bluuebunny/crossref_metadata_2025 huggingface dataset:
Looks like power: Automatic processing of power cues from briefly presented primes
Authors: Schneider Lisa J. , Molitor Jennifer , Neumann Roland
Published: April 2022

Power, as a ubiquitous feature of social relations, is frequently used in information processing. Due to its relevance for social interactions, we expected that power is automatically processed. In three experiments, participants categorized stimuli in a response window priming procedure as either powerful or power‐neutral. The stimuli were preceded by briefly presented primes that were either never used as targets or were also used as targets. We obtained evidence for an automatic, unintentional processing of power‐related pictures even when novel primes were processed. The effect even occurred when primes and targets did not share any perceptual features, such that primes had to be processed semantically. We further revealed correlations between the automatic processing of power cues and right‐wing authoritarianism, but not social dominance orientation status, or power ability. In sum, we show a stable priming effect indicating that power is automatically processed from briefly presented primes.
Epigallocatechin‐3‐O‐gallate ameliorates oxidative stress‐induced chondrocyte dysfunction and exerts chondroprotective effects via the Keap1/Nrf2/ARE signaling pathway
Authors: Zhu Wenrun , Tang Han , Cao Lu , Zhang Jin , Li Juncheng , Ma Duan , Guo Changan
Published: April 2022

Oxidative stress‐induced degeneration and dysfunction of chondrocytes play a key role in the pathological progression of osteoarthritis (OA), a common degenerative joint disease in the elderly. Epigallocatechin‐3‐O‐gallate (EGCG) increases Nrf2‐mediated antioxidase expression levels. We aimed to determine the effects of EGCG on C28/I2 human chondrocytes subjected to interleukin‐1β (IL‐1β)‐induced oxidative stress. EGCG suppressed IL‐1β‐induced oxidative stress, as indicated by decreased malondialdehyde (MDA) and reactive oxygen species (ROS) generation. Additionally, EGCG attenuated the IL‐1β‐induced reduction in cartilage matrix generated by chondrocytes by upregulating collagen II, aggrecan, sulfated proteoglycans, and SRY‐box transcription factor 9 (SOX9). EGCG reversed the IL‐1β‐induced increased cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), collagen X, and matrix metalloproteinases (MMPs). Furthermore, EGCG inhibited apoptosis and senescence of IL‐1β‐treated chondrocytes, as indicated by the decrease in mitochondrial membrane potential and senescence‐associated β‐galactosidase‐positive cells, respectively. Mechanically, EGCG upregulated nuclear factor erythroid 2‐related factor 2 (Nrf2), oxygenase‐1 (HO‐1), and NADPH quinone oxidoreductase1 (NQO1). The antioxidant and chondroprotective effects of EGCG were blocked by ML385, a Keap1/Nrf2/ARE signaling pathway inhibitor. Thus, EGCG ameliorated oxidative stress‐induced chondrocyte dysfunction and exerted chondroprotective effects via Keap1/Nrf2/ARE signaling. This provides a novel perspective on the molecular mechanisms underlying the therapeutic effects of EGCG on OA.
Elderly-onset generalized pustular psoriasis: a case series
Authors: Chao Jen-Ping , Tsai Tsen-Fang
Published: April 2022

Elderly-onset (> 60 years of age) atopic dermatitis and psoriasis have been reported to present special clinical phenotypes; however, the study of elderly-onset generalized pustular psoriasis (GPP) has been limited, mainly due to its rarity. Previous studies have shown that the mean age of GPP onset is around 40 years, and onset at > 60 years of age is extremely rare. We report a case series of seven patients with elderly-onset GPP. The clinical features of the seven patients were assessed, and all seven patient were analysed for presence of the c.115+6T>C mutation in the gene encoding for interleukin-36 receptor antagonist (IL36RN). These patients had an atypical clinical course and a lower frequency of the IL36RN c.115+6T>C mutation. IL36RN mutations may have a significant, dose-dependent effect on the onset age of GPP.
Progress in treatment of neuromyelitis optica spectrum disorders (NMOSD): Novel insights into therapeutic possibilities in NMOSD
Authors: Shi Mingchao , Chu Fengna , Jin Tao , Zhu Jie
Published: April 2022

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory demyelinating disorder of the central nervous system (CNS), which is a severely disabling disorder leading to devastating sequelae or even death. Repeated acute attacks and the presence of aquaporin‐4 immunoglobulin G (AQP4‐IgG) antibody are the typical characteristics of NMOSD. Recently, the phase III trials of the newly developed biologicals therapies have shown their effectiveness and good tolerance to a certain extent when compared with the traditional therapy with the first‐ and second‐line drugs. However, there is still a lack of large sample, double‐blind, randomized, clinical studies to confirm their efficacy, safety, and tolerability. Especially, these drugs have no clear effect on NMOSD patients without AQP4‐IgG and refractory patients. Therefore, it is of strong demand to further conduct large sample, double‐blind, randomized, clinical trials, and novel therapeutic possibilities in NMOSD are discussed briefly here.
Application of nanofat for treatment of traumatic faecal incontinence after sphincteroplasty – A pilot study
Authors: Barisic Goran , Andjelkov Katarina , Rosic Jovana , Miladinov Marko , Kotur‐Stеvuljevic Jelena , Dinic Tanja , Jelenkovic Jelenko , Krivokapic Zoran
Published: April 2022

Aim

The aim of this study was to investigate whether the application of nanofat containing stem cells improves continence in women who had previously undergone anal sphincteroplasty with unsatisfactory long‐term outcomes.

