bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum neurofilament light chain cut‐off definition for clinical diagnosis and prognosis of amyotrophic lateral sclerosis
Authors: Brousse Mehdi , Delaby Constance , De La Cruz Elisa , Kuhle Jens , Benkert Pascal , Mondesert Etienne , Ginestet Nelly , Hirtz Christophe , Camu William , Lehmann Sylvain , Esselin Florence
Published: April 2023

Background

The neurofilament light chain (NfL) assay is gradually becoming an essential diagnostic tool for the diagnosis of many neurological diseases including amyotrophic lateral sclerosis (ALS). Different methods for the determination of this biomarker in serum have been developed in recent years.

Methods

We measured blood NfL in 429 patients referred to the tertiary ALS center of Montpellier, France using two different ultrasensitive methods (Ella™ and Simoa™) and we compared the clinical performances of these two approaches. We also converted NfL values into age and body mass index‐adjusted Z‐scores to assess cut‐off values of this biomarker in this clinical context.

Results

We show comparable diagnostic and prognostic performance of Ella™ and Simoa™ technologies in ALS, with specificities and sensitivities exceeding 80% for both. We propose cut‐off values for serum NfL in this clinical context, thus enabling the routine clinical use of this biomarker.

Conclusion

The use of NfL in routine clinical practice will help predict survival and improve diagnostic accuracy by distinguishing ALS from other neurological diseases and motor neuron disease mimics.
Actigraphic correlates of neuropsychiatric symptoms in adults with focal epilepsy
Authors: Abboud Mark A. , Kamen Jessica L. , Bass John S. , Lin Lu , Gavvala Jay R. , Rao Sindhu , Smagula Stephen F. , Krishnan Vaishnav
Published: April 2023

Objectives

Disability in patients with epilepsy (PWEs) is multifactorial: beyond seizure frequency/severity, PWEs are prone to a range of neuropsychiatric, cognitive, and somatic comorbidities that significantly affect quality of life. Here, we explored how variations in seizure severity and the burden of self‐reported somatic/neuropsychiatric symptoms correlate with disruptions to 24 h activity patterns (rest‐activity rhythms [RARs]), determined through wrist accelerometry/actigraphy.

Methods

Multiday wrist‐actigraphy recordings were obtained from 59 adult patients with focal epilepsy (44% male, ages 18–72), who contemporaneously responded to validated psychometric instruments to measure anxiety, depression, sleepiness, and somatic symptoms. We conducted a similar in silico psychometric‐actigraphic correlation in a publicly available data set of 1747 Hispanic subjects (35% male, ages 18–65) from the Study of Latinos (SOL) Sueño Ancillary Study. RARs were analyzed via a sigmoidally‐transformed cosine model (quantifying amplitude, steepness, acrophase, and robustness) and nonparametric measures to estimate RAR stability, fragmentation, and sleep.

Results

Compared with matched SOL subjects, RARs from PWE subjects featured a significantly lower amplitude, a wider rest phase, and significantly more total daily sleep. Within PWEs, similar RAR distortions were associated with seizure intractability and/or anticonvulsant polytherapy, whereas high anxiety, depression, and somatic symptom scores were associated with lower RAR robustness and acrophase delay. We applied the SOL data set to train logistic regression models to dichotomously classify subjective anxiety, depression, and sleepiness symptoms using demographic and RAR parameters. When tested on PWEs, these models predicted prevalent anxiety and depression symptom burden (accuracy ~70%) but failed to predict subjective sleepiness.

Significance

Together these results demonstrate that RAR features may encode prevalent depression and anxiety symptoms in patients with focal epilepsy, potentially offering wearable‐derived endpoints to adjunct clinical care and drug/device trials. With larger PWE‐specific actigraphic‐psychometric data sets, we may identify RAR signatures that may more precisely correlate with varying seizure frequency, the burden of anticonvulsant therapy, and prevalent mood/anxiety symptoms.
Automated detection of focal seizures using subcutaneously implanted electrocardiographic device: A proof‐of‐concept study
Authors: Jeppesen Jesper , Christensen Jakob , Mølgaard Henning , Beniczky Sándor
Published: April 2023

Phase 2 studies showed that focal seizures could be detected by algorithms using heart rate variability (HRV) in patients with marked autonomic ictal changes. However, wearable surface electrocardiographic (ECG) devices use electrode patches that need to be changed often and may cause skin irritation. We report the first study of automated seizure detection using a subcutaneously implantable cardiac monitor (ICM; Confirm Rx, Abbott). For this proof‐of‐concept (phase 1) study, we recruited six patients admitted to long‐term video‐electroencephalographic monitoring. Fifteen‐minute epochs of ECG signals were saved for each seizure and for control (nonseizure) epochs in the epilepsy monitoring unit (EMU) and in the patients' home environment (1–8 months). We analyzed the ICM signals offline, using a previously developed HRV algorithm. Thirteen seizures were recorded in the EMU, and 41 seizures were recorded in the home‐monitoring period. The algorithm accurately identified 50 of 54 focal seizures (sensitivity = 92.6%, 95% confidence interval [CI] = 85.6%–99.6%). Twelve of the 13 seizures in the EMU were detected (sensitivity = 92.3%, 95% CI = 77.2%–100%), and 38 of the 41 seizures in the out‐of‐hospital setting were detected (sensitivity = 92.7%, 95% CI = 84.7%–100%). Four false detections were found in the 141 control (nonseizure) epochs (false alarm rate = 2.7/24 h). Our results suggest that automated seizure detection using a long‐term, subcutaneous ICM device is feasible and accurate in patients with focal seizures and autonomic ictal changes.
Backsourcing in the private and public sectors—A systematic review
Authors: Berlin Johan , Carlström Eric , Karlsson David
Published: April 2023

