bluuebunny/crossref_metadata_2025_split huggingface dataset:
The utility of lung ultrasound in COVID-19: A systematic scoping review
Authors: Trauer Michael M , Matthies Ashley , Mani Nick , McDermott Cian , Jarman Robert 
Published: August 2020

Introduction Lung ultrasound (LUS) has an established evidence base and has proven useful in previous viral epidemics. An understanding of the utility of LUS in COVID-19 is crucial to determine its most suitable role based on local circumstances. Method Online databases, specialist websites and social media platforms were searched to identify studies that explore the utility of LUS in COVID-19. Case reports and recommendations were excluded. Findings In total, 33 studies were identified which represent a rapidly expanding evidence base for LUS in COVID-19. The quality of the included studies was relatively low; however, LUS certainly appears to be a highly sensitive and fairly specific test for COVID-19 in all ages and in pregnancy. Discussion There may be LUS findings and patterns that are relatively specific to COVID-19; however, specificity may also be influenced by factors such as disease severity, pre-existing lung disease, operator experience, disease prevalence and the reference standard. Conclusion LUS is almost certainly more sensitive than chest radiograph for COVID-19 and has several advantages over computed tomography and real-time polymerase chain reaction. High-quality research is needed into various aspects of LUS including: diagnostic accuracy in undifferentiated patients; triage and prognostication; monitoring progression and guiding interventions; the persistence of residual LUS findings; inter-observer agreement and the role of contrast-enhanced LUS.
Activity measurement in pediatric chronic fatigue syndrome
Authors: Loiacono Bernardo , Sunnquist Madison , Nicholson Laura , Jason Leonard A 
Published: August 2020

Objectives Individuals with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) experience debilitating symptoms, including post-exertional malaise, an intensification of symptoms after physical or cognitive exertion. Previous studies found differences in the activity levels and patterns of activity among individuals with ME and CFS, compared to healthy controls; however, limited research exists on the activity levels of pediatric patients. The objective of this study was to examine differences in activity between healthy children and youth with ME and CFS. Methods The present study examines the objective (i.e., ActiGraphy) and self-reported levels of activity among children (ages 5 to 17) enrolled in a community-based study of pediatric CFS. Results Children with ME and CFS evidenced lower activity levels than healthy control children. Moreover, participants with ME and CFS evidenced increased nighttime activity and delayed initiation of daytime activity. Participants’ self-reported activity data significantly correlated with their ActiGraph data, suggesting that children with ME and CFS are able to accurately describe their activity level. Discussion This study highlights differences in activity level and diurnal/nocturnal activity patterns between healthy children and those with ME and CFS. These differences should be considered in identifying appropriate supports and accommodations for children with ME and CFS.
A rare case report of apixaban-induced lichenoid eruption
Authors: Patil Tanvi , Hanna Suzanne , Torre Wayne 
Published: August 2020

With recent increase in the use of direct oral anticoagulants (DOACs), several new cases of adverse drug reactions (ADRs) have been identified in pharmacovigilance surveys. These ADRs can result in significant mortality and morbidity if not identified and treated promptly. It is important for physicians to recognize that immunologically mediated delayed hypersensitivity reactions, although rare in occurrence, can have significant impact on patient’s quality of life. To the best of our knowledge, we report the first case of lichenoid eruption associated with apixaban. We further provide evidence of tolerance to rivaroxaban in the same patient. Plain language summary Apixaban-induced lichenoid eruption Well documented case reports, although providing evidence of probable causal relationship between a drug and specific adverse drug reactions (ADRs), can increase awareness amongst clinicians treating patients with direct oral anticoagulants (DOACs), especially with its rapid utilization. Rare ADRs are difficult to detect as clinical trials of DOACs lacked enough patient sample, making post-marketing reporting of such events important so both patients and clinicians can be vigilant to help with prompt recognition of such symptoms. We report the first case of lichenoid eruption hypersensitivity reaction associated with apixaban in patient with tolerance to rivaroxaban.
Vedolizumab is effective and safe in elderly inflammatory bowel disease patients: a binational, multicenter, retrospective cohort study
Authors: Cohen Nathaniel Aviv , Plevris Nikolas , Kopylov Uri , Grinman Anna , Ungar Bella , Yanai Henit , Leibovitzh Haim , Isakov Naomi Fliss , Hirsch Ayal , Ritter Einat , Ron Yulia , Shitrit Ariella Bar‐Gil , Goldin Eran , Dotan Iris , Horin Shomron Ben , Lees Charlie W , Maharshak Nitsan 
Published: August 2020

