bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer’s Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments
Authors: Hoang Karen , Watt Hilary , Golemme Mara , Perry Richard J. , Ritchie Craig , Wilson Danielle , Pickett James , Fox Chris , Howard Robert , Malhotra Paresh A. 
Published: August 2022

Abstract
Background
Guanfacine is a α2A adrenergic receptor agonist approved for treating attention deficit hyperactivity disorder (ADHD). It is thought to act via postsynaptic receptors in the prefrontal cortex, modulating executive functions including the regulation of attention. Attention is affected early in Alzheimer’s disease (AD), and this may relate to pathological changes within the locus coeruleus, the main source of noradrenergic pathways within the brain. Given that cholinergic pathways, also involved in attention, are disrupted in AD, the combination of noradrenergic and cholinergic treatments may have a synergistic effect on symptomatic AD. The primary objective of the NorAD trial is to evaluate the change in cognition with 12 weeks of treatment of extended-release guanfacine (GXR) against a placebo as a combination therapy with cholinesterase inhibitors in participants with mild to moderate Alzheimer’s disease.

Methods/design
NorAD is a 3-month, single-centre, randomised, double-blind, placebo-controlled, phase III trial of extended-release guanfacine (GXR) in participants with mild to moderate Alzheimer’s disease. A total of 160 participants will be randomised to receive either daily guanfacine or placebo in combination with approved cholinesterase treatment for 12 weeks. The primary outcome is the change in cognition, as measured by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), from baseline to follow-up in the treatment group compared to the placebo group. Secondary outcomes include the change in additional cognitive measures of attention (Tests of Attention: Trails A and B, digit-symbol substitution, Test of Everyday Attention and CANTAB-RVP), neuropsychiatric symptoms (Neuropsychiatric Inventory), caregiver burden (Zarit Burden Interview) and activities of daily living (Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory). From July 2020, observation of change following cessation of treatment is also being assessed.

Discussion
There is strong evidence for early noradrenergic dysfunction in Alzheimer’s disease. The NorAD trial aims to determine whether guanfacine, a noradrenergic alpha-2 agonist, improves attention and cognition when used in addition to standard cholinergic treatment.

Trial registration
ClinicalTrials.govNCT03116126. Registered on 14 April 2017
EudraCT: 2016-002598-36
Postoperative fasting is associated with longer ICU stay in oncologic patients undergoing elective surgery
Authors: Fachini Caroline , Alan Claudio Z. , Viana Luciana V. 
Published: August 2022

Abstract
Background
Cancer patients present nutritional and complications risks during the postoperative period. Fasting contributes to surgical catabolic damage. This study evaluates the consequence of fasting time on the surgical outcomes of cancer patients undergoing elective surgeries.

Methods
Prospective cohort, evaluating two categories of patients according to postoperative fasting: less than or greater than 24 h. Outcomes: Hospitalization time, 28-day mortality, ICU stay and infection rates.

Discussion
We included 109 patients (57% men, 60 ± 15 years, BMI: 26 ± 5 kg/m2, SAPS3 43 ± 12), hepatectomy was the most frequent surgery (13.8%), and colon and rectum were the most common neoplasia (18.3%). The ICU stay was longer in postoperative fasting > 24 h (5.5 [4–8.25] vs. 3 [2–5] days, p < 0.001). Fasting > 24 h persisted as a risk factor for longer length of stay (LOS) in the ICU after adjustments. There were no differences in the mortality analysis within 28 days and total hospitalization time between groups. A tendency to experience more infections was observed in patients who fasted > 24 h (34.8% vs. 16.3%, p = 0.057). Onset of diet after the first 24 h postoperatively was a risk factor for longer ICU stay in cancer patients who underwent major surgeries.

