bluuebunny/crossref_metadata_2025 huggingface dataset:
Silicate minerals as a direct source of limiting nutrients: Siderophore synthesis and uptake promote ferric iron bioavailability from olivine and microbial growth
Authors: Van Den Berghe Martin , Merino Nancy , Nealson Kenneth H. , West A. Joshua
Published: June 2021

Iron is a micronutrient critical to fundamental biological processes including respiration and photosynthesis, and it can therefore impact primary and heterotrophic productivity. Yet in oxic environments, iron is highly insoluble, rendering it, in principle, unavailable as a nutrient for biological growth. Life has “solved” this problem via the invention of iron chelates, known as siderophores, that keep iron available for microbial productivity. In this work, we examined the impact of siderophore synthesis on the speciation, mobility, and bioavailability of iron from rock‐forming silicate minerals—shedding new light on the mechanisms by which microbes use mineral substrates to support primary productivity, as well as the consequent effects on silicate dissolution. Growth experiments were performed with Shewanella oneidensis MR‐1 in an oxic, iron‐depleted minimal medium, amended with olivine minerals as the sole source of iron. Experiments included the wild‐type strain MR‐1, and a siderophore synthesis gene deletion mutant strain (ΔMR‐1). Relative to MR‐1, ΔMR‐1 exhibited a very pronounced growth penalty and an extended lag phase. However, substantial growth of ΔMR‐1, comparable to MR‐1 growth, was observed when the mutant strain was provided with siderophores in the form of either filtrate from a well‐grown MR‐1 culture, or commercially available deferoxamine. These observations suggest that siderophores are critical for S. oneidensis to acquire iron from olivine. Growth‐limiting concentrations of deferoxamine amendments were observed to be ≤5–10 µM, concentrations significantly lower than previously recorded as necessary to impact mineral dissolution rates. X‐ray photoelectric spectroscopy analyses of the incubated olivine surfaces suggest that siderophores deplete mineral surface layers of ferric iron. Combined, these results demonstrate that low micromolar concentrations of siderophores can effectively mobilize iron bound within silicate minerals, supporting very significant biological growth in limiting environments. The specific mechanism would involve siderophores removing a protective layer of nanometer‐thick iron oxides, enhancing silicate dissolution and nutrient bioavailability.
Flowers, Women, and Work in the Socialist Fairy Tale: Toward a Feminist, Materialist, and Ecocritical Approach
Authors: Sheedy Melissa
Published: June 2021

Hedwig Dohm's 1870 fairy tale “Blumenduft,” a tale of a princess who finds fulfillment in work, illustrates the merits of industry alongside the failings of royalty. A century later, East German production company DEFA released Dornröschen (1971), echoing similar discourses through the traditionally feminine craft of spinning. Unlike the Grimm paradigm of passive princesses, diligence in these tales is not associated with marriage or domesticity. Rather, labor is tied to broader social structures, and the conventional nature‐culture binary is divided along class‐based lines. Both narratives evoke the Grimm tradition to suit new sociocultural contexts and showcase female empowerment enacted via “natural” interventions. Through the framework of feminist material ecocriticism, this article examines the connections between nature, women, and the working classes in these tales. A close analysis of these texts reveals the critical and political dimensions of nature and narrative as well as the enduring relevance of German fairy tales.
Sites of Imagination and Memory: Museums and the Remediation of Grimms' Märchen for the Twenty‐first Century
Authors: Sterling‐Hellenbrand Alexandra
Published: June 2021

In the two centuries since their first publication in 1812, the Grimms' Kinder‐ und Hausmärchen have become multi‐faceted prisms for cultural production and memorial processes; in short, they function as sites of memory. Over time, the Kinder‐ und Hausmärchen have generated culturally entangled narratives that demonstrate a palimpsestic intertextuality in their numerous adaptations. This essay argues that these fairy tales have become realized and remediated not only as sites of memory but also as projects of imagination in two twenty‐first‐century museums. The Nibelungenmuseum in Worms (2001) exploits fairy‐tale resonances from German Romanticism to Walt Disney in order to interrogate the role of the Kinder‐ und Hausmärchen in propagating a toxic medievalism that the museum in turn cross‐examines. The Grimmwelt museum in Kassel (2015) re‐historicizes and engages these fairy tales in the context of the Grimms' entire oeuvre.
Effect of early intensive rehabilitation on the clinical outcomes of patients with acute stroke
Authors: Oyanagi Keiichi , Kitai Takeshi , Yoshimura Yoshihiro , Yokoi Yuki , Ohara Nobuyuki , Kohara Nobuo , Sakai Nobuyuki , Honda Akihiro , Onishi Hideaki , Iwata Kentaro
Published: June 2021

Aim

Intensive rehabilitation effectively improves physical functions in patients with acute stroke, but the frequency of intervention and its cost‐effectiveness are poorly studied. This study aimed to examine the effect of early high‐frequency rehabilitation intervention on inpatient outcomes and medical expenses of patients with stroke.

Methods

The study retrospectively included 1759 patients with acute stroke admitted to the Kobe City Medical Center General Hospital between 2013 and 2016. Patients with a transient ischemic attack, subarachnoid hemorrhage, and those who underwent urgent surgery were excluded. Patients were divided into two groups according to the frequency of rehabilitation intervention: the high‐frequency intervention group (>2 times/day, n = 1105) and normal‐frequency intervention group (<2 times/day, n = 654). A modified Rankin scale score ≤2 at discharge, immobility‐related complications and medical expenses were compared between the groups.

