bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Transfer Learning-Based COVID-19 Prediction Using Chest X-Rays
Authors: Kumar Saurabh , Mishra Shweta , Singh Sunil Kumar
Published: October 2021

The novel coronavirus disease (COVID-19) is spreading very rapidly across the globe because of its highly contagious nature and is declared as a pandemic by the World Health Organization (WHO). Scientists are endeavouring to ascertain the drugs for its efficacious treatment. Because, until now, no full-proof drug is available to cure this deadly disease. Therefore, identifying COVID-19 positive people and quarantining them can be an effective solution to control its spread. Many machine learning and deep learning techniques are being used quite effectively to classify positive and negative cases. In this work, a deep transfer learning-based model is proposed to classify the COVID-19 cases using chest X-rays or CT scan images of infected persons. The proposed model is based on the ensembling of DenseNet121 and SqueezeNet1.0, which is named as DeQueezeNet. The model can extract the importance of various influential features from the X-ray images, which are effectively used to classify the COVID-19 cases. The performance study of the proposed model depicts its effectiveness in terms of accuracy and precision. A comparative study has also been done with the recently published works, and it is observed that the performance of the proposed model is significantly better.
Synergy Versus Trade-Off: The Influence of National Philanthropic Environment and Industry on the Relationship Between Research and Development and Corporate Social Responsibility
Authors: Randrianasolo Arilova A. , Semenov Alexey V.
Published: October 2021

International marketing research has demonstrated that research and development (R&D) and corporate social responsibility (CSR) are firm capabilities that can lead to competitive advantages in the international marketplace. A synergy versus trade-off dilemma on the R&D–CSR relationship has emerged as an important topic in the literature. The synergy approach suggests a positive link between R&D and CSR, whereas the trade-off approach suggests a negative link. The authors employ the resource-, institution-, and industry-based views to clarify this dilemma by examining two moderators at the country and industry levels. The authors envision that home-country national philanthropic environment (NPE) influences whether managers should take synergy or trade-off approach because NPE reflects the institutional pressures for firms to be more philanthropic. Further, because research finds that CSR differs between manufacturing and service firms, this industry categorization is hypothesized to moderate the effects of NPE on the R&D–CSR relationship. Estimating a hierarchical linear model with a sample of 888 firms across 15 countries, the authors show that in high-NPE countries, there is an R&D–CSR synergy, and in low-NPE countries, there is a trade-off. Furthermore, these relationships are relevant only within service industries rather than manufacturing industries.
Why People Who Know Less Think They Know about COVID-19: Evidence from US and Singapore
Authors: Lee Sangwon , Yamamoto Masahiro , Tandoc Edson C.
Published: October 2021

This study explores the effects of traditional media and social media on different types of knowledge about COVID-19. We also explore how surveillance motivation moderates the relationship between media use and different types of knowledge. Based on cross-national data from Singapore and the United States, we find that news seeking via social media is negatively related to factual knowledge and positively related to subjective knowledge and knowledge miscalibration. News seeking via traditional media is not significantly related to factual knowledge. Although the main effects are highly consistent across the two countries, we find some different interaction patterns across these countries.
Write Your Own Luck Campaign: Pentel’s Successful Advertising Strategy Based on Superstitious Beliefs in Thailand
Authors: Chinchanachokchai Punjaporn , Chinchanachokchai Sydney
Published: October 2021

The Pentel case study exhibits a success case of a global firm’s ability to incorporate cultural-specific values into an advertising campaign. Pentel used superstitious beliefs in the Thai culture to create the Write Your Own Luck campaign. The company launched a limited pen collection designed to be carried as lucky charms. Each pen version represented a unique type of luck it brought to its user. The campaign targeted Thai teens who were heavy users of social media. The campaign was launched through offline and online channels and received significant attention and awareness from the target audience. This case study represents a campaign that incorporates cultural beliefs and values of local consumers into an effective advertising campaign. The company achieved its goal of raising brand awareness and online engagement among the target audience.
Efficacy of oclacitinib for the control of feline atopic skin syndrome: correlating plasma concentrations with clinical response
Authors: Carrasco Isaac , Ferrer Lluis , Puigdemont Anna
Published: October 2021

Objectives

The aim of this study was to assess the efficacy of a new therapeutic regimen of oclacitinib for the control of feline atopic skin syndrome (FASS) and to correlate plasma levels of this drug with clinical effects.

Methods

Twenty-eight client-owned cats with a clinical diagnosis of FASS were recruited. Oclacitinib was administered at 1 mg/kg q12h for 2 weeks and then at 1 mg/kg q24h for a further 2 weeks. At the study outset (D0), and 7 (D7) and 28 (D28) days after starting treatment, clinical lesions were assessed using a validated scoring system (SCORing Feline Allergic Dermatitis [SCORFAD]) and pruritus was graded via an adapted visual analogue scale (PVAS). At the same time points, plasma oclacitinib levels and haematological variables were measured.

