bluuebunny/crossref_metadata_2025 huggingface dataset:
Butyrate enhances Clostridioides difficile sporulationin vitro
Authors: Baldassare Michelle A. , Bhattacharjee Disha , Coles Julian D. , Nelson Sydney , McCollum C. Alexis , Seekatz Anna M.
Published: April 2023

Short chain fatty acids (SCFAs) are products of bacterial fermentation that help maintain important gut functions such as the intestinal barrier, signaling, and immune homeostasis. The main SCFAs acetate, propionate, and butyrate have demonstrated beneficial effects for the host, including importance in combatting infections caused by pathogens such asClostridioides difficile. Despite the potential role of SCFAs in mitigatingC. difficileinfection, their direct effect onC. difficileremains unclear. Through a set ofin vitroexperiments, we investigated how SCFAs influenceC. difficilegrowth, sporulation, and toxin production. Similar to previous studies, we observed that butyrate decreased growth ofC. difficilestrain 630 in a dose-dependent manner. The presence of butyrate also increasedC. difficilesporulation, with minimal increases in toxin production. RNA-Seq analysis validated our experimental results, demonstrating increased expression of sporulation-related genes in conjunction with alternative metabolic and relatedC. difficileregulatory pathways, such as the carbon catabolite repressor, CcpA. Collectively, these data suggest that butyrate may signal alternativeC. difficilemetabolic pathways, thus modifying its growth and virulence to persist in the gut environment.

IMPORTANCE

Several studies suggest that butyrate may be important in alleviating gut infections, such as reducing inflammation caused by the healthcare-associatedClostridioides difficile. While studies in both animal models and human studies correlate high levels of butyrate with reducedC. difficileburden, the direct impact of butyrate onC. difficileremains unclear. Our study demonstrates that butyrate directly influencesC. difficileby increasing its sporulation and modifying its metabolism, potentially using butyrate as a biomarker to shift survival strategies in a changing gut environment. These data point to additional therapeutic approaches to combatC. difficilein a butyrate-directed manner.
Understanding the Mechanisms ofSalmonellaTyphimurium resistance to Cannabidiol
Authors: Ibrahim Iddrisu , Ayariga Joseph Atia , Xu Junhuan , Abugri Daniel A. , Boakai Robertson K. , Ajayi Olufemi S.
Published: April 2023

The emergence of multidrug resistance poses a huge risk to public health globally. Yet these recalcitrant pathogens continue to rise in incidence rate with resistance rates significantly outpacing the speed of antibiotic development. This therefore presents an aura of related health issues such as untreatable nosocomial infections arising from organ transplants, surgeries, as well as community acquired infections that are related to people with compromised immunity e.g., diabetic and HIV patients etc. There is a global effort to fight multidrug resistant pathogens spearheaded by the World Health Organization, thus calling for research into novel antimicrobials agents to fight multiple drug resistance. Previously, our laboratory demonstrated that Cannabidiol (CBD) was an effective antimicrobial against Salmonella Typhimurium (S. Typhimurium). However, we observed resistance development over time. To understand the mechanisms S. Typhimurium uses to develop resistance to Cannabidiol (CBD), we studied the abundance of bacteria lipopolysaccharide (LPS) and membrane sterols of both susceptible and resistant S. Typhimurium. Using real-time quantitative polymerase chain reaction (rt qPCR), we also analyzed the expression of selected genes known for aiding resistance development in S. Typhimurium. We discovered that there was a significantly higher expression of blaTEM, fimA, fimZ, and integrons in the CBD-resistant bacteria, and these were also accompanied by a shift in abundance in cell surface molecules such as lipopolysaccharide (LPS) and sterols.
Concurrent infection of human brain with multiple species of Lyme disease spirochetes
Authors: Golovchenko Maryna , Opelka Jakub , Vancova Marie , Sehadova Hana , Kraliková Veronika , Dobias Martin , Raska Milan , Krupka Michal , Sloupenská Kristyna , Rudenko Natalie
Published: April 2023

Lyme disease (LD) spirochetes are well known to be able to disseminate into the tissues of infected hosts, including humans. The diverse strategies used by spirochetes to avoid the host immune system and persist in the host include active immune suppression, induction of immune tolerance, phase and antigenic variation, intracellular seclusion, and, importantly, incursion into immune privileged sites such as the brain. Invasion of immune privileged sites, like the brain allows the spirochetes not only escape from the host immune system but also can reduce the efficacy of antibiotic therapy.

Here we present a case of the detection of DNA of spirochetes fromBorrelia burgdorferisensu lato complex from multiple loci of LD patient’s post-mortem brain. The presence of co-infection withBorrelia burgdorferisensu stricto andBorrelia gariniiin LD patient’s brain was confirmed by PCR. The presence of atypical spirochete morphology was confirmed by immunohistochemistry of the brain samples and also in tissues of experimental mice, infected withBorreliaby simultaneous injection of spirochetes subcutaneously and intraperitoneally. Even though both spirochete species were simultaneously present in brain, the brain regions where the two species were detected were different and non-overlapping.
Selective effects of estradiol on human corneal endothelial cells
Authors: Han Seoyoung , Mueller Christian , Wuebbolt Caitlin , Kilcullen Sean , Nayyar Varinda , Calle Gonzalez Brayan , Mahdavi Fard Ali , Floss Jamie C. , Morales Michael J. , Patel Sangita P.
Published: April 2023