Results

The high‐frequency intervention group had a significantly shorter time to first rehabilitation (median [interquartile range], 19.0 h [13.1–38.4] vs. 24.7 h [16.1–49.4], P < 0.001) and time to first mobilization (23.3 h [8.7–47.2] vs. 22.8 h [5.7–62.3], P = 0.65) than the normal‐frequency intervention group. Despite higher disease severity, the high‐frequency intervention group exhibited favorable outcomes at discharge (modified Rankin scale, ≤2; adjusted odds ratio, 1.89; 95% confidence interval, 1.25–2.85; P = 0.002). No significant differences were observed between the two groups concerning the rate of immobility‐related complications and total medical expenses during hospitalization.

Conclusions

High‐frequency intervention was associated with improved outcomes and decreased medical expenses in patients with stroke. Our results may contribute to reducing medical expenses by increasing the efficiency of care delivery. Geriatr Gerontol Int 2021; 21: 623–628.
Association of regional white matter hyperintensity volumes with cognitive dysfunction and vascular risk factors in patients with amnestic mild cognitive impairment
Authors: Hirao Kentaro , Yamashita Fumio , Sakurai Shu , Tsugawa Akito , Haime Rieko , Fukasawa Raita , Sato Tomohiko , Kanetaka Hidekazu , Umahara Takahiko , Sakurai Hirofumi , Hanyu Haruo , Shimizu Soichiro
Published: June 2021

Aim

White matter hyperintensities (WMH) obtained by magnetic resonance imaging (MRI) have been reported to promote neurodegeneration and cognitive decline in patients with mild cognitive impairment (MCI). However, little is known about the association between regional WMH (rWMH) and cognitive dysfunction in MCI. We hence investigated the associations between rWMH volumes and cognitive dysfunction in MCI.

Methods

Thirty‐eight subjects with amnestic MCI were analysed. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on a T2‐FLAIR MRI using a 3D‐slicer, and regional PVH and DWMH (rPVH and rDWMH) volumes were calculated. The associations of rPVH and rDWMH volumes with cognition and blood levels of various molecules were investigated. Furthermore, rPVH and rDWMH volumes were compared between MCI with vascular risk factors, such as hypertension, diabetes mellitus (DM), and dyslipidemia, and those without these risk factors.

Results

rPVH volume (bilateral cornu frontale, pars parietalis, and cornu occipitale) positively correlated with Trail Making Test‐A/B scores and CysC level, whereas rDWMH volume did not correlate with any of the items. rPVH volumes (right cornu frontale, bilateral pars parietalis and cornu occipitale, and right pars temporalis) and rDWMH volumes (left frontal and parietal lobes) were significantly larger in MCI patients with DM than in those without.

Conclusions

PVH volumes (bilateral areas of cornu frontale, pars parietalis, and cornu occipitale) were closely associated with attention and executive dysfunction. Serum CysC level and DM were associated with WMH volume, suggesting that CysC level and DM might be important markers for determining treatment strategies for white matter abnormalities in MCI. Geriatr Gerontol Int 2021; 21: 644–650.
Dihydroergotamine infusion for pediatric refractory headache: A retrospective chart review
Authors: Srouji Rasha , Schenkel Sara R. , Forbes Peter , Cahill Jennifer E.
Published: June 2021

Background

Headaches are a common symptom in children. Children with refractory headaches may be admitted for inpatient treatment with intravenous dihydroergotamine mesylate (DHE). However, very few studies have characterized these patients and their treatment outcomes using validated, self‐reported, pain scales.

Objective

The objective of this study was to describe demographic and clinical characteristics of children admitted for DHE infusion, determine DHE treatment outcomes by means of numeric pain scale ratings, and explore associations between treatment outcomes and clinical characteristics.

Methods

Retrospective chart review was completed in patients ages 5–21 admitted for DHE infusion from January 2013 to July 2018 at a large, pediatric academic medical center and community‐based satellite center. All primary headache types were included.

Results

A total of 200 unique admissions for DHE were available for analysis. Overall, patients were predominantly White (87.5%, 175/200) and female (80.0%, 160/200) with an average age of 15.4 years (SD 2.3). Common comorbidities included obesity (42.0%, 81/193), anxiety (41.0%, 82/200), and depression (20.0%, 40/200). The mean length of stay was 2.4 days (SD 1.10; range 1–8 days). Most headaches (65.0%, 130/200) met the International Classification of Headache Disorders, 3rd edition criteria for migraine, followed by new daily persistent headache (25.5%, 51/200). Mean DHE maximum dose was 5.3 (SD 2.17; range 0.5–14.5 mg) with most patients requiring 3.5–6.5 mg. DHE was typically terminated at six doses (range 1–15). The most frequently reported adverse event was nausea (5.5%, 11/200). There was no difference in pain severity at admission across headache types, with an average baseline pain score of 8.1 (SD 1.6). Posttreatment reduction in pain score was statistically significant (range: −3.2 to −4.9; each p < 0.001) across all headache types. Overall, 84.0% (168/200) of the patients had some improvement in pain. More than half of the patients (53.5%, 107/200) showed at least moderate improvement (≥50.0% reduction in pain score), and 18.0% (36/200) had full headache resolution. Limited patients (16.0%, 32/200) experienced no improvement in pain.