Method

This prospective pilot study included nine women with various degrees of anal incontinence who had previously undergone anal sphincteroplasty due to obstetric trauma. In all patients, the Wexner Incontinence Score (WS) and Faecal Incontinence Quality of Life Score (FIQLS), as well as anal manometry and endoanal ultrasound measurements, were performed before the procedure and during follow‐up. In all patients, liposuction was performed and 50 ml of raw lipoaspirate was obtained and processed using a NanoFat Kit device. Approximately 20 ml of the mechanically emulsified and filtrated fat was obtained and the anal sphincter complex was infiltrated with it. Patient follow‐up was conducted in person or via telephone 6 and 12 months after the procedure.

Results

The squeeze pressure was significantly increased 6 months after the procedure (p = 0.01). The external anal sphincter measured at the 12 o'clock position was significantly thicker (p = 0.04). A significant decrease in the WS was observed both 6 and 12 months after the procedure compared with baseline values (p < 0.05 for both).

Conclusion

This study is the first to show that the application of nanofat as an injectable product improves continence in patients with unsatisfactory results after sphincteroplasty, suggesting it to be a promising and effective therapeutic tool. The procedure is safe and can be easily performed as an ambulatory procedure.
Speech and augmentative and alternative communication needs in young children with cerebral palsy
Authors: Hidecker Mary Jo Cooley
Published: April 2022

This commentary is on the original article by Long et al. on pages 1096–1105 of this issue.
State work–family contexts and the wage gap by gender and parenthood
Authors: Strader Eiko
Published: April 2022

Objective

This article examines the association between state‐level work–family resources and earnings disparities by gender and parenthood.

Background

The wage gap between childless men and women in the United States has narrowed, but the gap between mothers and fathers remains robust. Gendered division of labor and reduced labor force participation of women around childbirth have been raised as underlying causes. In the absence of national support, some states and migrant domestic workers have been filling the care gap, but it is unclear whether these factors are associated with the wage gap.

Method

Individual‐level data from the 2012 American Community Survey were merged with state‐level data collected for 2010. Multilevel linear regression models were used to explore variation in earnings across states, accounting for compositional differences and selection into the labor force.

Results

Temporary Disability Insurance, which enables new birth mothers to take paid leave, was robustly associated with narrower gaps between mothers and fathers. Unpaid private‐sector leave expansion and more intensive globalization of domestic work were associated with narrower gender wage gaps among parents with lower education. Provision of Head Start supplemental funding was associated with narrower wage gaps between mothers and fathers with higher education.

Conclusions

Although mothers earned more in states with more work–family resources, the wage gap remained mostly unchanged because fathers similarly earned more in states with better work–family context.

Implications

The results reflect the fragmented and incomplete nature of work–family support in the United States and calls for more comprehensive intervention strategies to reduce the wage gap.
Groundwater Spatiotemporal Data Analysis Tool: Case Studies, New Features and Future Developments
Authors: Jones Wayne R. , Rock Luc , Wesch Alexandra , Marzusch Emanuel , Low Marnie
Published: April 2022

Groundwater Spatiotemporal Data Analysis Tool (GWSDAT) is an open‐source, user‐friendly, software application for the visualization and interpretation of groundwater monitoring data. Since its first release, over 8 years ago, it has become increasingly well established and is now a globally adopted tool. Despite its widespread use, there is little published material considering the application of GWSDAT. The primary purpose of this article is to demonstrate the different benefits of using GWSDAT by considering a cross‐section of real case studies. The first case study is an example of using GWSDAT to provide evidence to support a proposal to reduce sampling frequency. The next case study discusses the use of GWSDAT to support the recommendation for site closure. The third case study considers how GWSDAT can be used to identify gaps in a monitoring network. The final case study reports on the application of the, newly introduced, well redundancy analysis feature in GWSDAT. Finally, the road map for future developments in the optimization of monitoring network and the motivation for doing this in a spatiotemporal framework is discussed
Experiences of men who have sex with men when initiating, implementing and persisting with HIV pre‐exposure prophylaxis
Authors: Gillespie David , Wood Fiona , Williams Adam , Ma Richard , de Bruin Marijn , Hughes Dyfrig A. , Jones Adam T. , Couzens Zoë , Hood Kerenza
Published: April 2022

Introduction

HIV pre‐exposure prophylaxis (PrEP) involves the use of antiretroviral medication in HIV‐negative individuals considered to be at risk of acquiring HIV. It has been shown to prevent HIV and has been available in Wales since July 2017. Measuring and understanding adherence to PrEP is complex as it relies on the simultaneous understanding of both PrEP use and sexual activity. We aimed to understand the experiences of men who have sex with men (MSM) living in Wales initiating, implementing and persisting with HIV PrEP.

