bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Monocyte Chemotactic Protein-1 Accompanying Pro-Inflammatory Processes are Associated with Progressive Hearing Impairment and Bilateral Disability of Meniere’s Disease
Authors: Iinuma Ryota , Okuda Hiroshi , Obara Natsuko , Matsubara Yoshitaka , Aoki Mitsuhiro , Ogawa Takenori
Published: December 2021

Background: The progression of hearing impairment and the bilateral involvement of Meniere’s disease (MD) may depend on the disease duration and aging. Recent studies reported that MD might involve dysfunction of the microvascular circulation damaged due to inflammatory changes. Objectives: The aim of this study was to determine that the progress of the MD’s hearing impairment and bilateral disability may be associated with the pathogenesis of several pro-inflammatory processes. Patients and Methods: We recruited 30 unilateral MD patients (56.8 ± 14.7 years old), 7 bilateral MD patients (65.3 ± 13.9 years old), and 17 age-matched control subjects (53.5 ± 14.4 years old, p > 0.05). We measured the plasma vascular endothelial growth factor (VEGF), plasma interleukin-6 (IL-6), plasma tumor-necrosis factor α (TNFα), and plasma monocyte chemotactic protein-1 (MCP-1). Results: The bilateral MD group and the unilateral MD group had higher plasma MCP-1 (204.7 ± 41.0 pg/mL and 169.5 ± 32.0 pg/mL) than the control group (149.2 ± 30.7 pg/mL) (p < 0.05). There was no significant difference in plasma TNFα, IL-6, and VEGF among 3 groups (p > 0.05). There was a strong correlation between the plasma MCP-1 and age in MD patients (r = 0.58, p < 0.01); however, no significant correlation between the plasma MCP-1 and age was found in control subjects (p > 0.05). The plasma MCP-1 significantly correlated with the average hearing level of 500, 1,000, 2,000, and 4,000 Hz, and the maximum slow phase eye velocity in caloric test in the better side (p < 0.05). Also, the plasma MCP-1 showed significant positive correlations with the plasma IL-6 (r = 0.49, p < 0.01) and plasma TNFα (r = 0.32, p < 0.05) in MD group. Conclusions: Our results suggest that the increased plasma MCP-1 accompanying pro-inflammatory processes are associated with the progression of the hearing impairment and the bilateral disability of MD.
Predictors of Airway Hyperresponsiveness in Symptomatic Children with Normal Spirometry and Suspicious of Possible Asthma
Authors: Reinsberg Max , Siebert Stephanie , Dreher Charlotte , Bogs Thomas , Ganschow Rainer , Yavuz S. Tolga
Published: December 2021

Background: Asthma diagnosis may be challenging particularly in patients with mild symptoms without an obstructive pattern in spirometry. Detection of airway hyperresponsiveness (AHR) by a positive methacholine challenge (MCC) is still an important diagnostic tool to confirm the presence of asthma with reasonable certainty. However, it is time consuming and could be exhausting for patients. We aimed to identify the predictive factors for AHR in children with respiratory symptoms without obstructive pattern in spirometry. Methods: Data from children who had undergone MCC were analyzed retrospectively. The demographic features of patients along with laboratory results were collected. Results: A total of 123 children with a median age of 10.5 years were enrolled. AHR was detected in 81 children (65.8%). The age of the children with AHR was significantly younger. The prevalences of aeroallergen sensitization, nocturnal cough, wheezing, and a baseline forced expiratory flow at 75% of vital capacity (FEF75) <65% were significantly more frequent in children with AHR. Multivariate logistic regression analysis revealed age, ever wheezing, nocturnal cough, tree pollen allergy, and FEF75 <65% as independent predictors of AHR. A weighted clinical risk score was developed (range, 0–75 points). At a cutoff point of 35, the presence of AHR is predicted with a specificity of 90.5% and a positive predictive value of 91.5%. Conclusion: In children suspected of having asthma, but without an obstructive pattern in the spirometry, combining independent predictors, which can be easily obtained in clinical practice, might be used to identify children with AHR.
Advanced Imaging Approaches to Reveal Molecular Mechanisms Governing Neuroendocrine Secretion
Authors: Riachy Lina , Ferrand Thomas , Chasserot-Golaz Sylvette , Galas Ludovic , Alexandre Stéphane , Montero-Hadjadje Maité
Published: December 2021

Identification of the molecular mechanisms governing neuroendocrine secretion and resulting intercellular communication is one of the great challenges of cell biology to better understand organism physiology and neurosecretion disruption-related pathologies such as hypertension, neurodegenerative, or metabolic diseases. To visualize molecule distribution and dynamics at the nanoscale, many imaging approaches have been developed and are still emerging. In this review, we provide an overview of the pioneering studies using transmission electron microscopy, atomic force microscopy, total internal reflection microscopy, and super-resolution microscopy in neuroendocrine cells to visualize molecular mechanisms driving neurosecretion processes, including exocytosis and associated fusion pores, endocytosis and associated recycling vesicles, and protein-protein or protein-lipid interactions. Furthermore, the potential and the challenges of these different advanced imaging approaches for application in the study of neuroendocrine cell biology are discussed, aiming to guide researchers to select the best approach for their specific purpose around the crucial but not yet fully understood neurosecretion process.
Reducing Health Care Burden of Emergency General Surgery with a 24-Hour Dedicated Emergency General Surgery Service
Authors: Roy J. David , Hardy W. Johnson , Roberts Morgan E. , Stahl Joseph E. , Butts C. Caleb , Simmons Jon D. , Barber William H.
Published: December 2021

Background

Emergency general surgery (EGS) diagnoses account for 11% of surgical admissions and 50% of surgical mortality. In this population, 7 specific operations are associated with 80.3% of deaths, 78.9% of complications, and 80.2% of hospital costs. In 2016, our institution established a comprehensive in-house EGS service. Herein, we hypothesize that formation of a dedicated EGS service is associated with a significant reduction in morbidity for patients undergoing the most common EGS procedures.

