bluuebunny/crossref_metadata_2025 huggingface dataset:
A new mechanism for crisis management success
Authors: Hosen Mosharrof , Liew Chee Yoong , Lim Ai‐Fen , Hameed Irfan , Rehman Hafiz Mudassir
Published: April 2024

The goal of this study is to present a thorough analysis of the ways that organisational culture (OC) and risk assessment competencies of leaders affect the creation of strategic frameworks, especially about high‐quality crisis decision‐making. A self‐administered questionnaire was distributed to 436 organisational personnel; 304 valid responses were received, and these were analysed using variance‐based structural equation modelling. The findings show that OC, leadership risk assessment and a strategic management plan (SMP) are favourable predictors of high‐quality crisis decision‐making. According to this research, every variable strengthens the link between SMP quality and crisis decisions. The study is supported by an integrated method for understanding complex organisational facts. Practical ramifications for leadership development include strengthening leaders' capacity to appraise risk, considering OC and employing an SMP to guarantee that, when making sound crisis judgements, they are both innovative and compliant with organisational ethics.
Enhancement of acyl‐CoA precursor supply for increased avermectin B1a production by engineering meilingmycin polyketide synthase and key primary metabolic pathway genes
Authors: Yang Mengyao , Hao Yi , Liu Gang , Wen Ying
Published: April 2024

Avermectins (AVEs), a family of macrocyclic polyketides produced by Streptomyces avermitilis, have eight components, among which B1a is noted for its strong insecticidal activity. Biosynthesis of AVE “a” components requires 2‐methylbutyryl‐CoA (MBCoA) as starter unit, and malonyl‐CoA (MalCoA) and methylmalonyl‐CoA (MMCoA) as extender units. We describe here a novel strategy for increasing B1a production by enhancing acyl‐CoA precursor supply. First, we engineered meilingmycin (MEI) polyketide synthase (PKS) for increasing MBCoA precursor supply. The loading module (using acetyl‐CoA as substrate), extension module 7 (using MMCoA as substrate) and TE domain of MEI PKS were assembled to produce 2‐methylbutyrate, providing the starter unit for B1a production. Heterologous expression of the newly designed PKS (termed Mei‐PKS) in S. avermitilis wild‐type (WT) strain increased MBCoA level, leading to B1a titer 262.2 μg/mL – 4.36‐fold higher than WT value (48.9 μg/mL). Next, we separately inhibited three key nodes in essential pathways using CRISPRi to increase MalCoA and MMCoA levels in WT. The resulting strains all showed increased B1a titer. Combined inhibition of these key nodes in Mei‐PKS expression strain increased B1a titer to 341.9 μg/mL. Overexpression of fatty acid β‐oxidation pathway genes in the strain further increased B1a titer to 452.8 μg/mL – 8.25‐fold higher than WT value. Finally, we applied our precursor supply strategies to high‐yield industrial strain A229. The strategies, in combination, led to B1a titer 8836.4 μg/mL – 37.8% higher than parental A229 value. These findings provide an effective combination strategy for increasing AVE B1a production in WT and industrial S. avermitilis strains, and our precursor supply strategies can be readily adapted for overproduction of other polyketides.
Alcohol consumption and accelerated biological ageing in middle‐aged and older people: A longitudinal study from two cohorts
Authors: Chen Hongxiang , Yin Jianzhong , Xiang Yi , Zhang Ning , Huang Zitong , Zhang Yuan , Tang Dan , Wang Ziyun , Baimayangji  , Chen Liling , Jiang Xiaoman , Xiao Xiong , Zhao Xing
Published: April 2024

Background and aims

The relationship between alcohol consumption and age‐related diseases is inconsistent. Biological age (BA) serves as both a precursor and a predictor of age‐related diseases; however, longitudinal associations between alcohol consumption and BA in middle‐aged and older people remain unclear. We measured whether there was a longitudinal association between drinking frequency and pure alcohol intake with BA among middle‐aged and older people.

Design and setting and participants

This study involved two prospective cohort studies, set in Southwestern China and the United Kingdom. A total of 8046 participants from the China Multi‐Ethnic Cohort study (CMEC) and 5412 participants from the UK Biobank (UKB), aged 30–79 years, took part, with complete data from two waves of clinical biomarkers.

Measurements

BA was calculated by the Klemera Doubal's method. Accelerated BA equalled BA minus chronological age. Drinking frequency and pure alcohol intake were obtained through self‐reported questionnaires. Drinking frequency in the past year was classified as current non‐drinking, occasional (monthly drinking) and regular (weekly drinking).

Findings

Compared with consistent current non‐drinkers, more frequent drinkers [CMEC: β = 0.46, 95% confidence interval (CI) = 0.13–0.80; UKB: β = 0.65, 95% CI = 0.01–1.29)], less frequent drinkers (CMEC: β = 0.62, 95% CI = 0.37–0.87; UKB: β = 0.54, 95% CI = −0.01–1.09), consistent occasional drinkers (CMEC: β = 0.51, 95% CI = 0.23–0.79; UKB: β = 0.63, 95% CI = 0.13–1.13) and consistent regular drinkers (CMEC: β = 0.56, 95% CI = 0.17–0.95; UKB: β = 0.46, 95% CI = 0.00–0.91) exhibited increased accelerated BA. A non‐linear relationship between pure alcohol intake and accelerated BA was observed among consistent regular drinkers.