Fuchs endothelial corneal dystrophy (FECD) results from genetic and environmental factors triggering mitochondrial and oxidative stress in corneal endothelial cells (CEnCs) leading to CEnC death and corneal opacification. FECD is more common in women than men, but the basis for this observation is unknown. Because FECD is commonly diagnosed around the time of the menopausal transition in women when estrogen levels decrease precipitously, we studied the effects of the potent estrogen,17-β estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of human CEnCs (HCEnCs) under conditions of physiologic 2.5% O2([O2]2.5) and under hyperoxic stress ([O2]A: room air + 5% CO2). We hypothesized that E2 would counter the stresses of the hyperoxic environment in HCEnCs. HCEnCs were treated ± 10 nM E2 for 7-10 days at [O2]2.5and [O2]Afollowed by measurements of cell density, viability, reactive oxygen species (ROS), mitochondrial morphology, oxidative DNA damage, ATP levels, mitochondrial respiration (O2consumption rate [OCR]), and glycolysis (extracellular acidification rate [ECAR]). There were no significant changes in HCEnC density, viability, ROS levels, oxidative DNA damage, OCR, and ECAR in response to E2 under either O2condition. We found that E2 disrupted mitochondrial morphology in HCEnCs from female donors but not male donors at the [O2]Acondition. ATP levels were significantly higher at [O2]2.5compared to [O2]Ain HCEnCs from female donors only, but were not affected by E2. Our findings demonstrate the overall resilience of primary HCEnCs against hyperoxic stress. The selective detrimental effects of hyperoxia and estradiol on HCEnCs from female but not male donors suggests mechanisms of toxicity based upon cell-sex in addition to hormonal environment.
Accurate transcriptome-wide identification and quantification of alternative polyadenylation from RNA-seq data with APAIQ
Authors: Long Yongkang , Zhang Bin , Tian Shuye , Chan Jia Jia , Zhou Juexiao , Li Zhongxiao , Li Yisheng , An Zheng , Liao Xingyu , Wang Yu , Sun Shiwei , Xu Ying , Tay Yvonne , Chen Wei , Gao Xin
Published: April 2023

Alternative polyadenylation (APA) enables a gene to generate multiple transcripts with different 3′ ends, which is dynamic across different cell types or conditions. Many computational methods have been developed to characterize sample-specific APA using the corresponding RNA-seq data, but suffered from high error rate on both polyadenylation site (PAS) identification and quantification of PAS usage (PAU), and bias toward 3′ untranslated regions. Here we developed a tool for APA identification and quantification (APAIQ) from RNA-seq data, which can accurately identify PAS and quantify PAU in a transcriptome-wide manner. Using 3′ end-seq data as the benchmark, we showed that APAIQ outperforms current methods on PAS identification and PAU quantification, including DaPars2, Aptardi, mountainClimber, SANPolyA, and QAPA. Finally, applying APAIQ on 421 RNA-seq samples from liver cancer patients, we identified >540 tumor-associated APA events and experimentally validated two intronic polyadenylation candidates, demonstrating its capacity to unveil cancer-related APA with a large-scale RNA-seq data set.
Understanding structural distortions in hybrid layered perovskites with the n = 1 Ruddlesden–Popper structure
Authors: Liu Tianyu , Holzapfel Noah P. , Woodward Patrick M.
Published: April 2023

A symmetry mode analysis yields 47 symmetrically distinct patterns of octahedral tilting in hybrid organic–inorganic layered perovskites that adopt the n = 1 Ruddlesden–Popper (RP) structure. The crystal structures of compounds belonging to this family are compared with the predictions of the symmetry analysis. Approximately 88% of the 140 unique structures have symmetries that agree with those expected based on octahedral tilting alone, while the remaining compounds have additional structural features that further lower the symmetry, such as asymmetric packing of bulky organic cations, distortions of metal-centered octahedra or a shift of the inorganic layers that deviates from the a/2 + b/2 shift associated with the RP structure. The structures of real compounds are heterogeneously distributed amongst the various tilt systems, with only 9 of the 47 tilt systems represented. No examples of in-phase ψ-tilts about the a and/or b axes of the undistorted parent structure were found, while at the other extreme ∼66% of the known structures possess a combination of out-of-phase ϕ-tilts about the a and/or b axes and θ-tilts (rotations) about the c axis. The latter combination leads to favorable hydrogen bonding interactions that accommodate the chemically inequivalent halide ions within the inorganic layers. In some compounds, primarily those that contain either Pb2+ or Sn2+, favorable hydrogen bonding interactions can also be achieved by distortions of the octahedra in combination with θ-tilts.
New cocrystals of heterocyclic drugs: structural, antileishmanial, larvicidal and urease inhibition studies
Authors: Murtaza Ghulam , Khan Majid , Farooq Saba , Choudhary M. Iqbal , Yousuf Sammer
Published: April 2023