Conclusions

Treatment with DHE resulted in at least some improvement for most patients regardless of headache type or number of doses. Clinical trials stratified by headache type and comorbid factors could help clarify treatment algorithms to optimize patient outcomes.
A scoping review of practice recommendations for clinicians’ communication of uncertainty
Authors: Medendorp Niki M. , Stiggelbout Anne M. , Aalfs Cora M. , Han Paul K. J. , Smets Ellen M. A. , Hillen Marij A.
Published: June 2021

Background

Health‐care providers increasingly have to discuss uncertainty with patients. Awareness of uncertainty can affect patients variably, depending on how it is communicated. To date, no overview existed for health‐care professionals on how to discuss uncertainty.

Objective

To generate an overview of available recommendations on how to communicate uncertainty with patients during clinical encounters.

Search strategy

A scoping review was conducted. Four databases were searched following the PRISMA‐ScR statement. Independent screening by two researchers was performed of titles and abstracts, and subsequently full texts.

Inclusion criteria

Any (non‐)empirical papers were included describing recommendations for any health‐care provider on how to orally communicate uncertainty to patients.

Data extraction

Data on provided recommendations and their characteristics (eg, target group and strength of evidence base) were extracted. Recommendations were narratively synthesized into a comprehensible overview for clinical practice.

Results

Forty‐seven publications were included. Recommendations were based on empirical findings in 23 publications. After narrative synthesis, 13 recommendations emerged pertaining to three overarching goals: (a) preparing for the discussion of uncertainty, (b) informing patients about uncertainty and (c) helping patients deal with uncertainty.

Discussion and conclusions

A variety of recommendations on how to orally communicate uncertainty are available, but most lack an evidence base. More substantial research is needed to assess the effects of the suggested communicative approaches. Until then, health‐care providers may use our overview of communication strategies as a toolbox to optimize communication about uncertainty with patients.

Patient or public contribution

Results were presented to stakeholders (physicians) to check and improve their practical applicability.
A comparative study of Kimura’s disease and IgG4‐related disease: similarities, differences and overlapping features
Authors: Wang Xingen , Ng Chi‐Sing , Yin Weihua
Published: June 2021

Aims

To compare the fibroinflammatory diseases Kimura’s disease (KD) and immunoglobulin (Ig)G4‐related disease (IgG4RD) and to explore their possible relationship.

Methods and results

Forty‐six cases of KD and 29 IgG4RD from our institution diagnosed from 2011 to 2020 were studied. They were compared with each other on clinical, pathological and immunohistological features. There were similar clinical features, except that IgG4RD affected an older patient population, with more frequent salivary gland involvement and KD affected head and neck lymph nodes, and showed blood eosinophilia more frequently than IgG4RD. IgG4RD exhibited frequent storiform fibrosis and obliterative phlebitis, while KD showed more frequent tissue eosinophilia, eosinophilic abscess, germinal centre eosinophilic deposit and vascularisation. Twenty to 30% of KD had more than 50 IgG4+ plasma cells (PC) per high‐power field (HPF) and IgG4/IgG+PC ratio exceeding 40%. These parameters, however, occurred in 100% of IgG4RD. Significantly more KD had >10 IgE+PC/HPF and lymphoid germinal centre IgE reticular staining compared to IgG4RD. All these histological and immunohistological features are overlapping in the two diseases, although they differed with statistical significance.

Conclusion

Our study confirmed that there is significant overlap in clinical, pathological and immunohistological features between KD and IgG4RD. It is important to recognise these overlapping features, and correlation with a clinicopathological picture is required in differential diagnoses. The overlapping features also suggest a possible close relationship between KD and IgG4RD, which could represent different facets of a continuous fibroinflammatory disease spectrum.
PRINCIPLES OF NARRATIVE REASON
Authors: IMAZ‐SHEINBAUM MARIANA
Published: June 2021

Jouni‐Matti Kuukkanen has theorized that narrative does not involve rational content. Rather, he suggested, narrative is only a descriptive practice consisting of singular statements. Kuukkanen thus divorced the rational and narrative frameworks, arguing that historiography belongs to the former and not the latter. This article establishes a new conceptual framework that provides a revised understanding of narrative as a rational practice. I argue that the principles of organization brought to light by the Gestalt school of experimental psychology illuminate the underlying organizational logic that historians engage with when constructing narratives. To illustrate how these principles operate in historical narratives and how they are rational, I examine classic historical works such as Karl Marx's introduction of the concept of surplus value; Giambattista Vico's Autobiography and Jacob Burckhardt's The Civilization of the Renaissance; Reinhart Koselleck's Futures Past; and E. P. Thompson's The Making of the English Working Class and Johan Huizinga's Waning of the Middle Ages. My analysis shows that narrative entails its own kind of explanatory structure. It is a way of thinking that provides meaning and structure to that which is otherwise unstructured and undetermined. Finally, my new framework offers a foundation for the rational evaluation of narratives by showing how the context of discovery and the context of justification cannot be separated in the case of narrative histories.
REQUIRED: A THEORY OF ALLOWABLE GAPS
Authors: Gorman Jonathan
Published: June 2021