Results

Among 18 cats completing the study, PVAS and SCORFAD improved by ⩾50% in 61% and 88% of animals, respectively. Mean PVAS decreased significantly between D0 and D7 and between D0 and D28 (both P <0.001) but not between D7 and D28. Likewise, mean SCORFAD values decreased significantly between D0 and D7 and between D0 and D28 (both P <0.001) but not between D7 and D28. On D7 and D28, plasma oclacitinib concentrations varied widely from 0 to 1443.2 ng/ml and from from 0 to 1177.7 ng/ml, respectively. Oclacitinib concentrations showed no correlation with clinical effects (SCORFAD and PVAS).

Conclusions and relevance

Oclacitinib emerged as being safe and effective to control clinical signs of FASS. A mean dose of 1 mg/kg, even without extending twice-daily treatment beyond the first 2 weeks, could be a suitable therapeutic regimen. Plasma drug levels did not seem useful to predict clinical response during treatment.
Tourism and environmental performance: New evidence using a threshold regression analysis
Authors: Lv Zhike , Xu Ting
Published: October 2021

To verify whether the effect of tourism on environmental performance differs by the level of tourism development, a panel threshold regression approach is applied to observe the effects of tourism on environmental performance in 97 countries over the 2002–2012 periods. Our results suggest that tourism always has a significant negative influence on the environmental performance, implying that tourism will unavoidably result in environmental degradation, irrespective of how high the level of tourism development. However, when tourism development exceeds a certain value, tourism will relatively have less influence on environmental performance. In terms of policy implications, given that tourism wills inevitably worse environmental quality, the policymakers should consider the optimal level of tourism development at around the estimated threshold level to minimize the negative impact of tourism on the environment.
Comparing the characteristics of EFL students’ multimodal composing and traditional monomodal writing: The case of a reading-to-write task
Authors: Cho Hyejin , Kim YouJin
Published: October 2021

Although digital multimodal composing (DMC) is receiving increasing attention in language classrooms, the extent to which it contributes to students’ writing practices is controversial. In order to understand the affordances of DMC compared to traditional monomodal writing in school contexts, it is pertinent to compare DMC and traditional writing using academic integrated-skills tasks. The current study aims to investigate the relationship between the quality of Korean high school students’ multimodal composing and that of the same students’ traditional monomodal writing, as well as content and language alignment. Thirty-one Korean high school students carried out a summary-reflection task through DMC and traditional monomodal writing. After reading a short fable by Aesop, students summarized and reflected on the text. While students used only one mode in traditional writing (i.e. English text), they utilized multiple modes in DMC (e.g. pictures, movies). Students’ task outcomes were scored using analytic rubrics, and texts were coded in terms of the content and linguistic features students retrieved from the text (i.e. alignment) and their degree of reflection. The results showed that there were no statistically significant differences in the quality, content and language alignment, or amount of reflection in writing outcomes between students’ DMC and traditional monomodal writing.
Percutaneous Transluminal Angioplasty for Below-the-Elbow Critical Hand Ischemia: A Systematic Review
Authors: Awad El-Karim Ghassan , Kennedy Sean A. , Ferraresi Roberto , Addas Jamil A.K. , Oreopoulos George D. , Jaberi Arash , Tan Kong Teng , Mafeld Sebastian
Published: October 2021

Purpose:

To perform a systematic review assessing the safety and efficacy of percutaneous transluminal angioplasty (PTA) for treatment of critical hand ischemia (CHI) due to below-the-elbow (BTE) obstructive arterial disease.

Materials and Methods:

MEDLINE and EMBASE systematic searches were performed from inception to December 2020 to identify studies assessing PTA for management of BTE obstructive arterial disease. Three independent reviewers performed abstract selection, data extraction, and quality assessment. The Newcastle-Ottawa Scale was used to assess individual study bias for non-randomized controlled trials.

Results:

Eight studies comprising 176 patients with obstructive BTE vessel disease were included. All studies had a score >5 on the Newcastle-Ottawa Scale, indicative of high quality. All studies used low-profile balloons (1.5–4 mm) for PTA of stenotic lesions or chronic total occlusions (CTOs). The weighted average technical success and clinical success rates were 89.3% (range = 82%–100%) and 69.9% (range = 19%–100%), respectively, at a mean follow-up of 29.7 ± 17.1 months. The short-term (<30 days) complication rate was low at 4.7% and most commonly included access site hematomas, pseudoaneurysms, and radial artery perforation or re-thrombosis. Nearly 20% of patients required an amputation, and most (96%) were minor (either distal phalanges or digits). Only 2 patients required above-wrist amputations. The primary and secondary patency rate at 5 years were 38% and 54%, respectively. The cumulative 5-year mortality rate was 33.1%.