Conclusions

In middle‐aged and older people, any change in drinking frequency and any amount of pure alcohol intake seem to be positively associated with acceleration of biological ageing, compared with maintaining abstinence.
The social life of illegality: Suspicion and surveillance against African migrants in urban India
Authors: Gill Bani
Published: April 2024

The turn of the 21st century has witnessed a rising trend of migration from the African continent to cities across India. Accompanying such flows have been racial tensions and policing spectacles, including incidents of violence, vandalism, and evictions against African migrants and their pathologization as “illegal.” These subtle yet pervasive forms of migrant policing by state and citizen actors constitute what I call the social life of “illegality” that is characterized by distinctive modes of suspicion and surveillance. Based upon ethnography conducted in an “unplanned” settlement of Delhi cohabitated by both African and Indian residents, I illuminate how caste‐race‐religion informed indexes of difference contribute to the multi‐sensorial racialization of African migrants as suspicious. In emplacing such dynamics within changing spatial economies and the moral anxieties accompanying such transitions, I further demonstrate quotidian practice of microsurveillance against African migrants as sustaining their position as rent‐paying clients who are nonetheless maintained in their racial alterity. The social life of “illegality” thus refocuses attention on the sensorial and emplaced registers that illegalize migrants, above and beyond documentation, thereby furthering a discussion on migrant “illegality” as enmeshed within racialized imaginaries, urban transformations, and alternate modes of governmentality.
Cholecystectomy in the red centre: a review of the surgical outcomes in Central Australia in a five‐year period
Authors: Barbaro Antonio , Paredes Steven Ronald , Tran Steven , Kaur Harleen , Arayne Aisha Abdulmoeed , Senaratne Jayantha
Published: April 2024

Background

Despite the high rates of cholecystectomy in Australia, there is minimal literature regarding the outcomes of cholecystectomy in rural Central Australia within the Northern Territory. This study aims to better characterize the outcomes for patients undergoing cholecystectomy in Central Australia and review clinical and patient characteristics, which may affect outcomes.

Method

A retrospective case–control study was performed using data obtained from medical records for all patients undergoing cholecystectomy at Alice Springs Hospital in the Northern Territory from January 2018 until December 2022. Patient characteristics were gathered, and key outcomes examined included: inpatient mortality and 30‐day mortality, bile duct injury, bile leak, return to theatre, conversion to open, duration of procedure, length of stay, and up‐transfer to a tertiary referral centre.

Results

A total of 466 patients were included in this study. Majority of the patients were female and there was a large portion of Indigenous Australians (56%). There were no inpatient mortalities, or 30‐day mortalities recorded. There were two bile leaks and/or bile duct injuries (0.4%) and two unplanned returned to theatres (0.4%). Indigenous Australians were more likely to require an emergency operation and had a longer median length of stay (P < 0.001).

Conclusion

Cholecystectomy can be performed safely and to a high standard in Central Australia. Surgeons in Central Australia must appreciate the nuances in the management of patients who come from a significantly different socioeconomic background, with complex medical conditions when compared to metropolitan centres.
Autocrine activation of P2X7 receptors mediates catecholamine secretion in chromaffin cells
Authors: Maldifassi María Constanza , Guerra‐Fernández María José , Ponce Daniela , Alfonso‐Bueno Samuel , Maripillán Jaime , Vielma Alex H. , Báez‐Matus Ximena , Marengo Fernando D. , Acuña‐Castillo Claudio , Sáez Juan C. , Martínez Agustín D. , Cárdenas Ana M.
Published: April 2024

Background and Purpose

ATP is highly accumulated in secretory vesicles and secreted upon exocytosis from neurons and endocrine cells. In adrenal chromaffin granules, intraluminal ATP reaches concentrations over 100 mM. However, how these large amounts of ATP contribute to exocytosis has not been investigated.

Experimental Approach

Exocytotic events in bovine and mouse adrenal chromaffin cells were measured with single cell amperometry. Cytosolic Ca2+ measurements were carried out in Fluo‐4 loaded cells. Submembrane Ca2+ was examined in PC12 cells transfected with a membrane‐tethered Ca2+ indicator Lck‐GCaMP3. ATP release was measured using the luciferin/luciferase assay. Knockdown of P2X7 receptors was induced with short interfering RNA (siRNA). Direct Ca2+ influx through this receptor was measured using a P2X7 receptor‐GCamp6 construct.

Key Results

ATP induced exocytosis in chromaffin cells, whereas the ectonucleotidase apyrase reduced the release events induced by the nicotinic agonist dimethylphenylpiperazinium (DMPP), high KCl, or ionomycin. The purinergic agonist BzATP also promoted a secretory response that was dependent on extracellular Ca2+. A740003, a P2X7 receptor antagonist, abolished secretory responses of these secretagogues. Exocytosis was also diminished in chromaffin cells when P2X7 receptors were silenced using siRNAs and in cells of P2X7 receptor knockout mice. In PC12 cells, DMPP induced ATP release, triggering Ca2+ influx through P2X7 receptors. Furthermore, BzATP, DMPP, and KCl allowed the formation of submembrane Ca2+ microdomains inhibited by A740003.

