bluuebunny/crossref_metadata_2025 huggingface dataset:
A meta-review of methods of measuring and monitoring safety in primary care
Authors: O’Connor Paul , Madden Caoimhe , O’Dowd Emily , Byrne Dara , Lydon SinÉad
Published: August 2021

Background

A major barrier to safety improvement in primary care is a lack of safety data. The aims of this systematic meta-review (registration: CRD42021224367) were to identify systematic reviews of studies that examine methods of measuring and monitoring safety in primary care; classify the methods of measuring and monitoring safety in the included systematic reviews using the five safety domains of Vincent et al.’s framework and use this information to make recommendations for improving the measurement and monitoring of safety in primary care.

Methods

Four databases (Medline, Academic Search Complete, Web of Science and CINAHL) and the grey literature were screened in November 2020, with searches updated in January 2021. Systematic reviews were included if they addressed the measurement of patient safety in primary care and were published in English. Studies were assessed using the Critical Appraisal Skills Programme for systematic reviews.

Results

A total of 6904 papers were screened, with 13 systematic reviews included. A commonly reported method of measuring ‘past harm’ was through patient record review. The most frequent methods for assessing the ‘reliability of safety critical processes’ were checklists, observations and surveys of staff. Methods used to assess ‘sensitivity to operations’ included observation, staff surveys, interviews, focus groups, active monitoring and simulated patients. Safety climate surveys were a commonly used as an approach to assess ‘anticipation and preparedness’. A number of the reviews concluded that safety data could, and should, be used for ‘integration and learning’. The main limitation of the meta-review was that it was of systematic reviews only.

Conclusions

Many of the methods for measuring and monitoring safety are readily available, quick to administer, do not require external involvement and are inexpensive. However, there is still a need to improve the psychometric properties of many measures. Researchers must support the development of psychometrically sound safety measures that do not over burden primary care practitioners. Policymakers must consider how primary care practitioners can be supported to implement these measures.
The Value of Targeted Ultrasound for the Primary Evaluation of Breast Symptoms in Pregnant Women of All Ages
Authors: Holtz Jamie N , Woodard Genevieve A , Hayward Jessica H , Ray Kimberly M , Kannan Neeta , Greenwood Heather I , Joe Bonnie N , Lee Amie Y
Published: August 2021

Objective

Data on breast imaging in symptomatic pregnant women are limited. Our aim was to assess the value of targeted breast US for the primary evaluation of breast symptoms in pregnant women of all ages.

Methods

This IRB-approved retrospective study included all pregnant patients who underwent targeted US for focal breast symptoms at an academic imaging facility over an 18-year period (2000–2018). Clinical, imaging, and pathology results were reviewed. Malignant outcomes were determined by histology. Benign outcomes were confirmed by pathology or ≥2 years of follow-up. Descriptive statistics and 2 × 2 contingency table analyses were performed at the presentation level.

Results

The study cohort comprised 178 presentations in 175 pregnant women. Mean age was 34.7 years (standard deviation, 5.2). The majority (153/178, 86.0%) were more than 30 years old. At presentation, 42.1% (75/178) were in the first trimester of pregnancy, 27.0% (48/178) in the second, and 29.8% (53/178) in the third. The most common presenting symptom was a palpable lump (162/178, 91.0%), followed by focal pain (7/178, 3.9%). The vast majority (174/178, 97.8%) of cases were non-malignant. However, targeted US detected all 4 malignancies (cancer detection rate, 22/1000; negative predictive value 136/136, 100%). Sensitivity and specificity were 100% (4/4) and 78.2% (136/174), respectively.

Conclusion

Benign causes of symptoms in pregnant women were far more common; malignancy was rare, accounting for only 2.2% (4/178) of cases. Targeted breast US detected all malignancies, supporting US as the primary imaging modality for evaluating symptomatic pregnant women, regardless of age.
Mental Health Without Well-being
Authors: Wren-Lewis Sam , Alexandrova Anna
Published: August 2021

What is it to be mentally healthy? In the ongoing movement to promote mental health, to reduce stigma, and to establish parity between mental and physical health, there is a clear enthusiasm about this concept and a recognition of its value in human life. However, it is often unclear what mental health means in all these efforts and whether there is a single concept underlying them. Sometimes, the initiatives for the sake of mental health are aimed just at reducing mental illness, thus implicitly identifying mental health with the absence of diagnosable psychiatric disease. More ambitiously, there are high-profile proposals to adopt a positive definition, identifying mental health with psychic or even overall well-being. We argue against both: a definition of mental health as mere absence of mental illness is too thin, too undemanding, and too closely linked to psychiatric value judgments, while the definition in terms of well-being is too demanding and potentially oppressive. As a compromise, we sketch out a middle position. On this view, mental health is a primary good, that is, the psychological preconditions of pursuing any conception of the good life, including well-being, without being identical to well-being.
Germline SUCLG2 Variants in Patients With Pheochromocytoma and Paraganglioma
Authors: Hadrava Vanova Katerina , Pang Ying , Krobova Linda , Kraus Michal , Nahacka Zuzana , Boukalova Stepana , Pack Svetlana D , Zobalova Renata , Zhu Jun , Huynh Thanh-Truc , Jochmanova Ivana , Uher Ondrej , Hubackova Sona , Dvorakova Sarka , Garrett Timothy J , Ghayee Hans K , Wu Xiaolin , Schuster Bjoern , Knapp Philip E , Frysak Zdenek , Hartmann Igor , Nilubol Naris , Cerny Jiri , Taieb David , Rohlena Jakub , Neuzil Jiri , Yang Chunzhang , Pacak Karel
Published: August 2021

Background

Pheochromocytoma and paraganglioma (PPGL) are neuroendocrine tumors with frequent mutations in genes linked to the tricarboxylic acid cycle. However, no pathogenic variant has been found to date in succinyl-CoA ligase (SUCL), an enzyme that provides substrate for succinate dehydrogenase (SDH; mitochondrial complex II [CII]), a known tumor suppressor in PPGL.