This article provides a systematic review of the literature on backsourcing. The aim is to synthesize existing literature in order to compare and analyze similarities and differences in backsourcing in the private and public sectors. The study asks questions about: which methods and theories have been used, why backsourcing has been implemented, and what reasons have been described for backsourcing. The study is based on an analysis of 500 articles about backsourcing and 33 articles in the final data set. The results show that backsourcing is primarily caused by: increased costs, lack of quality, and contract problems in the private sector, along with loss of control, cost saving, and changed strategy in the public sector. The study's synthesis highlights three explanations for how backsourcing is managed and interpreted in both the sectors. The article contributes specifically to summarizing current research on backsourcing, synthesizing how backsourcing has been studied, illustrating gaps in the research, as well as explaining relevant differences between private and public backsourcing.
Examining actor–partner effects between social dominance, relationship power, sexism, and marital quality
Authors: Ymamgulyyeva Aysoltan , Kafescioğlu Nilüfer , Harma Mehmet
Published: April 2023

Objective

This study aimed to investigate the actor–partner effects of attitudes toward group‐based inequality as measured by social dominance orientation (SDO) and marital quality, and the indirect actor–partner effects of SDO on marital quality via ambivalent sexism and partners' perceptions of their own relationship power toward their partner.

Background

Previous research suggests that certain social attitudes play a role in relationship processes. However, it is unclear whether broader views on social inequality could have an effect on partners' marital quality.

Method

Ninety heterosexual married couples in Turkey (N = 180) responded via an online survey on SDO, marital quality, relationship power, and ambivalent sexism. Actor–partner interdependence model (APIM) and actor–partner interdependence model of mediation (APIMeM) were conducted to examine the direct and indirect actor–partner effects.

Results

For indirect effects, men's SDO was negatively associated with their marital quality through their relationship power and hostile sexism. No significant indirect effects were found for women. However, women's relationship power was positively and their benevolent sexism was negatively associated with their own and their partners' marital quality.

Conclusion

Our findings help develop a more comprehensive understanding of how the political, social, and personal aspects of our lives are connected with one another.

Implications

Our study points to the importance of exploring the topic of men's and women's views toward social inequality and its effects on their close relationships in clinical practice and relational education.
Being our best: Understanding the relationship between empowerment and employee engagement among midlevel student affairs professionals
Authors: McNaughtan Jon , Garza Tiberio , Eicke Dustin , Garcia Hugo A. , Bodine Al‐Sharif Mary Ann
Published: April 2023

Over the last few decades, there has been a significant increase in the number of student service personnel, yet demand has outstripped this growth leading to turnover and low employee satisfaction. Scholars and practitioners alike have called for increased levels of empowerment of these workers, but the outcomes of this approach need further analysis. We utilize data from a survey of international centre directors in the United States and employ a partial least squares‐based structural equation modelling to investigate the relationship between empowerment and employ perceptions including work satisfaction, organizational commitment, perspective of leadership and personal engagement. Specifically, trust meaning and personal consequence are strong components of empowerment in this sample. Our results indicate a positive relationship between empowerment and job satisfaction, organizational commitment and perspectives on leadership. In addition, we find that organizational commitment mediates the relationship between empowerment and personal engagement.
Developing a comprehensive leadership development model in higher education context: A co‐design approach
Authors: Dinh Ngoc Bich Khuyen , Zhu Chang , Qi Zhengwen , Kondakci Yasar
Published: April 2023

Higher education (HE) in the changing context requires leadership training and development as a vital element for university governance and innovation. While there are several theoretical frameworks on leadership development, most of them are outcome evaluation‐oriented. Consequently, there is a lack of a leadership development model which emphasises both design process and expected outcomes. In addition to this, HE leadership development has been gradually transformed toward complexity and flexibility due to the volatile external environment of the 21st century. Thus, instead of having a development programme that simply focuses on individual skill enhancement, a comprehensive leadership development programme that equally fosters leaders' competencies (leader development) and develops collective leadership (leadership development) is increasingly utilised. Unfortunately, previous theoretical frameworks fail to take into consideration these new features. The main aim of this study was to develop a comprehensive theoretical model for academic leadership development (ALD) that promotes both leader development and leadership development. In the present study, 24 academic leaders, lecturers and researchers from five European and six Chinese HE institutions co‐designed the ALD model. The constructed model consists of four main dimensions: theoretical core, types of training and providers, training format and ultimate goals. The results contribute to developing, promoting and enhancing leadership development in academic settings.
Comparative analysis of reciprocating and flat‐side heat‐treated rotary single‐file systems: Design, metallurgical characteristics, and mechanical performance
Authors: Martins Jorge N. R. , Silva Emmanuel J. N. L. , Baruwa Abayomi O. , Pereira da Costa Rui , Braz Fernandes Francisco M. , Versiani Marco A.
Published: April 2023

Aim

To compare two flat‐side single‐file rotary instruments with three single‐file reciprocating systems through a multimethod assessment.