Methods

All patients undergoing one of the most common EGS procedures within 2 days of admission were identified from 1/1/2013 to 5/9/2019 via a retrospective chart review. Patients were cohorted as pre- and post-EGS implementation. The primary outcome measure was the overall complication rate. Secondary endpoints included mortality, individual complication rate, time to operation, overnight operation, and length of stay. Finally, both cohorts were benchmarked to national outcomes.

Results

718 patients met inclusion criteria (pre-EGS = 409 and post-EGS = 309). Overall complication rate decreased significantly (19.8% vs 13.9%, P = .0387) and overnight operations increased significantly in the post-EGS group (7.8%-16.5%, P = .0003). Pre-EGS complications were higher than national data in all but 1 procedure group, whereas post-EGS complications rates were lower in all but 2 categories.

Discussion

Implementation of a dedicated EGS service line was associated with a significant decrease in complication rate among the most complication-prone EGS procedures. Number of operations within 24 hours did not increase significantly; however, overnight operations did increase. Our results indicate that establishing a service-specific EGS line is reasonable and beneficial.
Effects of Nature Values and Regulatory Fit of Message Framing on Message Evaluation and Actual Pro-Environmental Donations
Authors: Woltin Karl-Andrew , Sneddon Joanne , Bardi Anat
Published: December 2021

Messages are often tailored to individual differences, as fit is believed to influence behavior. We examine the effects of regulatory fit (i.e., matching promotion/prevention message framing to people’s promotion/prevention orientation) and the priority that individuals attribute to nature values, on the evaluation of climate change messages and donations to pro-environmental charities. We measured participants’ ( n = 570) regulatory focus on ensuring positive outcomes (promotion) versus avoiding negative outcomes (prevention), and nature values. Participants evaluated a promotion- or prevention-framed text (highlighting ensuring the welfare of the environment or avoiding its destruction) and were then invited to donate part of their remuneration to pro-environmental or other charities. Participants who prioritized nature values evaluated the promotion-framed text more favorably the stronger their promotion focus was, but only endorsement of nature values predicted donations. This highlights the importance of measuring actual pro-environmental behavior, as positive message evaluations did not result in donations.
Factors Contributing to Posttraumatic Growth Following Bereavement
Authors: Ryan Angela P. , Ripley Jennifer
Published: December 2021

Multiple factors have been studied to determine their relationship to posttraumatic growth, with findings suggesting the importance of resiliency (Bensimon, 2012), social support (Tedeschi & Calhoun, 2004), event centrality (Taku et al., 2014), religious coping (Pargament et al., 2006), relationship to the deceased (Oginska–Bulik, 2015), and the circumstance of passing (Feigelman et al., 2009). This study investigated the relationship of these identified factors with posttraumatic growth in a sample of 165 bereaved individuals. Regression results indicated that the overall model predicted scores on posttraumatic growth ( R 2 = .473, R 2 adj = .456, F (5, 159) = 28.51, p < .001), with most robust effects found in social support ( β = .281), religious commitment ( β = .289), and event centrality ( β = .410). This indicates bereavement experiences can result in significant growth in individuals, particularly those who seek social support, identify the event as an essential part of their experience, and identify religion as an important aspect of their routine.
Finite-element simulation of semi-solid metal processing of tool steel encased in carbon steel
Authors: Paixão Ritter Eduardo , Tempel Stumpf Felipe
Published: December 2021

The semi-solid metal processing allows for the production of components with complex geometries allied to lower forming forces. In the case of X210Cr12 tool steel, one big advantage of semi-solid metal processing is that it produces a microstructure free of precipitated chromium carbides, resulting in higher resistance to cyclic stresses. However, the application of this process in steels is limited until now due to technical difficulties, such as high temperatures, the necessity of a precise control of temperature, and the narrow liquidus–solidus range. For that reason, a preliminary numerical assessment of the forming procedure is highly welcome, in order to reduce potential errors in the final component. In this paper, we propose a methodology for the numerical simulation of semi-solid metal processing in steel samples under hot compression. We show that it is possible to use multilinear hardening plasticity models whose only input are the flow stress curves of each material. We also show that it is mandatory that these experimental curves are obtained through tensile tests performed at the same temperature as the working/simulated component. To validate the methodology, a full-scale experiment is undertaken so that the deformed sample can be compared to the numerical results. It is concluded that the methodology is suited for the assessment of mechanical quantities during the finite-element analysis of semi-solid processing of steel.
Thermal, mechanical, and electrical properties of difunctional and trifunctional epoxy blends with nanoporous materials
Authors: J Ganesan , S Jeyadevi , S Siva Kaylasa Sundari , M Arunjunai Raj , G Pitchaimari , CT Vijayakumar
Published: December 2021