Methods

A cohort of 352 patients with apparently sporadic PPGL underwent genetic testing using a panel of 54 genes developed at the National Institutes of Health, including the SUCLG2 subunit of SUCL. Gene deletion, succinate levels, and protein levels were assessed in tumors where possible. To confirm the possible mechanism, we used a progenitor cell line, hPheo1, derived from a human pheochromocytoma, and ablated and re-expressed SUCLG2.

Results

We describe 8 germline variants in the guanosine triphosphate–binding domain of SUCLG2 in 15 patients (15 of 352, 4.3%) with apparently sporadic PPGL. Analysis of SUCLG2-mutated tumors and SUCLG2-deficient hPheo1 cells revealed absence of SUCLG2 protein, decrease in the level of the SDHB subunit of SDH, and faulty assembly of the complex II, resulting in aberrant respiration and elevated succinate accumulation.

Conclusions

Our study suggests SUCLG2 as a novel candidate gene in the genetic landscape of PPGL. Large-scale sequencing may uncover additional cases harboring SUCLG2 variants and provide more detailed information about their prevalence and penetrance.
Challenges in the Diagnosis and Management of Recurrent and Severe Clostridioides difficile Infection in Children
Authors: Sattler Matthew M , Crews Jonathan D
Published: August 2021

Children with Clostridioides difficile infection (CDI) can experience recurrent or severe disease. Recurrent CDI occurs in 20%-30% of children with an initial CDI episode. A careful clinical evaluation is important to distinguish recurrent CDI from other disorders that cause recurring gastrointestinal symptoms. Multiple treatment options exist for recurrent CDI, but the optimal therapeutic approach remains undefined. Severe or fulminant CDI can result in poor outcomes and significant morbidity in children. Since there is not a validated definition for severe CDI in children, physicians must use their clinical judgment to identify patients with severe CDI to institute appropriate therapy. In this review, we describe the diagnostic and management challenges in caring for children with recurrent and severe CDI.
Neutral CGM as damped Ly α absorbers at high redshift
Authors: Stern Jonathan , Sternberg Amiel , Faucher-Giguère Claude-André , Hafen Zachary , Fielding Drummond , Quataert Eliot , Wetzel Andrew , Anglés-Alcázar Daniel , El-Badry Kareem , Kereš Dušan , Hopkins Philip F
Published: August 2021

Recent searches for the hosts of z ∼ 4 damped Ly α absorbers (DLAs) have detected bright galaxies at distances of tens of kpc from the DLA. Using the FIRE-2 cosmological zoom simulations, we argue that these relatively large distances are due to a predominantly cool and neutral inner circumgalactic medium (CGM) surrounding high-redshift galaxies. The inner CGM is cool because of the short cooling time of hot gas in ${\lesssim}10^{12}\, {\rm M_{\odot }}$ haloes, which implies that accretion and feedback energy are radiated quickly, while it is neutral due to high volume densities and column densities at high redshift that shield cool gas from photoionization. Our analysis predicts large DLA covering factors (${\gtrsim}50{{\ \rm per\ cent}}$) out to impact parameters ∼0.3[(1 + z)/5]3/2Rvir from the central galaxies at z ≳ 1, equivalent to a proper distance of ${\sim}21\, M_{12}^{1/3} \left(\left(1+z\right)/5\right)^{1/2}\, {\rm kpc}$ (Rvir and M12 are the halo virial radius and mass in units of $10^{12}\, {\rm M_{\odot }}$, respectively). This implies that DLA covering factors at z ∼ 4 may be comparable to unity out to a distance ∼10 times larger than stellar half-mass radii. A predominantly neutral inner CGM in the early universe suggests that its mass and metallicity can be directly constrained by absorption surveys, without resorting to the large ionization corrections as required for ionized CGM.
Identification of emission-line stars in transition phase from pre-main sequence to main sequence
Authors: Bhattacharyya Suman , Mathew Blesson , Banerjee Gourav , Anusha R , Paul K T , Kartha Sreeja S
Published: August 2021

Pre-main-sequence (PMS) stars evolve into main-sequence (MS) phase over a period of time. Interestingly, we found a scarcity of studies in existing literature that examine and attempt to better understand the stars in PMS to MS transition phase. The purpose of this study is to detect such rare stars, which we named as ‘transition phase’ (TP) candidates – stars evolving from the PMS to the MS phase. We identified 98 TP candidates using photometric analysis of a sample of 2167 classical Be (CBe) and 225 Herbig Ae/Be (HAeBe) stars. This identification is done by analysing the near- and mid-infrared excess and their location in the optical colour–magnitude diagram. The age and mass of 58 of these TP candidates are determined to be between 0.1–5 Myr and 2–10.5 M⊙, respectively. The TP candidates are found to possess rotational velocity and colour excess values in between CBe and HAeBe stars, which is reconfirmed by generating a set of synthetic samples using the machine learning approach.
Radius measurement in binary stars: simulations of intensity interferometry
Authors: Rai Km Nitu , Basak Soumen , Saha Prasenjit
Published: August 2021