BackgroundImmune modulating therapies are associated with an increased risk of infections and malignancies. This is of particular concern in elderly inflammatory bowel disease patients. This study aims to compare the safety and efficacy of vedolizumab between young and elderly inflammatory bowel disease patients.MethodsA binational, multicentre, retrospective, cohort study was performed from 2015 to 2019. Patients who underwent treatment with vedolizumab and were followed for at least 14 weeks were studied. They were divided according to age into groups: 40 years or less or 60 years or older. Clinical and endoscopic responses at weeks 14 and 52 and infection development were compared between young and elderly inflammatory bowel disease patient groups.ResultsThere were 144 patients (82 Crohn’s disease and 62 ulcerative colitis) in the elderly cohort and 140 patients (83 Crohn’s disease and 57 ulcerative colitis) in the young cohort. The average age was 70.2 ± 7.3 years and 29.6 ± 5.7 years, respectively. Clinical and endoscopic responses were comparable between the groups (week 52 remission of Crohn’s disease: 40% vs. 35%, P  = 0.7; week 52 remission of ulcerative colitis: 48% vs. 51%, P  = 0.84). Previous anti‐tumour necrosis factor biological therapy was independently associated with poor clinical remission rates at week 52 (Crohn’s disease: odds ratio 0.23, 95% confidence interval 0.06–0.79; P  = 0.02 and ulcerative colitis: odds ratio 0.10 95% confidence interval 0.01–0.74; P  = 0.024). There were significantly more infections in the elderly cohort (2% vs. 12%, P  = 0.002), none of which were fatal.ConclusionsVedolizumab is equally effective in elderly and young inflammatory bowel disease patients. The findings of this study demonstrate an increased risk of infections among the elderly treated with vedolizumab, which may be related to their age and underlying diseases.
Prevalence and Type of Sexual Dysfunction in Female Patients Receiving Antidepressant Medications
Authors: Grover Sandeep , Kate Natasha , Mishra Eepsita , Avasthi Ajit 
Published: August 2020

Aim: To assess the prevalence and typology of sexual dysfunction in female patients receiving antidepressant medications using the Arizona Sexual Experience Scale (ASEX). Method: A cross-sectional design was employed. A total of 71 married women with various psychiatric disorders receiving antidepressants for at least 3 months’ were evaluated on ASEX, Brief Adherence Rating Scale, Medication Adherence Questionnaire, and Global Assessment of Functioning (GAF) scale. Subjects with a history of sexual dysfunction prior to psychotropic intake, menopause, severe interpersonal relationship problems with spouse, or chronic medical illness were excluded. Results: The study sample had the mean age of 37.35 (SD: 6.82) years. More than four-fifth (80.2%) of patients had sexual dysfunction as per the ASEX. Using a cutoff score of 4 or more to define sexual dysfunction in various domains, decreased desire was seen in 81.7%, reduced arousal was seen in 80.3%, poor vaginal lubrication was seen in 76.1%, reduced satisfaction was seen in 57.7%, and reduced ability to reach orgasm was seen in 50.7%. Despite this, few patients (13.3%) discussed their sexual dysfunction with their treating psychiatrist. Sexual dysfunction did not influence the medication adherence. Conclusions: Sexual dysfunction is quite prevalent in female patients receiving antidepressant medications; however, this is not adequately discussed by the patient or the treating psychiatrist.
Impact of gemtuzumab ozogamicin on MRD and relapse risk in patients with NPM1-mutated AML: results from the AMLSG 09-09 trial
Authors: Kapp-Schwoerer Silke , Weber Daniela , Corbacioglu Andrea , Gaidzik Verena I. , Paschka Peter , Krönke Jan , Theis Frauke , Rücker Frank G. , Teleanu Maria-Veronica , Panina Ekaterina , Jahn Nikolaus , Herzig Julia , Kubanek Lena , Schrade Anika , Göhring Gudrun , Fiedler Walter , Kindler Thomas , Schroeder Thomas , Mayer Karin T. , Lübbert Michael , Wattad Mohammed , Götze Katharina S. , Horst Heinz A. , Koller Elisabeth , Wulf Gerald , Schleicher Jan , Bentz Martin , Krauter Jürgen , Bullinger Lars , Krzykalla Julia , Benner Axel , Schlenk Richard F. , Thol Felicitas , Heuser Michael , Ganser Arnold , Döhner Hartmut , Döhner Konstanze 
Published: August 2020

