in @entity0 who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893. FINDINGS: 527 adult @entity0 were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with @entity7 (48 @entity0 ) and 20% with @entity9 (52 @entity0 ), with an adjusted treatment difference of -1  0% (95% CI -7  8 to 5  7). Because the upper bound of the 95% CI (5  7%) did not exceed 10%, non-inferiority was shown. Most @entity0 (247 [96%] receiving @entity7 and 255 [98%] receiving @entity9 ) had treatment-emergent adverse events (p=0  122); the most common were @entity5 (174 [68%] vs 180 [69%]) and @entity4 (152 [59%] vs 158 [61%]). Proportions of @entity0 with treatment-emergent adverse events by system organ class were similar overall. However, @entity7 -treated @entity0 had a lower frequency of @entity3 (23 [9%] vs 42 [16%]; p=0  016), @entity6 (39 [15%] vs 69 [27%]; p=0  002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0  037). Drug-related adverse events were reported in 109 (42%) @entity0 receiving @entity7 and 155 (60%) receiving @entity9 (p<0  001). INTERPRETATION: @entity7 was non-inferior to @entity9 for the primary treatment of suspected @entity1 . @entity7 was well tolerated compared with @entity9 , with fewer study-drug-related adverse events. Our results support the use of @entity7 for the primary treatment of @entity0 with @entity1 . FUNDING: Astellas Pharma Global Development, Basilea Pharmaceutica International.

title: @entity7 versus @entity9 for primary treatment of XXXX caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial.

answer: @entity1


abstract: BACKGROUND: @entity7 is a novel @entity8 with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of @entity7 versus @entity9 in @entity0 with @entity1 . METHODS: This was a phase 3, double-blind, global multicentre, comparative-group study. @entity0 with suspected @entity1 were randomised in a 1:1 ratio using an interactive voice-web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active @entity2 at baseline, to receive @entity7 372 mg (prodrug; equivalent to 200 mg @entity7 ; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or @entity9 (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in @entity0 who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in @entity0 who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893. FINDINGS: 527 adult @entity0 were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with @entity7 (48 @entity0 ) and 20% with @entity9 (52 @entity0 ), with an adjusted treatment difference of -1  0% (95% CI -7  8 to 5  7). Because the upper bound of the 95% CI (5  7%) did not exceed 10%, non-inferiority was shown. Most @entity0 (247 [96%] receiving @entity7 and 255 [98%] receiving @entity9 ) had treatment-emergent adverse events (p=0  122); the most common were @entity5 (174 [68%] vs 180 [69%]) and @entity4 (152 [59%] vs 158 [61%]). Proportions of @entity0 with treatment-emergent adverse events by system organ class were similar overall. However, @entity7 -treated @entity0 had a lower frequency of @entity3 (23 [9%] vs 42 [16%]; p=0  016), @entity6 (39 [15%] vs 69 [27%]; p=0  002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0  037). Drug-related adverse events were reported in 109 (42%) @entity0 receiving @entity7 and 155 (60%) receiving @entity9 (p<0  001). INTERPRETATION: @entity7 was non-inferior to @entity9 for the primary treatment of suspected @entity1 . @entity7 was well tolerated compared with @entity9 , with fewer study-drug-related adverse events. Our results support the use of @entity7 for the primary treatment of @entity0 with @entity1 . FUNDING: Astellas Pharma Global Development, Basilea Pharmaceutica International.

title: @entity7 versus XXXX for primary treatment of @entity1 caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial.

answer: @entity9


abstract: Motile cilia and flagella exhibit many waveforms as outputs of dynein activation sequences on the highly conserved axoneme. Motility change of sperm in the reproductive tract is difficult to study and remains an important area of investigation. Sperm typically execute a sinusoidal waveform. Increased viscosity in the medium induces somewhat unusual arc-line and helical waveforms in some sperm. However, whether the latter two waveforms occur in vivo is not known. Using green fluorescence protein imaging, we show that @entity0 sperm in the uterus move in circular foci via arc-line waves, predominantly in a tail-leading orientation. From the uterus, a small fraction of the sperm enters the seminal receptacle (SR) in parallel formations. After sperm storage and coincident with fertilization of the egg, the sperm exit the SR via head-leading helical waves. Consistent with the observed bidirectional movements, the sperm show the ability to propagate both base-to-tip and tip-to-base flagellar waves. Numerous studies have shown that sperm motility is regulated by intraflagellar @entity1 concentrations; in particular, the @entity2 @entity1 channel has been shown to affect sperm storage. Our analyses here suggest that @entity2 is required for the sperm to adopt the correct waveform and movement orientation during SR entry. A working model for the sperm's SR entry movement is proposed.

title: XXXX sperm motility in the reproductive tract.

