bluuebunny/crossref_metadata_2025 huggingface dataset:
Gadoteridol-enhanced MRI of the breast: can contrast agent injection rate impact background parenchymal enhancement?
Authors: Marzocca Flaminia , Moffa Giuliana , Landi Valerio Nispi , Panzironi Giovanna , Kirchin Miles A , Pediconi Federica , Galati Francesca
Published: July 2021

Background

Normal background parenchymal enhancement (BPE) is a dynamic parameter affected by multiple factors.

Purpose

To determine whether contrast agent injection rate affects the degree of BPE in women undergoing breast magnetic resonance imaging (MRI).

Material and Methods

A total of 85 patients included in our prospective study randomly received 0.1 mmol/kg gadoteridol at a rate of 3 mL/s (group A; n = 46) or 2 mL/s (group B; n = 39). Breast MRI was performed at 3T using a standard protocol including postcontrast axial 3D GRE T1-weighted sequences. Two expert breast radiologists, blinded to clinical and radiological information, independently quantified BPE on early postcontrast subtracted images, assigning a score of 1–4. Mean comparison and regression analysis were performed to assess the influence of injection rate on BPE.

Results

Groups were homogeneous in terms of age and final BI-RADS score. The mean BPE score was significantly lower among patients in group A (mean of two readers: 1.36 vs. 1.90; P < 0.01) with 70%–72% of patients assigned a BPE score of 1, compared with 36%–38% of patients in group B. Lower BPE scores were noted with the higher flow rate in subgroup analyses of both pre- and postmenopausal women, although the effect was more evident in premenopausal women. Regression analysis confirmed that the likelihood of a BPE 1 score was significantly increased with a higher flow rate ( P < 0.01). The inter-reader agreement was excellent (0.83).

Conclusion

A higher contrast agent injection flow rate (3 mL/s) during breast MRI significantly reduces the degree of BPE, potentially allowing improved diagnostic accuracy by reducing false-positive and false-negative findings.
Audit of low tidal volume ventilation in patients with hypoxic respiratory failure in a tertiary Australian intensive care unit
Authors: Wilkins David , Lane Andrew S , Orde Sam R
Published: July 2021

A low tidal volume ventilation (LTVV) strategy improves outcomes in patients with acute respiratory distress syndrome (ARDS). Subsequently, a LTVV strategy has become the standard of care for patients receiving mechanical ventilation. This strategy is poorly adhered to within intensive care units (ICUs). A retrospective analysis was conducted of prescribed tidal volumes in mechanically ventilated patients with hypoxic respiratory failure between April 2013 and March 2017. Data collection included the establishment of a new data-entry box for patient height in March 2016, aimed at assisting the calculation of LTVV. We reviewed 836 ICU admissions, comprising 19,884 hours of ventilation. A total of 92% of admissions lacked patient height recording. When height was recorded, 54% of hours of ventilation were LTVV adherent. Non-LTVV hours for both groups involved higher tidal volumes (38%) rather than lower tidal volumes (8%). Non–LTVV-adherent hours were significantly ( P<0.001) more likely to be associated with patient mortality than LTVV-adherent hours were. For all hours of ventilation, mean tidal volume before March 2016 was significantly higher (496 (standard deviation (SD) 101) ml, compared to after March 2016 (451 (SD 107) ml, P<0.001, 95% confidence interval for true difference in means 42 to 48 ml). However, this trend gradually reversed over time. There was a clinician preference for multiples of 50 ml. There was poor adherence to LTVV strategy in patients with hypoxic respiratory failure, which was associated with an increase in patient mortality. An electronic medical record intervention was successful in producing change, but this was not sustainable over time. Clinician ventilation prescribing habits were based on numerical simplicity rather than evidence-based practice.
Vortex breakdown mechanics of a laminar confined swirling flow with large expansion ratio using a non-uniform finite difference approximation
Authors: Granados-Ortiz F-J , Rodríguez-Tembleque L , Ortega-Casanova J
Published: July 2021

Abrupt expansions are a very frequent geometry in mechanical engineering systems, i.e. in combustion chambers, valves, heat exchangers or impinging cooling devices. However, despite the large number of devices that use this geometry, the expanded flow behaviour still needs further research to understand and predict the full system performance. This paper presents the application of the non-uniform finite difference approximation method developed in Sanmiguel et al. for the numerical characterisation of a confined swirling laminar jet discharging with a large expansion ratio. This investigation can be considered an extension of previous work by Revuelta, but now a swirling flow is generated by a rotating pipe upstream the expansion. The structures found when a fully-developed rotating Hagen-Poiseuille flow discharges into a much larger pipe section are summarised in a bifurcation diagram, whose coordinates are the Reynolds number of the jet ( Rej) and the swirl parameter ( L), for which the time-dependent, axisymmetric and incompressible Navier-Stokes equations are integrated numerically. For values of the jet Reynolds number below 200, there is a critical value of the swirl parameter above which stable vortex breakdown appears. For values of the Reynolds number above 200, three different behaviours are observed, and each performance appears for a critical value of the swirl parameter. When increasing the swirl parameter from zero, the flow becomes axisymmetrically unstable, showing an oscillatory behaviour. If further increasing the swirl intensity, the oscillatory flow coexists with a vortex breakdown bubble and, finally, a steady vortex breakdown is reached. The expansion ratio ε considered in all the simulations is 1[Formula: see text]. In previous literature, the exactness of the limiting critical Rej and L values that define these behaviours has been found to be influenced by the variability in the inlet profile conditions, which affects the expanded flow. This enhances the importance in the present investigation to accurately simulate the discharge pipe inlet profiles.
Empowerment-Based Education in Urological Patients: A Scoping Review
Authors: Villa Giulia , Galli Emanuele , Azzimonti Vittoria , Doneda Marianna , Giannetta Noemi , Manara Duilio Fiorenzo
Published: July 2021

