bluuebunny/crossref_metadata_2025 huggingface dataset:
O016 Characterizing K-Complexes in PTSD Patients
Authors: Coussens S , Chatburn A , Malagutti N , Denson T
Published: December 2024

Introduction

K-complexes play a crucial role in sleep maintenance. Disturbances in these processes are linked to sleep disorders such as insomnia. Post-traumatic stress disorder (PTSD) features substantial disruption of sleep patterns. This study aims to retrospectively analyze sleep studies of PTSD patients to identify changes in the amplitude of K-complexes which help understanding PTSD-related sleep disruption.

Methods

150 sleep recordings of individuals diagnosed with PTSD from the BigSleep data repository will be examined. These recordings will be compared to those of 150 age- and sex-matched controls from the same source. By measuring the characteristics of K-complexes in both clinical and healthy populations, we hope to uncover distinctive patterns associated with PTSD-related sleep disturbances.

Results

Preliminary analysis of a small subset of data suggests a reduced amplitude of K-complexes in PTSD patients. This finding may suggest impaired stimulus gating during sleep, which may contribute to disrupted sleep in PTSD. If these results are corroborated in the larger dataset, it could provide valuable insights into neural mechanisms underlying sleep disturbances in PTSD.

Conclusion

By identifying specific EEG markers, such as altered K-complex characteristics, we may be better able to understand the neurobiological underpinnings of sleep disturbances associated with PTSD. Our ongoing analysis seeks to confirm preliminary findings and potentially pave the way for an evidence-based, mechanistic understanding of sleep disruption in trauma.
O033 Identifying risk factors for probable insomnia development during late pregnancy: Preliminary findings from an Australian cohort study
Authors: Crowther M , Hughes* J , Clayton* K , Bennett C , Davey M , Drummond S , Manber R , Mol B , Mortimer D , O’Connor D , Rolnik D , Ryan J , Wiley J , Bei B
Published: December 2024

Pregnancy insomnia symptoms are prevalent and associated with adverse parent and infant outcomes. Psychosocial and cognitive factors may contribute to the development and persistence of insomnia symptoms. To date, there is little evidence exploring these risk factors before the onset of probable insomnia disorder.

To investigate the development of probable insomnia (Insomnia Severity Index: ISI ≥10 with sufficient sleep opportunity) at late pregnancy, we examined a cohort of parents without existing probable insomnia (≤7 ISI) at 26-32 weeks of gestation. We then surveyed this cohort again later in pregnancy (five weeks postbaseline) and conducted multiple logistic regression to calculate the odds of probable insomnia at later pregnancy, based on baseline risk factors. Risk factors included: other children, mental health history, sleep reactivity (Ford Insomnia Response to Stress Test), beliefs about sleep (Dysfunction Beliefs and Attitudes about Sleep Scale), and emotional support (PROMIS Emotional support).

A total of 159 (mean age: 32.9 ±3.7 years) parents were included in the present analysis with 12.4% of these meeting the criteria for probable insomnia at later pregnancy. When considering all risk factors for probable insomnia (other children, mental health history, sleep reactivity, beliefs about sleep, and emotional support), only emotional support showed significantly increased odds of insomnia development (OR: 0.90, p=0.027).

Lower perceived emotional support is associated with increased odds of new onset probable insomnia during late pregnancy. Future research should further explore potential mechanisms underlying these associations, and whether targeting emotional support may lower the risk of insomnia development.
O036 Performance characteristics of a contactless under-mattress sleep analyser in a clinical sleep laboratory: Are automated sleep analysers ready for prime time?
Authors: Stewart G , Flood J , Tong B , Cohen G , Cistulli P
Published: December 2024

Introduction

Contactless under-mattress sleep analysers which estimate sleep architecture and breathing disturbances have the potential to alleviate wait times for diagnostic sleep studies and enable multi-night sleep assessments.

Objective

To evaluate the performance characteristics of a commercially available pneumatic under-mattress sleep analyser (UMSA) during overnight laboratory-based polysomnography (PSG) in an unselected sleep clinic population.