answer: @entity0


abstract: INTRODUCTION: The @entity3 ((P)RR) contributes to the regulation of the tissue renin-angiotensin system (RAS) and the function of V-ATPase, which are essential for Wnt signaling. Thus, (P)RRs may be involved in the control both of feto-placental and maternal circulation during pregnancy. This study was conducted to clarify how placental (P)RR expression and plasma soluble (P)RR [s(P)RR] levels are associated with blood pressure elevations and renal function during pregnancy. METHODS: We conducted a cross-sectional study, conducted at Saitama medical center in 2010-2013. Preeclamptic @entity0 (n  =  16) diagnosed according to the criteria of Japan Society of Obstetrics and Gynecology and normotensive pregnant @entity0 (n  =  15) participated in the study. We measured the expression of (P)RR in the placenta, plasma s(P)RR levels, systolic blood pressure (SBP), and estimated glomerular filtration rate (eGFR). RESULTS: Placental expression of (P)RR was significantly higher in preeclamptic @entity0 than in normotensive pregnant @entity0 . The plasma s(P)RR levels were significantly higher in preeclamptic @entity0 than in normotensive pregnant @entity0 . Systolic blood pressure (SBP) was positively correlated with placental (P)RR levels (P  =  0.0001) and plasma s(P)RR levels (P  =  0.005) in all pregnant @entity0 . In preeclamptic @entity0 , SBP was positively correlated with placental (P)RR levels (P  =  0.004), but not with plasma s(P)RR levels (P  =  0.15). The eGFR was negatively correlated with placental (P)RR levels (P  =  0.02) and plasma s(P)RR levels (P  =  0.0002) in all pregnant @entity0 . In preeclamptic @entity0 , eGFR was negatively correlated with plasma s(P)RR levels (P  =  0.006), but not with placental (P)RR levels (P  =  0.93). DISCUSSION: Placental (P)RR can be involved in blood pressure regulation via the tissue RAS. On the other hand, plasma s(P)RR may be involved in the pathogenesis of @entity1 in @entity2 .

title: Placental (pro)renin receptor expression and plasma soluble (pro)renin receptor levels in XXXX .

answer: @entity2


abstract: We investigated whether immunosuppressive therapy using @entity6 (mPSL) with or without @entity1 (CsA) could benefit @entity0 with @entity7 ( @entity7 ). Eligibility criteria for this study were a clinical diagnosis of @entity7 with less than 5% blast in peripheral blood, less than 10% blast in bone marrow and advanced @entity5 . Among 73 @entity0 with @entity7 , 18 eligible and consecutive @entity0 (8 @entity0 and 10 @entity0 ), aged 48 to 87 years (median: 66.5 years) were assigned to receive mPSL pulse therapy (1,000 mg daily for 3 consecutive days, followed by tapering oral @entity4 ; n= 12) or mPSL pulse with CsA therapy (4 to 5 mg/kg administered twice daily; n= 6). Six of 18 @entity0 (33.3%; 3 of 10 @entity0 with @entity3 , 2 of 6 @entity0 with @entity9 , 1 of 2 @entity0 with CMMoL) responded to immunosuppressive therapy. Four @entity0 responded to mPSL pulse alone, and two @entity0 responded to mPSL pulse with CsA. One of 6 @entity0 with @entity2 and 5 of 12 @entity0 with normocellular or @entity2 responded to immunosuppressive therapy. No @entity0 with @entity8 responded to the therapy. The duration of response ranged from 4 to 59 months (median: 14 months). Although a significant difference was observed between responders and nonresponders in the survival rate ( P<0.05), no significant difference was found in clinical characteristics at entry between responders and nonresponders. In responders, mean hemoglobin levels were significantly increased ( P<0.01), and the required red cell transfusion dose was significantly reduced ( P<0.01). It is possible that immunosuppressive therapy might be effective for a certain subset of @entity0 with @entity7 .

title: Immunosuppressive therapy for @entity7 : efficacy of @entity6 pulse therapy with or without XXXX .

answer: @entity1


abstract: We investigated whether immunosuppressive therapy using @entity6 (mPSL) with or without @entity1 (CsA) could benefit @entity0 with @entity7 ( @entity7 ). Eligibility criteria for this study were a clinical diagnosis of @entity7 with less than 5% blast in peripheral blood, less than 10% blast in bone marrow and advanced @entity5 . Among 73 @entity0 with @entity7 , 18 eligible and consecutive @entity0 (8 @entity0 and 10 @entity0 ), aged 48 to 87 years (median: 66.5 years) were assigned to receive mPSL pulse therapy (1,000 mg daily for 3 consecutive days, followed by tapering oral @entity4 ; n= 12) or mPSL pulse with CsA therapy (4 to 5 mg/kg administered twice daily; n= 6). Six of 18 @entity0 (33.3%; 3 of 10 @entity0 with @entity3 , 2 of 6 @entity0 with @entity9 , 1 of 2 @entity0 with CMMoL) responded to immunosuppressive therapy. Four @entity0 responded to mPSL pulse alone, and two @entity0 responded to mPSL pulse with CsA. One of 6 @entity0 with @entity2 and 5 of 12 @entity0 with normocellular or @entity2 responded to immunosuppressive therapy. No @entity0 with @entity8 responded to the therapy. The duration of response ranged from 4 to 59 months (median: 14 months). Although a significant difference was observed between responders and nonresponders in the survival rate ( P<0.05), no significant difference was found in clinical characteristics at entry between responders and nonresponders. In responders, mean hemoglobin levels were significantly increased ( P<0.01), and the required red cell transfusion dose was significantly reduced ( P<0.01). It is possible that immunosuppressive therapy might be effective for a certain subset of @entity0 with @entity7 .

