bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioequivalence of two oral formulations of tebipenem pivoxil hydrobromide in healthy subjects
Authors: Gupta Vipul K. , Patel Gina , Gasink Leanne , Bajraktari Floni , Lei Yang , Jain Akash , Srivastava Praveen , Talley Angela K.
Published: April 2022

Tebipenem pivoxil hydrobromide (TBP‐PI‐HBr) is a novel oral carbapenem prodrug of tebipenem (TBP), the active moiety, currently in development for treating serious bacterial infections. This study assessed the bioequivalence (BE) of the clinical trial and registration tablet formulations of TBP‐PI‐HBr and evaluated the effect of food on the pharmacokinetics (PKs) of tebipenem. This was a single center, open‐label, randomized, single‐dose, three‐sequence, four‐period crossover, BE, and food‐effect study. Subjects received single 600 mg oral doses of TBP‐PI‐HBr as the reference clinical trial tablet (treatment A) and test registration tablet (treatment B) formulations in alternating sequence while fasting, and then the test formulation under fed conditions. Whole blood samples were collected predose and at specified intervals up to 24 h postdose to evaluate TBP PK parameters. Safety and tolerability were monitored. Thirty‐six healthy, adult subjects were enrolled and completed the study. The criteria for BE were met for the TBP‐PI‐HBr test (registration tablet) and reference (clinical trial tablet) formulations as the 90% confidence intervals for the geometric mean ratios for TBP area under the curve (AUC)0‐t, AUC0‐inf, and maximum plasma concentration (Cmax) fell within the established 80% to 125% BE limits. Dosing with food had no meaningful effect on TBP PK parameters. Five (14%) subjects reported adverse events (AEs) of mild severity. No deaths, serious AEs, or discontinuations due to AEs were reported, and no clinically relevant electrocardiograms, vital signs, or safety laboratory findings were observed. The study results demonstrate the BE of oral TBP‐PI‐HBr registration and clinical trial tablet formulations and indicate that TBP‐PI‐HBr can be administered without regard to meals.
What areas of everyday functioning are affected by theory of mind deficits in recent‐onset schizophrenia spectrum disorders?
Authors: Achim Amélie M. , Thibaudeau Élisabeth , Huot Andréanne , Cellard Caroline , Roy Marc‐André
Published: April 2022

Aim

Functional recovery is now a recognized treatment goal for schizophrenia. It is therefore important to better understand the cognitive and psychological factors that influence functioning. Theory of mind (ToM) deficits are common in schizophrenia and have been linked to greater impairments in functioning. The current study aimed to identify which specific areas of functioning are linked to ToM in a group of 54 patients with a recent‐onset of a schizophrenia spectrum disorder.

Methods

ToM was assessed with the Combined Stories Test (COST). Several areas of functioning were rated based on an extensive semi‐structured interviews.

Results

Among the different areas of functioning that were examined, ToM showed a significant, positive relationship with ratings for productive activities (e.g. work or school) as well as with collaboration to psychiatric care.

Conclusion

These results suggest that ToM can impair functioning especially in situations in which patients need to collaborate with others, including the interactions with the clinical team.
Chinese childbearing decision‐making in mainland China in the post‐one‐child‐policy era
Authors: Su‐Russell Chang , Sanner Caroline
Published: April 2022

In 2016, China enacted its two‐child policy, further lifted to a three‐child policy in 2021, in response to low birth rates and imbalanced sex ratios resulting from the almost 40‐year one‐child policy. Despite this, China's birthrate is at a historic low as fewer parents are having children. Now more than ever, inductive explorations are needed to understand what motivates Chinese parents to have first and second children in the post‐one‐child policy era, particularly explorations that situate individual decision‐making within the larger social context. Individual and relational choices occur in larger sociopolitical contexts. Understanding these “personal” actions involves considering how micro and macro processes inform each other. In this study, we elicited qualitative responses from Chinese mothers (N = 117) with two children in early childhood (firstborn ≤8 years old) from Liao Ning province. Most mothers were well educated, employed, and married to children's fathers. Using inductive thematic analysis procedures, we coded qualitative responses about the factors that motivated mothers to have first and second children. Our data revealed that (a) mothers expressed different reasons for having firstborns compared to secondborns, and (b) decision‐making occurred against a backdrop of interacting micro‐level and macro‐level influences (e.g., cultural norms, national policy changes). In particular, mothers described the decision to have secondborns as more deliberative than with firstborns, considering long‐term benefits siblinghood and shared demands of elderly caregiving. If efforts to stimulate the national birthrate are likely to succeed, policymakers should consider micro‐level as well as macro‐level factors that shape mothers' childbearing decision‐making.
Resilient biotic response to long‐term climate change in the Adriatic Sea
Authors: Scarponi Daniele , Nawrot Rafał , Azzarone Michele , Pellegrini Claudio , Gamberi Fabiano , Trincardi Fabio , Kowalewski Michał
Published: April 2022