Methodology

A total of 290 new NiTi single‐file rotary (AF F One Blue 25/0.06 and Platinum V.EU 25/0.06) and reciprocating (One Files Blue R25, Reciproc Blue R25, Reciproc R25) instruments were selected, carefully examined for any major deformations, and evaluated regarding their macroscopic and microscopic design, nickel and titanium elements ratio, phase transformation temperatures, and mechanical performance (time/rotation to fracture, maximum torque, angle of rotation, microhardness, maximum bending, and buckling strengths). One‐way anova post hoc Tukey, T‐test, and nonparametric Mood's median tests were used for statistical comparisons (α = 5%).

Results

Tested instruments had identical blade counts and near‐identical helical angles of approximately 24° (rotary instruments) and 151° (reciprocating instruments). The flat‐side analysis revealed a few inconsistencies, such as discontinuity segments, different orientations, and gaps in the homogeneity of the bluish colour. Microscopically, flat‐side instruments exhibited blade discontinuity and an incomplete S‐shaped cross‐section. The surface finish was smoother for One Files Blue and more irregular for both rotary instruments. There were distinct phase transformation temperatures amongst all instruments. All heat‐treated instruments were in R‐phase arrangement, and Reciproc was in R‐phase plus austenite at test temperature (20°C). Compared with the reciprocating instruments, both flat‐side instruments exhibited lower results in the cyclic fatigue tests using two different clockwise kinematics, maximum torque, angle of rotation, and maximum buckling strength (p < .05). The rotary systems also exhibited low flexibility (p < .05). AF F One Blue had the lowest microhardness, whilst Reciproc had the highest value.

Conclusion

This multimethod investigation revealed that the flat‐side rotary instruments underperformed the reciprocating instruments regarding cyclic fatigue (with two different clockwise kinematics), maximum torque, angle of rotation, maximum buckling strength, and flexibility. Manufacturing inconsistencies were also observed in some of the flat‐side instruments, including discontinuity segments, different orientations, and in the homogeneity of their bluish colour given by the heat treatment.
Robbery victimization of Mexican migrants while crossing the border
Authors: Torre Cantalapiedra Eduardo , Hernández Campos Carlos Manuel
Published: April 2023

We analyse the factors associated with Mexican migrants being victims of robbery or assault while crossing the US–Mexico border, based on an analytical model of the victimization of migration in transit. Drawing on Emif Norte survey, we analyse the prevalence of victimization of robbery or assault to migrants according to migrant's sociodemographic characteristics as well as the journey characteristics, and we use a logistic regression model to assess the way in which such characteristics are associated with being victim of that crime. Findings suggest that migrants who crossed through Tamaulipas and those who hired coyotes in transit or at the border have higher odds of being robbed or assaulted, in contrast, the individual sociodemographic characteristics and crossing with family/friends are not associated with being robbed or assaulted.
Aspirin deprescribing in primary prevention of cardiovascular disease: a prospective risk–benefit approach
Authors: Scarfo Nicholas L. , Thomas Vinod , Mayboroda Markian S. , Hewage Udul
Published: April 2023

Background

Current evidence and practice guidelines do not recommend aspirin for primary prevention of cardiovascular disease (CVD). Insufficient all‐cause mortality benefits juxtaposed to increased gastrointestinal bleeding rates are well established. Pharmacists are well placed to assess the clinical appropriateness of aspirin in CVD and initiate deprescribing as required with medical colleagues.

Aim

The aim of this study was to identify medical inpatients taking aspirin for primary prevention of CVD and initiate deprescribing utilising a risk‐benefit approach.

Methods

A single‐arm prospective feasibility study of general medicine patients admitted to a major tertiary hospital over 5 weeks (July–August 2020) was conducted. Screened patients were categorised as either taking aspirin for primary or secondary prevention. A 5‐year benefit–risk analysis of bleeding and cardiovascular risk was calculated using a validated tool from the Cardiac Society of Australia and New Zealand to guide recommendations.

Results

This study screened 277 patients, of which 71 patients were identified as taking aspirin. Ten of these patients (14%) were categorised as taking aspirin for primary prevention and thus were deemed suitable for deprescribing. The analysis showed that aspirin continuance would, on average, increase major bleeding events by 39%, whilst reducing major cardiovascular events by 13.4%. Pharmacists recommended aspirin cessation in seven of the cases identified, and deprescribing was successful in five cases.

Conclusions

This study described an impactful pharmacist‐led initiative utilising a validated aspirin‐specific tool to conduct risk–benefit analysis to reduce potential major bleeding associated with inappropriate aspirin use.
Reduced gastrointestinal‐related hospitalisation costs following rescheduling of over‐the‐counter codeine‐containing compound analgesics in Australia: results of a single hospital audit in South Australia
Authors: Mathias Ryan , Howes Bejamin , Cock Victoria , Cock Charles
Published: April 2023

Background

Codeine‐containing compound analgesics (CCCAs) are associated with dependence and, when taken in excess, significant risks of harm. A previous audit showed significant costs related to admissions for gastrointestinal (GI) complications of CCCA. Based on this and other evidence of harm, the Australian Therapeutic Goods Administration changed CCCAs to prescription only in 2018.