This review essay on Paul A. Roth's The Philosophical Structure of Historical Explanation follows Roth in accepting the notion of a “narrative sentence” (from Danto's Analytical Philosophy of History) and takes up Roth's view that a narrative explanation elucidates that which it constructs. I also analyze the “relating of events” within a temporal frame, but I come to different conclusions than Roth does: I deny any necessary connection between a narrative explanation and a narrative sentence and object to Roth's insistence on “nonstandardization” as a necessary feature of a narrative explanation. I argue that a “passage of time” is characteristic of all our descriptions, regardless of whether they are scientific, historical, or anything else. Like Roth, I draw on the work of W. V. O. Quine to address the pragmatic question of how large a “unit of empirical significance” is to be, and I show that different practical situations may require different practical decisions about what sizes of unit are required, with whole narratives being units of significance in themselves. Problems of the epistemic structure of narratives remain, and I argue that relating a passage of time requires a theory that enables us to preclude any temporal gaps. A theory of conceptual linkage of any stripe seems incapable of doing that.
Priors in a Bayesian audit: How integration of existing information into the prior distribution can improve audit transparency and efficiency
Authors: Derks Koen , de Swart Jacques , van Batenburg Paul , Wagenmakers Eric‐Jan , Wetzels Ruud
Published: June 2021

Auditors often have prior information about the auditee before starting the substantive testing phase. We show that applying Bayesian statistics in substantive testing allows for integration of this information into the statistical analysis through the prior distribution. For example, an auditor might have performed an audit last year, they might have information on certain controls in place, or they might have performed analytical procedures in an earlier stage of the audit. Incorporating this information directly in the statistical procedure enables auditors to tailor their sampling plan to the auditee, thereby increasing audit transparency and efficiency. However, defining a suitable prior distribution can be difficult because what constitutes a suitable prior depends on the specifics of the audit and the auditee. To help the auditor in constructing a prior distribution we introduce five methodologies, consider their pros and cons, and give examples of how to apply them in practice.
Exploratory insights into audit fee increases: A field study into board member perceptions of auditor pricing practices
Authors: Goddard Francis , Schmidt Martin
Published: June 2021

Audit research documents audit fee discounts associated with an auditor change, and that audit fees revert to average levels within a few years. This paper provides exploratory insights into the perceptions of board members vis‐à‐vis pricing practices used by auditors to achieve audit fee increases. In semi‐structured interviews with 12 respondents (10 board members and two audit managers), we elicit perceptions on initial audit fee discounts, auditor pricing practices and client reactions to these pricing practices. The key findings indicate that auditors combine two pricing practices to achieve audit fee increases. First, they negotiate higher fees prior to the annual audit cycle, citing changes in client structure/size and the institutional environment. Second, they charge higher than negotiated fees after completing the audit (‘extra‐billing’), citing justifications such as chargeable hour overruns and findings warranting additional work. Potentially, such auditor pricing practices have negative implications for audit quality and damage the auditor–client relationship.
Knowledge, attitudes, and practices associated with personal health care on urticaria in peripheral health facilities of Yaoundé, Cameroon (Sub‐Saharan Africa)
Authors: Kouotou Emmanuel Armand , Nansseu Jobert Richie N. , Tounouga Dahlia Noelle , Otsali Noa Raissa Katy , Ndjitoyap Ndam Elie Claude
Published: June 2021

Background

Urticaria is an acute or chronic inflammatory dermatosis that is characterized by erythematous, edematous, itchy, and transient urticarial plaques that cover the skin and mucous membranes. The aim of this study was to evaluate the knowledge of consulting staff on urticaria in Yaoundé, Cameroon, as well as the attitudes and practices resulting from it.

Methods

We conducted a descriptive cross‐sectional study. The participants were enrolled from January to April 2017 in 25 health facilities in Yaoundé, Cameroon. The sample consisted of health personnel including doctors, nurses, and nursing aids. Data were collected using a self‐administered questionnaire; the evaluation scores for each heading were established. Data processing was done using the SPSS software Version 21.

Results

We recruited 101 participants, with a sex ratio of 0.4 (73/101 were female); 44.6% of the participants were doctors, and 50% of our participants had less than 5 years of professional experience. The level of knowledge on urticaria was insufficient for 40.6% of the staff enrolled. Attitudes towards urticaria were incorrect for 36.6% of staff, and 95% of our sample had harmful practices.

Conclusion

Our study reveals that skills of the health care provider regarding urticaria are generally poor and do not enable them to ensure an adequate management of the disease.
Failure of integration or symbol of racism: The case of soccer star Mesut Özil
Authors: Waas Sabine
Published: June 2021

In May 2018, Mesut Özil, a third‐generation Turkish immigrant, was photographed with Turkey's President Recep Tayyip Erdoğan. This incident was constructed by the media and politicians as an endorsement for Erdoğan in the upcoming Turkish election and resulted in a public discussion about Özil's loyalty to German democratic values. The debate intensified especially after the World Cup and led to Özil's resignation from the national team via social media on 22 July 2018, where he cited racism against him as one of his reasons. Newspapers, news magazines and tabloids all over the world covered the story, discussing racism and the failure of German integration policies. Through a qualitative media content analysis of German national newspapers and tabloid press articles following the publication of the photograph of Erdoğan and Özil on 14 May 2018, this paper will analyse how Özil was portrayed in the media.
Fibroblasts and macrophages: Collaborators in tissue homeostasis
Authors: Franklin Ruth A.
Published: June 2021