Prostate, kidney, and bladder cancer are the three most frequently diagnosed urological cancers. Educational programs could teach patients to become experts in disease management. The aim of this scoping review was to explore the literature to identify the educational requirements and strategies for improving and implementing educational processes for urological patients undergoing surgery. We searched several databases, including PubMed, CINAHL, Embase, Scopus, PsycINFO, and Cochrane Library. All adult patients undergoing urological educational interventions were included in the review. Of 3,197 initially identified articles, 42 were retained. Urological patients undergoing prostatectomy, cystectomy, and nephrectomy require cognitive, psychological, and functional support. For each level of support, several methods exist to provide support, including informational brochures, preoperative counseling, telephone support, online content, educational videos, support groups, individual stress management interventions, peer support, online interventions, partner support, and various educational programs that help the patient manage negative effects associated with the urological intervention.
Evaluation of Bivalirudin as the Primary Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2–Associated Acute Respiratory Failure
Authors: Bissell Brittany D. , Gabbard Taylor , Sheridan Erica A. , Baz Maher A. , Davis George A. , Ather Ayesha
Published: July 2021

Background

Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population.

Objective

The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19–associated respiratory failure.

Methods

This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h.

Results

There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%.

Conclusion and Relevance

In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.
Speculative Experimentation, Exclusion, and Uneven Material Agencies: A Response to Mirka Koro’s Egon Guba Lecture
Authors: Kuntz Aaron M.
Published: July 2021

This article was presented as a response to Dr. Mirka Koro’s Egon Guba Lecture offered at the 2021 American Educational Research Association Conference.
I thought we were vibin’: A qualitative exploration of sexual agency and consent in young people
Authors: Schobert Kelsey , Cooper Spring , Fries Noelle , Sonia Chervillil Mary
Published: July 2021

While there is much attention paid to the connection between social boundaries and consent, the relationship between consent literacy and sexual agency has not yet been explored. This qualitative analysis, which is part of a larger mixed-methods study, sought to explore the relationship between consent literacy and sexual agency in young people. Participants ( n = 18) were recruited from nonprofit organizations and were asked to complete a 30–40 minutes semi-structured interview and two questionnaires. Through our grounded theory approach to the analysis of the interviews, we identified three overarching themes and several sub-themes. The main themes were as follows: (1) Young people develop a broad understanding of sexual agency and consent through various social and environmental influences; (2) Most of consent is conceptualized through non-verbal cues (“vibes”), prior communication, and past experience with the person; (3) There are notable differences in demonstrable sexual agency between males and females and non-binary individuals, and between individuals participating in heterosexual versus queer sex acts in establishing and negotiating consent. These results provide preliminary evidence that sexual agency and consent literacy share similarities as they are being used in practice during sexual interactions. Further research is needed to deepen our understanding of how these constructs are related in order to improve levels of consent literacy.
Ultrasonic monitoring of stress and cracks of the 1/3 scale mock-up of nuclear reactor concrete containment structure
Authors: Xue Qi , Larose Eric , Moreau Ludovic , Thery Romain , Abraham Odile , Henault Jean-Marie
Published: July 2021

To evaluate the stress level and damage of a reinforced concrete containment wall (similar to those used in nuclear power plants) and its reaction to pressure variations, we conducted successive ultrasonic experiments on the exterior surface of the containment wall in the gusset area for three consecutive years (2017, 2018 and 2019). During each experiment, the pressure inside the containment wall increased gradually from 0 MPa to 0.43 MPa and then decreased back to 0 MPa. From the analysis of the ultrasonic coda waves obtained in the multiple scattering regime (80–220 kHz), we performed Coda Wave Interferometry to calculate the apparent velocity changes in the structure (denoted by dV/ V a) and Coda Wave Decorrelation (DC) measurements to produce 3D cartographies of stress and crack distribution. From three source–receiver pairs, located at the top, middle and bottom of the experimental region, we observe that coda waves dilate, shrink and remain almost unchanged, respectively. This corresponds to the decreasing, increasing and invariant pressure inside the concrete. The comparison of 3 years’ results demonstrates that the variation of dV/ V a and DC under the same pressure test increases through the years, which indicates the progressive deterioration and ageing of the concrete. From a large collection of source–receiver pairs at different times, the spatial–temporal variations of dV/ V a and DC are then used to produce a map of the structural velocity and scattering changes, respectively. We observe a decreasing velocity on the top part and an increasing in the middle one, which is in line with the dV/ V a analysis. The reconstructed scattering changes (or structural changes) highlight the active region during the inflation–deflation procedure, corresponding to the opening and closing (and sometimes the development) of cracks. The larger magnitude in 2019 than in 2017 indicates the increasing damage in the concrete.
Prognostic Value of Bleeding in Gastrointestinal Stromal Tumors: A Meta-Analysis
Authors: Fan Xin , Han He , Sun Zhiyu , Zhang Liwen , Chen Gong , Mzee Said Abdulrahman Salim , Yang Hanqing , Chen Jixiang
Published: July 2021