Conclusion and Implications

Autocrine activation of P2X7 receptors constitutes a crucial feedback system that amplifies the secretion of catecholamines in chromaffin cells by favouring submembrane Ca2+ microdomains.
Long noncoding RNA SNHG3 interacts with microRNA‐502‐3p to mediate ITGA6 expression in liver hepatocellular carcinoma
Authors: Guo Juncheng , Zhang Jianquan , Xiang Yang , Zhou Shuai , Yang Yijun , Zheng Jinfang
Published: April 2024

SNHG3, a long noncoding RNA (lncRNA), has been linked to poor outcomes in patients with liver hepatocellular carcinoma (LIHC). In this study, we found that SNHG3 was overexpressed in LIHC and associated with poor outcomes in patients with LIHC. Functional assays, including colony formation, spheroid formation, and in vivo assays showed that SNHG3 promoted stemness of cancer stem cells (CSC) and tumor growth in vivo by interacting with microRNA‐502‐3p (miR‐502‐3p). miR‐502‐3p inhibitor repressed the tumor‐suppressing effects of SNHG3 depletion. Finally, by RNA pull‐down, dual‐luciferase reporter assay, m6A methylation level detection, and m6A‐IP‐qPCR assays, we found that miR‐502‐3p targeted YTHDF3 to regulate the translation of integrin alpha‐6 (ITGA6) and targeted HBXIP to inhibit the m6A modification of ITGA6 through methyltransferase‐like 3 (METTL3). Our study revealed that SNHG3 controls the YTHDF3/ITGA6 and HBXIP/METTL3/ITGA6 pathways by repressing miR‐502‐3p expression to sustain the self‐renewal properties of CSC in LIHC.
Cutibacterium acnes‐derived extracellular vesicles promote tumor growth in renal cell carcinoma
Authors: Jingushi Kentaro , Kawashima Atsunari , Tanikawa Sayaka , Saito Takuro , Yamamoto Akinaru , Uemura Toshihiro , Sassi Nesrine , Ishizuya Yu , Yamamoto Yoshiyuki , Kato Taigo , Hatano Koji , Hase Hiroaki , Nonomura Norio , Tsujikawa Kazutake
Published: April 2024

Bacterial flora are present in various parts of the human body, including the intestine, and are thought to be involved in the etiology of various diseases such as multiple sclerosis, intestinal diseases, cancer, and uterine diseases. In recent years, the presence of bacterial 16S rRNA genes has been revealed in blood, which was previously thought to be a sterile environment, and characteristic blood microbiomes have been detected in various diseases. However, the mechanism and the origin of the bacterial information are unknown. In this study, we performed 16S rRNA metagenomic analysis of bacterial DNA in serum extracellular vesicles from five healthy donors and seven patients with renal cell carcinoma and detected Cutibacterium acnes DNA as a characteristic bacterial DNA in the serum extracellular vesicles of patients with renal cell carcinoma. In addition, C. acnes DNA was significantly reduced in postoperative serum extracellular vesicles from patients with renal cell carcinoma compared with that in preoperative serum extracellular vesicles from these patients and was also detected in tumor tissue and extracellular vesicles from tumor tissue‐associated microbiota, suggesting an association between C. acnes extracellular vesicles and renal cell carcinoma. C. acnes extracellular vesicles were taken up by renal carcinoma cells to enhance their proliferative potential. C. acnes extracellular vesicles also exhibited tumor‐promoting activity in a mouse model of renal cancer allografts with enhanced angiogenesis. These results suggest that extracellular vesicles released by C. acnes localized in renal cell carcinoma tissues act in a tumor‐promoting manner.
Syndromic craniosynostosis caused by a novel missense variant in MAP4K4: Expanding the genotype–phenotype relationship in RASopathies
Authors: Yoon Jihoon G. , Yu Jung Woo , Shim Kyu Won , Kim Yong Oock , Lee Min Goo
Published: April 2024

RASopathies represent a distinct class of neurodevelopmental syndromes caused by germline variants in the Ras/MAPK pathways. Recently, a novel disease‐gene association was implicated in MAPK kinase kinase kinase 4 (MAP4K4), which regulates the upstream signals of the MAPK pathways. However, to our knowledge, only two studies have reported the genotype–phenotype relationships in the MAP4K4‐related disorder. This study reports on a Korean boy harboring a novel de novo missense variant in MAP4K4 (NM_001242559:c.569G>T, p.Gly190Val), revealed by trio exome sequencing, and located in the hotspot of the protein kinase domain. The patient exhibited various clinical features, including craniofacial dysmorphism, language delay, congenital heart defects, genitourinary anomalies, and sagittal craniosynostosis. Our study expands the phenotypic association of the MAP4K4‐related disorder to include syndromic craniosynostosis, thereby providing further insights into the role of the RAS/MAPK pathways in the development of premature fusion of calvarial sutures.
The use and abuse of moral theories in conservation debate about killing animals
Authors: Coghlan Simon , Cardilini Adam
Published: April 2024

Recent ethical debate about compassionate conservation has invoked moral theories to oppose or support traditional practices of killing animals to protect biodiversity and ecosystems. The debate has featured the mainstream moral theories of consequentialism and utilitarianism, deontology, and virtue ethics. We identify problematic applications and critique of these moral theories in conservation discussions. Problems include a lack of clarity when invoking moral theories, misunderstanding and mischaracterizing theories, and overlooking features and circumstances affecting a theory's application. A key omission in the debate is a detailed discussion of the moral significance of animals and nature. We then examine the role of moral theory as such in ethical discussion, contrasting moral theory with ethical outlooks that center, for example, forms of love and care. Our aim is to advance the ethical debate about harming animals in conservation.
“They don't trust me”: Service providers reflections of father‐centric treatment and engagement
Authors: Garcia Antonio , Pérez‐Figueroa Rafael , Cozart David , Cook Victoria , Damron Jeff , Clark Shelby , Eubank Kendra
Published: April 2024

Objective

This study sought to illuminate the barriers service providers experience in delivering healing services to enhance father and child well‐being.

