bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of hormone replacement therapy with mortality in colorectal cancer survivor: a systematic review and meta-analysis
Authors: Jang Yeu-Chai , Huang Hsi-Lan , Leung Chi Yan 
Published: December 2019

Abstract
Background
Hormone replacement therapy (HRT) use has shown to be associated with a reduced risk of colorectal cancer, however, its impact on survival among women with colorectal cancer remains uncertain. This meta-analysis aimed to systematically assess the survival benefit of HRT use in patients with colorectal cancer.

Methods
PRISMA guidelines for the reporting of meta-analyses were followed. We systematically searched PubMed, Embase, Cochrane library, Scopus, and PsycINFO from inception to 12 January 2019, with no language restrictions, for randomized controlled trials and cohort studies reporting the association between hormone replacement therapy and risk of colorectal cancer mortality or all-cause mortality in colorectal cancer survivors. We used the Newcastle-Ottawa Scale to assess the risk of bias of the included studies. We summarized the association as hazard ratio (HR; 95% CI) using random-effects meta-analysis. The study protocol was registered in PROSPERO (CRD42017071914).

Results
Of 1648 articles identified, five cohorts including 10,013 colorectal cancer survivors were included in this meta-analysis. Compared with women with no prior use of HRT, those reporting current use of HRT had lower risks of colorectal cancer-specific mortality (HR, 0.71 [95% CI, 0.62–0.80], I2 = 0%) and overall mortality (HR, 0.74 [95% CI, 0.67–0.81], I2 = 0%). Low between-study variance was also suggested by the narrow prediction interval for colorectal cancer-specific mortality (0.58–0.86) and overall mortality (0.63–0.87), which indicated that a future study will show survival benefits in women with current HRT use compared with those with no HRT exposure. Inverse associations with colorectal cancer-specific (HR, 1.02 [95% CI, 0.82–1.28], I2 = 0%) and overall mortality (HR, 1.07 [95% CI, 0.90–1.27], I2 = 0%) were not observed for former users of HRT. Sensitivity analyses revealed no differences in the risk estimates between two groups.

Conclusions
The findings suggest that the current use of HRT is associated with lower risks of colorectal cancer-specific and overall mortality in patients with colorectal cancer. Further investigations to elucidate the underlying mechanism are warranted.
Does high-grade dysplasia/carcinoma in situ of the biliary duct margin affect the prognosis of extrahepatic cholangiocarcinoma? A meta-analysis
Authors: Ke Qiao , Wang Bin , Lin Nanping , Wang Lei , Liu Jingfeng 
Published: December 2019

Abstract
Background
High-grade dysplasia/carcinoma in situ (HGD/CIS) of the biliary duct margin was found to not affect the prognosis of patients with extrahepatic cholangiocarcinoma by recent studies, but it has not yet reached a conclusion.

Methods
Eligible studies were searched by PubMed, PMC, MedLine, Embase, the Cochrane Library, and Web of Science, from Jan. 1, 2000 to Jun. 30, 2019, investigating the influences of surgical margin status of biliary duct on the prognosis of patients with resectable extrahepatic cholangiocarcinoma. Overall survival (OS) and local recurrence were evaluated by odds ratio (OR) with 95% confidence interval (CI).

Results
A total of 11 studies were enrolled in this meta-analysis, including 1734 patients in the R0 group, 194 patients in the HGD/CIS group, and 229 patients in the invasive carcinoma (INV) group. The pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and R0 group was 0.98 (95% CI 0.65~1.50), 1.01 (95% CI 0.73~1.41), and 0.98 (95% CI 0.72~1.34), respectively. The pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and INV group was 1.83 (95% CI 1.09~3.06), 4.52 (95% CI 2.20~9.26), and 3.74 (95% CI 2.34~5.96), respectively. Subgroup analysis of extrahepatic cholangiocarcinoma at early stage showed that the pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and R0 group was 0.54 (95% CI 0.21~1.36), 0.75 (95% CI 0.35~1.58), and 0.74 (95% CI 0.40~1.37), respectively, and the pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and INV group was 3.47 (95% CI 1.09~11.02), 9.12 (95% CI 2.98~27.93), and 9.17 (95% CI 2.95~28.55), respectively. However, the pooled OR for the incidence of local recurrence between HGD/CIS group and R0 group was 3.54 (95% CI 1.66~7.53), and the pooled OR for the incidence of local recurrence between HGD/CIS group and INV group was 0.93 (95% CI 0.50~1.74).