Background:

Gastrointestinal bleeding is the most common clinical manifestation of gastrointestinal stromal tumor. It is of great significance to the prognosis of patients. But the results are controversial. The purpose of this study was to evaluate the relationship between gastrointestinal bleeding and clinical prognosis in patients with GIST.

Methods:

A systematic literature search was performed in Pumbed, Cochrane Library, EMBASE, ClinicalTrials.gov , CNKI, VIP and wanfang databases with the pattern of unlimited languages. 12 studies with 2781 individuals were included in the final analysis. The overall survival (OS), recurrence-free survival/disease-free survival (RFS/DFS) and related factors affecting bleeding in patients with gastrointestinal stromal tumor (GIST) were extracted. Hazard ratio (HR) and 95% confidence interval (CI) were used for in the meta-analysis.

Results:

A total of 12 articles were included in the study, including 2781 patients with GIST, including 845 patients with gastrointestinal bleeding. The OS of GIST patients with gastrointestinal bleeding was significantly worse (HR = 2.54, 95% CI = 1.13-5.73, P = 0.025). But there was no significant difference in RFS between gastrointestinal bleeding patients and non-bleeding patients (HR = 1.35, 95% CI = 0.70-2.61, P = 0.371). Further analysis of the related factors of GI bleeding in GIST patients was observed, besides the aging factor (HR = 1.02, 95% CI = 0.69-1.50, P = 0.929), Small intestinal stromal tumor (HR = 0.56, 95% CI = 0.41-0.76, P < 0.001), tumor diameter ≥ 5 cm (HR = 2.09, 95% CI = 1.20-3.63, P = 0.009), Mitotic index ≥ 5/50 HPF (HR = 1.66, 95% CI = 1.11-2.49, P = 0.014) and tumor rupture (HR = 2.04, 95% CI = 1.0-3.82, P = 0.026) all increased the risk of GI bleeding in patients with GIST.

Conclusions:

The OS of GIST patients with GI bleeding was worse than non-GI bleeding, but had no significant effect on RFS. Nevertheless the aging factor, the location of GIST in the small intestine, tumor diameter ≥ 5 cm, Mitotic index ≥ 5/50 HPF and tumor rupture all increased the risk of GI bleeding in patients with GIST.
Teachers’ Perceptions of Handwriting Legibility Versus the German Systematic Screening for Motoric-Handwriting Difficulties (SEMS)
Authors: Franken Anita M. , Harris Susan R.
Published: July 2021

Handwriting problems impact school achievement. The purpose of this pilot study was to evaluate the agreement between teachers’ opinions and the German Systematische Erfassung motorischer Schreibstörungen’s (SEMS) handwriting test and to estimate the prevalence of handwriting problems. This was a prospective, correlational study. Teachers’ ratings of handwriting from German children (Grades 2 and 4) were compared to SEMS scores. The agreement was calculated with Gwet’s AC2; preliminary cutoffs and prevalence were assessed with receiver–operating characteristic curves. SEMS accurately identified Grade 2 children with handwriting problems (specificity = 98.21%, sensitivity = 100%) but fewer Grade 4 children with handwriting difficulties than did teachers (specificity 97.67%, sensitivity 28.57%). Grade 4 item agreement supports the SEMS’ ability to assess underlying handwriting dimensions as perceived by teachers. Teachers identified 12.70% of Grade 2 children versus SEMS 11.11% and 14% of Grade 4 children versus SEMS 6%. The SEMS supports clinical observations and provides information about underlying handwriting dimensions. Because handwriting is used primarily at school, the opinions of teachers are also critical.
Effect of Forearm Position on Glenohumeral External Rotation Measurements in Baseball Players
Authors: Kibler W. Ben , Sciascia Aaron , Pike John Stuart Mattison , Howell Michael , Wilk Kevin E.
Published: July 2021

Background:

Alterations in glenohumeral internal rotation (GIR), glenohumeral external rotation (GER), and the total arc of motion (TAM) have been linked with increased injury risk in the shoulder and elbow. These motions have been routinely measured with the forearm in neutral rotation (GIRN, GERN, TAMN). GER capacity appears to be especially important. The throwing motion, however, requires forearm pronation as GER occurs to achieve optimal cocking (GERP). No previous studies have evaluated GERP to determine GER capacity or pronated TAM (TAMP) values.

