bluuebunny/crossref_metadata_2025 huggingface dataset:
Opportunistic diagnosis of osteoporosis, fragile bone strength and vertebral fractures from routine CT scans; a review of approved technology systems and pathways to implementation
Authors: Aggarwal Veena , Maslen Christina , Abel Richard L. , Bhattacharya Pinaki , Bromiley Paul A , Clark Emma M. , Compston Juliet E. , Crabtree Nicola , Gregory Jennifer S. , Kariki Eleni P. , Harvey Nicholas C. , Ward Kate A. , Poole Kenneth E. S.
Published: July 2021

Osteoporosis causes bones to become weak, porous and fracture more easily. While a vertebral fracture is the archetypal fracture of osteoporosis, it is also the most difficult to diagnose clinically. Patients often suffer further spine or other fractures, deformity, height loss and pain before diagnosis. There were an estimated 520,000 fragility fractures in the United Kingdom (UK) in 2017 (costing £4.5 billion), a figure set to increase 30% by 2030. One way to improve both vertebral fracture identification and the diagnosis of osteoporosis is to assess a patient’s spine or hips during routine computed tomography (CT) scans. Patients attend routine CT for diagnosis and monitoring of various medical conditions, but the skeleton can be overlooked as radiologists concentrate on the primary reason for scanning. More than half a million CT scans done each year in the National Health Service (NHS) could potentially be screened for osteoporosis (increasing 5% annually). If CT-based screening became embedded in practice, then the technique could have a positive clinical impact in the identification of fragility fracture and/or low bone density. Several companies have developed software methods to diagnose osteoporosis/fragile bone strength and/or identify vertebral fractures in CT datasets, using various methods that include image processing, computational modelling, artificial intelligence and biomechanical engineering concepts. Technology to evaluate Hounsfield units is used to calculate bone density, but not necessarily bone strength. In this rapid evidence review, we summarise the current literature underpinning approved technologies for opportunistic screening of routine CT images to identify fractures, bone density or strength information. We highlight how other new software technologies have become embedded in NHS clinical practice (having overcome barriers to implementation) and highlight how the novel osteoporosis technologies could follow suit. We define the key unanswered questions where further research is needed to enable the adoption of these technologies for maximal patient benefit.
Generation Influences Perceived Coolness But Not Favorable Attitudes Toward Cool Hotel Brands
Authors: Chen Feier (Faye) , Quadri-Felitti Donna , Mattila Anna S.
Published: July 2021

Although cool brands are increasingly popular in the marketplace, there is scant research examining generational differences in consumers’ coolness perceptions. To address this gap, the present research investigates consumers’ perceived coolness of hotels and the consequent brand attitudes among four generations of consumers. Our findings suggest that perceived coolness of a hotel brand varies across generations. Baby Boomers’ perceptions of cool hotels are different from younger generations including Gen Z, Millennials, and Gen X. However, all generations show positive attitudes toward hotel brands that they recognize as cool due to perceived autonomy. This research contributes to the hospitality literature on hotel branding. Managerial implications for hospitality marketers are discussed.
Comparison of clinical characteristics and outcomes between alcohol-induced and gallstone-induced acute pancreatitis: An Australian retrospective observational study
Authors: Garcia Santiago Cegarra , Toolis Michael , Ubels Max , Mollah Taha , Paul Eldho , Pandey Ashish , Thia Brandon , Wong Tricia , Tiruvoipati Ravindranath
Published: July 2021

Objectives:

To compare the characteristics and outcomes of patients presenting to hospital with alcohol-induced and gallstone-induced acute pancreatitis.

Methods:

Retrospective study of all patients with alcohol-induced or gallstone-induced pancreatitis during the period 1 June 2012 to 31 May 2016. The primary outcome measure was hospital mortality. Secondary outcome measures included hospital length of stay, requirements for intensive care unit admission, intensive care unit mortality, mechanical ventilation, renal replacement therapy, requirement of inotropes and total parenteral nutrition.

Results:

A total of 642 consecutive patients (49% alcohol; 51% gallstone) were included. No statistically significant differences were found between alcohol-induced and gallstone-induced acute pancreatitis with respect to hospital mortality, requirement for intensive care unit admission, intensive care unit mortality and requirement for mechanical ventilation, renal replacement therapy, inotropes or total parenteral nutrition. There was significant difference in hospital length of stay (3.07 versus 4.84; p  < 0.0001). On multivariable regression analysis, Bedside Index of Severity in Acute Pancreatitis score (estimate: 0.393; standard error: 0.058; p < 0.0001) and admission haematocrit (estimate: 0.025; standard error: 0.008; p = 0.002) were found to be independently associated with prolonged hospital length of stay.