Fibroblasts and macrophages are universal cell types across all mammalian tissues. These cells differ in many ways including their cellular origins; dynamics of renewal, recruitment, and motility within tissues; roles in tissue structure and secretion of signaling molecules; and contributions to the activation and progression of immune responses. However, many of the features that make these two cell types unique are not opposing, but instead complementary. This review will present cell‐cell communication in this context and discuss how complementarity makes fibroblasts and macrophages highly compatible partners in the maintenance of tissue homeostasis.
Deciding to discontinue prescribed psychotropic medication: A qualitative study of service users’ experiences
Authors: Watts Mike , Murphy Esther , Keogh Brian , Downes Carmel , Doyle Louise , Higgins Agnes
Published: June 2021

Many mental health service users decide to discontinue their psychotropic medication at some stage in the treatment process; however, few studies have captured these experiences. This study aimed to explore people’s experiences of coming off medication. A qualitative descriptive design and individual interviews with 23 people who experienced coming off medication were employed. COREQ checklist was used. Data were analysed using inductive and deductive approaches and six major themes were developed. Findings suggest that while medication was useful for many in the short‐term, the adverse effects had significant impact and contributed to the decision to come off medication. Participants also reported being driven by a questioning of the biomedical model of treatment and the belief that there were other strategies to manage their distress. Mixed experiences of support from healthcare professionals for the medication cessation process were reported. The discontinuation process was often difficult resulting in changes in mood and behaviour which for many culminated in relapse of distress, rehospitalization and return to medication. To support the process of coming off and staying off medication, participants identified a range of useful strategies but particularly highlighted the importance of peer support. Findings from this study demonstrate the importance of mental health nurses having a collaborative discussion with service users which may support safer decision‐making and lessen the risk of people discontinuing medication abruptly. Finding also indicates a need for robust studies that develop and test interventions to support people who wish to discontinue psychotropic medications.
Negative‐pressure wound therapy for donor‐site closure in radial forearm free flap: A systematic review and meta‐analysis
Authors: Shimada Kazuki , Ojima Yosuke , Ida Yukiko , Komiya Takako , Matsumura Hajime
Published: June 2021

Negative‐pressure wound therapy (NPWT) is often used for skin graft site dressing, and several studies have reported that its use improves skin graft failure in the forearm flap donor site. The present systematic review aimed to evaluate the efficacy of NPWT with skin graft for donor‐site closure in radial forearm free flap (RFFF) reconstruction. A systematic search in PubMed, Web of Science, and Cochrane Library databases was conducted. The search terms used for PubMed were ([radial forearm]) AND ([donor]) AND ([negative pressure or vacuum]). This review was registered in the International Prospective Register of Systematic Reviews and performed in accordance with the preferred reporting items for systematic reviews and meta‐analyses statement. Three prospective randomised controlled trials and three retrospective comparative studies were included. Compared with conventional bolster dressing, the use of NPWT dressing did not lead to significant improvements in partial skin graft loss, tendon exposure, and other complications. NPWT improved hand functionality earlier; nonetheless, the cost of the device and dressings was a disadvantage. The use of NPWT for skin graft fixation in the RFFF donor site is not generally recommended.
Eligibility for Baroreflex Activation Therapy and medication adherence in patients with apparently resistant hypertension
Authors: Schäfer Ann‐Kathrin , Kuczera Tim , Wurm‐Kuczera Rebecca , Müller Dieter , Born Ellen , Lipphardt Mark , Plüss Marlene , Wallbach Manuel , Koziolek Michael
Published: June 2021

Uncontrolled hypertension is a main risk factor for cardiovascular morbidity. Baroreflex activation therapy (BAT) is an effective therapy option addressing true resistant hypertension. We evaluated patients’ eligibility for BAT in a staged assessment as well as adherence to antihypertensive drug therapy. Therefore, we analyzed files of 345 patients, attending the hypertension clinic at University Medicine Göttingen. Additionally, gas chromatographic‐mass spectrometric urine analyses of selected individuals were performed evaluating their adherence. Most common cause for a revoked BAT recommendation was blood pressure (BP) control by drug adjustment (54.2%). Second leading cause was presence of secondary hypertension (31.6%). Patients to whom BAT was recommended (59 (17.1%)) were significantly more often male (67.8% vs. 43.3%, P = .0063), had a higher body mass index (31.8 ± 5.8 vs. 30.0 ± 5.7 kg/m², P = .0436), a higher systolic office (168.7 ± 24.7 vs. 147.7 ± 24.1 mmHg, P < .0001), and 24h ambulatory BP (155.0 ± 14.6 vs. 144.4 ± 16.8 mmHg, P = .0031), took more antihypertensive drugs (5.8 ± 1.3 vs. 4.4 ± 1.4, P < .0001), and suffered more often from numerous concomitant diseases. Eventually, 27 (7.8%) received a BAT system. In the toxicological analysis of 75 patients, mean adherence was 75.1%. 16 patients (21.3%) showed non‐adherence. Thus, only a small number of patients eventually received a BAT system, as treatable reasons for apparently resistant hypertension could be identified frequently. This study is—to our knowledge—the first report of a staged assessment of patients’ suitability for BAT and underlines the need for a careful examination and indication. Non‐adherence was proven to be a relevant issue concerning apparently resistant hypertension and therefore non‐eligibility for interventional antihypertensive therapy.
Enforcing European Privacy Regulations from Below: Transnational Fire Alarms and the General Data Protection Regulation*
Authors: Jang Woojeong , Newman Abraham L.
Published: June 2021

