bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for the Metformin Aneurysm Trial (MAT): a placebo-controlled randomised trial testing whether metformin reduces the risk of serious complications of abdominal aortic aneurysm
Authors: Golledge Jonathan , Arnott Clare , Moxon Joseph , Monaghan Helen , Norman Richard , Morris Dylan , Li Qiang , Jones Greg , Roake Justin , Bown Matt , Neal Bruce 
Published: December 2021

Abstract
Background
Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms.

Methods
MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05).

Discussion
Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design.

Trial registration
Australian Clinical Trials ACTRN12618001707257. Registered on 16 October 2018
Robotic versus Open Pancreatoduodenectomy for Pancreatic and Periampullary Tumors (PORTAL): a study protocol for a multicenter phase III non-inferiority randomized controlled trial
Authors: Jin Jiabin , Shi Yusheng , Chen Mengmin , Qian Jianfeng , Qin Kai , Wang Zhen , Chen Wei , Jin Weiwei , Lu Fengchun , Li Zheyong , Wu Zehua , Jian Li , Han Bing , Liang Xiao , Sun Chuandong , Wu Zheng , Mou Yiping , Yin Xiaoyu , Huang Heguang , Chen Hao , Gemenetzis Georgios , Deng Xiaxing , Peng Chenghong , Shen Baiyong 
Published: December 2021

Abstract
Background
Pancreatoduodenectomy is a complex and challenging procedure that requires meticulous tissue dissection and proficient suturing skills. Minimally invasive surgery with the utilization of robotic platforms has demonstrated advantages in perioperative patient outcomes in retrospective studies. The development of robotic pancreatoduodenectomy (RPD) in specific has progressed significantly, since first reported in 2003, and high-volume centers in pancreatic surgery are reporting large patient series with improved pain management and reduced length of stay. However, prospective studies to assess objectively the feasibility and safety of RPD compared to open pancreatoduodenectomy (OPD) are currently lacking.

Methods/design
The PORTAL trial is a multicenter randomized controlled, patient-blinded, parallel-group, phase III non-inferiority trial performed in seven high-volume centers for pancreatic and robotic surgery in China (> 20 RPD and > 100 OPD annually in each participating center). The trial is designed to enroll and randomly assign 244 patients with an indication for elective pancreatoduodenectomy for malignant periampullary and pancreatic lesions, as well as premalignant and symptomatic benign periampullary and pancreatic disease. The primary outcome is time to functional recovery postoperatively, measured in days. Secondary outcomes include postoperative morbidity and mortality, as well as perioperative costs. A sub-cohort of 128 patients with pancreatic adenocarcinoma (PDAC) will also be compared to assess the percentage of patients who undergo postoperative adjuvant chemotherapy within 8 weeks, in each arm. Secondary outcomes in this cohort will include patterns of disease recurrence, recurrence-free survival, and overall survival.

Discussion
The PORTAL trial is designed to assess the feasibility and safety of RPD compared to OPD, in terms of functional recovery as described previously. Additionally, this trial will explore whether RPD allows increased access to postoperative adjuvant chemotherapy, in a sub-cohort of patients with PDAC.

Trial registration
ClinicalTrials.govNCT04400357. Registered on May 22, 2020
A mechanism-based proof of concept study on the effects of duloxetine in patients with painful knee osteoarthritis
Authors: Ammitzbøll Nadia , Arendt-Nielsen Lars , Bertoli Davide , Brock Christina , Olesen Anne Estrup , Kappel Andreas , Drewes Asbjørn Mohr , Petersen Kristian Kjær 
Published: December 2021

Abstract
Background
The global burden of osteoarthritis (OA) is steadily increasing due to demographic and lifestyle changes. The nervous system can undergo peripheral and central neuroplastic changes (sensitization) in patients with OA impacting the options to manage the pain adequately. As a result of sensitization, patients with OA show lower pressure pain thresholds (PPTs), facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM). As traditional analgesics (acetaminophen and non-steroidal anti-inflammatory drugs) are not recommended for long-term use in OA, more fundamental knowledge related to other possible management regimes are needed. Duloxetine is a serotonin-noradrenalin reuptake inhibitor, and analgesic effects are documented in patients with OA although the underlying fundamental mechanisms remain unclear. The descending pain inhibitory control system is believed to be dependent on serotonin and noradrenalin. We hypothesized that the analgesic effect of duloxetine could act through these pathways and consequently indirectly reduce pain and sensitization. The aim of this mechanistic study is to investigate if PPTs, TSP, CPM, and clinical pain parameters are modulated by duloxetine.