Conclusions:

PTA for CHI due to BTE obstructive arterial disease is feasible with a high technical success rate and a low short-term complication rate. Additional long-term comparative studies are required to unequivocally establish the clinical benefit of endovascular treatment compared with conservative management or surgical bypass.
Retrograde Carotid Stenting Using Newly Released Venous Stent for Cerebral Malperfusion in Type A Aortic Dissection
Authors: Mukherjee Dipankar , Lewis Elizabeth , Spinosa David , Tang Daniel , Ryan Liam
Published: October 2021

Stanford Type A aortic dissections (TAAD) should be considered for repair, given the involvement of branch vessels which can result in malperfusion, specifically cerebral malperfusion secondary to dissection of the innominate and carotid arteries. This is a case report with a focus on four patients presenting with both acute and chronic symptomatic TAAD, with extension into the innominate and common carotid arteries. In all four cases, the decision to intervene utilizing a hybrid endovascular approach was made to increase perfusion to the brain and alleviate symptoms. Through the use of retrograde carotid stenting utilizing both the VICI venous stent (Boston Scientific, Marlborough, MA) and Abre self-expanding Nitinol stent (Medtronic, Minneapolis, MN) we obtained good results, specifically absence of symptoms and return to normal function of the patients.
The Income Elasticity of Gross Sports Betting Revenues in Nevada: Short-Run and Long-Run Estimates
Authors: Can Ege , Nichols Mark W.
Published: October 2021

In May 2018, the Supreme Court overturned the Professional and Amateur Sports Protection Act, thereby allowing all states to offer sports betting. Prior to this, Nevada was the only state with unrestricted sports betting. Using sports betting data from Nevada, we estimate long-run and short-run income elasticities to determine the growth and volatility of sports betting as a tax base. Sports gambling grows at a similar rate as state income and is stable and insensitive to short-run shocks to income. However, the amount of money kept by casinos, and hence the state, is small compared to other traditional tax bases.
Post-Tracheostomy Vascular Injury to the Anomalous Thymic Branch Managed by Endovascular Coiling
Authors: Ray Nirmalya , Ahuja Chirag Kamal , Kumar Ajay , Panda Naresh , Singh Paramjeet
Published: October 2021

Background

Tracheostomy-related arterial haemorrhage can be devastating especially if arising from an obscure anomalous vessel which can potentially complicate treatment decision.

Methods

We report a case of non-Hodgkin’s lymphoma with upper airway obstruction, who had profuse bleeding, post-tracheostomy, from the stomal site. CT angiography showed presence of a pseudoaneurysm adjacent to the tracheostomy site which was confirmed on catheter angiography to be arising from anomalous thymic branch of right common carotid artery (CCA). Superselective cannulation of the anomalous thymic artery was done using a microcatheter with subsequent coil embolization.

Results

Post-coiling, the bleeding stopped immediately and the patient recovered. He was under oncology care till 3 months following embolization and was doing well.

Conclusions

The emergency physicians should be aware of this rare variation of thymic artery while performing tracheostomy. Ultrasound as point-of-care device may help mitigate these complications. Endovascular embolization is a minimally invasive and effective management option for an injured arterial branch from a tracheostomy.
ASK a Midwife: A Qualitative Study Protocol
Authors: Stone Nancy I. , Thomson Gill , Tegethoff Dorothea
Published: October 2021

Midwife-led institutions, also called free-standing birth centres, offer birth assistance to women at low risk for complications. Free-standing birth centres, because they are the institutions that provide low intervention birth assistance, also present the possibility to conduct research on the skills and knowledge that are necessary to provide safe care for women who are at low risk for complications desiring an out-of-hospital birth. The aim of this study is to reveal the skills and knowledge necessary to provide care at low intervention births in free-standing birth centres in Germany for midwives post-certification. The theoretical and methodological standpoint of this study is hermeneutic phenomenology. In-depth qualitative methods will be used that are particularly sensitive to the research participants and their social context and allow for complexity, detail and context. The research sites are free-standing birth centres in Germany. Three strands of data will be collected. Each birth centre has its own quality management handbook. From this handbook, the chapter concerning the induction of new midwives will be analysed. Small focus groups will be held in ten birth centres throughout Germany; and data will be collected from 10 to 20 midwives during their induction period at the birth centre. The data collection methods will be open-ended interviews, data capture, journaling and non-participant observation with the new midwives. In-depth data analysis will reveal midwives’ experiences of skill acquisition in free-standing birth centres. The findings will be used to produce key recommendations for training midwives to work in birth centres.
Blasius–Rayleigh–Stokes flow of nanofluid past an isothermal magnetized surface
Authors: Ishaq Airal , Ahmad Adeel
Published: October 2021

The present article investigated the unsteady flow of a nanofluid past an isothermal magnetized plate emanating from a moving slot. This unique form of unsteady boundary layer flow is analogous to stretching/shrinking sheet problems subject to the direction of motion of the slot. Governing partial differential equation can be reduced into a similar form using the Blasius–Rayleigh–Stokes variable. The consequences of the movable slot and magnetic field on flow and heat transfer of nanofluid are examined by solving the problem numerically. The behavior of the magnetic field in the presence of nanoparticles is also examined. Effects of the magnetic field upon the existence of dual solutions for the specific range of moving slot parameter are also studied in detail.
The Death of the Data Subject
Authors: Hull Gordon
Published: October 2021

