bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-thinking benign inflammation of the lactating breast: Classification, prevention, and management
Authors: Douglas Pamela
Published: April 2022

Despite the known benefits of breastfeeding for both infant and mother, clinical support for problems such as benign inflammation of the lactating breast remain a research frontier. Breast pain associated with inflammation is a common reason for premature weaning. Multiple diagnoses are used for benign inflammatory conditions of the lactating breast which lack agreed or evidence-based aetiology, definitions, and treatment. This article is the second in a three-part series. This second review analyses the heterogeneous research literature concerning benign lactation-related breast inflammation from the perspectives of the mechanobiological model and complexity science, to re-think classification, prevention, and management of lactation-related breast inflammation. Benign lactation-related breast inflammation is a spectrum condition, either localized or generalized. Acute benign lactation-related breast inflammation includes engorgement and the commonly used but poorly defined diagnoses of blocked ducts, phlegmon, mammary candidiasis, subacute mastitis, and mastitis. End-stage (non-malignant) lactation-related breast inflammation presents as the active inflammations of abscess, fistula, and septicaemia, and the inactive condition of a galactocoele. The first preventive or management principle of breast inflammation is avoidance of excessively high intra-alveolar and intra-ductal pressures, which prevents strain and rupture of a critical mass of lactocyte tight junctions. This is achieved by frequent and flexible milk removal. The second preventive or management principle is elimination of the mechanical forces which result in high intra-alveolar pressures. This requires elimination of conflicting vectors of force upon the nipple and breast tissue during milk removal; avoidance of focussed external pressure applied to the breast, including avoidance of lump massage or vibration; and avoidance of other prolonged external pressures upon the breast. Three other key preventive or management principles are discussed. Conservative management is expected to be effective for most, once recommendations to massage or vibrate out lumps, which worsen micro-vascular trauma and inflammation, are ceased.
Impacto sanitario de la prohibición total de publicidades de tabaco en Argentina
Authors: Konfino Jonatan , Salgado María Victoria , Penko Joanne , Coxson Pamela , Fernández Alicia , Pichon-Riviere Andrés , Bibbins-Domingo Kirsten , Mejía Raúl
Published: April 2022

Health impact of the total ban on advertising of tobacco products

The objective was to estimate the health impact of the total ban on advertising of tobacco products in terms of avoided cardiovascular events in those over 35 years of age in Argentina.

The Cardiovascular Disease Policy Model (CVDPM) was used, which is a Markov simulation model used to represent and project mortality and morbidity due to cardiovascular disease (CVD) in the population aged 35 or over. It constitutes a demographic-epidemiological model, which represents the population between 35 and 95 years of age and uses a logistic regression model based on the Framingham equation to estimate the annual incidence of cardiovascular disease. We assumed that implementing a complete ban on the advertising of tobacco products would lead to a 9% reduction in tobacco consumption.

The complete ban on advertising could prevent 15,164 deaths over a period of 10 years, of which 2610 would be the result of coronary heart disease and 747 due to stroke. These reductions would mean an annual decrease of 0.46% of total deaths, 0.60% of deaths from coronary heart disease and 0.33% in deaths from stroke. In addition, during the same period, it would avoid 6630 acute myocardial infarctions and 2851 strokes (reductions of 1.35% and 0.40%, respectively).

We hope that these findings might contribute to the strengthening of sanitary tobacco control policies in Argentina based on the remarkable benefits of banning the advertising of tobacco products in full and in line with current global recommendations.
Cytotoxic Effect of Puya chilensis Collected in Central Chile
Authors: Echeverria-Echeverria César , Valderrama-Villarroel Aly , Ortega Marcelo , Contreras Rodrigo A. , Zúñiga Gustavo E. , Alvarado-Soto Leonor , Ramírez-Tagle Rodrigo
Published: April 2022

This study sought to evaluate the pharmacological activity of metabolites isolated from the dried and lyophilized ethanol extracts as well as other solvent fractions of the currently endangered Puya chilensis Molina (Chagual) by analyzing their effects on a human hepatocellular carcinoma (HCC) cell line. We identified several active metabolites from Chagual extracts and two, in particular, carnosol, were found in all the prepared fractions. In addition, Chagual exhibited considerable cytotoxicity against the cancer cell line used in this study, with a half-maximal inhibitory concentration (IC50) of 0.44 ± 0.11 and 0.27 ± 0.04 after a 72-hour treatment and, therefore, has the potential for further investigation as a source of candidate therapeutic agents.
An fsQCA Analysis of Qualified Immunity and Police Use of Force: An Applied Sociology Approach
Authors: Gran Søren
Published: April 2022

Police officers are expected to serve and protect civilians. Yet cases of police officers harming, sometimes killing, people they are expected to serve and protect have received renewed attention in the United States. Notable cases have led to protests, calls for reforms, and disputes about roles of police officers. This study employs Applied Sociology approaches to questions around reforms of policing in the United States. This study examines reforms to legal protections police enjoy through use of force and qualified immunity laws. Analyzing data for the 50 U.S. states and Washington, DC, this study examines whether legal protections police officers possess are associated with excessive use of force against civilians. This study finds that civilian killings by police tend to be higher in states whose governments are characterized as beyond civilian control. Where Republicans control state government and police officers enjoy broad protections, police killings of civilians tend to be higher. This study finds that racial conflict may be a powerful factor related to police killings of civilians. Applied Sociology demonstrates that reforms should concentrate on not only legal protections police enjoy but also societal structures shaping their efforts to serve and protect civilians.
Three-Dimensional-Printed Lesser Metatarsal Replacement: The First Case Report
Authors: Madi Naji S. , Chopra Aman , Parekh Selene G.
Published: April 2022