Preserving adaptive capacities of coastal ecosystems, which are currently facing the ongoing climate warming and a multitude of other anthropogenic impacts, requires an understanding of long‐term biotic dynamics in the context of major environmental shifts prior to human disturbances. We quantified responses of nearshore mollusk assemblages to long‐term climate and sea‐level changes using 223 samples (~71,300 specimens) retrieved from latest Quaternary sediment cores of the Adriatic coastal systems. These cores provide a rare chance to study coastal systems that existed during glacial lowstands. The fossil mollusk record indicates that nearshore assemblages of the penultimate interglacial (Late Pleistocene) shifted in their faunal composition during the subsequent ice age, and then reassembled again with the return of interglacial climate in the Holocene. These shifts point to a climate‐driven habitat filtering modulated by dispersal processes. The resilient, rather than persistent or stochastic, response of the mollusk assemblages to long‐term environmental changes over at least 125 thousand years highlights the historically unprecedented nature of the ongoing anthropogenic stressors (e.g., pollution, eutrophication, bottom trawling, and invasive species) that are currently shifting coastal regions into novel system states far outside the range of natural variability archived in the fossil record.
Iron deficiency anemia and bleeding management in pediatric patients with Bernard‐Soulier syndrome and Glanzmann Thrombasthenia: A single‐institution analysis
Authors: Lee Annika , Maier Cheryl L. , Batsuli Glaivy
Published: April 2022

Introduction

Frequent and severe bleeding events (SBE) in patients with inherited qualitative platelet disorders Bernard‐Soulier Syndrome (BSS) and Glanzmann Thrombasthenia (GT) can lead to secondary iron deficiency anemia (IDA). SBE are primarily treated with platelet transfusions or recombinant activated factor VII (rFVIIa) infusions. The impact of IDA on bleeding management and disease outcomes is understudied.

Aim

To evaluate bleeding management, outcomes, and any association with IDA in pediatric patients with BSS and GT.

Methods

Retrospective chart‐review of pediatric patients with BSS or GT followed at a single hemophilia treatment center between 2007 and 2019.

Results

We identified 14 patients with BSS (n = 2) or GT (n = 12). Patients received rFVIIa (7%), platelet transfusions (7%), or a combination of both (57%) for SBE. Eleven patients (79%) had IDA requiring oral and/or intravenous iron replacement and 50% required red blood cell transfusions. Due to recurrent SBE and refractory IDA, three patients (21%) received rFVIIa prophylaxis at 90 μg/kilogram 2‐3 times/week for ≥15 months. Patients initiated on rFVIIa prophylaxis had a median baseline hemoglobin of 9.8 g/dL (min‐max: 8.0–10.7 g/dL) compared to 11.7 g/dL (8.4–13.8 g/dL) for patients treated on‐demand. Following initiation of rFVIIa prophylaxis, median hemoglobin and ferritin increased by 1.3 g/dL (0.7–2.5 g/dL) and 14.6 ng/mL (0.2–42.9 ng/mL), respectively, and bleeding rates were reduced by 7–78%.

Conclusion

IDA is a known complication of recurrent bleeding events in individuals with inherited bleeding disorders. Routine monitoring for IDA may help improve bleeding management and reduce bleed burden in BSS/GT.
A study of Italian young adults’ transnational mobility to Australia: The reproduction of unequal trajectories in the host society
Authors: Giardiello Mauro , Cuervo Hernan , Capobianco Rosa
Published: April 2022

In this article, we examine the mobility patterns of a group of Italian young adults migrating to Australia in the search of new education, labour and lifestyle opportunities. The article represents a contribution to the study of the link between youth mobility and unequal trajectories through the elaboration of a new conceptual framework based on the theory of epistemological fallacy that points to the growing disjuncture between the expectations of individual autonomy and the unequal distribution of resources to achieve them. This conceptual framework contributes to elucidate the paradox of mobility that drives young people between the aspiration to mobility and the reproduction of the structural factors that influence their success. We draw on data from a mixed methods research project examining the mobility of Italian young adults to Australia. Participants imagined mobility as a way of exiting insecurities and precarities in their local context to a more open and meritocratic society, but the analysis of their trajectories in the host country reflects similar patterns of stratification as experienced in the context of origin.
Predictors of influenza severity among hospitalized adults with laboratory confirmed influenza: Analysis of nine influenza seasons from the Valencia region, Spain
Authors: Derqui Nieves , Nealon Joshua , Mira‐Iglesias Ainara , Díez‐Domingo Javier , Mahé Cedric , Chaves Sandra S.
Published: April 2022

Purpose

Influenza hospitalizations contribute substantially to healthcare disruption. We explored the impact of ageing, comorbidities and other risk factors to better understand associations with severe clinical outcomes in adults hospitalized with influenza.

Methods

We analysed multi‐season data from adults ≥18 years, hospitalized with laboratory‐confirmed influenza in Valencia, Spain. Severity was defined as intensive care unit (ICU) admission, assisted ventilation and/or death. Generalized estimating equations were used to estimate associations between risk factors and severity. Rate of hospital discharge was analysed with a cumulative incidence function.

Results

Only 26% of influenza patients had their primary discharge diagnosis coded as influenza. Comorbidities were associated with severity among adults aged 50–79 years, with the highest odds ratio (OR) in patients with ≥3 comorbidities aged 50–64 years (OR = 6.7; 95% CI: 1.0–44.6). Morbid obesity and functional dependencies were also identified risk factors (ORs varying from 3 to 5 depending on age). The presence of increasing numbers of comorbidities was associated with prolonged hospital stay.