title: Immunosuppressive therapy for @entity7 : efficacy of XXXX pulse therapy with or without @entity1 .

answer: @entity6


abstract: We investigated whether immunosuppressive therapy using @entity6 (mPSL) with or without @entity1 (CsA) could benefit @entity0 with @entity7 ( @entity7 ). Eligibility criteria for this study were a clinical diagnosis of @entity7 with less than 5% blast in peripheral blood, less than 10% blast in bone marrow and advanced @entity5 . Among 73 @entity0 with @entity7 , 18 eligible and consecutive @entity0 (8 @entity0 and 10 @entity0 ), aged 48 to 87 years (median: 66.5 years) were assigned to receive mPSL pulse therapy (1,000 mg daily for 3 consecutive days, followed by tapering oral @entity4 ; n= 12) or mPSL pulse with CsA therapy (4 to 5 mg/kg administered twice daily; n= 6). Six of 18 @entity0 (33.3%; 3 of 10 @entity0 with @entity3 , 2 of 6 @entity0 with @entity9 , 1 of 2 @entity0 with CMMoL) responded to immunosuppressive therapy. Four @entity0 responded to mPSL pulse alone, and two @entity0 responded to mPSL pulse with CsA. One of 6 @entity0 with @entity2 and 5 of 12 @entity0 with normocellular or @entity2 responded to immunosuppressive therapy. No @entity0 with @entity8 responded to the therapy. The duration of response ranged from 4 to 59 months (median: 14 months). Although a significant difference was observed between responders and nonresponders in the survival rate ( P<0.05), no significant difference was found in clinical characteristics at entry between responders and nonresponders. In responders, mean hemoglobin levels were significantly increased ( P<0.01), and the required red cell transfusion dose was significantly reduced ( P<0.01). It is possible that immunosuppressive therapy might be effective for a certain subset of @entity0 with @entity7 .

title: Immunosuppressive therapy for XXXX : efficacy of @entity6 pulse therapy with or without @entity1 .

answer: @entity7


abstract: BACKGROUND: Extrahepatic bile duct injuries remain severe complications during cholecystectomies and often require reconstruction by bilioenteric @entity0 (i.e., hepaticojejunostomy), which comes with further long-term complications (e.g., recurring @entity1 , @entity6 ). In the case of inherent @entity7 or during liver transplant, artificial or engineered bile ducts could allow novel surgical strategies without the need for hepaticojejunostomy. METHODS: We present data on the implantation of in vitro-generated neo-bile ducts in 5 @entity10 . The neo-bile ducts were engineered through decellularization of allogeneic blood vessels and recellularization with autologous cholangiocytes. On postoperative days 0, 1, 7, and 14, blood samples were taken and analyzed ( @entity9 aminotransferase, @entity8 aminotransferase, @entity3 , alkaline phosphatase, @entity4 , and leukocytes). Magnetic resonance cholangiopancreatography was performed on postoperative day 14 on 1 @entity5 . Fourteen days after implantation, the @entity5 were sacrificed and the bile ducts were explanted. RESULTS: All @entity5 survived the complete study period without severe complications. None of the @entity5 showed signs of biliary leakage or @entity2 . The neo-bile ducts were infiltrated by neutrophils, and neoangiogenesis was observed around and into the implanted tissue. CONCLUSION: We present a novel strategy for extrahepatic bile duct replacement by implantation of an autologous neo-bile duct generated ex vivo. Whether the presented technique allows the long-term replacement of native bile ducts must be further evaluated.

title: Implantation of a Tissue-Engineered Neo-Bile Duct in XXXX .

