bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel lipophilic amiloride derivative efficiently kills chemoresistant breast cancer cells
Authors: Hu Michelle , Liu Ruiwu , Castro Noemi , Loza Sanchez Liliana , Rueankham Lapamas , Learn Julie A. , Huang Ruiqi , Lam Kit S. , Carraway Kermit L.
Published: August 2024

Derivatives of the potassium-sparing diuretic amiloride are preferentially cytotoxic toward tumor cells relative to normal cells, and have the capacity to target tumor cell populations resistant to currently employed therapeutic agents. However, a major barrier to clinical translation of the amilorides is their modest cytotoxic potency, with estimated IC50 values in the high micromolar range. Here we report the synthesis of ten novel amiloride derivatives and the characterization of their cytotoxic potency toward MCF7 (ER/PR-positive), SKBR3 (HER2-positive) and MDA-MB-231 (triple negative) cell line models of breast cancer. Comparisons of derivative structure with cytotoxic potency toward these cell lines underscore the importance of an intact guanidine group, and uncover a strong link between drug-induced cytotoxicity and drug lipophilicity. We demonstrate that our most potent derivative called LLC1 is preferentially cytotoxic toward mouse mammary tumor over normal epithelial organoids, acts in the single digit micromolar range on breast cancer cell line models representing all major subtypes, acts on cell lines that exhibit both transient and sustained resistance to chemotherapeutic agents, but exhibits limited anti-tumor effects in a mouse model of metastatic breast cancer. Nonetheless, our observations offer a roadmap for the future optimization of amiloride-based compounds with preferential cytotoxicity toward breast tumor cells.
The molecular basis of the anticancer effect of statins
Authors: Buccioli Giovanni , Testa Carolina , Jacchetti Emanuela , Pinoli Pietro , Carelli Stephana , Ceri Stefano , Raimondi Manuela T.
Published: August 2024

Statins, widely used cardiovascular drugs that lower cholesterol by inhibiting HMG-CoA reductase, have been increasingly recognized for their potential anticancer properties. This study elucidates the underlying mechanism, revealing that statins exploit Synthetic Lethality, a principle where the co-occurrence of two non-lethal events leads to cell death. Our computational analysis of approximately 37,000 SL pairs identified statins as potential drugs targeting genes involved in SL pairs with metastatic genes. In vitro validation on various cancer cell lines confirmed the anticancer efficacy of statins. This data-driven drug repurposing strategy provides a molecular basis for the anticancer effects of statins, offering translational opportunities in oncology.
Concise synthesis of a light/temperature/pH/CO2-quadruple responsive azobenzene functionalized homopolymer for reversible photopatterning
Authors: Wang Ke , Si Meiyu , Liu Xiaofang , Wang Zilong , Liu Guiyan , Zeng Yongfei
Published: August 2024

A novel light/temperature/pH/CO2-quadruple responsive azobenzene functionalized homopolymer that can be used in optical storage, P(Azo-N-EO2MA), has been synthesized and its responses to stimuli are found to be sensitive and reversible.
Dual‐inertia flywheel energy storage system for electric vehicles
Authors: Mehraban Abbas , Ghanbari Teymoor , Farjah Ebrahim
Published: August 2024

Managing the high‐rate‐power transients of Electric Vehicles (EVs) in a drive cycle is of great importance from the battery health and drive range aspects. This can be achieved by high power‐density storage, such as a high‐speed Flywheel Energy Storage System (FESS). It is shown that a variable‐mass flywheel can effectively utilise the FESS useable capacity in most transients close to optimal. Novel variable capacities FESS is proposed by introducing Dual‐Inertia FESS (DIFESS) for EVs. The feasibility of the proposed concept is evaluated by deriving the size of a Single‐Inertia FESS (SIFESS) for a battery EV, which runs the well‐known Urban Dynamometer Driving Schedule. The sizing framework consists of an Energy Management System using the constrained Pontryagin's minimum principle and a proposed sizing algorithm. Then, by splitting the derived SIFESS inertia into two separate inertias, the appropriate engaging control of inertias is determined for some driving cycles including, the Artemis Urban, Braunschweig City, and Worldwide Harmonised Light‐duty Vehicles Test Cycle. The dual inertias suitable sizes are derived using a proposed algorithm, which targets maximising the FESS useable capacity. The results show that compared to the SIFESS, the DIFESS can employ the FESS's useable capacity more effectively.
Higher education and the transition to adulthood: socioeconomic inequality in college students’ self-narratives
Authors: Silver Blake R.
Published: August 2024

How does socioeconomic status relate to the self-narratives youth craft in higher education? This article examines in-depth interviews with 96 students at a broad-access public university to illuminate how narratives of the transition to adulthood are shaped by socioeconomic inequality among youth who enroll in the same postsecondary institution. Although most students across backgrounds agreed that they were “not yet adults,” there were differences in the ways they described their paths to adulthood. Less socioeconomically advantaged students characterized their journeys as stalled, focusing on difficulties obtaining traditional markers of adulthood. These participants struggled to incorporate college experiences into their narratives and engaged in self-deprecation and self-blame. Meanwhile, more socioeconomically advantaged students highlighted personal growth in college to portray themselves as individuals with potential, who were positioned for future success. These findings provide unique insight into higher education’s role in cultural reproduction and have implications for students’ opportunities transitioning to postbaccalaureate life.
Blackstone's Counter Fraud Professionals' Handbook
Authors: Betts Michael J , Eshelby Laura , Whitehouse-Hayes David
Published: August 2024