Hypothesis:

There would be significant differences between GERN and TAMN and between GERP and TAMP.

Study Design:

Cross-sectional.

Level of Evidence:

Level 3.

Methods:

Sixty asymptomatic male Minor League Baseball players (32 pitchers, 28 position players) participated in the study and were tested on the first day of spring training. Passive range of motion measurements were recorded using a long-arm bubble goniometer for GIRN, GERN, and GERP on both arms. TAM was calculated separately as the sum of internal and external rotational measurements under neutral and pronated conditions.

Results:

Within pitchers and position players, all measurements were statistically reduced for the throwing arm ( P ≤ 0.03) except for GERN of the pitchers. GERP measures were significantly less than GERN for both arms of each group ( P < 0.01): pitchers throwing arm +11.8°/nonthrowing arm +4.8°, position players throwing arm = +8.6°/nonthrowing arm +4.0°.

Conclusion:

The forearm position of pronation, which appears to be mediated by tightness of the biceps, decreases GER capacity and TAM. GER and TAM should be calculated in neutral and pronated positions, considering that 80% of the players have a demonstrated difference between 8° and 12°.

Clinical Relevance:

Measurement of GERP more accurately reflects the GER required in throwing, allows better quantification of the motion capacity necessary to withstand the loads in throwing, and may suggest interventions for at risk athletes.
Effect of switching glatiramer acetate formulation from 20 mg daily to 40 mg three times weekly on immune function in multiple sclerosis
Authors: Ito Kouichi , Ito Naoko , Yadav Sudhir K , Suresh Shradha , Lin Yong , Dhib-Jalbut Suhayl
Published: July 2021

Background

Many RRMS patients who had been treated for over 20 years with GA 20 mg/ml daily (GA20) switched to 40 mg/ml three times-a-week (GA40) to reduce injection-related adverse events. Although GA40 is as effective as GA20 in reducing annualized relapse rate and MRI activity, it remains unknown how switching to GA40 from GA20 affects the development of pathogenic and regulatory immune cells.

Objective

To investigate the difference in immunological parameters in response to GA20 and GA40 treatments.

Methods

We analyzed five pro-inflammatory cytokines (IL-1β, IL-23, IL-12, IL-18, TNF-α), and three anti-inflammatory/regulatory cytokines (IL-10, IL-13, and IL-27) in serum. In addition, we analyzed six cytokines (IFN-γ, IL-17A, GM-CSF, IL-10, IL-6, and IL-27) in cultured PBMC supernatants. The development of Th1, Th17, Foxp3 Tregs, M1-like, and M2-like macrophages were examined by flow cytometry. Samples were analyzed before and 12 months post switching to GA40 or GA20.

Results

Pro- and anti-inflammatory cytokines were comparable between the GA40 and GA20 groups. Development of Th1, Th17, M1-like macrophages, M2-like macrophages, and Foxp3 Tregs was also comparable between the two groups.

Conclusions

The immunological parameters measured in RRMS patients treated with GA40 three times weekly are largely comparable to those given daily GA20 treatment.
Introduction: Smartphone-based visual normativity: Approaches from digital anthropology and communication studies
Authors: Miller Daniel , Wang Xinyuan
Published: July 2021

In this special issue, we would like to take this opportunity to demonstrate the value and strength of a conversation between digital anthropology and communication studies around the topic of visual communication and the use of the smartphone.
Do English Language Development Curriculum Materials Matter for Students’ English Proficiency?
Authors: Lê Quỳnh Tiên Nguyên , Polikoff Morgan S.
Published: July 2021

Castañeda v. Pickard mandated that educational programs for emergent bilinguals be tested for program efficacy. As English language development (ELD) curricular materials are one part of an instructional program, we assess this mandate by examining the effectiveness of ELD materials in Texas, a large, diverse U.S. state with large numbers of emergent bilingual (EB) students. Using local linear matching, we find robust evidence that schools that do not purchase any ELD curricula have significantly lower English language proficiency scores relative to schools that purchase state-adopted ELD materials. In contrast, there is no significant difference between schools that adopt the two most popular ELD curricula in the state. This study suggests that curriculum materials matter for EBs’ English proficiency and implies that states should take a more active role in ensuring students have access to these materials.
Stent Embolization Mimicking Acute Myocardial Infarction
Authors: Huda Syed Arqum , Kahlown Sara Akram , Pathmanathan Anojan , Farooqi Muhammad Saad , Charlamb Mark
Published: July 2021