Methods

We conducted semistructured interviews with MSM PrEP users in Wales who participated in a cohort study of PrEP use and sexual behaviour. Following completion of the cohort study, participants were invited to take part in a semistructured interview about their experiences of taking PrEP. We aimed to include both individuals who had persisted with and discontinued PrEP during the study. The interview topic guide was informed by the ABC taxonomy for medication adherence and the theory of planned behaviour. We analysed our data using reflexive thematic analysis.

Results

Twenty‐one participants were interviewed, five having discontinued PrEP during the cohort study. The developed themes focused on triggers for initiating PrEP, habitual behaviour, drivers for discontinuation and engagement with sexual health services. Stigma surrounding both PrEP and HIV permeated most topics, acting as a driver for initiating PrEP, an opportunity to reduce discrimination against people living with HIV, but also a concern around the perception of PrEP users.

Conclusion

This is the first study to investigate PrEP‐taking experiences incorporating established medication adherence taxonomy. We highlight key experiences regarding the initiation, implementation and persistence with PrEP and describe how taking PrEP may promote positive engagement with sexual health services. These findings may be useful for informing PrEP rollout programmes and need to be explored in other key populations.

Patient and Public Contribution

PrEP users, in addition to PrEP providers and representatives of HIV advocacy and policy, were involved in developing the topic guide for this study.
Facial skin ageing: Key concepts and overview of processes
Authors: Zargaran David , Zoller Florence , Zargaran Alexander , Weyrich Tim , Mosahebi Afshin
Published: April 2022

Introduction

The face is a cosmetically sensitive region where the process of ageing is most clearly manifested. With increased focus on anti‐ageing and longevity, more anti‐senescent treatments are being proposed despite limited evidence. This study outlines the pathways and mechanisms underpinning the biological process of ageing in the face.

Methods

Comprehensive searches of MEDLINE, EMBASE, Cochrane Library and CINAHL from inception to 2020. Inclusion criteria included all empirical human research studies specific to facial ageing features, written in the English language.

Results

A total of 65 papers met inclusion criteria for analysis. Pathways were subdivided into intrinsic and extrinsic senescence mechanisms. Intrinsic pathways included genetics, generation of reactive oxygen species and hormonal changes. Extrinsic pathways included photoageing and damage to skin layers. The combined intrinsic and extrinsic pathway alterations result in wrinkles, higher laxity, slackness and thinning of the skin. Skin functions such as barrier immune function, wound healing, thermoregulation and sensory function are also impaired.

Conclusion

The ageing process is unique to the individual and depends on the interplay between an individual's genetics and external environmental factors. Through understanding the molecular and cellular mechanisms, an appreciation of the consequent structural and functional changes can be achieved. Based on this knowledge, further research can focus on how to slow or impede the ageing process and identify specific targets to develop and evolve new treatment strategies.
How do students with intellectual disabilities tell stories? An investigation of narrative macrostructure and microstructure
Authors: Altman Carmit , Avraham Ilanit , Meirovich Shlomit Shnitzer , Lifshitz Hefziba
Published: April 2022

Individuals with intellectual disability may have limited narrative skills. The novelty of this study lies in the examination of strengths and weaknesses which may enable a more facilitative approach to narrative and other storytelling‐based methodologies among adults with intellectual disability who study in an academic enrichment program in comparison to typical students with the same chronological age. Seventeen adult students with intellectual disability and 16 typically developing students, produced narratives which were examined for microstructure (e.g., length, lexis, grammaticality, and complexity) macrostructure (e.g., goals, attempts, and outcomes) and Internal state terms (ISTs). The findings indicate that in spite of weakness of adults with intellectual disability in terms of coherence, syntactic complexity, and grammatical sentences, they exhibit strengths in narrative macrostructure story scheme and use IST. With increasing age, narratives performance of adults with intellectual disability continues to advance possibly due to maturity, life experience and indirect exposure to the environment.
Multi‐site proficiency testing for validation and standardization of assays to detect specific pathogen‐free viruses, coronaviruses, and other agents in nonhuman primates
Authors: Yee JoAnn L. , Grant Richard , Haertel Andrew J. , Allers Carolina , Carpenter Amanda B. , Van Rompay Koen K. A. , Roberts Jeffrey A.
Published: April 2022

In efforts to increase rigor and reproducibility, the USA National Primate Research Centers (NPRCs) have focused on qualification of reagents, cross‐laboratory validations, and proficiency testing for methods to detect infectious agents and accompanying immune responses in nonhuman primates. The pathogen detection working group, comprised of laboratory scientists, colony managers, and leaders from the NPRCs, has championed the effort to produce testing that is reliable and consistent across laboratories. Through multi‐year efforts with shared proficiency samples, testing percent agreement has increased from as low as 67.1% for SRV testing in 2010 to 92.1% in 2019. The 2019 average agreement for the four basic SPF agents improved to >96% (86.5% BV, 98.9 SIV, 92.1 SRV, and 97.0 STLV). As new pathogens such as SARS coronavirus type 2 emerge, these steps can now be quickly replicated to develop and implement new assays that ensure rigor, reproducibly, and quality for NHP pathogen detection.
Do religious transitions from early to established adulthood predict filial elder‐care norms?
Authors: Hwang Woosang , Kim Jeung Hyun , Brown Maria T. , Silverstein Merril
Published: April 2022

Objective

This study employs multiple religious dimensions and a developmental perspective to identify distinct classes of religiosity among young adults in early and middle adulthood, and to describe how transition patterns in religiosity classes are associated with filial elder‐care norms in midlife.