Many heterocycles have been developed as drugs due to their capacity to interact productively with biological systems. The present study aimed to synthesize cocrystals of the heterocyclic antitubercular agent pyrazinamide (PYZ,1, BCS III) and the commercially available anticonvulsant drug carbamazepine (CBZ,2, BCS class II) to study the effect of cocrystallization on the stability and biological activities of these drugs. Two new cocrystals, namely, pyrazinamide–homophthalic acid (1/1) (PYZ:HMA,3) and carbamazepine–5-chlorosalicylic acid (1/1) (CBZ:5-SA,4), were synthesized. The single-crystal X-ray diffraction-based structure of carbamazepine–trans-cinnamic acid (1/1) (CBZ:TCA,5) was also studied for the first time, along with the known cocrystal carbamazepine–nicotinamide (1/1) (CBZ:NA,6). From a combination drug perspective, these are interesting pharmaceutical cocrystals to overcome the known side effects ofPYZ(1) therapy, and the poor biopharmaceutical properties ofCBZ(2). The purity and homogeneity of all the synthesized cocrystals were confirmed by single-crystal X-ray diffraction, powder X-ray diffraction and FT–IR analysis, followed by thermal stability studies based on differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Detailed intermolecular interactions and the role of hydrogen bonding towards crystal stability were evaluated quantitativelyviaHirshfeld surface analysis. The solubility ofCBZat pH 6.8 and 7.4 in 0.1 NHCl and H2O were compared with the values of cocrystalCBZ:5-SA(4). The solubility ofCBZ:5-SAwas found to be significantly improved at pH 6.8 and 7.4 in H2O. All the synthesized cocrystals3–6exhibited a potent urease inhibition (IC50values range from 17.32 ± 0.89 to 12.3 ± 0.8 µM), several times more potent than standard acetohydroxamic acid (IC50 = 20.34 ± 0.43 µM).PYZ:HMA(3) also exhibited potent larvicidal activity againstAedes aegypti. Among the synthesized cocrystals,PYZ:HMA(3) andCBZ:TCA(5) were found to possess antileishmanial activity against the miltefosine-induced resistant strain ofLeishmania major, with IC50values of 111.98 ± 0.99 and 111.90 ± 1.44 µM, respectively, in comparison with miltefosine (IC50 = 169.55 ± 0.20 µM).
Leave it in! Analyzing the responses to a proposal to remove governmental accounting from the certified public accountant examination
Authors: Flasher Renee , Didia Lydia , Skomra Justyna
Published: April 2023

Purpose

Leveraging lobbying theory, the authors analyze responses to the American Institute of Certified Public Accountants (AICPA) proposal suggesting the removal of state and local governmental accounting from the content tested on the uniform certified public accountant (CPA) examination. Furthermore, the authors compare the responses to a prior exam content review to place the uniqueness of the more recent response in perspective.

Design/methodology/approach

The authors examine 181 comment letters obtained from the AICPA website. In addition, the relative concentration of governmental entities across the USA is studied for correlation with the response rate.

Findings

Consistent with lobbying theory, the authors find that participating governmental entities overwhelmingly argued for the retention of governmental accounting. In contrast, most other groups of respondents (accounting firms, state societies, etc.) had at least one letter that agrees with the removal of the content.

Originality/value

While the letter writers appear to be successful in retaining the governmental accounting content on the CPA exam, the majority of the detailed content has been placed within a specialized area on the new version of the CPA exam, expected to be deployed in 2024. This means that fewer CPA candidates will be exposed to governmental accounting than under the current regime. It has implications for governmental units seeking qualified candidates to fill their staffing needs especially as fewer universities offer governmental accounting courses.
Where to fish in the forest? Tree characteristics and contiguous seagrass features predict mangrove forest quality for fishes and crustaceans
Authors: Wanjiru Caroline , Nagelkerken Ivan , Rueckert Sonja , Harcourt William , Huxham Mark
Published: April 2023

Mangroves often support rich fish and crustacean communities, although faunal abundance and diversity show strong spatiotemporal variability. Consistent patterns in mangrove animal communities might be dictated by forest characteristics, by seascape context or by some combination of these factors. Predicting drivers of spatial heterogeneity in mangrove faunal communities can better support the zoning of forests for management purposes, for example by identifying sites important for fisheries nursery provision.

We sampled 14 sites within a large (4000 ha) mangrove forest in Kenya, quarterly over a period of 2 years. There were clear and consistent differences in the quality of sites for fish and crustacean abundance and diversity.

Forest characteristics (as summarised by the complexity index, CI) and seascape metrics (the presence, area and configuration of contiguous seagrass) were strong predictors of site differences. However, they showed opposite influences on dominant members of the fish and crustacean faunas, with CI correlated negatively with fishes and positively with crustaceans, and seagrass area correlated positively with fishes and negatively with crustaceans.

Synthesis and applications. Sites within the same mangrove forest exhibit consistent differences in fish and crustacean abundance. However, the fish and crustacean communities (and particularly dominant species within them) act differently in response to forest and seascape characteristics. Old growth, mature forest, set in a seascape of seagrass patches with bare sediment, was associated with highest crustacean abundance. In contrast, denser smaller trees and seascapes with larger, continuous areas of seagrass correlated better with fish abundance. Zoning for management, as mandated in new Kenyan policy, will need to consider these differences in seascape use between fish and crustaceans.
Volatile Mining Revenues and State Government Budget Decisions
Authors: Freebairn John , Griffiths William
Published: April 2023

Mining royalties provide a volatile source of revenue for state governments in Australia. We explore the effects of changes in royalty revenue received by a state government on current‐year budget decisions about expenditure, tax revenue and the budget surplus. The literature postulates different models for how lower‐level government budget decisions respond to a revenue windfall from a higher level of government. Empirical evidence on these models over 1998–2019 provides strong evidence that over a half of a royalty windfall becomes a change in budget expenditure. Estimates of changes to tax revenues and the surplus are not definitive nor robust.
Dreaming for the World: A Jungian Study of Dreams During the COVID‐19 Pandemic1
Authors: Landau Ronnie , Brooke Roger , Martin Ned , Lampe Anna , Stich Brianna
Published: April 2023