Venous thromboembolism is associated with significant morbidity and mortality if left untreated. Anticoagulation is the cornerstone of treatment. Venous stents are a relatively newer entity that are increasingly being used to treat venous stenosis/occlusion. It is a safe procedure, but complications include vein rupture, arterial puncture, retroperitoneal bleeding, and in-stent thrombosis. Stent migration is a rare but potentially fatal complication. We present a case of venous stent embolization to the heart that presented as a non-ST segment elevation myocardial infarction.
Patient-Centered Telehealth Solution for Observed Urine Collections in Substance Use Disorder Care Delivery During COVID-19 and Beyond
Authors: Brett Alexa , Foster Heather , Joseph Michael , Warrington Jill S.
Published: July 2021

Patients with substance use disorder (SUD) rely upon urine drug testing to support treatment adherence and to mitigate relapse. Before the onset of coronavirus 2019 (COVID-19), the logistical challenges of randomized observed collections for urine drug testing for the patient were significant. During COVID-19, these barriers were often insurmountable. Since SUD patients represent a population at a higher risk for complications from COVID-19, an alternative strategy to support COVID-19 testing was urgently needed. We designed and deployed a telehealth-based solution in which patients could use mobile devices to connect with trained collection professionals to perform observed urine collections, often referred to a UA (urinalysis). The solution was designed with patient-centered best practices for telehealth, stigma prevention, trauma-informed, empathy and compassion, and to remove barriers to access to care. This approach demonstrated high patient satisfaction scores thereby proving that it is possible to provide urine collection services in the patient’s home via a telehealth technology, while still upholding SUD testing integrity best practices. This study lays the path for a more patient-centered way to support this population.
Lessons Learned Transitioning from Traditional Premedical and Medical Education to E-learning Platforms during the COVID-19 Pandemic within the United Arab Emirates
Authors: O’Sullivan Siobhán M. , Khraibi Ali A. , Chen Wei , Corridon Peter R.
Published: July 2021

Educational systems across the globe were disrupted by the COVID-19 pandemic, and faculty, staff, and students had to rapidly transition to e-learning platforms. These groups had little preparation to cope with the challenges of this newly adopted system. However, as we begin to emerge from the COVID-19 era, efforts are being made to assess the impact of this transition and develop a framework of best practices to help educators prepare for possible future disruptions. This commentary aims to discuss some of the challenges associated with the rapid transition to the new academic environment, including the modes of instruction employed, technical obstacles encountered, student responses to change and efforts made to evaluate didactic and practical aspects of the curriculum in the contexts of premedical and medical education, at the newly established College of Medicine at Khalifa University of Science and Technology in the United Arab Emirates.
On Conversion Talk in Indian Clinical Contexts: A Pilot Venture
Authors: Chatterjee Aritra , Mukherjee Tilottama
Published: July 2021

Conversion therapies are founded on the premises of altering one’s sexual orientation/gender identity to compulsory cis-heterosexuality. They target LGBTQIA+ individuals globally and negatively impact their psychosexual health and well-being. These therapies were not discredited explicitly in the Indian mental health context until 2020. In the current article, two case vignettes are sampled from self-identified transgender individuals who faced conversion efforts in various capacities, their families, and health care professionals being collateral stakeholders in the process. These case vignettes are shaped from first-person narrative accounts elicited from the participants in narrative inquiry format through virtual interactive sessions. The cases are critically discussed in the light of the present clinical-scientific consensus and future implications. The routes to more affirmative mental health ecosystems are explored through probable intersectoral linkages.
Association between lung function and future risks of diabetes, asthma, myocardial infarction, hypertension and all-cause mortality
Authors: Shah Chintal H. , Reed Robert M. , Liang Yulan , Zafari Zafar
Published: July 2021

Background

While forced expiratory volume in 1 s (FEV1) is a hallmark of disease progression in chronic obstructive lung diseases, little is known about the relationship between baseline FEV1and future risks of other medical conditions.

Objective

The aim of this study was to investigate the association between baseline FEV1and future risks of diabetes, asthma, myocardial infarction, hypertension and all-cause mortality.

Methods

We used data from the National Health and Nutrition Examination Survey and its Epidemiological Follow-Up Study. Our data provided longitudinal follow-up of the original cohort for up to 12 years. We used two competing risks approaches, the cause-specific hazard model and the Fine–Gray sub-distribution hazard model, to measure the associations between baseline FEV1and future risks of the outcomes of interest. All models were adjusted for major confounding factors.

Results

The final sample included 3020 participants (mean±sdbaseline age 44.64±13.44 years). In the cause-specific hazard model, for every per cent increase in the baseline per cent predicted FEV1, the hazard of the event reduced by 2.5% (HR 0.975; 95% CI 0.958–0.994) for diabetes, 4.3% (HR 0.957; 95% CI 0.932–0.983) for asthma and 1.8% (HR 0.982; 95% CI 0.971–0.992) for all-cause mortality. There was no statistically significant association between baseline per cent predicted FEV1and future risks of myocardial infarction (HR 0.987; 95% CI 0.970–1.004) and hypertension (HR 0.998; 95% CI 0.992–1.005). Consistent results were observed for the Fine–Gray sub-distribution hazard model.