Mass and radius measurements of stars are important inputs for models of stellar structure. Binary stars are of particular interest in this regard, because astrometry and spectroscopy of a binary together provide the masses of both stars as well as the distance to the system, while interferometry can both improve the astrometry and measure the radii of the stars. In this work, we simulate parameter recovery from intensity interferometry, especially the challenge of disentangling the radii of two stars from their combined interferometric signal. Two approaches are considered: separation of the visibility contributions of each star with the help of differing brightness ratios at different wavelengths, and direct fitting of the intensity correlation to a multiparameter model. Full image reconstructions is not attempted. Measurement of angular radii, angular separation, and first-order limb-darkening appears readily achievable for bright binary stars with current instrumentation.
A new approach of estimating the galactic thermal dust and synchrotron polarized emission template in the microwave bands
Authors: Adak Debabrata
Published: August 2021

The Internal Linear Combination (ILC) method has been extensively used to extract the cosmic microwave background (CMB) anisotropy map from foreground contaminated multifrequency maps. However, the performance of simple ILC is limited and can be significantly improved by heavily constraint equations, dubbed constrained ILC (cILC). The standard ILC and cILC work on spin-0 fields. Recently, a generalised version of ILC has been developed, named polarization ILC (PILC), in which Q ± iU at multiple frequencies are combined using complex coefficients to estimate Stokes Q and U maps. A statistical moment expansion method has recently been developed for high-precision modelling of the galactic foregrounds. This paper develops a semiblind component separation method combining the moment approach of foreground modelling with a generalised version of the PILC method for heavily constraint equations. The algorithm is developed in pixel space over a spin-2 field. We demonstrate the performance of the method on three sets of absolutely calibrated simulated maps at WMAP and Planck frequencies with varying foreground models. We apply this component separation technique in simultaneous estimation of Stokes Q and U maps of the thermal dust at 353 GHz and synchrotron at 30 GHz. We also recover both dust and synchrotron maps at 100 and 143 GHz, where separating two components is challenging.
An observational determination of the evolving extragalactic background light from the multiwavelength HST/CANDELS survey in the Fermi and CTA era
Authors: Saldana-Lopez Alberto , Domínguez Alberto , Pérez-González Pablo G , Finke Justin , Ajello Marco , Primack Joel R , Paliya Vaidehi S , Desai Abhishek
Published: August 2021

The diffuse extragalactic background light (EBL) is formed by ultraviolet (UV), optical, and infrared (IR) photons mainly produced by star formation processes over the history of the Universe and contains essential information about galaxy evolution and cosmology. Here, we present a new determination of the evolving EBL spectral energy distribution using a novel approach purely based on galaxy data aiming to reduce current uncertainties on the higher redshifts and IR intensities. Our calculations use multiwavelength observations from the UV to the far-IR of a sample of approximately 150 000 galaxies detected up to z ∼ 6 in the five fields of the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey from the Hubble Space Telescope. This is one of the most comprehensive and deepest multiwavelength galaxy data sets ever obtained. These unprecedented resources allow us to derive the overall EBL evolution up to z ∼ 6 and its uncertainties. Our results agree with cosmic observables estimated from galaxy surveys and γ-ray attenuation such as monochromatic luminosity densities, including those in the far-IR, and star formation rate densities, also at the highest redshifts. Optical depths from our EBL approximation, which will be robust at high redshifts and for γ-rays up to tens of TeV, will be reported in a companion paper.
From aniline to phenol: carbon-nitrogen bond activation via uranyl photoredox catalysis
Authors: Hu Deqing , Zhou Yilin , Jiang Xuefeng
Published: August 2021

Carbon-nitrogen bond activation, via uranyl photoredox catalysis with water, enabled the conversion of 40 protogenetic anilines, 8 N-substituted anilines and 9 aniline-containing natural products/pharmaceuticals to the corresponding phenols in an ambient environment. A single-electron transfer process between a protonated aniline and uranyl catalyst, which was disclosed by radical quenching experiments and Stern-Volmer analysis, facilitated the following oxygen atom transfer process between the radical cation of protonated anilines and uranyl peroxide originating from water-splitting. 18O labeling and 15N tracking unambiguously depicted that the oxygen came from water and amino group left as ammonium salt. The 100-fold efficiency of the flow operation demonstrated the great potential of the conversion process for industrial synthetic application.
Implementation and Use of Workplace-Based Assessment in Clinical Learning Environments: A Scoping Review
Authors: Anderson Hannah L. , Kurtz Joshua , West Daniel C.
Published: August 2021

Purpose

Workplace-based assessment (WBA) serves a critical role in supporting competency-based medical education (CBME) by providing assessment data to inform competency decisions and support learning. Many WBA systems have been developed, but little is known about how to effectively implement WBA. Filling this gap is important for creating suitable and beneficial assessment processes that support large-scale use of CBME. As a step toward filling this gap, the authors describe what is known about WBA implementation and use to identify knowledge gaps and future directions.

Method

The authors used Arksey and O’Malley’s 6-stage scoping review framework to conduct the review, including: (1) identifying the research question; (2) identifying relevant studies; (3) study selection; (4) charting the data; (5) collating, summarizing, and reporting the results; and (6) consulting with relevant stakeholders.

Results

In 2019–2020, the authors searched and screened 726 papers for eligibility using defined inclusion and exclusion criteria. One hundred sixty-three met inclusion criteria. The authors identified 5 themes in their analysis: (1) Many WBA tools and programs have been implemented, and barriers are common across fields and specialties; (2) Theoretical perspectives emphasize the need for data-driven implementation strategies; (3) User perceptions of WBA vary and are often dependent on implementation factors; (4) Technology solutions could provide useful tools to support WBA; and (5) Many areas of future research and innovation remain.