This project explores what dreams might reveal about the collective psyche’s response to the COVID‐19 pandemic in its first year, before the development of vaccines. A brief survey, distributed to Jungian colleagues and organizations, and to various social media sites, invited people to submit online a dream related to the COVID‐19 pandemic. Four hundred and thirty‐six dreams were submitted. Forty additional Russian dreams were collected and submitted by Russian colleagues. Using qualitative research methods based on phenomenological hermeneutics, the researchers categorized and counted the range of COVID imagery. In addition, the researchers describe a range of psychic responses to the pandemic, including horror, grief, sickness, social discord, and violence, but also images of healing and transformation, increased sense of community, and spiritual renewal. Several healing nightmares are presented. Healing alchemical and anima/animus imagery is described. Twelve dreams are introduced and presented. It is concluded that the collective psyche, rooted in the Self, is a healing resource for social and cultural trauma. This project supports Beradt’s (1968) inspirational study of dreaming in Nazi Germany, as well as recent studies of COVID‐related dreams and recent publications on the social nature of dreaming.
Trends in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) infection and vaccine antibody prevalence in a multi‐ethnic inner‐city antenatal population: A cross‐sectional surveillance study
Authors: Andreeva Daria , Gill Carolyn , Brockbank Anna , Hejmej Joanna , Conti‐Ramsden Fran , Doores Katie J. , Seed Paul T. , Poston Lucilla ,   the eLIXIR Partnership
Published: April 2023

Objective

To determine severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) seroprevalence in pregnancy in an inner‐city setting and assess associations with demographic factors and vaccination timing.

Design

Repeated cross‐sectional surveillance study.

Setting

London maternity centre.

Sample

A total of 906 pregnant women attending nuchal scans, July 2020–January 2022.

Methods

Blood samples were tested for IgG antibodies against SARS‐CoV‐2 nucleocapsid (N) and spike (S) proteins. Self‐reported vaccination status and coronavirus disease 2019 (COVID‐19) infection were recorded. Multivariable regression models determined demographic factors associated with seroprevalence and antibody titres.

Main outcome measures

Immunoglobulin G N‐ and S‐protein antibody titres.

Results

Of the 960 women, 196 (20.4%) were SARS‐CoV‐2 seropositive from previous infection. Of these, 70 (35.7%) self‐reported previous infection. Among unvaccinated women, women of black ethnic backgrounds were most likely to be SARS‐CoV‐2 seropositive (versus white adjusted risk ratio [aRR] 1.88, 95% CI 1.35–2.61,p < 0.001). Women from black and mixed ethnic backgrounds were least likely to have a history of vaccination with seropositivity to S‐protein (versus white aRR 0.58, 95% CI 0.40–0.84,p = 0.004; aRR 0.56, 95% CI 0.34–0.92,p = 0.021, respectively). Double vaccinated, previously infected women had higher IgG S‐protein antibody titres than unvaccinated, previously infected women (mean difference 4.76 fold‐change, 95% CI 2.65–6.86,p < 0.001). Vaccination timing before versus during pregnancy did not affect IgG S‐antibody titres (mean difference −0.28 fold‐change, 95% CI −2.61 to 2.04,p = 0.785).

Conclusions

This cross‐sectional study demonstrates high rates of asymptomatic SARS‐CoV‐2 infection with women of black ethnic backgrounds having higher infection risk and lower vaccine uptake. SARS‐CoV‐2 antibody titres were highest among double‐vaccinated, infected women.
Prognostic impact of noninvasive areas in resected pathological stage IA lung adenocarcinoma
Authors: Kinoshita Fumihiko , Shimokawa Mototsugu , Takenaka Tomoyoshi , Okamoto Tatsuro , Taguchi Kenichi , Oda Yoshinao , Yoshizumi Tomoharu
Published: April 2023

Main Problems

In non‐small‐cell lung cancer, ground‐glass opacity on computed tomography imaging reflects pathological noninvasiveness and is a favorable prognostic factor. However, the significance of pathological noninvasive areas (NIAs) has not been fully revealed. In this study, we aimed to elucidate the prognostic impact of NIAs on lung adenocarcinoma.

Methods

We analyzed 402 patients with pathological stage (p‐Stage) IA lung adenocarcinoma who underwent surgery in 2013–2016 at two institutions and examined the association of the presence of NIAs with clinicopathological factors and prognosis. Furthermore, after using propensity‐score matching to adjust for clinicopathological factors, such as age, sex, smoking history, pathological invasive area size, pathological T factor (p‐T), p‐Stage, and histological subtype (lepidic predominant adenocarcinoma [LPA] or non‐LPA), the prognostic impact of NIAs was evaluated.

Results

Patients were divided into NIA‐present (N = 231) and NIA‐absent (N = 171) groups. Multivariable analysis showed that NIA‐present was strongly associated with earlier p‐T, earlier p‐Stage, LPA, and epidermal growth factor receptor mutation. Kaplan–Meier survival analysis showed that the NIA‐present group displayed a better prognosis than the NIA‐absent group in disease‐free survival (DFS) and overall survival (OS) (5‐year DFS 94.6% vs. 87.2%, 5‐year OS 97.2% vs. 91.1%). However, after adjusting for clinicopathological factors by propensity score matching, no significant differences in prognosis were identified between the NIA‐present and NIA‐absent groups (5‐year DFS 92.4% vs 89.6%, 5‐year OS 95.6% vs 94.3%).