This paper situates the data privacy debate in the context of what I call the death of the data subject. My central claim is that concept of a rights-bearing data subject is being pulled in two contradictory directions at once, and that simultaneous attention to these is necessary to understand and resist the extractive practices of the data industry. Specifically, it is necessary to treat the problems facing the data subject structurally, rather than by narrowly attempting to vindicate its rights. On the one hand, the data industry argues that subjects of biometric identification lack legal standing to pursue claims in court, and Facebook recently denied that that its facial recognition software recognizes faces. On the other hand, industry takes consent to terms of service and arbitration clauses to create enforceable legal subject positions, while using promises of personalization to create a phenomenological subject that is unaware of the extent to which it is being manipulated. Data subjects thus have no legal existence when it is a matter of corporate liability, but legal accountability when it is a matter of their own liability. Successful reform should address the power asymmetries between individuals and data companies that enable this structural disempowerment.
The dominance of item learning in the location-specific proportion congruence paradigm
Authors: Bugg Julie M , Suh Jihyun , Colvett Jackson S
Published: October 2021

Prior research has shown that various cues are exploited to reactively adjust attention, and such adjustments depend on learning associations between cues and proportion congruence. This raises the intriguing question of what will be learned when more than one cue is available, a question that has implications for understanding which cue(s) will dominate in guiding reactive adjustments. Evidence from a picture-word Stroop task demonstrated that item learning dominated over location learning in a location-specific proportion congruence (LSPC) paradigm, a pattern that may explain the difficulty researchers have faced in replicating and reproducing the LSPC effect. One goal was to reproduce this pattern using a non-overlapping two-item set design that more closely matched prior studies, and another goal was to examine generalisability of the pattern to two other tasks. Using a prime-probe, colour–word Stroop task (Experiment 1), and a flanker task (Experiment 2), we again found clear dominance of item learning. In Experiment 3, we attempted to disrupt item learning and promote location learning by using a counting procedure that directed participants’ attention to location. Once again, we found the same pattern of item dominance. In addition, in none of the experiments did we find evidence for conjunctive (location–item) learning. Collectively, the findings suggest item learning is neither design- or task-specific; rather, it is robust, reliable, and not easily disrupted. Discussion centres on factors dictating dominance of item- over location-based adjustments and implications for the broader literature on LSPC effects.
Kinetics of polymerase chain reaction positivity in patients with Clostridioides difficile infection
Authors: Saha Srishti , Yadav Devvrat , Pardi Ryan , Patel Robin , Khanna Sahil , Pardi Darrell
Published: October 2021

Background:

Polymerase chain reaction (PCR) is a sensitive test for diagnosing Clostridioides difficile infection (CDI) and could remain positive following resolution of CDI. The kinetics of PCR positivity following antibiotics for CDI is unknown. We studied this and whether it predicted CDI recurrence.

Methods:

Adults with CDI from October 2009 to May 2017 were included. Serial stool samples within 60 days of treatment were collected. Recurrent CDI was defined as diarrhea after interim symptom resolution with positive stool PCR within 56 or 90 days of treatment completion. Contingency table analysis was used to assess the risk of recurrence.

Results:

Fifty patients were included [median age: 51 (range = 20–86) years, 66% women]. Treatment given was metronidazole, 50% (25); vancomycin, 44% (22); both, 4% (2); and fidaxomicin, 2% (1). Median duration of treatment for all 50 patients was 14 (range = 8–60) days. The median duration of treatment in patients who got prolonged therapy (>14 days) ( n = 10) was 47 (range = 18–60) days. Median time to negative PCR was 9 (95% CI, 7–14) days from treatment initiation, which did not differ by antibiotics given ( p = 0.5). A positive PCR during or after treatment was associated with a higher risk of recurrence at 56 days ( p = 0.02) and at 90 days ( p = 0.009).

Conclusion:

The median time to negative PCR in CDI was 9 days from treatment initiation. The PCR positivity during or after treatment may be useful for recurrence prediction; larger studies are needed to validate these results.
Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension
Authors: Farha Samar , Comhair Suzy , Hou Yuan , Park Margaret M. , Sharp Jacqueline , Peterson Laura , Willard Belinda , Zhang Renliang , DiFilippo Frank P. , Neumann Donald , Tang W.H. Wilson , Cheng Feixiong , Erzurum Serpil
Published: October 2021