Conclusion

Our data suggest that lower per cent predicted FEV1values at baseline were significantly associated with higher future risks of diabetes, asthma and all-cause mortality.
Cospeciation of coronavirus and paramyxovirus with their bat hosts in the same geographical areas
Authors: Liang Jie , Zhu Chunchao , Zhang Libiao
Published: July 2021

Background

Bat-borne viruses are relatively host specific. We hypothesize that this host specificity is due to coevolution of the viruses with their hosts. To test this hypothesis, we investigated the coevolution of coronavirus and paramyxovirus with their bat hosts. Published nucleotide sequences of the RNA-dependent RNA polymerase (RdRp) gene of 60 coronavirus strains identified from 37 bat species, the RNA polymerase large (L) gene of 36 paramyxovirus strains from 29 bat species, and the cytochrome B (cytB) gene of 35 bat species were analyzed for coevolution signals. Each coevolution signal detected was tested and verified by global-fit cophylogenic analysis using software ParaFit, PACo, and eMPRess.

Results

Significant coevolution signals were detected in coronaviruses and paramyxoviruses and their bat hosts, and closely related bat hosts were found to carry closely related viruses.

Conclusions

Our results suggest that paramyxovirus and coronavirus coevolve with their hosts.
Putative genes in alkaloid biosynthesis identified in Dendrobium officinale by correlating the contents of major bioactive metabolites with genes expression between Protocorm-like bodies and leaves
Authors: Wang Zhaojian , Jiang Weimin , Liu Yingying , Meng Xiaoxi , Su Xinglong , Cao Mengyang , Wu Liping , Yu Nianjun , Xing Shihai , Peng Daiyin
Published: July 2021

Background

Dendrobium officinale, an endangered Chinese herb, possesses extensive therapeutic effects and contains bioactive ingredients such as major polysaccharides, alkaloids, and minimal flavonoids. We first obtained the protocorm-like bodies (PLBs) of this plant through tissue culture in order to determine the distribution of the main secondary metabolites in each organelle and the PLBs. We then analyzed the correlation between gene expression level from comparative transcriptome sequencing and metabolite content in different organs to identify putative genes encoding enzymes involved in the biosynthesis of polysaccharides, alkaloids, and flavonoids.

Results

We used seeds as explants for protocorm induction and PLB propagation of D. officinale. The optimal medium formula for PLB propagation was 1/2 MS + α-NAA 0.5 mg·L− 1 + 6-BA 1.0 mg·L− 1 + 2, 4-D 1.5–2.0 mg·L− 1 + potato juice 100 g·L− 1. Stems, PLBs and leaves of D. officinale had the highest content of polysaccharides, alkaloids and flavonoids, respectively. Naringenin was only produced in stem; however, PLBs with high alkaloid content can replace other organs producing alkaloids. The hot water extraction method outperformed the ultrasound-assisted extraction method for extracting polysaccharides from D. officinale. A comparative transcriptome analysis of PLBs and leaves of D. officinale revealed differential expression of genes encoding enzymes involved in polysaccharide, alkaloid and flavonoid biosynthetic pathways. Putative genes encoding enzymes involved in these biosynthetic pathways were identified. Notably, we identified genes encoding the alkaloid biosynthesis enzymes strictosidine β-D-Glucosidase, geissoschizine synthase and vinorine synthase in D. officinale.

Conclusions

The identification of candidate genes encoding enzymes involved in metabolite biosynthesis will help to explore and protect this endangered species and facilitate further analysis of the molecular mechanism of secondary metabolite biosynthesis in D. officinale.
Oral Misoprostol alone versus oral misoprostol followed by oxytocin for labour induction in women with hypertension in pregnancy (MOLI): protocol for a randomised controlled trial
Authors: Bracken Hillary , Lightly Kate , Mundle Shuchita , Kerr Robbie , Faragher Brian , Easterling Thomas , Leigh Simon , Turner Mark , Alfirevic Zarko , Winikoff Beverly , Weeks Andrew
Published: July 2021

Background

Every year approximately 30,000 women die from hypertensive disease in pregnancy. Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour induction. Usually, once active labour has commenced, the misoprostol is replaced with an intravenous oxytocin infusion if ongoing stimulation is required. However, some studies have shown that oral misoprostol can be continued into active labour, a simpler and potentially more acceptable protocol for women. To date, these two protocols have never been directly compared.

Methods

This pragmatic, open-label, randomised trial will compare a misoprostol alone labour induction protocol with the standard misoprostol plus oxytocin protocol in three Indian hospitals. The study will recruit 520 pregnant women being induced for hypertensive disease in pregnancy and requiring augmentation after membrane rupture. Participants will be randomised to receive either further oral misoprostol 25mcg every 2 h, or titrated intravenous oxytocin. The primary outcome will be caesarean birth. Secondary outcomes will assess the efficacy of the induction process, maternal and fetal/neonatal complications and patient acceptability. This protocol (version 1.04) adheres to the SPIRIT checklist. A cost-effectiveness analysis, situational analysis and formal qualitative assessment of women’s experience are also planned.