answer: @entity10


abstract: PURPOSE: To assess the effectiveness of anti-tuberculous treatment in @entity0 with @entity3 and either active @entity5 ( @entity2 ) in a non-endemic community. METHODS: Retrospective study of @entity0 with @entity3 , non-ocular evidence of latent or active @entity2 and no other identified cause of @entity3 who underwent a 6-month course of standard anti-tuberculous chemotherapy. Response to treatment was assessed at 6 and 12 months after initiation of treatment. RESULTS: A total of 27 @entity0 were included of whom 59% were female. In all, 19 were Asian, 4 Caucasian, and 4 Black. More than half of @entity0 had a history of contact with another @entity0 treated for @entity2 . @entity1 resolved after chemotherapy in 70.3% of @entity0 , 18.5% had a change in the nature of their @entity1 and 11.1% had no benefit. CONCLUSIONS: There were no @entity3 features characteristic of @entity2 and a wide range of manifestations was seen ranging from non-granulomatous anterior @entity3 to occlusive @entity4 . @entity2 is not endemic in the United Kingdom, therefore consideration of ethnicity, immigration, and history of @entity2 contact remain important to direct investigations. In a @entity0 with @entity3 and @entity5 , a full 6-month course of anti-tuberculous chemotherapy is recommended although it may not be curative of the @entity3 .

title: Presumed tuberculous XXXX : diagnosis, management, and outcome.

answer: @entity3


abstract: Intractable @entity5 and @entity3 cause tremendous suffering in those affected and in their families. The impaired ability to function of those affected imposes a heavy burden on society as a whole. Existing data suggest that lesion procedures offer benefit to a large proportion (ranging from about 35%-70%) of @entity0 with intractable @entity5 and @entity3 . The literature also suggests that although serious long-term adverse events have occurred, these are relatively infrequent overall. Methodologic limitations of the earlier reports on any of these procedures were described previously in this article. The major academic centers conducting this work have since been obtaining systematic prospective data using modern assessment tools. Nevertheless, even with improved methodologies, more recent studies confront some remaining issues that have been difficult to overcome fully. First, the number of @entity0 who have received any one procedure has been relatively small, constraining statistical power. This limits the ability of researchers to enhance @entity0 selection based on clinical characteristics. This is important, because @entity0 with intractable @entity5 and @entity3 referred for neurosurgery have high rates of comorbid Axis I diagnoses, @entity4 , and @entity1 , which may have value in predicting response. Other features, such as age of onset, chronicity, and symptom subtypes, may be likewise useful. Another key factor in response may be postoperative management, which has varied most over time but also across @entity0 enrolled in trials. As noted previously, randomized controlled trials of neurosurgical treatment for intractable @entity2 have not been reported, although one has been proposed for gamma knife capsulotomy in intractable @entity5 [23]. The development of deep brain stimulation has also made sham-controlled studies possible and also allows within- @entity0 designs to be considered. Bearing these problems in mind, the literature does provide important guidance on a number of key points, including approaches to referral, @entity0 selection, and the need for long-term prospective follow-up and postoperative management. Nevertheless, important gaps in knowledge remain in all these areas. Research is expected to narrow these gaps in a number of ways, including @entity0 selection, optimizing the procedures themselves, and understanding the mechanisms of therapeutic action. Neuroimaging studies will play a key role in achieving these aims (see the article by Rauch in this issue). So will cross-species translational research on the anatomy and physiology of the pathways implicated in the pathophysiology and response to treatment in these disorders. Future research in @entity2 neurosurgery must proceed cautiously. A recent editorial statement of the @entity5 -DBS Collaborative Group [26] recommends a minimum set of standards for any multidisciplinary teams contemplating work in this domain. The rationale for those standards is found throughout this issue and is especially developed in the article by Fins. The need for safe and effective therapeutic options for @entity0 suffering with these severe illnesses is just as clear. The experience over the last several decades provides grounds for careful optimism that refined lesion procedures or reversible deep brain stimulation may relieve suffering and improve the lives of @entity0 with these devastating disorders.

title: Neurosurgery for intractable XXXX and @entity3 : critical issues.