Conclusions

Influenza clinical outcomes are aggravated by the presence of comorbidities and ageing. Increased awareness of influenza among hospitalized patients could prompt clinical and public health interventions to reduce associated burden.
Quality of life in neurofibromatosis 1: development and validation of a tool dedicated to cutaneous neurofibromas in adults
Authors: Fertitta L. , Bergqvist C. , Armand M.L. , Moryousef S. , Ferkal S. , Jannic A. , Ravaud P. , Tran V.T. , Ezzedine K. , Wolkenstein P.
Published: April 2022

Background

Cutaneous neurofibromas (cNF), present in 95% of individuals with neurofibromatosis 1 (NF1), are considered as one of the greatest medical burden because of physical disfigurement. No specific score evaluates their impact on quality of life (QoL).

Objective

To develop a specific score assessing cNF‐related QoL.

Methods

Through a multidisciplinary workshop including 10 patients, 3 expert‐in‐NF1 physicians, 3 health care workers (nurses and psychologist) and 1 methodologist, the French version of the Skindex‐16 was modified by adding 3 items. The new cNF‐Skindex was validated among patients with NF1 recruited in the ComPaRe online cohort, in France (N = 284). Construct validity was assessed by comparing it with the EQ‐5D‐5L, its visual analogue scale and the MYMOP2 and by assessing its association with patients' characteristics. Reliability was assessed by a test–retest. An English version of the tool was developed using a back‐forward translation.

Results

A total of 228 individuals with NF1, with cNF answered the 19‐item questionnaire. These items fitted into 3 domains: emotions, symptoms, functioning. One was dropped during analysis because >90% responders were not concerned. The cNF‐Skindex significantly correlated with the EQ‐5D‐5L (N = 193) and MYMOP2 (N = 210) indicating good external validity: rs 0.38 (P < 0.001), and 0.58 (P < 0.001), respectively. Having >50 cNF was the only independent variable associated with the total score cNF‐Skindex (β = 15.88, 95%CI 6.96–24.81, P = 0.001), and with the 3 sub‐scores: ‘functioning’ (β = 2.65, 95%CI 0.71–4.59, P = 0.008), ‘emotions’ (β = 17.03, 95%CI 4.11–29.96, P = 0.010) and ‘symptoms’ (β = 3.90, 95%CI 1.95–5.85, P < 0.001). Test–retest reliability (N = 133) found an ICC at 0.96 demonstrating good reproducibility.

Conclusion

The cNF‐Skindex demonstrated excellent psychometric properties. The global and sub‐scores were increased with higher number of cNF arguing for its use in further trials aiming to reduce their number or prevent their development. Cross‐cultural validation and evaluation of its responsiveness are the next steps.
Moderate‐to‐severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real‐world experience
Authors: Stingeni L. , Bianchi L. , Antonelli E. , Caroppo E.S. , Ferrucci S.M. , Ortoncelli M. , Fabbrocini G. , Nettis E. , Schena D. , Napolitano M. , Gola M. , Bonzano L. , Rossi M. , Belloni Fortina A. , Balato A. , Peris K. , Foti C. , Guarneri F. , Romanelli M. , Patruno C. , Savoia P. , Fargnoli M.C. , Russo F. , Errichetti E. , Bianchelli T. , Bianchi L. , Pellacani G. , Feliciani C. , Offidani A. , Corazza M. , Micali G. , Milanesi N. , Malara G. , Chiricozzi A. , Tramontana M. , Hansel K. ,   DADA – Dupilumab for Atopic Dermatitis of the Adolescence Study Group
Published: April 2022

Background

Moderate‐to‐severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side‐effects. Dupilumab was recently approved for treatment of adolescent AD.

Objectives

A multicentre, prospective, real‐world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate‐to‐severe AD was conducted. The main AD clinical phenotypes were also examined.

Methods

Data of adolescents with moderate‐to‐severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes.

Results

One hundred and thirty‐nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait‐like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS‐CoV‐2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty‐eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event.

Conclusions

Dupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID‐19 pandemic era.
Divergent selection on behavioural and chemical traits between reproductively isolated populations of Drosophila melanogaster
Authors: Jin Bozhou , Barbash Daniel A. , Castillo Dean M.
Published: April 2022

Speciation is driven by traits that can act to prevent mating between nascent lineages, including male courtship and female preference for male traits. Mating barriers involving these traits evolve quickly because there is strong selection on males and females to maximize reproductive success, and the tight co‐evolution of mating interactions can lead to rapid diversification of sexual behaviour. Populations of Drosophila melanogaster show strong asymmetrical reproductive isolation that is correlated with geographic origin. Using strains that capture natural variation in mating traits, we ask two key questions: which specific male traits are females selecting, and are these traits under divergent sexual selection? These questions have proven extremely challenging to answer, because even in closely related lineages males often differ in multiple traits related to mating behaviour. We address these questions by estimating selection gradients for male courtship and cuticular hydrocarbons for two different female genotypes. We identify specific behaviours and particular cuticular hydrocarbons that are under divergent sexual selection and could potentially contribute to premating reproductive isolation. Additionally, we report that a subset of these traits are plastic; males adjust these traits based on the identity of the female genotype they interact with. These results suggest that even when male courtship is not fixed between lineages, ongoing selection can act on traits that are important for reproductive isolation.
Engaging in coparenting changes in couple therapy: Two contrasting cases
Authors: Eira Nunes Cindy , Antonietti Jean‐Philippe , Darwiche Joëlle
Published: April 2022