Discussion

Avoiding oxytocin and continuing low dose misoprostol into active labour may have a number of benefits for both women and the health care system. Misoprostol is heat stable, oral medication and thus easy to store, transport and administer; qualities particularly desirable in low resource settings. An oral medication protocol requires less equipment (e.g. electronic infusion pumps) and may free up health care providers to assist with other aspects of the woman’s care. The simplicity of the protocol may also help to reduce human errors associated with the delivery of intravenous infusions. Finally, women may prefer to be mobile during labour and not restricted by an intravenous infusion. There is a need, therefore, to assess whether augmentation using oral misoprostol is superior clinically and economically to the standard protocol of intravenous oxytocin.

Trial registration

Clinical Trials.gov, NCT03749902, registered on 21st Nov 2018.
Predictors of the surgical outcome of propeller perforator flap reconstruction, focusing on the effective safe distance between the perforator and the wound edge
Authors: Wang Peng , Lin Fang , Ma Yunhong , Wang Jianbing , Zhou Ming , Rui Yongjun
Published: July 2021

Background

Soft tissue defects in the distal third of the leg and malleolus are difficult to cover and often require free tissue transfer, even for small-sized defects. Propeller flaps were designed as an alternative to free tissue transfer, but are reportedly associated with high complication rates. The aim of our study was to assess our institutional experience with the propeller flap technique and to predict its outcome in lower-limb reconstruction.

Methods

All patients who had undergone propeller flap reconstruction of a distal leg defect between 2013 and 2018 were included. Demographic, clinical, and follow-up data were analyzed.

Results

Complications occurred in 17 of 82 propeller flaps (20.7%), comprising 11 cases of partial necrosis and six of total necrosis. There were no significant differences in age, sex, body mass index smoking, diabetes mellitus, and soft tissue defect sites between the groups of patients with versus without flap necrosis (p > 0.05). In univariate analysis, there were also no significant differences between these two groups in the length and width of the fascial pedicle, and the ratio of the flap length to the flap width (p > 0.05). Interestingly, there were significant differences between the two groups in the distance between the flap perforator, the shortest distance from the perforator to the defect location, and the rotation angle of the flap (p < 0.05). In multivariable logistic regression analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs), the shortest distance from the perforator to the defect location was a significant risk factor for flap complications (p = 0.000; OR = 0.806). Receiver operating characteristic curve analysis showed that when the shortest distance from the flap to the wound was less than 3.5 cm, the necrosis rate of the flap was markedly increased (AUC = 76.1); this suggests that the effective safe flap–wound distance was 3.5 cm.

Conclusions

Propeller flaps are a reliable option for reconstruction in carefully selected patients with traumatic defects of the lower limb and malleolus. We found that the effective safe distance was 3.5 cm from the flap to the wound.
Development and validation of a score to predict mortality in ICU patients with sepsis: a multicenter retrospective study
Authors: Weng Jie , Hou Ruonan , Zhou Xiaoming , Xu Zhe , Zhou Zhiliang , Wang Peng , Wang Liang , Chen Chan , Wu Jinyu , Wang Zhiyi
Published: July 2021

Background

Early and accurate identification of septic patients at high risk for ICU mortality can help clinicians make optimal clinical decisions and improve the patients’ outcomes. This study aimed to develop and validate (internally and externally) a mortality prediction score for sepsis following admission in the ICU.

Methods

We extracted data retrospectively regarding adult septic patients from one teaching hospital in Wenzhou, China and a large multi-center critical care database from the USA. Demographic data, vital signs, laboratory values, comorbidities, and clinical outcomes were collected. The primary outcome was ICU mortality. Through multivariable logistic regression, a mortality prediction score for sepsis was developed and validated.

Results

Four thousand two hundred and thirty six patients in the development cohort and 8359 patients in three validation cohorts. The Prediction of Sepsis Mortality in ICU (POSMI) score included age ≥ 50 years, temperature < 37 °C, Respiratory rate > 35 breaths/min, MAP ≤ 50 mmHg, SpO2 < 90%, albumin ≤ 2 g/dL, bilirubin ≥ 0.8 mg/dL, lactate ≥ 4.2 mmol/L, BUN ≥ 21 mg/dL, mechanical ventilation, hepatic failure and metastatic cancer. In addition, the area under the receiver operating characteristic curve (AUC) for the development cohort was 0.831 (95% CI, 0.813–0.850) while the AUCs ranged from 0.798 to 0.829 in the three validation cohorts. Moreover, the POSMI score had a higher AUC than both the SOFA and APACHE IV scores. Notably, the Hosmer–Lemeshow (H–L) goodness-of-fit test results and calibration curves suggested good calibration in the development and validation cohorts. Additionally, the POSMI score still exhibited excellent discrimination and calibration following sensitivity analysis. With regard to clinical usefulness, the decision curve analysis (DCA) of POSMI showed a higher net benefit than SOFA and APACHE IV in the development cohort.