Abstract
Monitoring of measurable residual disease (MRD) provides prognostic information in patients with Nucleophosmin1-mutated (NPM1mut) acute myeloid leukemia (AML) and represents a powerful tool to evaluate treatment effects within clinical trials. We determined NPM1mut transcript levels (TLs) by quantitative reverse-transcription polymerase chain reaction and evaluated the prognostic impact of NPM1mut MRD and the effect of gemtuzumab ozogamicin (GO) on NPM1mut TLs and the cumulative incidence of relapse (CIR) in patients with NPM1mut AML enrolled in the randomized phase 3 AMLSG 09-09 trial. A total of 3733 bone marrow (BM) samples and 3793 peripheral blood (PB) samples from 469 patients were analyzed. NPM1mut TL log10 reduction ≥ 3 and achievement of MRD negativity in BM and PB were significantly associated with a lower CIR rate, after 2 treatment cycles and at end of treatment (EOT). In multivariate analyses, MRD positivity was consistently revealed to be a poor prognostic factor in BM and PB. With regard to treatment effect, the median NPM1mut TLs were significantly lower in the GO-Arm across all treatment cycles, resulting in a significantly greater proportion of patients achieving MRD negativity at EOT (56% vs 41%; P = .01). The better reduction in NPM1mut TLs after 2 treatment cycles in MRD positive patients by the addition of GO led to a significantly lower CIR rate (4-year CIR, 29.3% vs 45.7%, P = .009). In conclusion, the addition of GO to intensive chemotherapy in NPM1mut AML resulted in a significantly better reduction in NPM1mut TLs across all treatment cycles, leading to a significantly lower relapse rate.
Neutrophils from hereditary hemochromatosis patients are protected from iron excess and are primed
Authors: Renassia Cyril , Louis Sabine , Cuvellier Sylvain , Boussetta Nadia , Deschemin Jean-Christophe , Borderie Didier , Bailly Karine , Poupon Joel , Dang Pham My-Chan , El-Benna Jamel , Manceau Sandra , Lefrère François , Vaulont Sophie , Peyssonnaux Carole 
Published: August 2020

AbstractIron is required for the oxidative response of neutrophils to allow the production of reactive oxygen species (ROS). However, neutrophil function may be severely altered in conditions of iron overload, as observed in chronically transfused patients. Therefore, a tight regulation of neutrophil iron homeostasis seems to be critical for avoiding iron toxicity. Hepcidin is the key iron regulator in organisms; however, no studies have investigated its role in maintaining neutrophil iron homeostasis or characterized neutrophil function in patients with hereditary hemochromatosis (HH), a common iron overload genetic disorder that results from a defect in hepcidin production. To explore these issues, we studied 2 mouse models of iron overload: an experimentally induced iron overload model (EIO), in which hepcidin is increased, and a genetic HH model of iron overload with a deletion of hepatic hepcidin. We found that iron-dependent increase of hepatic hepcidin results in neutrophil intracellular iron trapping and consecutive defects in oxidative burst activity. In contrast, in both HH mouse models and HH patients, the lack of hepcidin expression protects neutrophils from toxic iron accumulation. Moreover, systemic iron overload correlated with a surprising neutrophil priming and resulted in a more powerful oxidative burst. Indeed, important factors in neutrophil priming and activation, such as tumor necrosis factor α (TNF-α), VCAM-1, and ICAM-1 are increased in the plasma of HH patients and are associated with an increase in HH neutrophil phagocytosis capacity and a decrease in L-selectin surface expression. This is the first study to characterize neutrophil iron homeostasis and associated functions in patients with HH.
Biological and structural characterization of murine TRALI antibody reveals increased Fc-mediated complement activation
Authors: Zeeuw van der Laan Eveline A. N. , van der Velden Saskia , Bentlage Arthur E. H. , Larsen Mads D. , van Osch Thijs L. J. , Mok Juk Yee , Brasser Giso , Geerdes Dionne M. , Koeleman Carolien A. M. , Nouta Jan , Semple John W. , Porcelijn Leendert , van Esch Wim J. E. , Wuhrer Manfred , van der Schoot C. Ellen , Vidarsson Gestur , Kapur Rick 
Published: August 2020