Following the task analysis method, this study aimed to confirm the relevance of our model of resolving coparenting dissatisfaction to differentiate between two contrasting couples undergoing couple therapy. The model under study described the steps through which couples resolve coparenting issues in couple therapy for parents. Two contrasting couples were selected from a sample of parents undergoing systemic couple therapy. We analyzed videotaped discussions about the couple's coparenting relationship to select one couple whose interaction quality improved after therapy and one couple who worsened. Records of therapy sessions were rated by two independent coders to verify whether the model of coparenting change was present. Results showed that the couple that improved after therapy presented almost all the steps of the model whereas the couple that worsened after therapy presented only two steps. This study supported the relevance of the model and its various components to discriminate between two contrasting cases.
The effects of measurement parameters on the cancerous cell nucleus characterisation by atomic force microscopy in vitro
Authors: Zhu Jiajing , Tian Yanling , Yan Jin , Hu Jing , Wang Zuobin , Liu Xianping
Published: April 2022

Cancer is now responsible for the major leading cause of death worldwide. It is noteworthy that lung cancer has been recognised as the highest incidence (11.6%) and mortality (18.4%) for combined sexes among a variety of cancer diseases. Therefore, it is of great value to investigate the mechanical properties of lung cancerous cells for early diagnosis. This paper focus on the influence of measurement parameters on the measured central Young's moduli of single live A549 cell in vitro based on the force spectroscopy mode of atomic force microscopy (AFM). The effects of the measurement parameters on the measured central Young's moduli were analysed by fitting the force–depth curves utilising the Sneddon model. The results revealed that the Young's moduli of A549 cells increased with the larger indentation force, higher indentation speed, less retraction time, deeper Z length and lower purity percentage of serum. The Young's moduli of cells increased first and then decreased with the increasing dwell time. Hence, this research may have potential significance to provide reference for the standardised detection of a single cancerous cell in vitro using AFM methodologies.
Distinguishing Cushing's disease from the ectopic ACTH syndrome: Needles in a haystack or hiding in plain sight?
Authors: Hayes Aimee R. , Grossman Ashley B.
Published: April 2022

In the context of ACTH‐dependent Cushing's syndrome, ectopic ACTH secretion from a neuroendocrine tumour is not uncommon, and needs to be carefully differentiated from pituitary‐dependent Cushing's syndrome, Cushing's disease, in order to optimise therapy. Some cases may be quite obvious, while in others the diagnosis may be difficult to confirm and the source of ACTH problematic, as many clinical and biochemical tests may overlap with Cushing's disease. Imaging is essential, but needs to be interpreted in the light of both anatomical as well as functional imaging modalities. In this review we summarise some of the main diagnostic problems, and emphasise the multimodal and interdisciplinary nature of the diagnostic pathways.
Osteohistological description of ostrich and emu long bones, with comments on markers of growth
Authors: Ong Nathan , Hart‐Farrar Brenna , Tremaine Katie , Woodward Holly N.
Published: April 2022

Ostriches and emus are among the largest extant birds and are frequently used as modern analogs for the growth dynamics of non‐avian theropod dinosaurs. These ratites quickly reach adult size in under 1 year, and as such do not typically exhibit annually deposited growth marks. Growth marks, commonly classified as annuli or lines of arrested growth (LAGs), represent reduced or halted osteogenesis, respectively, and their presence demonstrates varying degrees of developmental plasticity. Growth marks have not yet been reported from ostriches and emus, prompting authors to suggest that they have lost the plasticity required to deposit them. Here we observe the hind limb bone histology of three captive juvenile emus and one captive adult ostrich. Two of the three juvenile emus exhibit typical bone histology but the third emu, a 4.5‐month‐old juvenile, exhibits a regional arc of avascular tissue, which we interpret as a growth mark. As this mark is not present in the other two emus from the same cohort and it co‐occurs with a contralateral broken fibula, we suggest variable biomechanical load as a potential cause. The ostrich exhibits a complete ring of avascular, hypermineralized bone with sparse, flattened osteocyte lacunae. We identify this as an annulus and interpret it as slowing of growth. In the absence of other growth marks and lacking the animal's life history, the timing and cause of this ostrich's reduced growth are unclear. Even so, these findings demonstrate that both taxa retain the ancestral developmental plasticity required to temporarily slow growth. We also discuss the potential challenges of identifying growth marks using incomplete population data sets and partial cortical sampling.
The Accuracy of Post and Core Fabricated with Digital Technology
Authors: Piangsuk, Tarin , Dawson, Deborah V. , El‐Kerdani, Tarek , Lindquist, Terry J.
Published: April 2022

Purpose

To compare the accuracy of post and cores created with three different fabricating techniques: direct conventional, machine milling, and three‐dimensional (3D) printing.

