bluuebunny/crossref_metadata_2025 huggingface dataset:
P123 Identifying differences in sleep spindle activity in children with excessive daytime sleepiness
Authors: Shetty M , Plunkett G , Davey M , Nixon G , Walter L , Horne R
Published: December 2024

Background

Sleep spindles have been hypothesised to protect the sleeping brain from external stimuli and thus promote sleep. We aimed to identify differences in sleep spindle activity between children with narcolepsy, idiopathic hypersomnolence (IH) and subjectively sleepy children (with a normal multiple sleep latency test), and if there was any association between spindle activity with quality of life or severity of daytime sleepiness.

Methods

Spindles were manually identified from both C4 and F4 EEG signals during N2 and N3 sleep in 25 children with narcolepsy, 6 with IH and 21 with subjective sleepiness. Spindles were classified as Fast or Slow. Spindle activity was characterised as number, average duration (s), density (spindles/min) and intensity (density x average duration). Parents completed OSA-18 and ESS-CHAD questionnaires.

Results

Both F4 and C4 Slow and Slow&Fast spindle durations were longer in children with narcolepsy (p<0.001) and IH (p<0.05) compared to subjectively sleepy children. In the subjective sleepy children, all activity measures for all C4 spindles were negatively correlated with emotional symptoms and C4 Slow spindle density and intensity were negatively correlated with sleep disturbance on the OSA-18. Duration of C4 Fast spindles was positively correlated (p<0.05) with the ESS-CHAD score.

Conclusions

The increased duration of frontal and central spindles in children with narcolepsy and IH likely represents an attempt to stabilise sleep during NREM. Our preliminary finding of a relationship between reduced spindle activity and daytime symptoms requires further assessment with questionnaires tailored to children with excessive daytime sleepiness.
P124 Modifying overnight patient care to improve sleep: nurses’ perspectives on barriers and enablers to changing delivery of care
Authors: Tu L , Casey P , Considine J , Yang M , Balanathan S , McCarthy P , Trewella R , Young A
Published: December 2024

Background

Studies demonstrate sleep loss during hospitalisation is common, with patients averaging 5.7 hours of sleep per night. This is well short of the recommended 7 to 9 hours for optimal recovery. Preceding an intervention to improve sleep through modifying the physical environment and delivery of care, we first need to understand nurses’ perspectives on changing delivery of overnight care, to identify behaviour change techniques that will best support change in practice.

Methods

This exploratory, cross-sectional study will survey respiratory ward nurses (n=42) in a tertiary hospital. Nurses will be invited to complete a voluntary electronic survey, comprising participant characteristics (e.g., sex, age, years of experience) and 35 5-point Likert scale items informed by the Theoretical Domains Framework (TDF). Results, reported as descriptive statistics, will be mapped to domains of the TDF and the Behaviour Change Wheel to determine the behaviour change techniques that will enable implementation of the practice change.

Progress to date

The draft “Sleep in Hospital: A Survey of Nurses’ Perspectives” has been completed, incorporating nursing co-design and will undergo pilot-testing and finalisation during June. Following ethical approval, surveys will be distributed, data collected, and analysed prior to SDU 2024.

Intended outcome and impact

To our knowledge, this is the first Australian study to investigate enablers and barriers to implementing changes in nursing care to sleep in hospital. The results will inform our understanding of how to enable change in care delivery to improve patients’ sleep, with the potential to enhance patient experience and healthcare outcomes.
P125 Identification of potential fatigue risks associated with Marine Pilot Transfer operations
Authors: van den Berg M , Zaslona J , Wu L , Signal L
Published: December 2024

Introduction

Helicopter-based Marine Pilot Transfer operations involve transporting marine pilots to offshore vessels. These operations occur around the clock from remote locations. Helicopter crew work a ‘fly-in-fly-out’ schedule from their homebase usually located in a different time zone. This study monitored helicopter crew across ~21-day tours to identify potential fatigue risks.

Methods

Sleep was monitored with actigraphy and diaries. At the end of each shift, crew completed ratings of fatigue, sleepiness, and workload and a 5-minute PVT. Shifts were grouped by end times in 4x6-hourly bins. Linear mixed models investigated sleep and operational factors associated with fatigue, sleepiness, and performance at end of shifts.

Results

Data was collected from 15 helicopter crew across 21-day tours. Shifts ranged from 1.6-11 hours (n=220) with 1-14 sectors flown per shift. At the end of a shift, higher fatigue and sleepiness ratings were associated with less prior sleep (p<.05), longer shifts (p <.05), higher workload (p <.05), and end shift timing (p<.05). Fatigue and sleepiness were greater when shifts ended between 0001-0600, and for sleepiness also between 0601-1200. Higher workload was associated with slower response speed and slowest 10% of responses (p<.05). End of shift PVT performance was slower in the first week of the tour compared to later weeks.