Blackstone’s Counter Fraud Professionals’ Handbook is a collection of highly practical, up-to-date chapters covering a range of essential subjects in counter fraud. Developed from a detailed understanding of the modern counter fraud professional’s needs, this series seeks to explain the relevant law, practice, theory, and procedure, with first-hand insights from those involved in the development of the Government Counter Fraud Profession. This includes an overview of the evolving threat from fraud, bribery, and corruption. It sets out how to move to a more preventative and proactive approach to counter fraud via the application of fraud risk assessment, as well as detection and measurement techniques to understand the fraud landscape in which organizations are operating and improving the overall response. This text offers practical straightforward advice to practitioners dealing with fraud and economic crimes. The book covers many disciplines and updates to build awareness and for planning an effective response. This includes essential approaches for effective gathering of intelligence and how to undertake professional and effective investigations, and the fundamental role of leadership in a counter fraud context. These in turn inform the most effective disposal routes including prosecutions, other civil and criminal sanctions, as well stand-alone or parallel redress options. It sets out how this holistic approach can reduce the harm caused and ultimately protect individuals, businesses, and the public sector from the harm and damage that fraud causes.
Preventing Fraud
Authors: Betts Michael J , Eshelby Laura , Whitehouse-Hayes David
Published: August 2024

This chapter explores the importance of fraud prevention. It introduces the activity and approaches to be adopted to effectively lead, manage, and measure the impact of fraud prevention. It includes consideration of how risk, use of data, control evaluation, and fraud awareness are key areas for effective fraud prevention. It details the essential knowledge to prevent fraud including an understanding of fraud and fraudsters and their methods of attack. It explains the prevention techniques to be required within an organization. The chapter explains the principles of ‘designing out’ fraud across a range of projects and organizations, with applicability in a range of different working environments/sectors. The human element of detection will be emphasized, as will how to develop effective awareness campaigns to upskill those connected with an organization to detect fraud.
Prosecution, Sanctions, and Redress
Authors: Betts Michael J , Eshelby Laura , Whitehouse-Hayes David
Published: August 2024

This chapter provides an overview of the different routes to taking action to counter fraud, including from a disciplinary, civil, and criminal perspective. It introduces the practices to adopt when working with regulatory bodies and how to form partnership agreements for one-off or ongoing operations. It explains the benefits and challenges of the different routes, and how to effectively manage a response which is conducted in parallel (parallel proceedings, criminal, and civil). It describes an overview of the different sanctions and redress options available, including from a civil and criminal legal context. The focus will be the articulation of the range of options available to a practitioner in counter fraud, and the steps to take to introduce, vary, or amend an existing sanctions policy from an organizational perspective. The chapter introduces key principles when developing a sanctions and redress policy, including adherence to legislative frameworks, reasonableness, and proportionality.
Countering Bribery and Corruption
Authors: Betts Michael J , Eshelby Laura , Whitehouse-Hayes David
Published: August 2024

This chapter explores the recent developments and best practices available for the counter fraud professional to detect, prevent, and investigate bribery and corruption. It references the Government Counter Bribery and Corruption Standard and details its practical application. It describes what products the professional should consider when building a counter corruption framework within an organization and what process guidance should be implemented. It explains the investigation of bribery from a professional’s perspective with a review of the legislation and tools readily available. It includes relevant checklists and diagrams illustrating the key dynamics of corruption and bribery. The provisions of the UK Bribery Act 2010 are explained in practitioners’ terms to make it an effective tool for the prevention and investigation of bribery. The legislation relating to failing to present bribery by commercial organizations is explained and fully illustrated by way of diagrams and easy-to-use checklists. A number of recent cases are explored and the lessons learned detailed; these include the Airbus case and Rolls-Royce. A detailed analysis of these cases is presented to inform the counter fraud professional of what to look for in similar cases. A counter bribery and corruption toolkit is provided which will include extensive signposting to the available sources of information and guidance.
“The Greatest Young Preacher Ever Lived”
Authors: Alcántara Jared E
Published: August 2024

This chapter examines the first decade of Joseph H. Jackson’s pastorate at Olivet Baptist Church, the 1940s, through establishing the necessary context for his ministry: Chicago during the second major wave of the Great Migration. It analyzes the new wave of migration to Chicago (and elsewhere) in the 1940s into the 1950s, an underanalyzed and oft-neglected wave, to explain how Chicago was transformed during this era. After establishing Jackson’s context for ministry, it examines his development as an ambitious leader, a powerful preacher, and an advocate for improved race relations. During this period, Jackson transformed Olivet from a nationally known church to an international phenomenon.
Conclusion
Authors: Alcántara Jared E
Published: August 2024