Background

There is a broad consensus that religiosity is associated with strong intergenerational ties, including the willingness to provide support and care for older parents. Less is known regarding how transitions in religiosity from early to middle adulthood predict filial eldercare norms in midlife.

Methods

The sample consisted of 365 young adults participating in the Longitudinal Study of Generations in 2000 (mean age = 23 years) and 2016 (mean age = 39 years) waves. We conducted latent class and latent transition analyses to address study aims.

Results

Analyses indicate three latent classes of religiosity in both 2000 and 2016 waves: strongly religious, weakly religious, and doctrinally religious. Those who remained weakly religious and who declined in religiosity between 2000 and 2016 held weaker filial elder‐care norms in 2016 compared to those who remained strongly religious.

Conclusion

Our findings add a developmental perspective to the literature on religion and filial norms and suggest that trends toward irreligion and increased secularly may portend weakening responsibility for aging parents among middle‐aged adults.
Clinical manifestations of SARS‐CoV‐2 infection in neonates and the probability of maternal transmission
Authors: Mahfouz Mohammad EM , Elrewiny Mohamed , Abdel‐Moneim Ahmed S
Published: April 2022

Aim

This study aimed to measure the incidence of SARS‐CoV‐2 infection in neonates from infected mothers and to screen disease severity in neonates.

Methods

We conducted a population‐based cohort study of neonates from SARS‐CoV‐2‐positive mothers, enrolling mothers who tested positive for SARS‐CoV‐2 and their neonates. Eleven infants <25 days old presenting with SARS‐CoV‐2 infection were also included in the study. We recorded clinical symptoms of SARS‐CoV‐2‐positive mothers and their neonates.

Results

One of 126 babies born to SARS‐CoV‐2‐infected mothers was found to be positive (0.79%). The referred positive neonates were either asymptomatic or suffered from symptoms ranging from mild respiratory distress to pneumonia. Most SARS‐CoV‐2‐positive neonates showed neutropenia and lymphocytosis. Most of the SARS‐CoV‐2‐infected mothers (n = 126) were either asymptomatic (46, 36.5%) or showed mild respiratory distress (66, 52.4%). However, pneumonia and severe respiratory distress were reported in 14 (11.1%) of the SARS‐CoV‐2‐infected mothers. There were no deaths of either SARS‐CoV‐2‐infected mothers or neonates.

Conclusion

We conclude that mothers transmitted infection to their neonates at a very low rate. Disease in neonates is usually mild, although some babies have severe disease. SARS‐CoV‐2 infection in late pregnancy usually leads to mild maternal disease, but severe disease is reported in approximately one‐tenth of the infected women.
Evaluation of dissimilar intestinal bacteria incorporated feeds on growth of ornamental fish Swordtail Xiphophorus helleri
Authors: Rajan M.R. , Brindha G.
Published: April 2022

Four dissimilar bacterial colonies were isolated from the intestine of ornamental fish Swordtail Xiphophorus helleri through serial dilution. The isolated colonies were identified as Enterobacter sp., Bacillus sp., Streptococcus sp. and Pseudomonas sp. using biochemical tests. Enzyme productivity and antibacterial activity of intestinal bacteria of Swordtail were carried out against pathogens such as Enterococcus faecalis, Shigella flexneri, Streptococcus pyogenes and Klebshilla pneumoniae along with commercial antibiotic Tetracycline. Based on biochemical tests, enzyme productivity and antibacterial activity mass multiplication of Enterobacter sp., Bacillus sp. and Streptococcus sp. were done in nutrient broth. Four different feeds such as feed I (Control) (without bacteria), Feed II (1ml Bacillus sp.), Feed III (1 ml of each of Bacillus sp. and Streptococcus sp.) and Feed IV (1 ml each of Bacillus sp., Streptococcus sp. and Enterobacter sp.) were prepared. A total of 60 fishes were used for the study. Feed utilization parameters of the Swordtail were estimated after 21 days. Based on the antibacterial test, the Bacillus sp. and Enterobacter sp. have higher inhibition. Most of the feed utilization parameters were higher in feed IV. From the results, it was concluded that the combination of three dissimilar bacteria in the feed enhanced the growth of the Swordtail.
When Do Mediators Say “No”? The Case of American Resistance to Mediating the Gulf Diplomatic Crisis
Authors: Vuković Siniša , Martin Danielle
Published: April 2022