In the present study, the aim is to synthesize the particulate nanocomposites with difunctional and trifunctional epoxy blend as matrix and synthesized nanoporous materials as fillers. Organic/inorganic hybrid networks were prepared by the novel solvent free method. Viscoelastic, thermal, and electrical properties of di- and trifunctional epoxy and the effect of different nanoparticles in the particulate nanocomposites have been studied by dynamic mechanical analyzer, thermogravimetry (TGA), and dielectric strength. Epoxy mixed with different compositions of TGPAP and particulate nanocomposites by the addition of different types of nanomaterials shows higher storage modulus than the pure epoxy. The addition of TGPAP and nanofillers decreases the thermal stability of epoxy matrix. The evolved gas analysis (TG-FTIR) was also done in order to study the products formed during degradation. An increase in dielectric strength and impact strength (4%) was also observed in the particulate nanocomposites.
New Nutrient Intake Recommendations are Needed for Childbearing
Authors: Wynn Margaret , Wynn Arthur
Published: December 2021

British recommendations (DRVs and RNIs) include hardly any increments for pregnancy. British recommendations for protein are likely to cause unsatisfactory birthweight. What is the normal nutrient intake in pregnancy of healthy women? What evidence is there of special requirements for folate, iron, magnesium or iodine? New recommendations for nutrient intakes in pregnancy should be the responsibility of the Food Standards Agency and a survey of the diets of pregnant women is needed.
Fluid flow and heat transfer around square cylinder with dual splitter plates arranged at novel positions
Authors: Dey Prasenjit
Published: December 2021

In this paper, the effect of the dual splitter plates on the fluid flow and heat transfer characteristics around a regular square cylinder for a low Reynolds number flow ( Re = 100) is presented. The placement of the dual splitter plates is novel of its kind as these plates are located at the top and bottom surfaces of the cylinder rather than the conventional locations, that is, at the upstream and downstream of the cylinder. Here, two splitter plates of the same width ( w) with varying lengths and location are considered. A numerical investigation is performed using the open-source code, OpenFOAM. A base solver, icoFOAM is used after modifying the code by incorporating the energy equation in it. The primary wake bubble is found closer to the cylinder rear surface when the dual plates are introduced. It is also noticed that the separation angle and the recirculation length are smaller in the dual plates cases than that are in the cases without the dual plates. A mixed effect of the dual plates on the fluid forces is observed in the present study. A maximum reduction on the mean drag coefficient and root mean square of the lift coefficient is found as 3% and 24%, and maximum increment as 75% and 87%, respectively. However, a substantial enhancement on the overall heat transfer is noticed with the dual plates compared to that of the bare cylinder. A maximum enhancement of 40% is observed in the heat transfer around the square cylinder. In addition, thermal-hydraulic performance is calculated for finding the trade-off between the fluid forces and the heat transfer. The maximum value of thermal-hydraulic performance is found as 1.35 in the present study depending on the mean drag coefficient and 3.65 depending on the root mean square of the lift coefficient. Further, a novel combined thermo-fluid regime is defined for the square cylinder with dual splitter plates from which the location of the plates can be determined according to the demand on the heat transfer and fluid forces.
Notification of STI test results by text messaging: Why do patients refuse? Cross-sectional study in a Parisian sexual health centre
Authors: Charron Jalal , Troude Pénélope , de La Rochebrochard Elise , Segouin Christophe , Piron Prescillia
Published: December 2021

Text messaging has been used to notify patients of results after sexually transmitted infection (STI) testing. This study aimed to characterise the population who refused notification of results by short message services (SMS) and to explore their reasons for refusing. From January to August 2018, 1180 patients coming for STI testing in a Parisian sexual health centre were offered SMS notification of their results, completed a self-administered questionnaire and were included in the study. Factors associated with refusal of SMS notification were explored using logistic regression models. Reasons for refusal were analysed following a qualitative content analysis methodology. In the study population, 7.3% [95% CI 5.8–8.8] of patients refused SMS notification. In the multivariate logistic regression model, male gender and older age were associated with refusal, as were non-French nationality, having forgone health care for economic reasons and being unemployed. Qualitative analysis showed that preferring face-to-face medical contact (32%) and anxiety about the test result (29%) were the main reasons given by patients for refusal. Socially disadvantaged patients may have more limited access to technology and be less at ease using it in a health context. Preference for face-to-face medical contact may reflect the need for human support in vulnerable populations.
The political consequences of housing (un)affordability
Authors: Ansell Ben , Cansunar Asli
Published: December 2021

The enormous growth in house prices in Europe since the 1990s has led to increasing concerns about the affordability of housing for ordinary citizens. This article explores the relationship between housing affordability – house prices relative to incomes – and the demand for redistributive and housing policy, using data drawn from European and British social surveys and an analysis of British elections. It shows that, as unaffordability rises, citizens appear in aggregate to become less supportive of redistribution, interventionist housing policy and left-wing parties. However, this aggregate rise, driven by the predominance of homeowners in most European countries, masks a growing polarization in preferences between renters and owners in less affordable regions.
Positioning, Articulating, and Crafting Conceptual Articles on Entrepreneurship
Authors: Chrisman James J. , Fang Hanqing C. , Steier Lloyd
Published: December 2021