Conclusion:

Hospital mortality did not differ between patients with alcohol-induced and gallstone-induced acute pancreatitis. The duration of hospital stay was longer with gallstone-induced pancreatitis. Bedside Index of Severity in Acute Pancreatitis score and admission haematocrit were independently associated with hospital length of stay.
Different dose of new generation proton pump inhibitors for the treatment of Helicobacter pylori infection: A meta-analysis
Authors: Gao Wenwen , Zhang Xiang , Yin Yanhui , Yu Shuwen , Wang Lu
Published: July 2021

The evidence on whether high-dose new generation proton pump inhibitors (PPIs) including rabeprazole and esomeprazole achieve a higher eradication rate of Helicobacter pylori has not been assessed. The primary comparison was eradication and adverse events (AEs) rate of standard (esomeprazole 20 mg bid, rabeprazole 10 mg bid) versus high-dose (esomeprazole 40 mg bid, rabeprazole 20 mg bid) PPIs. Sub-analyses were performed to evaluate the eradication rate between Asians and Caucasians, clarithromycin-resistance (CAM-R) strains, and clarithromycin-sensitivity (CAM-S) strains of different dose PPIs. We conducted a literature search for randomized controlled trials comparing high-with standard-dose esomeprazole and rabeprazole for H. pylori eradication and AEs. A total of 12 trials with 2237 patients were included. The eradication rate of high-dose PPIs was not significantly superior to standard-dose PPIs regimens: 85.3% versus 84.2%, OR 1.09 (0.86–1.37), P = 0.47. The high dose induced more AEs than those of the standard dose, but didn’t reach statistical significance (OR 1.25, 95% CI: 0.99–1.56, P = 0.06). Subgroup analysis showed that the difference in eradication rate of PPIs between high- and standard-dose groups were not statistically significant both in Asians (OR 0.99, 95% CI 0.75–1.32, P = 0.97) and Caucasians (OR 1.27, 95% CI 0.84–1.92, P = 0.26). Furthermore, there were similar eradication rates in CAM-S (OR 1.2; 95% CI 0.58–2.5; P = 0.63) and CAM-R strains (OR 1.08; 95% CI 0.45–2.56; P = 0.87) between the standard-and high-dose groups. High and standard dosages of new generation of the PPIs showed similar H. pylori eradication rates and AEs as well as between Asian versus Caucasian populations, with or without clarithromycin-resistance. However, further studies are needed to confirm.
The effectiveness of Colchicine as an anti-inflammatory drug in the treatment of coronavirus disease 2019: Meta-analysis
Authors: Golpour Monireh , Mousavi Tahoora , Alimohammadi Mina , Mosayebian Ali , Shiran Mohammadreza , Alizadeh Navaei Reza , Rafiei Alireza
Published: July 2021

A recently discovered coronavirus, SARS-CoV-2, caused a global respiratory disease pandemic called COVID-19. Many studies have shown the excessive activation of the innate immune response that leads to the adverse outcomes of COVID-19, and anti-inflammatory drugs are very useful in the treatment and management of this infection. The activities of Colchicine, one of the anti-inflammatory drugs, target several pathways related to excessive inflammation of COVID-19. This study aimed to evaluate the efficacy of Colchicine in the treatment of COVID-19 using a meta-analysis approach. Scopus, Pubmed, Google scholars, Web of Science, and Science direct were used to search all the randomized controlled trials, case-control, and cross-sectional studies that have evaluated the efficacy of Colchicine as a treatment for COVID-19 (up to 28 May 2021). The overall effect of Colchicine versus the control group was determined using a random-effects model meta-analysis where we compared changes (i.e. mean differences—Colchicine group vs Control group) between the two conditions in test scores indicative of hospitalization time (day) and mortality rate. The results illustrated Colchicine therapy is associated with a decreased mortality rate in COVID-19 patients and associated with a decrease in hospitalization time (day) in COVID-19 patients. Present preliminary data shows that Colchicine has a beneficial effect on coronavirus disease care in 2019. Therefore, Colchicine can be a good suggestion in the management of COVID-19.
Toxic Stress in a Mid-Sized Urban Community: An Initial Needs Assessment of Families with Children in Maywood, IL
Authors: McCune Erin , Wojtowicz Jennifer , Adams William , Sigman Garry , Williams Collette , Ahn Pauline , Ciliberti Ashley , Hatchett Lena , O’Keefe Julie
Published: July 2021

Background

Loyola Medical Center is located in Maywood, IL, a community that faces high rates of poverty, violence, and barriers to healthcare. These factors can contribute to toxic stress, which has been shown to negatively impact children’s health.

Objectives

The goal of this project was to partner with community organizations to obtain a baseline needs assessment from families in Maywood regarding sources of toxic stress and to identify interventions of interest.

Methods

In total, 75 anonymous surveys were collected from the Loyola Outpatient Center Pediatric Clinic and a Maywood community center. Survey responses were statistically analyzed in order to determine toxic stressors most commonly impacting families in Maywood as well as interventions of most interest to the community.

Results

There were 78 respondents for a response rate of approximately 71%. The most common stressors were smoking in the home (33.3%), food insecurity (29.5%), and exposure to violence (26.9%). In this sample, Black respondents were 11.5 times more likely than non-Black respondents to report that their child was exposed to violence in the community – even after controlling for concern about their child’s behavior which served as a surrogate measure of the child’s exposure to toxic stress (P = 0.001). Further, those living with food insecurity were 7.40 times more likely to report that access to food and transportation vouchers were important ( P < .001). For every 1-point increase in the total toxic stress score, respondents were 1.35 times more likely to report that increasing access to mental health resources was important to them, though this was not significant ( P = .10).