Conclusion
With the current data, we concluded that HGD/CIS would increase the risk of local recurrence compared with R0, although it did not affect the prognosis of patients with extrahepatic cholangiocarcinoma regardless of TNM stage. However, the conclusion needs to be furtherly confirmed.
Survival analysis of local excision vs total mesorectal excision for middle and low rectal cancer in pT1/pT2 stage and intermediate pathological risk
Authors: Lai I-Li , You Jeng-Fu , Chern Yih-Jong , Tsai Wen-Sy , Chiang Jy-Ming , Hsieh Pao-Shiu , Hung Hsin-Yuan , Yeh Chien-Yuh , Chiang Sum-Fu , Lai Cheng-Chou , Tang Rei-Ping , Chen Jinn-Shiun , Hsu Yu-Jen 
Published: December 2019

Abstract
Background
Local excision (LE) is a feasible treatment approach for rectal cancers in stage pT1 and presents low pathological risk, whereas total mesorectal excision (TME) is a reasonable treatment for more advanced cancers. On the basis of the pathology findings, surgeons may suggest TME for patients receiving LE. This study compared the survival outcomes between LE with/without chemoradiation and TME in mid and low rectal cancer patients in stage pT1/pT2, with highly selective intermediate pathological risk.

Methods
This retrospective study included 134 patients who received TME and 39 patients who underwent LE for the treatment of intermediate risk (pT1 with poor differentiation, lymphovascular invasion, perineural invasion, relatively large tumor, or small-sized pT2 tumor) rectal cancer between 1998 and 2016.

Results
Overall survival (OS), disease-free survival (DFS), and cumulative recurrence rate (CRR) were similar between the LE (3-year DFS 92%) and TME (3-year DFS 91%) groups. Following subgrouping into an LE with adjuvant therapy group and a TME without adjuvant therapy group, the compared survival outcomes (OS, DFS, and CRR) were found not to be statistically different. The temporary and permanent ostomy rates were higher in the TME group than in the LE group (p < 0.001). Rates of early and late morbidity following surgery were higher in the TME group (p = 0.005), and LE had similar survival compared with TME.

Conclusion
For patients who had mid and low rectal cancer in stage pT1/pT2 and intermediate pathological risk, LE with chemoradiation presents an alternative treatment option for selected patients.
URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion
Authors: Su Shao-Hua , Wu Yi-Fang , Lin Qi , Wang Da-Peng , Hai Jian 
Published: December 2019

AbstractBackgroundPrevious studies reported that URB597 (URB) had therapeutic potential for treating chronic cerebral hypoperfusion (CCH)-induced neuroinflammation and autophagy dysfunction. However, the interaction mechanisms underlying the CCH-induced abnormal excessive autophagy and neuroinflammation remain unknown. In this study, we investigated the roles of impaired autophagy in nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing (NLRP) 3 inflammasome activation in the rat hippocampus and the underlying mechanisms under the condition of induced CCH as well as the effect of URB treatment.MethodsThe CCH rat model was established by bilateral common carotid artery occlusion (BCCAo), and rats were randomly divided into 11 groups as follows: (1) sham-operated, (2) BCCAo; (3) BCCAo+autophagy inhibitor 3-methyladenine (3-MA), (4) BCCAo+lysosome inhibitor chloroquine (CQ), (5) BCCAo+microglial activation inhibitor minocycline, (6) BCCAo+ROS scavengerN-acetylcysteine (NAC), (7) BCCAo+URB, (8) BCCAo+URB+3-MA, (9) BCCAo+URB+CQ, (10) BCCAo+URB+minocycline, (11) BCCAo+URB+NAC. The cell localizations of LC3, p62, LAMP1, TOM20 and NLRP3 were assessed by immunofluorescence staining. The levels of autophagy-related proteins (LC3, p62, LAMP1, BNIP3 and parkin), NLRP3 inflammasome-related proteins (NLRP3, CASP1 and IL-1β), microglial marker (OX-42) and proinflammatory cytokines (iNOS and COX-2) were evaluated by western blotting, and proinflammatory cytokines (IL-1β and TNF-a) were determined by ELISA. Reactive oxygen species (ROS) were assessed by dihydroethidium staining. The mitochondrial ultrastructural changes were examined by electron microscopy.ResultsCCH induced microglial overactivation and ROS accumulation, promoting the activation of the NLRP3 inflammasome and the release of IL-1β. Blocked autophagy and mitophagy flux enhanced the activation of the NLRP3-CASP1 inflammasome pathway. However, URB alleviated impaired autophagy and mitophagy by decreasing mitochondrial ROS and microglial overactivation as well as restoring lysosomal function, which would further inhibit the activation of the NLRP3-CASP1 inflammasome pathway.ConclusionThese findings extended previous studies indicating the function of URB in the mitigation of chronic ischemic injury of the brain.
Dosimetric factors associated with long-term patient-reported outcomes after definitive radiotherapy of patients with head and neck cancer
Authors: Hayakawa Toyokazu , Kawakami Shogo , Soda Itaru , Kainuma Takuro , Nozawa Marika , Sekiguchi Akane , Miyamoto Shunsuke , Yamashita Taku , Ishiyama Hiromichi 
Published: December 2019