The European Union is a global leader in data protection. Nevertheless, its efforts to shape market practice have been criticized as bureaucratic and lacking citizen participation. The adoption of the General Data Protection Regulation (GDPR) has again stoked a heated implementation debate, focusing either on the law's complexity or its new enforcement sanctions. This article draws attention to a less explored provision, Article 80, which allows third parties including non‐governmental organizations to bring complaints for investigation. Empirically, the article demonstrates how NGOs are playing a bottom up role in transforming policy implementation. Theoretically, the article suggests that the legislation offers a novel governance tool – transnational fire alarms – in which third parties enhance accountability in the enforcement phase of the multilevel governance process. The article has implications for the evolution of privacy and data security within Europe as well as the interaction between transnational civil society and pan‐regional democracy.
Evolutionary origins of viviparity consistent with palaeoclimate and lineage diversification
Authors: Recknagel Hans , Kamenos Nicholas A. , Elmer Kathryn. R.
Published: June 2021

It is of fundamental importance for the field of evolutionary biology to understand when and why major evolutionary transitions occur. Live‐bearing young (viviparity) is a major evolutionary change and has evolved from egg‐laying (oviparity) independently in many vertebrate lineages and most abundantly in lizards and snakes. Although contemporary viviparous squamate species generally occupy cold climatic regions across the globe, it is not known whether viviparity evolved as a response to cold climate in the first place. Here, we used available published time‐calibrated squamate phylogenies and parity data on 3,498 taxa. We compared the accumulation of transitions from oviparity to viviparity relative to background diversification and a simulated binary trait. Extracting the date of each transition in the phylogenies and informed by 65 my of global palaeoclimatic data, we tested the nonexclusive hypotheses that viviparity evolved under the following: (a) cold, (b) long‐term stable climatic conditions and (c) with background diversification rate. We show that stable and long‐lasting cold climatic conditions are correlated with transitions to viviparity across squamates. This correlation of parity mode and palaeoclimate is mirrored by background diversification in squamates, and simulations of a binary trait also showed a similar association with palaeoclimate, meaning that trait evolution cannot be separated from squamate lineage diversification. We suggest that parity mode transitions depend on environmental and intrinsic effects and that background diversification rate may be a factor in trait diversification more generally.
Association between serum ferritin, incident primary liver cancer, and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: A nested case–control study
Authors: Zhu Zhikai , Yin Jian , Dawsey Sanford M , Liu Bin , Freedman Neal D , Yin Liangyu , Taylor Philip R , Cui Jianfeng , Fan Jinhu , Liu Yuanli , Chen Wen , Qiao Youlin , Abnet Christian C
Published: June 2021

Background and Aim

Previous studies suggest that serum ferritin may be associated with higher risk of liver cancer. However, additional studies of the association are needed. It is also not clear whether serum ferritin is associated with mortality from chronic liver disease (CLD).

Methods

We performed a nested case–control study in the Linxian Nutrition Intervention Trials. Baseline serum ferritin was measured for 226 incident primary liver cancer cases, 281 CLD mortalities diagnosed, and 1061 age‐matched, gender‐matched, and trial‐matched controls. We used multivariable logistic regression models to calculate odds ratios and 95% confidence intervals. Subgroup analysis and interaction tests were performed by age, gender, alcohol drinking, hepatitis B virus seropositivity (HBV+)/hepatitis C virus seropositivity (HCV+), and trial.

Results

Participants with serum ferritin in the highest quartile, as compared with those in the lowest quartile, had an increased risk of CLD mortality (odds ratio = 1.72, 95% confidence interval = 1.12, 2.64, P‐trend < 0.01). Moreover, the association with higher serum ferritin was stronger among alcohol drinkers and those who were HCV+ (P‐interaction < 0.05). For incident liver cancer, risk estimates were above one but were not statistically significant.

Conclusion

In this study, higher levels of serum ferritin at baseline were associated with subsequent mortality from CLD, particularly if combined with alcohol drinking or viral hepatitis. Further work is warranted to confirm our findings.
Formal and informal social participation and elder mistreatment in a national sample of older adults
Authors: Yang Emmy Z. , Kotwal Ashwin A. , Lisha Nadra E. , Wong Jaclyn S. , Huang Alison J.
Published: June 2021

Background/Objectives

Older adults' susceptibility to mistreatment may be affected by their participation in social activities, but little is known about relationships between social participation and elder mistreatment.

Design

Cross‐sectional analysis.

Setting/Participants

National probability sample of older community‐dwelling U.S. adults interviewed in 2015–2016, including 1268 women and 973 men (mean age 75 years and 76 years, respectively; 82% non‐Hispanic white).

Measurements

Frequency of participation in formal activities (organized meetings, religious services, and volunteering) and informal social activities (visiting friends and family) was assessed by questionnaire. Elder mistreatment included emotional (four items), physical (two items), and financial mistreatment (two items) since age 60. Multivariable logistic regression examined associations between each type of social participation and elder mistreatment among men and women, adjusting for age, race/ethnicity, education, and comorbidity.