Graphical Abstract
Decreased self-reported receiving of social touch and social support predict loneliness in healthy adults
Authors: Araújo Cássia Regina Vieira , Mota Bruna Eugênia Ferreira , Campagnoli Rafaela Ramos , Rocha-Rego Vanessa , Volchan Eliane , Souza Gabriela Guerra Leal 
Published: August 2022

AbstractLoneliness has emerged as a public health concern. Previous research has reported its deleterious effects on physical and mental health; however, some specific psychophysiological mechanisms in healthy adults remain to be elucidated. The aim of the current study is to investigate whether self-reported social support and social touch (giving and receiving social touch), as well as resting heart rate variability (HRV), are significant negative predictors of loneliness in healthy adults. The study sample consists of 120 healthy students (50% female) with a mean age of 21.85 years old (DP= 2.21). The students were asked to complete a psychiatric screening questionnaire utilizing loneliness, social support, and social touch scales. HRV was derived from an electrocardiographic signal recorded for 15 min, with the participant relaxed in a supine position. Linear regression analyses were conducted to evaluate loneliness as a function of social support, social touch (giving or receiving touch), and resting HRV. The results show that social support (p< 0.001) and social touch, specifically receiving touch (p< 0.002), accounted for a significant proportion of the variance in loneliness. However, neither giving touch nor resting HRV was a significant predictor of loneliness. The current study highlights specific psychosocial factors in healthy adults that should be considered as promising pathways in order to reduce or work toward preventing loneliness, thus promoting better health and well-being.
Extracellular vesicles in idiopathic pulmonary fibrosis: pathogenesis and therapeutics
Authors: Fujita Yu 
Published: August 2022

AbstractIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease that occurs due to increased fibrosis of lung tissue in response to chronic injury of the epithelium. Therapeutic options for IPF remain limited as current therapies only function to decrease disease progression. Recently, extracellular vesicles (EVs), including exosomes and microvesicles, have been recognized as paracrine communicators through the component cargo. The population of cell-specific microRNAs and proteins present in EVs can regulate gene expressions of recipient cells, resulting in modulation of biological activities. EV cargoes reflect cell types and their physiological and pathological status of donor cells. Many current researches have highlighted the functions of EVs on the epithelial phenotype and fibroproliferative response in the pathogenesis of IPF. Furthermore, some native EVs could be used as a cell-free therapeutic approach for IPF as vehicles for drug delivery, given their intrinsic biocompatibility and specific target activity. EV-based therapies have been proposed as a new potential alternative to cell-based approaches. The advantage is that EVs, depending on their source, may be less immunogenic than their parental cells, likely due to a lower abundance of transmembrane proteins such as major histocompatibility complex (MHC) proteins on the surface. In the last decade, mesenchymal stem cell (MSC)-derived EVs have been rapidly developed as therapeutic products ready for clinical trials against various diseases. Considering EV functional complexity and heterogeneity, there is an urgent need to establish refined systemic standards for manufacturing processes and regulatory requirements of these medicines. This review highlights the EV-mediated cellular crosstalk involved in IPF pathogenesis and discusses the potential for EV-based therapeutics as a novel treatment modality for IPF.
Artificial intelligence for prostate MRI: open datasets, available applications, and grand challenges
Authors: Sunoqrot Mohammed R. S. , Saha Anindo , Hosseinzadeh Matin , Elschot Mattijs , Huisman Henkjan 
Published: August 2022

AbstractArtificial intelligence (AI) for prostate magnetic resonance imaging (MRI) is starting to play a clinical role for prostate cancer (PCa) patients. AI-assisted reading is feasible, allowing workflow reduction. A total of 3,369 multi-vendor prostate MRI cases are available in open datasets, acquired from 2003 to 2021 in Europe or USA at 3 T (n = 3,018; 89.6%) or 1.5 T (n = 296; 8.8%), 346 cases scanned with endorectal coil (10.3%), 3,023 (89.7%) with phased-array surface coils; 412 collected for anatomical segmentation tasks, 3,096 for PCa detection/classification; for 2,240 cases lesions delineation is available and 56 cases have matching histopathologic images; for 2,620 cases the PSA level is provided; the total size of all open datasets amounts to approximately 253 GB. Of note, quality of annotations provided per dataset highly differ and attention must be paid when using these datasets (e.g., data overlap). Seven grand challenges and commercial applications from eleven vendors are here considered. Few small studies provided prospective validation. More work is needed, in particular validation on large-scale multi-institutional, well-curated public datasets to test general applicability. Moreover, AI needs to be explored for clinical stages other than detection/characterization (e.g., follow-up, prognosis, interventions, and focal treatment).
Diagnostic value of hybrid FDG-PET/MR imaging of chronic osteomyelitis
Authors: Hulsen Dennis Jan Willem , Mitea Cristina , Arts Jacobus J. , Loeffen Daan , Geurts Jan 
Published: August 2022