answer: @entity5


abstract: Intractable @entity5 and @entity3 cause tremendous suffering in those affected and in their families. The impaired ability to function of those affected imposes a heavy burden on society as a whole. Existing data suggest that lesion procedures offer benefit to a large proportion (ranging from about 35%-70%) of @entity0 with intractable @entity5 and @entity3 . The literature also suggests that although serious long-term adverse events have occurred, these are relatively infrequent overall. Methodologic limitations of the earlier reports on any of these procedures were described previously in this article. The major academic centers conducting this work have since been obtaining systematic prospective data using modern assessment tools. Nevertheless, even with improved methodologies, more recent studies confront some remaining issues that have been difficult to overcome fully. First, the number of @entity0 who have received any one procedure has been relatively small, constraining statistical power. This limits the ability of researchers to enhance @entity0 selection based on clinical characteristics. This is important, because @entity0 with intractable @entity5 and @entity3 referred for neurosurgery have high rates of comorbid Axis I diagnoses, @entity4 , and @entity1 , which may have value in predicting response. Other features, such as age of onset, chronicity, and symptom subtypes, may be likewise useful. Another key factor in response may be postoperative management, which has varied most over time but also across @entity0 enrolled in trials. As noted previously, randomized controlled trials of neurosurgical treatment for intractable @entity2 have not been reported, although one has been proposed for gamma knife capsulotomy in intractable @entity5 [23]. The development of deep brain stimulation has also made sham-controlled studies possible and also allows within- @entity0 designs to be considered. Bearing these problems in mind, the literature does provide important guidance on a number of key points, including approaches to referral, @entity0 selection, and the need for long-term prospective follow-up and postoperative management. Nevertheless, important gaps in knowledge remain in all these areas. Research is expected to narrow these gaps in a number of ways, including @entity0 selection, optimizing the procedures themselves, and understanding the mechanisms of therapeutic action. Neuroimaging studies will play a key role in achieving these aims (see the article by Rauch in this issue). So will cross-species translational research on the anatomy and physiology of the pathways implicated in the pathophysiology and response to treatment in these disorders. Future research in @entity2 neurosurgery must proceed cautiously. A recent editorial statement of the @entity5 -DBS Collaborative Group [26] recommends a minimum set of standards for any multidisciplinary teams contemplating work in this domain. The rationale for those standards is found throughout this issue and is especially developed in the article by Fins. The need for safe and effective therapeutic options for @entity0 suffering with these severe illnesses is just as clear. The experience over the last several decades provides grounds for careful optimism that refined lesion procedures or reversible deep brain stimulation may relieve suffering and improve the lives of @entity0 with these devastating disorders.

title: Neurosurgery for intractable @entity5 and XXXX : critical issues.

answer: @entity3


abstract: The reflex mediated mechanical response was studied in the ankle flexors and ankle extensors of healthy and @entity1 subjects at maintained contractions from low to high concentration levels. This was done by a technique where muscle stretches could be applied during contractions with stretch reflex responses present or during contractions where the stretch reflex was absent. Stretch responses without stretch reflexes were obtained during contractions elicited by electrical stimulation. The validity of this method is discussed in details and it is concluded that the stretch responses during electrical stimulation can give a correct estimate of the non-reflex muscle response. The method is difficult to carry out in many @entity0 subjects and a number of precautions have to be taken. In healthy subjects a large reflex mediated mechanical response was found in the ankle flexors and ankle extensors, with the largest response at low and intermediate contraction levels. Surprisingly the reflex mediated mechanical response was found to be of equal size in the ankle extensors of @entity1 @entity0 and control subjects at all contraction levels. In the ankle flexors no reflex mediated mechanical response was present in the @entity0 contrary to the findings in the control subjects. A method was developed to predict the reflex mediated mechanical response from the reflex mediated EMG response. The method was successfully applied in the ankle flexors. In the ankle extensors the measured reflex mediated mechanical response was a factor of 2.5 lower than the EMG predicted mechanical reflex response. It was concluded that the method cannot be applied in situations where a large synchronized EMG response occurs--as it does in the ankle extensors. An increased EMG response was found in the ankle extensors in @entity1 @entity0 , but this was not followed by an increased mechanical reflex response. This emphasizes that conclusions drawn from EMG results should be done with caution. Stretch reflexes are increased in @entity1 @entity0 during clinical examination. This is in contrast to the findings under our experimental conditions, where the reflex mediated response during maintained contraction was decreased in the ankle flexors and unchanged in the ankle extensors of @entity1 @entity0 . Others have found that the H-reflex is modulated in healthy subjects in relation to different motor tasks. It was proposed that healthy subjects set the reflex in a facilitated state in relation to ongoing contraction under our experimental conditions and perhaps in a more inhibited state in the clinical test situation.(ABSTRACT TRUNCATED AT 400 WORDS)

title: Mechanical and electromyographic stretch responses in XXXX and healthy subjects.

answer: @entity1


abstract: OBJECTIVE: Malignant transformation of @entity3 has been observed, particularly in perianal @entity3 in @entity2 ( @entity2 ) @entity0 . The prevalence of @entity4 in @entity6 and non- @entity2 -related @entity3 , however, is unknown. We investigated @entity4 originating from perianal and @entity6 in both @entity2 @entity0 and non- @entity2 @entity0 from nine large, mostly tertiary referral, hospitals in The Netherlands. METHODS: @entity0 suffering from fistulizing disease and either @entity5 or @entity4 between January 1990 and January 2007 were identified using the nationwide automated pathology database (PALGA). Clinical and histopathological data were collected and verified using hospital @entity0 -charts and reported by descriptive statistics. The total @entity2 -population comprised 6058 @entity0 . RESULTS: In a study-period of 17 years, 2324 @entity0 with any @entity3 were reported in PALGA. In 542 @entity0 , @entity5 or @entity4 was also mentioned. After initial review and additional detailed chart review, 538 @entity0 were excluded, mainly because the @entity4 was not related to the @entity3 . In the remaining four @entity0 , all suffering from @entity2 , @entity4 originating from the @entity3 -tract was confirmed. The @entity1 developed 25 years (IQR 10-38) after @entity2 diagnosis, and 10 years (IQR 6-22) after @entity3 diagnosis. Median age at time of @entity4 diagnosis was 48.3 years (IQR 43-58). Only one @entity0 had clinical symptoms indicative for @entity4 . In three other @entity0 , the @entity4 was found coincidently. CONCLUSIONS: @entity4 complicating perianal or enterocutaneous @entity3 -tracts is a rare finding. Only 4 out of 6058 @entity2 @entity0 developed a @entity3 -associated @entity4 . We could not identify any malignant transformations in non- @entity2 -related @entity3 in our 17 years study-period.