Methods
This proof of concept study is a randomized, placebo-controlled, double-blinded, crossover trial, which compares PPTs, TSP, and CPM before and after 18 weeks of duloxetine and placebo in forty patients with knee OA. The intervention periods include a titration period (2 weeks), treatment period (60 mg daily for 14 weeks), and a discontinuation period (2 weeks). Intervention periods are separated by 2 weeks.

Discussion
Duloxetine is recommended for the treatment of chronic pain, but the underlying mechanisms of the analgesic effects are currently unknown. This study will investigate if duloxetine can modify central pain mechanisms and thereby provide insights into the underlying mechanisms of the analgesic effect.

Trial registration
ClinicalTrials.govNCT04224584. Registered on January 6, 2020. EudraCT 2019-003437-42. Registered on October 22, 2019. The North Denmark Region Committee on Health Research Ethics N-20190055. Registered on October 31, 2019.
Microbial degradation and community structure analysis of hydroxyl-terminated polybutadiene (HTPB)
Authors: Zhang Ying , Zou Min , Lodhi Adil Farooq , Deng Yu-lin 
Published: December 2021

AbstractHydroxyl-terminated polybutadiene (HTPB) is a curing adhesive that is commonly used in the production of ammunition, and it emerged during the time of war. After entering the peaceful era, several countries around the globe have focused on the destruction of expired ammunition using safe and economical methods in terms of consumption of energy. Microorganisms exhibit a highly efficient and environment friendly degradation capability for variety of refractory substances. Therefore, in this study we screened five strains of microorganisms from five environmental soil samples for their ability to degrade HTPB. These microorganisms were identified as Microbacterium trichothecenolyticum, Microbacterium esteraromaticum, Arthrobacter pascens, Pseudonocardia carboxydivorans and Ochrobactrum anthropic based on 16S rRNA gene similarity index. We observed the uncorroded and corroded HTPB sample through scanning electron microscopy and observed the formation of lot of holes and gullies in HTPB after corrosion. An 18S rRNA gene clone library was constructed for HTPB-degrading fungi. Based on the results of library evaluation, it was found that the structure of the HTPB-degrading fungi community was relatively simple. A total of 54 positive clones were obtained. These clones represented some uncultured microorganisms that were closely related to Scytalidium lignicola, Pseudokahliella and Gonostomum strenuum. This study will help in the implementation of environment friendly degradation strategies for HTPB degradation.
Modular control of multiple pathways of Corynebacterium glutamicum for 5-aminolevulinic acid production
Authors: Ge Fanglan , Li Xiaokun , Ge Qingrong , Zhu Di , Li Wei , Shi Fenghui , Chen Hongjin 
Published: December 2021