Conceptual articles are important for theory building but the special challenges of developing conceptual articles on entrepreneurship has not been fully considered. We begin to fill this gap by discussing the nature of conceptual articles on entrepreneurship, particularly those geared for publication in Entrepreneurship Theory and Practice. We introduce three dimensions of the entrepreneurship discipline—uniqueness, relevance, and multiplicity—and discuss how they can affect the positioning of conceptual articles and the articulation of their contribution. We also enumerate some basic principles for crafting good conceptual articles and present guidelines based on our discussion.
Behavior and modeling of post-heated circular concrete specimens repaired with fiber-reinforced polymer composites
Authors: Elhamnike Seyed Mehrdad , Abbaszadeh Rasoul , Razavinasab Vahid , Ziaadiny Hadi
Published: December 2021

Exposure of buildings to fire is one of the unexpected events during the life of the structure. The heat from the fire can reduce the strength of structural members, and these damaged members need to be strengthened. Repair and strengthening of concrete members by fiber-reinforced polymer (FRP) composites has been one of the most popular methods in recent years and can be used in fire-damaged concrete members. In this paper, in order to provide further data and information about the behavior of post-heated circular concrete columns confined with FRP composites, 30 cylindrical concrete specimens were prepared and subjected under four exposure temperatures of 300, 500, 700, and 900. Then, specimens were repaired by carbon fiber reinforced polymer composites and tested under axial compression. Results indicate that heating causes the color change, cracks, and weight loss of concrete. Also, with the increase of heating temperature, the shape of stress–strain curve of FRP-retrofitted specimens will change. Therefore, the main parts of the stress–strain curve such as ultimate stress and strain and the elastic modulus will change. Thus, a new stress–strain model is proposed for post-heated circular concrete columns confined by FRP composites. Results indicate that the proposed model is in a good agreement with the experimental data.
‘SKAM Italia did it again’. The multiple lives of a format adaptation from production to audience experience
Authors: Antonioni Stefania , Barra Luca , Checcaglini Chiara
Published: December 2021

SKAM Italia, the Italian version of the Norwegian SKAM format, was first released in Spring 2018 and has reached its fourth season in May 2020, overcoming several industrial struggles and slowly engaging an increasing, young and local audience. This article aims to integrate a production–distribution and reception perspective, showing how they mutually reinforce the series’ identity: the peculiarity of SKAM’s distribution system fostered the audience’s engagement, until its complicated production history brought the series to a more conventional circulation. Mutual exchanges between professionals and audiences on a global level are always counterbalanced by national negotiations, influencing the series’ life cycle.
Should Degree of Third Molar Eruption Influence Operative Management of Mandibular Angle Fractures? A Systematic Review
Authors: Kotha Vikas S. , de Ruiter Brandon J. , Knudsen M. Grace , Nicoleau Marvin , Davidson Edward H.
Published: December 2021

Study Design

Systematic review.

Objective

There is a growing trend toward evidence-based management of third molars in the fracture line of mandibular angle fractures (MAFs). This study aimed to differentiate MAF fixation complications by degree of third molar eruption and by extraction strategy in patients undergoing Champy fixation.

Methods

PubMed, EMBASE, OVID, SCOPUS, the Cochrane Library, and clinicaltrials.gov were queried through May 2020 for English-language publications for MAFs with third molar involvement for this systematic review. Bias was assessed using author-defined criteria. Relative risk (RR) of post-operative complications associated with extracted unerupted and retained partially erupted third molars (Group I) was calculated against controls of retained unerupted and extracted partially erupted third molars (Group II).

Results

Ten studies reported complications by eruption or extraction; however, only one study stratified complications by both eruption and extraction to meet inclusion criteria. The risk of bias was medium as only cases meeting defined follow-up were included. 73 cases (N) were included: 34 qualified for Group I and 39 for Group II. Quantitative synthesis of individual case data demonstrated significantly higher complication rate in Group I compared to Group II (23.5% vs 5.1%) (RR 4.6, 95% CI 1.04–20.1). No significant differences were observed between groups for infectious complications, mechanical complications, nonunion, or dehiscence. Reoperation was required significantly more often for Group I ( P = .043).

Conclusions

For MAFs involving the third molar, concomitant extraction of unerupted as well as retention of partially erupted third molars increases risk of complications with Champy fixation technique. For these patients, alternative strategies for fixation should be considered.
Exploring the Ethics of Implementation of Epigenomics Technologies in Cancer Screening: A Focus Group Study
Authors: Bunnik Eline M , Bolt Ineke LLE
Published: December 2021

New epigenomics technologies are being developed and used for the detection and prediction of various types of cancer. By allowing for timely intervention or preventive measures, epigenomics technologies show promise for public health, notably in population screening. In order to assess whether implementation of epigenomics technologies in population screening may be morally acceptable, it is important to understand – in an early stage of development – ethical and societal issues that may arise. We held 3 focus groups with experts in science and technology studies (STS) (n = 13) in the Netherlands, on 3 potential future applications of epigenomic technologies in screening programmes of increasing scope: cervical cancer, female cancers and ‘global’ cancer. On the basis of these discussions, this paper identifies ethical issues pertinent to epigenomics-based population screening, such as risk communication, trust and public acceptance; personal responsibility, stigmatisation and societal pressure, and data protection and data governance. It also points out how features of epigenomics (eg, modifiability) and changing concepts (eg, of cancer) may challenge the existing evaluative framework for screening programmes. This paper aims to anticipate and prepare for future ethical challenges when epigenomics technologies can be tested and introduced in public health settings.
Magnesiobermanite, MgMn3+2(PO4)2(OH)2⋅4H2O, the Mg analogue of bermanite: Description and crystal structure
Authors: Elliott Peter
Published: December 2021

