bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of matrix metalloproteinases in patients with pulmonary hypertension: data from a prospective study
Authors: Marc Adriana , Pop Calin , Sitar-Taut Adela-Viviana , Budisan Liviuta , Berindan-Neagoe Ioana , Pop Dana 
Published: December 2021

Abstract
Background
Despite several therapies, pulmonary hypertension (PH) is still a severe disease which can lead to right heart failure. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in cardiac and vascular remodeling in PH. Therefore, these biomarkers play an important role in PH patients. This study investigated whether TIMP-4, MMP-2, and N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) plasma levels are useful in assessing the severity of PH and other clinical or echocardiographic parameters.

Methods
The concentrations of MMP-2, TIMP-4, and NT-proBNP in 68 PH patients were compared with those of 12 controls without PH. All patients underwent a physical examination, echocardiography, and were checked for the presence of cardiovascular risk factors; also, plasma concentrations of MMP-2, TIMP-4, NT-proBNP, total cholesterol, and triglycerides were determined.

Results
In PH patients, significantly elevated plasma levels of TIMP-4 (PH: 2877.99 ± 1363.78 pg/ml, control: 2028.38 ± 762.67 pg/ml, p = 0.0068) and NT-proBNP ( PH: 2405.00 pg/ml—5423.47 ± 6703.38 pg/ml, control: 411.0000 pg/ml—421.75 ± 315.37 pg/ml, p = 0.01) were detected. We also observed that MMP-2 and NT-proBNP were significantly increased in patients with higher WHO functional class (p = 0.001 for MMP-2, p = 0.008 for NT-proBNP), higher pressure in the pulmonary artery (p = 0.002 for MMP-2, p = 0.001 for NT-proBNP), and more severe tricuspid regurgitation (p = 0.001 for MMP-2, p = 0.009 for NT-proBNP). TIMP-4 was elevated in patients with more severe pressure in the pulmonary artery (p = 0.006).

Conclusions
The plasma levels of TIMP-4 and NT-proBNP are higher in PH patients. MMP-2 and NT-proBNP correlates with different PH parameters severity (WHO functional class, sPAP severity, TV regurgitation severity). Therefore, plasmatic levels of MMP-2 and NT-proBNP at this kind of patients reflect disease severity and may have a prognostic role. MMP-2 can help assess the beneficial effects of PH pharmacotherapy on tissue remodeling. These remodeling biomarkers may not have a diagnostic value but they have the potential to predict survival. Nevertheless, a greater understanding of the involvement of MMPs in PH is mandatory to further explore the prognostic role and the possibilities of therapeutic MMP inhibition in PH.
Early experience with an opt-in research register - Scottish Health Research Register (SHARE): a multi-method evaluation of participant recruitment performance
Authors: Shi Wen , Vasishta Shobna , Dow Louise , Cavellini Daniella , Palmer Colin , McKinstry Brian , Sullivan Frank 
Published: December 2021

Abstract
Background
Recruiting participants to a clinical study is a resource-intensive process with a high failure rate. The Scottish Health Research Register (SHARE) provides recruitment support service which helps researchers recruit participants by searching patients’ Electronic Health Records (EHRs). The current study aims to evaluate the performance of SHARE in participant recruitment.

Methods
Recruitment projects eligible for evaluation were those that were conducted for clinical trials or observational studies and finished before 2020. For analysis of recruitment data, projects with incomplete data were excluded. For each project we calculated, from SHARE records, 1) the fraction of the participants recruited through SHARE as a percentage of the number requested by researchers (percentage fulfilled), 2) the percentage of the potential candidates provided by SHARE to researchers that were actually recruited (percentage provided and recruited), 3) the percentage of the participants recruited through SHARE of all the potentially eligible candidates identified by searching registrants’ EHRs (percentage identified and recruited). Research teams of the eligible projects were invited to participate in an anonymised online survey. Two metrics were derived from research teams’ responses, including a) the fraction of the recruited over the study target number of participants (percentage fulfilled), and b) the percentage of the participants recruited through SHARE among the candidates received from SHARE (percentage provided and recruited).