Alterations in metabolism and bioenergetics are hypothesized in the mechanisms leading to pulmonary vascular remodeling and heart failure in pulmonary hypertension (PH). To test this, we performed metabolomic analyses on 30 PH individuals and 12 controls. Furthermore, using 2‐[18F]fluoro‐2‐deoxy‐D‐glucose positron emission tomography, we dichotomized PH patients into metabolic phenotypes of high and low right ventricle (RV) glucose uptake and followed them longitudinally. In support of metabolic alterations in PH and its progression, the high RV glucose group had higher RV systolic pressure (p < 0.001), worse RV function as measured by RV fractional area change and peak global longitudinal strain (both p < 0.05) and may be associated with poorer outcomes (33% death or transplantation in the high glucose RV uptake group compared to 7% in the low RV glucose uptake group at five years follow‐up, log‐ranked p = 0.07). Pathway enrichment analysis identified key metabolic pathways including fructose catabolism, arginine‐nitric oxide metabolism, tricarboxylic acid cycle, and ketones metabolism. Integrative human protein‐protein interactome network analysis of metabolomic and transcriptomic data identified key pathobiological pathways: arginine biosynthesis, tricarboxylic acid cycle, purine metabolism, hypoxia‐inducible factor 1, and apelin signaling. These findings identify a PH metabolomic endophenotype, and for the first time link this to disease severity and outcomes.
SARS-CoV-2 RNA in the Cerebrospinal Fluid of a Patient with Long COVID
Authors: Viszlayová Daša , Sojka Martin , Dobrodenková Silvia , Szabó Szabolcs , Bilec Ondrej , Turzová Mária , Ďurina Juraj , Baloghová Barbara , Borbély Zoltán , Kršák Martin
Published: October 2021

Over 10% of COVID-19 convalescents report post-COVID-19 complications, namely, ‘long COVID’ or ‘post-COVID syndrome,’ including a number of neuro-psychiatric symptoms. The pathophysiology of COVID-19 in the central nervous system is poorly understood but may represent post-COVID injury, ongoing sterile maladaptive inflammation, or SARS-CoV-2 persistence. We describe a long COVID patient with SARS-CoV-2 RNA in the cerebrospinal fluid, which seems important, specifically due to recent reports of gray matter volume loss in COVID-19 patients. Further studies of SARS-CoV2 RNA, markers of inflammation, and neuronal damage in the CSF of patients with long COVID would be useful and should address whether the CNS can serve as a reservoir of SARS-CoV-2, clarify the pathway by which COVID-19 contributes to CNS dysfunction, and how best to therapeutically address it.
The hormonal suppression as first-line treatment of lingual thyroid: A case report
Authors: Knežević Snežana , Dugalić Anđelka , Dugalić Branimir
Published: October 2021

Ectopic thyroid gland is a rare anomaly in the development of the thyroid gland. It is defined as any thyroid tissue that is not found on its usual topography. We present the case of a 62-year-old patient with difficulty swallowing solid food, occasional sore throat, hoarse voice, and difficulty speaking. The patient was in hypothyroid status. Thyroid scintigraphy and magnetic resonance imaging visualized a nodular mass on the base of the tongue, suprahyoid, and mediosagittal. The pathohistological finding revealed normal thyroid tissue with few colloidal changes, ruled out tumour infiltration and specific inflammatory process. She received hormonal suppression treatment as a first-line treatment. The patient showed significant improvement in symptoms with reduction of the dyspnea and the dysphagia and normalization of thyroid hormone tests.
COVID-19 and Digital Primary Education: Impact and Strategies for Sustainable Development
Authors: Maity Sudarshan , Sahu Tarak Nath , Sen Nabanita
Published: October 2021

The present study is based on primary data of 720 students from primary schools in West Bengal, India. With adherence to the Logistic Regression Model, the study investigates and analyses the factors that influence digital learning of primary students during the COVID-19 pandemic situation. Further with the application of Welch’s t-test, comparative study have been conducted based on parameters as village and city school students, private and government school students and gender discrimination. The findings conclude that the school structure; willingness of the school and teachers to conduct virtual classes; availability and accessibility of high-speed internet and economic capability of parents to bear the exorbitant internet charges are significant dimensions in virtual learning of primary section students. The study also confirms that during the pandemic girl students and students from village government schools are the worst hit in comparison to boys who are from city-based schools and private schools respectively.
Third-party type 2 innate lymphoid cells prevent and treat GI tract GvHD
Authors: Bruce Danny W. , Kolupaev Oleg , Laurie Sonia J. , Bommiasamy Hemamalini , Stefanski Heather , Blazar Bruce R. , Coghill James M. , Serody Jonathan S.
Published: October 2021

Acute graft-versus-host disease (aGVHD), mediated by the recognition of host major histocompatibility complex/peptide polymorphisms by donor T cells, remains a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). aGVHD most commonly involves the gastrointestinal tract, liver, and skin; symptomatic aGVHD is treated with corticosteroids. Steroid-nonresponsive aGVHD is a significant problem for patients undergoing allo-HSCT, with <15% of these patients alive 1 year after diagnosis. Previously, we found that the infusion of donor innate lymphoid type 2 (ILC2) cells could prevent and treat aGVHD of the lower gastrointestinal tract with no effect on the graft-versus-leukemia response. This approach for clinical translation is cumbersome, as it would require the generation of donor-derived ILC2 cells for each recipient. Thus, the ability to use third-party ILC2 cells would provide an “off-the-shelf” reagent that could be used to treat and/or prevent aGVHD. Here, we show that third-party ILC2 cells enhance the survival of allo-HSCT recipients. Treatment required at least 4 weekly infusions of ILC2 cells. Mechanistically, we show that ILC2 cell function was completely lost if the cells could not express both interleukin-13 (IL-13) and amphiregulin. Finally, we show that the activity of IL-13 has a greater dependence on the expression of the IL-13R on host rather than donor bone marrow cells. The ability to generate third-party ILC2 cells offers a new avenue for the prevention of aGVHD.
Vemurafenib acts as a molecular on-off switch governing systemic inflammation in Langerhans cell histiocytosis
Authors: Eder Sebastian K. , Schwentner Raphaela , Ben Soussia Philipp , Abagnale Giulio , Attarbaschi Andishe , Minkov Milen , Halbritter Florian , Hutter Caroline
Published: October 2021