Magnesiobermanite, MgMn3+2(PO4)2(OH)2⋅4H2O, is a new secondary phosphate mineral and the Mg analogue of bermanite found in a granitic pegmatite at the White Rock No.2 quarry situated in the Bimbowrie Conservation Park, South Australia, Australia. Magnesiobermanite occurs as aggregates of twinned, bladed to tabular crystals, up to 1.2 mm across. Individual crystals are up to 0.3 mm in length. The crystals are orange–red to brownish red, with a vitreous lustre and a salmon-pink streak. The mineral is brittle with a conchoidal fracture and a good cleavage on {100}. The mineral is biaxial (–), with α = 1.690(2), β = 1.719(2) and γ = 1.734(2) (white light). The calculated 2V is 70.4°. Electron microprobe analyses provided: MgO 9.59, Mn2O3 27.41, Fe2O3 8.84, Al2O3 0.18, P2O5 33.27, H2O 20.94, total 100.23 wt.%. The empirical formula (based on 14 O atoms) is: Mg1.02(Mn3+1.49Fe3+0.47Al0.02)1.98(PO4)2.01(OH)1.95⋅4.01H2O. Magnesiobermanite is monoclinic, space group P21, with the unit-cell parameters: a = 5.4215(11), b = 19.072(4), c = 5.3889(11) Å, β = 110.21(3)°, V = 522.89(18) Å3 and Z = 2. The crystal structure was refined to an R1 index of 2.43% based on for 3222 observed reflections with Fo > 4σ(Fo). Magnesiobermanite is isostructural with bermanite, Mn2+Mn3+2(PO4)2(OH)2⋅4H2O, from which it derives its name. The structure is based upon a sheet of the form [(M(OH)2(PO4)2] in the (010) plane. Sheets are linked in the b direction by [M3(H2O)4O2] octahedra and by hydrogen bonds.
Is there a role for anti-CD20 antibodies in CLL?
Authors: Shah Harsh R. , Stephens Deborah M.
Published: December 2021

Anti-CD20 monoclonal antibodies (mAbs) have revolutionized the treatment of chronic lymphocytic leukemia (CLL) by improving survival of patients with CLL in conjunction with chemotherapy. However, the novel targeted agents such as Bruton tyrosine kinase inhibitors (BTKis) and venetoclax have now mostly replaced chemotherapy in frontline treatment of CLL. Several clinical trials have been conducted to examine the role of anti-CD20 mAbs in combination with BTK inhibitors and venetoclax. Addition of rituximab to ibrutinib does not improve progression-free survival (PFS) of treatment-naive patients with CLL, possibly related to ibrutinib's antagonistic effect on anti-CD20 antibodies. Alternatively, addition of a glycoengineered anti-CD20 mAb obinutuzumab to a more selective BTKi acalabrutinib may improve PFS but does not improve overall survival of patients with CLL in the frontline setting, pending long-term follow-up. Thus, we suggest that the addition of an anti-CD20 mAb to a BTKi is of most benefit to patients with autoimmune cytopenia or rapidly progressive disease. In contrast to BTKis, combination of fixed-duration venetoclax and anti-CD20 mAb can induce deep remission with high rates of undetectable minimal residual disease, correlating with improved survival of patients with CLL in both frontline and relapsed/refractory settings. In this review, we discuss clinical trials of BTKis and venetoclax that have investigated the role of anti-CD20 mAbs in frontline and relapsed settings of CLL treatment. We also provide an algorithm suggesting how anti-CD20 mAbs may be incorporated in the treatment of patients with CLL, including specific scenarios.
Unexplained arterial thrombosis: approach to diagnosis and treatment
Authors: May Jori E. , Moll Stephan
Published: December 2021

Arterial thrombotic events in younger patients without a readily apparent etiology present significant diagnostic and management challenges. We present a structured approach to diagnosis with consideration of common causes, including atherosclerosis and embolism, as well as uncommon causes, including medications and substances, vascular and anatomic abnormalities, systemic disorders, and thrombophilias. We highlight areas of management that have evolved within the past 5 years, including the use of dual-pathway inhibition in atherosclerotic disease, antithrombotic therapy selection in embolic stroke of undetermined source and left ventricular thrombus, the role of closure of patent foramen ovale for secondary stroke prevention, and the thrombotic potential of coronavirus disease 2019 infection and vaccination. We conclude with a representative case to illustrate the application of the diagnostic framework and discuss the importance of consideration of bleeding risk and patient preference in determining the appropriate management plan.
Clinical trial considerations in sickle cell disease: patient-reported outcomes, data elements, and the stakeholder engagement framework
Authors: Badawy Sherif M.
Published: December 2021