Abstract5-aminolevulinic acid (ALA) has broad potential applications in the medical, agricultural and food industries. Several strategies have been implemented successfully to try to improve ALA synthesis. Nonetheless, the low yield has got in the way of large-scale bio-manufacture of 5-ALA. In this study, we explored strain engineering strategies for high‐level 5‐ALA production in Corynebacterium glutamicum F343 using the C4 pathway. Initially, the glutamate dehydrogenase-encoding gene gdhA was deleted to reduce glutamate yield. Then the C4 pathway was introduced in the gdhA mutant strain F2-A (∆gdhA + hemA), resulting in a 5-ALA yield of up to 3.2 g/L. Furthermore, the accumulations of downstream metabolites such as heme, porphobilinogen, and protoporphyrin IX, were decreased. After evaluating the mechanisms of this synthetic pathway by RNA-Seq, the results showed that genes involved in both the C5 pathway and heme pathways were down-regulated in strain F2-A (∆gdhA + hemA). Interestingly, upstream genes of succinyl-CoA in the tricarboxylic acid (TCA) cycle, such as icd, lpdA, were up-regulated, while its downstream genes, including sucC, sucD, sdhB, sdhA, sdhCD, were down-regulated. These changes amplify the sources of succinyl-CoA and reduce its expenditure, before pulling the carbon flux to produce 5-ALA. Furthermore, the down-regulation of most genes of the heme pathway could reduce the drainage of 5‐ALA, which further enhance its accumulation. To alleviate competition between glyoxylate and the TCA cycle, the isocitrate dehydrogenase-encoding gene aceA was also knocked out, resulting in 3.86 g/L of 5‐ALA. Finally, the fermentation conditions were optimized, resulting in a maximum 5-ALA yield of 5.6 g/L. Overall, the blocking of the glutamate synthesis pathway could be a powerful strategy to re-allocate the carbon flux to produce 5-ALA. It could also enable the efficient synthesis of other TCA derivatives in C. glutamicum.
Vitamin D and its association with symptom severity in knee osteoarthritis: a cross sectional study at a national referral hospital in Uganda
Authors: Namutebi Fiona , Kayima James , Kaddumukasa Mark 
Published: December 2021

Abstract
Background
Vitamin D deficiency is highly prevalent among patients with osteoarthritis. It is associated with joint pain, stiffness and worse physical function. Whether vitamin D deficiency is associated with osteoarthritis is controversial. We investigated serum vitamin D levels and its association with symptom severity in patients with knee osteoarthritis.

Methods
Between January 2020 to March and May 2020, we conducted a cross sectional study at a national referral hospital in Uganda. Using the American College of Rheumatology clinical criteria, 107 consenting adults were diagnosed with knee osteoarthritis. A questionnaire captured patient demographics and clinical characteristics. Joint pain, stiffness and physical function severity were assessed and graded based on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). We determined serum vitamin D levels by electrochemilumniscence immunoassay. The data were analysed and adjusted for age, sex, education, occupation, family history, body mass index (BMI) and calcium supplementation.

Results
Of the 107 patients, 92 (86%) patients were females, mean (SD) age was 58.1 (12.6) years. Nearly 65% of the patients had suboptimal serum vitamin D levels < 30 ng/ml. The median (Q1, Q3) WOMAC joint scores were as follows: pain 8.0 (5, 11), stiffness 1 (0, 2), physical function 29.0 (16, 41) and total WOMAC 39.0 (21, 54). Spearman correlations between serum vitamin D levels with symptom severity were as follows: joint pain (r = 0.18, p = 0.06), stiffness (r = 0.13, p = 0.17), physical function (r = 0.09, p = 0.36) and total WOMAC (r = 0.13, p = 0.19).

Conclusion
Serum vitamin D levels are not associated with joint pain, stiffness and physical function severity. Older age and higher BMI are associated with vitamin D deficiency in patients with knee osteoarthritis attending a national referral hospital rheumatology clinic in Uganda. Suboptimal vitamin D is an independent risk factor for total mortality in the general population. Clinical guidelines and further studies to determine age and BMI ranges required for vitamin D screening are needed in patients with osteoarthritis in Uganda. Patients are advised to keep a normal BMI.
Brain tumors in the first two years of life
Authors: Enayet Abdelrhman 
Published: December 2021

Abstract
Background
Brain tumors in the first years of life are frequently encountered recently with the advancement in neuroimaging, neurosurgery and neuroanethesia where early diagnosis of these lesions became available even before birth. Their management is challenging where the surgery is technically demanding, radiotherapy is omitted in this age because of its late sequelae and chemotherapy role may be beneficial, but it is limited also by its side effects and neurotoxicity. The aim of this article is to review the current literature about the brain tumors in the first two years of life, their diagnosis and treatment.