Aims

We aimed to identify the costs associated with codeine‐related GI complications and whether the schedule change in 2018 led to a reduced clinical and financial strain on the health care system.

Methods

We conducted an audit of GI admissions and associated costs of CCCAs at a tertiary teaching hospital in Adelaide between 2016 and 2020. Patients were grouped by 2‐year time periods before (group 1) and following (group 2) schedule change. Costs for the index presentation were multiplied for subsequent presentations. Costs and outcomes were compared for groups (standard statistics; P value < 0.05 significant.)

Results

Three hundred forty patients (group 1, n = 164; group 2, n = 119) were identified, with the majority of these admitted due to nonsteroidal anti‐inflammatory drugs (NSAIDs) only. For CCCAs (NSAID‐containing), the same patients were admitted repeatedly with a reduction from 31 to eight admissions (P = 0.005), following rescheduling. The total cost of CCCA admissions was reduced from AU$ 561 691 for group 1 to AU$ 261 764 for group 2 (P < 0.001).

Conclusions

Australian rescheduling of CCCAs in 2018 resulted in a reduction in hospital admissions and costs related to GI complications. The cost savings, even in a single hospital department, were substantial.
Analysis of Part 1 of the latest Austroads Guidelines, June 2022
Authors: Beran Roy G. , Devereux John A.
Published: April 2023

The Austroads Fitness to Drive Guidelines were updated in 2022. Most of the focus to date has been on Part 2 of the Guidelines, which provide guidance as to specific medical conditions. Less attention has been paid to Part 1 of the Guidelines, which cover a medical practitioner's ethical and legal obligations. This paper addresses the imbalance by considering and amplifying the obligations discussed in Part 1 of the Guidelines.
Identifying factors associated with terrorist attack locations by data mining and machine learning
Authors: Bridgelall Raj
Published: April 2023

While studies typically investigate the socio‐economic factors of perpetrators to comprehend terrorism motivations, there was less emphasis placed on factors related to terrorist attack locations. Addressing this knowledge gap, this study conducts a multivariate analysis to determine attributes that are more associated with terrorist attacked locations than others. To tackle the challenge of identifying pertinent attributes, the methodology merges a Global Terrorism Database with relevant socio‐economic attributes from the literature. The workflow then trains 11 machine learning (ML) models on the combined data set. Among the 75 attributes assessed, 10 improved the predictability of targeted locations, with population and public transportation infrastructure being key factors. After optimizing hyperparameters, a multi‐layer perceptron—a type of artificial neural network—exhibited superior predictive performance, achieving an area under the curve score of 89.3%, classification accuracy of 88.1% and a harmonically balanced precision and recall score of 87.3%. In contrast, support vector machines demonstrated the poorest performance. The study also revealed that race, age, gender, marital status, income level and home values did not improve predictive performance. The ML workflow developed can aid policymakers in quantifying risks and making objective decisions regarding resource allocation to safeguard public health.
Microstructures and photovoltaic effect of KNbO3–SrCo0.5Hf0.5O3−δ ferroelectric semiconductors
Authors: Su Mingwei , Su Qi , Deng Tingcong , Gao Qingyuan , Yuan Changlai , Xiong Jian , Liu Xiao , Lei Wen , Xu Jiwen , Liu Fei , Zhou Changrong , Rao Guang Hui
Published: April 2023

Polarization is one of the unique properties of ferroelectric materials; yet the polarization mechanism for enhancing ferroelectric photovoltaic performance is rarely been investigated, particularly in terms of bandgap variation. In this work, the effect of high‐field polarization on the enhanced photovoltaic performance of a ferroelectric ceramic, 0.98KNbO3–0.02SrCo0.5Hf0.5O3−δ (KNSCH2), was explored in terms of bandgap variation. The bandgap of the KNSCH2 sample shrank after polarization because of the increase in potential energy band overlap and the upward shift of the valence band due to increased oxygen‐vacancy defects. The polarization optimized the energy band structure of KNSCH2, promoting the separation and transport of photoinduced carriers and thus further enhancing its photovoltaic performance. The KNSCH2 sample shows a twofold enhancement in Jsc after 60 kV/cm polarization. The degree of the lattice distortion of KNSNH2 increased following polarization, causing a minute increase in its cell asymmetry. The reasons for the bandgap narrowing and the creation of sub‐bandgaps in the KNSCH samples were also investigated. This work opened new doors to understanding the mechanisms underlying the polarization‐enhanced photovoltaic performance of ferroelectric materials.
The photic‐aphotic divide is a strong ecological and evolutionary force determining the distribution of ciliates (Alveolata, Ciliophora) in the ocean
Authors: Santoferrara Luciana F. , Qureshi Aleena , Sher Amina , Blanco‐Bercial Leocadio
Published: April 2023