When do mediators say “no” and refuse to manage an escalating conflict, even if they meet all of the prerequisites for jumpstarting a peacemaking process? Empirical studies to date have focused primarily on factors that facilitate the start of mediation efforts. Surprisingly, very little is known about the reasons that motivate third parties' refusal to engage. Working against the backdrop of conceptual frameworks that indicate when mediators say “yes,” this article offers a novel framework for analysis that explicates three conditions that dissuade third parties from mediating. Using the case of the U.S. resistance to mediate the Gulf diplomatic crisis, the article shows that mediators will refuse to mediate conflicts that are characterized by high levels of power symmetry, pronounced structural linkage with conflicting parties, and extensive strategic interests in the conflict‐affected area.
Three‐dimensional assessment of tongue cancer prognosis by preoperative MRI
Authors: Li Chenyao , Zhu Ling , Guo Yibo , Ji Tong , Ren Zhenhu
Published: April 2022

Purpose

To obtain the relative volume by measuring the tongue volume and the lesion volume, and further explore its relationship with the prognosis of patients, hoping to supplement the TNM staging with a new index.

Methods

ITK‐SANP software was used to outline the patients’ MRI. After MRI reconstruction and measurement, slicer software was used to estimate tumor volume.

Results

A total of 64 patients with tongue cancer who met the inclusion criteria were included in the study. The estimated tumor volume after MRI reconstruction revealed a significant and robust correlation with tumor stage (p < 0.05, Rs = 0.6207) and a substantial and medium correlation with early lymph node metastasis (p < 0.05, Rs = 0.4873).

Conclusions

We classified tongue cancer into three grades based on tumor volume (Stage I, tumors smaller than 1500 mm³; Stage II, tumors 1500–9000 mm³; and Stage III, tumors larger than 9000 mm³), and such grading could be used as a reference for tumor staging, lymph node metastasis, and patient prognosis to a certain extent.
The association of severe pain experienced in the pediatric intensive care unit and postdischarge health‐related quality of life: A retrospective cohort study
Authors: Smith Mallory B. , Killien Elizabeth Y. , Dervan Leslie A. , Rivara Frederick P. , Weiss Noel S. , Watson Robert Scott
Published: April 2022

Background

Pain may be a modifiable risk factor for lower health‐related quality of life after pediatric critical illness.

Aim

To evaluate the association between severe pain experienced in the (pediatrc intensive care unit) and postdischarge health‐related quality of life.

Methods

This was a retrospective cohort study. Children aged 1 month to 18 years admitted to the pediatric intensive care unit and enrolled in the Seattle Children's Hospital Outcomes Assessment Program were included. Pain was assessed every 2 h by bedside nursing staff using a behavioral pain scale or numeric pain scale. A day of severe pain was defined as a pediatric intensive care unit day with ≥25% of pain scores ≥7/10. Baseline (preadmission) and postdischarge (median 6 weeks) health‐related quality of life was assessed by the Pediatric Quality of Life Inventory (PedsQL™) or the Stein Jessop Functional Status II‐R (FS II‐R, for children with developmental disability). The cohort was stratified by diagnosis category (surgical vs. medical), and associations were measured using linear regression models.

Results

Among 546 patients, 11.9% experienced ≥1 day of severe pain. In multivariable linear regression, each day of severe pain was independently associated with a lower postdischarge health‐related quality of life score by 3.6 points (95% CI −6.3 to −0.9) adjusted for baseline health‐related quality of life score, age, baseline cognitive function, days with multi‐organ dysfunction, pediatric intensive care unit length of stay, and decline in overall function. This association was stronger among surgical patients than medical patients with each day of severe pain resulting in a lower postdischarge health‐related quality of life score by 5.3 points (95% CI −9.6 to −0.9) versus 2.6 points (95% CI −5.8 to 0.6). Surgical patients had lower postdischarge emotional functioning than physical functioning subdomain scores.

Conclusions

Children who experience severe pain in the pediatric intensive care unit have lower postdischarge health‐related quality of life adjusting for baseline health‐related quality of life, particularly among children who have undergone surgery. Attention to pain management may be important to improve postdischarge health‐related quality of life.
Riboflavin integrates cellular energetics and cell cycle to regulate maize seed development
Authors: Tian Qiuzhen , Wang Gang , Ma Xuexia , Shen Qingwen , Ding Mengli , Yang Xueyi , Luo Xiaoli , Li Rongrong , Wang Zhenghui , Wang Xiangyang , Fu Zhiyuan , Yang Qinghua , Tang Jihua , Wang Guifeng
Published: April 2022