Results

Forty percent of women and 22% of men reported at least one form of mistreatment (emotional, physical, or financial). Women reporting at least monthly engagement in formal social activities were more likely to report emotional mistreatment (adjusted odds ratio (AOR) 1.59, 95% confidence interval (CI) 1.09–2.33). Among men, monthly organized meeting attendance was associated with increased odds of emotional mistreatment (AOR 1.34, 95% CI 1.01–1.93). Weekly informal socializing was inversely associated with emotional mistreatment (AOR 0.59, 95% CI 0.44–0.78) and financial mistreatment (AOR 0.59, 95% CI 0.42–0.85) among women.

Conclusion

In this national cohort, older adults who were frequently engaged in formal social activities reported similar or higher levels of mistreatment than those with less frequent organized social participation. Older women with regular informal contact with family or friends were less likely to report some kinds of mistreatment. Strategies for detecting and mitigating elder mistreatment should consider differences in patterns of formal and informal social participation and their potential contribution to mistreatment risk.
Polypharmacy among older adults with dementia compared with those without dementia in the United States
Authors: Growdon Matthew E. , Gan Siqi , Yaffe Kristine , Steinman Michael A.
Published: June 2021

Background/objectives

In older persons with dementia (PWD), extensive medication use is often unnecessary, discordant with goals of care, and possibly harmful. The objective of this study was to determine the prevalence and medication constituents of polypharmacy among older PWD attending outpatient visits in the United States.

Design

Cross‐sectional analysis.

Setting and participants

PWD and persons without dementia (PWOD) aged ≥65 years attending outpatient visits recorded in the nationally representative National Ambulatory Medical Care Survey (NAMCS), 2014–2016.

Measurements

PWD were identified as those with a diagnosis of dementia on the NAMCS encounter form and/or those receiving an anti‐dementia medication. Visits with PWD and PWOD were compared in terms of sociodemographic, practice/physician factors, comorbidities, and prescribing outcomes. Regression analyses examined the effect of dementia diagnosis on contributions by clinically relevant medication categories to polypharmacy (defined as being prescribed ≥5 prescription and/or nonprescription medications).

Results

The unweighted sample involved 918 visits for PWD and 26,543 visits for PWOD, representing 29.0 and 780 million outpatient visits. PWD had a median age of 81 and on average had 2.8 comorbidities other than dementia; 63% were female. The median number of medications in PWD was eight compared with three in PWOD (p < 0.001). After adjustment, PWD had significantly higher odds of being prescribed ≥5 medications (AOR 3.0; 95% CI: 2.1–4.3) or ≥10 medications (AOR 2.8; 95% CI: 2.0–4.2) compared with PWOD. The largest sources of medications among PWD were cardiovascular and central nervous system medications; usage from other categories was generally elevated in PWD compared with PWOD. PWD had higher odds of receiving at least one highly sedating or anticholinergic medication (AOR 2.5; 95% CI: 1.6–3.9).

Conclusion

In a representative sample of outpatient visits, polypharmacy was extremely common among PWD, driven by a wide array of medication categories. Addressing polypharmacy in PWD will require cross‐cutting and multidisciplinary approaches.
Pushed Past the Limit? How Japanese Banks Reacted to Negative Rates
Authors: HONG GEE HEE , KANDRAC JOHN
Published: June 2021

We investigate how the surprise introduction of negative interest rate policy (NIRP) in Japan affected banks' lending and risk‐taking behavior. Equity prices of Japanese financial firms fell sharply despite the accommodative policy, and we document the characteristics that heighten Japanese banks' exposure to NIRP. We exploit the cross‐sectional variation in the change of share prices around the announcement to measure banks' differential exposure to NIRP. Consistent with the risk taking channel, we find that more exposed banks insulated their profits from the adverse effects of NIRP by boosting risk‐taking behavior and increasing credit supply relative to less exposed banks.
Parvovirus B19 in Pregnancy: A Case Review
Authors: Hunter Linda A. , Ayala Nina K.
Published: June 2021

Parvovirus B19 has been identified as the cause of erythema infectiosum, a common childhood illness. Also known as fifth disease, this virus is highly contagious among school‐age children, especially during the winter months when outbreaks within classrooms are widespread. The majority of adults have had the infection in childhood and are immune to recurrence. Approximately 40% of childbearing‐age individuals, however, remain nonimmune and susceptible to infection. If acquired during pregnancy, parvovirus B19 infection can have devastating fetal consequences, especially if contracted in the second trimester. Vertical transmission of parvovirus B19 occurs more readily during this gestational period, and fetal loss rates of 8% to 17% have been reported as a result of severe fetal anemia and hydrops fetalis. Unfortunately, adults with parvovirus B19 infection are often asymptomatic and do not exhibit the classic slapped‐cheek rash seen in childhood. More commonly, adults will exhibit atypical symptoms such as joint arthralgias. Maternal history of direct exposure to a confirmed case within the family or the presence of atypical symptoms warrants serum antibody screening. Although the presence of immunoglobulin G confirms immunity, any immunoglobulin M positivity will require ongoing fetal surveillance for evidence of fetal anemia and hydrops fetalis. Serial ultrasound imaging for 8 to 12 weeks with Doppler measurements of the peak systolic velocity in the middle cerebral artery are the mainstays of fetal monitoring. Referral to a maternal‐fetal medicine specialist with experience in fetal blood sampling and intrauterine transfusion is recommended for any cases of hydrops fetalis or if a concern for severe fetal anemia exists.
Phosphorylation of trans‐active response DNA‐binding protein‐of 43 kDa promotes its cytoplasmic aggregation and modulates its function in tau mRNA stability and exon 10 alternative splicing
Authors: Wu Ruozhen , Zhou Dingwei , Shen Xin , Chen Feng , Liu Fei , Gu Jianlan
Published: June 2021