Abstract
Background
Magnetic resonance imaging (MRI) and 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) Positron Emission Tomography, paired with Computed Tomography (PET/CT) are commonly used modalities in the complicated diagnostic work-up of osteomyelitis. PET/MRI is a relatively novel hybrid modality with suggested applications in bone infection imaging, based on expert opinion and previous qualitative research. 18F-FDG PET/MRI has the advantages of reduced radiation dose, more soft tissue information, and is deemed more valuable for surgical planning compared to 18F-FDG PET/CT. The goal of this study is to quantitatively assess the diagnostic value of hybrid 18F-FDG PET/MRI for chronic osteomyelitis.

Methods
A retrospective analysis was performed by a nuclear medicine physician and radiologist on 36 patients with 18F-FDG PET/MRI scans for suspected osteomyelitis. Sensitivity, specificity, and accuracy were determined with the clinical assessment by the orthopaedic surgeon (based on subsequent intraoperative microbiology or long-term follow-up) as the ground truth. Standardized uptake values (SUV) were measured and analysed by means of receiver operating characteristics (ROC).

Results
This first study to quantitatively report the diagnostic value of 18F-FDG PET/MRI yielded a sensitivity, specificity, and accuracy of 78%, 100%, and 86% respectively. Area under the ROC curve was .736, .755, and .769 for the SUVmax, target to background ratio, and SUVmax_ratio respectively. These results are in the same range and not statistically different compared to diagnostic value for 18F-FDG PET/CT imaging of osteomyelitis in literature.

Conclusions
Based on the aforementioned advantages of 18F-FDG PET/MRI and the diagnostic value reported here, the authors propose 18F-FDG PET/MRI as an alternative to 18F-FDG PET/CT in osteomyelitis diagnosis, if available.
“Blocked broken heart syndrome”: an unusual case of a complete atrioventricular block complicating a Takotsubo cardiomyopathy
Authors: Briosa A. , Santos J. , Gomes A. C. , Simões O. , Miranda R. , Almeida S. , Brandão L. , Pereira H. 
Published: August 2022

Abstract
Background
Complete heart block is considered a unique and rare complication of Takotsubo cardiomyopathy, an otherwise self-resolving disease. When this occurs, there is a double clinical dilemma: first to find out which triggered the other and second, to decide whether or not to implant a permanent pacemaker.

Case presentation
We present a case of a 77 years-old female patient, with previous medical history of arterial hypertension, diabetes mellitus, dyslipidemia and bifascicular block known since 2013. She came to the emergency department after recurrent syncopal episodes. At admission a complete heart block was diagnosed, and it was implanted a single chamber temporary pacemaker. The patient remained in disproportional acute decompensated heart failure despite pacemaker implantation. She denied chest pain although referring an episode of self-limiting chest pain 2 days before, after an argument with the family. Blood analysis showed an important rise in NTproBNP and troponin levels. Transthoracic echocardiogram showed a dilated left ventricle with akinesia of apical and mid segments, hyperkinesia of basal segments and severely depressed left ventricle ejection fraction. Coronary angiography showed no significant lesions and the diagnosis of Takotsubo cardiomyopathy was suspected. During the following days, she recovered her own intrinsic rhythm. Electrocardiogram evolved with deep T-wave inversion and prolonged QT interval and transthoracic echocardiogram showed resolution of the previous alterations. Despite complete reversion of rhythm alteration, it was decided to implant a permanent pacemaker.

Conclusions
We describe a rare, life-threatening and often underdiagnosed complication of the stress cardiomyopathy. Furthermore, we performed a literature revision of this rare complication and discussed the therapeutic challenge encountered in such patients.
Two decades of implantable cardioverter defibrillator implantation and follow-up at a South African referral centre: trends, indications and long-term outcomes in a resource-limited setting
Authors: Mkoko Philasande , Solomon Kayla , Chin Ashley 
Published: August 2022

Abstract
Background
More than two-thirds of cardiovascular deaths occur in low- and middle-income countries. Sudden cardiac deaths (SCD) from ventricular arrhythmias are an important cause of cardiovascular deaths. Implantable cardioverter defibrillators (ICD) are an important therapeutic strategy for detecting and terminating ventricular arrhythmias in patients at risk of SCD. The profile of patients treated with ICDs in South Africa is unknown. Further, with changing lines of evidence, the implantation trends are undetermined. The objectives of this study were to determine the profile of ICD recipients and implantation trends in a South African quaternary hospital.