Riboflavin is the precursor of essential cofactors for diverse metabolic processes. Unlike animals, plants can de novo produce riboflavin through an ancestrally conserved pathway, like bacteria and fungi. However, the mechanism by which riboflavin regulates seed development is poorly understood. Here, we report a novel maize (Zea mays L.) opaque mutant o18, which displays an increase in lysine accumulation, but impaired endosperm filling and embryo development. O18 encodes a rate‐limiting bifunctional enzyme ZmRIBA1, targeted to plastid where to initiate riboflavin biosynthesis. Loss of function of O18 specifically disrupts respiratory complexes I and II, but also decreases SDH1 flavinylation, and in turn shifts the mitochondrial tricarboxylic acid (TCA) cycle to glycolysis. The deprivation of cellular energy leads to cell‐cycle arrest at G1 and S phases in both mitosis and endoreduplication during endosperm development. The unexpected up‐regulation of cell‐cycle genes in o18 correlates with the increase of H3K4me3 levels, revealing a possible H3K4me‐mediated epigenetic back‐up mechanism for cell‐cycle progression under unfavourable circumstances. Overexpression of O18 increases riboflavin production and confers osmotic tolerance. Altogether, our results substantiate a key role of riboflavin in coordinating cellular energy and cell cycle to modulate maize endosperm development.
Disentangling cognitive inflexibility in major depressive disorder: A transcranial direct current stimulation study
Authors: Koshikawa Yosuke , Nishida Keiichiro , Yamane Tomonari , Yoshimura Masafumi , Onohara Ai , Ueda Satsuki , Ishii Ryouhei , Kinoshita Toshihiko , Morishima Yosuke
Published: April 2022

Background

Cognitive dysfunction is a persistent residual symptom in major depressive disorders (MDDs) that hinders social and occupational recovery. Cognitive inflexibility is a typical cognitive dysfunction in MDD and refers to difficulty in switching tasks, which requires two subcomponents: forgetting an old task and adapting to a new one. Here, we aimed to disentangle the subcomponents of cognitive inflexibility in MDD and investigate whether they can be improved by transcranial direct current stimulation (tDCS) on the prefrontal cortex.

Methods

The current study included 20 patients with MDD (seven females) and 22 age‐matched healthy controls (HCs) (seven females). The participants received anodal tDCS on either the dorsomedial prefrontal cortex (DMPFC) or dorsolateral prefrontal cortex (DLPFC) in a crossover design. Before and after the application of tDCS, the participants performed a modified Wisconsin Card Sorting Test, in which the task‐switching rules were explicitly described and proactive interference from a previous task rule was occasionally released.

Results

We found that the behavioral cost of a task switch was increased in patients with MDD, but that of proactive interference was comparable between patients with MDD and HCs. The response time for anodal DMPFC tDCS was decreased compared with that for anodal tDCS on the DLPFC in MDD.

Conclusions

These findings suggest that cognitive inflexibility in MDD is primarily explained by the difficulty to adapt to a new task and environment, and that tDCS on the DMPFC improves behavioral performance during cognitively demanding tasks that require conflict resolution.
Semiparametric Latent Class Analysis of Recurrent Event Data
Authors: Zhao Wei , Peng Limin , Hanfelt John
Published: April 2022

Recurrent event data frequently arise in chronic disease studies, providing rich information on disease progression. The concept of latent class offers a sensible perspective to characterize complex population heterogeneity in recurrent event trajectories that may not be adequately captured by a single regression model. However, the development of latent class methods for recurrent event data has been sparse, typically requiring strong parametric assumptions and involving algorithmic issues. In this work, we investigate latent class analysis of recurrent event data based on flexible semiparametric multiplicative modelling. We derive a robust estimation procedure through novelly adapting the conditional score technique and utilizing the special characteristics of multiplicative intensity modelling. The proposed estimation procedure can be stably and efficiently implemented based on existing computational routines. We provide solid theoretical underpinnings for the proposed method, and demonstrate its satisfactory finite sample performance via extensive simulation studies. An application to a dataset from research participants at Goizueta Alzheimer's Disease Research Center illustrates the practical utility of our proposals.
Cross‐inoculation of rhizobiome from a congeneric ruderal plant imparts drought tolerance in maize (Zea mays) through changes in root morphology and proteome
Authors: Zhang Ziliang , Jatana Bhupinder Singh , Campbell Barbara J. , Gill Jasmine , Suseela Vidya , Tharayil Nishanth
Published: April 2022

Rhizobiome confer stress tolerance to ruderal plants, yet their ability to alleviate stress in crops is widely debated, and the associated mechanisms are poorly understood. We monitored the drought tolerance of maize (Zea mays) as influenced by the cross‐inoculation of rhizobiota from a congeneric ruderal grassAndropogon virginicus(andropogon‐inoculum), and rhizobiota from organic farm maintained under mesic condition (organic‐inoculum). Across drought treatments (40% field capacity), maize that receivedandropogon‐inoculumproduced two‐fold greater biomass. This drought tolerance translated to a similar leaf metabolomic composition as that of the well‐watered control (80% field capacity) and reduced oxidative damage, despite a lower activity of antioxidant enzymes. At a morphological‐level, drought tolerance was associated with an increase in specific root length and surface area facilitated by the homeostasis of phytohormones promoting root branching. At a proteome‐level, the drought tolerance was associated with upregulation of proteins related to glutathione metabolism and endoplasmic reticulum‐associated degradation process. Fungal taxa belonging to Ascomycota, Mortierellomycota, Archaeorhizomycetes, Dothideomycetes, and Agaricomycetes inandropogon‐inoculumwere identified as potential indicators of drought tolerance. Our study provides a mechanistic understanding of the rhizobiome‐facilitated drought tolerance and demonstrates a better path to utilize plant–rhizobiome associations to enhance drought tolerance in crops.
Dissipation-enabled hydrodynamic conductivity in a tunable bandgap semiconductor
Authors: Tan Cheng , Ho Derek Y. H. , Wang Lei , Li Jia I. A. , Yudhistira Indra , Rhodes Daniel A. , Taniguchi Takashi , Watanabe Kenji , Shepard Kenneth , McEuen Paul L. , Dean Cory R. , Adam Shaffique , Hone James
Published: April 2022