Results
Forty-four projects were eligible for inclusion. Recruitment data for 24 projects were available (20 excluded because of missingness or incompleteness). Survey invites were sent to all the eligible research teams and received 12 responses. Analysis of recruitment data shows the overall percentage fulfilled was 34.2% (interquartile 13.3–45.1%), the percentage provided and recruited 29.3% (interquartile 20.6–52.4%) and percentage identified and recruited 4.9% (interquartile 2.6–10.2%). Based on the data reported by researchers, percentage fulfilled was 31.7% (interquartile 5.8–59.6%) and percentage provided and recruited was 20.2% (interquartile 8.2–31.0%).

Conclusions
SHARE may be a valuable resource for recruiting participants for some clinical studies. Potential improvements are to expand the registrant base and to incorporate more data generated during patients’ different health care encounters into the candidate-searching step.
Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study
Authors: Suzuki Fumitaka , Suzuki Yoshiyuki , Karino Yoshiyasu , Tanaka Yasuhito , Kurosaki Masayuki , Yatsuhashi Hiroshi , Atarashi Tomofumi , Atsukawa Masanori , Watanabe Tsunamasa , Enomoto Masaru , Kudo Masatoshi , Maeda Naoto , Kohno Hiroshi , Joko Kouji , Michitaka Kojiro , Miki Koichiro , Takahashi Kazuhiro , Ide Tatsuya , Fujiyama Shigetoshi , Kohno Tomoko , Itoh Hiroshi , Tsukamoto Sakiyo , Suzuki Yuko , Kawano Yoshiaki , Sugiura Wataru , Kumada Hiromitsu 
Published: December 2021

Abstract
Background
Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA.

Methods
In this multicenter, single-arm, open-label, phase 4 clinical study, 75 participants currently treated with ETV 0.5 mg once daily were switched to TDF 300 mg once daily for 96 weeks.

Results
At week 48, 3/74 participants (4%) achieved 0.25 log10 reduction of HBsAg levels from baseline (the primary endpoint). Mean HBsAg reduction was −0.14 log10 IU/mL and 12% (9/74) achieved 0.25 log10 reduction by 96 weeks. No participants achieved HBsAg seroclearance. HBsAg reduction at weeks 48 and 96 was numerically greater in participants with higher alanine aminotransferase levels (≥ 60 U/L). Seventeen participants (25%) achieved HBeAg seroclearance up to week 96. No participants experienced viral breakthrough. All drug-related adverse events (18 participants [24%]) were mild in intensity, including an increase in urine beta-2-microglobulin (15 participants [20%]).

Conclusions
In conclusion, HBsAg reduction was limited after switching from ETV to TDF in this study population. Further investigation is warranted to better understand the clinical impact of switching from ETV to TDF.
ClinicalTrials.gov: NCT03258710 registered August 21, 2017. https://clinicaltrials.gov/ct2/show/NCT03258710?term=NCT03258710&draw=2&rank=1
Ultrasound contrast agent Sonazoid for the diagnosis of hepatic epithelioid angiomyolipoma: a case report
Authors: Huang Zhe , Xin Jun-yi , Li Kai-yan 
Published: December 2021

Abstract
Background
An angiomyolipoma usually occurs in the kidneys and rarely in the liver. Hepatic epithelioid angiomyolipoma (HEAML), a rare variant of angiomyolipoma, possesses malignant potential and mimics the imaging features of hepatocellular carcinoma. Sonazoid® (perfluorobutane microbubbles), a new contrast agent that facilitates hepatic parenchyma-specific Kupffer phase imaging on contrast-enhanced ultrasonography (CEUS), is useful for the detection and characterization of focal liver lesions.

Case presentation
A 30-year-old man with HEAML underwent CEUS using Sonazoid®, in which new concepts for ultrasonography-based differentiation between HEAML and hepatocellular carcinoma were applied.