Discussion

The key fatigue risks in this operation are associated with high workload and/or long periods of work at a less than ideal circadian phase. A multi-faceted approach, including on-going education, management of possible jetlag at the beginning of their tour, and monitoring of high-risk shifts is recommended.
P127 OSA-specific hypoxic burden predicts dampened autonomic function in children with Down syndrome
Authors: Walter L , Bhatnagar D , Ong M , Davey M , Nixon G , Horne R , Edwards B
Published: December 2024

Background

Hypoxic burden (HB) has been associated with cardiovascular disease in adults with obstructive sleep apnoea (OSA) but has not been assessed in typically developing (TD) children with sleep disordered breathing (SDB), nor children with Down syndrome (DS) who have a higher incidence of SDB with more severe hypoxia. We assessed whether HB in TD children and children with DS was related to heart rate variability (HRV) as an indicator of poor cardiovascular outcomes.

Methods

Children (3-19 y, n=44) with DS and TD children matched for SDB severity, age and sex underwent overnight polysomnography and were grouped into primary snoring (PS), Mild or Moderate/Severe (MS) OSA. HRV was analysed using power spectral analysis of the electrocardiograph.

Results

Children with MS OSA in both groups had higher HB compared with children with PS (p<0.001 for both) and Mild OSA (p<0.01 for both). Children with DS and PS or Mild OSA had higher HB compared with TD children (PS p<0.01; Mild OSA p<0.05). There was no difference between the groups for children with MS OSA. HB significantly predicted dampened sympathetic and parasympathetic activity (low frequency power) only in children with DS; R² 0.12, β -11.31, SE 2.75, p=0.02.

Conclusion

HB increased with increasing OSA severity, was higher in children with DS and PS or Mild OSA, and significantly predicted dampened autonomic function in children with DS. The potential contribution of the adverse effects of HB on autonomic function adds weight to the importance of identifying and treating SDB in children with DS.
P128 Don’t drop the F-bomb: Paramedic perceptions, attitudes, and behaviours surrounding fatigue
Authors: Wanstall S , Naweed A , Brown B , Crowther M , Rayner T , Adams R , Reynolds A
Published: December 2024

Introduction

Fatigue is prevalent among paramedics internationally, with negative effects on occupational performance and safety, individual well-being, and organisational service delivery. Thus, effective fatigue management is critical. This study aimed to understand paramedic perceptions, attitudes, and behaviours surrounding fatigue.

Methods

A qualitative methodology involving a semi-structured interview and scenario invention task was utilised to understand paramedic (n = 30) experiences of fatigue and explore related perceptions, attitudes, and behaviours. Data were inductively analysed utilising reflexive thematic analysis with a constructivist grounded theory approach.

Results

Eight organising themes were constructed under three global themes: (1) ‘Fatigue is a complex experience’, reflecting perceived complexity and multidimensionality of fatigue as a construct and experience; (2) ‘We have to look after ourselves’, reflecting attitudes about paramedic identities and relationships with organisations, and how these influence attitudes toward fatigue and fatigue management; and (3) ‘Working in the trenches’, reflecting how attitudes impact paramedics acting on fatigue, and coping strategies employed when working fatigued. Together, findings highlighted complex relationships between paramedics and their identities, job roles, and organisations, which influence effective and safe fatigue management.

Discussion

Paramedic perceptions, attitudes, and behaviours surrounding fatigue pose barriers to effective individual and organisational fatigue management. Understanding how paramedics perceive and interact with fatigue is a key factor in designing, implementing, and evaluating fatigue risk management strategies, including fatigue and relevant sleep health education and interventions. Addressing organisational culture, fatigue education, and fatigue risk management design could be considered for improving positive worker engagement with individual and organisational management strategies.
P133 Exploring the treatment journey of Obstructive Sleep Apnoea: A scoping review on the perspectives of Chinese Patients
Authors: Zhu X , Bin Y , Smith L , Cistulli P , Cheung J
Published: December 2024

Background

Globally, obstructive sleep apnoea (OSA) is a common sleep-related breathing disorder, thought to affect up to 23.6% of patients of Chinese ethnicity. However, little is known about the perspectives of the Chinese patient population and the key factors underpinning their health behaviours and treatment engagement. This scoping review aims to systematically synthesise the literature to understand Chinese patient perspectives towards OSA and its management.

Methods

A systematic search was conducted on 28 Jul 2023 across CINAHL, Embase, Medline, PsycINFO, and Scopus in Chinese and English for studies including the concepts: obstructive sleep apnoea, Chinese adult patients, treatments (CPAP, surgery, mandibular devices, pharmacotherapy, positional therapy, complementary therapies, lifestyle changes), and psycho-social-behavioural factors. Search results were screened and data extracted by 2 independent reviewers.

Results

From 679 results, 43 studies conducted in China, Hong Kong, Taiwan and Singapore were included in this review, comprising 15,358 adults (mean age: 48 years, 78% male). Evaluated outcomes included beliefs about OSA, treatment preferences, acceptance, satisfaction, and adherence. Considerable heterogeneity was observed in the measurement of treatment acceptance and satisfaction, coupled with insufficient reporting of factors influencing treatment preference. Notable limitations included the under-representation of older women and migrant Chinese populations and the limited coverage of health beliefs and health behavioural change.