title: Malignant transformation of perianal and XXXX is rare: results of 17 years of follow-up from The Netherlands.

answer: @entity6


abstract: AIM: To evaluate the specific inhibition of maxizyme directing against mutant-type @entity1 gene (mtp53) at codon 249 in exon 7 (AGG-AGT) in vitro. METHODS: Two different monomers of anti-mtp53 maxizyme (maxizyme right MzR, maxizyme left MzL) and control mutant maxizyme (G(5)-A(5)) were designed by computer and cloned into vector pBSKU6 (pBSKU6MzR, pBSKU6MzL). After being sequenced, the restrictive endonuclease site in pBSKU6MzR was changed by PCR and then U6MzR was inserted into pBSKU6MzL, the recombinant vector was named pU6Mz and pU6asMz (mutant maxizyme). Mtp53 and wild-type @entity1 (wtp53) gene fragments were cloned into pGEM-T vector under the T7 promoter control. The @entity3 -labeled mtp53 transcript was the target mRNA. Cold maxizyme transcripts were incubated with @entity3 -labeled target RNA in vitro and radioautographed after denaturing @entity2 gel electrophoresis. RESULTS: In cell-free systems, pU6Mz showed a specific cleavage activity against target mRNA at 37 degrees and 25 mM MgCL(2). The cleavage efficiency of pU6Mz was 42 %, while pU6asMz had no inhibitory effect. Wtp53 was not cleaved by pU6Mz either. CONCLUSION: pU6Mz had a specific catalytic activity against mtp53 in cell-free system. These lay a good foundation for studying the effects of anti-mtp53 maxizyme in HCC cell lines. The results suggest that maxizyme may be a promising alternative approach for treating @entity0 containing mtp53.

title: Maxizyme-mediated specific inhibition on mutant-type XXXX in vitro.

answer: @entity1


abstract: @entity1 ( @entity1 ) is a proinflammatory monocyte- and macrophage-derived cytokine that has potent vasorelaxant effects on vascular smooth muscle cells (VSMC). VSMC themselves also express both @entity1 - and beta-genes, suggesting that @entity1 may be an autocrine regulator of VSMC function. The present study demonstrates that @entity0 saphenous vein VSMC (HSVSMC) produce @entity2 ( @entity2 ), a specific inhibitor of @entity1 action. @entity2 was produced constitutively in most experiments, and its production was upregulated by @entity4 and by @entity3 . @entity2 produced by HSVSMC remained predominately cell associated and was not detectable extracellularly. Furthermore, reverse transcription-polymerase chain reaction analysis and cDNA sequencing indicated that HSVSMC express the alternatively spliced form of @entity2 which lacks the signal peptide present in secreted @entity2 . HSVSMC also produced @entity1 and the precursor form but not the mature form of @entity3 . These results suggest that HSVSMC lack active @entity5 . Like @entity2 , @entity3 precursor and @entity1 remained cell associated, predominately in the cytosolic fraction. @entity3 induced production of both @entity2 and @entity1 at each time point and concentration tested. In contrast, platelet-derived growth factor and transforming growth factor-beta augmented production of @entity2 , but not that of @entity1 . These results are suggestive of an autocrine role for cell-associated @entity2 , as well as for @entity1 and @entity3 , in the regulation of VSMC function.

title: @entity0 vascular smooth muscle cells produce an intracellular form of XXXX receptor antagonist.