Conclusions

Knowledge of WBA as an implemented practice to support CBME remains constrained. To remove these constraints, future research should aim to generate generalizable knowledge on WBA implementation and use, address implementation factors, and investigate remaining knowledge gaps.
A Quality Improvement Initiative to Provide Timely Central Vascular Access in a Neonatal Intensive Care Unit
Authors: Kristoff Kimberly , Wang Rui , Munson David , Dysart Kevin , Stracuzzi Lauren , Wade Kelcey , Birnbaum Shira
Published: August 2021

Background:

Timely central venous access is essential in the care of critically ill neonates. Peripherally inserted central catheters (PICCs) are the preferred form of central venous access when umbilical venous catheters cannot be placed or are discontinued. However, time delays increase risk for injury from peripheral intravenous lines and may contribute to inconsistent delivery of necessary fluids and medications.

Purpose:

The aim of this quality improvement project was to decrease wait times for PICC placement in the neonatal intensive care unit (NICU).

Methods:

A unit-based PICC team was developed consisting of NICU nurses and attending neonatologists and implemented in 2 phases. Data were collected from chart reviews before, during, and after implementation of the team. We tracked time between PICC order and placement and number of attempts. Hospital metrics on peripheral intravenous line infiltrations and central line–associated blood stream infection were also monitored. At the end of the project, we continued tracking outcomes to determine whether gains would be sustained past the project period.

Results:

Implementation of a unit-based interdisciplinary specialty team led to a 50% reduction in mean PICC wait times from 1.2 days to 0.58 days. Benefits of the initiative were sustained past the initial project period.

Implications for Practice:

The development of a dedicated, local team played a key role in improving vascular access in the NICU.

Implications for Research:

Proximity of specialized teams provides a solution to address gaps in care in the NICU.
Management of Salter-Harris II distal femur fractures – what is the state of practice? A survey of Pediatric Orthopaedic Society of North America membership
Authors: Weltsch Daniel , Williams Brendan A. , Gohel Shivani , Ganley Theodore J. , Baldwin Keith D.
Published: August 2021

Appropriate treatment of Salter-Harris (SH) II distal femoral physeal fractures is crucial due to risks of growth arrest and angular deformity. Low incidence renders sufficiently powered, prospective research difficult. This study aimed to assess the current state of management of these fractures on the basis of the Pediatric Orthopaedic Society of North America (POSNA) membership experience. POSNA members were surveyed via an emailed REDCAP survey. Questions included respondent demographics, experience, practice environment and clinical questions regarding preferred treatment and postoperative management based, in part, on an illustrative case of a nighttime presentation of a displaced SH-II distal femur fracture. Descriptive statistics were performed to summarize the preferred management among POSNA members. Twenty-eight percent (376/1344) of contacted POSNA members responded to the survey meeting sample size criteria of membership representation. Respondents’ median years in practice were 17 (IQR 7–27). Surgical management of the presented case was preferred by most (96.3%) respondents. If no vascular compromise was present (ABI >0.9), most (86.6%) felt it was appropriate to wait for intervention on the following day. One-third (32.7%) of respondents considered every SH-II as an indication for surgical treatment. Screw fixation is the most common implant selection for operatively managed injuries, with the majority choosing not to electively remove screws. Those who opted for pin fixation tended to remove pins by 3–4 weeks postoperatively. For immediate postoperative immobilization, long leg casting (44.4%) was selected more commonly than splinting or knee immobilizers. Nearly all (99.7%) respondents preferred follow-up until skeletal maturity. In cases of suspected growth arrest, 76% felt MRI was necessary for further evaluation. Operative management of SH-II distal femur fractures is preferred among POSNA members, particularly in cases of displaced fractures or when closed reduction had failed. Except for immediate postoperative immobilization preferences, pediatric orthopedic surgeons appear to have a majority consensus regarding treatment practices, postoperative management and indications and timing of hardware removal.

Level of evidence

Level V Expert Opinion.
Epidemiology of Neck Pain and Its Impact on Quality-of-Life—A Population-Based, Cross Sectional Study in Singapore
Authors: Hey Hwee Weng Dennis , Lim Joel Xue Yi , Ong Jing Zhi , Luo Nan
Published: August 2021

Study Design.

Cross-sectional, epidemiological study.

Objective.

This study aims to describe the prevalence, risk factors, disability, and quality of life (QoL) burden of neck pain.

Summary of Background Data.

Neck pain is an increasingly common symptom that results in significant disability and loss of QoL to the individual, and imposes a considerable economic burden to developed countries.

Methods.

A cross-sectional, questionnaire-based study was conducted via multistage random sampling of public households in Singapore on individuals aged 21 and older. Questionnaires were administered face-to-face by trained interviewers. Data analyzed included the prevalence and characteristics of neck pain, its relationship with sociodemographic factors, and its association on QoL and disability via validated questionnaires: EQ5D questionnaire and Neck Disability Index (NDI), respectively.

Results.

A total of 626 individuals with a median age of 52.0 years (interquartile range 37.0–67.0), and even sex distribution of males (54.0%) and females (46.0%) were included in this study. A total of 144 individuals reported neck pain over the past 6 months, giving a 6-month period prevalence of 23.0%. Among them, nine (6.3%) had chronic, whereas 12 (8.3%) had severe neck pain. Female sex was the only significant risk factor for neck pain on multivariate analysis, with a risk ratio of 1.34 (95% confidence interval [CI] 1.00–1.80, P = 0.049). Individuals with neck pain had mean raw NDI scores of 4.91 ± 6.25, with higher disability seen with increasing pain duration and intensity (P < 0.001 and P = 0.002 respectively). Compared to individuals without neck pain, those with neck pain had poorer QoL with lower EQ5D-Index scores (0.84 ± 0.25 vs. 0.93 ± 0.15; 95% CI 0.046–0.132, P < 0.001) and EQ5D-VAS scores (68.76 ± 14.59 vs. 73.86 ± 13.64; 95% CI 2.510–7.697, P < 0.001).