Patients with sickle cell disease (SCD) have significant impairment in their quality of life across the life span as a consequence of serious disease burden with several SCD-related complications. A number of disease-modifying therapies are currently available, yet long-term clinical benefits in real-world settings remain unclear. Over the past few years, a number of important initiatives have been launched to optimize clinical trials in SCD in different ways, including: (1) established panels through a partnership between the American Society of Hematology (ASH) and the US Food and Drug Administration; (2) the ASH Research Collaborative SCD Clinical Trials Network; (3) the PhenX Toolkit (consensus measures for Phenotypes and eXposures) in SCD; and (4) the Cure Sickle Cell Initiative, led by the National Heart, Lung, and Blood Institute. Electronic patient-reported outcomes assessment is highly recommended, and patient-reported outcomes (PROs) should be evaluated in all SCD trials and reported using Standard Protocol Items Recommendations for Interventional Trials guidelines. Patient-centered outcomes research (PCOR) approaches and meaningful stakeholder engagement throughout the process have the potential to optimize the execution and success of clinical trials in SCD with considerable financial value. This article reviews several clinical trial considerations in SCD related to study design and outcomes assessment as informed by recent initiatives as well as patient-centered research approaches and stakeholder engagement. A proposed hematology stakeholder-engagement framework for clinical trials is also discussed.
Impaired myelopoiesis in congenital neutropenia: insights into clonal and malignant hematopoiesis
Authors: Warren Julia T. , Link Daniel C.
Published: December 2021

A common feature of both congenital and acquired forms of bone marrow failure is an increased risk of developing acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Indeed, the development of MDS or AML is now the major cause of mortality in patients with congenital neutropenia. Thus, there is a pressing clinical need to develop better strategies to prevent, diagnose early, and treat MDS/AML in patients with congenital neutropenia and other bone marrow failure syndromes. Here, we discuss recent data characterizing clonal hematopoiesis and progression to myeloid malignancy in congenital neutropenia, focusing on severe congenital neutropenia (SCN) and Shwachman-Diamond syndrome. We summarize recent studies showing excellent outcomes after allogenic hematopoietic stem cell transplantation for many (but not all) patients with congenital neutropenia, including patients with SCN with active myeloid malignancy who underwent transplantation. Finally, we discuss how these new data inform the current clinical management of patients with congenital neutropenia.
Management of hemolytic transfusion reactions
Authors: Hendrickson Jeanne E. , Fasano Ross M.
Published: December 2021

Delayed hemolytic transfusion reactions (DHTRs) in patients with sickle cell disease are underappreciated and potentially fatal. Patients with DHTRs typically have symptoms of pain or dark urine days to weeks following a red blood cell (RBC) transfusion. In instances of DHTRs with hyperhemolysis, the patient's hemoglobin (Hgb) may be significantly lower than it was pretransfusion, and the Hgb A may drop by more than 50%. In most cases, at least 1 RBC alloantibody and sometimes multiple RBC alloantibodies can be identified during the DHTR, with those antibodies presumably having fallen below the level of detection at the time of the implicated transfusion. However, in up to one-third of cases, no new RBC alloantibodies can be identified posttransfusion. Complement is increasingly being appreciated to play a role in DHTRs and hyperhemolysis, not only due to classic pathway activation (with complement fixed antibody bound to RBCs) but also due to alternative pathway activation (resulting in part from plasma free heme). As such, anti-C5 inhibition has recently been reported to be effective at mitigating hemolysis in the setting of some severe DHTRs. Transfusion avoidance during DHTRs is recommended if possible, with long-term transfusion support advice being less clear; for example, a history of a severe DHTR may lead to questions regarding the safety of transfusions prior to curative therapies such as stem cell transplantation or gene therapy. A better understanding of antibody-positive and antibody-negative DHTRs, including patient- or disease-specific risk factors, is necessary to improve transfusion safety.
Genetic insights into the regulatory pathways for continuous flowering in a unique orchid Arundina graminifolia
Authors: Ahmad Sagheer , Lu Chuqiao , Gao Jie , Ren Rui , Wei Yonglu , Wu Jieqiu , Jin Jianpeng , Zheng Chuanyuan , Zhu Genfa , Yang Fengxi
Published: December 2021

Background

Manipulation of flowering time and frequency of blooming is key to enhancing the ornamental value of orchids. Arundina graminifolia is a unique orchid that flowers year round, although the molecular basis of this flowering pattern remains poorly understood.

Results

We compared the A. graminifolia transcriptome across tissue types and floral developmental stages to elucidate important genetic regulators of flowering and hormones. Clustering analyses identified modules specific to floral transition and floral morphogenesis, providing a set of candidate regulators for the floral initiation and timing. Among candidate floral homeotic genes, the expression of two FT genes was positively correlated with flower development. Assessment of the endogenous hormone levels and qRT-PCR analysis of 32 pathway-responsive genes supported a role for the regulatory networks in floral bud control in A. graminifolia. Moreover, WGCNA showed that flowering control can be delineated by modules of coexpressed genes; especially, MEgreen presented group of genes specific to flowering.