Materials and methods

Thirteen extracted single root central incisors were selected. Root canal treatment and tooth preparation for crown were performed on all teeth. Post space preparation of 11 mm was created using prefabricated fiber post drill to standardize post space width and length. Root canal impressions were performed on all teeth using polyvinyl siloxane impression material. Each impression was then three dimensionally scanned using an extraoral lab scanner. The scanned impressions were used to design digital files of post and cores with 3Shape CAD software. The digitally designed post and cores were used to fabricate 3D printed and milled post and core resin patterns. The same teeth were used to fabricate post and core with conventional technique (direct duplication of root canal with resin pattern). All posts were then scanned before being invested and then cast using base metal educational alloy. The metal post and cores were tried in with sample teeth and manually adjusted until found to be clinically acceptable. The post and cores were scanned in different stages to perform digital volume measurement using Geomagic Control software to determine accuracy. Pairwise comparisons were accomplished using exact version of the sign test (α = 0.05).

Results

These three techniques of post and core fabrication showed different results in the various stages of fabrication. The accuracy of 3D printed resin pattern (26.89 ±11.09 mm3) was found to be inferior compare to milled resin pattern (28.20 ±11.41 mm3, p = 0.0002). However, dimensional stability of the 3D printed resin pattern before and after casting (0.56 ±0.95 mm3) was found to be superior to milled resin pattern (0.79 ±0.89 mm3) and direct resin pattern (2.51 ±1.38 mm3, p = 0.00002). All three techniques showed significant volume reduction after adjustment (p = 0.0002). In the final stage, the adjusted metal post and core fabricated with three different techniques showed no statistical different in accuracy (p = 0.15).

Conclusion

Digitally fabricated post and cores have the same degree of accuracy as those fabricated using the gold standard direct conventional post and core technique.
Chronic stress increases DNA methylation of the GR promoter in the central nucleus of the amygdala of female rats
Authors: Louwies Tijs , Greenwood‐Van Meerveld Beverley
Published: April 2022

The central pathophysiological mechanisms underlying irritable bowel syndrome (IBS), a female‐predominant gastrointestinal disorder characterized by abdominal pain and abnormal bowel habits, remain poorly understood. IBS patients often report that chronic stress exacerbates their symptoms. Brain imaging studies have revealed that the amygdala, a stress‐responsive brain region, of IBS patients is overactive when compared to healthy controls. Previously, we demonstrated that downregulation of the glucocorticoid receptor (GR) in the central nucleus of the amygdala (CeA) underlies stress‐induced visceral hypersensitivity in female rats. In the current study, we aimed to evaluate in the CeA of female rats whether chronic water avoidance stress (WAS) alters DNA methylation of the GR exon 17 promoter region, a region homologous to the human GR promoter. As histone deacetylase (HDAC) inhibitors are able to change DNA methylation, we also evaluated whether administration of the HDAC inhibitor trichostatin A (TSA) directly into the CeA prevented WAS‐induced increases in DNA methylation of the GR exon 17 promoter. We found that WAS increased overall and specific CpG methylation of the GR promoter in the CeA of female rats, which persisted for up to 28 days. Administration of the TSA directly into the CeA prevented these stress‐induced changes of DNA methylation at the GR promoter. Our results suggest that, in females, changes in DNA methylation are involved in the regulation of GR expression in the CeA. These changes in DNA methylation may contribute to the central mechanisms responsible for stress‐induced visceral hypersensitivity.
Comparison of perianal skin barrier function with moisturizer application in Japanese full‐term newborns
Authors: Majima Yuka , Kobayashi Yasue
Published: April 2022

Background/Objectives

Some full‐term newborns present with erythema and irritation of the buttocks and perianal area as early as the first 4 days of their lives. The effect of moisturizers in protecting this vulnerable skin has not been rigorously studied. This study aimed to clarify whether there is a difference in perianal skin barrier function with and without moisturizer application in the first month of life.

Methods

Comparative investigation of 118 full‐term newborns was performed, and they were allocated to intervention (n = 63) and control groups (n = 55). The intervention group received moisturizer application to the perianal area, and the control group received care without application of moisturizer to the perianal area from the first day of life until the 1‐month visit. Transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin surface pH in the perianal area were measured as the indicators of skin barrier function on days 1 and 5 after birth and at the 1‐month visit.

Results

At the 1‐month visit, TEWL was significantly decreased (intervention, 19.4 g/m2/h; control, 25.8 g/m2/h; p = .00) and SCH was significantly increased (intervention, 58.8 arbitrary units (a.u.); control, 46.5 a.u.; p = .00) in newborns using perianal moisturizer. The skin surface pH was not significantly different.

Conclusions

The use of moisturizer was effective in protecting the skin barrier function of the perianal skin. Further investigations are needed to determine the effect on the frequency and extent of rashes in the perianal area.
Using Folded Seats‐Votes Curves to Compare Partisan Bias in the 2020 Presidential Election with Partisan Bias in the Five Other Presidential Elections in the 21st Century
Authors: Cervas Jonathan , Grofman Bernard
Published: April 2022

Using a folded seats‐votes curve, we examine partisan bias in the 2020 presidential election and compare it to partisan bias in the five other presidential elections in the twenty‐first century. 2020 and 2016 are extreme outliers with respect to the absolute magnitude of partisan bias in the Electoral College. In 2016, 2020, and 2000 bias runs in a pro‐Republican direction; in the other three elections in this century, the opposite is true. But partisan bias can vary with where on the seats‐vote curve we look to find bias, and we identify the lowest vote share at which there is no partisan bias (if such exists).
The Helsinki Bike-Sharing System—Insights Gained from a Spatiotemporal Functional Model
Authors: Piter Andreas , Otto Philipp , Alkhatib Hamza
Published: April 2022