Different procedures have been reported for severe and recurrent lesser toes deformity. These included DuVries metatarsophalangeal joint arthroplasty, resection arthroplasty, partial proximal phalangectomy, syndactylization, or lesser toe amputation. In the presence of a failed metatarsal head resection, the surgeon is faced with limited salvage options including Hoffman procedure or lesser toe amputation. The 3D printing technology has allowed orthopaedic surgeons to expand the therapeutic arsenal to address challenging situations. We herein present the first case of 3D-printed second lesser metatarsal replacement performed after a failed second metatarsal head resection.

Level of Evidence: V
Charles Bonnet Syndrome in a Patient With Acute Glaucoma Following Carotid Endarterectomy
Authors: Huffer Andrew A. , Jung Hoon C. , Tang Gale L.
Published: April 2022

Acute neovascular glaucoma is an extremely rare complication following carotid artery revascularization that can lead to permanent vision loss. We describe an unusual case of acute glaucoma following carotid endarterectomy presenting with mechanical pupillary dilation and vivid visual hallucinations consistent with the Charles Bonnet Syndrome. This case highlights the importance of screening patients complaining of vision loss or eye pain for neovascular eye changes prior to carotid revascularization. These patients’ eye health should be closely monitored peri-operatively.
Race, Socioeconomic Status, and Mothers’ Parental Stress
Authors: Yan Hope Xu
Published: April 2022

Studies on parenting and mental health have documented both racial differences in mothers’ parental stress levels and mixed evidence on the impacts of mothers’ socioeconomic status (SES) on their parental stress. Less is known about how the association between mothers’ SES and parental stress varies by race, or to what extent this variation contributes to racial differences in mothers’ levels of parental stress. This study addresses these questions using data from the second wave of Early Childhood Longitudinal Study: 2010–2011 Kindergarten Class ( N = 8,548). The ordinary least squares (OLS) regression and Blinder-Oaxaca decomposition results show that compared with white and Asian mothers, low income and education have more detrimental impacts on black and Hispanic mothers’ feelings of parental stress. This racially diverse association between mothers’ SES and parental stress is an important reason why Asian mothers face higher parental stress than black and Hispanic mothers.
Does Proactive Personality Moderate the Relationship Between Servant Leadership and Psychological Ownership and Resilience?
Authors: Najam Usama , Mustamil Norizah Binti Mohd
Published: April 2022

Using the conservation of resource perspective, this study empirically tested the moderating role of follower proactive personality between servant leadership and follower positive outcomes (psychological resilience and ownership). Previous literature remained confined to the theories that highlights the positive impact of servant leadership on the followers, ignoring the contingency perspective. The positive outcomes of servant leadership may not be categorized as a generic remedy for every employee working under a servant leader as each individual perceived resource gain may vary. Data of 348 responses gathered from the higher education institute faculty members working in Pakistan’s public sector universities using a self-reported questionnaire. The results indicate that servant leadership along with follower proactive personality work as a key ingredient in developing positive follower resilience. This study also found that it is not servant leadership alone itself that is positive, but its influence on followers also affected by the proactive personality type of the followers.
Exploring Mindfulness and Leadership Development: Lessons Learnt Using Grounded Theory Through the Study of the Performing Arts
Authors: Babu Vimal , Kumar Amresh , Kumar Vipin
Published: April 2022

The article investigates mindfulness mechanisms and leadership attributes as reflected by performing artists. This qualitative study analyses major categories to develop a theoretical framework of mindful leadership development employing performing arts. The present study uses interpretivism to explore respondents’ experiences and unique phenomena. The grounded theory (GT) methodology aided in exploring grounded data and theory construction. Abstract core category ‘immense concentration and self-control’ captured the abstract and inclusive meaning as understood by the participants in this study. The qualitative coding analysis helped explore the data-driven abstract phenomena. Results of the present study exhibited that all performing artists require high concentration and self-control to exemplify mesmerizing Koodiyattam performing arts. Theoretical reflections on the relationships between the relevant categories are provided in depth. The connections of five major categories between mindfulness mechanisms, leadership attributes, motivation components, values and beliefs, and personality dispositions are particularly intriguing.
Perceived Listening Difficulties of Adult Cochlear-Implant Users Under Measures Introduced to Combat the Spread of COVID-19
Authors: Perea Pérez Francisca , Hartley Douglas E.H. , Kitterick Pádraig T. , Wiggins Ian M.
Published: April 2022