The bulk of knowledge on marine ciliates is from shallow and/or sunlit waters. We studied ciliate diversity and distribution across epi‐ and mesopelagic oceanic waters, using DNA metabarcoding and phylogeny‐based metrics. We analyzed sequences of the 18S rRNA gene (V4 region) from 369 samples collected at 12 depths (0–1000 m) at the Bermuda Atlantic Time‐series Study site of the Sargasso Sea (North Atlantic) monthly for 3 years. The comprehensive depth and temporal resolutions analyzed led to three main findings. First, there was a gradual but significant decrease in alpha‐diversity (based on Faith's phylogenetic diversity index) from surface to 1000‐m waters. Second, multivariate analyses of beta‐diversity (based on UniFrac distances) indicate that ciliate assemblages change significantly from photic to aphotic waters, with a switch from Oligotrichea to Oligohymenophorea prevalence. Third, phylogenetic placement of sequence variants and clade‐level correlations (EPA‐ng and GAPPA algorithms) show Oligotrichea, Litostomatea, Prostomatea, and Phyllopharyngea as anti‐correlated with depth, while Oligohymenophorea (especially Apostomatia) have a direct relationship with depth. Two enigmatic environmental clades include either prevalent variants widely distributed in aphotic layers (the Oligohymenophorea OLIGO5) or subclades differentially distributed in photic versus aphotic waters (the Discotrichidae NASSO1). These results settle contradictory relationships between ciliate alpha‐diversity and depth reported before, suggest functional changes in ciliate assemblages from photic to aphotic waters (with the prevalence of algivory and mixotrophy vs. omnivory and parasitism, respectively), and indicate that contemporary taxon distributions in the vertical profile have been strongly influenced by evolutionary processes. Integration of DNA sequences with organismal data (microscopy, functional experiments) and development of databases that link these sources of information remain as major tasks to better understand ciliate diversity, ecological roles, and evolution in the ocean.
Critically feminizing family science: Using femme theory to generate novel approaches for the study of families and relationships
Authors: Hoskin Rhea Ashley , Serafini Toni
Published: April 2023

How do values, beliefs, and assumptions about femininity shape relational experiences? To answer this question, we critically feminize family science by applying femme theory to the field. Through this analysis, we present some of the ways that femmephobia (i.e., the systematic devaluation and regulation of femininity across all bodies and identities) is established in childhood and perpetuated throughout various relational contexts across the life course. Specifically, we examine how femmephobia is socialized via families, systematically normalized and perpetuated throughout childhood, and how it shapes gender‐based violence risk, perpetration, and tactics. We demonstrate how femme theory illuminates the importance of disentangling the intersectional axes of gender, sexuality, and gender expression, thereby generating novel approaches for family and relationship science and interventions that promote systemic social change. Subordinating and regulating femininity affects all individuals, making its disruption of critical importance for the prevention of gender‐based violence and the promotion of healthy families and relationships.
Monetary Policy and Net Exports Externalities in the Small Open Economy
Authors: SHIM JAE HUN
Published: April 2023

We extend a New Keynesian small open economy dynamic stochastic general equilibrium (DSGE) model with nontradable goods and intermediate inputs. We show that the optimal monetary policy in the small open economy is not necessarily isomorphic to the closed economy due to net exports externalities. The optimal policymaker is willing to take advantage of the externalities and to raise the real value of home production, along with stabilizing composite domestic inflation. Also, we rank alternative monetary policy rules, estimate the optimal monetary policy rule associated with welfare, and show that setting interest rates toward their target levels of composite domestic inflation and net exports is desirable.
Illiquidity, R&D Investment, and Stock Returns
Authors: AHMED SHAMIM , BU ZIWEN , YE XIAOXIA
Published: April 2023

We propose a dynamic model of research and development (R&D) venture, which predicts that the positive relation between the firm's R&D investment and the expected stock returns strengthens with illiquidity. Consistent with the model's prediction, empirical evidence based on cross‐sectional regressions and double‐sorted portfolios largely suggests a stronger and positive R&D–return relation among illiquid stocks. A further analysis shows that the important role of illiquidity in the R&D–return relation cannot be explained by factors, such as financial constraints, innovation ability, and product market competition. Collectively, our results suggest that stock illiquidity is an independent driver of the R&D premium.
Monetary Policy Communication: Perspectives from Former Policymakers at the ECB
Authors: Ehrmann Michael , Holton Sarah , Kedan Danielle , Phelan Gillian
Published: April 2023

A survey on monetary policy communication among former members of the Governing Council of the European Central Bank (ECB) reveals that enhancing credibility and trust is viewed as the most important objective of communication. Respondents judge communication with financial markets and experts as adequate, but see room for improvement in communicating with the public. The central bank objective is seen as the most important topic. Several respondents perceived the ECB's inflation aim of “below, but close to, 2%” that was in place at the time as ambiguous and in need of clarification. Overall, there is broad consensus on various communication issues.
Spontaneous activity of specific C‐nociceptor subtypes from diabetic patients and mice: Involvement of reactive dicarbonyl compounds and (sensitized) transient receptor potential channel A1
Authors: Becker Anna K. , Babes Alexandru , Düll Miriam M. , Khalil Mohammad , Kender Zoltan , Gröner Jan , Namer Barbara , Reeh Peter W. , Sauer Susanne K.
Published: April 2023

Background

Diabetic metabolism causes changes of the chemical milieu including accumulation of reactive carbonyl species, for example, methylglyoxal (MGO). MGO activates chemosensitive TRPA1 on nociceptors, but the contribution to neuronal pathophysiology causing pain and hyperalgesia in diabetic neuropathy is not fully understood.

Methods

We employed single‐nerve‐fiber recordings in type 2 diabetes patients with (spDN) and without cutaneous pain (DN) and in streptozotocin‐diabetic and healthy mice. In mice, we measured Ca++ transients in cultured DRG neurons and stimulated CGRP release from hairy skin.