Methods

To date, simultaneous UMSA and PSG recordings have been obtained in 74 individuals. After removing studies with insufficient sleep duration (i.e., Total Sleep Time (TST) <5-h, n=7) or recording discrepancies (n=12), TST, rapid-eye movement (REM) duration and apnoea-hypopnea index (AHI) were compared between UMSA and PSG.

Results

Average TST (416±56 vs 355±7min, p<0.001) and REM duration (83±48 vs 60±34min, p=0.006) were significantly longer for UMSA than PSG, while mean AHI (19.4±24.2 vs 16.3±21.6 events/h, p=0.495) was similar. Mean AHI difference between UMSA and PSG was 3.1 events/h with 95% limits of agreement between -23.6 to 29.8 events/h. The sensitivity, specificity, and area under the receiver operating curve (AUC) at a threshold of AHI≥5 was 78.6%, 56.5% and 0.744AUC. At a threshold of AHI≥15 the sensitivity, specificity, and AUC were 80.0%, 69.4% and 0.902AUC.

Conclusions

Estimates of TST and REM duration from an under-mattress sleep analyser were not comparable to laboratory-based polysomnography. Mean AHI was similar albeit with large limits of agreement and the under-mattress sleep analyser had moderate diagnostic accuracy to detect an AHI>5 when compared to polysomnography. Caution is required in the application of under-mattress sleep analysers for research and clinical purposes.
O038 Vigilance Testing Accelerated List (ViTAL) week reduces sleep laboratory waiting times
Authors: Huddle S , Young A , O’Driscoll D
Published: December 2024

Introduction

Vigilance testing (MSLT and MWT) is time consuming and labour intensive, requiring close to a 24h admission for five-nap MSLTs. Combined with increased referrals for hypersomnia, waiting times for vigilance testing has increased. Modelled on High Intensity Theatre Lists (UK), we re-directed sleep laboratory resources to run an intensive Vigilance Testing Accelerated List (ViTAL) over 1-week.

Methods

Resource planning and redirection was co-designed with all laboratory staff. All processes ran concurrently for 5 days to maximise throughput. Four beds were allocated for vigilance tests (i.e. 20 vigilance tests), with the remaining two beds available for urgent studies. Urgent sleep study scoring continued; all other operations were suspended. Following approval from hospital executive, laboratory staffing was reconfigured to cover all shifts and other key staff were consulted (kitchen, cleaning).

Results

18 of the 20 slots were filled (15 MSLTs, 3 MWTs). Average wait time for vigilance tests reduced from 98 to 42 days. There was no negative impact on wait-times for regular PSG bookings (52 vs 42 days) or PSG scoring turnaround times (8.7 vs 4.7 days) compared to 1 month prior to ViTAL week. To maintain staffing for all shifts, two of six staff worked over their weekly rostered hours.

Conclusion

This temporary re-direction of resources was effective in managing a ballooning waitlist. Patient response and staff acceptance was high in the setting of co-design. If performed intermittently, this could be a useful tool to reduce waitlist times, noting sustained increases in workload may leave staff susceptible to burnout.
O069 At home lighting intervention as an adjunct to antidepressant treatment: A pilot study
Authors: Fitton R , Phillips A , McGlashan E , Cain S
Published: December 2024

Evening light exposure is disruptive to sleep and circadian rhythms. This disruption may be amplified for people taking Selective-Serotonin Reuptake Inhibitors (SSRIs), as SSRIs increase sensitivity to the non-visual effects of light. Minimising the amount of evening light exposure may therefore improve antidepressant treatment responses by minimising disruption and improving sleep and mood. We investigated the potential of a home-lighting intervention focused on minimising evening light to reduce depressive symptoms in individuals taking an SSRI. Individuals taking an SSRI who reported moderate or high levels of depressive symptoms, assessed via the Beck Depression Inventory, were recruited (N=24). After completing a baseline week of at-home monitoring of sleep, light, and mood, participants were randomly allocated to four weeks of a smart light intervention (n=12) or a control condition (n=11). Participants in the light intervention group were asked to replace their existing evening lighting with dimmed/warm smart lights. There was no difference in depressive symptoms between groups during the baseline week. Following the intervention period, participants in the intervention group reported significantly reduced depressive symptoms compared to those in the control group, with a large effect (d=2.11) and an average shift from severe to mild depressive symptoms. The intervention group showed a significant reduction in evening light following the intervention, averaging a 21 lux difference in change scores compared to the control group (d=1.11). We conclude that at-home light interventions that reduce evening light exposure hold promise as an adjunctive treatment for individuals experiencing depression while taking SSRIs.
O079 The effect of long-term CPAP on subclinical markers of coronary artery disease in clinic patients with OSA
Authors: Goh J , McArdle N , Sansom K , Shenoy B , Harvey C , Rea C , Dhaliwal S , Reynor A , Ling I , Keenan B , Maislin G , Pack A , McQuillan B , Hung J , Hillman D , Singh B
Published: December 2024