Understanding the usage patterns for bike-sharing systems is essential in terms of supporting and enhancing operational planning for such schemes. Studies have demonstrated how factors such as weather conditions influence the number of bikes that should be available at bike-sharing stations at certain times during the day. However, the influences of these factors usually vary over the course of a day, and if there is good temporal resolution, there could also be significant effects only for some hours/minutes (rush hours, the hours when shops are open and so forth). Thus, in this paper, an analysis of Helsinki's bike-sharing data from 2017 is conducted that considers full temporal and spatial resolutions. The station hire data are analysed in a spatiotemporal functional setting, where the number of bikes at a station is defined as a continuous function of the time of day. For this completely novel approach, we apply a functional spatiotemporal hierarchical model to investigate the effect of environmental factors and the magnitude of the spatial and temporal dependence. Challenges in computational complexity are faced using a Monte Carlo subsampling approach. The results show the necessity of splitting the bike-sharing stations into two clusters based on the similarity of their spatiotemporal functional observations in order to model the station hire data of Helsinki's bike-sharing system effectively.
Efficient Manifold Approximation with Spherelets
Authors: Li Didong , Mukhopadhyay Minerva , Dunson David B.
Published: April 2022

In statistical dimensionality reduction, it is common to rely on the assumption that high dimensional data tend to concentrate near a lower dimensional manifold. There is a rich literature on approximating the unknown manifold, and on exploiting such approximations in clustering, data compression, and prediction. Most of the literature relies on linear or locally linear approximations. In this article, we propose a simple and general alternative, which instead uses spheres, an approach we refer to as spherelets. We develop spherical principal components analysis (SPCA), and provide theory on the convergence rate for global and local SPCA, while showing that spherelets can provide lower covering numbers and mean squared errors for many manifolds. Results relative to state-of-the-art competitors show gains in ability to accurately approximate manifolds with fewer components. Unlike most competitors, which simply output lower-dimensional features, our approach projects data onto the estimated manifold to produce fitted values that can be used for model assessment and cross validation. The methods are illustrated with applications to multiple data sets.
Visualization of energy‐based device‐induced thermal tissue alterations using bimodal ex‐vivo confocal microscopy with digital staining. A proof‐of‐concept study
Authors: Fredman Gabriella , Christensen Rikke Louise , Ortner Vinzent Kevin , Haedersdal Merete
Published: April 2022

Background

Ex‐vivo confocal microscopy (EVCM) enables examination of tissue alterations immediately after treatment with energy‐based devices (EBDs). This proof‐of‐concept study aimed to describe EBD‐induced tissue effects in ex‐vivo porcine skin after treatment with microneedle radiofrequency (MNRF) and ablative fractional CO2‐laser (AFL) using EVCM.

Materials and Methods

Ex‐vivo porcine skin was treated with MNRF and AFL. Three cryosections from each intervention were stained with acridine orange (AO) and scanned with EVCM. Reflectance confocal microscopy (RCM, 638 nm) and fluorescence confocal microscopy (FCM, 488 nm) images were captured and evaluated individually, after image fusion, and after digital hematoxylin and eosin (H&E) staining.

Results

Bimodal EVCM was able to visualize EBD‐induced thermal alterations in porcine skin. In RCM mode, the full width and depth of the vertically aligned microscopic treatment zones (MTZs) were displayed with clear demarcation to surrounding intact skin. In FCM mode, the ablation of the epidermis after AFL was prominent in contrast with the almost intact epidermis observed in MNRF treated skin. In fusion mode, fluorescence signal from AO marked the surrounding coagulation zone (CZ) from both interventions, with enhanced discrimination between ablation and coagulation. Digitally H&E‐stained images closely resembled conventional histopathology but proved superior in terms of visualization of the CZ.

Conclusion

Bimodal EVCM with digital H&E‐staining facilitates the identification and qualitative evaluation of thermal alterations induced by treatment with EBD. By providing high‐resolution images comparable to standard histology, EVCM is a useful tool in the research and development of EBD to visualize and evaluate device‐tissue interactions.
Screening DHHCs of S‐acylated proteins using an OsDHHCcDNA library and bimolecular fluorescence complementation in rice
Authors: Tian Ye , Zeng Hui , Wu Jicai , Huang Jian , Gao Qiang , Tang Dongying , Cai Lipeng , Liao Zhaoyi , Wang Yan , Liu Xuanming , Lin Jianzhong
Published: April 2022