Conclusion.

Our findings show that neck pain is a prevalent condition with chronicity and severity of symptoms associated with reduced QoL and increased disability. Population sample health scores can serve as potential reference targets in disease management and aid national health care policy-making.

Level of Evidence: 3
Association of Lumbar MRI Findings with Current and Future Back Pain in a Population-based Cohort Study
Authors: Kasch Richard , Truthmann Julia , Hancock Mark J. , Maher Christopher G. , Otto Markus , Nell Christopher , Reichwein Niklas , Bülow Robin , Chenot Jean-François , Hofer Andre , Wassilew Georgi , Schmidt Carsten Oliver
Published: August 2021

Study Design.

Population-based cohort study.

Objective.

We examined associations between common lumbar degenerative changes observed on magnetic resonance imaging (MRI) and present or future low back pain (LBP).

Summary of Background Data.

The association between lumbar MRI degenerative findings and LBP is unclear. Longitudinal studies are sparse.

Methods.

Participants (n = 3369) from a population-based cohort study were imaged at study entry, with LBP status measured at baseline and 6-year follow-up. MRI scans were reported on for the presence of a range of MRI findings. LBP status was measured on a 0 to 10 scale. Regression models were used to estimate the cross-sectional and longitudinal associations between individual and multiple MRI findings and LBP severity. Separate longitudinal analyses were conducted for participants with and without baseline pain.

Results.

MRI findings were present in persons with and without back pain at baseline. Higher proportions were found in older age groups. 76.4% of participants had a least one MRI finding and 8.3% had five or more different MRI findings. Cross-sectionally, most MRI findings were slightly more common in those with LBP and pain severity was slightly higher in those with MRI findings (ranging from 0.06 for high intensity zone to 0.83 for spondylolisthesis). In the longitudinal analyses, we found most MRI findings were not associated with future LBP-severity regardless of the presence or absence of baseline pain. Compared to zero MRI findings, having multiple MRI findings (five or more) was associated with mildly greater pain-severity at baseline (0.84; 0.50–1.17) and greater increase in pain-severity over 6 years in those pain free at baseline (1.21; 0.04–2.37), but not in those with baseline pain (−0.30; −0.99 to 0.38).

Conclusion.

Our study shows that the MRI degenerative findings we examined, individually or in combination, do not have clinically important associations with LBP, with almost all effects less than one unit on a 0 to 10 pain scale.

Level of Evidence: 3
LINC00987 knockdown inhibits the progression of acute myeloid leukemia by suppressing IGF2BP2-mediated PA2G4 expression
Authors: Liu Chunyan , Ma Yanfei , Wang Ruihuan , Su Guohong
Published: August 2021

This study aimed to investigate the role and potential mechanisms of LINC00987 in acute myeloid leukemia (AML) progression. The expression of LINC00987 in bone marrow specimens of AML patients and cell lines was measured by quantitative reverse transcription PCR (RT-qPCR). Small interfering RNA targeting LINC00987 (si-LINC00987) was transfected into AML cell lines HL-60 and KG-1, and the proliferation, invasion and apoptosis were detected with Cell Counting Kit-8 (CCK-8), Transwell and flow cytometry, respectively. Moreover, the binding between LINC00987 and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) was validated with an RNA pull-down assay. Co-immunoprecipitation assay was used to verify the binding between IGF2BP2 and proliferation-associated 2G4 (PA2G4). Then rescue experiments were performed to explore the effects of LINC00987/IGF2BP2/PA2G4 axis on HL-60 and KG-1 cell functions. Additionally, HL-60 cells transfected with si-LINC00987 were injected into mice, followed by the evaluation of xenograft tumor growth. LINC00987 was upregulated in AML patient specimens and cell lines. LINC00987 knockdown inhibited proliferation and invasion and promoted apoptosis in AML cells. LINC00987 could bind with IGF2BP2 and promote its expression, and IGF2BP2 overexpression reversed the effects of LINC00987 knockdown on the proliferation, invasion and apoptosis in AML cells. Besides, IGF2BP2 could bind with PA2G4. IGF2BP2 knockdown inhibited proliferation and invasion, and promoted apoptosis in AML cells, whereas PA2G4 overexpression reversed these effects. Additionally, the LINC00987 knockdown inhibited the xenograft tumor growth of AML in vivo. Knockdown of LINC00987 inhibits AML cell proliferation and invasion, and promotes apoptosis in vitro and reduces tumor growth in vivo by suppressing IGF2BP2-mediated PA2G4 expression.
Does bevacizumab carry a hope for metastatic triple-negative breast cancer in the era of immunotherapy?
Authors: Mohamed Rehab F. , Bakri HebatAllah M. , abdelfattah Ola N. , Eid Samir
Published: August 2021