Following the outbreak of the COVID-19 pandemic, public-health measures introduced to stem the spread of the disease caused profound changes to patterns of daily-life communication. This paper presents the results of an online survey conducted to document adult cochlear-implant (CI) users’ perceived listening difficulties under four communication scenarios commonly experienced during the pandemic, specifically when talking: with someone wearing a facemask, under social/physical distancing guidelines, via telephone, and via video call. Results from ninety-four respondents indicated that people considered their in-person listening experiences in some common everyday scenarios to have been significantly worsened by the introduction of mask-wearing and physical distancing. Participants reported experiencing an array of listening difficulties, including reduced speech intelligibility and increased listening effort, which resulted in many people actively avoiding certain communication scenarios at least some of the time. Participants also found listening effortful during remote communication, which became rapidly more prevalent following the outbreak of the pandemic. Potential solutions identified by participants to ease the burden of everyday listening with a CI may have applicability beyond the context of the COVID-19 pandemic. Specifically, the results emphasized the importance of visual cues, including lipreading and live speech-to-text transcriptions, to improve in-person and remote communication for people with a CI.
Difficulty with Oral Health Complications in Adolescents with Developmental Disability and Obesity
Authors: Bhoopathi V. , Wells C. , Ramos-Gomez F. , Atchison K.A.
Published: April 2022

Introduction:

Developmental disabilities (DDs), obesity, and dental caries are highly prevalent health conditions among adolescents. Evidence indicates that a significant proportion of adolescents with DDs are obese, and those with obesity and dental caries share common risk factors.

Objective:

In this first-ever US-based cross-sectional national study, we assessed the likelihood of adolescents with DDs and obesity experiencing chronic difficulty with decayed teeth, toothaches, bleeding gums, and eating and swallowing due to a health condition among adolescents with DDs and obesity compared to adolescents with no DDs or obesity.

Methods:

For this secondary data analysis study, we used data of 68,942 adolescents aged 10 to 17 y from the 2016 through 2019 National Survey of Children’s Health. Weighted descriptive and bivariate analyses were conducted. Four multiple logistic regression models predicting chronic difficulty in the past 12 mo with decayed teeth, toothaches, bleeding gums, and eating and swallowing due to a health condition were conducted, controlling for other variables.

Results:

The adjusted odds ratio (aOR) of experiencing chronic difficulty in the past 12 mo for adolescents with no DDs or obesity was significantly lower for decayed teeth (aOR, 0.64; 95% confidence interval [CI], 0.51–0.80; P < 0.0001), toothaches (aOR, 0.43; 95% CI, 0.30–0.60; P < 0.0001), bleeding gums (aOR, 0.48; 95% CI, 0.33–0.70; P < 0.0001), and eating or swallowing due to a health condition (aOR, 0.34; 95% CI, 0.20–0.57; P < 0.0001) compared to adolescents with both DDs and obesity.

Conclusions:

Results from this study indicate that DD adolescents with obesity have more/greater impending oral health needs than adolescents with no DDs or obesity.

Knowledge Transfer Statement:

Results of this study highlight the high oral health needs and the chronic difficulty adolescents with developmental disabilities and obesity experience compared to adolescents without developmental disabilities and obesity. Targeted oral health policies and interventions that will promote oral health among this high-risk group are recommended.
Development of a Machine Learning Algorithm for Prediction of Complications and Unplanned Readmission Following Primary Anatomic Total Shoulder Replacements
Authors: Devana Sai K , Shah Akash A , Lee Changhee , Jensen Andrew R , Cheung Edward , van der Schaar Mihaela , SooHoo Nelson F
Published: April 2022

Background

The demand and incidence of anatomic total shoulder arthroplasty (aTSA) procedures is projected to increase substantially over the next decade. There is a paucity of accurate risk prediction models which would be of great utility in minimizing morbidity and costs associated with major post-operative complications. Machine learning is a powerful predictive modeling tool and has become increasingly popular, especially in orthopedics. We aimed to build a ML model for prediction of major complications and readmission following primary aTSA.

Methods

A large California administrative database was retrospectively reviewed for all adults undergoing primary aTSA between 2015 to 2017. The primary outcome was any major complication or readmission following aTSA. A wide scope of standard ML benchmarks, including Logistic regression (LR), XGBoost, Gradient boosting, AdaBoost and Random Forest were employed to determine their power to predict outcomes. Additionally, important patient features to the prediction models were indentified.

Results

There were a total of 10,302 aTSAs with 598 (5.8%) having at least one major post-operative complication or readmission. XGBoost had the highest discriminative power (area under receiver operating curve AUROC of 0.689) of the 5 ML benchmarks with an area under precision recall curve AURPC of 0.207. History of implant complication, severe chronic kidney disease, teaching hospital status, coronary artery disease and male sex were the most important features for the performance of XGBoost. In addition, XGBoost identified teaching hospital status and male sex as markedly more important predictors of outcomes compared to LR models.