Conclusion

The data demonstrate that toxic stressors, health risks and unmet social needs are prevalent in the Maywood community, which puts local children at risk for future adverse health outcomes. With this information, pediatricians at Loyola Medical Center can work with community organizations to allocate resources to address toxic stressors in Maywood.
Forecasting the Crude Oil Prices Volatility With Stochastic Volatility Models
Authors: Oyuna Dondukova , Yaobin Liu
Published: July 2021

In this article, the stochastic volatility model is introduced to forecast crude oil volatility by using data from the West Texas Intermediate (WTI) and Brent markets. Not only that the model can capture stylized facts of multiskilling, extended memory, and structural breaks in volatility, it is also more frugal in parameterizations. The Euler–Maruyama scheme was applied to approximate the Heston model. On the contrary, the root mean square error (RMSE) and the mean average error (MAE) were used to approximate the generalized autoregressive conditional heteroskedasticity (GARCH)–type models (symmetric and asymmetric). Based on the approximation results obtained, the study established that the stochastic volatility model fits oil return data better than the traditional GARCH-class models.
Prevalence of Protein and Pre-Workout Supplement Use among High School Football Players and Potential Product Contamination
Authors: Shoshan Tal , Post Eric
Published: July 2021

The purpose was to determine the prevalence of protein and pre-workout supplement usage in high school football players and how many products contained banned substances or dangerous ingredients. A national sample of 102 high school football players was recruited via Qualtrics Research Panels to complete a cross-sectional online questionnaire. Data were summarized as means with standard deviations (SDs) and frequencies with proportions (%). A majority (59.8%) of high school football players reported currently using a protein supplement. Just under one-third (29.4%) reported currently using pre-workout supplements. Five participants reported using a pre-workout product that contained a known NCAA banned substance. Many of the products used contain banned, regulated elsewhere, or unknown substances. Secondary school ATs must educate athletes regarding the use of nutritional supplements and the potential dangers of ingesting banned or unknown substances.
Nonurgent Patients’ Preferences for Emergency Department Versus General Practitioner and Effects of Incentives: A Discrete Choice Experiment
Authors: Su Yuliu , Sharma Shrutivandana , Ozdemir Semra , Chow Wai Leng , Oh Hong-Choon , Tiah Ling
Published: July 2021

Objective. This study investigates potential of a new financial incentive policy, the GP-referral discount scheme introduced in Singapore, in reducing nonurgent emergency department (ED) visits, and compares it with alternative interventions. Methods. A discrete choice experiment (DCE) was designed to elicit patients’ preferences for ED and general practitioner (GP) under hypothetical nonurgent medical conditions. Through latent class multinomial logistic regression, choice models were estimated to quantify how patients’ choices are influenced by GP-referral discount, other ED/GP attributes (waiting time, test facilities, and payment), patient demographics, and their perception of severity. The choice models were used to predict uptake of the GP-referral discount scheme and other countermeasures suggested by these models. Results. Survey responses from 849 respondents recruited from a public hospital in Singapore were included in the study. The choice model identified two prominent classes of patients, one of which was highly sensitive to GP-referral discount and the other to test-facility-availability. Patients’ perceptions of severity (“critical” v. “not critical” enough to go to ED directly) were highly significant in influencing preference heterogeneity. Predictive analysis based on the choice model showed that GP-referral discount is more effective when patients visit ED expecting “shorter” waits, as opposed to test-facility provision at GPs and perception-correction measures that showed stronger effects under “longer” expected waits. Conclusions. The new GP-referral financial incentive introduced in Singapore can be effective in reducing nonurgent ED visits, if it reasonably covers the (extra) cost of visiting a GP. It may serve as a complement to test-facility provision at GPs or perception-correction measures, as the financial incentive and the latter two measures appear to influence distinct classes (discount-sensitive and facility-sensitive) of patients.
Do You Prefer Safety to Social Participation? Finnish Population-Based Preference Weights for the Adult Social Care Outcomes Toolkit (ASCOT) for Service Users
Authors: Nguyen Lien , Jokimäki Hanna , Linnosmaa Ismo , Saloniki Eirini-Christina , Batchelder Laurie , Malley Juliette , Lu Hui , Burge Peter , Trukeschitz Birgit , Forder Julien
Published: July 2021

Introduction. The Adult Social Care Outcomes Toolkit (ASCOT) was developed in England to measure people’s social care–related quality of life (SCRQoL). Objectives. The aim of this article is to estimate preference weights for the Finnish ASCOT for service users (ASCOT). In addition, we tested for learning and fatigue effects in the choice experiment used to elicit the preference weights. Methods. The analysis data ( n = 1000 individuals) were obtained from an online survey sample of the Finnish adult general population using gender, age, and region as quotas. The questionnaire included a best-worst scaling (BWS) experiment using ASCOT. Each respondent sequentially selected four alternatives (best, worst; second-best, second-worst) for eight BWS tasks ( n = 32,000 choice observations). A scale multinomial logit model was used to estimate the preference parameters and to test for fatigue and learning. Results. The most and least preferred attribute-levels were “I have as much control over my daily life as I want” and “I have no control over my daily life.” The preference weights were not on a cardinal scale. The ordering effect was related to the second-best choices. Learning effect was in the last four tasks. Conclusions. This study has developed a set of preference weights for the ASCOT instrument in Finland, which can be used for investigating outcomes of social care interventions on adult populations. The learning effect calls for the development of study designs that reduce possible bias relating to preference uncertainty at the beginning of sequential BWS tasks. It also supports the adaptation of a modelling strategy in which the sequence of tasks is explicitly modelled as a scale factor.
Final results of the PUPs B-LONG study: evaluating safety and efficacy of rFIXFc in previously untreated patients with hemophilia B
Authors: Nolan Beatrice , Klukowska Anna , Shapiro Amy , Rauch Antoine , Recht Michael , Ragni Margaret , Curtin Julie , Gunawardena Sriya , Mukhopadhyay Sutirtha , Jayawardene Deepthi , Winding Bent , Fischer Kathelijn , Liesner Raina
Published: July 2021