Methods
This was a retrospective review of all patients implanted with ICDs at Groote Schuur Hospital from 01 January 1998 to 31 December 2020. A standardised data collection form was used to collect baseline demographic data, information on clinical presentation and ICD follow-up data for the history of ICD shock therapies.

Results
A total of 253 ICDs were implanted; 75% for secondary prevention and 25% for primary prevention. 67.2% of the implanted ICDs were single-chamber ICDs, dual-chamber ICDs were implanted in 12.3% and Cardiac resynchronisation with a defibrillator (CRT-D) in 20.6%. There was an upward trajectory of ICD implantations during the study period. Increasing numbers of dual-chamber devices and CRT-D were implanted over time. ICD recipients had a mean (standard deviation) age of 50 (14) years and were predominantly male (69%). Primary prevention ICD recipients were younger than secondary prevention recipients, with a mean (SD) age of 46 (14) years versus 51 (14) years, p = 0.019. The secondary prevention group presented with ventricular tachycardia in 81%, ventricular fibrillation in 13% and cardiopulmonary resuscitation without documented heart rhythm in 5.3% (10/190). After a median (interquartile range) follow-up of 44 (15; 93) months, there was an overall mortality rate of 16.2%, with no mortality difference between the primary and secondary prevention patient groups.

Conclusion
There is an increase in the annual number of ICDs implanted at a South African referral centre. ICDs are predominantly implanted for secondary prevention. However, over time the number of devices implanted for primary prevention is steadily increased. During follow-up, there was no mortality difference between the primary prevention and the secondary prevention groups.
Wilms tumor 1 gene expression in acute myeloid leukemia: prognostic significance and usefulness in minimal residual disease monitoring—a case–control study
Authors: Donia Hanaa Mahmoud , Elsweify Nada Mahmoud , Farahat Nahla Mohamed , Nadwan Eman Attia 
Published: August 2022

AbstractBackgroundMinimal residual disease (MRD), which is characterized as leukemic cells at a level below morphologic detection, has been connected to the risk of relapse in acute myeloid leukemia. In 80–90% of acute myeloid leukemia (AML) patients, the Wilms tumor (WT1) gene is overexpressed at the mRNA level. In our prospective study, a total of 55 patients were enrolled in the study. Group I involved 40 AML patients and group II involved 15 patients healthy controls.WT1gene expression was quantified using quantitative real-time PCR on bone marrow samples from AML patients at initial diagnosis and at day 28 after induction chemotherapy, and compared to 15 healthy controls in group II. Follow up of patients for prognosis evaluation was assessed. IBM SPSS software was used to capture and analyses the data.ResultsAt diagnosis, the meanWT1transcript value in AML patients was substantially higher than the expression observed in control patient’s Bone marrow. There was no statistically relevant relationship between the onset of relapse andWT1expression. Patients withWT1overexpression at diagnosis had a shorter overall survival than patients with negativeWT1expression.ConclusionsWilms tumor 1 gene expression was found to be significantly higher in AML patients than control cases, overall, our results confirmed the prognostic significance ofWT1overexpression in AML patients. Our findings support the application of MRD in AML patients based on WT1 overexpression.
Effectiveness of Cricoid and Paratracheal Pressures in Occluding the Upper Esophagus Through Induction of Anesthesia and Videolaryngoscopy: A Randomized, Crossover Study
Authors: Kim Hyerim , Chang Jee-Eun , Won Dongwook , Lee Jung-Man , Kim Tae Kyong , Kim Min Jong , Min Seong-Won , Hwang Jin-Young 
Published: August 2022

BACKGROUND:
Maneuvers for preventing passive regurgitation of gastric contents are applied to effectively occlude the esophagus throughout rapid sequence induction and intubation. The aim of this randomized, crossover study was to investigate the effectiveness of cricoid and paratracheal pressures in occluding the esophagus through induction of anesthesia and videolaryngoscopy.