The conclusion considers Jackson’s complex legacy and ongoing significance. It highlights his understanding of power, more specifically, his reputation for being a kingmaker, conviction that Black communities must have power to wield it, commitment to working within the system to bring about change, and unhealthy attachment to maintaining power as a cautionary tale. Jackson’s legacy represents a challenge in that it is a mixed legacy. On the one hand, he was on the wrong side of the civil rights movement and grasped power too tightly. On the other hand, he appears to be forward thinking on economic empowerment, landownership, education, and racial-ethnic power dynamics in churches. He leaves behind a legacy that was both wrong and right, enigmatic and dynamic, infused with vice and virtue.
Curriculum and Assessment for Students with Differences and Disabilities
Authors: Hammel Alice M , Hourigan Ryan M
Published: August 2024

This chapter examines the scope and sequence of a successful music curriculum and successful inclusion strategies for including students with differences and disabilities. Examples at all levels (elementary and secondary) are included (e.g., band, orchestra, choir, and general music). In addition, assessment and data collection strategies are included. The strategies within the curricula study range from formative to summative and demonstrate ways to add size, color, pacing, and modality to lesson and unit planning. For more information on lesson planning, please see Teaching Music to Students with Differences and Disabilities (second edition). The ability to teach students at various places in their learning is demonstrated to show how we can adapt, modify (wind), and meet the needs of every student in our classrooms and ensembles.
Teaching Strategies for Performers with Differences and Disabilities
Authors: Hammel Alice M , Hourigan Ryan M
Published: August 2024

The demographics of our performing ensembles are constantly changing. Many school districts have moved toward a policy of full inclusion of students with differences and disabilities. This has led to an increased number of students with differences and disabilities in performing ensembles and has challenged many conductors to find ways to include many students with disabilities who were not previously a part of performing ensembles. The purpose of this chapter is to offer techniques for choral and instrumental conductors who teach performers with differences and disabilities and to suggest ideas for consideration for those who are preparing to conduct performing ensembles. These strategies come from extensive work researching, consulting with ensemble conductors, and working with parents of performers with differences and disabilities.
Fitting a progressive 3-state colorectal cancer model to interval-censored surveillance data under outcome-dependent sampling using a weighted likelihood approach
Authors: Akwiwu Eddymurphy U , Klausch Thomas , Jodal Henriette C , Carvalho Beatriz , Løberg Magnus , Kalager Mette , Berkhof Johannes , Coupé Veerle M H
Published: August 2024

To optimize colorectal cancer (CRC) surveillance, accurate information on the risk of developing CRC from premalignant lesions is essential. However, directly observing this risk is challenging since precursor lesions, that is, advanced adenomas (AAs), are removed upon detection. Statistical methods for multistate models can estimate risks, but estimation is challenging due to low CRC incidence. We propose an outcome-dependent sampling (ODS) design for this problem in which we oversample CRCs. More specifically, we propose a 3-state model for jointly estimating the time distributions from baseline colonoscopy to AA and from AA onset to CRC accounting for the ODS design using a weighted likelihood approach. We applied the methodology to a sample from a Norwegian adenoma cohort (1993-2007), comprising 1495 individuals (median follow-up $6.8$ years; IQR, 1.1-12.8) of whom 648 did and 847 did not develop CRC. We observed a 5-year AA risk of 13% and 34% for individuals having nonadvanced adenoma (NAA) and AA removed at baseline colonoscopy, respectively. Upon AA development, the subsequent risk to develop CRC in 5 years was 17% and age-dependent. These estimates provide a basis for optimizing surveillance intensity and determining the optimal trade-off between CRC prevention, costs, and use of colonoscopy resources.
Update: Prevention and Treatment of Parotid/Submandibular Gland Fistula/Sialocele Following Rhytidectomy With Botulinum Toxin A
Authors: Santos Pauline Joy F , McGill Michelle A , Kerendi Alex N , Nahai Foad
Published: August 2024

Dissecting deep to the superficial musculoaponeurotic system (SMAS), a popular option for facelifts, has the potential for injury to the parotid gland leading to postoperative sialoceles and fistulas. Similarly, deep plane procedures in the neck that include partial submandibular gland resection may lead to salivary gland leaks. We previously described the management of sialocele following rhytidectomy. Since then, administration of botulinum toxin A has emerged as the primary treatment and prevention of this rare complication. The technique of administration and dosage of botulinum toxin in the treatment algorithm is not well defined. We present a literature review and our current protocol for the most efficacious injection technique and dosing to prevent and treat injury to the parotid and submandibular glands.
Brain-penetrant complement inhibition mitigates neurodegeneration in an Alzheimer’s disease mouse model
Authors: Zelek Wioleta M , Bevan Ryan J , Nimmo Jacqui , Dewilde Maarten , De Strooper Bart , Morgan Bryan Paul
Published: August 2024

Complement activation is implicated in driving brain inflammation, self-cell damage and progression of injury in Alzheimer’s disease and other neurodegenerative diseases. Here, we investigate the impact of brain delivery of a complement-blocking antibody on neurodegeneration in an Alzheimer’s mouse model. We engineered a brain-penetrant recombinant antibody targeting the pro-inflammatory membrane attack complex.