Abstract
Background
The aim of this study was to explore the relationships between dosimetric parameters of organs at risk and patient-reported outcomes (PRO) after radiotherapy of patients with head and neck cancer.

Methods
PRO data of 53 patients with head and neck cancer treated with radiotherapy were prospectively collected. These data concerned health-related quality of life (HRQOL) and were collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and head and neck cancer module (QLQ-H&N35). Patients were divided into “severe-deterioration” and “mild-deterioration” groups on the basis of degree of deterioration HRQOL > 6 months after completing treatment. The relationships between HRQOL deteriorations and patient-related or dosimetry-related factors were evaluated. P < 0.0013 according to Bonferroni correction was considered to denote statistical significance.

Results
Regarding “trouble with social eating (HNSO)” and “coughing (HNCO),” there were significant differences between the severe-deterioration and mild-deterioration groups in mean dosages to the superior pharyngeal constrictor muscle (SPC) (HNSO: 62.5 Gy vs 54.2 Gy; p = 0.00029, and HNCO: 61.5 Gy vs 54.1 Gy; p = 0.0012) and parotid gland (HNSO: 24.1 Gy vs 20.5 Gy; p = 0.000056, and HNCO: 24.2 Gy vs 20.3 Gy; p = 0.00043). Regarding “nausea and vomiting,” there was a significant difference between the two groups in the mean dosage to the middle pharyngeal constrictor muscle (MPC: 61.9 Gy vs. 58.4Gy; P = 0.00059).

Conclusions
We found that dosages to the SPC and parotid gland were associated with severe deterioration in HRQOL attributable to difficulty in HNSO and HNCO, whereas dosage to the MPC was associated with severe deterioration attributable to nausea and vomiting.
Surface mineralized biphasic calcium phosphate ceramics loaded with urine-derived stem cells are effective in bone regeneration
Authors: Xing Fei , Li Lang , Sun Jiachen , Liu Guoming , Duan Xin , Chen Jialei , Liu Ming , Long Ye , Xiang Zhou 
Published: December 2019

Abstract
Background
Segmental bone defects caused by trauma, tumors, or infection are a serious challenge for orthopedists in the world. Recent developments in tissue engineering have provided a new treatment for segmental bone defects. Urine-derived stem cells (USCs) can be obtained noninvasively and might be a new kind of seed cells used in bone tissue regeneration. Therefore, the first aim of the present study was to investigate the biological characteristics of USCs. The second aim of the present study was to study the osteogenic effect of surface mineralized biphasic calcium phosphate ceramics (BCPs) loaded with USCs in vitro and in vivo.

Methods
We isolated USCs from the urine of healthy adult donors and evaluated the biological characteristics of USCs in vitro. We mineralized the surface of BCPs by simulated body fluid (SBF). Cell adhesion and proliferation of USCs on the surface mineralized BCPs were evaluated. Osteogenic proteins and genes of USCs on the surface mineralized BCPs were texted by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) assay. Critical-sized segmental bone defects model in New Zealand white rabbits were established and randomly divided into 4 groups (surface mineralized BCPs loaded with USCs, BCPs loaded with USCs, surface mineralized BCPs, and BCPs) based on the implant they received. The therapeutic efficacy of the scaffolds in a large bone defect at post-implantation was evaluated by imaging and histological examination.

Results
USCs isolated in our study expressed stem cell-specific phenotypes and had a stable proliferative capacity and multipotential differentiation capability. Surface mineralized BCPs promoted osteogenic proteins and genes expression of USCs without affecting the proliferation of USCs. After 10 weeks, the amount of new bone formation was the highest in the group of surface mineralized BCPs loaded with USCs.