METHODS:
After the induction of anesthesia in 40 adult patients, the location of the esophageal entrance relative to the glottis and location of the upper esophagus relative to the trachea at the low paratracheal region were assessed using an ultrasonography, and the outer diameter of the esophagus was measured on ultrasound before and during application of cricoid and paratracheal pressures of 30 N. Then, videolaryngoscopy was performed with the application of each pressure. During videolaryngoscopy, location of the esophageal entrance relative to the glottis under cricoid pressure was examined on the screen of videolaryngoscope, and the upper esophagus under paratracheal pressure was evaluated using ultrasound. The occlusion rate of the esophagus, and the best laryngeal view using the percentage of glottic opening scoring system were also assessed during videolaryngsocopy. Esophageal occlusion under each pressure was determined by inserting an esophageal stethoscope into the esophagus. If the esophageal stethoscope could not be advanced into the esophagus under the application of each pressure, the esophagus was regarded to be occluded.

RESULTS:
During videolaryngoscopy, esophagus was occluded in 40 of 40 (100%) patients with cricoid pressure and 23 of 40 (58%) patients with paratracheal pressure (difference, 42%; 95% confidence interval, 26–58; P < .001). Both cricoid and paratracheal pressures significantly decreased the diameter of the esophagus compared to no intervention in the anesthetized paralyzed state (P < .001, respectively). Ultrasound revealed that the compressed esophagus by paratracheal pressure in the anesthetized paralyzed state was partially released during videolaryngoscopy in 17 of 40 patients, in whom esophageal occlusion was unsuccessful. The best laryngeal view was not significantly different among the no intervention, cricoid pressure, and paratracheal pressure (77 [29] % vs 79 [30] % vs 76 [31] %, respectively; P = .064).

CONCLUSIONS:
The occlusion of the upper esophagus defined by inability to pass an esophageal stethoscope was more effective with cricoid pressure than with paratracheal pressure during videolaryngoscopy, although both cricoid and paratracheal pressures reduced the diameter of the esophagus on ultrasound in an anesthetized paralyzed state.
Outcomes and Disposition of Patients After Case Cancellation on Day of Surgery for Reasons Attributed to Medical or Anesthetic Care: A Retrospective Cohort Analysis
Authors: Tewfik George L. , Rodriguez-Aponte Carlos , Zhang Kathy , Ezzat Bishoy , Suri Pooja , Chaudhry Faraz 
Published: August 2022

BACKGROUND:
Many day-of-surgery cancellations are avoidable, and different strategies are used to prevent these costly adverse events. Despite these past analyses and evaluations of positive interventions, studies have not examined the final disposition of patients whose cases were canceled in this late manner. This study sought to determine whether surgical procedures canceled for medical or anesthetic reasons were ultimately rescheduled, and the time elapsed between cancellation and completion. In addition, the resolution of the underlying issue leading to cancellation was examined.

METHODS:
Two years of surgical case data were reviewed in the electronic health record to isolate all procedures canceled on the intended operative date. These cases were then filtered by the documented reason for cancellation into 2 categories: 1 for cases related to medical or anesthetic care and 1 for unrelated cases. Medical- or anesthetic-related cases were further categorized to better elucidate the underlying reason for cancellation. Cases were then traced to determine if and when the procedure was ultimately completed. If a case was rescheduled, the record was reviewed to determine whether the underlying reason for cancellation was resolved.

RESULTS:
A total of 4472 cases were canceled in the study period with only 20% associated with medical or anesthetic causes. Of these, 72% were rescheduled and 83% of all rescheduled cases resolved the underlying issue before the rescheduled procedure. Nearly half of all cases (47.8%) canceled on the day of surgery for reasons linked to medical and/or anesthetic care were due to acute conditions.

CONCLUSIONS:
Nearly a fifth of cases that are canceled on the date of surgery are never rescheduled and, if they are rescheduled, the delay can be substantial. Although the majority of patients whose procedure are canceled for reasons related to medical or anesthetic care have resolved the underlying issue that led to initial postponement, a significant portion of patients have no change in their status before the ultimate completion of their surgical procedure.