PUPs B-LONG evaluated the safety and efficacy of recombinant factor IX Fc fusion protein (rFIXFc) in previously untreated patients (PUPs) with hemophilia B. In this open-label, phase 3 study, male PUPs (age <18 years) with hemophilia B (≤2 IU/dL of endogenous factor IX [FIX]) were to receive treatment with rFIXFc. Primary end point was occurrence of inhibitor development, with a secondary end point of annualized bleed rate (ABR). Of 33 patients who received ≥1 dose of rFIXFc, 26 (79%) were age <1 year at study entry and 6 (18%) had a family history of inhibitors. Twenty-eight patients (85%) received prophylaxis; median dosing interval was 7 days, with an average weekly dose of 58 IU/kg. Twenty-seven patients (82%) completed the study. Twenty-one (64%), 26 (79%), and 28 patients (85%) had ≥50, ≥20, and ≥10 exposure days (EDs) to rFIXFc, respectively. One patient (3.03%; 95% confidence interval, 0.08% to 15.76%) developed a low-titer inhibitor after 11 EDs; no high-titer inhibitors were detected. Twenty-three patients (70%) had 58 treatment-emergent serious adverse events; 2 were assessed as related (FIX inhibition and hypersensitivity in 1 patient, resulting in withdrawal). Median ABR was 1.24 (interquartile range, 0.00-2.49) for patients receiving prophylaxis. Most (>85%) bleeding episodes required only 1 infusion for bleed resolution. In this first study reporting results with rFIXFc in pediatric PUPs with hemophilia B, rFIXFc was well tolerated, with the adverse event profile as expected in a pediatric hemophilia population. rFIXFc was effective, both as prophylaxis and in the treatment of bleeding episodes. This trial was registered at www.clinicaltrials.gov as #NCT02234310.
Prognostic impact of posttransplant FDG PET/CT scan in multiple myeloma
Authors: Kaddoura Marcella , Dingli David , Buadi Francis K. , Lacy Martha Q. , Gertz Morie A. , Dispenzieri Angela , Kapoor Prashant , Hwa Lisa , Fonder Amie , Hobbs Miriam , Hayman Suzanne , Lust John , Leung Nelson , Go Ronald S. , Lin Yi , Gonsalves Wilson , Kourelis Taxiarchis , Warsame Rahma , Kyle Robert A. , Broski Stephen M. , Rajkumar Vincent , Kumar Shaji
Published: July 2021

Multiple myeloma (MM) is a heterogeneous disease that may be evaluated by a broad array of imaging and laboratory techniques to measure disease activity and predict prognosis. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scanning has been shown to be predictive of patient outcomes throughout the disease course. We sought to corroborate these findings by examining the prognostic impact of PET/CT scanning in the posttransplant setting. We retrospectively analyzed PET/CT scans in 229 MM patients receiving an autologous stem cell transplant (ASCT) near day 100, and correlated these findings with time to progression(TTP) and overall survival (OS) to assess the impact of day 100 PET/CT scan findings as an independent prognostic factor. The median OS for the entire cohort was 61.5 months (95% confidence interval [CI], 49-75) and the median TTP was 18.5 months (95% CI, 15.4-21.8). Among patients with abnormal day 100 PET findings (PET+), median TTP was 12.4 months vs 24 months among those with normal PET findings (PET−) (P < .0001). The median OS in the PET+ group was 46 months compared with 99 months in the PET− group (P < .0001). We conclude that an abnormal PET/CT scan near day 100 post-ASCT is predictive of shorter TTP and OS, with prognostic significance retained after adjusting for disease response and other prognostic variables in MM.
A phase 2 trial of the histone deacetylase inhibitor panobinostat for graft-versus-host disease prevention
Authors: Perez Lia , Fernandez Hugo , Kharfan-Dabaja Mohamed , Khimani Farhad , Betts Brian , Mishra Asmita , Ayala Ernesto , Locke Frederick L. , Ochoa-Bayona Leonel , Nieder Michael , Pidala Joseph , Achille Alex , Powers John , Sahakian Eva , Thapa Ram , Wang Xuefeng , Anasetti Claudio
Published: July 2021

Immunomodulatory properties of histone deacetylase inhibitors represent a reasonable approach for acute graft-versus-host disease (aGVHD) prevention. We report a phase 2 trial evaluating panobinostat (PANO) administered over 26 weeks, starting on day −5 (5 mg orally 3 times a week) with tacrolimus initiated on day −3 plus sirolimus on day −1, with a median patient age of 58 years (range, 19-72 years) (n = 38). Donor source consisted of HLA 8/8–matched donors, related (n = 13) or unrelated (n = 25), using granulocyte colony-stimulating factor–stimulated peripheral blood stem cells. Myeloablative (n = 18) or reduced-intensity (n = 20) conditioning regimens were used for patients with acute myeloid leukemia (n = 17), myelodysplastic syndrome (n = 13), or other malignancies (n = 8). The cumulative incidence of aGVHD II-IV by day 100 was 18.4% (90% confidence interval [CI], 9.4% to 29.9%). Cumulative incidence of chronic GVHD at 1 year was 31.6% (90% CI, 19.5% to 44.3%). Adverse events related to PANO were thrombocytopenia (n = 5), leukopenia (n = 6), gastrointestinal toxicity (n = 3), rash (n = 4), renal failure/peripheral edema (n = 1), and periorbital edema (n = 1). At 1 year, overall survival was 89.5% (90% CI, 81.6% to 98.0%), relapse-free survival was 78.9% (90% CI, 68.8% to 90.6%), nonrelapse mortality was 2.6% (90% CI, 0.3% to 9.9%), and GVHD relapse-free survival was 60.5% (90% CI, 48.8% to 75.1%). PANO hits histone 3 as early as day 15 in CD8, CD4 and T regs. In conclusion, PANO combination met the primary study end point for aGVHD prevention and warrants further testing. This trial was registered at www.clinicaltrials.gov as #NCT02588339.
A thrombin-PAR1/2 feedback loop amplifies thromboinflammatory endothelial responses to the viral RNA analogue poly(I:C)
Authors: Subramaniam Saravanan , Ogoti Yamini , Hernandez Irene , Zogg Mark , Botros Fady , Burns Robert , DeRousse Jacob T. , Dockendorff Chris , Mackman Nigel , Antoniak Silvio , Fletcher Craig , Weiler Hartmut
Published: July 2021