Systemic administration of this antibody in APPNL-G-F mice reduced brain levels of complement activation products, demonstrating successful brain entry and target engagement. Prolonged treatment decreased synapse loss, amyloid burden and brain inflammatory cytokine levels, concomitant with cognitive improvement compared to controls. These results underscore the potential of brain-penetrant complement-inhibiting drugs as promising therapeutics, targeting downstream of amyloid plaques in Alzheimer’s disease.
“How do I put this gently?”: articulating the link between racial selectivity in the sexual market and neighborhood selection in the residential market of a global city
Authors: Boston Nicholas
Published: August 2024

The global city is acted upon by a myriad of forces—commercial, cultural, diasporic, digital, identitarian, and political to name a few—on local, national, and transnational scales that produce steadily morphing patterns and concentrations of LGBTQ+ residential settlement in and across neighborhoods. Research has sought to unpack the push–pull factors and adhesive elements that exert influence on such residential configurations. This forum piece ventures to articulate empirically one such pattern that has not been approached in the literature, but has, as the title portends, been addressed in anecdote gently (read: cautiously) for some time: the link between an individual’s stated racial preference in sexual-partner choice and that individual’s selection of a neighborhood to live in that has a high percentage of residents of the preferred race.
Elevation of serum carcinoembryonic antigen as a possible predictor of response to pulse methylprednisolone in acquired idiopathic generalized anhidrosis
Authors: Sakiyama Tomoki , Endo Yuichiro , Nakamizo Satoshi , Kabashima Kenji
Published: August 2024

Background

Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder primarily observed in Asian populations, particularly in Japan. Although pulse methylprednisolone therapy is an effective treatment for AIGA, predictors of therapeutic response remain poorly defined.

Objectives

To identify factors that predict the efficacy of pulse methylprednisolone therapy in patients with AIGA.

Methods

Data obtained from 32 patients with AIGA were assessed based on clinical, histopathological and serological examinations. Statistical analyses were conducted to explore predictors of response to pulse methylprednisolone therapy.

Results

The average age of participants was 32.1 years (SD 12.3); 66% were male and 34% female. The response to pulse methylprednisolone therapy was closely associated with the time from the onset to start of therapy (Wilcoxson’s rank sum test, P = 0.02, n = 27), with earlier intervention resulting in a better outcome. Notably, male patients and patients presenting with severe symptoms at diagnosis responded better to treatment. High serum carcinoembryonic antigen (CEA) levels and histological evidence of inflammation around sweat glands also correlated with a positive therapeutic response.

Conclusions

Earlier intervention, elevated serum CEA levels and inflammation around sweat glands are potential indicators of a successful response to pulse methylprednisolone therapy in patients with AIGA.
Pili annulati under the electron microscope: a case report and literature review
Authors: Chen Shengzhao , Yang Xiaoshuang , Lu Zhongfa
Published: August 2024

We report a 32-year-old woman whose hair has exhibited a distinctive pattern of black and white streaks under natural light. She underwent trichoscopic photography and scanning electron microscopy, leading to the identification of pili annulati. Trichoscopic photography revealed that the hair shafts were uniformly thick, with a pattern of alternating light and dark bands resembling beads. The scanning electron micrograph depicted a rough and cracked surface of the hair stem, with many grooves clearly visible. In addition, numerous air bubbles of varying sizes were observed within the hair cortex.
Cytomegalovirus complications in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: importance of routine monitoring and early therapeutic intervention
Authors: Takei Shingo , Hayashi Ryota , Hama Natsumi , Abe Riichiro
Published: August 2024

Fatal outcomes in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) are reported to be associated with cytomegalovirus (CMV) reactivation. However, CMV reactivation is observed not only in DIHS/DRESS but also in other diseases when high doses of corticosteroids are administered. Currently, it is difficult to distinguish whether CMV reactivation in DIHS/DRESS is caused by steroid-induced immunosuppression or the pathology of DIHS/DRESS. In this study, we describe the characteristic of CMV reactivation in patients with DIHS/DRESS (n = 22) by comparing the frequency of reactivation and its complications with those that occur in people with pemphigus vulgaris (PV) (n = 21) treated with high doses of corticosteroids. The frequency of CMV reactivation showed no difference between the DIHS/DRESS and PV groups. On the other hand, the frequency of CMV complications was higher in the DIHS than the PV group. Our data show the importance of monitoring for CMV complications, although CMV reactivation is not a unique consequence of DIHS/DRESS compared with other diseases treated with a high dose of corticosteroids.
Psychometric validity of the sum score of the Sniffin’ Sticks-Extended Test
Authors: Tolomeo Eva , Masala Carla , Aversa Antonio , Ottaviano Giancarlo , Gasperi Flavia , Menghi Leonardo , Parma Valentina , Liuzza Marco Tullio
Published: August 2024