Trans‐active response DNA‐binding protein of 43 kDa (TDP‐43) promotes tau mRNA instability and tau exon 10 inclusion. Aggregation of phosphorylated TDP‐43 is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Casein kinase 1ε (CK1ε) phosphorylates TDP‐43 at multiple sites, enhances its cytoplasmic aggregation, and modulates its function in tau mRNA processing. To determine roles of TDP‐43 site‐specific phosphorylation in its localization, aggregation, and function in tau mRNA processing, TDP‐43 was mutated to alanine or aspartic acid at Ser379, Ser403/404, or Ser409/410 to block or mimic phosphorylation. Site‐specific phosphorylation of TDP‐43 and its mutants by CK1ε was studied in vitro and in cultured cells. Cytoplasmic and nuclear TDP‐43 and phospho‐TDP‐43 were analyzed by western blots. Aggregation of TDP‐43 was assessed by immunostaining and level of radioimmunoprecipitation assay buffer‐insoluble TDP‐43. Green florescent protein tailed with tau 3′‐untranslated region and mini‐tau gene pCI/SI9‐LI10 were used to study tau mRNA stability and alternative splicing of tau exon 10. We found that phospho‐blocking mutations of TDP‐43 at Ser379, Ser403/404, or Ser409/410 were not effectively phosphorylated by CK1ε. Compared with TDP‐43, higher level of phosphorylated TDP‐43 in the cytoplasm was observed. Phospho‐mimicking mutations at these sites enhanced cytoplasmic aggregation of TDP‐43. Green florescent protein expression was not inhibited by phospho‐blocking mutants of TDP‐43, but tau exon 10 inclusion was further enhanced by phospho‐blocking mutations at Ser379 and Ser403/404. Phosphorylation of TDP‐43 at Ser379, Ser403/404, or Ser409/410 primes its phosphorylation by CK1ε, promotes TDP‐43 cytoplasmic aggregation, and modulates its function in tau mRNA processing in site‐specific manner.

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Small junction, big problems: Neuromuscular junction pathology in mouse models of amyotrophic lateral sclerosis (ALS)
Authors: Alhindi Abrar , Boehm Ines , Chaytow Helena
Published: June 2021

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with an extremely heterogeneous clinical and genetic phenotype. In our efforts to find therapies for ALS, the scientific community has developed a plethora of mouse models, each with their own benefits and drawbacks. The peripheral nervous system, specifically the neuromuscular junction (NMJ), is known to be affected in ALS patients and shows marked dysfunction across mouse models. Evidence of pathology at the NMJ includes denervated NMJs, changes in endplate size and loss of terminal Schwann cells. This review compares the temporal disease progression with severity of disease at the NMJ in mouse models with the most commonly mutated genes in ALS patients (SOD1, C9ORF72, TARDBP and FUS). Despite variability, early NMJ dysfunction seems to be a common factor in models with SOD1, TARDBP and FUS mutations, while C9ORF72 models do not appear to follow the same pattern of pathology. Further work into determining the timing of NMJ pathology, particularly in newer ALS mouse models, will confirm its pivotal role in ALS pathogenesis and therefore highlight the NMJ as a potential therapeutic target.
The relationship between inflammation markers and ketonuria in hyperemesis gravidarum
Authors: Soysal Cenk , Işıkalan Mehmet Murat , Bıyık İsmail , Erten Özlem , İnce Onur
Published: June 2021

Objective

Hyperemesis gravidarum is an illness that starts in early pregnancy and manifests itself with oral intake problems, electrolyte imbalance, ketonuria, and weight loss. Inflammation is closely associated with the hyperemesis gravidarum, and inflammatory indicators have been studied to understand its pathophysiology. This study investigates the relationship of ketonuria levels with inflammatory markers platelet‐to‐lymphocyte ratio (PLR), monocyte‐to‐lymphocyte ratio (MLR), and neutrophil‐to‐lymphocyte ratio (NLR) for hyperemesis gravidarum patients.

Material and Methods

This retrospective case control study was conducted at Kütahya Medical Sciences University Tertiary Research and Training Hospital between December 2019 and December 2020. A total of 173 pregnancies, 82 of them with hyperemesis gravidarum and 91 of them low‐risk pregnancies were included in the study. The patients' demographic profiles and laboratory parameters were recorded. The patients were divided into hyperemesis gravidarum and control groups and the groups were compared for the levels of inflammation markers. For the hyperemesis gravidarum group, the relationship between ketonuria levels and the inflammation severity was investigated.

Results

MLR, NLR, PLR levels were higher in the hyperemesis gravidarum group than the control group in a statistically significant way (p < 0.001 for all of the comparisons). The hyperemesis gravidarum group was subdivided into four groups based on their ketonuria levels, and their MLR, NLR, PLR levels were compared. The differences between the groups were statistically significant (p < 0.001) and the indicators increased with the ketonuria levels. Finally, ketonuria levels had a positive and significant correlation with MLR (rho =0.67, p < 0.001), PLR (rho =0.67, p < 0.001), and NLR (rho =0.8, p < 0.001).

Conclusion

Hyperemesis gravidarum patients have higher levels of hematologic inflammation indicators than healthy pregnant patients. For these patients, the levels of the indicators increase with ketonuria levels.