Activation of blood coagulation and endothelial inflammation are hallmarks of respiratory infections with RNA viruses that contribute significantly to the morbidity and mortality of patients with severe disease. We investigated how signaling by coagulation proteases affects the quality and extent of the response to the TLR3-ligand poly(I:C) in human endothelial cells. Genome-wide RNA profiling documented additive and synergistic effects of thrombin and poly(I:C) on the expression level of many genes. The most significantly active genes exhibiting synergistic induction by costimulation with thrombin and poly(I:C) included the key mediators of 2 critical biological mechanisms known to promote endothelial thromboinflammatory functions: the initiation of blood coagulation by tissue factor and the control of leukocyte trafficking by the endothelial-leukocyte adhesion receptors E-selectin (gene symbol, SELE) and VCAM1, and the cytokines and chemokines CXCL8, IL-6, CXCL2, and CCL20. Mechanistic studies have indicated that synergistic costimulation with thrombin and poly(I:C) requires proteolytic activation of protease-activated receptor 1 (PAR1) by thrombin and transactivation of PAR2 by the PAR1-tethered ligand. Accordingly, a small-molecule PAR2 inhibitor suppressed poly(I:C)/thrombin–induced leukocyte-endothelial adhesion, cytokine production, and endothelial tissue factor expression. In summary, this study describes a positive feedback mechanism by which thrombin sustains and amplifies the prothrombotic and proinflammatory function of endothelial cells exposed to the viral RNA analogue, poly(I:C) via activation of PAR1/2.
Ultrasound-activated nano-TiO2 loaded with temozolomide paves the way for resection of chemoresistant glioblastoma multiforme
Authors: Rehman Fawad Ur , Rauf Mohd Ahmar , Ullah Sajjad , Shaikh Sana , Qambrani Aqsa , Muhammad Pir , Hanif Sumaira
Published: July 2021

Background

Glioblastoma multiforme (GBM) is one of the most daunting issues to modern therapeutics, with a higher mortality rate post-diagnosis. Temozolomide (TMZ) is the only available treatment; however, the frequent resistance leaves the oncologists at a dead end. Therefore, new approaches to circumvent the GBM are highly desired. We have employed TiO2 nanosticks loaded with TMZ as nanomedicine for TMZ-resistant GBM resection in this contribution.

Results

The ultrasonication triple-action effect could greatly facilitate tumor ablation by enhancing the TiO2 nanosticks traversing across BBB, releasing the TMZ payload from TiO2 nanosticks and reactive oxygen species (ROS) generation from TiO2 nanosticks within the GBM milieu. The tumor ablation was confirmed by MTT and Annexin(v)-PI assays, apoptotic proteins expression via western blot and ROS level detection in vitro, whereas tumor volume, weight, survival rate, and relative photon flux in the xenograft and orthoptic TMZ-resistant GBM murine models as in vivo.

Conclusion

We found this nanomedicine-based ultrasound modality highly efficient in GBM treatment and is of future clinical application value due to the employment of already FDA-approved techniques and nanomedicine.
Elevated methylation of the vault RNA2-1 promoter in maternal blood is associated with preterm birth
Authors: You Young-Ah , Kwon Eun Jin , Hwang Han-Sung , Choi Suk-Joo , Choi Sae Kyung , Kim Young Ju
Published: July 2021

Background

Preterm birth, defined as parturition before 37 completed weeks of gestation, is associated with an increased risk of neonatal complications and death, as well as poor health and disease later in life. Epigenetics could contribute to the mechanism underlying preterm birth.

Results

Genome-wide DNA methylation analysis of whole blood cells from 10 women (5 term and 5 preterm deliveries) was performed using an Illumina Infinium HumanMethylation450 BeadChips array. We identified 1,581 differentially methylated CpG sites in promoter regions between term and preterm birth. Although the differences were not significant after correcting for multiple tests, seven CpGs on the genomically imprinted vault RNA2-1 (VTRNA2-1; also known as non-coding RNA, nc886 or miR-886) showed the largest differences (range: 26–39 %). Pyrosequencing verification was performed with blood samples from pregnant women recruited additionally (39 term and 43 preterm deliveries). In total, 28 (34.1 %) samples showed hypomethylation of the VTRNA2-1 promoter (< 13 % methylation), while 54 (65.9 %) samples showed elevated methylation levels between 30 and 60 %. Elevated methylation of VTRNA2-1 promoter was associated with an increased risk of preterm birth after adjusting for maternal age, season of delivery, parity and white blood cell count. The mRNA expression of VTRNA2-1 was 0.51-fold lower in women with preterm deliveries (n = 20) compared with women with term deliveries (n = 20).