A common tool to measure olfactory function is the Sniffin’ Sticks Test extended version (SSET). The SSET evaluates olfactory ability by summing the scores of three subtests: Threshold, Discrimination, and Identification. Recent meta-scientific literature revealed that many psychometric instruments currently in use have not been adequately validated, leading to a measurement crisis that raises concerns about the validity of the conclusions drawn with these instruments. Two examples of the measurement crisis are (i) the use of sum scores without testing their assumptions (e.g. unidimensionality and tau-equivalence), which indicate that all subtests have the same, stable relationship with their underlying construct, and (ii) the lack of assessment of measurement invariance across groups. Here, we aim to investigate the unidimensionality and tau-equivalence assumptions, internal consistency, and measurement invariance of sex and age groups of the SSET. We tested 988 (555 females, mean ± SD: 39.75 ± 18.60 years) participants with the Italian version of the SSET. The tau-equivalent model demonstrated excellent fit indices (CFI robust = 1, TLI robust = 1, RMSEA robust = 0, SRMR = 0.013), which best explain the data, indicating that all subtests are equally important in measuring olfactory function, but not necessarily equally precise. The results also revealed full measurement invariance across age groups and configural, partial metric, and scalar invariance across sexes, indicating that the use of latent means to compare sex groups should be chosen over raw scores. However, the SSET demonstrated moderate internal consistency. Future studies should clarify whether the reliability of the SSET can be increased.
Malondialdehyde-specific natural IgM inhibit NETosis triggered by culprit site–derived extracellular vesicles from myocardial infarction patients
Authors: Ondracek Anna S , Afonyushkin Taras , Aszlan Adrienne , Taqi Soreen , Koller Thomas , Artner Tyler , Porsch Florentina , Resch Ulrike , Sharma Smriti , Scherz Thomas , Spittler Andreas , Haertinger Maximilian , Hofbauer Thomas M , Ozsvar-Kozma Maria , Seidl Veronika , Beitzke Dietrich , Krueger Marcus , Testori Christoph , Lang Irene M , Binder Christoph J
Published: August 2024

Background and Aims

Neutrophil extracellular traps (NETs) trigger atherothrombosis during acute myocardial infarction (AMI), but mechanisms of induction remain unclear. Levels of extracellular vesicles (EV) carrying oxidation-specific epitopes (OSE), which are targeted by specific natural immunoglobulin M (IgM), are increased at the culprit site in AMI. This study investigated EV as inducers of NETosis and assessed the inhibitory effect of natural anti-OSE–IgM in this process.

Methods

Blood from the culprit and peripheral site of ST-segment elevation myocardial infarction (STEMI) patients (n = 28) was collected, and myocardial function assessed by cardiac magnetic resonance imaging (cMRI) 4 ± 2 days and 195 ± 15 days post-AMI. Extracellular vesicles were isolated from patient plasma and cell culture supernatants for neutrophil stimulation in vitro and in vivo, in the presence of a malondialdehyde (MDA)-specific IgM or an isotype control. NETosis and neutrophil functions were assessed via enzyme-linked immunosorbent assay and fluorescence microscopy. Pharmacological inhibitors were used to map signalling pathways. Neutrophil extracellular trap markers and anti-OSE–IgM were measured by ELISA.

Results

CD45+ MDA+ EV and NET markers were elevated at the culprit site. Extracellular vesicles induced neutrophil activation and NET formation via TLR4 and PAD4, and mice injected with EV showed increased NETosis. Malondialdehyde-specific IgM levels were inversely associated with citH3 in STEMI patient blood. An MDA-specific IgM inhibited EV-induced NET release in vitro and in vivo. CD45+ MDA+ EV concentrations inversely correlated with left ventricular ejection fraction post-AMI.

Conclusions

Culprit site–derived EV induce NETosis, while MDA-specific natural IgM inhibit this effect, potentially impacting outcome after AMI.
Comprehensive analyses of inhibition of the Chinese traditional food-packaging materials, Indocalamus latifolius leaves (Zongye) on Aspergillus flavus
Authors: Peng Wenjing , Ren Xiaoxu , Dai Haiting , Tai Bowen , Yang Bolei , Wang Gang , Li Xu , Xing Fuguo
Published: August 2024

Objectives

The contamination of Aspergillus flavus and aflatoxins (AFs) is one of the most serious safety problems in food and feed. The discovery and application of plant-sourced antifungal agents are hot topics in mycotoxin control. In this study, we aim to develop efficient strategies to control A. flavus and subsequent contamination by AFs.

Materials and Methods

We focused on Zongye essential oil, which was extracted from Indocalamus latifolius leaves (Zongye, the traditional food-packaging materials). Its antifungal and antitoxin activities were observed by volatile test, and the significant morphological and ultrastructural variations were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses. The main components of Zongye essential oil were analyzed by gas chromatography-mass spectrometry (GC-MS). RNA sequencing (RNA-Seq) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses were used to reveal the inhibitory mechanism.

Results

Among them, No. 2 Zongye essential oil completely inhibited the growth and toxin production of A. flavus after 10 µL treatment. Under Zongye essential oil treatment, evidently morphological and ultrastructural variations were observed, such as hyphae shrinkage, partial distortion, and a decrease in conidia number. Longifolene and linalool were the major constituents of Zongye essential oil, accounting for 9.55% and 7.95%, respectively, and linalool had stronger inhibitory effects on fungal growth and mycotoxin biosynthesis than longifolene. Based on the experimental results, the antifungal mechanism was proposed: down-regulations of membrane proteins (AFLA_005560, AFLA_019420, and AFLA_084310, etc.) and conidial genes (fblC, steA, and abaA, etc.) inhibited fungal development, and anti-aflatoxigenic activity might be due to significant down-regulation of AF cluster genes and global regulators (AtfA and AtfB).