Triple-negative breast cancer (TNBC) has a very high rate of recurrence. Our aim is to investigate the efficacy of bevacizumab, platinum and paclitaxel as first-line in metastatic TNBC (mTNBC). This study included 54 female patients with mTNBC. They received bevacizumab, carboplatin and paclitaxel every 21 day for six cycles then who progressed shifted to second-line chemotherapy and the responders continue another two cycles. The median progression-free survival (PFS) was 27 months [95% confidence interval (CI), 17.019–36.981]. There were two factors that affect PFS; visceral only metastasis (hazard ratio, 0.23; P =  0.05) and performance status 0 (hazard ratio = 0.16; P = 0.02) with C-index 0.77. The median overall survival (OS) was 55 months (95% CI, 38.973–71.027). There were two factors that affect OS; type of presentation (hazard ratio = 7.91; P = 0.02) and performance status 0 (hazard ratio = 0.12; P = 0.01) with C-index 0.73. In the final evaluation, three factors have their print on achieving either stable disease (SD) or complete response (CR). Patients having ≤3 sites of metastasis odds ratio (OR) 3.92 (P = 0.02), patients with visceral only metastasis OR was 13.20 (P = 0.001), those with performance status 0 had the highest OR 19.5 (P = 0.001) and the percentage of this prediction was 64.8, 70.4 and 70.4%, respectively. Bevacizumab, carboplatin and paclitaxel were well tolerated, continuation of bevacizumab is recommended as long as SD or CR responses are obtained and tolerated.
Circ_0003732 promotes osteosarcoma progression through regulating miR-377-3p/CPEB1 axis and Wnt/β-catenin signaling pathway
Authors: Zhou Zheng , Liu Tang , Li Zhihong , Wang Lu
Published: August 2021

Osteosarcoma is a prevalent malignant bone cancer. This study aimed to explore the biologic role and potential mechanism of circ_0003732 in osteosarcoma carcinogenesis. Quantitative real-time PCR was implemented to detect the RNA expression of circ_0003732, microRNA-377-3p (miR-377-3p) and cytoplasmic polyadenylation element-binding protein 1 (CPEB1). Cell proliferation was evaluated by cell counting kit-8 assay and colony formation assay. Transwell, wound healing and flow cytometry assays were employed to assess cell migration, invasion and apoptosis. In addition, the interaction between miR-377-3p and circ_0003732 or CPEB1 was validated by dual-luciferase reporter assay. The protein expression was detected by western blot assay or immunohistochemistry assay. Xenograft tumor assay was performed to explore the regulation of circ_0003732 on osteosarcoma tumor growth in vivo. Circ_0003732 was upregulated in osteosarcoma tissues and cells. Knockdown of circ_0003732 suppressed osteosarcoma cell proliferation, migration, invasion and triggered cell apoptosis in vitro, as well as reduced osteosarcoma tumor growth in vivo. Meanwhile, miR-377-3p could bind to circ_0003732 and CPEB1 and miR-377-3p inhibitor could reverse the effects of circ_0003732 silence on osteosarcoma cell progression. Furthermore, CPEB1 overexpression could overturn the suppressive impacts of miR-377-3p on osteosarcoma progression. In addition, circ_0003732 silence restrained Wnt/β-catenin signaling pathway via regulating miR-377-3p in osteosarcoma cells. Circ_0003732 might play a positive role in the malignant progression of osteosarcoma by regulating the miR-377-3p/CPEB1 axis and activating the Wnt/β-catenin signaling pathway, which might provide new insights for osteosarcoma therapy.
Hsa_circ_0014879 regulates the radiosensitivity of esophageal squamous cell carcinoma through miR-519-3p/CDC25A axis
Authors: Liu Zihao , Lu Xiyan , Wen Linchun , You Chuanwen , Jin Xiaowei , Liu Jingying
Published: August 2021

Circular RNAs (circRNAs) play critical roles in regulating the radiosensitivity of various cancers, including esophageal squamous cell carcinoma (ESCC). This research aimed to explore the role and potential mechanism of hsa_circ_0014879 in regulating ESCC radioresistance. The levels of hsa_circ_0014879, microRNA-519-3p (miR-519-3p) and cell division cycle 25A (CDC25A) were measured using quantitative real-time PCR or western blot. Cell proliferation was evaluated by colony formation assay. Cell migration and invasion were assessed by transwell and scratch assays. The levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by western blot. Xenograft assay was used to analyze the effect of hsa_circ_0014879 on radiosensitivity in vivo. The binding relationship among hsa_circ_0014879, miR-519-3p and CDC25A was confirmed by dual-luciferase reporter assay. Hsa_circ_0014879 and CDC25A were upregulated, whereas miR-519-3p was downregulated in radio-resistant ESCC tissues and cells. Depletion of hsa_circ_0014879 suppressed the proliferation, migration and invasion of radio-resistant ESCC cells. Hsa_circ_0014879 knockdown elevated radiosensitivity of radio-resistant cells by modulating miR-519-3p. Moreover, miR-519-3p enhanced the radiosensitivity of radio-resistant cells by targeting CDC25A. Also, hsa_circ_0014879 upregulated CDC25A via sponging miR-519-3p. Hsa_circ_0014879 silencing enhanced the radiosensitivity of ESCC via regulating the miR-519-3p/CDC25A pathway.
Physical Rehabilitation in the ICU: A Systematic Review and Meta-Analysis*
Authors: Wang Yi Tian , Lang Jenna K. , Haines Kimberley J. , Skinner Elizabeth H. , Haines Terry P.
Published: August 2021

OBJECTIVES:

Significant variability exists in physical rehabilitation modalities and dosage used in the ICU. Our objective was to investigate the effect of physical rehabilitation in ICU on patient outcomes, the impact of task-specific training, and the dose-response profile.

DATA SOURCES:

A systematic search of Ovid MEDLINE, Cochrane Library, EMBASE, and CINAHL plus databases was undertaken on the May 28, 2020.