Conclusion

We report a well calibrated XGBoost ML algorithm for predicting major complications and 30-day readmission following aTSA. History of prior implant complication was the most important patient feature for XGBoost performance, a novel patient feature that surgeons should consider when counseling patients.
Childhood neglect and its implications for physical health, neurobiology and development—A scoping review of the literature
Authors: Jackson Annette L , Frederico M. , Cleak H. , Perry B. D.
Published: April 2022

There is much evidence of the many risks posed by childhood neglect. A scoping review of the literature found 467 articles on 345 studies from 38 countries reporting a large number of problems for children and adults associated with childhood neglect. After describing the broader scoping review, this paper presents findings specific to physical health, neurobiology and development. Across different neglect sub-types, different populations and different research methods, the weight of research demonstrates substantial risk from neglect including, at the most extreme, fatal outcomes for children. Physical health problems associated with neglect cover many health areas including the cardiovascular, respiratory and central nervous systems for children and adults. Studies from neuroscience have also shown wide-ranging atypical neurobiological structures and networks following different neglect sub-types especially for children exposed to institutional neglect. Similarly, studies have reported many developmental outcomes associated with neglect especially related to cognitive development. Physical health, neurobiology and general development are interrelated in healthy childhood and in the presence or aftermath of childhood neglect.
Tailored isn't always better: Impact of standardized versus tailored training on intention to use measurement-based care
Authors: Kassab Hannah , Scott Kelli , Boyd Meredith R. , Puspitasari Ajeng , Endicott David , Lewis Cara C.
Published: April 2022

Background: Brief educational trainings are often used for disseminating and implementing evidence-based practices (EBPs). However, many accessible trainings are ubiquitously standardized. Tailored training focused on modifying individual or contextual factors that may hinder EBP implementation is recommended, but there is a dearth of research comparing standardized versus tailored training. This study sought to: (a) assess the impact of MBC training on clinician intention to use measurement-based care (MBC); (b) compare the effect of standardized versus tailored training on clinician intention to MBC; and (c) identify clinician-level predictors of intention. Methods: Clinicians ( n = 152) treating adult clients with depression at 12 community mental health clinics were randomized to either tailored or standardized MBC training. Clinic-specific barriers and facilitators were used to inform training content and structure tailoring. Linear mixed modeling tested the association between training condition and post-training intention to use MBC, as well as hypothesized individual-level predictors of post-training intention (e.g., age, gender). Results: Clinician intention pre- and post-training increased across training conditions ( B = 0.38, t = −5.95, df = 36.99, p < .01, Cohen's d = 0.58). Results of linear mixed modeling procedures suggest no significant difference in clinician intention between conditions post-training ( B = −0.03, SE = .19, p > .05, Cohen's d = .15). Only baseline intention emerged as a predictor of post-training intention ( B = 0.39, SE = .05, p < .05). Conclusions: These findings suggest the additional effort to tailor training may not yield incremental benefit over standardized training, at least in the short term. As a result, implementation efforts may be able to reserve time and finances for other elements of implementation beyond the training component.

Plain Language Summary

Educational training is a common approach for enhancing knowledge about research-supported mental health treatments. However, these trainings are often not tailored to meet the needs of the trainees, and there is insufficient evidence about whether tailoring might improve the impact of training compared to a one-size-fits-all, standard version. This study compared the impact of a tailored versus standard training on mental health clinician’s intentions to use measurement-based (MBC) care for monitoring treatment progress for clients with depression. Study results indicated that intention to use MBC improved for clinicians receiving both the tailored and standard training after training completion. There were no differences in intention to use MBC care when the two types of training were compared. These study findings suggest that tailoring, which may require substantial time and effort, may not be a necessary step to improve the short-term impact of educational trainings.
Case of an Exotic Skin and Soft Tissue Infection Associated with Cyclone Ockhi
Authors: Sivadasan Sreekumar , Reghukumar Aravind , Gurudas Athul , V. Sasidharan Kiran Kumar , Nair Sruti P.
Published: April 2022

Vibrio vulnificus is a halophilic marine gram-negative bacillus that is known to cause fulminant primary septicemia and complicated skin and soft tissue infections in humans. Vibrio vulnificus is referred to as flesh-eating bacteria. In the absence of timely detection and treatment, it results in sepsis with mortality of 50% and septic shock with mortality as high as 100%. Primary septicemia occurs following ingestion of contaminated seafood, and wound infections are acquired following exposure of open wounds to contaminated seawater. Early clinical suspicion and initiation of the appropriate antibiotics is essential to ensure good clinical outcome in case of Vibrio vulnificus septicemia. Here we report the case of a fisherman injured in cyclone Ockhi admitted to our hospital with lower limb cellulitis, who was diagnosed as Vibrio vulnificus wound infection. This case emphasizes the importance of history and clinical examination in antibiotic stewardship.
Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis
Authors: Wang ShengPeng , Wang Bianbian , Shi Yue , Möller Tanja , Stegmeyer Rebekka I. , Strilic Boris , Li Ting , Yuan Zuyi , Wang Changhe , Wettschureck Nina , Vestweber Dietmar , Offermanns Stefan
Published: April 2022