answer: @entity1


abstract: @entity1 ( @entity1 ) is a proinflammatory monocyte- and macrophage-derived cytokine that has potent vasorelaxant effects on vascular smooth muscle cells (VSMC). VSMC themselves also express both @entity1 - and beta-genes, suggesting that @entity1 may be an autocrine regulator of VSMC function. The present study demonstrates that @entity0 saphenous vein VSMC (HSVSMC) produce @entity2 ( @entity2 ), a specific inhibitor of @entity1 action. @entity2 was produced constitutively in most experiments, and its production was upregulated by @entity4 and by @entity3 . @entity2 produced by HSVSMC remained predominately cell associated and was not detectable extracellularly. Furthermore, reverse transcription-polymerase chain reaction analysis and cDNA sequencing indicated that HSVSMC express the alternatively spliced form of @entity2 which lacks the signal peptide present in secreted @entity2 . HSVSMC also produced @entity1 and the precursor form but not the mature form of @entity3 . These results suggest that HSVSMC lack active @entity5 . Like @entity2 , @entity3 precursor and @entity1 remained cell associated, predominately in the cytosolic fraction. @entity3 induced production of both @entity2 and @entity1 at each time point and concentration tested. In contrast, platelet-derived growth factor and transforming growth factor-beta augmented production of @entity2 , but not that of @entity1 . These results are suggestive of an autocrine role for cell-associated @entity2 , as well as for @entity1 and @entity3 , in the regulation of VSMC function.

title: XXXX vascular smooth muscle cells produce an intracellular form of @entity1 receptor antagonist.

answer: @entity0


abstract: BACKGROUND: Chrysotile @entity4 accounts for more than 90% of the @entity4 used worldwide and exposure is associated with @entity4 ( @entity4 -related @entity3 ) and other @entity1 , but the molecular mechanisms involved are not fully understood. A common pathogenic mechanism for these @entity1 is represented by epithelial-mesenchymal transition (EMT), through which epithelial cells undergo a morphological transformation to take on a mesenchymal phenotype. In the present work we propose that chrysotile @entity4 induces EMT through a mechanism involving a Tranforming Growth Factor beta ( @entity6 )-mediated signaling pathway. OBJECTIVES: To investigate the role of chrysotile @entity4 in inducing EMT trying to elucidate the molecular mechanisms involved in this event. METHODS: @entity0 bronchial epithelial cells BEAS-2B were incubated with 1   g/cm(2) chrysotile @entity4 for up to 72 h and several markers of EMT were investigated. Experiments with the specific inhibitors for @entity6 , @entity10 ( @entity10 ) and Akt were carried out in order to confirm their involvement in @entity4 -induced EMT. Real time PCR, Western blot and gelatin zymographies were performed to detect the mRNA and protein expression changes of these markers. RESULTS: Chrysotile @entity4 activates a @entity6 -mediated signaling pathway, which implicates the contribution of Akt, @entity10 , and @entity8 . The activation of this pathway in BEAS-2B cells was associated with a decrease in the epithelial markers ( @entity9 and @entity7 ), and an increase in the mesenchymal markers (a-smooth muscle actin, @entity5 , metalloproteinases and fibronectin). CONCLUSIONS: Our findings suggest that chrysotile @entity4 induces EMT, a common event in @entity2 , at least in part by eliciting the @entity6 -mediated Akt/ @entity10 / @entity8 pathway.

title: Effect of Chrysotile Exposure in XXXX Bronchial Epithelial Cells: Insights on the Pathogenic Mechanisms of Asbestos-Related Diseases.

answer: @entity0


abstract: OBJECTIVES. Vocal fold @entity1 can have a significant impact on a @entity0 's quality of life. The aim of this study was to analyze, in terms of vocal improvement and motility recovery, the post-vocal treatment results of @entity0 with unilateral vocal fold @entity1 (UVFP) who underwent early voice therapy. Study design. A 7 years prospective study of @entity0 with an UVFP who underwent our multidimensional diagnostic-therapeutic assessment. MATERIAL AND METHODS. Seventy-four @entity0 with UVFP were included in the study. All @entity0 underwent a voice therapy based on forcible exercises supplemented by manipulations and maneuvers. A pre and post-treatment objective voice evaluation and self-assessment was made. RESULTS: Out of 74 @entity0 with UVFP, 51 (68.9%) recovered vocal fold motility. In 23 (31.1%), UVFP persisted after voice therapy. In this group of @entity0 , a complete glottal closure was seen in 5 before voice therapy and in 13 after; An important and significant (p <0.0001) reduction in fundamental frequency (F(o)) was found; a manifest improvement was seen for the mean values of Jitter (Jitt%; p = 0.001), Shimmer (Shim%; p <0.0001) and noise-to-harmonic ratio (NHR) (p <0.0001). The same statistical comparisons calculated for male @entity0 alone was not significant for Jitt% (0.102), Shim% (0.112) and NHR (0.155), as a result of the reduced number of @entity0 in this group. Voice Handicap Index (VHI) values showed a clear and significant improvement and mean maximum phonation time (MPT) increased significantly. CONCLUSION. Early voice therapy based on an energetic approach, combined with @entity0 co-operation, motivation and understanding through educated participation in the voice restoration process, strengthen the idea that @entity0 with UVFP have a good chance of recovering vocal fold motility or improving their voice quality.

title: The role of early voice therapy in the incidence of motility recovery in unilateral vocal fold XXXX .