Conclusions

Candidate gene selection coupled with hormonal regulators brings a robust source to understand the intricate molecular regulation of flowering in precious orchids.
Latent profile analysis of cognitive decline and depressive symptoms after intracerebral hemorrhage
Authors: Keins Sophia , Abramson Jessica R. , Castello Juan Pablo , Pasi Marco , Charidimou Andreas , Kourkoulis Christina , DiPucchio Zora , Schwab Kristin , Anderson Christopher D. , Gurol M. Edip , Greenberg Steven M. , Rosand Jonathan , Viswanathan Anand , Biffi Alessandro
Published: December 2021

Background

Cognitive impairment and depressive symptoms are highly prevalent after Intracerebral Hemorrhage (ICH). We leveraged Latent Profile Analysis (LPA) to identify profiles for cognitive decline and depression onset after ICH. We also investigated differences in clinical, genetic and neuroimaging characteristics across patients’ profiles.

Methods

We analyzed data from the ICH study conducted at Massachusetts General Hospital between January 1998 and December 2019. We collected information from electronical health records, follow-up interviews, CT and MRI imaging, and APOE genotype. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for cognitive decline and depression onset after ICH; 2) identify clinical, neuroimaging and genetic factors predicting individuals’ likelihood to express a specific profile.

Results

We followed 784 ICH survivors for a median of 45.8 months. We identified four distinct profiles in cognitive and depressive symptoms after ICH: low depression and dementia risk, early-onset depression and dementia, late-onset depression and dementia, high depression with low dementia risk. Cerebral small vessel disease severity and APOE genotype were specifically associated with the late-onset profile (both p < 0.05). Acute hematoma characteristics (size, intraventricular extension) and functional disability were specifically associated with the early-onset profile (all p < 0.05).

Conclusion

We identified four distinct profiles for cognitive and depressive symptoms after ICH, each displaying specific associations with individual patients’ clinical, genetic and neuroimaging data. These associations reflect separate biological mechanisms influencing dementia and depression risk after ICH. Our findings support employing LPA in future ICH studies, and is likely applicable to stroke survivors at large.
Reversible cerebral vasoconstriction syndrome with cardiac involvement during treatment for iron deficiency anemia: caser report
Authors: Oguchi Kenya , Fukushima Kazuhiro , Nakamura Akinori , Takei Yo-ichi
Published: December 2021

Background

The diagnosis and therapy of reversible cerebral vasoconstriction syndrome (RCVS) tends to focus on neurological symptoms, but less attention has been paid the occurrence of extracerebral lesion such as the myocardium.

Case presentation

A 40-year-old woman taking iron supplements for iron deficiency anemia due to menorrhagia had suffered from a thunderclap headache and seizure. Brain magnetic resonance imaging revealed high-intensity lesions bilaterally in the cerebellar and cerebral hemispheres. Her symptoms once subsided with steroids and anticonvulsant therapy; however, she experienced a severe headache again while bathing and was transferred to our hospital. Based on the clinical course and imaging data, she was diagnosed as having RCVS triggered by a rapid improvement of anemia. At the same time, she had cardiac involvement revealed by electro and echocardiographs despite without chest symptoms. After the administration of a calcium channel blocker and nitrite, her cerebral and cardiac involvements were rapidly improved.

Conclusions

The case presented RCVS with transient myocardial damage. With RCVS, we should always pay attention to the complication of extracerebral lesions.
The clinical effects of high-frequency oscillatory ventilation in the treatment of neonatal severe meconium aspiration syndrome complicated with severe acute respiratory distress syndrome
Authors: Yang Guang , Qiao Yunxia , Sun Xinxin , Yang Tiandan , Lv Aiying , Deng Min
Published: December 2021

Objective

To explore the efficacy and safety of high-frequency oscillatory ventilation (HFOV) in the treatment of severe meconium aspiration syndrome (MAS) complicated with severe acute respiratory distress syndrome (ARDS).

Methods

A total of 65 infants with severe MAS complicated with severe ARDS were included in the study. The clinical efficacy of treatment for the HFOV group (n = 31) and the conventional mechanical ventilation (CMV) group (n = 34) was retrospectively analysed. The partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), PaO2/fraction of inspired oxygen (FiO2), and oxygen index values before and at 6, 12, 24, 48, and 72 h after mechanical ventilation, the mechanical ventilation time, oxygen inhalation time, incidence of complications, and outcomes of the two groups were compared.

Results

At 6, 12, 24, and 48 h after mechanical ventilation, the PaO2 in the HFOV group was significantly higher than in the CMV group, while the PaCO2 in the HFOV group was significantly lower than in the CMV group (P < 0.05). At 6, 12, 24, 48, and 72 h after mechanical ventilation, PaO2/FiO2 in the HFOV group was significantly higher than in the CMV group, and the OI in the HFOV group was significantly lower than in the CMV group (P < 0.05). Mechanical ventilation time, oxygen inhalation time, and the incidence of air leakage were significantly lower in the HFOV than in the CMV group (P < 0.05).

Conclusions

Overall, HFOV can effectively improve lung ventilation and oxygenation function, shorten ventilator treatment time, and reduce the incidence rate of air leakage for neonatal MAS, making it a safe and effective treatment option.
Mortality by opioid poisoning in children and teenagers and opioid prescriptions
Authors: Cranfield Elise , Ashcroft Elizabeth , Forget Patrice
Published: December 2021

Background

No comparisons between mortality from opioids in children and teenagers and opioid prescription patterns have been made in England.

Aim

To investigate if an association exists between mortality rates from opioid poisoning in persons aged 19 years old and under and community opioid prescription in England.