Langerhans cell histiocytosis (LCH) is a neoplasm marked by the accumulation of CD1A+CD207+ cells. It is most commonly driven by a somatic, activating mutation in the BRAF serine-threonine kinase (BRAFV600E). Multisystem disease with risk-organ involvement requires myelotoxic chemotherapy, making BRAF-inhibitors an attractive treatment option. Here, we present a comprehensive analysis of the course of an LCH patient treated with the combination of vemurafenib and salvage chemotherapy who achieved sustained clinical and molecular remission. We show that there is no relationship between peripheral blood BRAFV600E levels and clinical presentation during treatment with vemurafenib, but that vemurafenib leads to a fast, efficient, but reversible inhibition of clinical manifestations of systemic inflammation. In line, serum levels of inflammatory cytokines exactly mirror vemurafenib administration. Genotyping analysis identified the BRAFV600E mutation in multiple hematopoietic cell types, including NK cells and granulocytes. Single-cell transcriptome analyses of peripheral blood and bone marrow cells at time of diagnosis and during treatment indicate that RAF-inhibition abrogates the expression of inflammatory cytokines previously implicated in LCH such as IL1B and CXCL8. Together, our data suggest that while the CD1A+CD207+ histiocytes are the hallmark of LCH, other BRAF-mutated cell populations may contribute significantly to morbidity in patients with multisystem LCH.
A p.Arg127Gln variant in GPIbα LRR5 allosterically enhances affinity for VWF: a novel form of platelet-type VWD
Authors: Bury Loredana , Falcinelli Emanuela , Kuchi Bhotla Haripriya , Mezzasoma Anna Maria , Guglielmini Giuseppe , Tischer Alexander , Moon-Tasson Laurie , Auton Matthew , Gresele Paolo
Published: October 2021

Gain-of-function (GOF) variants in GP1BA cause platelet-type von Willebrand disease (PT-VWD), a rare inherited autosomal dominant bleeding disorder characterized by enhanced platelet GPIbα to von Willebrand factor (VWF) interaction, and thrombocytopenia. To date, only 6 variants causing PT-VWD have been described, 5 in the C-terminal disulfide loop of the VWF-binding domain of GPIbα and 1 in the macroglycopeptide. GOF GP1BA variants generate a high-affinity conformation of the C-terminal disulfide loop with a consequent allosteric conformational change on another region of GPIbα, the leucine-rich-repeat (LRR) domain. We identified a novel GP1BA variant (p.Arg127Gln) affecting the LRR5 domain of GPIbα in a boy with easy bruising and laboratory test results suggestive of PT-VWD. We thus aimed to investigate the impact of the p.Arg127Gln variant on GPIbα affinity for VWF and GPIbα structure. Chinese hamster ovary cells expressing p.Arg127Gln GPIbα showed increased binding of VWF induced by ristocetin and enhanced tethering on immobilized VWF as compared with cells expressing wild-type GPIbα. Surface plasmon resonance confirmed that p.Arg127Gln enhances the binding affinity of GPIbα for VWF. Hydrogen-deuterium exchange mass spectrometry showed that p.Arg127Gln of LRR, while having little effect on the dynamics of the LRR locally, enhances the conformational dynamics of the GPIbα C-terminal disulfide loop structure. Our data demonstrate for the first time that GOF variants outside the GPIbα C-terminal disulfide loop may be pathogenic and that aminoacidic changes in the LRR may cause allosterically conformational changes in the C-terminal disulfide loop of GPIbα, inducing a conformation with high affinity for VWF.
Use of Singing for Lung Health as an alternative training modality within pulmonary rehabilitation for COPD: a randomised controlled trial
Authors: Kaasgaard Mette , Rasmussen Daniel Bech , Andreasson Karen Hjerrild , Hilberg Ole , Løkke Anders , Vuust Peter , Bodtger Uffe
Published: October 2021

Background

Pulmonary rehabilitation (PR) is a cornerstone in chronic obstructive pulmonary disease (COPD) management. However, PR adherence is generally low, and barriers include availability, economic issues, motivation and an inability to attend or perform physical training. Therefore, alternative, evidence-based PR activities are required. Singing may have benefits for quality of life (QoL), respiratory control and well-being in COPD, but the impact on the PR key outcome, physical exercise capacity, is uncertain.