Conclusions

Our current study suggests that the prognostic impact of the presence of NIAs on lung adenocarcinoma is due to differences in clinicopathological factors.
Cultural accountability in the annual report: The case of First Nations entities in Australia
Authors: Norris Ellie , Kutubi Shawgat , Greenland Steven
Published: April 2023

Australia's Aboriginal and Torres Strait Islander not‐for‐profit organisations (NFPs) are vital to the cultural and social fabric of the communities they represent. Yet while such entities are obligated to publish annual financial and non‐financial information, little is known about the role of these reports in terms of delivering accountability to culturally diverse stakeholders. This benchmark study is among the first to use grounded accountability theory to compare the results from quantitative content and qualitative thematic analysis of annual reporting across 100 Aboriginal and Torres Strait Islander NFPs. Our analysis reveals the communication of ‘cultural accountability’ that sets these entities apart from other NFPs. Implications of these findings for accountability practices in non‐Anglo‐Saxon cultural contexts are discussed.
Genome‐wide analyses reveal novel opioid use disorder loci and genetic overlap with schizophrenia, bipolar disorder, and major depression
Authors: Holen Børge , Shadrin Alexey A. , Icick Romain , Filiz Tahir T. , Hindley Guy , Rødevand Linn , O'Connell Kevin S. , Hagen Espen , Frei Oleksandr , Bahrami Shahram , Cheng Weiqiu , Parker Nadine , Tesfaye Markos , Jahołkowski Piotr , Karadag Naz , Dale Anders M. , Djurovic Srdjan , Smeland Olav B. , Andreassen Ole A.
Published: April 2023

Opioid use disorder (OUD) and mental disorders are often comorbid, with increased morbidity and mortality. The causes underlying this relationship are poorly understood. Although these conditions are highly heritable, their shared genetic vulnerabilities remain unaccounted for. We applied the conditional/conjunctional false discovery rate (cond/conjFDR) approach to analyse summary statistics from independent genome wide association studies of OUD, schizophrenia (SCZ), bipolar disorder (BD) and major depression (MD) of European ancestry. Next, we characterized the identified shared loci using biological annotation resources. OUD data were obtained from the Million Veteran Program, Yale‐Penn and Study of Addiction: Genetics and Environment (SAGE) (15 756 cases, 99 039 controls). SCZ (53 386 cases, 77 258 controls), BD (41 917 cases, 371 549 controls) and MD (170 756 cases, 329 443 controls) data were provided by the Psychiatric Genomics Consortium. We discovered genetic enrichment for OUD conditional on associations with SCZ, BD, MD and vice versa, indicating polygenic overlap with identification of 14 novel OUD loci at condFDR < 0.05 and 7 unique loci shared between OUD and SCZ (n = 2), BD (n = 2) and MD (n = 7) at conjFDR < 0.05 with concordant effect directions, in line with estimated positive genetic correlations. Two loci were novel for OUD, one for BD and one for MD. Three OUD risk loci were shared with more than one psychiatric disorder, at DRD2 on chromosome 11 (BD and MD), at FURIN on chromosome 15 (SCZ, BD and MD) and at the major histocompatibility complex region (SCZ and MD). Our findings provide new insights into the shared genetic architecture between OUD and SCZ, BD and MD, indicating a complex genetic relationship, suggesting overlapping neurobiological pathways.
Three‐dimensional bioprinting of artificial organs: How close are we to its clinical application?
Authors: Han Jason J.
Published: April 2023

A patient recently received a 3D‐printed outer ear made out of her own cells. An endoscopic 3D bioprinter was able to print biomaterials in situ. In this decade, we may at last see the application of 3D bioprinters in the creation of complex, clinically viable artificial organs.
No evidence for regeneration of pectines in the scorpion Euscorpius italicus (Herbst, 1800)
Authors: Stemme Torben
Published: April 2023

Although scorpions have comparatively low regenerative potential, legs and pedipalps are able to regenerate some structures in an often incomplete manner. The most intriguing scorpion appendages are the ventrally located pectines. These organs are equipped with numerous sensilla that scan the substrate for mechanosensory‐ and chemosensory cues. Due to their ventral position and frequent substrate contact, pectines are vulnerable to traumatic injuries. Pecten malformations have been hypothesized to be the result of incomplete regeneration. To investigate their regeneration capabilities, the pectines of postembryonic stages of Euscorpius italicus (Herbst, 1800) were amputated before the second moult at three different positions. Data on intermoult periods and the number of pectinal teeth were gathered for approximately 2.5 years. The regeneration process on exuviae of up to six moulting events was documented by photographs and confocal laser‐scanning microscopy. Regardless of the amputation site, no evidence for regenerative capabilities of pectines in E. italicus could be reported. Thus, incomplete regenerations mentioned in the literature are likely the result of simple wound healing. Depending on habitat complexity, substrate contact time of the pectines seem to differ, which might be interpreted as a trade‐off between highest sensory input and the avoidance of traumatic injury of the pectines.
The influence of socioeconomic status and appearance‐reality understanding on pre‐schoolers' sharing and generosity
Authors: Hashim Nawal , Fischer Nastassja L. , Kim Elizabeth B. , Yeung Wei‐Jun Jean , Yu Rongjun
Published: April 2023

Prosocial behaviour can be defined as any voluntary action that is performed to benefit another individual. Despite accumulating evidence of the importance of environmental variables (e.g., socioeconomic status; SES), and individual characteristics (e.g., theory of mind – ToM – skills), in influencing prosocial behaviours in young children, it is unknown how these factors relate to the underlying motivations for prosocial behaviours. Accordingly, both extrinsically (sharing) and intrinsically (generosity)‐guided prosocial behaviours are measured in this study. We explore the influences of SES and ToM skills on young children's sharing behaviour and generosity, while controlling their age, working memory and language skills. Sixty‐six 4‐ to 6 year olds (Mage = 5.24 years, SD = 0.73) from diverse SES (measured by parental education level) and ethnic backgrounds in Singapore completed tasks assessing the ToM measures of false belief and appearance‐reality understanding, working memory, language skills, generosity, and sharing behaviour. The results of hierarchical regression analyses demonstrate that the father's education level and children's appearance‐reality understanding were significant predictors of sharing, after controlling for age, working memory, language skills, and the mother's education level. Children's appearance‐reality understanding was the sole predictor of children's generosity. Our findings highlight the impact of children's ability to hold different views of reality and their family's education levels on the development of sharing and generosity in early childhood.
Pseudomonas aeruginosa in tracheal aspirate: Colonization, infection, and recurrence
Authors: de Souza Nunes Larissa Hermann , Bernardi Lora João Felipe , Fanhani Cracco Luiz Augusto , da Costa Manuel Janice Alexandra , Westarb Cruz June Alisson , Telles Joao Paulo , Tuon Felipe Francisco
Published: April 2023