Conclusions

VTRNA2-1 is a noncoding transcript to environmentally responsive epialleles. Our results suggest that elevated methylation of the VTRNA2-1 promoter may result in increased risk of PTB caused by the pro-inflammatory cytokines. Further studies are needed to confirm the association of VTRNA2-1 methylation with preterm birth in a large population, and to elucidate the underlying mechanism.
Transcriptomal dissection of soybean circadian rhythmicity in two geographically, phenotypically and genetically distinct cultivars
Authors: Yue Yanlei , Jiang Ze , Sapey Enoch , Wu Tingting , Sun Shi , Cao Mengxue , Han Tianfu , Li Tao , Nian Hai , Jiang Bingjun
Published: July 2021

Background

In soybean, some circadian clock genes have been identified as loci for maturity traits. However, the effects of these genes on soybean circadian rhythmicity and their impacts on maturity are unclear.

Results

We used two geographically, phenotypically and genetically distinct cultivars, conventional juvenile Zhonghuang 24 (with functional J/GmELF3a, a homolog of the circadian clock indispensable component EARLY FLOWERING 3) and long juvenile Huaxia 3 (with dysfunctional j/Gmelf3a) to dissect the soybean circadian clock with time-series transcriptomal RNA-Seq analysis of unifoliate leaves on a day scale. The results showed that several known circadian clock components, including RVE1, GI, LUX and TOC1, phase differently in soybean than in Arabidopsis, demonstrating that the soybean circadian clock is obviously different from the canonical model in Arabidopsis. In contrast to the observation that ELF3 dysfunction results in clock arrhythmia in Arabidopsis, the circadian clock is conserved in soybean regardless of the functional status of J/GmELF3a. Soybean exhibits a circadian rhythmicity in both gene expression and alternative splicing. Genes can be grouped into six clusters, C1-C6, with different expression profiles. Many more genes are grouped into the night clusters (C4-C6) than in the day cluster (C2), showing that night is essential for gene expression and regulation. Moreover, soybean chromosomes are activated with a circadian rhythmicity, indicating that high-order chromosome structure might impact circadian rhythmicity. Interestingly, night time points were clustered in one group, while day time points were separated into two groups, morning and afternoon, demonstrating that morning and afternoon are representative of different environments for soybean growth and development. However, no genes were consistently differentially expressed over different time-points, indicating that it is necessary to perform a circadian rhythmicity analysis to more thoroughly dissect the function of a gene. Moreover, the analysis of the circadian rhythmicity of the GmFT family showed that GmELF3a might phase- and amplitude-modulate the GmFT family to regulate the juvenility and maturity traits of soybean.

Conclusions

These results and the resultant RNA-seq data should be helpful in understanding the soybean circadian clock and elucidating the connection between the circadian clock and soybean maturity.
Comparison of accuracy of two uncalibrated pulse contour cardiac output monitors in off-pump coronary artery bypass surgery patients using pulmonary artery catheter-thermodilution as a reference
Authors: Mukkamala Ramakrishna , Kohl Benjamin A. , Mahajan Aman
Published: July 2021

Background

Cardiac output (CO) is a key measure of adequacy of organ and tissue perfusion, especially in critically ill or complex surgical patients. CO monitoring technology continues to evolve. Recently developed CO monitors rely on unique algorithms based on pulse contour analysis of an arterial blood pressure (ABP) waveform. The objective of this investigation was to compare the accuracy of two monitors using different methods of pulse contour analysis – the Retia Argos device and the Edwards Vigileo-FloTrac device – with pulmonary artery catheter (PAC)-thermodilution as a reference.

Methods

Fifty-eight patients undergoing off-pump coronary artery bypass surgery formed the study cohort. A total of 572 triplets of CO measurements from each device – Argos, Vigileo-FloTrac (third generation), and thermodilution – were available before and after interventions (e.g., vasopressors, fluids, and inotropes). Bland–Altman analysis accounting for repeated measurements per subject and concordance analysis were applied to assess the accuracy of the CO values and intervention-induced CO changes of each pulse contour device against thermodilution. Cluster bootstrapping was employed to statistically compare the root-mean-squared-errors (RMSE = √(μ2 + σ2), where μ and σ are the Bland–Altman bias and precision errors) and concordance rates of the two devices.

Results

The RMSE (mean (95% confidence intervals)) for CO values was 1.16 (1.00–1.32) L/min for the Argos device and 1.54 (1.33–1.77) L/min for the Vigileo-FloTrac device; the concordance rate for intervention-induced CO changes was 87 (82–92)% for the Argos device and 72 (65–78)% for the Vigileo-FloTrac device; and the RMSE for the CO changes was 17 (15–19)% for the Argos device and 21 (19–23)% for the Vigileo-FloTrac device (p < 0.0167 for all comparisons).