Background

Manifestations of structural barriers, such as racism, mother‐centric practices, and disproportionate incarceration among Black and Brown fathers prevail. Little is known, however, about how providers describe barriers they encounter toward engaging fathers in services to equip them with the capacity to coparent effectively.

Method

A convenience sample of providers (n = 24) representing a diverse array of child and family service systems responded to questions from a semistructured interview guide. Thematic analyses were conducted to describe how providers engage with fathers and their perceptions of barriers related to their ability to engage them in services.

Results

Findings revealed three types of barriers, each representing a separate theme: micro (biases, colorblindness), societal (devaluation of fathers' role), and systemic (racism, mother‐centrism). Strategies to address barriers included implementing strengths‐based practices, creating spaces to engage in reflexivity, and investing in father‐centric programming. Most strategies involved modifying the micro context, conveying that future efforts should focus on developing procedures and policies that will enhance micro practices.

Conclusion

This study captured the experiences of change agents and healers working with fathers and families. Their experiences illuminate obstacles they must contend with at the micro, societal, and systemic levels of practice.

Implications

Providers indicated that fathers will not benefit from services unless organizations embrace father‐centric, strength‐based healing practices and allocate space to engage in reflexivity about biases and the impact of systemic racism.
14‐day tailored PCR‐guided triple therapy versus 14‐day non‐Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open‐label randomized noninferiority controlled trial
Authors: Amiot Aurelien , Hacoon Jérémy , Heluwaert Frederic , Mion François , Lamarque Dominique , Moussata Driffa , Mimouni Maroua , Delchier Jean‐Charles , Durand‐Zaleski Isabelle , Audureau Etienne , Bastuji‐Garin Sylvie ,   for the HEPYSE Study Group
Published: April 2024

Background

The systematic use of susceptibility testing and tailored first‐line treatment for Helicobacter pylori eradication has yet to be established.

Aim

To compare 14‐day tailored PCR‐guided triple therapy to 14‐day non‐Bismuth concomitant quadruple therapy for first‐line Helicobacter pylori eradication.

Patients and Methods

We performed a multicenter, parallel‐group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14‐day tailored PCR‐guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14‐day non‐Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication.

Results

We screened 991 patients for eligibility and randomized 241 patients. The first‐line eradication rate was 99.2% in the tailored PCR‐guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at −0.68%). Both first‐line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR‐guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR‐guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population.

Conclusion

In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14‐day tailored PCR‐guided triple therapy as a first‐line H. pylori eradication therapy compared to 14‐day non‐Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).
Study on the magnetoelectric effect, ferroelectric and optical investigation of (1−x) BCT + x NZLFO multiferroic composite
Authors: Rahman M. Atikur , Hasan Zahid , Rouf Hasan Khaled , Alam M. Khurshed , Hossain A. K. M. Akther , Khan M. N. I. , Mohammad M. R. , Alodhayb Abdullah , Mohammad Saikh , Haldhar Rajesh , Hossain M. Khalid
Published: April 2024

This study investigates the magnetoelectric coupling effect in dual‐phase multiferroic composites prepared using a solid‐state reaction method. The composites were fabricated with the formula (1−x)Ba₀.₇₇Ca₀.₂₃TiO₃(BCT) + xNi₀.₆Zn₀.₂₅La₀.₁₅Fe₂O₄(NZLFO), where x varied from 0% to 100% in 10% increments. Ca‐doped BaTiO₃ served as the ferroelectric phase, while La‐doped Ni–Zn ferrite acted as the ferromagnetic phase. The effects of varying ferrite content (x) on structural, optical, ferroelectric, electrical, and magnetoelectric properties were comprehensively analyzed. X‐ray diffraction (XRD) with Rietveld refinement revealed a spinel cubic structure for the ferrite phases and a tetragonal structure for the perovskite phases. The study observed a moderate influence of ferrite concentration on the lattice parameters of BCT and an opposing effect on the lattice parameters of NZLFO. Optical measurements indicated higher light absorption in the visible range compared to the UV region and wide optical bandgap. Magnetic properties, characterized by saturation magnetization, exhibited a dependence on temperature, with a Curie temperature (Tc) of 700 K. Electrical resistivity displayed a maximum at x = 50% and remained constant at high frequencies. The study also confirmed the presence of electric polarization induced by a magnetic field, with the highest magnetoelectric coefficient observed at x = 10%. These findings demonstrate the successful fabrication of dual‐phase multiferroic composites with tunable properties through controlled ferrite content. The observed magnetoelectric coupling suggests potential applications in multifunctional devices.
The multifaceted life of macrophages in white adipose tissue: Immune shift couples with metabolic switch
Authors: Wang Qun , Hartig Sean M. , Ballantyne Christie M. , Wu Huaizhu
Published: April 2024

White adipose tissue (WAT) is a vital endocrine organ that regulates energy balance and metabolic homeostasis. In addition to fat cells, WAT harbors macrophages with distinct phenotypes that play crucial roles in immunity and metabolism. Nutrient demands cause macrophages to accumulate in WAT niches, where they remodel the microenvironment and produce beneficial or detrimental effects on systemic metabolism. Given the abundance of macrophages in WAT, this review summarizes the heterogeneity of WAT macrophages in physiological and pathological conditions, including their alterations in quantity, phenotypes, characteristics, and functions during WAT growth and development, as well as healthy or unhealthy expansion. We will discuss the interactions of macrophages with other cell partners in WAT including adipose stem cells, adipocytes, and T cells in the context of various microenvironment niches in lean or obese condition. Finally, we highlight how adipose tissue macrophages merge immunity and metabolic changes to govern energy balance for the organism.
Exosomal HSPB1, interacting with FUS protein, suppresses hypoxia‐induced ferroptosis in pancreatic cancer by stabilizing Nrf2 mRNA and repressing P450
Authors: Zhang Lun , Yang Liuxu , Du Keyuan
Published: April 2024