Background

In view of the current uncertainty about the relationship between obstructive sleep apnoea (OSA) and development of major adverse cardiovascular events (MACE) we studied the long-term effect of continuous positive airway pressure (CPAP) on important subclinical markers known to be on the causal pathway to coronary artery disease (CAD)

Methods

We used our database of sleep clinic patients (n=4,226) who had baseline phenotypic assessments, between 2006 and 2010, including level 1 polysomnography to determine the presence and severity of OSA. We performed follow-up assessments between 2019-22 on 2 groups of consenting participants who were alive and free of MACE at baseline and during the follow-up period: those with long-term good CPAP use and those with poor or no use. We will compare follow-up High sensitivity Troponin-I and coronary calcium scores between groups, using propensity score matching methods.

Progress to date

A total of 263 patients completed follow-up assessments and will undergo propensity score matching. Of these, 134 had good CPAP use and 129 had no or poor CPAP use. The two groups had similar baseline characteristics: median age 62 vs 60 years, male 67% vs 64%, body-mass-index 32.6 vs 30.0kg/m2 respectively.

Intended outcome and impact

This project is intended to provide further insight into the relationship between OSA and risk for developing CAD, by studying the effect of long-term good CPAP use, compared to no or poor CPAP use, on changes in established sub-clinical biomarkers of coronary disease.
P031 Does obstructive sleep apnea severity impact sleep spindles in schizophrenia?
Authors: Cho G , Husein N , Faris S , Marshall N , Espinel Diaz P , Yee B , Lambert T , Grunstein R , D’Rozario A
Published: December 2024

Introduction

Patients with schizophrenia have a high prevalence of obstructive sleep apnea (OSA). Sleep disturbance and sleep spindle deficits are observed in both schizophrenia and OSA patients. But whether the spindle deficits seen in schizophrenia are modified across a broad spectrum of OSA severity remains unclear

Methods

We analysed overnight electrocephalography (EEG) from schizophrenia patients with suspected OSA (n=29, mean age=44 yrs, gender (F:M) = 7:22, AHI range=0.0-123.4/hr) and a non-schizophrenia control group (n=29, mean age=44 yrs, gender (F:M) = 7:22, AHI range=8.6-106.6/hr) selected with a similar age and gender distribution. Sleep spindles (11-16Hz) were identified using a validated automated algorithm at a central EEG electrode site. A linear regression model was used to assess the differences between people with and without schizophrenia and examine the association between OSA severity (Apnea-Hypopnea Index; AHI) and its interaction with schizophrenia.

Results

The schizophrenia group had lower NREM sleep spindle density compared with controls (0.6/min vs 1.8/mins; p<0.05). Sleep apnea severity (AHI) was not associated with spindle density, schizophrenia did not modify this association. We incidentally observed that the schizophrenia group had increased N1 (58.4 vs 15.0 minutes) and N3 (85.7 vs 25.1 minutes) sleep, and reduced N2 (195.7 vs 250.8 minutes) and REM (46.5 vs 69.0 minutes) sleep (all p<0.05).