STUDY SELECTION:

Randomized controlled trials and controlled clinical trials investigating physical rehabilitation commencing in the ICU in adults were included. Outcomes included muscle strength, physical function, duration of mechanical ventilation, ICU and hospital length of stay, mortality, and health-related quality of life. Two independent reviewers assessed titles, abstracts, and full texts against eligibility criteria.

DATA EXTRACTION:

Details on intervention for all groups were extracted using the template for intervention description and replication checklist.

DATA SYNTHESIS:

Sixty trials were included, with a total of 5,352 participants. Random-effects pooled analysis showed that physical rehabilitation improved physical function at hospital discharge (standardized mean difference, 0.22; 95% CI, 0.00–0.44), reduced ICU length of stay by 0.8 days (mean difference, –0.80 d; 95% CI, –1.37 to –0.23 d), and hospital length of stay by 1.75 days (mean difference, –1.75 d; 95% CI, –3.03 to –0.48 d). Physical rehabilitation had no impact on the other outcomes. The intervention was more effective in trials where the control group received low-dose physical rehabilitation and in trials that investigated functional exercises.

CONCLUSIONS:

Physical rehabilitation in the ICU improves physical function and reduces ICU and hospital length of stay. However, it does not appear to impact other outcomes.
Comparison of antimuscarinic drugs to beta adrenergic agonists in overactive bladder: A literary review
Authors: Wani Mudassir M. , Sheikh Mohammad I. , Bhat Tahir , Bhat Zubair , Bhat Arshad
Published: August 2021

Background:

The purpose of this study was to carry an extended literature review to compare antimuscarnics with beta adrenergic agonists (mirabegron) in treatment of overactive bladder.

Materials and methods:

A literature review was carried out, using key words in different databases including MEDLINE, PUBMED, and EMBASE. All relevant published articles during last 5 years with full texts available were included in this review for critical analysis and evaluation. In total, there were 20 studies including 7 systemic reviews, 6 retrospective cohort, 3 prospective cohort, 2 randomized controlled trials, and 2 cross sectional studies.

Results:

After critical evaluation the results were considered under parameters of efficacy, adverse effects, adherence and persistence, tolerability, cost-effectiveness. In 9 studies efficacy was evaluated, 5 studies dealt with adverse effects, same number evaluated adherence and persistence. Cost effectiveness was compared in 3 and same number of studies also compared tolerability.

Conclusions:

To conclude, we found mirabegron is as efficacious as any other antimuscarnics, has better tolerability (including elderly), has better adverse effect profile, is cost effective, has better persistence and adherence rates at 12 months.
Findings From a Provider-Led, Mindfulness-Based, Internet-Streamed Yoga Video Addressing the Psychological Outcomes of Breast Cancer Survivors
Authors: Flanagan Jane M. , Post Kathryn , Hill Rebecca , Winters Loren N.
Published: August 2021

The aim of this study was to explore the psychological outcomes of a mindfulness-based Internet-streamed yoga video in breast cancer survivors. A one-group, repeated-measures, purposive sample using a directed qualitative descriptive and convergent mixed-methods approach was used. Participants were recruited from breast oncology practices across 2 settings in the northeastern United States in April 2019. Education about the video was provided, and the link to the video was sent to participants. Demographic information, Knowing Participation in Change Short Form (KPCSF), Short Warwick-Edinburgh Mental Well-being Scale (WEMWBS), and the Generalized Anxiety Distress Scale (GAD-7) were obtained at baseline and at 2 and 4 weeks. A semistructured interview was conducted at 4 weeks. Thirty-five women (mean age = 56 years) participated. A one-group, repeated-measures analysis of variance indicated statistically significant changes occurred in all measures between week 0 and week 4: decreased GAD (t = −2.97, P = .004), improved WEMWBS (t = 2.52, P = .008), and increased KPC (t = 2.99, P = .004). Qualitative findings suggest the overall experience of the video was positive and the women would recommend its use to others. Improvements in all psychological measures were achieved with video use. Findings indicate an improvement in psychological measures and support the theory of Knowing Participation in Change. This work further contributes to accessible, flexible interventions available through the Internet and/or mobile applications aimed at improving breast cancer survivorship.
The Impact of an Online Mindfulness-Based Stress Reduction Program on Sleep Quality of Nurses Working in COVID-19 Care Units
Authors: Nourian Manijeh , Nikfarid Lida , Khavari Amir Mohammad , Barati Mohaddeseh , Allahgholipour Amir Reza
Published: August 2021

The coronavirus disease-2019 (COVID-19) epidemic is associated with impaired sleep quality in nurses for several reasons. The present study aimed to determine the effect of an online mindfulness-based stress reduction (MBSR) program on improving the sleep quality of nurses working in the COVID-19 care units. In this randomized controlled clinical trial study, all nurses in the 2 COVID-19 patient care units were randomly assigned to the control and intervention groups. The MBSR program was implemented online for 7 weeks for the intervention group by a trainer. The Pittsburgh Sleep Quality Index (PSQI) was completed online by the participants in both groups before and after the intervention. The results of the data analysis indicated that the intervention improved the scores of subjective sleep quality, sleep latency, and sleep efficiency in the intervention group. In the control group, there was a significant increase in the scores of subjective sleep quality, daily performance, and the total index score in the posttest. Besides, there was a significant difference between the 2 groups in only 2 components of sleep latency and subjective sleep quality. The MBSR program can be an effective intervention to improve the sleep quality of nurses working in COVID-19 intensive care units who are at risk of sleep quality disorders in stressful situations.
Effect of Linked-color Imaging on the Detection of Adenomas in Screening Colonoscopies
Authors: dos Santos Carlos E.O. , Malaman Daniele , Arciniegas Sanmartin Ivan D. , Onófrio Fernanda d.Q. , Pereira-Lima Júlio C.
Published: August 2021

Objectives:

Linked-color imaging (LCI) is a new image-enhancement option that emphasizes mucosal surface contrast, facilitating the differentiation between colorectal lesions and normal mucosa. This study aimed to evaluate the potential of LCI to increase the detection of colorectal adenomas in screening colonoscopies.