Conclusion

A novel antifungal agent, Zongye essential oil, was identified, and its inhibitory mechanism was comprehensively clarified, which is helpful to control AF contamination in an environmentally friendly way.
Finding the missing men with tuberculosis: a participatory approach to identify priority interventions in Uganda
Authors: Nidoi Jasper , Pulford Justin , Wingfield Tom , Rachael Thomson , Ringwald Beate , Katagira Winceslaus , Muttamba Winters , Nattimba Milly , Namuli Zahra , Kirenga Bruce
Published: August 2024

Gender impacts exposure and vulnerability to tuberculosis (TB) evidenced by a higher prevalence of both TB disease and missed TB diagnoses among men, who significantly contribute to new TB infections. We present the formative research phase of a study, which used participatory methods to identify gender-specific interventions for systematic screening of TB among men in Uganda. Health facility-level data were collected at four Ugandan general hospitals (Kawolo, Gombe, Mityana and Nakaseke) among 70 TB stakeholders, including healthcare workers, TB survivors, policymakers and researchers. Using health-seeking pathways, they delineated and compared men’s ideal and actual step-by-step TB health-seeking processes to identify barriers to TB care. The stepping stones method, depicting barriers as a ‘river’ and each ‘steppingstone’ as a solution, was employed to identify interventions which would help link men with TB symptoms to care. These insights were then synthesized in a co-analysis meeting with 17 participants, including representatives from each health facility to develop a consensus on proposed interventions. Data across locations revealed the actual TB care pathway diverted from the ideal pathway due to health system, community, health worker and individual-level barriers such as delayed health seeking, unfavourable facility operating hours and long waiting times that conflicted with men’s work schedules. Stakeholders proposed to address these barriers through the introduction of male-specific services; integrated TB services that prioritize X-ray screening for men with cough; healthcare worker training modules on integrated male-friendly services; training and supporting TB champions to deliver health education to people seeking care; and engagement of private practitioners to screen for TB. In conclusion, our participatory co-design approach facilitated dialogue, learning and consensus between different health actors on context-specific, person-centred TB interventions for men in Uganda. The acceptability, effectiveness and cost effectiveness of the package will now be evaluated in a pilot study.
A telomere-to-telomere gap-free reference genome of Chionanthus retusus provides insights into the molecular mechanism underlying petal shape changes
Authors: Wang Jinnan , Xu Dong , Sang Ya Lin , Sun Maotong , Liu Cuishuang , Niu Muge , Li Ying , Liu Laishuo , Han Xiaojiao , Li Jihong
Published: August 2024

Chionanthus retusus, an arbor tree of the Oleaceae family, is an ecologically and economically valuable ornamental plant for its remarkable adaptability in landscaping. During C. retusus breeding, we observed diverse floral shapes; however, no available genome for C. retusus has hindered the widespread identification of genes related to flower morphology. Thus, a de novo telomere-to-telomere (T2T) gap-free genome was generated. The assembly, incorporating high-coverage and long-read sequencing data, successfully yielded two complete haplotypes (687 and 683 Mb). The genome encompasses 42 864 predicted protein-coding genes, with all 46 telomeres and 23 centromeres in one haplotype. Whole-genome duplication analysis revealed that C. retusus underwent one fewer event of whole-genome duplication after differentiation compared to other species in the Oleaceae family. Furthermore, flower vein diversity was the main reason for the differences in floral shapes. Auxin-related genes were responsible for petal shape formation on genome-based transcriptome analysis. Specifically, the removal and retention of the first intron in CrAUX/IAA20 resulted in the production of two transcripts, and the differences in the expression levels of CrAUX/IAA20 resulted in the variations of flower veins. Compared to transcripts lacking the first intron, transcripts with intron retention caused more severe decreases in the number and length of flower veins in transgenic Arabidopsis thaliana. Our findings will deepen our understanding of flower morphology development and provide important theoretical support for the cultivation of Oleaceae.
A career working on fish
Authors: Vøllestad Leif Asbjørn
Published: August 2024

The fishes are an extremely diverse and interesting group of vertebrates, and provide protein and joy to humans throughout the globe. When I was asked if I could write an essay about my career as a fish ecologist my first thought was: what is there to write about? After some thought I decided to give it a try. I describe how I ended up studying fish and the diversity of fish and topics that I have worked on during my career. My path has included a lot of stochastic events, and I did not have a long-term goal or plan. My road has been a long and winding one, requiring collaboration with people with diverse backgrounds and competences. Teaching and supervision have also been a large part of my career. Many students later became colleagues, and some have become friends. Society and the university have changed over time; I include some comments on university education at the end.
Human-provided food increases aggregation but does not change activity budgets in an urban wading bird
Authors: Wilson Cali A , Hernandez Sonia , Weil Julia N , Ezenwa Vanessa O , Altizer Sonia , Hall Richard J
Published: August 2024