Methods

In this randomised controlled trial (NCT03280355), we investigated the effectiveness of 10 weeks of PR, including either “Singing for Lung Health” (SLH) training or standard physical exercise training (PExT). The primary outcome was a change in exercise capacity (6-min walk distance (6MWD)) from baseline to post-PR. Secondary outcomes were changes in QoL (St George's Respiratory Questionnaire (SGRQ)), Hospital Anxiety and Depression Score (HADS), lung function, dyspnoea and adherence.

Results

We included 270 COPD patients, and 195 completed the study. Demographics across groups were comparable, and both groups improved significantly in 6MWD and SGRQ score. SLH was non-inferior to PExT in improving 6MWD (mean±sd13.1±36.3 mversus14.1±32.3 m, p=0.81; difference 1.0 m, 95% CI −7.3–9.3 m) with 21.8% and 25.0%, respectively (p=0.57), reaching the 6MWD minimal important difference of 30 m. We found no significant between-group differences concerning SGRQ, HADS, lung function, dyspnoea or adherence.

Conclusion

Our study suggests that SLH is non-inferior to PExT in improving 6MWD during a 10-week PR programme. Future studies addressing reproducibility, long-term effects and health economics are needed.
Chronic cough in Germany: results from a general-population survey
Authors: Virchow J. Christian , Li Vicky W. , Fonseca Eileen , Salmen Helena , Martin Ashley , Brady Joanne , Jannowitz Christina , Schelfhout Jonathan
Published: October 2021

Background

Chronic cough (CC) which is defined ≥8 weeks is a common condition in clinical practice. However, estimates of prevalence and associated comorbidities in German adults and key subgroups of age and gender are lacking.

Methods

Cross-sectional study based on a representative panel of 15 020 adult subjects of the general population who completed the German National Health and Wellness Survey, reporting CC and questions about comorbidities. Lifetime and 12-month prevalence are presented as unweighted estimates.

Results

The lifetime CC prevalence was 6.5% (range across age groups 5.1%–8.3%) and the 12-month prevalence was 4.9% (range 3.7–5.7%). The prevalence of diagnosed CC was 2.8% (range 0.9–4.1%) and the prevalence of persons currently on any prescription to treat CC was 0.6% (range 0.2–1.4%). Respondents who experienced CC were 52.0±17.0 years old, with a higher prevalence in those aged 50 years and older. Persons with CC had higher morbidity scores and were diagnosed with an increased number of comorbidities, most frequently diagnoses of the respiratory system (71.0%), followed by digestive tract disorders (34.0%) and sleep disorders (37.6%).

Conclusions

In a broadly representative sample of German adults, lifetime and 12-month prevalence of CC was greatest in current and former smokers and those older ≥50 years of age. Comorbidities are frequent and may complicate management of these patients.
The risk of respiratory tract infections and antibiotic use in a general population and among people with asthma
Authors: Kisiel Marta A. , Zhou Xingwu , Björnsson Eythor , Holm Mathias , Dahlman-Höglund Anna , Wang Juan , Svanes Cecilie , Norbäck Dan , Franklin Karl A. , Malinovschi Andrei , Johannessen Ane , Schlünssen Vivi , Janson Christer
Published: October 2021

Aim

The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals.

Method

This study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25–54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations.

Results

In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53–3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18–4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood.

Conclusion

In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma.
Sarcoidosis in Iceland: a nationwide study of epidemiology, clinical picture and environmental exposure
Authors: Haraldsdóttir Sigríður Ólína , Jonasson Jon Gunnlaugur , Jorundsdottir Kristin Bara , Hannesson Haraldur Jon , Gislason Thorarinn , Gudbjornsson Bjorn
Published: October 2021

Background

This nationwide study aimed to elucidate the incidence and clinical characteristics of tissue-verified sarcoidosis in Iceland. A secondary aim was to analyse sex differences and identify possible environmental factors contributing to the pathological process.

Materials and methods

This is a descriptive study covering 36 years (January 1, 1981 through December 31, 2016). Histopathological reports and electronic hospital discharge registries were reviewed in context for granulomas and/or sarcoidosis. National data were used for comparison regarding smoking habits and occupation, adjusted for age, sex and year of diagnosis. The data were stored in FileMaker and calculations were made by extracting data from this database to the statistical software package R.

Results

A total of 418 patients (54% females) were diagnosed with tissue-verified sarcoidosis. The incidence rate was 4.15/100 000/year, similar among females and males. The mean age at diagnosis was higher among females (53.0±14.2 years) than males (48.2±13.8 years). Fatigue was the most frequent single symptom (49.7%), but when all respiratory symptoms were grouped, they were the most frequent symptoms (60%). No significant difference was found between smoking status and sarcoidosis. Possible hazardous exposure in the workplace was reported by 19.4% of the cases.