Electronic transport in the regime where carrier-carrier collisions are the dominant scattering mechanism has taken on new relevance with the advent of ultraclean two-dimensional materials. Here, we present a combined theoretical and experimental study of ambipolar hydrodynamic transport in bilayer graphene demonstrating that the conductivity is given by the sum of two Drude-like terms that describe relative motion between electrons and holes, and the collective motion of the electron-hole plasma. As predicted, the measured conductivity of gapless, charge-neutral bilayer graphene is sample- and temperature-independent over a wide range. Away from neutrality, the electron-hole conductivity collapses to a single curve, and a set of just four fitting parameters provides quantitative agreement between theory and experiment at all densities, temperatures, and gaps measured. This work validates recent theories for dissipation-enabled hydrodynamic conductivity and creates a link between semiconductor physics and the emerging field of viscous electronics.
Classification of human chronic inflammatory skin disease based on single-cell immune profiling
Authors: Liu Yale , Wang Hao , Taylor Mark , Cook Christopher , Martínez-Berdeja Alejandra , North Jeffrey P. , Harirchian Paymann , Hailer Ashley A. , Zhao Zijun , Ghadially Ruby , Ricardo-Gonzalez Roberto R. , Grekin Roy C. , Mauro Theodora M. , Kim Esther , Choi Jaehyuk , Purdom Elizabeth , Cho Raymond J. , Cheng Jeffrey B.
Published: April 2022

Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell–profiled CD45
+
immune cell transcriptomes from skin samples of 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, and 7 healthy controls). Our data revealed active proliferative expansion of the T
reg
and Trm components and universal T cell exhaustion in human rashes, with a relative attenuation of antigen-presenting cells. Skin-resident memory T cells showed the greatest transcriptional dysregulation in both atopic dermatitis and psoriasis, whereas atopic dermatitis also demonstrated recurrent abnormalities in ILC and CD8
+
cytotoxic lymphocytes. Transcript signatures differentiating these rash types included genes previously implicated in T helper cell (T
H
2)/T
H
17 diatheses, segregated in unbiased functional networks, and accurately identified disease class in untrained validation data sets. These gene signatures were able to classify clinicopathologically ambiguous rashes with diagnoses consistent with therapeutic response. Thus, we have defined major classes of human inflammatory skin disease at the molecular level and described a quantitative method to classify indeterminate instances of pathologic inflammation. To make this approach accessible to the scientific community, we created a proof-of-principle web interface (RashX), where scientists and clinicians can visualize their patient-level rash scRNA-seq–derived data in the context of our T
H
2/T
H
17 transcriptional framework.
Anaesthetic management of a patient with complex, cyanotic congenitally corrected transposition of great arteries for electrophysiological study and thermoablation
Authors: Chen Jinghui , Tan Shi Hui , Chee Sheryl Wei Lin , Kothandan Harikrishnan
Published: April 2022

Congenitally corrected transposition of great arteries (ccTGA) is a rare congenital heart disease, and little literature is available that describes its anaesthetic management. We present the perioperative management of a patient with complex, cyanotic ccTGA who underwent electrophysiological study with catheter ablation under general anaesthesia. Good understanding of the patient’s complex cardiac anatomy and physiology and multidisciplinary communication are vital to facilitate the successful care of the patient.
Late onset AMACR deficiency with metabolic stroke-like episodes and seizures
Authors: Tanti Matthew J , Maguire Melissa J , Warren Daniel J , Bamford John
Published: April 2022

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal disorder causing pristanic acid accumulation. Only 16 cases have been described so far. A female in her seventh decade presented with episodes of dysphasia, headache and sensory disturbance inconsistent with migraine, epilepsy or transient ischaemic attack. An MRI demonstrated unusual changes in the pons, red nuclei, thalami and white matter. Mitochondrial disease was suspected but detailed testing was negative. After eight years of symptoms, she developed a febrile encephalopathy with hemispheric dysfunction, focal convulsive seizures and coma. Her condition stabilised after one month. Lacosamide was continued for seizure prevention. The diagnosis remained elusive until whole genome sequencing revealed AMACR deficiency. Pristanic acid levels were highly elevated and dietary modification was recommended. Genetic peroxisomal disorders can present in older age; our patient is the oldest in the AMACR deficiency literature. Novel features in our case include central apnoea, dystonia and rapid eye movement behaviour disorder.
Cochlear implantation after deafness fromPasteurella multocidameningitis
Authors: Warner Jeffrey Dewitt , Tilak Ashwini Milind , Manickavel Sudhir , Walsh Erika
Published: April 2022

A woman in her late 40s who works as a veterinary technician represented to the emergency department with increasing headache, confusion, neck stiffness, subjective fevers and distorted hearing 2 days after diagnosis of viral infection at an outside emergency department.