Introduction

Pseudomonas aeruginosa respiratory infections are challenging, and the risk of recurrence is a frequent problem. The aim of this study was to investigate the risk factors associated with the presence of P. aeruginosa, and the risk factors related to the recurrence and death of lower airway infections in inpatients in a Brazilian hospital.

Methods

Retrospective cohort with inpatients that had a sample of airways culture (tracheal aspirate or bronchoalveolar lavage) with the detection of P. aeruginosa. The patients with clinical criteria of infection were classified as ventilator‐associated, hospital‐acquired, or community‐acquired pneumonia. P. aeruginosa in respiratory samples without symptoms was considered colonization. The antimicrobial treatment adequacy and the clinical data were evaluated. Outcome variables included mortality and recurrence.

Results

One hundred and fifty‐four patients were included in the study, most of them were men, and the majority (102) were considered infected. The average length of stay was superior to 30 days. Previous pulmonary disease was associated with the occurrence of colonization. Aminoglycosides were the most active drug according to susceptibility tests and were successfully used as monotherapy. Septic shock was a risk factor for death in the infected patients. The use of adequate antimicrobial therapy was associated with major survival, independent of the infection classification.

Conclusion

It is possible to evaluate clinical data associated with recurrence and mortality in patients with different lung infections by P. aeruginosa. Aminoglycoside monotherapy is safe and effective in P. aeruginosa respiratory infections.
IRF2BPL as a novel causative gene for progressive myoclonus epilepsy
Authors: Gardella Elena , Michelucci Roberto , Christensen Hanne M. , Fenger Christina D. , Reale Chiara , Riguzzi Patrizia , Pasini Elena , Albini‐Riccioli Luca , Papa Valentina , Foschini Maria Pia , Cenacchi Giovanna , Furia Francesca , Marjanovic Dragan , Hammer Trine B. , Møller Rikke S. , Rubboli Guido
Published: April 2023

IRF2BPL has recently been described as a novel cause of neurodevelopmental disorders with multisystemic regression, epilepsy, cerebellar symptoms, dysphagia, dystonia, and pyramidal signs. We describe a novel IRF2BPL phenotype consistent with progressive myoclonus epilepsy (PME) in three novel subjects and review the features of the 31 subjects with IRF2BPL‐related disorders previously reported. Our three probands, aged 28–40 years, harbored de novo nonsense variants in IRF2BPL (c.370C > T, p.[Gln124*] and c.364C > T; p.[Gln122*], respectively). From late childhood/adolescence, they presented with severe myoclonus epilepsy, stimulus‐sensitive myoclonus, and progressive cognitive, speech, and cerebellar impairment, consistent with a typical PME syndrome. The skin biopsy revealed massive intracellular glycogen inclusions in one proband, suggesting a similar pathogenic pathway to other storage disorders. Whereas the two older probands were severely affected, the younger proband had a milder PME phenotype, partially overlapping with some of the previously reported IRF2BPL cases, suggesting that some of them might be unrecognized PME. Interestingly, all three patients harbored protein‐truncating variants clustered in a proximal, highly conserved gene region around the “coiled‐coil” domain. Our data show that PME can be an additional phenotype within the spectrum of IRF2BPL‐related disorders and suggest IRF2BPL as a novel causative gene for PME.
Males show their best side revisited – Effects of predation pressure on laterality in wild guppies
Authors: Sundin Josefin , Näslund Joacim , Mateos‐González Fernando , Ashworth William , Amcoff Mirjam
Published: April 2023

The ability to detect and avoid predators has been suggested as one of the main drivers for behavioral lateralization. This is supported by studies reporting that animals from high‐predation environments are more lateralized than those from low‐predation environments. Some studies, however, have shown no effect of predator regime on lateralization. Lateralized behavior can also be driven by phenotypic asymmetry, where the more attractive side of the body is preferentially displayed during male–female interaction and courtship. The importance of fluctuating asymmetry for mate choice has been highly debated for a number of reasons. Here, we revisited the concepts of predator‐induced behavioral lateralization and phenotypic asymmetry using wild Trinidadian guppiesPoecilia reticulatafrom three different stream systems. Using fish collected from both high‐ and low‐predation environments, we quantified behavioral lateralization in terms of directional turning bias, measured right–left body color asymmetry, and investigated whether a male side‐showing preference was present in male–female interaction trials. We found that guppies were, at best, moderately lateralized on average (across all populations), without any general effect of predator regime. There were some slight stream‐dependent side biases in color asymmetry, but this did not translate into a side‐showing preference in any of the populations in the interaction trials. Some significant observed effects align with previously published results, but these were dependent on stream‐origin and were not repeated across different experiments, complicating interpretation. We conclude that when investigating the effects of predation regime in general, and such effects on behavioral lateralization or fluctuating asymmetry in particular, attention must be focused toward several factors such as experimental assay used and population origin, and broad generalizations from results stemming from experiments including only one population should be avoided.
Allergen desensitization reduces the severity of relapsed alopecia areata in dust‐mite allergic patients
Authors: Zeng Zixun , Li Shuifeng , Ye Yanting , Ling Yunxia , Gong Yugang , Zi Xue , Yang Jian , McElwee Kevin J. , Zhang Xingqi
Published: April 2023