Discussion

Factors influencing patient engagement with OSA treatments are multifactorial. Patients’ health beliefs and sociocultural factors play important role in treatment acceptance and adherence. Future research should focus on patient-centered approaches to identify strategies to promote behavioral change and provide culturally sensitive care.
CryptKeeper: a negative design tool for reducing unintentional gene expression in bacteria
Authors: Roots Cameron T , Barrick Jeffrey E
Published: December 2024

Foundational techniques in molecular biology—such as cloning genes, tagging biomolecules for purification or identification, and overexpressing recombinant proteins—rely on introducing non-native or synthetic DNA sequences into organisms. These sequences may be recognized by the transcription and translation machinery in their new context in unintended ways. The cryptic gene expression that sometimes results has been shown to produce genetic instability and mask experimental signals. Computational tools have been developed to predict individual types of gene expression elements, but it can be difficult for researchers to contextualize their collective output. Here, we introduce CryptKeeper, a software pipeline that visualizes predictions of Escherichia coli gene expression signals and estimates the translational burden possible from a DNA sequence. We investigate several published examples where cryptic gene expression in E. coli interfered with experiments. CryptKeeper accurately postdicts unwanted gene expression from both eukaryotic virus infectious clones and individual proteins that led to genetic instability. It also identifies off-target gene expression elements that resulted in truncations that confounded protein purification. Incorporating negative design using CryptKeeper into reverse genetics and synthetic biology workflows can help to mitigate cloning challenges and avoid unexplained failures and complications that arise from unintentional gene expression.
Discretionary powers and ostensible discretionary trusts
Authors: Lupoi Maurizio
Published: December 2024

A relationship of confidence was at the heart of trusts embodying discretionary powers until the end of the XIX century. Modern discretionary trusts are centred on powers of appointment in respect of beneficiaries who are only discretionary objects. Modern discretionary trusts are dubbed “ostensible” discretionary trusts when the discretion held by the trustee is severely curtailed by settlors, who often double as trustees. The pre-eminence of settlors of ostensible discretionary trusts is such that there is no relationship of confidence between them and their trustees. Ostensible discretionary trusts are invalid because all the basic characters of trusts fail.
Efficacy of avilamycin on the incidence and severity of diarrhea associated with pathogenic Escherichia coli and the subsequent growth performance of nursery pigs
Authors: Weiland Sarah A , Chang Petra L , Puls Chris L , Evelsizer Robert W , Carr Scott N , Frederick Brent , Ebarb Sara , Ritter Matt J
Published: December 2024

A total of 3,329 commercial crossbred barrows and gilts were used to compare the efficacy of avilamycin on incidence and severity of diarrhea and growth performance of pigs naturally infected with Escherichia coli. An incomplete block design was used with a 2 × 4 factorial arrangement of treatments: 1) Stocking density (Single: 0.67 sq. m/pig vs. Double: 0.33 sq. m/pig) and 2) Nursery medication program [Nonmedicated control fed for 56 d (CON) vs. 80.5 mg/kg avilamycin fed for 21 d (AVI21) vs. 80.5 mg/kg avilamycin fed for 42 d (AVI42) vs. 55.1 mg/kg carbadox fed for 21 d (CAR21)]. Subjective diarrhea scores were collected weekly on each pen according to a 3-point scale. Pigs were weighed on days 0, 21, 42, and 56 of the study. Pigs had ad libitum access to feed and water throughout the study. Diets were formulated to meet or exceed NRC (2012) recommendations. Fecal swabs from pigs were collected and confirmed the presence of hemolytic E. coli within the first two weeks of study. During the first 21 d, feeding AVI21 and AVI42 lowered (P < 0.05) diarrhea severity compared to controls, with CAR21 being intermediate. In the second 21 d, feeding AVI42 lowered (P < 0.05) diarrhea incidence and severity compared to the other treatments. In general, feeding medication resulted in lower maximum diarrhea scores compared to nonmedicated controls. For the overall study period (day 0 to 56), there were no (P > 0.05) stocking density × nursery medication program interactions for growth performance measures. A significant interaction (P < 0.05) was observed for day 0 to 42; feed conversion did not differ between double and single stocking density treatments for AVI42, whereas for CON, AVI21, and CAR21, feed conversion was lower in the single stocking density treatment. For the overall study period, there was no effect (P > 0.05) of nursery medication program on final BW, ADG, ADFI, or incidence of morbidity and mortality. Overall G:F was improved (P < 0.05) for pigs fed avilamycin compared to carbadox, with controls being intermediate. Double stocking resulted in lower overall ADFI (P < 0.05) and improved G:F (P < 0.05) compared to single stocking, but increased overall morbidity and mortality and diarrhea severity, incidence, and overall scores (P < 0.05). The results of this study demonstrate relatively similar performance with improved feed conversion and improvements in diarrhea incidence and severity for pigs fed avilamycin compared to carbadox.
Enhancing adapted physical activity training for community organizations: co-construction and evaluation of training modules
Authors: Saadawi Nour , Best Krista L , Pastore Olivia L , Périnet-Lacroix Roxanne , Tomasone Jennifer R , Légaré Mario , de Serres-Lafontaine Annabelle , Sweet Shane N
Published: December 2024