Main body
Brain tumors in the first two years of life encompass mainly fetal/congenital tumors and infantile tumors. They account for 1.4–18% of cases of pediatric brain tumor, and most of them are diagnosed in the first year of life. The main histopathologies diagnosed are glial tumors, choroid plexus tumors, medulloblastoma and other embryonal tumors, teratoma and ependymoma. They are mainly supratentorial. Large head and bulging fontanelles are the main presenting symptoms and signs secondary to increased intracranial pressure secondary to large tumors or associated hydrocephalus. Prenatal and postnatal ultrasonography represents the initial imaging step in the diagnosis that should be complemented by MRI and CT brain. The main and first line of treatment of infantile brain tumors is surgical excision as the prognosis is directly related to the extent of resection besides surgery offers specimens for histopathological diagnosis and adjuvant chemotherapy is given for residual irresectable cases and malignant tumors with the main aim to delay radiotherapy beyond the age of three years.

Conclusion
Brain tumors in the first two years of life are a challenging group of different histopathological entities with underlying specific molecular characterization and genetic predispositions. They have aggressive behavior and general poor prognosis with limited options of management. Individualized multidisciplinary management for each case is needed, and future studies for therapeutic medications targeting underlying molecular biology may improve their outcome.
Simultaneous Quantification of Aromatase Inhibitors and Estrogens in Postmenopausal Breast Cancer Patients
Authors: Bertelsen Bjørn-Erik , Viste Kristin , Helland Thomas , Hagland Magnus , Søiland Håvard , Geisler Jürgen , Lende Tone Hoel , Lønning Per Eystein , Sagen Jørn V , Mellgren Gunnar , Almås Bjørg 
Published: December 2021

Abstract

Context
Currently there are no assays that can simultaneously quantify serum levels of the third-generation aromatase inhibitors (AIs): letrozole, anastrozole, and exemestane, and the ultra-low levels of estrogens in postmenopausal breast cancer patients on AI treatment. Such measurements may be pivotal for the determination of optimal and individualized treatment regimens. We aimed at developing a liquid chromatography–tandem mass spectrometry (MS/MS) method for simultaneous assessment of letrozole, anastrozole, exemestane, and 17-hydroxyexemestane as well as subpicomolar levels of estradiol and estrone.

Methods
Internal standards, calibrators, serum samples, and quality controls were in fully automated steps transferred to a deep-well plate for a 2-step liquid-liquid extraction. The extracts were reconstituted and analytes were separated chromatographically using 2 serially coupled columns, then subject to MS/MS in electrospray ionization mode. The method was thoroughly validated and is traceable to 2 accredited estrogen methods.

Results
The measurement range for estrone and estradiol was 0.2 to 12 000 pmol/L and 0.8 to 13 000 pmol/L, and covered the expected therapeutic range for the AIs. All analytes had a precision of less than or equal to 13%, and accuracies within 100 ± 8%. As proof of concept, AI and estrogen levels were determined in serum samples from postmenopausal breast cancer patients under treatment.

Conclusion
We present here an assay suitable for the simultaneous measurement of serum levels of all third-generation AIs and ultra-low levels of estrogens, providing a powerful new tool to study drug efficacy and compliance. The method is highly valuable for postmenopausal patients whose pretreatment estradiol levels are below the threshold of detection for most routine assays, but still require suppression.
Association Between Frailty and Clinical Outcomes and Quality of Life in Older Adults Following Hip Fracture Surgery: A Retrospective Cohort Study
Authors: Zhao Hong , Wei Peiyao , Feng Yi 
Published: December 2021

BACKGROUND:
Hip fracture is a serious event in the older population and is associated with morbidity, mortality, and disability among those who survive. Emerging evidence suggests that frailty is pertinent to the clinical outcomes of older patients with hip fracture.