Atopy may be a facilitating factor in some alopecia areata (AA) patients with early disease onset and more severe/extensive AA. The underlying immune mechanisms are unknown, but allergen responses may support a pro‐inflammatory environment that indirectly promotes AA. To investigate the long‐term effect of allergen immunotherapy (AIT) against house dust mite (HDM) allergy on disease severity and prognosis for AA patients. An observational comparative effectiveness study was conducted on 69 AA patients with HDM allergy. 34 patients received conventional/traditional AA treatment (TrAA) plus AIT (AIT‐TrAA), and 35 patients received TrAA alone. Serum total immunoglobulin E (tIgE), HDM specific IgE (sIgE), HDM specific IgG4 (sIgG4) and cytokines (IL‐4, IL‐5, IL‐10, IL‐12, IL‐13, IL‐33, IFNγ) were quantified in these patients, together with 58 non‐allergic AA patients and 40 healthy controls. At the end of the 3‐year desensitization course, the AIT‐TrAA group presented with lower SALT scores than the TrAA group, especially in non‐alopecia totalis/universalis (AT/U) patients and pre‐adolescent AT/U patients (age ≤ 14). In patients with elevated tIgE levels before AIT, a decrease in tIgE was correlated to reduced extent of AA on completion of the AIT course. After desensitization, elevation of IL‐5 and decrease of IL‐33 were observed in HDM allergic‐AA patients. Desensitization to HDM in allergic AA patients reduces the severity of relapse‐related hair loss over the 3‐year AIT treatment course, possibly via opposing Th2 dominance. This adjunctive treatment may help reduce disease severity and curtail the disease process in allergic patients with AA.
Human epidermis organotypic cultures, a reproducible system recapitulating the epidermis in vitro
Authors: Agarwal Rishika , Dittmar Tanja , Beer Hans‐Dietmar , Kunz Michael , Müller Simon , Kappos Elisabeth A. , Contassot Emmanuel , Navarini Alexander A.
Published: April 2023

The translatability of research is highly dependent on models that recapitulate human tissues and organs. Here, we describe a procedure for the generation of human epidermis organotypic cultures (HEOCs) from primary keratinocytes isolated from foreskin and adult skin as well as from an immortalized keratinocyte cell line (KerTr). We tested several media conditions to develop a defined HEOC growing and expansion media. We characterized the HEOCs and show that in optimal culture conditions they express the proliferation marker Ki67, the basement membrane protein collagen 17 (col17) and the epidermal differentiation markers keratin 15 (K15), keratin 14 (K14), keratin 5 (K5), keratin 10 (K10), keratin 1 (K1), transglutaminase 1 (TGM1), transglutaminase 3 (TGM3) and filaggrin (FLG). Thus, they recapitulate the human epidermis and are stratified from the basal layer to the stratum corneum. These HEOC can be generated reproducibly on a large scale, making it an invaluable model for screening therapeutic compounds and also for the study of pathologies affecting the epidermis.
Time series forecasting based on a novel ensemble‐based network and variational mode decomposition
Authors: Nazarieh Fatemeh , Naderi Dehkordi Mohammad
Published: April 2023

Statistical and computational intelligence methods contain weaknesses in handling nonlinearity, non‐stationarity and noise. This research develops a novel decomposition ensemble‐based network named VMD‐DENetwork for time series forecasting over different horizons. A robust decomposition technique called variational mode decomposition (VMD) is applied to decompose the input sequence into several intrinsic modes in a non‐recursive manner. The optimal number of intrinsic modes is selected based on a comprehensive analysis to ensure the stability of the framework. The proposed DENetwork is developed based on stacking architecture and constitutes heterogeneous learners to model the nonlinear and complex relationships. It combines a convolutional neural network, long short‐term memory and an extreme learning machine. A firefly optimization algorithm is adopted for utilizing hyperparameters of the proposed model to enhance the efficiency of VMD‐DENetwork. The forecasting performance is verified by using six real‐world data sets from the New York Mercantile and International Petroleum Exchange. The final obtained results are compared with several peer‐advanced algorithms using the root mean squared error (RMSE), mean absolute error (MAE), Theil inequality coefficient (TIC) and correlation coefficient (R) metrics. The experimental results confirm that the proposed model demonstrates outstanding prediction performance. The employed optimization algorithm is compared with three frequently used bio‐inspired optimization algorithms, and their performance is tested using standard CEC benchmarks.
Priming effect stimulates carbon release from thawed permafrost
Authors: He Mei , Li Qinlu , Chen Leiyi , Qin Shuqi , Kuzyakov Yakov , Liu Yang , Zhang Dianye , Feng Xuehui , Kou Dan , Wu Tonghua , Yang Yuanhe
Published: April 2023