Conclusions
This case report provides clinicians and radiologists with a reference for distinguishing HEAML from hepatocellular carcinoma based on CEUS using Sonazoid®.
Case reports of invasive mucormycosis associated neutropenic enterocolitis in leukemic children: diagnostic and treatment challenges and review of literature
Authors: Amanati Ali , Zekavat Omid Reza , Foroutan Hamidreza , Azh Omidreza , Tadayon Ali , Monabati Ahmad , Anbardar Mohammad Hossein , Bozorgi Haleh 
Published: December 2021

Abstract
Background
Bacterial enterocolitis is one of the most common neutropenic fever complications during intensive chemotherapy. Despite aggressive antibacterial treatments, this complication usually imposes high morbidity and mortality in cancer patients. Management of bacterial neutropenic enterocolitis are well known; however, management of fungal neutropenic enterocolitis may be more challenging and needs to be investigated. Prompt diagnosis and treatment may be life-saving, especially in patients at risk of mucormycosis-associated neutropenic enterocolitis.

Case presentation
We report two mucormycosis-associated neutropenic enterocolitis cases in pediatric leukemic patients receiving salvage chemotherapy for disease relapse. Both patients' clinical signs and symptoms differ from classical bacterial neutropenic enterocolitis. They were empirically treated as bacterial neutropenic enterocolitis with anti-gram-negative combination therapy. Despite broad-spectrum antimicrobial treatment, no clinical improvement was achieved, and both of them were complicated with severe abdominal pain necessitating surgical intervention. Mucormycosis is diagnosed by immunohistopathologic examination in multiple intraoperative intestinal tissue biopsies. Both patients died despite antifungal treatment with liposomal amphotericin-B and surgical intervention.

Conclusion
Mucormycosis-associated neutropenic enterocolitis is one of the most unfavorable and untreatable side effects of salvage chemotherapy in leukemic children with disease relapse. This report could be of considerable insight to the clinicians and scientists who counter the enigma of fungal infections during febrile neutropenia and help to understand better diagnosis and management.
A novel de novo truncating TRIM8 variant associated with childhood-onset focal segmental glomerulosclerosis without epileptic encephalopathy: a case report
Authors: Shirai Yoko , Miura Kenichiro , Kaneko Naoto , Ishizuka Kiyonobu , Endo Amane , Hashimoto Taeko , Kanda Shoichiro , Harita Yutaka , Hattori Motoshi 
Published: December 2021

Abstract
Background
Heterozygous truncating variants in the Tripartite motif containing 8 (TRIM8) gene have been reported to cause epileptic encephalopathy, both with and without proteinuria. A recent study showed a lack of TRIM8 protein expression, with suppressor of cytokine signaling 1 (SOCS1) overexpression, in podocytes and tubules from a patient with a TRIM8 variant, who presented with epileptic encephalopathy and focal segmental glomerulosclerosis (FSGS). To date, no patients with TRIM8 variants who presented with nephrotic syndrome but without neurological manifestations have been described.

Case presentation
An 8-year-old girl presented with nephrotic syndrome, without epilepsy or developmental delay. Her kidney biopsy specimens showed FSGS and cystic dilatations of the distal tubules. Whole-exome sequencing identified a novel de novo heterozygous variant in the C-terminal encoding portion of TRIM8 (c.1461C > A), resulting in a premature stop codon (p.Tyr487*). Reverse transcription-polymerase chain reaction using peripheral blood mononuclear cells identified the mRNA sequence of the mutant allele, which confirmed an escape from nonsense-mediated mRNA decay. Immunofluorescence studies showed a lack of TRIM8 expression in glomerular and tubular cells and cystic dilatation of distal tubules. Immunohistochemical studies showed overexpression of SOCS1 in glomerular and tubular cells.

Conclusions
We reported a patient with FSGS, associated with a de novo heterozygous TRIM8 variant, without any neurological manifestations. Our results expanded the clinical phenotypic spectrum of TRIM8 variants.
Renal function in β-thalassemia major patients treated with two different iron-chelation regimes
Authors: Tanous Osama , Azulay Yossi , Halevy Raphael , Dujovny Tal , Swartz Neta , Colodner Raul , Koren Ariel , Levin Carina 
Published: December 2021

Abstract
Background
Renal injury in transfusion dependent β thalassemia patients (TDT) has been attributed to iron overload, chronic anemia and iron-chelation therapy (ICT) toxicity. We studied renal function in TDT patients treated with two different ICT regimes.