answer: @entity1


abstract: @entity9 are expressed in the @entity0 kidney, but the factors that regulate this expression remain unknown. To try to understand what these might be, we have measured the renal levels of @entity9 mRNAs by the ribonuclease protection-assay technique after a number of clearly defined renal/hemodynamic insults. 1) Six hours after the induction of @entity1 and @entity2 , there was a threefold increase in @entity6 mRNA and a simultaneous threefold decrease in @entity5 mRNA. This indicates that, in this situation, these two ET isoforms are differentially controlled and emphasizes the need for assay techniques capable of distinguishing between them. 2) One day after application of a 0.2-mm clip to the left renal artery, there was a > 2.5-fold induction of @entity6 mRNA in that kidney, which persisted for 10 days. A smaller rise in @entity6 mRNA was seen in the contralateral organ. After 2 days, @entity5 mRNA levels were reduced by approximately 50% in the clipped organ. Both @entity7 (an angiotensin-converting enzyme inhibitor, 7.5 mg/kg daily) and @entity8 (a nonselective ET receptor antagonist, 100 mg/kg daily) substantially reduced the elevation in @entity6 mRNA seen in the clipped kidney after 2 days, suggesting that the generation of @entity4 and the action of ET itself are involved in the mechanism by which clipping stimulates @entity6 expression. By contrast, @entity7 , but not @entity8 , prevented the reduction in @entity5 mRNA levels. 3) Renal denervation, dietary salt restriction, or diuretic treatment ( @entity3 ) did not alter renal expression of @entity6 or @entity5 .(ABSTRACT TRUNCATED AT 250 WORDS)

title: Expression of XXXX in the @entity0 kidney.

answer: @entity9


abstract: @entity9 are expressed in the @entity0 kidney, but the factors that regulate this expression remain unknown. To try to understand what these might be, we have measured the renal levels of @entity9 mRNAs by the ribonuclease protection-assay technique after a number of clearly defined renal/hemodynamic insults. 1) Six hours after the induction of @entity1 and @entity2 , there was a threefold increase in @entity6 mRNA and a simultaneous threefold decrease in @entity5 mRNA. This indicates that, in this situation, these two ET isoforms are differentially controlled and emphasizes the need for assay techniques capable of distinguishing between them. 2) One day after application of a 0.2-mm clip to the left renal artery, there was a > 2.5-fold induction of @entity6 mRNA in that kidney, which persisted for 10 days. A smaller rise in @entity6 mRNA was seen in the contralateral organ. After 2 days, @entity5 mRNA levels were reduced by approximately 50% in the clipped organ. Both @entity7 (an angiotensin-converting enzyme inhibitor, 7.5 mg/kg daily) and @entity8 (a nonselective ET receptor antagonist, 100 mg/kg daily) substantially reduced the elevation in @entity6 mRNA seen in the clipped kidney after 2 days, suggesting that the generation of @entity4 and the action of ET itself are involved in the mechanism by which clipping stimulates @entity6 expression. By contrast, @entity7 , but not @entity8 , prevented the reduction in @entity5 mRNA levels. 3) Renal denervation, dietary salt restriction, or diuretic treatment ( @entity3 ) did not alter renal expression of @entity6 or @entity5 .(ABSTRACT TRUNCATED AT 250 WORDS)

title: Expression of @entity9 in the XXXX kidney.

answer: @entity0


abstract: The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 @entity1 with medium and high-risk @entity0 . @entity1 AND METHODS: After a first standard dosed FEC course (5- @entity8 600 mg/m(2), @entity6 60 mg/mg(2) and @entity5 600 mg/m(2)), @entity1 who did not reach @entity7 grade III or IV were randomised to standard doses (group standard) or doses tailored to achieve @entity7 (group tailored) at courses 2-7. @entity1 who achieved @entity7 grade III or more after the first course were not randomised but continued on standard doses (group registered). RESULTS: Both planned and actually delivered number of courses (seven) were the same in all three arms. The relative dose intensity was increased by a factor of 1.31 (E 1.22, C 1.43) for @entity1 in the tailored arm compared to the expected on standard dose. Ninety percent of the @entity1 in the tailored arm achieved @entity7 grade III-IV compared with 29% among @entity1 randomised to standard dosed therapy. Dose tailoring was associated with acceptable acute non-haematological @entity2 with more @entity9 , @entity3 , @entity4 and fatigue. CONCLUSION: Dose tailoring according to @entity7 was feasible. It led to an increased dose intensity and was associated with acceptable excess of acute non-haematological @entity2 .

title: Dose-tailoring of FEC adjuvant chemotherapy based on @entity7 is feasible and well tolerated. XXXX and dose intensity in the Scandinavian Breast Group phase 3 adjuvant Trial SBG 2000-1.

answer: @entity2