Climate warming leads to widespread permafrost thaw with a fraction of the thawed permafrost carbon (C) being released as carbon dioxide (CO2), thus triggering a positive permafrost C‐climate feedback. However, large uncertainty exists in the size of this model‐projected feedback, partly owing to the limited understanding of permafrost CO2 release through the priming effect (i.e., the stimulation of soil organic matter decomposition by external C inputs) upon thaw. By combining permafrost sampling from 24 sites on the Tibetan Plateau and laboratory incubation, we detected an overall positive priming effect (an increase in soil C decomposition by up to 31%) upon permafrost thaw, which increased with permafrost C density (C storage per area). We then assessed the magnitude of thawed permafrost C under future climate scenarios by coupling increases in active layer thickness over half a century with spatial and vertical distributions of soil C density. The thawed C stocks in the top 3 m of soils from the present (2000–2015) to the future period (2061–2080) were estimated at 1.0 (95% confidence interval (CI): 0.8–1.2) and 1.3 (95% CI: 1.0–1.7) Pg (1 Pg = 1015 g) C under moderate and high Representative Concentration Pathway (RCP) scenarios 4.5 and 8.5, respectively. We further predicted permafrost priming effect potential (priming intensity under optimal conditions) based on the thawed C and the empirical relationship between the priming effect and permafrost C density. By the period 2061–2080, the regional priming potentials could be 8.8 (95% CI: 7.4–10.2) and 10.0 (95% CI: 8.3–11.6) Tg (1 Tg = 1012 g) C year−1 under the RCP 4.5 and RCP 8.5 scenarios, respectively. This large CO2 emission potential induced by the priming effect highlights the complex permafrost C dynamics upon thaw, potentially reinforcing permafrost C‐climate feedback.
Zinc Isotope Measurement by MC‐ICP‐MS in Geological Certified Reference Materials
Authors: Wang Jing , Tang Dong‐Mei , Yuan Qing‐Han , Su Ben‐Xun , Li Wen‐Jun , Gao Bing‐Yu , Bao Zhi‐An , Zhao Ye
Published: April 2023

Here we present an analytical method for Zinc (Zn) isotopic measurements using “standard‐sample bracketing” on a Nu Sapphire multi‐collector inductively coupled plasma‐mass spectrometer. The effects of Zn mass fraction and HNO3 molarity mismatch between the standard and the sample, as well as the presence of matrix elements have been evaluated. Long‐term reproducibility of better than ±0.03‰ for δ66Zn (2s) was routinely obtained. Accurate measurements were achieved when CNi/CZn < 0.001, CTi/CZn < 0.03, CBa/CZn < 0.05, CNa/CZn and CAl/CZn < 0.5, CMg/CZn < 0.1, CFe/CZn < 5 and CCu/CZn as well as CCd/CZn < 10. High‐precision Zn isotopic determination were performed on twenty‐one widely available geological certified reference materials, with an overall range of ~ 0.62‰ (0.15 to 1.07‰), which is nearly twenty times the current analytical precision (0.03), and the results are in agreement with most previously published data within 2s. Among them, δ66ZnJMC 3‐0749L of eleven geological certified reference materials are reported for the first time: 0.22 ± 0.03‰ (dolerite, DR‐N), 0.23 ± 0.02‰ (gabbro, GSR‐10), 0.20 ± 0.04‰ (microgabbro, PM‐S), 0.15 ± 0.02‰ (andesite, GSR‐2), 0.22 ± 0.08‰ (diorite, GSR‐9), 0.19 ± 0.07‰ (syenite, GSR‐7), 0.30 ± 0.06‰ (granite, GSR‐1), 0.25 ± 0.00‰ (rhyolite, GSR‐11), 0.37 ± 0.01‰ (shale, GSR‐5), 0.21 ± 0.03‰ (limestone, GSR‐6) and 0.20 ± 0.03‰ (hornblendite, GSR‐15). The novel Zn isotopic data from these certified reference materials can be used for future interlaboratory comparisons.
Power and the perception of pregnancy in the academy
Authors: Percival Carter Erin
Published: April 2023

Becoming pregnant as an academic is risky. Many who want to become or find themselves pregnant structure their lives and careers to try to mitigate the potential negative effects of pregnancy on their future careers. Yet research continues to suggest that having been pregnant or being a mother significantly reduces the likelihood of career success compared to either being child‐free or a father. While in some cases success is defined as research productivity, in many cases, it is defined as simply remaining in academia. Governments, societies, and institutions bemoan the resulting “leaky pipelines” and speculate as to the causes of seemingly reinforced glass ceilings. Yet, underlying so many of the formal and informal conversations, norms, and policies surrounding pregnancy and academia is an implicit assumption that pregnancy and pregnant people are the problem to be solved and solutions thus require repairing some deficit created in the individual by pregnancy. In this article, I argue that pregnancy discrimination in academia is in large part a problem resulting from power and how it is wielded against pregnant people, both by institutions and by individuals. Using both a personal narrative account of the process, experience, and outcomes of pregnancy in the academy resulting in filing a formal Title IX complaint and a review of contemporary research on power, discrimination, and pregnancy, I explore how academic structures and systems nominally tasked with supporting equity can instead serve to exaggerate power differences and foster discrimination.
Comparative effects of three delivery systems of oral potassium on upper gastrointestinal mucosa
Authors: McLoughlin J C
Published: April 2023

Forty‐five healthy volunteers were recruited into a single‐blind randomly allocated parallel group study to determine the effects on the gastric mucosa of three different oral potassium supplements — (K‐Contin ContinusR) tablets, (Napp); Slow‐K tablets, (Ciba); Micro‐K Extencaps, (A H Robins).

The volunteers were gastroscoped initially and after one week of treatment with one of the potassium tablets taken in conjunction with glycopyrrolate to delay gastric emptying. Post‐treatment, seven out of 15 volunteers taking Slow‐K tablets showed erosions and two showed hyperaemia only. Of the 15 taking Micro‐K, one showed erosions and two showed hyperaemia only. None of those given K‐Contin tablets showed erosions, but four showed hyperaemia only.