Conclusion

Our preliminary findings suggest that sleep spindle deficits observed in schizophrenia are not further impaired by OSA severity. Future research exploring the possible therapeutic effects of OSA treatment on sleep spindles and restoring sleep architecture in schizophrenia are now warranted.
P040 How do Children with Neurodisability Use Technology Around Bedtime? Results from a Cross-Sectional Survey
Authors: Shin I , Anderson M , Robinson J , Vandeleur M , Waters K , Chawla J
Published: December 2024

Introduction

Anecdotally caregivers of children with neurodisability (ND) express that using an electronic device before bed helps to calm their child and prepare them for sleep. The aim of this study was to determine how children with ND use technology prior to bedtime.

Methods

Caregivers of children 1-18yrs with a diagnosed ND condition, undergoing a sleep study at one of 3 tertiary hospitals completed a study-designed questionnaire exploring the type, frequency and nature of technology use by their child around bedtime. Sleep-related symptoms experienced by their child (e.g, daytime tiredness) were also reported. Descriptive statistical analysis was performed, and results were stratified by age, sex and underlying ND condition.

Results

133 completed responses were available for analysis (55% male, median age 11yrs). 32% of participants were reported to “always” use a screen-based device around bedtime, 19% “often”, 25% sometimes, 8% rarely and 16% never. 47% reported their child used a device “everyday” prior to bedtime. 59% of parents felt that use of a device helped their child around bedtime. There was a positive association between the frequency of technology use at bedtime and sleep symptoms reported.

Conclusion

Bedtime digital technology usage was high in children with ND and appeared to be associated with greater report of sleep symptoms. However, more than half of parents felt the technology was helpful for their child around bedtime. Comparison to a group of neurotypical children is underway and will determine if recommendations for device usage in children with ND around bedtime require adaptation.
P045 Association between childhood cystic fibrosis lung disease and adolescent sleep and mental health
Authors: Pham H , Vandeleur M , Mainzer R , Jordan B , Clark N , Du Berry C , Schultz A , Ramsay K , Pettigrew G , Harper A , McCappin S , Carzino R , Ranganathan S
Published: December 2024

Background

Sleep disruption imposes deleterious physiological and psychological effects. We aimed to describe the relationship between school age respiratory health on adolescent sleep disturbance and mental health symptoms in people living with cystic fibrosis.

Methods

We conducted a prospective longitudinal study of adolescents aged 10 to 18 years from October 2020 to June 2024. Sleep was evaluated via serial measures of the pediatric daytime sleepiness scale (PDSS) and sleep disturbance scale for children (SDSC), while mental health was assessed with the Patient Health Questionnaire-9 (PHQ-9) for depression and Generalised Anxiety Disorder-7 (GAD-7) for anxiety. Respiratory health was measured alongside, using FEV1 percent predicted and multiple breath washout (MBW). Childhood chest CT scan were previously collected via DEFEND CF (Biomarkers to define the treatment end-points for pulmonary exacerbations in CF) and scored using the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF).

Linear regression was used to estimate mean difference in sleep and mental health change per school age CT bronchiectasis score.

Results

64 adolescents were studied. 56% of participants experienced sleep disturbance symptoms, 45% for mental health symptoms, with no significant association between childhood bronchiectasis score and adolescent PDSS, SDSC scores. Adolescent anxiety and depression scores also did not significantly correlate with childhood bronchiectasis scores.

Conclusion

While childhood bronchiectasis score did not predict adolescent sleep or mental health, sleep disturbance and symptoms of anxiety and depression were prevalent in the cohort. The need for ongoing monitoring and support in these areas remains crucial for adolescents with cystic fibrosis.
P095 Temporalis and Masseter EMG leads in the assessment of Sleep Bruxism scoring in individuals with Obstructive Sleep Apnea and Sleep Bruxism
Authors: Chow S , Leow L , Song P , Nur Izzianie B
Published: December 2024

Study Objectives

Sleep bruxism (SB) is defined as the repetitive jaw muscle activity characterized by the clenching or grinding of teeth. Untreated SB may lead to dental complications, orofacial pain, OSA and insomnia. We postulate that SB scoring is more accurate with the addition of bilateral masseter and temporalis EMG leads (SB leads) to conventional PSG.