Ferroptosis is a new type of programmed cell death, which has been involved in the progression of tumours. However, the regulatory network of ferroptosis in pancreatic cancer is still largely unknown. Here, using datasets from GEO and TCGA, we screened HSPB1, related to the P450 monooxygenase signalling, a fuel of ferroptosis, to be a candidate gene for regulating pancreatic cancer cell ferroptosis. We found that HSPB1 was enriched in the exosomes derived from human pancreatic cancer cell lines SW1990 and Panc‐1. Then, hypoxic SW1990 cells were incubated with exosomes alone or together with HSPB1 siRNA (si‐HSPB1), and we observed that exosomes promoted cell proliferation and invasion and suppressed ferroptosis, which was reversed by si‐HSPB1. Moreover, we found a potential binding affinity between HSPB1 and FUS, verified their protein interaction by using dual‐colour fluorescence colocalization and co‐IP assays, and demonstrated the promoting effect of FUS on oxidative stress and ferroptosis in hypoxic SW1990 cells. Subsequently, FUS was demonstrated to bind with and stabilize the mRNA of Nrf2, a famous anti‐ferroptosis gene that negatively regulates the level of P450. Furthermore, overexpressing FUS and activating the Nrf2/HO‐1 pathway (using NK‐252) both reversed the inhibitory effect of si‐HSPB1 on exosome functions. Finally, our in vivo studies showed that exosome administration promote tumour growth in nude mice of xenotransplantation, which was able to be eliminated by knockdown of HSPB1. In conclusion, exosomal HSPB1 interacts with the RNA binding protein FUS and decreases FUS‐mediated stability of Nrf2 mRNA, thus suppressing hypoxia‐induced ferroptosis in pancreatic cancer.
Retinoids in the treatment of photoageing: A histological study of topical retinoid efficacy in black skin
Authors: Halai P. , Kiss O. , Wang R. , Chien A. L. , Kang S. , O'Connor C. , Bell M. , Griffiths C. E. M. , Watson R. E. B. , Langton A. K.
Published: April 2024

Background

Photoageing describes complex cutaneous changes that occur due to chronic exposure to solar ultraviolet radiation (UVR). The ‘gold standard’ for the treatment of photoaged white skin is all‐trans retinoic acid (ATRA); however, cosmetic retinol (ROL) has also proven efficacious. Recent work has identified that black skin is susceptible to photoageing, characterized by disintegration of fibrillin‐rich microfibrils (FRMs) at the dermal–epidermal junction (DEJ). However, the impact of topical retinoids for repair of black skin has not been well investigated.

Objectives

To determine the potential of retinoids to repair photoaged black skin.

Methods

An exploratory intervention study was performed using an in vivo, short‐term patch test protocol. Healthy but photoaged black volunteers (>45 years) were recruited to the study, and participant extensor forearms were occluded with either 0.025% ATRA (n = 6; 4‐day application due to irritancy) or ROL (12‐day treatment protocol for a cosmetic) at concentrations of 0.3% (n = 6) or 1% (n = 6). Punch biopsies from occluded but untreated control sites and retinoid‐treated sites were processed for histological analyses of epidermal characteristics, melanin distribution and dermal remodelling.

Results

Treatment with ATRA and ROL induced significant acanthosis (all p < 0.001) accompanied by a significant increase in keratinocyte proliferation (Ki67; all p < 0.01), dispersal of epidermal melanin and restoration of the FRMs at the DEJ (all p < 0.01), compared to untreated control.

Conclusions

This study confirms that topical ATRA has utility for the repair of photoaged black skin and that ROL induces comparable effects on epidermal and dermal remodelling, albeit over a longer timeframe. The effects of topical retinoids on black photoaged skin are similar to those reported for white photoaged skin and suggest conserved biology in relation to repair of UVR‐induced damage. Further investigation of topical retinoid efficacy in daily use is warranted for black skin.
Inshore and offshore marine migration pathways of Atlantic salmon post‐smolts from multiple rivers in Scotland, England, Northern Ireland, and Ireland
Authors: Rodger Jessica R. , Lilly Jessie , Honkanen Hannele M. , del Villar Diego , Kennedy Richard , Maoiléidigh Niall Ó. , Boylan Patrick , Rosell Robert , Morris David J. , O'Neill Ross , Waters Catherine , Cotter Deirdre , Wilkie Lorna , Barkley Andrea , Green Amy , Beck Samantha V. , Ribbens Jamie , Henderson Jim , Parke Debbie , Kettle‐White Alan , Ballantyne Lucy , Marshall Shona , Hopper Paul , Gauld Niall , Godfrey Jason D. , Chapman Lauren E. , Thorburn James , Drumm Alan , Whoriskey Fred , Shields Brian , Ramsden Philip , Barry James , Millane Michael , Roche William , Armstrong John D. , Wells Alan , Walton Silas , Fletcher Melanie , Bailey David M. , Whyte Bill , McGill Ross , Bilsby Mark , Whelan Ken , Bean Colin W. , Adams Colin E.
Published: April 2024