Patients and methods
We studied 36 TDT patients: 26 received deferasirox (DFX) and 10 were treated with deferoxamine (DFO) +/− deferiprone (DFP).

Results
Increased uNAG was found in 30% of the DFX group vs. 10% of the DFO+/−DFP group, the mean uNAG level in the DFX group was significantly higher than in the DFO+/−DFP group, (P < 0.05). A moderate negative correlation was found between uNAG levels and mean serum ferritin for the prior 10 years (P = 0.03), more pronounced for the DFO+/−DFP group. Twenty nine patients had had their renal function evaluated 10 years earlier; eGFR significantly declined in patients switched to DFX (P = 0.0093) but not in patients who continued DFO+/−DFP.

Conclusions
A high prevalence of renal tubular damage was observed in our TDT patients, particularly those treated with DFX; uNAG was negatively associated with mean 10-year serum ferritin, suggesting ICT’s involvement in tubular injury. A significant decline in eGFR compared to a decade earlier was observed only in patients currently treated with DFX. Strict follow-up of renal function in TDT patients is warranted.
The association of workplace smoke-free policies on individual smoking and quitting-related behaviours
Authors: Lin Haoxiang , Li Min , Chen Meijun , Liu Yihua , Lin Yuting , Liu Zhao , Zheng Zhijie , Chang Chun 
Published: December 2021

Background
Our study aims to provide information about workplace smoke-free (SF) policy coverage in mainland China and to assess the relationship between workplace SF policies and secondhand smoke (SHS) exposure, current smoking, smoking harm awareness and quitting intention among smokers.

Method
Data from the 2018 Asia Best Workplace Mainland China programme were used to address these aims. This cross-sectional study included 14,195 employees from the 2018 survey and 14,953 employees from the 2019 survey. Logistic regression with year-fixed effects was applied to these data. The dependent variables were SHS exposure, smoking or smoking harm awareness. The explanatory variable was the SF workplace policy.

Results
A total of 21,275 participants (73.0%) reported working under SF policies. The overall prevalence of smoking and SHS exposure were 20.3% and 52.5%, respectively. The workplace SF policy was significantly associated with lower SHS exposure (OR: 0.48, 95% CI: 0.45–0.51), lower current smoking employees (OR: 0.81, 95% CI: 0.76–0.87) and higher awareness of smoking harm (OR: 1.76, 95% CI: 1.61–1.91). However, workplace SF policy was not significantly associated with quitting intention (OR: 0.99, 95% CI: 0.84–1.16).

Conclusion
Our study identified that although most companies had established workplace SF policies, the overall prevalence of SHS exposure remained very high. Workplace SF policy is associated with lower SHS exposure, lower overall current smoking and higher awareness of smoking harm. These findings provide valuable evidence to promote such policies in all workplaces.
Risk factors of opioid use associated with an enhanced-recovery programme after total knee arthroplasty
Authors: Cao Guorui , Xiang Shiqi , Yang Minglu , Quan Songtao , Yao Junna , Cai Litao , Feng Wei , Yang Xiuli , Xu Hong , Huang Zeyu , Zhang Shaoyun , Yue Chen , Tan Honglue , Pei Fuxing 
Published: December 2021

Abstract
Background
Characterizing the impacts of postoperative opioid use on total knee arthroplasty (TKA) patients may help optimize the pain management after TKA. The aim of the study is to examine the prevalence and risk factors for opioid use with an enhanced-recovery programme after primary TKA.

Methods
We identified 361 patients undergoing TKA, and separated those on the basis of whether to receive opioid use after surgery. Themultivariate logistic regression model was used to identify independent risk factors for opioid use after primary TKA. Length of stay (LOS) and postoperative complications were also recorded and compared.

Results
The prevalence of opioid use after primary TKA was 23.0%. The significant risk factor was the longer operative time (OR [odds ratio] = 1.017, 95% CI [confidence interval] = 1.001 to 1.032, p = 0.034) and the protective factor was the utilization of tranexamic acid(OR= 0.355, 95% CI = 0.161 to 0.780, p = 0.010). In addition, the LOS was longer in opioid group (p < 0.05).