Conclusion
USCs, from non-invasive sources, have good application prospects in the field of bone tissue engineering. Surface mineralized BCPs can significantly enhance osteogenic potential of USCs without changing biological characteristics of BCPs. Surface mineralized BCPs loaded with USCs are effective in repairing of critical-sized segmental bone defects in rabbits.
Iron treatment of pregnant sows in a Danish herd without iron deficiency anemia did not improve sow and piglet hematology or stillbirth rate
Authors: Bhattarai Sheeva , Framstad Tore , Nielsen Jens Peter 
Published: December 2019

AbstractBackgroundAnemia characterized by low hemoglobin concentration (HbC) is common in indoor housed pregnant sows. Iron is essential for hemoglobin synthesis and a number of metabolic processes including DNA synthesis and regulation of enzyme systems. In sows, anemia has been linked to lower HbC in piglets and increased occurrence of stillbirths. Therefore, the main objective of this study was to evaluate the effect of iron injection on hematology of pregnant sows and their offspring. Other objectives were to evaluate the effect of this injection on the probability of stillbirths and to study the tolerability of injected iron.ResultsA sow herd with bi-weekly batch farrowing was selected for the study and 100 sows at mid-gestation were randomly assigned to either a treatment (FeT) or a control (FeC) group. At the time of recruitment to the study (baseline), 46% of the sows in the herd were anemic with a HbC less than 103 g/L. However, none of the anemic sows had iron deficiency anemia on erythrocyte characterization. HbC decreased numerically during gestation in both the FeT (− 2.48 g/L) and FeC (− 2.99 g/L) groups but the decrease was insignificant between the groups (P = 0.79). Likewise, the change from baseline to farrowing and from baseline to post-farrowing in other hematologic variables was similar for both groups. The percentage of transferrin saturation was not statistically different between groups (P = 0.14). There was a batch effect (week of breeding) in most of the hematologic variables. The probability of stillbirth in the two groups did not differ (P = 0.94). None of the hematologic variables in piglets was significantly different between the two groups. The sows tolerated the iron injection well.ConclusionsIntramuscular injection of two doses of 2500 mg iron 2 weeks apart at mid-gestation did neither change hematologic variables in sows nor in the piglets at farrowing. Similarly, iron treatment did not reduce the probability of stillbirths among the offspring. The sows recruited in this study tolerated the iron injections well. Further characterization of erythrocytes did not support that sows had iron deficiency anemia at baseline. Therefore, further studies on animals with well-defined anemia and with focus on the iron regulating hormone hepcidin are recommended.
Chinese pediatric Tuina on children with acute diarrhea: study protocol for a randomized sham-controlled trial
Authors: Lu Taoying , Zhang Huiyan , Yin Lingjia , Cai Jianxiong , Li Meiling , Dai Lin , Zhu Conghao , Zhang Yongping , Xiang Feng , Wang Li , Li Lu , Wang Lixin , Wu Darong 
Published: December 2019

Abstract
Background
Acute pediatric diarrhea is one of the most common causes of morbidity and mortality worldwide and seriously affects the health of children. Previous studies have shown that pediatric Tuina, a traditional Chinese medicine therapy, has potential therapeutic benefits for acute pediatric diarrhea. However, the evidence for its effectiveness is insufficient due to the lack of high-quality clinical studies. Our aim is to evaluate the efficacy of Chinese pediatric Tuina for children aged 0–6 years with acute diarrhea.

Methods/design
This study is a randomized, double-blind, sham-controlled trial. We will include 122 children with acute diarrhea from Dongguan Kanghua Hospital in Guangdong province, China. The patients will be allocated into either the pediatric Tuina group or the sham Tuina group in a 1:1 ratio. The treatment will last for 3 days followed by an 11-day follow-up period. Both groups will receive usual care. In addition, the experimental group will receive 15–25 min of Chinese pediatric Tuina, while the control group will receive 15–25 min of sham pediatric Tuina. Both groups will receive treatments once per day, for 3 consecutive days. Primary outcome measures are diarrhea days from baseline and diarrhea times on the third day. Secondary outcome measures are the global change rating and period of days when the stool character changes to normal. Safety assessments will be monitored during each visit.

Discussion
This clinical trial is designed to evaluate the efficacy of pediatric Tuina for children with acute diarrhea. We expect results to provide solid evidence and support for pediatric Tuina as an appropriate treatment for children with acute diarrhea.