In urban areas, animals often aggregate at higher densities, move less, and alter their diets to consume anthropogenic food, all of which can affect wildlife health and the transmission of infectious diseases. However, it is unknown whether short-term changes in behavior associated with urban resources scale up to more pervasive long-term behavioral changes across landscape types. In this study, we used observational field data to explore how food provisioning affects behaviors relevant to parasite transmission in American white ibis (Eudocimus albus), a waterbird that has recently habituated to urban habitats and anthropogenic food. We found that ibis flock densities more than doubled during short intervals when birds were actively provisioned with food. We then explored activity budgets among urban sites with different levels of provisioning, and found that foraging time decreased with flock size and provisioning levels. Lastly, we compared ibis behavior in more natural wetland sites against urban sites, and found minimal to no differences in behaviors measured here. These results suggest that urbanization and provisioning alter ibis behaviors in ways that could influence, e.g. exposure to parasites in the short-term, but this has not yet resulted in significant long-term changes in activity budgets. Further studies of how urbanization and intentional feeding influences wildlife behavior can inform management strategies to benefit both wildlife and human health.
The SAMI galaxy survey: on the importance of applying multiple selection criteria for finding Milky Way analogues
Authors: Tuntipong Sujeeporn , van de Sande Jesse , Croom Scott M , Barsanti Stefania , Bland-Hawthorn Joss , Brough Sarah , Bryant Julia J , Casura Sarah , Fraser-McKelvie Amelia , Lawrence Jon S , Ristea Andrei , Sweet Sarah M , Zafar Tayyaba
Published: August 2024

Milky Way analogues (MWAs) provide an alternative insight into the various pathways that lead to the formation of disc galaxies with similar properties to the Milky Way (MW). In this study, we explore different selection techniques for identifying MWAs in the Sydney-AAO (Australian Astronomical Observatory) Multi-object Integral field spectrograph (SAMI) Galaxy Survey. We utilize a nearest neighbours method to define MWAs using four selection parameters including stellar mass ($M_{\star }$), star formation rate ($\rm SFR$), bulge-to-total ratio ($B/T$), and disc effective radius ($R_{\rm {e}}$). Based on 15 different selection combinations, we find that including $M_{\star }$ and SFR is essential for minimizing biases in the average MWA properties as compared to the MW. Furthermore, given the MW’s smaller than average size, selection combinations without $R_{\rm {e}}$ result in MWAs being too large. Lastly, we find that $B/T$ is the least important parameter out of the four tested parameters. Using all four selection criteria, we define the top 10 most MW-like galaxies in the GAMA and Cluster regions of the SAMI survey. These most MW-like galaxies are typically barred spirals, with kinematically cold rotating discs and reside in a wide range of environments. Surprisingly, we find no significant differences between the MWAs selected from the GAMA and Cluster regions. Our work highlights the importance of using multiple selection criteria for finding MWAs and also demonstrates potential biases in previous MWA studies.
Exploring the relationship between genetic instability and health outcomes in acute and chronic post-COVID syndrome
Authors: Martins Bruna Alves Alonso , Garcia Ana Leticia Hilario , Borges Malu Siqueira , Picinini Juliana , Serpa Enaile Tuliczewski , Nobles Daiane Dias Ribeiro , Silva Luana Letícia , Dalberto Daiana , Hansen Alana Witt , Spilki Fernando Rosado , Schuler-Faccini Lavínia , Rampelotto Pabulo Henrique , Da Silva Juliana
Published: August 2024

The COVID-19 pandemic has led to the emergence of acute and chronic post-COVID syndromes, which present diverse clinical manifestations. The underlying pathophysiology of these conditions is not yet fully understood, but genetic instability has been proposed as a potential contributing factor. This study aimed to explore the differential impact of physical and psychological health factors on genetic instability in individuals with acute and chronic post-COVID syndromes. In this study, three groups of subjects were analyzed: a control group, an acute post-COVID group, and a chronic post-COVID group, with a total of 231 participants. The participants were assessed using a questionnaire for long-COVID-19COVID, and female participants reported more symptoms than male participants in areas related to fatigue, memory, mental health, and well-being during the chronic phase. Genetic instability was assessed using the comet assay, and participants’ physical and psychological profiles were evaluated. The overall results showed no significant differences in DNA damage, as measured by the comet assay, among the three groups, suggesting that genetic instability, as assessed by this method, may not be a primary driver of the distinct clinical presentations observed in post-COVID syndromes. However, when gender was considered, male participants in the acute long COVID group exhibited higher levels of genetic instability compared to females. Multiple linear regression analysis revealed that gender, age, and waist circumference were significant predictors of DNA damage. Among females in the acute group, sexual health, and eye-related symptoms significantly influenced the increase in DNA damage. These findings indicate the need for further investigation on the gender-specific differences in genetic instability and their potential implications for the pathophysiology of post-COVID syndromes. Exploring alternative markers of genetic instability and the interplay between genetic, inflammatory, and cellular processes could provide valuable insights for the management of these debilitating post-viral sequelae.
The dual interpretation of edge time series: Time-varying connectivity versus statistical interaction
Authors: Merritt Haily , Mejia Amanda , Betzel Richard
Published: August 2024