Methods

A retrospective analysis was undertaken for 2016 to 2019, comparing community opioid prescriptions and mortality rates from opioid poisoning.

Results

The number of opioid prescriptions decreased over the study period (− 2.4%, p < 0.001). Most deaths due to opioid poisoning in children and teenagers were seen in those under one year old and those aged between 15 and 19 years old (Kruskal-Wallis: p = 0.12; Dunn’s test: p = 0.01). Deaths in all age ranges did not change significantly (Poisson Regression Analysis: p > 0.05).

Conclusion

Despite the reduction in community opioid prescriptions, there was no decrease in the number of deaths in children and teenagers due to opioid poisoning.
Long-term ambient PM2.5 exposure associated with cardiovascular risk factors in Chinese less educated population
Authors: Lin Jianfeng , Zheng Hua , Xia Peng , Cheng Xinqi , Wu Wei , Li Yang , Ma Chaochao , Zhu Guangjin , Xu Tao , Zheng Yali , Qiu Ling , Chen Limeng
Published: December 2021

Introduction

Long-term exposure to ambient air pollution is related to major cardiovascular risk factors including diabetes, hypertension, hyperlipidemia and overweight, but with few studies in high-concentration nations like China so far. We aimed to investigate the association between long-term exposure to ambient fine particulate matter (particles with an aerodynamic diameter ≤ 2.5 μm, PM2.5) and major cardiovascular risk factors in China.

Methods

Adult participants with selected biochemical tests were recruited from the Chinese Physiological Constant and Health Condition (CPCHC) survey conducted from 2007 to 2011. Gridded PM2.5 data used were derived from satellite-observed data with adjustment of ground-observed data. District-level PM2.5 data were generated to estimate the association using multivariate logistic regression model and generalized additive model.

Results

A total of 19,236 participants from the CPCHC survey were included with an average age of 42.8 ± 16.1 years, of which nearly half were male (47.0%). The annual average PM2.5 exposure before the CPCHC survey was 33.4 (14.8–53.4) μg/m3, ranging from 8.0 μg/m3 (Xiwuqi) to 94.7 μg/m3 (Chengdu). Elevated PM2.5 was associated with increased prevalence of hypertension (odds ratio (OR) =1.022, 95% confidence interval (95%CI): 1.001, 1.043) and decreased prevalence of overweight (OR = 0.926, 95%CI: 0.910, 0.942). Education significantly interacted with PM2.5 in association with all the interesting risk factors. Each 10 μg/m3 increment of PM2.5 was associated with increased prevalence of diabetes (OR = 1.118, 95%CI: 1.037, 1.206), hypertension (OR = 1.101, 95%CI: 1.056, 1.147), overweight (OR = 1.071, 95%CI: 1.030, 1.114) in participants with poor education, but not in well-educated population. PM2.5 exposure was negatively associated with hyperlipidemia in all participants (OR = 0.939, 95%CI: 0.921, 0.957). The results were robust in all the sensitivity analyses.

Conclusion

Association between long-term PM2.5 exposure and cardiovascular risk factors might be modified by education. PM2.5 was associated with a higher prevalence of diabetes, hypertension, and overweight in a less-educated population with time-expose dependency. Long-term exposure to PM2.5 might be associated with a lower prevalence of hyperlipidemia.
Physical activity levels after low anterior resection for rectal cancer: one-year follow-up
Authors: Asnong Anne , D’Hoore André , Wolthuis Albert , Van Molhem Yves , Van Geluwe Bart , Laenen Annouschka , Devoogdt Nele , De Groef An , De Vrieze Tessa , Van Calster Charlotte , Geraerts Inge
Published: December 2021

Background

Overall survival rates after rectal cancer have increased. Therefore, functional outcomes rightly deserve more interest. The aims of this study were to assess progression in total, sports, occupational and household physical activity levels of rectal cancer survivors, from preoperatively to 12 months after surgery/stoma closure and to explore predictive factors.

Methods

Multi-center prospective study with 125 patients who underwent low anterior resection for rectal cancer. The Flemish Physical Activity Computerized Questionnaire was completed concerning all physical activity levels at baseline (past preoperative year) and at 1, 4, 6 and 12 months after surgery/stoma closure. At these timepoints, questionnaires (LARS−/ COREFO-questionnaire) regarding bowel symptoms were also filled out. Results were analyzed using linear mixed models for repeated measures.

Results

Total physical activity levels up to 12 months remained significantly lower than preoperative. Occupational and sports physical activity levels remained significantly lower until 6 and 4 months postoperative, respectively. Predictive factors for decreased physical activity levels at a specific timepoint were: younger age and no stoma (total physical activity, 1 month), low/mid rectal tumor, no stoma, non-employed status (total, 4 months), higher COREFO-scores (occupational, 4 months) and non-employed status (total, 12 months). At all timepoints, lower COREFO-scores were associated with higher total physical activity levels; male gender and lower educational levels with higher occupational levels; younger age, normal BMI, employed status and adjuvant therapy with higher sports levels; and female gender, lower educational level and unemployed status with higher household levels.

Conclusions

One year after rectal cancer treatment, total physical activity levels were still not recovered. Rectal cancer patients, especially those at risk for decreased physical activity levels and with major bowel complaints, should be identified and guided to increase their activities.

Trial registration

This trial has been registered at Netherlands Trial Register (NTR6383, 23/01/2017).