S‐acylation is an important lipid modification that primarily involves DHHC proteins (DHHCs) and associated S‐acylated proteins. No DHHC–S‐acylated protein pair has been reported so far in rice (Oryza sativa L.) and the molecular mechanisms underlying S‐acylation in plants are largely unknown. We constructed an OsDHHC cDNA library for screening corresponding pairs of DHHCs and S‐acylated proteins using bimolecular fluorescence complementation assays. Five DHHC–S‐acylated protein pairs (OsDHHC30–OsCBL2, OsDHHC30–OsCBL3, OsDHHC18–OsNOA1, OsDHHC13–OsNAC9, and OsDHHC14–GSD1) were identified in rice. Among the pairs, OsCBL2 and OsCBL3 were S‐acylated by OsDHHC30 in yeast and rice. The localization of OsCBL2 and OsCBL3 in the endomembrane depended on S‐acylation mediated by OsDHHC30. Meanwhile, all four OsDHHCs screened complemented the thermosensitive phenotype of an akr1 yeast mutant, and their DHHC motifs were required for S‐acyltransferase activity. Overexpression of OsDHHC30 in rice plants improved their salt and oxidative tolerance. Together, these results contribute to our understanding of the molecular mechanism underlying S‐acylation in plants.
A Solanum lycopersicoides reference genome facilitates insights into tomato specialized metabolism and immunity
Authors: Powell Adrian F. , Feder Ari , Li Jie , Schmidt Maximilian H.‐W. , Courtney Lance , Alseekh Saleh , Jobson Emma M. , Vogel Alexander , Xu Yimin , Lyon David , Dumschott Kathryn , McHale Marcus , Sulpice Ronan , Bao Kan , Lal Rohit , Duhan Asha , Hallab Asis , Denton Alisandra K. , Bolger Marie E. , Fernie Alisdair R. , Hind Sarah R. , Mueller Lukas A. , Martin Gregory B. , Fei Zhangjun , Martin Cathie , Giovannoni James J. , Strickler Susan R. , Usadel Björn
Published: April 2022

Wild relatives of tomato are a valuable source of natural variation in tomato breeding, as many can be hybridized to the cultivated species (Solanum lycopersicum). Several, including Solanum lycopersicoides, have been crossed to S. lycopersicum for the development of ordered introgression lines (ILs), facilitating breeding for desirable traits. Despite the utility of these wild relatives and their associated ILs, few finished genome sequences have been produced to aid genetic and genomic studies. Here we report a chromosome‐scale genome assembly for S. lycopersicoides LA2951, which contains 37 938 predicted protein‐coding genes. With the aid of this genome assembly, we have precisely delimited the boundaries of the S. lycopersicoides introgressions in a set of S. lycopersicum cv. VF36 × LA2951 ILs. We demonstrate the usefulness of the LA2951 genome by identifying several quantitative trait loci for phenolics and carotenoids, including underlying candidate genes, and by investigating the genome organization and immunity‐associated function of the clustered Pto gene family. In addition, syntenic analysis of R2R3MYB genes sheds light on the identity of the Aubergine locus underlying anthocyanin production. The genome sequence and IL map provide valuable resources for studying fruit nutrient/quality traits, pathogen resistance, and environmental stress tolerance. We present a new genome resource for the wild species S. lycopersicoides, which we use to shed light on the Aubergine locus responsible for anthocyanin production. We also provide IL boundary mappings, which facilitated identifying novel carotenoid quantitative trait loci of which one was likely driven by an uncharacterized lycopene β‐cyclase whose function we demonstrate.
Diversity and similarity of wheat powdery mildew resistance among three allelic functional genes at the Pm60 locus
Authors: Zou Shenghao , Shi Wenqi , Ji Jiahao , Wang Huanming , Tang Yansheng , Yu Dazhao , Tang Dingzhong
Published: April 2022

Cultivated wheat is continually exposed to various pathogens. Blumeria graminis f. sp. tritici (Bgt) causes powdery mildew disease and significant yield loss. Pm60 was cloned from Triticum urartu and confers race‐specific powdery mildew resistance in wheat. Pm60a and Pm60b are allelic variants of Pm60 and have two leucine‐rich repeat motifs deletions and insertions, respectively, which were detected in other T. urartu accessions. Through map‐based cloning, virus‐induced gene silencing, and stable transformation assays, we demonstrated that Pm60a and Pm60b conferred Bgt E09 resistance resembling that provided by Pm60. However, the homozygous Pm60a (but not Pm60 or Pm60b) transformants driven by the native promoters lacked race‐specific resistance when they were inoculated with Bgt E18. As all three T. urartu accessions contained the three foregoing alleles, they had high resistance to Bgt E18. Pyramiding Pm60a with either of the allelic genes in F1 plants did not cause mutual allele suppression or interference with Bgt E18 resistance. Deletion (but not insertion) of the two leucine‐rich repeat motifs in Pm60a substantially narrowed the resistance spectrum. In T. urartu accession PI428210, we identified another locus adjacent to Pm60a and resistant to Bgt E18. Characterization of the alleles at the Pm60 locus revealed their diversity and similarity and may facilitate wheat breeding for resistance to powdery mildew disease caused by B. graminis f. sp. tritici.
A new high‐prevalence LW antigen detected by an antibody in an Indigenous Australian homozygous for LW*A c.309C>A variant
Authors: Lopez Genghis H. , Wilson Brett , Millard Glenda M. , Cawthorne Tanya L. , Grey Dianne E. , Fong Elizabeth A. , Flower Robert L. , Hyland Catherine A. , Liew Yew‐Wah
Published: April 2022

Background and Objectives

The LW gene encodes the LW glycoprotein that carries the antigens of the LW blood group system. LW antigens are distinct from D antigen, however, they are phenotypically related and anti‐LW antibodies are often mistaken as anti‐D. An antibody was detected in an Australian patient of Aboriginal descent who consistently typed as LW(a+b−). This study aimed to describe the antibody recognizing a high‐prevalence antigen on the LW glycoprotein.