Diagnosis ofPasteurella multocidawas made from blood cultures and lumbar puncture. Intravenous ceftriaxone was administered for 21 days. By the time of resolution of acute meningitis, she had become completely deaf bilaterally. MRI revealed faint early ossification/possible labyrinthitis ossificans of the basal cochlea, which was confirmed on surgical exploration during the placement of cochlear implants bilaterally 42 days later. We discuss how the atypical features of this infection lead to diagnostic delay and high morbidity, the unique imaging/surgical findings resulting from the infection, and the clinical utility of early and bilateral cochlear implantation in this and similar cases.
Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials
Authors: Core Jason Q , Hua Peiying , Daniel Ebenezer , Grunwald Juan E , Jaffe Glenn , Maguire Maureen G , Ying Gui-shuang
Published: April 2022

Background

Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD).

Methods

Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium fluid, and foveal thickness of retinal layers were evaluated at baseline and during 2-year follow-up. Comparisons of outcomes between thiazolidinedione usage groups were adjusted by macular neovascularisation lesion type in multivariable regression models.

Results

Patients taking thiazolidinedione (n=30) had lower adjusted mean VA score at baseline (difference −6.2 letters; p=0.02), greater proportion with intraretinal fluid (IRF) at year 2 (75% vs 50%, adjusted OR 2.8; p=0.04), greater mean decrease in subretinal tissue complex thickness from baseline at year 1 (difference −75.1 um; p=0.02) and greater mean decrease in subretinal thickness at year 1 (difference −41.9 um; p=0.001) and year 2 (difference −43.3 um; p=0.001).

Conclusions

In this exploratory analysis, patients with diabetes taking thiazolidinediones and treated with bevacizumab or ranibizumab for nAMD had worse baseline mean VA, greater reductions in subretinal and subretinal tissue complex thickness from baseline, and greater proportions with IRF comparing to patients not taking thiazolidinediones.

Trial registration number

ClinicalTrials.govNCT00593450.
Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma
Authors: Alonso-Nocelo Marta , Ruiz-Cañas Laura , Sancho Patricia , Görgülü Kıvanç , Alcalá Sonia , Pedrero Coral , Vallespinos Mireia , López-Gil Juan Carlos , Ochando Marina , García-García Elena , David Trabulo Sara Maria , Martinelli Paola , Sánchez-Tomero Patricia , Sánchez-Palomo Carmen , Gonzalez-Santamaría Patricia , Yuste Lourdes , Wörmann Sonja Maria , Kabacaoğlu Derya , Earl Julie , Martin Alberto , Salvador Fernando , Valle Sandra , Martin-Hijano Laura , Carrato Alfredo , Erkan Mert , García-Bermejo Laura , Hermann Patrick C , Algül Hana , Moreno-Bueno Gema , Heeschen Christopher , Portillo Francisco , Cano Amparo , Sainz Bruno
Published: April 2022

Objective

The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models.

Design

Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies,K-Ras+/LSL-G12D;Trp53LSL-R172H;Pdx1-Cremice (KPC) and theK-Ras+/LSL-G12D;Pdx1-Cremice (KC) were crossed withLoxl2allele floxed mice (Loxl2Exon2fl/fl) or conditionalLoxl2overexpressing mice (R26Loxl2KI/KI) to generate KPCL2KOor KCL2KOand KPCL2KIor KCL2KImice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation.

Results

Using these PDAC mouse models, we show that whileLoxl2ablation had little effect on primary tumour development and growth, its loss significantly decreased metastasis and increased overall survival. We attribute this effect to non-cell autonomous factors, primarily ECM remodelling.Loxl2overexpression, on the other hand, promoted primary and metastatic tumour growth and decreased overall survival, which could be linked to increased EMT and stemness. We also identified tumour-associated macrophage-secreted oncostatin M (OSM) as an inducer of LOXL2 expression, and show that targeting macrophages in vivo affectsOsmandLoxl2expression and collagen fibre alignment.

Conclusion

Taken together, our findings establish novel pathophysiological roles and functions for LOXL2 in PDAC, which could be potentially exploited to treat metastatic disease.
Diversity in clinical research: public health and social justice imperatives
Authors: Varma Tanvee , Jones Camara P , Oladele Carol , Miller Jennifer
Published: April 2022

It is well established that demographic representation in clinical research is important for understanding the safety and effectiveness of novel therapeutics and vaccines in diverse patient populations. In recent years, the National Institutes of Health and Food and Drug Administration have issued guidelines and recommendations for the inclusion of women, older adults, and racial and ethnic minorities in research. However, these guidelines fail to provide an adequate explanation of why racial and ethnic representation in clinical research is important. This article aims to both provide the missing arguments for why adequate representation of racial and ethnic minorities in clinical research is essential and to articulate a number of recommendations for improving diversity going forward.

Appropriate racial and ethnic representation and fair inclusion help (1) increase the generalisability of clinical trial results, (2) equitably distribute any benefits of clinical research and (3) enable trust in the research enterprise.