Community-based physical activity programmes benefit persons with disabilities. However, there is a lack of evidence-based tools to support kinesiologists’ training in such programmes. This study aimed to co-create and evaluate physical activity training modules for community-based adapted physical activity (APA) programmes. In Phase 1, a working group (n = 8) consisting of staff, kinesiologists from two community-based APA programmes, and researchers met over four online meetings to discuss needs, co-create training modules, and assess usability. In Phase 2, a pre–post quasi-experimental design evaluated changes in capability, opportunity, and motivation of kinesiologists (n = 14) after completing the training modules, which included standardized mock client assessments and participant ratings of module feasibility. Means and standard deviations were computed for feasibility, followed by paired-samples t-tests, along with Hedge’s correction effect size. Mock client sessions underwent coding and reliability assessment. The working group meetings generated two main themes: training in (i) motivational interviewing and behaviour change techniques and (ii) optimizing APA prescription. Nine online training modules were created. In Phase 2, medium to large effects of training modules were observed in capability (Hedge’s g = 0.67–1.19) for 8/9 modules, opportunity (Hedge’s g = 0.77–1.38) for 9/9 modules, and motivation (Hedge’s g = 0.58–1.03) for 6/9 modules. In mock client assessments, over 78% of participants appropriately used five behaviour change techniques and, on average, participants demonstrated good use of motivational interviewing strategies.

The findings indicate that training kinesiologists was feasible and has the potential to enhance community-based physical activity programmes for persons with disabilities.
Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as mortality predictors in acute Aluminum phosphide (grain pills) poisoning: clinical insights and risk assessment
Authors: Sharif Asmaa F , Mabrouk Heba A , Abdo Sanaa A , Elwy Abdelhamid Mohamed , Fayed Manar M
Published: December 2024

Background

Aluminum phosphides (AlP) is a solid fumigant pesticide known for its high toxicity and mortality. Diagnosis of AlP is based on the history and clinical examination. The literature on the early prediction of adverse outcomes following AlP exposure is limited. Therefore, the current study aimed to investigate the role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte Ratio (PLR) as early accessible predictors of mortality in AlP-exposed patients.

Method

We conducted a retrospective cross-sectional study on 420 adult patients with acute AlP poisoning.

Results

This study reported mean NLR and PLR of 4.07 ± 3.82 and 182.97 ± 147.29, respectively. Patients with high NLR and PLR showed more severe presentation, indicated by the significantly lower Glasgow scales and higher poison severity score grades. Besides, the need for mechanical ventilation, vasopressor therapy, and ICU admission was significantly higher among patients with high NLR and PLR (P = 0.000). We observed a significantly higher proportion of mortality among patients with high NLR (69.5%) and PLR (87.4%) (P = 0.000). The NLR > 3.42, PLR > 172.5, and their combinations were significant predictors of mortality, showing area under curves above 0.94. Utilizing a combination of NLR and PLR yielded a modestly improved performance as a mortality predictor with a slight increase in the Youden index (0.81). The high NLR and high PLR groups had mean survival times of 28.851 and 16.256 h respectively.

Conclusion

These findings suggest that high NLR and PLR are associated with a worse prognosis and a higher mortality risk among patients with acute AlP poisoning.
Do Public Works Programs Have Sustained Impacts? A Review of Experimental Studies from LMICs
Authors: Bagga Aanchal , Holmlund Marcus , Khan Nausheen , Mani Subha , Mvukiyehe Eric , Premand Patrick
Published: December 2024

Many low- and middle-income countries (LMICs) have introduced public works programs that offer temporary cash-for-work opportunities to poor individuals. We review experimental evidence on the impacts of public works programs on participants over the short and medium run, providing new insights on whether they have sustained impacts. Our findings show that public works mainly increase employment and earnings during the program. Short-term positive effects tend to fade in the medium run, except in a few cases in which large impacts on savings or investments in self-employment activities are also observed. We find evidence of improvements in psychological well-being and women's empowerment in some cases, but not systematically, and with limitations in measurement. In some contexts, public works programs also improve market wages, affecting both participants and non-participants. We conclude by outlining directions for future research.
Molecular profiling unveils pyroptosis markers in preterm birth
Authors: Li Xiaoyun , Huang Zhulan , Bai Jiangtao , Che Aiwen , Zhou Jinhua , Yang Hongmei
Published: December 2024

Through a comprehensive examination of pyroptosis‐related differential expressed genes (PRDEGs), this work investigates the molecular complexities of spontaneous preterm birth (SPTB), also known as premature delivery, before the due date. Through the process of merging and correcting batch effects in the GSE120480 and GSE73714 datasets, we were able to identify 36 PRDEGs that exhibited significant expression differentiation in SPTB. Through functional enrichment and pathway analysis, their importance in amino acid transport and cytokine receptor interaction has been highlighted. Among the genes that have emerged as crucial, CEBPA, APOA1, and CEP55 have been identified. The relevance of these molecules was demonstrated using experimental knockdowns, which also suggested that they could be used as molecular biomarkers and therapeutic targets for SPTB.
Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization
Authors: Ewa Theressa , Panchwagh Neel , Tai Chin‐Hsien , Avula Leela Rani , Joseph Sarah , Rudloff Michael W. , Malik Nargis , Zhang Xianyu , Alewine Christine
Published: December 2024

Peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Peritoneal colonization is impaired in PDAC cells with knockout (KO) of the cancer surface antigen mesothelin (MSLN) or by introducing Y318A mutation in MSLN to prevent binding to mucin‐16 (MUC‐16). MSLN has a membrane‐bound form but is also shed to release soluble MSLN (sMSLN). Their individual roles in peritoneal metastasis are unknown. Here, a C‐terminal truncated MSLN mutant (∆591) incapable of cell membrane insertion but proficient in secretion was engineered. Expression of ∆591 MSLN failed to rescue peritoneal metastasis in MSLN KO cells and inhibited peritoneal colonization when overexpressed in WT PDAC cells. Exposing PDAC cells to conditioned medium (CM) containing excess sMSLN impaired cancer cell clustering in vitro and in peritoneal fluid in vivo, while CM containing only Y318A sMSLN did not. These data demonstrate that interaction of membrane‐bound MSLN with MUC‐16 promotes cell clustering that is critical for efficient peritoneal metastasis. However, peritoneal colonization by MSLN KO cells was rescued by expression of ∆591 mutant MSLN bearing Y318A mutation, suggesting that sMSLN also has a MUC‐16‐independent role in peritoneal spread. Alterations in inflammatory signaling pathways occurred following KO cell exposure to CM containing sMSLN, and CM from cancer cells with intact peritoneal metastasis provoked increased KO cell secretion of IL‐1α. While excess sMSLN inhibits cell clustering and peritoneal colonization, sMSLN may also promote PDAC peritoneal metastasis independent of MUC‐16.
Role of LIPIN 1 in regulating metabolic homeostasis in the retinal pigment epithelium
Authors: Usoltseva Anna S. , Litwin Christopher , Lee Michael , Hill Colton , Cai Jiyang , Chen Yan
Published: December 2024

Dysregulated lipid metabolism, characterized by the accumulation of lipid deposits on Bruch's membrane and in drusen, is considered a key pathogenic event in age‐related macular degeneration (AMD). The imbalance of lipid production, usage, and transport in local tissues, particularly in the retinal pigment epithelium (RPE), is increasingly recognized as crucial in AMD development. However, the molecular mechanisms governing lipid metabolism in the RPE remain elusive. LIPIN1, a multifunctional protein acting as both a modulator of transcription factors and a phosphatidate phosphatase (PAP1), is known to play important regulatory roles in lipid metabolism and related biological functions, such as inflammatory responses. While deficits in LIPIN1 have been linked to multiple diseases, its specific roles in the retina and RPE remain unclear. In this study, we investigated LIPIN1 in RPE integrity and function using a tissue‐specific knockout animal model. The clinical and histological examinations revealed age‐dependent degeneration in the RPE and the retina, along with impaired lipid metabolism. Bulk RNA sequencing indicated a disturbance in lipid metabolic pathways. Moreover, these animals exhibited inflammatory markers reminiscent of human AMD features, including deposition of IgG and C3d on Bruch's membrane. Collectively, our findings indicate that LIPIN1 is a critical component of the complex regulatory network of lipid homeostasis in the RPE. Disruption of LIPIN1‐mediated regulation impaired lipid balance and contributed to AMD‐related pathogenic changes.
Disulfidoptosis‐related molecular subtypes and prognostic model for optimizing drug therapy in metastatic osteosarcoma patients
Authors: Wang Xiaoping , Xie Chao , Lin Lijun
Published: December 2024

Disulfidotosis is a newly identified form of cell death associated with tumor response, patient outcomes, and cancer progression. This study aims to identify disulfidptosis‐related genes (DiRGs) and their role in osteosarcoma (OS) to predict prognosis and optimize drug therapy for better patient survival. Gene expression matrices and clinical information on OS were obtained from the TARGET and GEO databases. Unsupervised clustering analysis identified two DiRG molecular subgroups with significantly different intratumoral heterogeneity and tumor microenvironment cell infiltrating characteristics in OS. A robust disulfidptosis‐related prognostic model using five DiRGs was developed, demonstrating excellent predictive and prognostic power in OS with AUC values of 0.69, 0.78, and 0.85 for 1‐, 3‐, and 5‐year periods, respectively. Investigations into the impact of disulfidoptosis on immune status in OS patients across different risk subgroups revealed that a low immune score and compromised immune status were associated with an unfavorable prognosis for OS patients. INF2 and MEGF10 genes are highly reliable predictors of metastasis among the hub DiRG genes. The validation results indicate a robust correlation between the expression of INF2 and MEGF10 and the severity of malignancy and metastasis in OS. Six drugs targeting osteosarcoma metastasis were identified, with INF2‐BP‐1‐102 and MEGF10‐AS703569 showing the best docking scores, indicating their potential to treat OS metastasis effectively. These findings provide valuable insight into improving treatment for OS patients.
Exploring Burnout and Leadership Mitigation Plans in Academic Nursing Environments
Authors: Saylor Jennifer , Evans Jennifer , Goodolf Dawn , Martin Nia M. , Martinez-Hollingsworth Adrienne
Published: December 2024

Background:

Staff burnout in higher education may affect nursing department functionality. There is limited literature regarding staff burnout and its manifestations in nursing colleges and schools.