Results

In diabetic patients, we recorded a large proportion of pathologically altered nerve C‐fibers (79%). In spDN patients we found a higher percentage (72%) of spontaneously active C‐nociceptors than in DN patients (15%). The proportion of spontaneous activity was highest among pathological fibers with mechanoinsensitive fiber properties which are particularly sensitive to MGO in contrast to mechanosensitive fibers. Mouse polymodal nociceptors, in contrast to purely mechanosensitive C‐fibers, showed highest prevalence of TRPA1‐related chemosensitivity. In diabetic mice about 37% of polymodal nociceptors developed spontaneous activity and exhibited significantly greater MGO responses, indicating sensitized TRPA1 receptors. Low‐threshold mechanosensitive Aδ‐fibers were vigorously activated by MGO but independently of TRPA1 activation.

Interpretation

Our translational findings suggest that TRPA1‐expressing C‐nociceptors, which in human correspond to mechanoinsensitive and in mice to polymodal nociceptors, are especially vulnerable to develop spontaneous activity. Those two different nociceptor classes might share the functional role as dicarbonyl‐sensitive chemosensors and represent the critical nociceptor population that support the development of pain and hyperalgesia in diabetic neuropathy.
Nephrology‐tailored geriatric assessment as decision‐making tool in kidney failure
Authors: Berkhout‐Byrne Noeleen C. , Voorend Carlijn G. N. , Meuleman Yvette , Mooijaart Simon P. , Brunsveld-Reinders Anja H. , Bos Willem Jan W. , Van Buren Marjolijn
Published: April 2023

Background

Dialysis might not benefit all older patients with kidney failure, particularly those with multimorbid conditions and frailty. Patients' and healthcare professionals' awareness of the presence of geriatric impairments could improve outcomes by tailoring treatment plans and decisions for individual patients.

Objective

We aimed to explore the perspectives of patients and healthcare professionals on nephrology‐tailored geriatric assessment to fuel decision‐making for treatment choices in older patients with kidney failure.

Design

In an exploratory qualitative study using focus groups, participants discussed perspectives on the use and value of nephrology‐tailored geriatric assessment for the decision‐making process to start or forego dialysis.

Participants and Measurements

Patients (n = 18) with kidney failure, caregivers (n = 4), and professionals (n = 25) were purposively sampled from 10 hospitals. Interviews were audio‐recorded, transcribed verbatim and inductively analysed using thematic analysis.

Results

Three main themes emerged that supported or impeded decision‐making in kidney failure: (1) patient psycho‐social situation; (2) patient‐related factors on modality choice; (3) organisation of health care. Patients reported feeling vulnerable due to multiple chronic conditions, old age, experienced losses in life and their willingness to trade longevity for quality of life. Professionals recognised the added value of nephrology‐tailored geriatric assessment in three major themes: (i) facilitating continual holistic assessment, (ii) filling the knowledge gap, and (iii) uncovering important patient characteristics.

Conclusions

nephrology‐tailored geriatric assessment was perceived as a valuable tool to identify geriatric impairments in older patients with kidney failure. Integration of its outcomes can facilitate a more holistic approach to inform choices and decisions about kidney replacement therapy.
A cytoplasmic protein MoJMJD3 can reduce early appressorium formation and fungal virulence in Magnaporthe oryzae
Authors: Zhang Li , Zhang Mengyu , Liu Chaotian , Wu Zechi , Luo Zijian , Lu Min , Shi Yingying , Nan Zhangjie , Hu Die , Pan Jinbao , Wang Weixiang
Published: April 2023

Magnaporthe oryzae (M. oryzae) is a devastating pathogenic fungal disease that has a serious threat to the global rice security. Recently, an in‐depth study of the pathogenic mechanism and developmental process of M. oryzae became a primary model in the study of host–fungal pathogen interactions. Here, we have identified a gene MoJMJD3 (MGG_02032, accession XM_003708733) encoding the JumonjiC (JmjC) domain through bioinformatics analysis in M. oryzae. The ΔMojmjd3 deletion mutants showed defects in early appressorium formation and fungal virulence during pathogenesis. At 4 h after inoculation, the early appressorium formation of ΔMojmjd3 was decreased when compared with that of the wild‐type P131. Analysis of intracellular localization of MoJMJD3 with RFP fluorescence observation showed that MoJMJD3 was mainly localized in the cytoplasm of the conidia, appressoria, hyphae, and infective hyphae. Furthermore, by spray inoculation analysis, the ΔMojmjd3deletion mutants reduced virulence on the leaves of rice. These data suggest that MoJMJD3 plays important roles in fungal virulence during pathogenesis in M. oryzae.
Evaluation of responses to immunosuppressive therapy in dogs with suspected non‐regenerative immune‐mediated anaemia: 11 cases (2012‐2018)
Authors: Morishita K. , Sugawara‐Suda M. , Yamazaki J. , Sasaki N. , Nakamura K. , Ohta H. , Takiguchi M.
Published: April 2023

Objectives

We aimed to determine the response time to immunosuppressive therapy and time required to achieve a 5% increase in haematocrit among dogs with non‐regenerative immune‐mediated anaemia.