Conclusion
Considering the adverse health effects of opioid use, strategies need to be developed to prevent persistent opioid use after TKA. Reducing operative time and the application of tranexamic acid could lower the risk of opioid use with an enhanced-recovery programme after primary TKA.
Personal factors associated with carpal tunnel syndrome (CTS): a case-control study
Authors: Al Shahrani Eman , Al Shahrani Abeer , Al-Maflehi Nassr 
Published: December 2021

Abstract
Background
Carpal tunnel syndrome (CTS) is one of the most common nerve entrapments in the upper limb. In Saudi Arabia, few studies have investigated CTS in the general population. This study aimed to determine the association between personal factors and CTS.

Methods
A case-control study involved adults aged 18 and above. Cases were recruited from electrophysiology lab records as consecutive case series, while controls were individuals who were free of CTS symptoms according to the Boston Carpal Tunnel Questionnaire (BCTQ). The electronic medical records of participants were reviewed to obtain age, height, weight, medical conditions, and mobile numbers. Cases and controls were contacted via phone to complete a questionnaire that was designed based on previous literature. We used multivariate binary logistic regression to identify the personal factors significantly associated with CTS.

Results
A total of 95 cases and 190 controls were included. Most of the participants were female (84.2%) and Saudi (93%). Most of cases were above 45 years of age (73.7%), while 84.7% were 45 year – old or younger among the control group. Stratified logistic regression showed that performance of household chores was significantly associated with CTS. While physical exercise associated with decreased odds of CTS.

Conclusions
This study adds to the body of evidence on personal factors associated with CTS. However, the degree of differences in the age structure of the cases compared with the controls suggest that there is a considerable potential for residual confounding affecting the results.

Trial registration number
Not applicable.
Evaluation of the efficacy and safety of conventional and biportal endoscopic decompressive laminectomy in patients with lumbar spinal stenosis (ENDO-B trial): a protocol for a prospective, randomized, assessor-blind, multicenter trial
Authors: Park Hyun-Jin , Park Sang-Min , Song Kwang-Sup , Kim Ho-Joong , Park Si-Young , Kang Taewook , Kang Min-Seok , Heo Dong-Hwa , Park Choon-Keun , Lee Dong-Geun , Hwang Jin-Sub , Jang Jae-Won , Kim Jun-Young , Kim Jin-Sung , Lee Hong-Jae , Yoon Joon-Hyeok , Park Chang-Won , You Ki-Han 
Published: December 2021

Abstract
Background
Recent studies on biportal endoscopic spine surgery in patients with lumbar spinal stenosis have reported good clinical results. However, these studies have been limited by the small sample sizes and use of a retrospective study design. Therefore, we aim to compare the efficacy and safety of biportal endoscopic decompressive laminectomy with those of conventional decompressive laminectomy in a multicenter, prospective, randomized controlled trial.

Methods
This study will include 120 patients (60 per group, aged 20–80 years) with 1- or 2-level lumbar spinal stenosis, who will be recruited from six hospitals. The study will be conducted from July 2021 to December 2024. The primary outcome (Oswestry Disability Index at 12 months after surgery) will be evaluated through a modified intention-to-treat method. The secondary outcomes will include the following: visual analog scale score for low back and lower extremity radiating pain, EuroQol 5-dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scars, and some surgery-related variables. Radiographic outcomes will be analyzed using magnetic resonance imaging or computed tomography. All outcomes will be evaluated before the surgery and at 2 weeks, 3 months, 6 months, and 12 months postoperatively. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for reporting of clinical trial protocols.

Discussion
It is hypothesized that the efficacy and safety of biportal endoscopic and conventional decompressive laminectomy will be comparable in patients with lumbar spinal stenosis. The results of this trial will provide a high level of evidence for the efficacy and safety of the biportal endoscopic technique in patients with lumbar spinal stenosis and facilitate the development of clinical practice guidelines. Furthermore, the results of this study may indicate the feasibility of the biportal endoscopic technique for other types of spinal surgery.

Trial registration
The ENDO-B trial is registered at Clinical Research Information Service (CRIS, cris.nih.go.kr) (KCT0006057; April 52,021).