Study Design and Methods

Samples from the patient and her four siblings were investigated. DNA was genotyped by single nucleotide polymorphism (SNP)‐microarray and massively parallel sequencing (MPS) platforms. Red blood cells (RBCs) were phenotyped using standard haemagglutination techniques. Antibody investigations were performed using a panel of phenotyped RBCs from adults and cord blood cells.

Results

SNP‐microarray and MPS genotyped all family members as LW*A/A, (c.299A), predicting LW(a+b−). In addition, a novel LW*A c.309C>A single nucleotide variant was detected in all family members. The patient and one of her siblings (M4) were LW c.309C>A homozygous. Antibody from the patient reacted positive to all reagent panel RBCs and cord blood cells but negative with RBCs from LW(a−b−), Rhnull and sibling M4. Antibody failed to react with RBCs treated with dithiothreitol.

Conclusion

Antibody detected in the patient recognized a novel high‐prevalence antigen, LWEM, in the LW blood group system. LWEM‐negative patients who developed anti‐LWEM can be safely transfused with D+ RBCs, however, D− is preferred. Accurate antibody identification can help better manage allocation of blood products especially when D− RBCs are in short supply.
Nerve growth factor transfer from cardiomyocytes to innervating sympathetic neurons activates TrkA receptors at the neuro‐cardiac junction
Authors: Dokshokova Lolita , Franzoso Mauro , Di Bona Anna , Moro Nicola , Sanchez Alonso Jose Luis , Prando Valentina , Sandre Michele , Basso Cristina , Faggian Giuseppe , Abriel Hugues , Marin Oriano , Gorelik Julia , Zaglia Tania , Mongillo Marco
Published: April 2022

Sympathetic neurons densely innervate the myocardium with non‐random topology and establish structured contacts (i.e. neuro‐cardiac junctions, NCJ) with cardiomyocytes, allowing synaptic intercellular communication. Establishment of heart innervation is regulated by molecular mediators released by myocardial cells. The mechanisms underlying maintenance of cardiac innervation in the fully developed heart, are, however, less clear. Notably, several cardiac diseases, primarily affecting cardiomyocytes, are associated with sympathetic denervation, supporting the hypothesis that retrograde ‘cardiomyocyte‐to‐sympathetic neuron’ communication is essential for heart cellular homeostasis. We aimed to determine whether cardiomyocytes provide nerve growth factor (NGF) to sympathetic neurons, and the role of the NCJ in supporting such retrograde neurotrophic signalling. Immunofluorescence on murine and human heart slices shows that NGF and its receptor, tropomyosin‐receptor‐kinase‐A, accumulate, respectively, in the pre‐ and post‐junctional sides of the NCJ. Confocal immunofluorescence, scanning ion conductance microscopy and molecular analyses, in co‐cultures, demonstrate that cardiomyocytes feed NGF to sympathetic neurons, and that this mechanism requires a stable intercellular contact at the NCJ. Consistently, cardiac fibroblasts, devoid of NCJ, are unable to sustain SN viability. ELISA assay and competition binding experiments suggest that this depends on the NCJ being an insulated microenvironment, characterized by high [NGF]. In further support, real‐time imaging of tropomyosin‐receptor‐kinase‐A vesicle movements demonstrate that efficiency of neurotrophic signalling parallels the maturation of such structured intercellular contacts. Altogether, our results demonstrate the mechanisms which link sympathetic neuron survival to neurotrophin release by directly innervated cardiomyocytes, conceptualizing sympathetic neurons as cardiomyocyte‐driven heart drivers.

Key points

CMs are the cell source of nerve growth factor (NGF), required to sustain innervating cardiac SNs;

NCJ is the place of the intimate liaison, between SNs and CMs, allowing on the one hand neurons to peremptorily control CM activity, and on the other, CMs to adequately sustain the contacting, ever‐changing, neuronal actuators;

alterations in NCJ integrity may compromise the efficiency of ‘CM‐to‐SN’ signalling, thus representing a potentially novel mechanism of sympathetic denervation in cardiac diseases.
Design and Analysis of a Novel Reconfigurable Ankle Rehabilitation Exoskeleton Capable of Matching the Mobile Biological Joint Center in Real-Time
Authors: Wang Tun , Spyrakos-Papastavridis Emmanouil , Dai Jian S.
Published: April 2022

This paper proposes a novel reconfigurable exoskeleton for ankle rehabilitation, which is capable of realizing both static and dynamic rehabilitation exercises. The conceptual design is based on a reduced representation that regards the ankle–foot complex as a movable spherical joint, so as to better replicate the physical scenario. The screw theory-based analysis results indicate that in both rehabilitation modes, the proposed exoskeleton is capable of auto-matching its rotation center with that of the ankle complex no matter how the latter moves, once it is worn by the patients. In the 2-degrees-of-freedom (DOF) rehabilitation configuration, an analysis based on a 15-point reduced model provides the basis for assessing the kinematics performance in a case where the motion of complex's center is considered. Also, the results verify that the achieved workspace can always cover the prescribed rotation range without generating singularities, as long as the center moves within the defined cylindrical area. The demonstrated 3-DOF rehabilitation configuration possesses a partially decoupled-control capability. The singularity surface can be effectively expelled from the prescribed workspace by rotating the brace. Besides, the exoskeleton's dexterity varies smoothly in the whole workspace, and its performance can be further improved by evenly distributing the drive links.