Materials and Methods

Client‐owned dogs diagnosed with non‐regenerative immune‐mediated anaemia in Hokkaido University Veterinary Teaching Hospital between December 2012 and May 2018 were enrolled. The first treatment regimen included prednisolone (2 mg/kg/day) and ciclosporin (up to 10 mg/kg/day) for 8 weeks. Dogs that did not respond to the first regimen proceeded to the second regimen comprising prednisolone and mycophenolate mofetil (15 mg/kg, twice a day). Reticulocyte count and haematocrit were monitored every 1 to 2 weeks. Treatment response was defined as an absolute reticulocyte count more than 60×103/μL or increasing haematocrit.

Results

During the study period, 23 dogs fulfilled the inclusion criteria for non‐regenerative immune‐mediated anaemia. Twelve dogs were excluded from this study for various reasons and response to therapy was evaluated in the remaining 11 dogs. Treatment responses were observed in 8 of 11 dogs, and the median time to response was 39.5 days (range 8 to 92 days). Two responders were unable to continue the first treatment regimen and were switched to the second regimen owing to anorexia and nausea, possibly induced by ciclosporin; withdrawal of ciclosporin improved their symptoms. The time required to achieve a 5% increase in haematocrit was assessed in the other six dogs, with a median of 55.5 days (range 8 to 135 days).

Clinical Significance

Here we report the response to a standardised treatment protocol in dogs with non‐regenerative immune‐mediated anaemia. Knowledge of potential side effects and expected therapeutic outcomes may be of use for veterinary practitioners treating this condition.
Antibiotic therapy in dogs and cats in general practice in the United Kingdom before referral
Authors: del Solar Bravo R. E. , Sharman M. J. , Raj J. , Scudder C.
Published: April 2023

Objectives

To describe antibiotic prescription by veterinarians in general practices in the United Kingdom before referral and analyse if UK antibiotic stewardship guidelines were followed.

Materials and Methods

The clinical records from dogs and cats referred to the Internal Medicine and Oncology departments of two referral hospitals were retrospectively reviewed.

Results

There were 917 cases included, of which 486 (53.0%) had been prescribed antibiotics for the presentation they were subsequently referred for. Bacterial culture or cytology to guide antibiotic prescription had been performed in 43 of 486 (8.8%) and nine of 486 cases (1.8%) respectively. In four cases, both cytology and culture were performed. For those animals who had received antibiotics, 344 of 486 (70.8%) prescriptions did not comply with UK antibiotic stewardship guidelines. Following investigations at a referral centre, a bacterial aetiology was found or suspected in 17.9% of the cases that received antibiotics.

Clinical Significance

Use of diagnostics, including culture and cytology, to prove or determine the likelihood of a bacterial aetiology was infrequently performed before referral and may have contributed to overprescription of antibiotics. Encouraging veterinarians to undertake appropriate diagnostics, in combination with education around compliance with antibiotic stewardship guidelines, might reduce antibiotic prescription.
Antibiograms of field and hospital acquired equine neonatal bacterial fluid cultures in the Midwestern United States: 149 samples (2007‐2018)
Authors: Bookbinder Lauren C. , Mani Rinosh , Carr Elizabeth A.
Published: April 2023

Background

Contemporary data reflecting local pathogens and their antibiograms is necessary to select empirical antimicrobial therapy for equine neonates.

Hypothesis/Objectives

Describe bacterial isolates associated with equine neonatal infection and their antibiograms in the Midwestern United States. An increase in gram‐positive infection and antibiotic resistance compared to previous literature was expected.

Animals

Data from 149 fluid samples from 133 foals <30 days of age submitted for bacterial culture between January 2007 and December 2018.

Methods

A retrospective evaluation of equine neonatal fluid cultures was performed. Fluid submission type, bacterial culture and antibiogram, empirical antibiotic treatment, and foal outcome was included. Isolate susceptibility to individual antimicrobials and combination protocols relevant to equine practice were recorded. The effect of recorded variables on foal survival was evaluated using Fisher's exact or chi‐squared tests.

Results

Ninety bacterial isolates (78 aerobes and 12 anaerobes) were identified and gram‐positive organisms predominated (n = 50/90, 56%). Greater than 70% of aerobic isolates were susceptible to ampicillin, ceftiofur, chloramphenicol, trimethoprim/sulfamethoxazole, and all penicillin/aminopenicillin and aminoglycoside combinations. Seventy‐seven (n = 81/105) percent of foals survived. Survival was associated with a negative fluid culture and was not associated with empirical antimicrobial choice.

Conclusions and Clinical Importance

Gram positive and anaerobic isolates associated with equine neonatal fluid cultures exceed that of previous reports. Historical empirical antimicrobial choices for equine neonatal infection in the Midwestern United States are supported by local antibiogram results.
Modeling nonlinear flutter behavior of long‐span bridges using knowledge‐enhanced long short‐term memory network
Authors: Li Tao , Wu Teng
Published: April 2023