Methods

Full-night PSG of 25 individuals with OSA and history of SB were included. An independent sleep technologist (RPSGT) scored bruxism episodes according to the AASM criteria. The Bruxism Episode Index (BEI) measures the number of bruxism episodes per hour of sleep (<2: irrelevant SB; 2–4: mild/moderate SB; >4: severe SB.) SB-related EMG jaw muscle activity recorded are Rhythmic Masticatory Muscle Activity episodes and bursts (RMMA), which were scored using SB leads in addition to conventional PSG leads. Masseter and temporal EMG bursts with duration >0.25sec were selected according to published criteria. RMMA is categorized as phasic (≥3 rhythmic bursts 0.25-2sec) or tonic (sustained burst lasting >2sec). The same PSG were re-scored without these additional SB leads and the results were compared.

Results

Of the 25 PSGs without SB leads, incidence of none, mild to moderate and severe SB is 7, 11 and 7. With addition of the SB leads, incidence of none, mild to moderate and severe SB is 2, 5 and 18. Median Bruxism Episode Index (BEI) was 6.4 and 2.8 with and without SB leads respectively.

Conclusions

Conventional PSG without SB leads results in significant underestimation of SB incidence and severity.
P096 Sleep Behaviours and Nutritional Knowledge in Amateur and Professional Combat Sport Athletes
Authors: Dunican I , Galpin A , Turner M , Reale R
Published: December 2024

Introduction

Combat sports is a term applied to various competitive contact sports involving two competitors engaging in a bout or contest under a specific ruleset. Little is known about combat sports athletes’ sleep and nutritional knowledge. This study aimed to assess (i) sleep behaviours, (ii) alcohol and shiftwork disorders and (iii) the nutritional knowledge of combat sports athletes.

Methods

Participants completed various demographic questions and estimations of their body mass management practices and validated surveys, including the Athlete Sleep Behaviour Questionnaire (ASBQ), Shiftwork Disorder Screening Questionnaire (SWD), Alcohol Use Disorders Identification Test (AUDIT), and the Abridged Nutrition for Sports Knowledge Questionnaire (A-NSKQ).

Results

A total of 858 combat sports athletes completed the survey, 79% male, height of 177 ± 10 (cm), weight of 79 ± 15 (kgs). Sleep quality was average for all combat sport types, risk prevalence of shiftwork disorder at 11%. Amateur strikers, boxers and BJJ athletes consumed significantly more alcohol. Most combat sports athletes reduce weight for competition, with an overall nutritional knowledge average of 55%.

Conclusion

This study highlights a critical gap in the knowledge and practices of combat sport athletes in relation to sleep behaviours and disorders, alcohol consumption, and nutritional knowledge, emphasising the need for targeted educational interventions.
P109 Role of Multiple Sleep Latency Test (MSLT) in the workup of children with hypersomnolence
Authors: Malhotra N , Goyal V , Sclip K , Kilner D , Kapur N
Published: December 2024

Introduction

Hypersomnolence and excessive daytime sleepiness (EDS) can be idiopathic or associated with narcolepsy. The Multiple Sleep Latency Test (MSLT) is gold standard for diagnosing narcolepsy, though significant gaps currently exist in understanding the interpretation of MSLT in diagnosing and managing paediatric hypersomnolence. This retrospective study aims to describe a) a cohort of children investigated for hypersomnia and b) their MSLT outcomes.

Methods

Clinical, demographic, and MSLT data were retrospectively collected from children who underwent hypersomnolence investigation at a tertiary paediatric hospital (January 2015-December 2023). Data included age, gender, BMI, comorbidities, medications, polysomnography, MSLT results, diagnoses, treatment, and outcomes. The association between MSLT parameters and diagnostic outcomes was explored using American Sleep Association criteria.

Results

125 children (56F) were identified through our hospital database, with data on 72 (30F; median age 12.42 years, IQR=4.11) collected. 19 (26%) were HLA-positive for narcolepsy. MSLT parameters suggested narcolepsy in 13 (18.1%) children; 1 additional child had low orexin levels. Median sleep latency was significantly shorter in the narcolepsy group compared to non-narcolepsy (01:39 minutes vs. 12.58 minutes, p<0.001). No age or gender differences were observed between groups. Diagnostic PSG on the preceding night led to alternate diagnoses in 5 children.