Conclusion

The incidence of sarcoidosis in Iceland was higher than in an Asian population where the same inclusion criteria were applied. The clinical picture diverges partly from that in the Asian population but resembles that among other Caucasians. Fatigue and respiratory symptoms were predominant. The biphasic pattern of age at disease debut seen elsewhere among females was not evident in Iceland.
Blind inversion of multidimensional seismic data using sequential Tikhonov and total variation regularizations
Authors: Jahanjooy Saber , Riahi Mohammad Ali , Ghanbarnejad Moghanloo Hamed
Published: October 2021

The acoustic impedance (AI) model is key data for seismic interpretation, usually obtained from its nonlinear relation with seismic reflectivity. Common approaches use initial geologic and seismic information to constrain the AI model estimation. When no accurate prior information is available, these approaches may dictate false results at some parts of the model. The regularization of ill-posed underdetermined problems requires some constraints to restrict the possible results. Available seismic inversion methods mostly use Tikhonov or total variation (TV) regularizations with some adjustments. Tikhonov regularization assumes smooth variation in the AI model, and it is incurious about the rapid changes in the model. TV allows rapid changes, and it is more stable in the presence of noisy data. In a detailed realistic earth model that AI changes gradually, TV creates a staircasing effect, which could lead to misinterpretation. This could be avoided by using TV and Tikhonov regularization sequentially in the alternating direction method of multipliers and creating the AI model. The result of implementing our algorithm, sequential Tikhonov and total variation regularizations (STTVR), on 2D synthetic and real seismic sections indicates that the smaller details in the lithologic variations are accounted for as well as the general trend. STTVR can calculate major AI variations without any additional low-frequency constraints. The temporal and spatial transition of the calculated AI in real seismic data is gradual and close to a real geologic setting.
Piloting the use of objective structured clinical examinations (OSCEs) to assess undergraduate medical students’ clinical competence in psychiatry in Zimbabwe
Authors: Ruwizhu Tatenda , Nyamukapa Ropafadzo , Mazhandu Fungisai , Mutambara Julia , Mangezi Walter , Whitwell Susannah
Published: October 2021

This report describes a pilot project which involved undergraduate medical students’ clinical competence in psychiatry assessed through objective structured clinical examinations for the first time in Zimbabwe. The pilot describes how gaps in medical education can be addressed by collaborative partnerships that allow sharing of knowledge by local institutions and international experts.
A Validated Risk Prediction Model for Breast Cancer in US Black Women
Authors: Palmer Julie R. , Zirpoli Gary , Bertrand Kimberly A. , Battaglia Tracy , Bernstein Leslie , Ambrosone Christine B. , Bandera Elisa V. , Troester Melissa A. , Rosenberg Lynn , Pfeiffer Ruth M. , Trinquart Ludovic
Published: October 2021

PURPOSE

Breast cancer risk prediction models are used to identify high-risk women for early detection, targeted interventions, and enrollment into prevention trials. We sought to develop and evaluate a risk prediction model for breast cancer in US Black women, suitable for use in primary care settings.

METHODS

Breast cancer relative risks and attributable risks were estimated using data from Black women in three US population-based case-control studies (3,468 breast cancer cases; 3,578 controls age 30-69 years) and combined with SEER age- and race-specific incidence rates, with incorporation of competing mortality, to develop an absolute risk model. The model was validated in prospective data among 51,798 participants of the Black Women's Health Study, including 1,515 who developed invasive breast cancer. A second risk prediction model was developed on the basis of estrogen receptor (ER)–specific relative risks and attributable risks. Model performance was assessed by calibration (expected/observed cases) and discriminatory accuracy (C-statistic).

RESULTS

The expected/observed ratio was 1.01 (95% CI, 0.95 to 1.07). Age-adjusted C-statistics were 0.58 (95% CI, 0.56 to 0.59) overall and 0.63 (95% CI, 0.58 to 0.68) among women younger than 40 years. These measures were almost identical in the model based on estrogen receptor–specific relative risks and attributable risks.

CONCLUSION

Discriminatory accuracy of the new model was similar to that of the most frequently used questionnaire-based breast cancer risk prediction models in White women, suggesting that effective risk stratification for Black women is now possible. This model may be especially valuable for risk stratification of young Black women, who are below the ages at which breast cancer screening is typically begun.
Hyper power impulse magnetron – HyPIM – glow discharge
Authors: Morel E. , Rozier Y. , Minéa T.
Published: October 2021

Glow discharges are known to be limited for running at high currents (< 0.1 A · cm−2). Magnetically enhanced plasmas could overcome this limitation, typically for the magnetron operated in pulsed mode during a few 100μs. Hence, the current density could be increased by two decades, but it still stays below 10 A · cm−2. Here we report on a long (∼1 ms) pulsed operation of magnetrons, while preserving the glow mode, for current densities exceeding at least 3 times the highest current density reported for high power pulsed magnetrons. Even if the density of energy surpasses 7 J ·  cm−2, no arc transition was observed. Three target materials have been successfully tested: carbon (C), molybdenum (Mo) and tungsten (W) in helium atmosphere, from 5 to 30 Pa. Two key parameters are required to reach the Hyper Power Impulse Magnetron (HyPIM) glow mode: i) the accurate control of the maximum voltage during the pulse and ii) the use of the pre-ionization. Operating conditions of HyPIM will be presented and compared to other discharges.