Abstract
Transfusion-related acute lung injury (TRALI) remains a leading cause of transfusion-related deaths. In most cases, anti-leukocyte antibodies in the transfusion product trigger TRALI, but not all anti-leukocyte antibodies cause TRALI. It has been shown that the anti–major histocompatibility complex (MHC) class I antibody 34-1-2S (anti–H-2Kd) causes TRALI in BALB/c mice (MHC class I haplotype H-2Kd), whereas SF1.1.10 (anti–H-2Kd) does not. In C57BL/6 mice (MHC class I haplotype H-2Kb), TRALI only occurs when anti-MHC class I antibody AF6-88.5.5.3 (anti–H-2Kb) is administered together with a high dose of 34-1-2S. It remains unknown which specific antibody characteristics are responsible for eliciting TRALI. We therefore investigated several biological and structural features of 34-1-2S compared with other anti-MHC class I antibodies, which on their own do not cause TRALI: SF1.1.10 and AF6-88.5.5.3. No substantial differences were observed between the TRALI-causing 34-1-2S and the TRALI-resistant SF1.1.10 regarding binding affinity to H-2Kd. Regarding binding affinity to H-2Kb, only AF6-88.5.5.3 potently bound to H-2Kb, whereas 34-1-2S exhibited weak but significant cross-reactivity. Furthermore, the binding affinity to FcγRs as well as the Fc glycan composition seemed to be similar for all antibodies. Similar Fc glycosylation profiles were also observed for human TRALI-causing donor anti-HLA antibodies compared with human anti-HLA antibodies from control donors. 34-1-2S, however, displayed superior complement activation capacity, which was fully Fc dependent and not significantly dependent on Fc glycosylation. We conclude that TRALI induction is not correlated with Fab- and Fc-binding affinities for antigen and FcγRs, respectively, nor with the composition of Fc glycans; but increased Fc-mediated complement activation is correlated with TRALI induction.
Lymphangioleiomyomatosis: a clinical review
Authors: O'Mahony Anne M. , Lynn Evelyn , Murphy David J. , Fabre Aurelie , McCarthy Cormac 
Published: August 2020

Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease. There are two main types of LAM: sporadic, and LAM associated with the tuberous sclerosis complex (TSC), which is caused by mutations in theTSC1andTSC2genes. LAM is characterised by cystic lung disease resulting in progressive dyspnoea, renal angiomyolipomas and lymphatic complications. Pneumothorax occurs frequently (70%) and definitive management with pleurodesis is recommended as the risk of recurrence is high. Characteristic thin-walled cysts are seen on computed tomography and the presence of elevated serum levels of a vascular endothelial growth factor-D has good diagnostic specificity. Currently, no single clinical or serological factor has been shown to predict prognosis. However, over the past decade, significant advances in our understanding of the pathophysiology of LAM has led to improved recognition of this rare disease and identification of treatment options. Mechanistic target of rapamycin inhibitors slow the rate of lung function decline and can resolve chylous effusion and regress angiomyolipomas. Life expectancy in patients with LAM is favourable, with a mean transplant-free survival >20 years from the time of diagnosis. Continued advances in understanding the molecular basis of LAM will lead to improved therapeutic targets and the development of more robust prognostic indicators.Educational aimsTo illustrate the clinical features, common presentations and radiological features of LAMTo outline the diagnostic approach to LAM, including the role of VEGF-DTo review the current prognostic indicators in LAM, and outline the impact of lung function, hormonal status, VEGF-D and clinical presentation on outcomeTo inform clinicians on the management options for LAM both pharmacological and nonpharmacological
Sigmoid vaginoplasty in Mayer-Rokitansky-Kuster-Hauser syndrome
Authors: Amadou Magagi Ibrahim , Adamou Harissou , Oumarou Garba Souleymane , Halidou Maazou , Adakal Ousseini , Habou Oumarou , Abdoulaye Maman Bachir , Nayama Madi , Sani Rachid 
Published: August 2020