Purpose:

This study evaluated academic nurse leaders’ perceptions of burnout and mitigation strategies in colleges and schools of nursing.

Methods:

A descriptive, cross-sectional survey examined burnout and mitigation strategies among associate deans, business officers, and members of the Organizational Leadership Network (n = 105).

Results:

Among academic leaders, 57.14% noted that staff burnout was either a notable or a major challenge. Resignations (56.86%) and difficulties in backfilling staff positions (54.90%) were the 2 most common manifestations of staff burnout. However, only a small percentage had an active burnout mitigation strategy for faculty (13.33%) and staff (6.67%).

Conclusion:

There is a disconnect between acknowledging burnout as a pressing concern and implementing effective mitigation strategies. By creating a supportive work environment and encouraging professional development, leaders can significantly reduce burnout and enhance overall employee well-being.
Undergraduate Nursing Students’ Perceptions of Geriatric Care and Nursing Curriculum
Authors: Consolo Victoria , Clark Stephanie B. , Lippe Megan P.
Published: December 2024

Background:

The geriatric population in the United States is growing rapidly with an expected increase of 22% by 2040. Nursing students, however, consistently report negative attitudes toward caring for geriatric patients.

Purpose:

The purpose was to assess undergraduate nursing student perceptions of care for the geriatric population, how their nursing curriculum influenced these perceptions, and any perceived curricular changes, didactic or clinical, that could potentially improve students’ preparedness and desire to seek a career in geriatric nursing.

Methods:

Using a convergent parallel mixed methods approach, senior prelicensure nursing students completed a Likert-scale survey with additional open-ended questions to assess perceptions of geriatric care and how the current nursing curriculum relates to those perceptions.

Results:

Quantitative data identified that most students believed the didactic curriculum prepared them for geriatric care but did not increase their desire to work with geriatric patients. Qualitative data identified negative stereotypes and clinical experiences and revealed a lack of desire for geriatric care.

Conclusions:

Lack of desire for geriatric care was the norm for participants. Geriatric care should be more heavily weighted in academics, and educators should develop innovative methods that increase the desire of prelicensure students to commit to care for the geriatric population.
Mpox vaccine communication among sexually active men who have sex with men
Authors: Abara Winston E. , Carpino Tom , Atkins Kaitlyn , Hannah Marissa , Edwards O. Winslow , Renfro Kaytlin J. , Baral Stefan , Sanchez Travis , Learner Emily R. , Galloway Eboni , Lansky Amy
Published: December 2024

We assessed mpox vaccine communication and sexual behavior among U.S. MSM during the 2022 mpox outbreak. Less than 40% of respondents asked a new male sex partner about their mpox vaccination status. Mpox vaccine communication was positively associated with condomless anal sex and group sex. Mpox vaccine communication is low but may inform and sexual behaviors among MSM.
E. colitranscription factors regulate promoter activity by a universal, homeostatic mechanism
Authors: Parisutham Vinuselvi , Guharajan Sunil , Lian Melina , Rogers Hannah , Joyce Shannon , Noto Guillen Mariana , Brewster Robert C.
Published: December 2024

Transcription factors (TFs) may activate or repress gene expression through an interplay of different mechanisms, including RNA polymerase (RNAP) recruitment, exclusion, and initiation. TFs often have drastically different regulatory behaviors depending on promoter context and interacting cofactors. However, the detailed mechanisms by which each TF affects transcription and produce promoter-dependent regulation is unclear. Here, we discover that a simple model explains the regulatory effects ofE. coliTFs in a range of contexts. Specifically, we measure the relationship between basal promoter activity and its regulation by diverse TFs and find that the contextual changes in TF function are determined entirely by the basal strength of the regulated promoter: TFs exert lower fold-change on stronger promoters under a precise inverse scaling. Remarkably, this scaling relationship holds for both activators and repressors, indicating a universal mechanism of gene regulation. Our data, which spans between 100-fold activation to 1000-fold repression, is consistent with a model of regulation driven by stabilization of RNAP at the promoter for every TF. Crucially, this indicates that TFs naturally act to maintain homeostatic expression levels across genetic or environmental perturbations, ensuring robust expression of regulated genes.
Hi-C Calibration by Chemically Induced Chromosomal Interactions
Authors: Li Yi , Zou Fan , Bai Lu
Published: December 2024

The genome-wide chromosome conformation capture method, Hi-C, has greatly advanced our understanding of genome organization. However, its quantitative properties, including sensitivity, bias, and linearity, remain challenging to assess. Measuring these propertiesin vivois difficult due to the heterogenous and dynamic nature of chromosomal interactions. Here, using Chemically Induced Chromosomal Interaction (CICI) method, we create stable intra- and inter-chromosomal interactions in G1-phase budding yeast across a broad range of contact frequencies. Hi-C analysis of these engineered cell populations demonstrates that static intra-chromosomal loops do not generate Topologically Associated Domains (TADs) and only promote 3D proximity within ∼50kb flanking regions. At moderate sequencing depth, Hi-C is sensitive enough to detect interactions occurring in 5-10% of cells. It also shows no inherent bias toward intra-versus inter-chromosomal interactions. Furthermore, we observe a linear relationship between Hi-C signal intensity and contact frequency. These findings illuminate the intrinsic properties of the Hi-C assay and provide a robust framework for its calibration.
The sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway
Authors: Zhuang Wenwen , Park Minju , Jeong Junsu , Kim Hye Ryung , Jang YeEun , Seo Mi Seon , An Jin Ryeol , Park Hongzoo , Jung Won-Kyo , Choi Il-Whan , Park Won Sun
Published: December 2024