The extravasation of leukocytes is a critical step during inflammation that requires the localized opening of the endothelial barrier. This process is initiated by the close interaction of leukocytes with various adhesion molecules such as ICAM-1 on the surface of endothelial cells. Here we reveal that mechanical forces generated by leukocyte-induced clustering of ICAM-1 synergize with fluid shear stress exerted by the flowing blood to increase endothelial plasma membrane tension and to activate the mechanosensitive cation channel PIEZO1. This leads to increases in [Ca2+]i and activation of downstream signaling events including phosphorylation of tyrosine kinases sarcoma (SRC) and protein tyrosine kinase 2 (PYK2), as well as of myosin light chain, resulting in opening of the endothelial barrier. Mice with endothelium-specific Piezo1 deficiency show decreased leukocyte extravasation in different inflammation models. Thus, leukocytes and the hemodynamic microenvironment synergize to mechanically activate endothelial PIEZO1 and subsequent downstream signaling to initiate leukocyte diapedesis.
Prognostic impact ofDDX41germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study
Authors: Duployez Nicolas , Largeaud Laëtitia , Duchmann Matthieu , Kim Rathana , Rieunier Julie , Lambert Juliette , Bidet Audrey , Larcher Lise , Lemoine Jean , Delhommeau François , Hirsch Pierre , Fenwarth Laurène , Kosmider Olivier , Decroocq Justine , Bouvier Anne , Le Bris Yannick , Ochmann Marlène , Santagostino Alberto , Adès Lionel , Fenaux Pierre , Thomas Xavier , Micol Jean-Baptiste , Gardin Claude , Itzykson Raphael , Soulier Jean , Clappier Emmanuelle , Recher Christian , Preudhomme Claude , Pigneux Arnaud , Dombret Hervé , Delabesse Eric , Sébert Marie
Published: April 2022

DDX41 germline mutations (DDX41MutGL) are the most common genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia (AML). Recent reports suggest that DDX41MutGL myeloid malignancies could be considered as a distinct entity, even if their specific presentation and outcome remain to be defined. We describe here the clinical and biological features of 191 patients with DDX41MutGL AML. Baseline characteristics and outcome of 86 of these patients, treated with intensive chemotherapy in 5 prospective Acute Leukemia French Association/French Innovative Leukemia Organization trials, were compared with those of 1604 patients with DDX41 wild-type (DDX41WT) AML, representing a prevalence of 5%. Patients with DDX41MutGL AML were mostly male (75%), in their seventh decade, and with low leukocyte count (median, 2 × 109/L), low bone marrow blast infiltration (median, 33%), normal cytogenetics (75%), and few additional somatic mutations (median, 2). A second somatic DDX41 mutation (DDX41MutSom) was found in 82% of patients, and clonal architecture inference suggested that it could be the main driver for AML progression. DDX41MutGL patients displayed higher complete remission rates (94% vs 69%; P < .0001) and longer restricted mean overall survival censored at hematopoietic stem cell transplantation (HSCT) than 2017 European LeukemiaNet intermediate/adverse (Int/Adv) DDX41WT patients (5-year difference in restricted mean survival times, 13.6 months; P < .001). Relapse rates censored at HSCT were lower at 1 year in DDX41MutGL patients (15% vs 44%) but later increased to be similar to Int/Adv DDX41WT patients at 3 years (82% vs 75%). HSCT in first complete remission was associated with prolonged relapse-free survival (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88; P = .02) but not with longer overall survival (hazard ratio, 0.77; 95% confidence interval, 0.35-1.68; P = .5).
Determinants of long-term outcomes of splenectomy in pediatric autoimmune cytopenias
Authors: Pincez Thomas , Aladjidi Nathalie , Héritier Sébastien , Garnier Nathalie , Fahd Mony , Abou Chahla Wadih , Fernandes Helder , Dichamp Claire , Ducassou Stéphane , Pasquet Marlène , Bayart Sophie , Moshous Despina , Cheikh Nathalie , Paillard Catherine , Plantaz Dominique , Jeziorski Eric , Thomas Caroline , Guitton Corinne , Deparis Marianna , Marie Cardine Aude , Stephan Jean-Louis , Pellier Isabelle , Doré Eric , Benadiba Joy , Pluchart Claire , Briandet Claire , Barlogis Vincent , Leverger Guy , Leblanc Thierry
Published: April 2022

Splenectomy is effective in ∼70% to 80% of pediatric chronic immune thrombocytopenia (cITP) cases, and few data exist about it in autoimmune hemolytic anemia (AIHA) and Evans syndrome (ES). Because of the irreversibility of the procedure and the lack of predictions regarding long-term outcomes, the decision to undertake splenectomy is difficult in children. We report here factors associated with splenectomy outcomes from the OBS’CEREVANCE cohort, which prospectively includes French children with autoimmune cytopenia (AIC) since 2004. The primary outcome was failure-free survival (FFS), defined as the time from splenectomy to the initiation of a second-line treatment (other than steroids and intravenous immunoglobulins) or death. We included 161 patients (cITP, n = 120; AIHA, n = 19; ES, n = 22) with a median (minimum-maximum) follow-up of 6.8 years (1.0-33.3) after splenectomy. AIC subtype was not associated with FFS. We found that immunopathological manifestations (IMs) were strongly associated with unfavorable outcomes. Diagnosis of an IM before splenectomy was associated with a lower FFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.21-0.72, P = .003, adjusted for AIC subtype). Diagnosis of an IM at any timepoint during follow-up was associated with an even lower FFS (HR, 0.22; 95% CI, 0.12-0.39; P = 2.8 × 10−7, adjusted for AIC subtype) as well as with higher risk of recurrent or severe bacterial infections and thrombosis. In conclusion, our results support the search for associated IMs when considering a splenectomy to refine the risk-benefit ratio. After the procedure, monitoring IMs helps to identify patients with higher risk of unfavorable outcomes.
Platelet activation by SARS-CoV-2 implicates the release of active tissue factor by infected cells
Authors: Puhm Florian , Allaeys Isabelle , Lacasse Emile , Dubuc Isabelle , Galipeau Yannick , Zaid Younes , Khalki Loubna , Belleannée Clemence , Durocher Yves , Brisson Alain R. , Wolberg Alisa S. , Langlois Marc-André , Flamand Louis , Boilard Eric
Published: April 2022