The migratory behavior of Atlantic salmon (Salmo salar) post‐smolts in coastal waters is poorly understood. In this collaborative study, 1914 smolts, from 25 rivers, in four countries were tagged with acoustic transmitters during a single seasonal migration. In total, 1105 post‐smolts entered the marine study areas and 438 (39.6%) were detected on a network of 414 marine acoustic receivers and an autonomous underwater vehicle. Migration pathways (defined as the shortest distance between two detections) of up to 575 km and over 100 days at sea were described for all 25 populations. Post‐smolts from different rivers, as well as individuals from the same river, used different pathways in coastal waters. Although difficult to generalize to all rivers, at least during the year of this study, no tagged post‐smolts from rivers draining into the Irish Sea were detected entering the areas of sea between the Hebrides and mainland Scotland, which is associated with a high density of finfish aquaculture. An important outcome of this study is that a high proportion of post‐smolts crossed through multiple legislative jurisdictions and boundaries during their migration. This study provides the basis for spatially explicit assessment of the impact risk of coastal pressures on salmon during their first migration to sea.
Characterisation and correction of polarisation effects in fluorescently labelled fibres
Authors: Aggarwal Nandini , Marsh Richard , Marcotti Stefania , Shaw Tanya J , Stramer Brian , Cox Susan , Culley Siân
Published: April 2024

Many biological structures take the form of fibres and filaments, and quantitative analysis of fibre organisation is important for understanding their functions in both normal physiological conditions and disease. In order to visualise these structures, fibres can be fluorescently labelled and imaged, with specialised image analysis methods available for quantifying the degree and strength of fibre alignment. Here we show that fluorescently labelled fibres can display polarised emission, with the strength of this effect varying depending on structure and fluorophore identity. This can bias automated analysis of fibre alignment and mask the true underlying structural organisation. We present a method for quantifying and correcting these polarisation effects without requiring polarisation‐resolved microscopy and demonstrate its efficacy when applied to images of fluorescently labelled collagen gels, allowing for more reliable characterisation of fibre microarchitecture.
AEBP1 upregulation contributes to cervical cancer progression by facilitating cell proliferation, migration, and invasion
Authors: Liu Songjun , Gu Yanpin , Shi Yin , Yu Shuqian , Li Wu , Lv Wen
Published: April 2024

Background

Aberrant expression of adipocyte enhancer‐binding protein 1 (AEBP1) has been demonstrated to be involved in the tumorigenesis and progression of numerous cancers. This study was aimed to investigate the mechanism of AEBP1 in the development of cervical cancer.

Methods

The expression of AEBP1 in cervical cancer was assessed by immunohistochemistry. The function of AEBP1 on cell proliferation, migration, and invasion was determined by methyl thiazolyl tetrazolium assay, colony formation, and transwell assay. The activation of related signaling pathway was determined by western blot. The bioinformatics analysis was performed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results

Higher protein expression of AEBP1 was observed in patients with cervical cancer. Overexpressed AEBP1 promoted cell proliferation, migration, and invasion abilities in cervical cancer cells. Moreover, the research manifested that AEBP1 activated the phosphorylation of STAT3. GO and KEGG analysis showed that genes positively related to AEBP1 were highly enriched in functions like epithelial cell proliferation, muscle cell migration, myoblast migration, smooth muscle tissue development, ECM–receptor interaction, transcriptional misregulation in cancer, and proteoglycans in cancer. While genes negatively related to AEBP1 were associated with immunity, including inflammatory response, external‐stimulus response, neutrophil, granulocyte, and macrophage chemotaxis.

Conclusions

This study suggested that AEBP1 acts as an oncogened and might be a potential therapeutic target for the treatment of cervical cancer.
Provenance constraints on the Late Triassic ejecta layer from Churchwood Quarry, SW England: An impactite suite from Manicouagan
Authors: McGregor Maree , Spray John G. , McFarlane Christopher R. M.
Published: April 2024

In situ LA‐ICP‐MS/MS U‐Pb and Rb‐Sr geochronology combined with geochemical analysis and electron microscopy have been performed on ejecta components sampled from the Mid‐to‐Late Triassic Mercia Mudstone Group at Churchwood Quarry, SW England. The layer comprises altered impact spherules, melt‐rich and fragment‐rich accreted grain clusters (AGCs), along with shocked mineral phases. Late Triassic ages are obtained: a U‐Pb age of 219 ± 72 Ma from variably shock‐metamorphosed apatite and a Rb‐Sr age of 213 ± 31 Ma from melt‐rich AGCs. A post‐depositional U‐Pb age of 200 ± 7.5 Ma obtained from the carbonate host matrix correlates with an early Jurassic dolomitization event associated with regional marine transgression. Several links to the Manicouagan impact structure, Canada, are identified that complement previous provenance studies: (1) rare earth element compositions of impact spherules and melt‐rich AGCs match those of the Manicouagan impact melt sheet; (2) the preservation of Archean and Paleo‐ to Neoproterozoic target rock U‐Pb ages in zircon and apatite match those recorded within Manicouagan basement lithologies; and (3) impact spherules and melt‐rich AGCs record initial 87Sr/86Sr compositions that overlap with those of the Manicouagan impact melt sheet and the target rocks involved in their generation.
Synthesizing environmental, epidemiological and vector and parasite genetic data to assist decision making for disease elimination
Authors: Shrestha Himal , McCulloch Karen , Chisholm Rebecca H. , Armoo Samuel K. , Veriegh Francis , Sirwani Neha , Crawford Katie E. , Osei‐Atweneboana Mike Y. , Grant Warwick N. , Hedtke Shannon M.
Published: April 2024