Trial registration
ClinicalTrials.gov, NCT03005821. Registered on 29 December 2016.
Acupuncture for patients with insomnia disorder using resting-state functional magnetic resonance imaging: a protocol for a randomized controlled trial
Authors: Guo Jing , Yu Siyi , Liu Chunhong , Wang Guiling , Li Bin 
Published: December 2019

Abstract
Background
Insomnia is among the most prevalent of the sleep-related disorders. Insomnia disorder is associated with a brain hyperarousal state manifested by abnormal regional brain activity and resting state functional connectivity. Acupuncture improves sleep quality and modulates the hyperarousal state; however, the underlying neurobiological basis for improved sleep quality is poorly understood. The purpose of this clinical trial is to study the efficacy of acupuncture in the treatment of insomnia disorder. In addition, the neural mechanism by which acupuncture affects insomnia disorder will be explored using resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological parameters.

Methods and design
A randomized, patient- and assessor-blinded trial will be conducted. We will randomize (in a 1:1 ratio) 60 eligible patients with insomnia disorder into a real acupuncture group or a sham acupuncture group. Interventions will be administered three times per week over a 4-week period, with an 8-week follow-up period. The healthy control group will consist of 30 age- and sex-matched healthy individuals who sleep well without any treatment intervention.
All participants will undergo neuropsychological and rs-fMRI evaluations. The change in Pittsburgh Sleep Quality Index (PSQI) scores is the primary outcome parameter. The secondary outcome parameters include the Hyperarousal scale (HAS), rs-fMRI measurements, the Fatigue scale-14 (FS-14), the Hamilton depression scale (HAMD), the Hamilton anxiety scale (HAMA), a sleep diary, and an actigraph.
Assessment of all parameters will be performed at baseline, post-treatment, and during follow-up. Analyses will be implemented based on intention-to-treat.

Discussion
The study results will be used to clarify the effectiveness and elucidate the mechanism by which acupuncture improves sleep quality in patients with insomnia disorder.

Trial registration
Chinese Clinical Trials Register, ChiCTR1800015282. Registered on 20 March 2018.
ELEMENT TRIAL: study protocol for a randomized controlled trial on endoscopic ultrasound-guided biliary drainage of first intent with a lumen-apposing metal stent vs. endoscopic retrograde cholangio-pancreatography in the management of malignant distal biliary obstruction
Authors:   for the ELEMENT trial and for the Canadian Endoscopic Research Collaborative (CERC), Chen Yen-I , Callichurn Kashi , Chatterjee Avijit , Desilets Etienne , Fergal Donnellan , Forbes Nauzer , Gan Ian , Kenshil Sana , Khashab Mouen A. , Kunda Rastislav , Lam Eric , May Gary , Mohamed Rachid , Mosko Jeff , Paquin Sarto C. , Sahai Anand , Sandha Gurpal , Teshima Christopher , Barkun Alan , Barkun Jeffrey , Bessissow Ali , Candido Kristina , Martel Myriam , Miller Corey , Waschke Kevin , Zogopoulos George , Wong Clarence 
Published: December 2019

Abstract
Background & aims
Endoscopic ultrasound guided-biliary drainage (EUS-BD) is a promising alternative to endoscopic retrograde cholangiopancreatography (ERCP); however, its growth has been limited by a lack of multicenter randomized controlled trials (RCT) and dedicated devices. A dedicated EUS-BD lumen- apposing metal stent (LAMS) has recently been developed with the potential to greatly facilitate the technique and safety of the procedure. We aim to compare a first intent approach with EUS-guided choledochoduodenostomy with a dedicated biliary LAMS vs. standard ERCP in the management of malignant distal biliary obstruction.

Methods
The ELEMENT trial is a multicenter single-blinded RCT involving 130 patients in nine Canadian centers. Patients with unresectable, locally advanced, or borderline resectable malignant distal biliary obstruction meeting the inclusion and exclusion criteria will be randomized to EUS-choledochoduodenostomy using a LAMS or ERCP with traditional metal stent insertion in a 1:1 proportion in blocks of four. Patients with hilar obstruction, resectable cancer, or benign disease are excluded. The primary endpoint is the rate of stent dysfunction needing re-intervention. Secondary outcomes include technical and clinical success, interruptions in chemotherapy, rate of surgical resection, time to stent dysfunction, and adverse events.

Discussion
The ELEMENT trial is designed to assess whether EUS-guided choledochoduodenostomy using a dedicated LAMS is superior to conventional ERCP as a first-line endoscopic drainage approach in malignant distal biliary obstruction, which is an important and timely question that has not been addressed using an RCT study design.

Trial registration
Registry name: ClinicalTrials.gov. Registration number: NCT03870386. Date of registration: 03/12/2019.