The nonlinear characteristics of bridge aerodynamics preclude a closed‐form solution of limit‐cycle oscillation (LCO) amplitude and frequency in the post‐flutter stage. To address this issue, a long short‐term memory (LSTM) network is utilized as the reduced‐order modeling of nonlinear aeroelastic forces on the bridge deck section, and it is repeatedly employed to generate force inputs at spanwise nodes of a three‐dimensional (3D) finite element model (FEM) of the long‐span bridge (using spatial beam elements). All LSTM networks are dynamically coupled through FEM, and the 3D nonlinear flutter response is accordingly obtained. To improve the simulation accuracy and reduce the required training data of the standard LSTM network, both general knowledge (motivated by the gating mechanism and mathematical models for information processing) and domain knowledge (resulting from the basic understanding of bridge aerodynamics) are leveraged to, respectively, customize the LSTM cell and network architecture. In addition, a fast‐training algorithm effectively combining the linear convergence of stochastic gradient descent and superlinear convergence of modified Broyden–Fletcher–Goldfarb–Shanno is developed to improve the training efficiency of the obtained knowledge‐enhanced LSTM network. To further advance the computational efficiency of the coupled LSTM‐FEM nonlinear flutter analysis, the convolution‐based numerical integration is adopted in the finite element modeling of long‐span bridge dynamics. A case study of a long‐span suspension bridge under strong winds demonstrates the proposed 3D nonlinear flutter analysis presents high simulation efficiency and accuracy and can be utilized to effectively obtain the nonlinear LCO characteristics in a wide range of post‐flutter wind speeds.
Sequential aero‐structural optimization method for efficient bridge design
Authors: Cid Montoya Miguel
Published: April 2023

The recent development of aero‐structural optimization methods provides a powerful tool to achieve cost‐effective and safe designs for wind‐sensitive structures. However, pursuing holistic formulations involves adopting many design variables and constraints, which increases the computational burden preventing the application of nonlinear methods for accurately assessing aeroelastic responses. This paper proposes a sequential aero‐structural optimization (SASO) method to improve the efficiency of holistic wind‐resistant design optimization of wind‐sensitive structures. The original problem is uncoupled into two standalone optimization problems: a structural size optimization and an aeroelastic shape optimization, linked by an adaptive mapping surrogate and an outer loop. This strategy permits the design‐space dimensionality reduction and avoids the computation of multiple sensitivities with low influence on the design decisions. A long‐span bridge is successfully optimized. The convergence is drastically accelerated by minimizing the number of aeroelastic evaluations, opening the way to implement nonlinear aeroelastic performance‐based design optimization frameworks.
Auxin inhibits lignin and cellulose biosynthesis in stone cells of pear fruit via the PbrARF13‐PbrNSC‐PbrMYB132 transcriptional regulatory cascade
Authors: Xu Shaozhuo , Sun Manyi , Yao Jia‐Long , Liu Xiuxia , Xue Yongsong , Yang Guangyan , Zhu Rongxiang , Jiang Weitao , Wang Runze , Xue Cheng , Mao Zhiquan , Wu Jun
Published: April 2023

Stone cells are often present in pear fruit, and they can seriously affect the fruit quality when present in large numbers. The plant growth regulator NAA, a synthetic auxin, is known to play an active role in fruit development regulation. However, the genetic mechanisms of NAA regulation of stone cell formation are still unclear. Here, we demonstrated that exogenous application of 200 μM NAA reduced stone cell content and also significantly decreased the expression level of PbrNSC encoding a transcriptional regulator. PbrNSC was shown to bind to an auxin response factor, PbrARF13. Overexpression of PbrARF13 decreased stone cell content in pear fruit and secondary cell wall (SCW) thickness in transgenic Arabidopsis plants. In contrast, knocking down PbrARF13 expression using virus‐induced gene silencing had the opposite effect. PbrARF13 was subsequently shown to inhibit PbrNSC expression by directly binding to its promoter, and further to reduce stone cell content. Furthermore, PbrNSC was identified as a positive regulator of PbrMYB132 through analyses of co‐expression network of stone cell formation‐related genes. PbrMYB132 activated the expression of gene encoding cellulose synthase (PbrCESA4b/7a/8a) and lignin laccase (PbrLAC5) binding to their promotors. As expected, overexpression or knockdown of PbrMYB132 increased or decreased stone cell content in pear fruit and SCW thickness in Arabidopsis transgenic plants. In conclusion, our study shows that the ‘PbrARF13‐PbrNSC‐PbrMYB132’ regulatory cascade mediates the biosynthesis of lignin and cellulose in stone cells of pear fruit in response to auxin signals and also provides new insights into plant SCW formation.
Concurrent acute generalized exanthematous pustulosis in siblings
Authors: Pareek Sumiti , Mohta Alpana , Ghiya Bhikham Chand , Kumar Yogesh
Published: April 2023

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction triggered in most cases by drugs. It is characterized by abrupt onset and rapid evolution of fields of sterile pustules on an erythematous background. The role of genetic predisposition in this reactive disorder is being explored. We report the simultaneous occurrence of AGEP in two siblings after being exposed to the same drug.
Overcoming neutrality as an organizational learning impediment
Authors: Sweeting Karen D. , Haupt Brittany “Brie”
Published: April 2023

This article addresses the negative implications of neutrality in bureaucratic systems and public service. Neutrality employs a sameness approach that reinforces impartiality, invisibility, and indifference, resulting in what we term discriminatory blindness. After a brief illustrative review of neutrality in public service, we critique neutrality as an organizational impediment based on its veiled negative implications and disparate outcomes that fail to center the human experience and treat people based on how they are situated to ensure equity in outcomes. We propose a framework to forge ahead with eight actionable types of initiatives and learning constructs to raise the consciousness of public practitioners. We conclude with an action‐oriented and learning‐focused approach.