Conclusions

In comparison with CO measured by the PAC, the Argos device proved to be more accurate than the Vigileo-FloTrac device in CO trending and absolute CO measurement in patients undergoing off-pump coronary artery bypass surgery.
First recourse for care-seeking and associated factors among rural populations in the eastern Democratic Republic of the Congo
Authors: Bapolisi Wyvine Ansima , Karemere Hermès , Ndogozi Freddy , Cikomola Aimé , Kasongo Ghislain , Ntambwe Albert , Bisimwa Ghislain
Published: July 2021

Background

Access to quality healthcare is a global fundamental human right. However, in the Democratic Republic of the Congo, several parameters affect the choices of health service users in fragile, rural contexts (zones). The overarching aim of this study was to identify the first recourse of healthcare-seeking and the determinants of utilization of health centers (primary health care structures) in the rural health zones of Katana and Walungu.

Methods

A cross-sectional survey was conducted from June to September 2017. Consenting respondents comprised 1751 adults. Continuous data were summarized using means (standard deviation) and medians (interquartile range). We used Pearson’s chi-square test and Fisher exact test to compare proportions. Logistic regression was run to assess socio-determinants of health center utilization.

Results

The morbidity rate of the sample population for the previous month was 86.4% (n = 1501) of which 60% used health centers for their last morbid episode and 20% did not. 5.3% of the respondents patronized prayer rooms and 7.9% resorted to self-medication principally because the cost was low, or the services were fast. Being female (OR: 1.51; p = 0.005) and a higher level of education (OR: 1.79; p = 0.032) were determinants of the use of health centers in Walungu. Only the level of education was associated with the use of health centers in Katana (OR: 2.78; p = 0.045).

Conclusion

Our findings suggest that health centers are the first recourse for the majority of the population during an illness. However, a significant percentage of patients are still using traditional healers or prayer rooms because the cost is low. Our results suggest that future interventions to encourage integrated health service use should target those with lower levels of education.
Testing the effects of a prenatal depression preventive intervention on parenting and young children’s self-regulation and functioning (EPIC): protocol for a longitudinal observational study
Authors: Diebold Alicia , Johnson Jessica K. , Brennan Marianne , Ciolino Jody D. , Petitclerc Amelie , Wakschlag Lauren S. , Garfield Craig F. , Yeh Chen , Lovejoy Aiko , Zakieh Dana , Tandon S. Darius
Published: July 2021

Background

Perinatal depression is a pervasive public health concern that disproportionately affects low-income women and can have negative impacts on parenting and child developmental outcomes. Few interventions focus on preventing perinatal depression. Previous studies suggest that Mothers and Babies is efficacious in preventing the worsening of depressive symptoms and the onset of postpartum depression. This manuscript presents the protocol of the EPIC study (Effects of a Prenatal Depression Preventive Intervention on parenting and young children’s Self-Regulation and Functioning) to test the effects of Mothers and Babies on parenting and child developmental outcomes through 54 months postpartum. EPIC is an observational study that builds on a completed cluster-randomized trial (CRT). Innovations of this study are direct observations of a subsample of mother-child dyads and the inclusion of fathers/caregivers’ variables as moderators of maternal mental health.

Methods

For this study, we plan to enroll 738 women with children under 30 months old, ≥18 years old, and who speak English or Spanish. Additionally, 429 fathers, partners, or other adult caregivers will be recruited through women participating in the study. Women will be recruited through the parent study (intervention and control participants) or through one of 10 home visiting programs in Illinois (control participants). Data collection will take place through maternal self-report at five time points (when the child is 30, 36, 42, 48, and 54 months), paternal self-report at three time points (when the child is 30, 42, and 54 months), and through mother-child observations at three time points (when the child is 36, 42, and 48 months). Outcome domains include maternal mental health, cognitive-behavioral and parenting skills, and child self-regulation and functioning. Moderators include the contributions of fathers/caregivers, race-ethnicity, and socioeconomic disadvantage. Power and sample size were calculated assuming a two-sided 5% type I error rate and assumed analyses on the individual level.

Discussion

This study has several key strengths and innovations, as well as great potential significance to influence the long-term trajectories of parenting and child development via prenatal intervention.

Trial registration

The study was retrospectively registered at ClinicalTrials.gov (Identifier:NCT04296734) on March 5, 2020.
Mental health, compliance with measures and health prospects during the COVID-19 epidemic: the role of health literacy
Authors: Hermans Lize , Van den Broucke Stephan , Gisle Lydia , Demarest Stefaan , Charafeddine Rana
Published: July 2021

Background

The importance of health literacy in dealing with the COVID-19 epidemic has been emphasized but scarcely addressed empirically. In this study, the association of health literacy with mental health, compliance with COVID-19 preventive measures and health prospects was assessed in a Belgian context.

Methods

Data were extracted from the third of a series of cross-sectional online COVID-related surveys (n = 32,794). Data collection took place for 1 week starting the 28th of May 2020. People residing in Belgium and aged 18 years or older could participate. Data were collected on sociodemographic background, health literacy, multimorbidity, mental health (depression, anxiety, sleeping disorder, vitality), knowledge about COVID-19, compliance with COVID-19 measures (hygiene, physical distance, covering mouth and nose on public transport and in places where physical distance cannot be respected), and health prospects (risk for health when returning to normal life and possibility of infection). Prevalence Ratio (PR) of poor mental health, non-compliance with the measures and health prospects in relation to health literacy were calculated using Poisson regressions.