OBJECTIVE

Tofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor widely used to treat T2DM, but it also exhibits cardio-protective effects. This study investigated the vasodilatory action of tofogliflozin using rabbit femoral artery rings pre-contracted with phenylephrine.

APPROACH AND RESULTS

The femoral artery quickly separated from the rabbit and fix it to the organ bath chamber. Subsequently, administer an inhibitor that modulates vascular tension in the rings or remove the endothelium to assess its impact on vasodilation. The results showed the concentration-dependent induction of vasodilation by tofogliflozin, a response that remained unchanged following endothelial removal, pretreatment with the nitric oxide synthase (NOS) inhibitor L-NAME, or the inhibition of low- and intermediate-conductance Ca2+-activated K+channels (SKCaand IKCa) using apamin in combination with TRAM-34. Furthermore, pretreatment with the voltage-dependent K+(Kv) channel inhibitor 4-AP reduced the vasodilatory effects of tofogliflozin whereas pretreatment with the ATP-sensitive K+(KATP) channel inhibitor glibenclamide or the large-conductance Ca2+-activated K+(BKCa) channel inhibitor paxilline did not. Notably, our findings indicated that Kv7.X, rather than Kv1.5 or Kv2.1, is the primary Kv subtype involved in tofogliflozin-induced vasodilation. The vasodilatory effects of tofogliflozin were also significantly inhibited in femoral arterial rings pretreated with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin and cyclopiazonic acid (CPA). Tofogliflozin-induced vasodilation was unaltered in arterial rings exposed to the adenylyl cyclase inhibitor SQ 22536, the protein kinase A (PKA) inhibitor KT 5720, and the protein kinase G (PKG) inhibitor KT 582 whereas it was effectively reduced by the soluble guanylyl cyclase (sGC) inhibitor ODQ.

CONCLUSIONS

These findings suggest that tofogliflozin-induced vasodilation is mediated by the activation of the SERCA pump, the sGC/cGMP pathway, and Kv channels, but not the PKA signaling pathway, other K+channels, or endothelium-dependent mechanisms.
Systematic design of multiplex methylation-specific qPCR for cancer related biomarkers
Authors: Wang Joy , Lee Michelle Yiru , Lin Brian Boyuan , Wu Annie X.
Published: December 2024

Analysis of circulating cell-free DNA (cfDNA) methylation abnormalities has emerged as a powerful strategy for detecting various diseases, particularly cancers. This study demonstrates a process for developing a multiplex methylation-specific qPCR assay for cancer biomarker detection.

Analysis of circulating cell-free DNA (cfDNA) methylation abnormalities has emerged as a promising strategy for detecting various diseases, including cancer. While single-biomarker approaches may lack sensitivity, comprehensive next-generation sequencing (NGS) can be cumbersome and expensive. Multiplex methylation qPCR assays offer a practical intermediate solution by providing accurate, accessible, and affordable methylation biomarker detection. In this study, we demonstrated a process for developing a multiplex methylation-specific qPCR assay using colorectal cancer (CRC) methylation biomarkers as a case study. Starting with a set of CRC methylation biomarkers, we developed the Multiplex Methylation-specific qPCR (MMqPCR) algorithm to scan differentially methylated regions (DMRs) for methylation-specific PCR primer and probe design. We then established a systematic process to eliminate assay cross-reactions, reduce background noise, and assess multiplex compatibility. Using a low concentration of hypermethylated DNA (0.1%) in a digital analysis, we demonstrated a 95.8% detection rate with the multiplex strategy, significantly outperforming the singleplex approach (47.9%). The multiplex qPCR development principles and automated primer design algorithm presented here provide valuable tools for developing disease screening, detection or monitoring methods based on methylation analysis.
Unveiling the evolutionary history of European vipers and their venoms from a multi-omic approach
Authors: Talavera Adrián , Palmada-Flores Marc , Martínez-Freiría Fernando , Mochales-Riaño Gabriel , Burriel-Carranza Bernat , Estarellas Maria , Fernández-Guiberteau Daniel , Camina Álvaro , Ursenbacher Sylvain , Vörös Judit , Halpern Bálint , Pla Davinia , Calvete Juan José , Mikheyev Alexander S. , Marquès-Bonet Tomàs , Carranza Salvador
Published: December 2024