Platelets are hyperactivated in coronavirus disease 2019 (COVID-19). However, the mechanisms promoting platelet activation by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not well understood. This may be due to inherent challenges in discriminating the contribution of viral vs host components produced by infected cells. This is particularly true for enveloped viruses and extracellular vesicles (EVs), as they are concomitantly released during infection and share biophysical properties. To study this, we evaluated whether SARS-CoV-2 itself or components derived from SARS-CoV-2-infected human lung epithelial cells could activate isolated platelets from healthy donors. Activation was measured by the surface expression of P-selectin and the activated conformation of integrin αIIbβ3, degranulation, aggregation under flow conditions, and the release of EVs. We find that neither SARS-CoV-2 nor purified spike activates platelets. In contrast, tissue factor (TF) produced by infected cells was highly potent at activating platelets. This required trace amounts of plasma containing the coagulation factors FX, FII, and FVII. Robust platelet activation involved thrombin and the activation of protease-activated receptor (PAR)-1 and -4 expressed by platelets. Virions and EVs were identified by electron microscopy. Through size-exclusion chromatography, TF activity was found to be associated with a virus or EVs, which were indistinguishable. Increased TF messenger RNA (mRNA) expression and activity were also found in lungs in a murine model of COVID-19 and plasma of severe COVID-19 patients, respectively. In summary, TF activity from SARS-CoV-2–infected cells activates thrombin, which signals to PARs on platelets. Blockade of molecules in this pathway may interfere with platelet activation and the coagulation characteristic of COVID-19.
RODAN: a fully convolutional architecture for basecalling nanopore RNA sequencing data
Authors: Neumann Don , Reddy Anireddy S. N. , Ben-Hur Asa
Published: April 2022

Background

Despite recent progress in basecalling of Oxford nanopore DNA sequencing data, its wide adoption is still being hampered by its relatively low accuracy compared to short read technologies. Furthermore, very little of the recent research was focused on basecalling of RNA data, which has different characteristics than its DNA counterpart.

Results

We fill this gap by benchmarking a fully convolutional deep learning basecalling architecture with improved performance compared to Oxford nanopore’s RNA basecallers.

Availability

The source code for our basecaller is available at: https://github.com/biodlab/RODAN.
Identification of novel PHD-finger genes in pepper by genomic re-annotation and comparative analyses
Authors: Guk Ji-Yoon , Jang Min-Jeong , Kim Seungill
Published: April 2022

Background

The plant homeodomain (PHD)-finger gene family that belongs to zinc-finger genes, plays an important role in epigenetics by regulating gene expression in eukaryotes. However, inaccurate annotation of PHD-finger genes hinders further downstream comparative, evolutionary, and functional studies.

Results

We performed genome-wide re-annotation in Arabidopsis thaliana (Arabidopsis), Oryza sativa (rice), Capsicum annuum (pepper), Solanum tuberosum (potato), and Solanum lycopersicum (tomato) to better understand the role of PHD-finger genes in these species. Our investigation identified 875 PHD-finger genes, of which 225 (26% of total) were newly identified, including 57 (54%) novel PHD-finger genes in pepper. The PHD-finger genes of the five plant species have various integrated domains that may be responsible for the diversification of structures and functions of these genes. Evolutionary analyses suggest that PHD-finger genes were expanded recently by lineage-specific duplication, especially in pepper and potato, resulting in diverse repertoires of PHD-finger genes among the species. We validated the expression of six newly identified PHD-finger genes in pepper with qRT-PCR. Transcriptome analyses suggest potential functions of PHD-finger genes in response to various abiotic stresses in pepper.

Conclusions

Our data, including the updated annotation of PHD-finger genes, provide useful information for further evolutionary and functional analyses to better understand the roles of the PHD-finger gene family in pepper.
Genome-wide analysis and functional characterization of CHYR gene family associated with abiotic stress tolerance in bread wheat (Triticum aestivum L.)
Authors: Liu Hao , Yang Wenbo , Zhao Xingli , Kang Guozhang , Li Na , Xu Huawei
Published: April 2022

Background

CHY zinc-finger and RING finger (CHYR) proteins have been functionally characterized in plant growth, development and various stress responses. However, the genome-wide analysis was not performed in wheat.

Results

In this study, a total of 18 TaCHYR genes were identified in wheat and classified into three groups. All TaCHYR genes contained CHY-zinc finger, C3H2C3-type RING finger and zinc ribbon domains, and group III members included 1–3 hemerythrin domains in the N-terminus regions. TaCHYR genes in each group shared similar conserved domains distribution. Chromosomal location, synteny and cis-elements analysis of TaCHYRs were also analyzed. Real-time PCR results indicated that most of selected 9 TaCHYR genes exhibited higher expression levels in leaves during wheat seedling stage. All these TaCHYR genes were up-regulated after PEG treatment, and these TaCHYRs exhibited differential expression patterns in response to salt, cold and heat stress in seedling leaves. The growth of yeast cells expressing TaCHYR2.1, TaCHYR9.2 and TaCHYR11.1 were inhibited under salt and dehydration stress. Moreover, gene ontology (GO) annotation, protein interaction and miRNA regulatory network of TaCHYR genes were analyzed.