We present a framework for identifying when conditions are favourable for transmission of vector‐borne diseases between communities by incorporating predicted disease prevalence mapping with landscape analysis of sociological, environmental and host/parasite genetic data. We explored the relationship between environmental features and gene flow of a filarial parasite of humans, Onchocerca volvulus, and its vector, blackflies in the genus Simulium. We generated a baseline microfilarial prevalence map from point estimates from 47 locations in the ecological transition separating the savannah and forest in Ghana, where transmission of O. volvulus persists despite onchocerciasis control efforts. We generated movement suitability maps based on environmental correlates with mitochondrial population structure of 164 parasites from 15 communities and 93 vectors from only four sampling sites, and compared these to the baseline prevalence map. Parasite genetic distance between sampling locations was significantly associated with elevation (r = .793, p = .005) and soil moisture (r = .507, p = .002), while vector genetic distance was associated with soil moisture (r = .788, p = .0417) and precipitation (r = .835, p = .0417). The correlation between baseline prevalence and parasite resistance surface maps was stronger than that between prevalence and vector resistance surface maps. The centre of the study area had high prevalence and suitability for parasite and vector gene flow, potentially contributing to persistent transmission and suggesting the importance of re‐evaluating transmission zone boundaries. With suitably dense sampling, this framework can help delineate transmission zones for onchocerciasis and would be translatable to other vector‐borne diseases.
Determinants of microbiome composition: Insights from free‐ranging hybrid zebras (Equus quagga × grevyi)
Authors: Abraham Joel O. , Lin Bing , Miller Audrey E. , Henry Lucas P. , Demmel Margaret Y. , Warungu Rosemary , Mwangi Margaret , Lobura Patrick M. , Pallares Luisa F. , Ayroles Julien F. , Pringle Robert M. , Rubenstein Daniel I.
Published: April 2024

The composition of mammalian gut microbiomes is highly conserved within species, yet the mechanisms by which microbiome composition is transmitted and maintained within lineages of wild animals remain unclear. Mutually compatible hypotheses exist, including that microbiome fidelity results from inherited dietary habits, shared environmental exposure, morphophysiological filtering and/or maternal effects. Interspecific hybrids are a promising system in which to interrogate the determinants of microbiome composition because hybrids can decouple traits and processes that are otherwise co‐inherited in their parent species. We used a population of free‐living hybrid zebras (Equus quagga × grevyi) in Kenya to evaluate the roles of these four mechanisms in regulating microbiome composition. We analysed faecal DNA for both the trnL‐P6 and the 16S rRNA V4 region to characterize the diets and microbiomes of the hybrid zebra and of their parent species, plains zebra (E. quagga) and Grevy's zebra (E. grevyi). We found that both diet and microbiome composition clustered by species, and that hybrid diets and microbiomes were largely nested within those of the maternal species, plains zebra. Hybrid microbiomes were less variable than those of either parent species where they co‐occurred. Diet and microbiome composition were strongly correlated, although the strength of this correlation varied between species. These patterns are most consistent with the maternal‐effects hypothesis, somewhat consistent with the diet hypothesis, and largely inconsistent with the environmental‐sourcing and morphophysiological‐filtering hypotheses. Maternal transmittance likely operates in conjunction with inherited feeding habits to conserve microbiome composition within species.
Epidemiological patterns of candidaemia: A comprehensive analysis over a decade
Authors: Ferngren Gordon , Yu David , Unalan‐Altintop Tugce , Dinnétz Patrik , Özenci Volkan
Published: April 2024

Background

The prevalence of fungal bloodstream infections (BSI), especially candidaemia, has been increasing globally during the last decades. Fungal diagnosis is still challenging due to the slow growth of fungal microorganisms and need for special expertise. Fungal polymicrobial infections further complicate the diagnosis and extend the time required. Epidemiological data are vital to generate effective empirical treatment strategies.

Objectives

The overall aim of this project is to describe the epidemiology of monomicrobial candidaemia and polymicrobial BSI, both with mixed fungaemia and with mixed Candida/bacterial BSIs.

Methods

We conducted a single‐centre retrospective epidemiological study that encompasses 950,161 blood cultures during the years 2010 to 2020. The epidemiology of monomicrobial and polymicrobial candidaemia episodes were investigated from the electronic records.

Results

We found that 1334 candidaemia episodes were identified belonging to 1144 individual patients during 2010 to 2020. Candida albicans was the most prevalent species detected in candidaemia patients, representing 57.7% of these episodes. Nakaseomyces (Candida) glabrata and Candida parapsilosis complex showed an increasing trend compared to previous studies, whereas Candida albicans demonstrated a decrease. 19.8% of these episodes were polymicrobial and 17% presented with mixed Candida/bacterial BSIs while 2.8% were mixed fungaemia. C. albicans and N. glabrata were the most common combination (51.4%) in mixed fungaemia episodes. Enterococcus and Lactobacillus spp. were the most common bacteria isolated in mixed Candida/bacterial BSIs.