Abstract
Introduction
Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is characterized by congenital aplasia of the uterus and upper 2/3 of the vagina, with normal female secondary sexual characteristics and a normal karyotype (46, XX). The frequency is 1/4500–5000 female births. The aim of this study was to report the management of MRKH syndrome with sigmoid vaginoplasty.

Patients and method
This study included 4 patients recruited over a 4-year period from February 2016 to January 2019. MRKH syndrome was retained in the presence of normal secondary sexual characteristics with normal external genitalia associated with vaginal aplasia and uterine agenesis. The approach was a laparotomy and a perineal approach under general anesthesia. The procedure involved the removal of a sigmoidal colonic graft that was anastomosed with the vaginal dimple.

Results
The average age was 23 years. All patients had consulted for primary amenorrhea, infertility, and/or difficulties in sexual intercourse. The diagnosis of MRKH type 1 was retained in all patients. The average length of the vagina was 3.25 cm before surgery and 13.63 cm after surgery. The postoperative outcomes were uneventful in 3 patients. One patient developed anastomotic stenosis that was successfully treated with vaginal dilation for 2 weeks. The average postoperative follow-up was 30 months.

Conclusion
In the context of a low-resource setting, sigmoid transposition represents a good procedure to treat vaginal aplasia and restore a satisfactory sexual activity to patients with MRKH type 1.
Elucidating the fate of nanoparticles among key cell components of the tumor microenvironment for promoting cancer nanotechnology
Authors: Bromma Kyle , Bannister Aaron , Kowalewski Antonia , Cicon Leah , Chithrani Devika B. 
Published: August 2020

AbstractSuccessful integration of nanotechnology into the current paradigm of cancer therapy requires proper understanding of the interface between nanoparticles (NPs) and cancer cells, as well as other key components within the tumor microenvironment (TME), such as normal fibroblasts (FBs) and cancer-associated FBs (CAFs). So far, much focus has been on cancer cells, but FBs and CAFs also play a critical role: FBs suppress the tumor growth while CAFs promote it. It is not yet known how NPs interact with FBs and CAFs compared to cancer cells. Hence, our goal was to elucidate the extent of NP uptake, retention, and toxicity in cancer cells, FBs, and CAFs to further understand the fate of NPs in a real tumor-like environment. The outcome of this would guide designing of NP-based delivery systems to fully exploit the TME for a better therapeutic outcome. We used gold nanoparticles as our model NP system due to their numerous applications in cancer therapy, including radiotherapy and chemotherapy. A cervical cancer cell line, HeLa, and a triple-negative breast cancer cell line, MDA-MB-231 were chosen as cancer cell lines. For this study, a clinically feasible 0.2 nM concentration of GNPs was employed. According to our results, the cancer cells and CAFs had over 25- and 10-fold higher NP uptake per unit cell volume compared to FBs, respectively. Further, the cancer cells and CAFs had over 30% higher NP retention compared to FBs. There was no observed significant toxicity due to GNPs in all the cell lines studied. Higher uptake and retention of NPs in cancer cells and CAFs vs FBs is very important in promoting NP-based applications in cancer therapy. Our results show potential in modulating uptake and retention of GNPs among key components of TME, in an effort to develop NP-based strategies to suppress the tumor growth. An ideal NP-based platform would eradicate tumor cells, protect FBs, and deactivate CAFs. Therefore, this study lays a road map to exploit the TME for the advancement of “smart” nanomedicines that would constitute the next generation of cancer therapeutics.