Conclusions

These results increase our understanding of CHYR genes and provide robust candidate genes for further functional investigations aimed at crop improvement.
Higher chronic stress and less satisfaction with GP communication in migrants with unemployment experience: data from the representative German DEGS1 and the GPCare-1 study
Authors: Offenberg Luisa K. , Sommer Samira T. , Schmidt Manuela , Kasten Stefanie , Bockheim Florian , Gavrilov Boris , Hunzelar Carmen , Ikar Nur , Oberholz Maja P. S. , Paños-Willuhn Joana L. , Weltermann Birgitta
Published: April 2022

Background

The impact of unemployment on health is well studied. However, information on associations of unemployment, migration background and general practitioner-patient communication is scarce.

Methods

Data from the representative German Health Interview and Examination Survey for Adults (DEGS1) of individuals in working age (n = 5938) were analysed stratified by unemployment and migration background. Using official weighting factors, the prevalence of chronic stress, having ≥1 chronic disease, having a GP and GP visits in the last 12 months was determined. Multivariate regression models were analysed for associations between unemployment, migration background, and other socio-demographic characteristics with GP visits and chronic stress. Data from the General Practice Care-1 (GPCare-1) study (n = 813 patients) were analysed for differences in patient-physician communication between unemployed with and without migration background. Reverse proportional odds models were estimated for associations of unemployment and migration background with physician-patient communication.

Results

In the DEGS1, 21.5% had experienced unemployment (n = 1170). Of these, 31.6% had a migration background (n = 248). Compared to unemployed natives, unemployed with migration background had higher chronic stress (mean: 14.32 vs. 13.13, p = 0.02), while the prevalence of chronic disease was lower (21.7% vs. 30.2%, p = 0.03). They were less likely to have a GP (83.6% vs. 90%, p = 0.02), while GP visits were similar (mean: 3.7 vs. 3.3, p = 0.26). Migration background and unemployment experience were not associated with GP visits, while both factors were significantly associated with higher chronic stress (both: p < 0.01). In GPCare-1, 28.8% had ever experienced unemployment (n = 215). Of these, 60 had a migration background (28.6%). The unemployed with migration background reported less frequently that the GP gives them enough space to describe personal strains (46.5% vs. 58.2%; p = 0.03), and that their problems are taken very seriously by their GP (50.8% vs. 73.8%; p = 0.04). In multivariate analyses, migration background showed a lower probability of having enough space to describe personal strains and feeling that problems were taken very seriously.

Conclusion

Unemployment experience and migration background were associated with higher chronic stress. Only migration background was associated with less satisfaction regarding physician-patient communication.
Low serum free triiodothyronineis level predicts worse outcome of patients with severe fever with thrombocytopenia syndrome
Authors: Wang Li , Liu Youde , Yu Haifeng , Ding Kun , Zou Zhiqiang
Published: April 2022

Background

Severe fever with thrombocytopenia syndrome (SFTS) caused by phlebovirus results in neuropsychiatric symptoms, multiorgan dysfunction and significant mortality. We aimed to evaluate the thyroid function in SFTS patients, elucidate its association with neuropsychiatric manifestations, disease severity, and prognosis, retrospectively.

Methods

Serum levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were compared between survivors and non-survivors, between those with and without nervous symptoms at baseline, and at baseline and remission. Logistic regression analysis was utilized to determine independent risk factors for mortality. A risk model based on risk factors was constructed and its prognostic value was evaluated by receiver operating characteristic (ROC) curve.

Results

A total of 207 SFTS cases with thyroid function data enrolled from January 2016 to January 2020 were included with 34 patients (16.4%) died. Baseline serum levels of FT3, TSH (p < 0.001), and FT3/FT4 ratio (p < 0.05) were significantly decreased in nonsurvivors than in survivors. Prevalence of low serum FT3 in nonsurvivors (81.8%) was greater than in survivors (41.3%). FT3 level (p < 0.001) was markedly reduced in patients with central neurological symptoms than those without. FT3 and FT4 levels were increased in remission than at baseline (p < 0.001). Logistic regression analysis showed that age (OR 0.92, 95% CI 0.868–0.958) and serum FT3 level (OR 3.055, 95% CI 1.494–6.248) were the independent risk factors for mortality. A risk model based on age and FT3 had a high predictive value for mortality (AUC = 0.818, 95% CI 0.795–0.868) at a cutoff value of > 3.39.

Conclusions

Low serum FT3 level was associated with a worse outcome of SFTS patients.
Preconception leisure-time physical activity and family history of stroke and myocardial infarction associate with preterm delivery: findings from a Norwegian cohort
Authors: Engen Tone , Owe Katrine Mari , Horn Julie , Sulo Gerhard , Næss Øyvind Erik , Juliusson Petur Benedikt , Morken Nils-Halvdan , Egeland Grace Margrethe
Published: April 2022

Background

Preterm birth poses short and long-term health consequences for mothers and offspring including cardiovascular disease sequelae. However, studies evaluating preexisting family history of cardiovascular disease and risk factors, such as physical activity, as they relate prospectively to risk of delivering preterm are lacking.