Snake genomes attract significant attention from multiple disciplines, including medicine, drug bioprospection, and evolutionary biology, due to the unique features found in snakes, especially, the evolution of venom. However, genomic research within the family Viperidae has mostly focused to date on the subfamily Crotalinae, while overlooking Viperinae, the Old World vipers. Among Viperinae, European vipers (Vipera) have been the subject of extensive research because of their venoms, phylogeographic, and ecological diversification. Nevertheless, venom research in this group has been conducted using mostly proteomes alone, while phylogeography and systematics in the genus have relied on biased information from mitochondrial phylogenies. Here, we generated chromosome-level genome assemblies for threeViperaspecies and whole-genome sequencing data for 94 samples representing 15Viperataxa. This comprehensive dataset has enabled us to disentangle the phylogenomic relationships of this genus, affected by mito-nuclear discordance and pervaded by ancestral introgression. Population-level analyses in the Iberian Peninsula, where the three oldest lineages withinViperameet, revealed signals of recent adaptive introgression between ecologically dissimilar species, whereas chromosomal rearrangements isolate species occupying similar niches. Finally, using transcriptomic and proteomic data, we characterized theViperatoxin-encoding genes, in which opposing selective forces were unveiled as common drivers of the evolution of venom as an integrated phenotype.
A role for fibroblast and mural cell subsets in models of neuropathic pain
Authors: Villa-Hernandez Sara , Walker Julia Vlachaki , Hore Zoe , Fedele Laura , Zebochin Irene , Li Yuening , Davis Harvey , Kanda Takashi , Shimizu Fumitaka , Taams Leonie , Denk Franziska
Published: December 2024

Neuropathic pain is a particularly intractable type of chronic pain that can result from physical nerve damage due to surgery or entrapment. Here, we present data which suggest that a particular subclass of fibroblast and mural cells may be implicated in the sensory neuron dysfunction that is characteristic of this pain state.

In a mouse model of traumatic painful neuropathy, we used RNA sequencing, cell sorting and nerve tissue clearing to study mesenchymal lineage cells. We show that Pdgfrb+ fibroblasts and mural cells are increased in number for at least two months post-nerve damage and express high levels of known and putative pro-algesic mediators, which are further upregulated in neuropathy.

We go on to demonstrate that a human nerve pericyte line releases a selection of these pro-algesic mediators at protein level. Moreover, conditioned media from stimulated human pericytes induces intra-cellular changes in human induced pluripotent stem cell derived sensory neurons; these changes (phosphorylation of the transcription factor STAT3) have been previously linked to sensory neuron activation.

In summary, our data indicate that mesenchymal cell abnormalities should be considered when developing novel strategies to tackle neuropathic pain.
The mammalian protein MTCH1 can function as an insertase
Authors: Dimogkioka Anna Roza , Elias Anni , Rapaport Doron
Published: December 2024

The outer mitochondrial membrane (OMM) hosts a variety of proteins such as import machineries, enzymes, fission/fusion factors, and pore proteins. InSaccharomyces cerevisiae, the MIM complex, consisting of Mim1 and Mim2, mediates the insertion of α-helical proteins into the OMM. Until recently, it was unclear which proteins serve this function in higher eukaryotes. Recent studies identified MTCH2 as the insertase of α-helical proteins into the OMM in mammals. MTCH1 is a paralogue of MTCH2 but its general function and contribution to the biogenesis process are not clear. To better characterize MTCH1, we explored whether MTCH1 or MTCH2 could functionally replace Mim1/Mim2 in yeast. Expression of MTCH1 and MTCH2 in yeast cells lacking Mim1, Mim2, or both revealed that MTCH1, but not MTCH2, could compensate the growth defects upon deleting the MIM complex. Furthermore, MTCH1 could restore the biogenesis of MIM substrates, TOM complex stability, and morphology of mitochondria. These findings indicate that MTCH1 by itself has insertase activity and is a functional homologue of the MIM complex, despite the absence of any evolutionary relation between the mammalian and yeast insertases.
Further varieties of ancient endogenous retrovirus in human DNA
Authors: Frith Martin C.
Published: December 2024

A retrovirus inserts its genome into the DNA of a cell, occasionally a germ-line cell that gives rise to descendants of the host organism: it is then called an endogenous retrovirus (ERV). The human genome contains relics from many kinds of ancient ERV. Some relics contributed new genes and regulatory elements.

This study finds further kinds of ancient ERV, in the thoroughly-studied human genome version hg38: ERV-Hako, ERV-Saru, ERV-Hou, ERV-Han, and ERV-Goku. It also finds many relics of ERV-V, previously known from just two copies on chromosome 19 with placental genes. It finds a type of ERV flanked by MER41E long terminal repeats (LTRs), with surprisingly little similarity to the known MER41 ERV. ERV-Hako has subtypes that contain sequence from host genesSUSD6andSPHKAP: theSUSD6variant was transferred between catarrhine and platyrrhine primates. A retrovirus uses tRNA to prime reverse transcription: Hako is the only human ERV relic that used tRNA-Trp (tryptophan, symbol W), and HERV-W is misnamed because it used tRNA-Arg, based on the Genomic tRNA Database. One ERV-Saru LTR is the previously-described enhancer ofAIM2in innate immunity. This study contributes to understanding primate ERV history, but also shows that related ERVs can have drastic differences, challenging the goal of clearly annotating all ERV relics in genomes.