Results

People showing sufficient health literacy were less likely to suffer from anxiety disorders (PR = 0.47, 95% CI = [0.42–0.53]), depression (PR = 0.46, 95% CI = [0.40–0.52]) and sleeping disorders (PR = 0.85, 95% CI = [0.82–0.87]), and more likely to have optimal vitality (PR = 2.41, 95% CI = [2.05–2.84]) than people with low health literacy. They were less at risk of not complying with the COVID-19 measures (PR between 0.60 and 0.83) except one (covering mouth and nose in places where physical distance cannot be respected). Finally, they were less likely to perceive returning to normal life as threatening (PR = 0.70, 95% CI = [0.65–0.77]) and to consider themselves at risk of an infection with COVID-19 (PR = 0.75, 95% CI = [0.67–0.84]). The associations remained significant after controlling for COVID-19 knowledge and multimorbidity.

Conclusions

These results suggest that health literacy is a crucial factor in managing the COVID-19 epidemic and offer a perspective for future studies that target health literacy in the context of virus outbreaks.
Multidisciplinary management of difficult-to-treat drug resistant tuberculosis: a review of cases presented to the national consilium in Uganda
Authors: Baluku Joseph Baruch , Katuramu Richard , Naloka Joshua , Kizito Enock , Nabwana Martin , Bongomin Felix
Published: July 2021

Background

Patients with drug resistant tuberculosis (DR-TB) with comorbidities and drug toxicities are difficult to treat. Guidelines recommend such patients to be managed in consultation with a multidisciplinary team of experts (the “TB consilium”) to optimise treatment regimens. We describe characteristics and treatment outcomes of DR-TB cases presented to the national DR-TB consilium in Uganda between 2013 and 2019.

Methods

We performed a secondary analysis of data from a nation-wide retrospective cohort of DR-TB patients with poor prognostic indicators in Uganda. Patients had a treatment outcome documented between 2013 and 2019. Characteristics and treatment outcomes were compared between cases reviewed by the consilium with those that were not reviewed.

Results

Of 1,122 DR-TB cases, 189 (16.8%) cases from 16 treatment sites were reviewed by the consilium, of whom 86 (45.5%) were reviewed more than once. The most frequent inquiries (N = 308) from DR-TB treatment sites were construction of a treatment regimen (38.6%) and management of side effects (24.0%) while the most frequent consilium recommendations (N = 408) were a DR-TB regimen (21.7%) and “observation while on current regimen” (16.6%). Among the cases reviewed, 152 (80.4%) were from facilities other than the national referral hospital, 113 (61.1%) were aged ≥ 35 years, 72 (40.9%) were unemployed, and 26 (31.0%) had defaulted antiretroviral therapy. Additionally, 141 (90.4%) had hepatic injury, 55 (91.7%) had bilateral hearing loss, 20 (4.8%) had psychiatric symptoms and 14 (17.7%) had abnormal baseline systolic blood pressure. Resistance to second-line drugs (SLDs) was observed among 9 (4.8%) cases while 13 (6.9%) cases had previous exposure to SLDs. Bedaquiline (13.2%, n = 25), clofazimine (28.6%, n = 54), high-dose isoniazid (22.8%, n = 43) and linezolid (6.7%, n = 13) were more frequently prescribed among cases reviewed by the consilium than those not reviewed. Treatment success was observed among 126 (66.7%) cases reviewed.

Conclusion

Cases reviewed by the consilium had several comorbidities, drug toxicities and a low treatment success rate. Consilia are important “gatekeepers” for new and repurposed drugs. There is need to build capacity of lower health facilities to construct DR-TB regimens and manage adverse effects.
Analysis of risk factors for C5 nerve root paralysis after posterior cervical decompression
Authors: Liu Bo , Chu Yanchen , Ma Jinfeng , Tang Xiaojie , Pan Junpeng , Wu Chunbing , Chen Xiao , Zhao Chengliang , Wang Zhijie
Published: July 2021

Background

C5 nerve root paralysis is a nonnegligible complication after posterior cervical spine surgery (PCSS). The cause of its occurrence remains controversial. The purpose of this study was to analyse the incidence of and risk factors for C5 nerve root paralysis after posterior cervical decompression.

Methods

We retrospectively analysed the clinical data of 640 patients who underwent PCSS in the Department of Orthopaedics, Affiliated Hospital of Qingdao University from September 2013 to September 2019. According to the status of C5 nerve root paralysis after surgery, all patients were divided into paralysis and normal groups. Univariate and multivariate analyses were used to determine the independent risk factors for C5 nerve root paralysis. A receiver operating characteristic (ROC) curve was used to demonstrate the discrimination of all independent risk factors.

Results

Multivariate logistic regression analysis revealed that male sex, preoperative cervical spine curvature, posterior longitudinal ligament ossification, and preoperative C4/5 spinal cord hyperintensity were independent risk factors for paralysis, whereas the width of the intervertebral foramina was an independent protective factor for paralysis. The area under the curve (AUC) values of the T2 signal change at C4-C5, sex, cervical foramina width, curvature and posterior longitudinal ligament ossification were 0.706, 0.633, 0.617, 0.637, and 0.569, respectively.

Conclusions

Male patients with C4-C5 intervertebral foramina stenosis, preoperative C4-C5 spinal cord T2 high signal, combined with OPLL, and higher preoperative cervical spine curvature are more likely to develop C5 nerve root paralysis after surgery. Among the above five risk factors, T2 hyperintensity change in C4-C5 exhibits the highest correlation with C5 paralysis and strong diagnostic power. It seems necessary to inform patients who have had cervical spine T2 hyperintensity before surgery of C5 nerve root paralysis after surgery, especially those with altered spinal cord T2 signals in the C4-C5 segment.