Objectives

To evaluate whether preconception past-year weekly leisure-time physical activity or a family history of stroke or of myocardical infarction prior to age 60 years in first degree relatives associated, prospectively, with preterm delivery.

Design

Cohort study. Baseline data from Cohort Norway (1994–2003) health surveys were linked to the Medical Birth Registry of Norway for identification of all subsequent births (1994–2012). Logistic regression models provided odds ratios (OR) and 95% confidence intervals (CI) for preterm delivery (< 37 weeks gestation); multinomial logistic regression provided OR for early preterm (< 34 weeks) and late preterm (34 through to end of 36 weeks gestation) relative to term deliveries.

Results

Mean (SD) length of time from baseline health survey participation to delivery was 5.6 (3.5) years. A family history of stroke associated with a 62% greater risk for late preterm deliveries (OR 1.62; CI 1.07–2.47), while a family history of myocardial infarction associated with a 66% greater risk of early preterm deliveries (OR 1.66; CI 1.11–2.49). Sensitivity analyses, removing pregnancies complicated by hypertensive disorders of pregnancy, diabetes mellitus, and stillbirth deliveries, gave similar results. Preconception vigorous physical activity of three or more hours relative to less than 1 h per week associated with increased risk of early preterm delivery (OR 1.52; 95% CI 1.01–2.30), but not late or total preterm deliveries. Light physical activity of three or more hours per week relative to less activity prior to pregnancy was not associated with early, late, or total preterm deliveries.

Conclusions

Results suggest that family history of cardiovascular disease may help identify women at risk for preterm delivery. Further, research is needed regarding preconception and very early pregnancy vigorous physical activity and associated risks.
Survival outcomes in endometrial cancer patients according to diabetes: a systematic review and meta-analysis
Authors: McVicker Lauren , Cardwell Christopher R. , Edge Lauren , McCluggage W Glenn , Quinn Declan , Wylie James , McMenamin Úna C.
Published: April 2022

Background

Diabetes is an established risk factor for endometrial cancer development but its impact on prognosis is unclear and epidemiological studies to date have produced inconsistent results. We aimed to conduct the first systematic review and meta-analysis to compare survival outcomes in endometrial cancer patients with and without pre-existing diabetes.

Methods

We conducted a systematic search of MEDLINE, EMBASE and Web of Science databases up to February 2022 for observational studies that investigated the association between pre-existing diabetes and cancer-specific survival in endometrial cancer patients. Secondary outcomes included overall survival and progression or recurrence-free survival. Quality assessment of included studies was undertaken using the Newcastle–Ottawa Scale and a random-effects model was used to produce pooled hazard ratios (HRs) and 95% confidence intervals (CIs). (PROSPERO 2020 CRD42020196088).

Results

In total, 31 studies were identified comprising 55,475 endometrial cancer patients. Pooled results suggested a worse cancer-specific survival in patients with compared to patients without diabetes (n = 17 studies, HR 1.15, 95% CI 1.00–1.32, I2 = 62%). Similar results were observed for progression or recurrence-free survival (n = 6 studies, HR 1.23, 95% CI 1.02–1.47, I2 = 0%) and for overall survival (n = 24 studies, HR 1.42, 95% CI 1.31–1.54, I2 = 46%).

Conclusion

In this systematic review and meta-analysis, we show that diabetes is associated with a worse cancer-specific and overall survival in endometrial cancer patients.
Baseline soluble MICA levels act as a predictive biomarker for the efficacy of regorafenib treatment in colorectal cancer
Authors: Arai Jun , Otoyama Yumi , Fujita Ken-ichi , Goto Kaku , Tojo Masayuki , Katagiri Atsushi , Nozawa Hisako , Kubota Yutaro , Takahashi Takehiro , Ishida Hiroo , Tsunoda Takuya , Matsumoto Natsumi , Ogawa Keita , Nakagawa Ryo , Muroyama Ryosuke , Kato Naoya , Yoshida Hitoshi
Published: April 2022

Background

To evaluate the effect of regorafenib on soluble MHC class I polypeptide-related sequence A (MICA) (sMICA) level in vitro. In addition, we clinically examined whether its plasma levels were associated with regorafenib activity in terms of progression-free survival (PFS) in patients with CRC.

Methods

Human CRC cell line HCT116 and HT29 cells were treated with regorafenib and its pharmacologically active metabolites, M2 or M5 at the same concentrations as those in sera of patients. We also examined the sMICA levels and the area under the plasma concentration–time curve of regorafenib, M2 and M5.

Results

Regorafenib, M2, and M5 significantly suppressed shedding of MICA in human CRC cells without toxicity. This resulted in the reduced production of sMICA. In the clinical examination, patients with CRC who showed long median PFS (3.7 months) had significantly lower sMICA levels than those with shorter median PFS (1.2 months) (p = 0.045).

Conclusions

MICA is an attractive agent for manipulating the immunological control of CRC and baseline sMICA levels could be a predictive biomarker for the efficacy of regorafenib treatment.