Functional connectivity (FC) is frequently operationalized as a correlation. Many studies have examined changes in correlation networks across time, claiming to link time-varying fluctuations to ongoing mental operations and physiological processes. Other studies, however, have called these results into question, noting that statistically indistinguishable patterns of time-varying fluctuations can be obtained by windowing synthetic time series generated from ground-truth stationary correlation structure. Recently, we developed a technique for tracking rapid (framewise) fluctuations in network connectivity over time. Here, we show that these "edge time series" are mathematically equivalent to interaction terms in a specific family of general linear models. We exploit this fact to further demonstrate that time-varying connectivity carries explanatory power above and beyond brain activations. This observation suggests that time-varying connectivity is likely more than a statistical artifact.
Validation of 3D cryoEM single particle reconstruction correctness and handedness with Ewald’s sphere correction
Authors: Bromberg Raquel , Guo Yirui , Borek Dominika , Otwinowski Zbyszek
Published: August 2024

The correct description of quantum scattering places the observed scattering contributions on the Ewald’s sphere and its Friedel mate. In electron microscopy, due to the large radius of the Ewald’s sphere, these contributions are typically merged during data analysis. We present an approach that separates and factorizes these contributions into inversion-symmetric and inversion-antisymmetric components. The correlations between reconstructions derived from these symmetric and antisymmetric components enable the automatic determination of handedness and provide additional validation for the quality of 3D reconstructions. These correlations are robust enough to be routinely used in single-particle reconstructions, even at resolutions below the limit where the curvature of the Ewald’s sphere affects the overall signal-to-noise ratio.

Synopsis

The implementation of Ewald’s sphere correction that separates the chirality-sensitive component provides handedness determination and validation of 3D reconstruction.
Identification of the sex determination region and the development of a marker to distinguish males and females in megai abalone (Haliotis gigantea)
Authors: Kina Taito , Hara Motoyuki , Hirase Shotaro , Kikuchi Kiyoshi
Published: August 2024

Sex identification markers are of considerable value to aquaculture and fisheries as they enable pre-maturity prediction of the genotypic sex of individuals as well as of the sex ratio in offspring. For these reasons, extensive investigations of the mechanisms of sex determination have been conducted in commercially important finfish species, resulting in the development of sex identification markers for many of these. However, research on shellfish is still in its infancy stage. In this study, we investigated the genomic basis of sex determination in megai abalone (Haliotis gigantea), a gastropod species of economic importance in fisheries and aquaculture in East Asia, with the aim of developing a sex identification marker. Initially, we examined the applicability of sex identification markers reported for two otherHaliotisspecies, but found they were not transferable toH. gigantea.We then analyzed the sex chromosomes inH. giganteausing a whole-genome resequencing approach. By calculating the fixation index value between 10 females and 10 males, we identified a genomic region spanning approximately 2 Mb that exhibited nucleotide sequence divergence between the sexes (from the position 260,372 bp to 1,930,278 bp in chromosome 18). This region was located next to the pseudoautosomal region which is characterized by an absence of sequence differentiation between the sexes. In the divergent region, male-specific SNPs were identified but no female-specific SNPs were detected, indicating that this species has an XX-XY sex determination system. By exploring Indel polymorphisms in the divergent region, we successfully developed a codominant PCR marker for sex identification that could be applied to wild individuals from geographically distant locations. A cross-species analysis suggested that the sex determination region inH. giganteawas unlikely to be shared with the closely related speciesH. discus hannai. This raises the possibility of a widespread, rapid turnover of sex chromosomes or sex determination regions in abalones, similar to certain vertebrate lineages such as finfish.
Posterior specification of multi-lineage axial assembloids from human pluripotent stem cells
Authors: Kee N , Leboeuf M , Gómez S , Petitpré C , Mei I , Benlefki S , Hagey D , Dias JM , Lallemend F , EL Andaloussi S , Ericson J , Hedlund E
Published: August 2024

Elongation of the posterior body axis is driven by multi-potent neuromesodermal progenitors (NMPs), which both self-renew and simultaneously generate neural tube, neural crest, and presomitc mesoderm lineages at successive anterior posterior (A-P) levels. The ensuing diversification of these three NMP lineages is remarkably extensive, and also essential for an immense range of clinically important adult posterior body tissues. Here, we describe a human pluripotent stem cell protocol that successfully specifies authentic NMPs using a cocktail of seven factors (7F). 7F-NMPs express requisite markers, exhibit co-linearHOXactivation, and can be purposely specified into each of the three NMP daughter lineages, demonstrating genuine multi-potency. 3D assembly of neural tube, neural crest, and presomitic mesoderm spheroids followed by long-term floating culture derives mature, multi-compartment Posterior Axial Assembloids, or PAXAs. PAXAs constitute a complex heterogeneous tissue containing spinal motor neurons and interneurons, central and peripheral glia, connective tissues, muscle satellite cells and contractile muscle fibres. Together, 7F-NMP and PAXA protocols establish a versatile in vitro platform to model mechanisms of human posterior body axis development, and for the study of a wide range of human diseases.