Methods:

A prospective randomized study was conducted using white-light imaging (WLI), blue-laser imaging (BLI)-bright and LCI. The outcome measures were adenoma detection rate (ADR), mean number of adenomas per patient, and withdrawal time. Lesion characteristics such as size, morphology, location, and histology were also evaluated.

Results:

A total of 205 patients were randomized, and 251 adenomas were detected. The overall ADR was 62%. The ADR was 52.9% for WLI, 62.1% for BLI-bright, and 71% for LCI, and was significantly higher in the LCI group than in the WLI group (P=0.04). No significant difference was observed between LCI and BLI-bright (P=0.28) or BLI-bright and WLI (P=0.30). The mean number of adenomas per patient was 1.01, 1.03, and 1.62 for WLI, BLI-bright, and LCI, respectively, with a significant difference (P=0.02). Withdrawal time did not differ among the groups. A total of 71 adenomas were detected by WLI, 68 by BLI-bright, and 112 by LCI. There was no difference in the size and morphology of the adenomas detected, nor in the diagnosis of sessile serrated adenomas/polyps.

Conclusion:

LCI significantly increased the detection of adenomas in screening colonoscopies.
Risk of Severe COVID-19 Increased by Metabolic Dysfunction-associated Fatty Liver Disease
Authors: Tao Ziwen , Li Yueyue , Cheng Baoquan , Zhou Tao , Gao Yanjing
Published: August 2021

Background:

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in coronavirus disease-2019 (COVID-19) patients and whether it affects the outcomes of COVID-19 requires investigation.

Goals:

The aim was to determine the prevalence of MAFLD among COVID-19 patients and its influence on the outcomes of COVID-19 by meta-analysis.

Methods:

Our study protocol has been registered on PROSPERO (CRD42021242243). The studies published on PubMed, Embase, Cochrane Library, and Web of Science before March 11, 2021 were screened. The Newcastle-Ottawa scale (NOS) and Agency for Healthcare Research and Quality scale were used to assess the quality of the studies. Pooled analysis was conducted using the software RevMan version 5.3 and Stata version 15.0 SE. The stability of the results was assessed by sensitivity analysis. Publication bias was evaluated using funnel plots, Egger test, and trim-and-fill analysis.

Results:

Seven studies covering 2141 COVID-19 patients were included. It was confirmed that MAFLD increased the risk of severe COVID-19 (odds ratios: 1.80, 95% confidence interval: 1.53-2.13, P<0.00001). No association was found between the presence of MAFLD and the occurrence of COVID-19 death. The pooled prevalence of MAFLD among COVID-19 patients was 36% (95% confidence interval: 0.23-0.49, P<0.00001). Sensitivity analysis confirmed that the initial results were stable.

Conclusions:

MAFLD can increase the incidence of severe COVID-19, but the correlation between MAFLD and COVID-19 death has not been confirmed. Further investigation is needed to explore the possible mechanism of this association. Since MAFLD is common among patients infected with SARS-CoV-2, more care should be given to COVID-19 patients with underlying MAFLD.
Experience of a smartphone ambulatory ECG clinic for emergency department patients with palpitation: a single-centre cohort study
Authors: Cullen Julia , Reed Matthew J. , Muir Alexandra , Murphy Ross , Pollard Valery , Zangana Goran , Krupej Sean , Askham Sylvia , Holdsworth Patricia , Davies Lauren
Published: August 2021

Background and importance

Palpitation is one of the commonest presenting complaints to the emergency department (ED). Diagnosis depends on capturing an ECG during the episode. Unlike syncope, patients retain consciousness and therefore their ability to activate an ECG event recorder. The Investigation of Palpitation in the ED study demonstrated Food and Drug Administration approved AliveCor/Kardia device that links to a smartphone app was safe and effective. A Smartphone Palpitation and Pre-syncope Ambulatory Care Clinic was therefore established.

Objective(s)

To review the first year of patients attending the service to determine the number and cost-effectiveness of cardiac dysrhythmias diagnoses.

Design

Single-center cohort study.

Settings and participants

Royal Infirmary of Edinburgh, UK. All patients (over 16 years) presenting consecutively to ED with palpitation or pre-syncope, whose ECG was normal, had a compatible device and where an underlying cardiac dysrhythmia was possible were enrolled.

Intervention

Ambulatory Care Clinic utilizing the AliveCor/Kardia device.

Outcome measures and analysis

Number diagnosed with cardiac dysrhythmia and mean cost per diagnosis.

Main results

Between 24 July 2019 and 23 July 2020, 290 consecutive patients were referred of age 16–80 years (mean 43.3, SD 15.0). One hundred twenty (41.4%) were male. Two hundred thirty-seven (81.7%) were fitted with the device and 220 (75.9%) underwent full investigation. Seventeen of 237 (7.2%) patients had a cardiac diagnosis (12 atrial fibrillation/flutter, 5 supraventricular tachycardia and 1 atrial tachycardia).

Conclusions

There were 17 cardiac diagnoses (7.2%). The cost per symptomatic rhythm diagnosis was 358 GBP (~415 Euro) and the cost per cardiac dysrhythmia diagnosis was 4570 GBP (~5298 Euro). A smartphone-based event recorder clinic should be considered for ED palpitation patients.