Conclusion

POSMI was validated to be an effective tool for predicting mortality in ICU patients with sepsis.
Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection
Authors: Torices Silvia , Cabrera Rosalba , Stangis Michael , Naranjo Oandy , Fattakhov Nikolai , Teglas Timea , Adesse Daniel , Toborek Michal
Published: July 2021

Background

Neurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 to infect brains. While the mechanisms of this process are not fully understood, it has been proposed that SARS-CoV-2 can infect the cells of the neurovascular unit (NVU), which form the blood-brain barrier (BBB). The aim of the current study was to analyze the expression pattern of the main SARS-CoV-2 receptors in naïve and HIV-1-infected cells of the NVU in order to elucidate a possible pathway of the virus entry into the brain and a potential modulatory impact of HIV-1 in this process.

Methods

The gene and protein expression profile of ACE2, TMPRSS2, ADAM17, BSG, DPP4, AGTR2, ANPEP, cathepsin B, and cathepsin L was assessed by qPCR, immunoblotting, and immunostaining, respectively. In addition, we investigated if brain endothelial cells can be affected by the exposure to the S1 subunit of the S protein, the domain responsible for the direct binding of SARS-CoV-2 to the ACE2 receptors.

Results

The receptors involved in SARS-CoV-2 infection are co-expressed in the cells of the NVU, especially in astrocytes and microglial cells. These receptors are functionally active as exposure of endothelial cells to the SARS CoV-2 S1 protein subunit altered the expression pattern of tight junction proteins, such as claudin-5 and ZO-1. Additionally, HIV-1 infection upregulated ACE2 and TMPRSS2 expression in brain astrocytes and microglia cells.

Conclusions

These findings provide key insight into SARS-CoV-2 recognition by cells of the NVU and may help to develop possible treatment of CNS complications of COVID-19.
Modelling the impact of delaying vaccination against SARS-CoV-2 assuming unlimited vaccine supply
Authors: Amaku Marcos , Covas Dimas Tadeu , Coutinho Francisco Antonio Bezerra , Azevedo Raymundo Soares , Massad Eduardo
Published: July 2021

Background

At the moment we have more than 177 million cases and 3.8 million deaths (as of June 2021) around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far.

Methods

We propose a new mathematical model to estimate the impact of vaccination delay against the 2019 coronavirus disease (COVID-19) on the number of cases and deaths due to the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations.

Results

The model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths will occur by the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, for each month of delay the number of deaths increases monotonically in a logarithmic fashion, for both the State of Sao Paulo and Brazil as a whole.

Conclusions

Our model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time.
A feasibility trial of an intervention in alcohol dependence for structured preparation before detoxification versus usual care: the SPADe trial results
Authors: Kouimtsidis Christos , Houghton Ben , Gage Heather , Notley Caitlin , Maskrey Vivienne , Clark Allan , Holland Richard , Lingford-Hughes Anne , Punukollu Bhaskar , Touray Morro , Duka Theodora
Published: July 2021

Background

Individuals who are ‘moderately’ or ‘severely’ dependent consume alcohol at levels that are likely to have a severe impact on their own health and mortality, the health and behaviours of others (family members) and to have economic and social implications. Treatment guidelines suggest that treatment needs to be planned with medically assisted withdrawal (also referred to as detoxification), and aftercare support but outcomes are poor with low proportions engaging in after care and high relapse rates. An approach of structured preparation before alcohol detoxification (SPADe) puts an emphasis on introducing lifestyle changes, development of coping strategies for cravings, stress and emotions as well as introducing changes to the immediate family and social environment in advance of alcohol cessation. Such a pre-habilitation paradigm compliments the established treatment approach. The key research question was: can we design a large scale, randomised controlled trial (RCT) that will answer whether such an approach is more effective than usual care in helping individuals to maintain longer periods of alcohol abstinence?

Methods

This is a pragmatic, parallel, two-arm, feasibility RCT comparing SPADe and usual care against usual care only in maintaining alcohol abstinence in adults with alcohol dependence receiving care in two community addiction services in London. Feasibility outcomes, exploration of primary and secondary clinical outcomes and health economic outcomes are analysed. The trial follows the guidelines of phase 2 of the Medical Research Council (MRC) for complex interventions.

Results

We were able to recruit 48/50 participants during a period of 9 months. Retention in the trial for the whole period of the 12 months was 75%. Treatment compliance was overall 44%. Data completion for the primary outcome was 65%, 50% and 63% at 3, 6 and 12 months, respectively. The intervention group had more days abstinent in the previous 90 days at the 12 months (n = 54.5) versus control (n = 41.5).

Conclusions

The results of this feasibility trial indicate that with the appropriate modifications, a full multicentred trial would be possible to test the effectiveness and cost-effectiveness of a pre-habilitation approach such as the SPADe group intervention in addition to usual care against usual care only.

Trial registration

Name of registry: ISRCTN; Trial Registration Number: 14621127; Date of Registration: 22/02/2017.