METHODS:
We conducted a retrospective cohort study on older patients (aged ≥65 years) who underwent orthopedic repair with hip fracture under spinal or general anesthesia between June 1, 2019 and May 31, 2020. Demographic, surgical, and anesthetic features; chart-derived frailty index (CFI); occurrence of complications; and length of stay were retrospectively collected by reviewing patients’ anesthesia records and medical charts. Patients were divided into 2 groups according to their CFI: high CFI group (CFI, 3–5) and low CFI group (CFI, 0–2). The CFI was calculated as the addition of the patient’s conditions, including age >70 years, preoperative body mass index <18.5 kg/m2, hematocrit <35%, albumin <34 g/L, and serum creatinine >176.8 mol/L (2.0 mg/dL). The EuroQol 5-dimensional questionnaire (EQ-5D) was obtained through telephone interviews 12 months after surgery to assess mortality and long-term quality of life.

RESULTS:
During the study period, 381 patients met the inclusion criteria. Patients in the high CFI group had an increased incidence of delirium by 13.80% (95% confidence interval [CI], 6.31–21.29) (17 [16.6%] vs 8 [2.8%]; P < .001) compared to patients in the low CFI group. More patients in the high CFI group had pneumonia with an increased incidence of 17.71% (95% CI, 7.08–23.34) (40 [39.2%] vs 60 [21.5%]; P < .001) than patients in the low CFI group. Postoperative hospital stay was significantly longer in the high CFI group (8 [6–12] vs 7 [5–10] days; P = .0222) than in the low CFI group. More patients died in the high CFI group 1 year after surgery with an increased mortality of 19.33% (95% CI, 9.47–29.18) (26.4% [23/87] vs 7.1% [16/225]; P < .001) than patients in the low CFI group. A total of 64 patients in the high CFI group and 209 patients in the low CFI group completed the EQ-5D survey 1 year after surgery. The EQ-5D score in the high CFI group was significantly lower than that in the low CFI group (0.63 ± 0.22 vs 0.72 ± 0.22; P = .002).

CONCLUSIONS:
Frailty status is associated with adverse postoperative outcomes, mortality, and low quality of life 12 months after hip fracture surgery in older patients.
Preoperative Assessment of Anxiety and Depression Using Computerized Adaptive Screening Tools: A Pilot Prospective Cohort Study
Authors: Bass Victoria , Brown Frank , Beiser David G. , Peterson Tarren , Gibbons Robert D. , Nagele Peter 
Published: December 2021

BACKGROUND:
Serious mental health conditions (eg, anxiety and depression) are common in surgical patients, yet likely underassessed due to the time-consuming and cumbersome traditional screening process. A recently developed computerized adaptive mental health assessment tool (computerized adaptive test-mental health [CAT-MH]) allows rapid, precise, and accurate assessment of numerous mental health disorders, including anxiety and depression, without the need for a trained interviewer. The goal of this investigation was to determine the feasibility of administering CAT-MH for anxiety and depression in the preoperative setting and to obtain preliminary evidence of the prevalence of anxiety and depression in preoperative patients.

METHODS:
In this prospective cohort study, 100 adult patients scheduled for elective surgery were enrolled and asked to complete the CAT-MH in the preoperative clinic. Urgent and emergency surgeries were excluded as were pregnant patients. Primary feasibility outcomes were completion rate and time to completion. Secondary outcomes were prevalence estimates of anxiety and depression.

RESULTS:
All 100 enrolled patients completed the study. All patients were able to complete the mental health assessment (mean time: 3.6 ± 1.8 minutes standard deviation). Sixteen patients (16%) screened positive for anxiety (severity: mild, n = 7 [7%]; moderate, n = 7 [7%]); severe, n = 2 [2%]); 12 of 16 (75%) did not have a previous diagnosis of anxiety disorder. Twenty-eight (28%) patients screened positive for depression (severity: mild, n = 26 [26%]; moderate and severe, n = 1 each [1%]); 23 of 28 (82%) had no previous diagnosis of depressive disorder. Nineteen patients (19%) met the screening criteria for major depressive disorder; 14 of 19 (74%) of which had no previous diagnosis of major depressive disorder.

CONCLUSIONS:
The results of this pilot study support the feasibility of using CAT-MH in a preoperative evaluation and indicate that there is a substantial prevalence of undiagnosed anxiety and depression in surgical patients.