Conclusions

Polymicrobial growth with candidaemia is common, mostly being mixed Candida/bacterial BSIs. C. albicans was detected in more than half of all the candidaemia patients however showed a decreasing trend in time, whereas an increase is noteworthy in C. parapsilosis complex and N. glabrata.
A systematic review and meta‐analysis of the child‐level effects of family‐based interventions for the prevention of type 2 diabetes mellitus
Authors: Kurtzhals Mette , Bjerregaard Anne‐Louise , Hybschmann Jane , Müllertz Alberte Laura Oest , DeSilva Bianca , Elsborg Peter , Timm Anne , Petersen Therese Lockenwitz , Thygesen Lau Caspar , Kurtzhals Peter , Flensborg‐Madsen Trine , Bentsen Peter , Mygind Lærke
Published: April 2024

Aims

The purpose of this systematic review and meta‐analysis was to investigate the effects of family‐based health promotion interventions on child‐level risk factors for type 2 diabetes in vulnerable families.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) checklist for systematic reviews formed the methodological framework. CINAHL, Embase, MEDLINE, PsycINFO, and Web of Science were searched on January 12, 2024. The NTP‐OHAT Risk of Bias Assessment Tool was used to assess the risk of bias in the individual studies, and meta‐analyses were performed.

Results

The 4723 studies were identified, and 55 studies met the inclusion criteria. Results showed significant effects on children's body mass index (mean difference [MD], −0.18, 95% CI [−0.33 to −0.03], p = 0.02), body fat percentage (MD, −2.00, 95% CI [−3.31 to −0.69], p = 0.003), daily activity (standardized mean difference [SMD], 0.23, 95% CI [0.01; 0.44], p = 0.04), physical activity self‐efficacy (SMD, 0.73, 95% CI [0.36 to 1.10], p < 0.01), intake of snacks (MD, −0.10, 95% CI [−0.17 to −0.04], p = 0.002), and sugar‐sweetened beverages (SMD, −0.21, 95% CI [−0.42 to −0.01], p = 0.04). Subgroup analyses suggested that interventions aiming to change child and parent behavior simultaneously have larger effect on fasting glucose and nutrition consumption, and that interventions longer than 26 weeks have larger effects on body composition and physical activity behavior than shorter interventions.
Visual impairment and cognitive performance: A nationwide study of 1.4 million adolescents
Authors: Nitzan Itay , Derazne Estela , Afek Arnon , Einan‐Lifshitz Adi , Morad Yair , Yahalom Claudia , Peled Alon
Published: April 2024

Purpose

Previous research highlights the adverse effects of visual impairment (VI) on academic achievement in children, yet its impact on cognitive performance among adolescents and young adults remains under‐studied. Therefore, this investigation aimed to analyse this association in a nationwide sample of Israeli adolescents.

Methods

A retrospective population‐based cross‐sectional study was conducted among 1,410,616 Israeli‐born adolescents aged 16–19 years, who were assessed before mandatory military service between 1993 and 2017. The definition of VI was based on best‐corrected visual acuity (BCVA) measurements using a standard Snellen chart. Adolescents with BCVA worse than 6/9 in either or both eyes were classified as having unilateral or bilateral VI, respectively. Cognitive performance was measured using the General Intelligence Score (GIS), based on a validated four‐domain test. Relationships were analysed using regression models yielding adjusted odds ratios (ORs) for low (<−1 standard deviation [SD]) and high (≥1 SD) cognitive Z‐scores.

Results

Of 1,410,616 adolescents (56.1% men), 13,773 (1.0%) had unilateral and 3980 (0.3%) had bilateral VI. Unilateral VI was associated with adjusted ORs for low and high cognitive Z‐scores of 1.24 (1.19–1.30) and 0.84 (0.80–0.89), respectively. ORs were accentuated for bilateral VI, reaching 1.62 (1.50–1.75) and 0.81 (0.74–0.90) for low and high cognitive Z‐scores, respectively. Cognitive performance subscores mirrored these results, with the visual–spatial functioning subtest demonstrating the greatest effect size. These associations persisted in sub‐analyses restricted to adolescents with amblyopia‐related VI, mild VI and unimpaired health status.

Conclusions

Visual impairment, including mild and unilateral cases, is associated with reduced cognitive performance scores assessed in late adolescence. Further research is required to gain a comprehensive understanding of the dynamics underlying this relationship.
Evaluation of Apis mellifera brain morphophysiology in response to titanium dioxide nanoparticles and deltamethrin co‐exposure
Authors: Shahzad Kiran , Manzoor Farkhanda
Published: April 2024

Honeybees are important insects, both economically and as pollinators. While foraging, bees can come in contact with environmental pollutants such as pesticides, possibly in combination with other xenobiotic compounds that may compromise bee health. Our current study investigated the acute exposure to nanosized titanium dioxide, a common additive in food, cosmetics, paints and agricultural products, along with deltamethrin (DLT), a well‐known pyrethroid pesticide. The effects of binary exposure to titanium dioxide nanoparticles (TiO2‐NPs) nanoparticles at concentrations of 25, 50, 75 and 100 μg/mL with DLT were noted on Apis mellifera brain histology along with their possible synergism. In DLT‐ and combined TiO2‐NP‐DLT treated bees, survival rates were lowered and several histological alterations were observed including an increased number of cells with pyknotic nuclei, along with cytoplasmic vacuolization, chromatin compaction and degeneration indicating autophagic activity and a decrease in the cross‐sectional area of nanoparticle‐treated mushroom body calyces. A synergistic relationship between TiO2‐NPs and DLT was revealed, while LD50 for combined TiO2‐NP‐DLT treatment was 0.101, 0.09 and 0.02 μg/bee at 24, 48 and 72 h, respectively. In summary, results demonstrate that TiO2‐NP and DLT co‐exposure can induce damage in bee brain structures at higher concentrations, which indicates an additional risk factor for bee health in the field.