Discussion

While the data is only partially complete, interim analysis suggests narcolepsy is present in a minority of this cohort. PSG from the preceding night changed in the diagnosis in 5 children. However, the fifth nap did not change any outcomes, so the utility of this practice needs to be re-explored.
The lack of thematic continuity in dreams with scene and plot discontinuities
Authors: Stickgold Robert , Sangodeyi Funke
Published: December 2024

A central tenet of Freudian dream theory holds that there is thematic coherence within all dreams, even those containing scene and plot discontinuities. While other models support varying degrees of dream coherence, none address the question of how, or even whether, coherence can be identified in dreams with such discontinuities. Here, we objectively test the ability of judges to evaluate the coherence of individual dream narratives. Twenty reports with complete scene and plot discontinuities were collected, and half were cut apart at their discontinuities and their two halves spliced together with segments from dreams of other subjects. The remaining 10 reports were left intact. Judges correctly identified reports as intact or spliced only 57% of the time, a rate only slightly better than chance. Only 3 of the 20 reports, one intact and two spliced, were reliably scored correctly, while one intact report was mis-scored by 80% of the judges. Judges had no greater confidence in correct decisions than incorrect ones. Dream report features identified by the judges that were effectively used in scoring dreams included characters, locations and objects, while psychoanalytic content and writing style were least effectively used. In sum, we find no evidence that dream construction consistently results in identifiable thematic coherence. Rather, scene and plot discontinuities in many cases represent such complete breaks as to be unrecognizable. We conclude that the finding of continuity by those reading these reports reflects ineluctable synthetic activity in the mind of the dream researcher or analyst rather than in the mind of the dreamer.

This paper is part of the Festschrift in honor of Dr. Robert Stickgold.
Regressing from the Gold Standard: The UK’s Slavery and Human Trafficking Regulations and the Narrowing of Victim Protection
Authors: Haynes Jason
Published: December 2024

The UK’s 2022 Slavery and Human Trafficking (Definition of Victim) Regulations represent a significant departure from established international standards in human trafficking victim protection. This article critically examines how the Regulations’ definitional framework creates three fundamental concerns that risk excluding legitimate victims from protection. First, while Clause 3(5)(a) aligns with international law’s ‘means’ elements, Clause 3(6)(d) problematically narrows this list for those required to provide services or benefits, potentially excluding victims who face exploitation through means other than force, threats, or deception. Second, the Regulations create unnecessary ambiguity around child trafficking through Clause 3(5)(b)’s unclear phrasing ‘any method’, potentially requiring evidence of the ‘means’ element contrary to international law which recognizes children’s inherent vulnerability. Third, the Regulations fail to explicitly include certain forms of exploitation, such as ‘practices similar to slavery’ in Clause 3(6)’s characterization of exploitation, departing from both the Council of Europe Convention on Action against Trafficking in Human Beings (ECAT) and the Palermo Protocol’s established frameworks. Drawing on recent European Court of Human Rights jurisprudence, particularly V.C.L and A.N v United Kingdom, this article demonstrates how the Regulations’ restrictive approach conflicts with the UK’s international obligations and risks excluding vulnerable groups from protection, including migrant workers, child victims, and those subjected to debt bondage or forced marriage. The analysis reveals how these limitations, coupled with the broader ‘hostile environment’ policy context, create significant barriers to victim identification and support. This article argues for urgent amendment of the Regulations to align with the Palermo Protocol’s comprehensive definition of trafficking victims, ensuring adequate protection for all forms of exploitation and maintaining the UK’s commitment to international protection standards.
Effects of direct-fed microbials supplementation on in vitro and ex vivo ruminal fermentation and nutrient degradability in lactating Holstein dairy cows
Authors: Oyebade Adeoye O , Arriola Kathy , Queiroz Oscar , Cappellozza Bruno I , Vyas Diwakar
Published: December 2024

We conducted two experiments to evaluate the effect of direct-fed microbials (DFM) on fermentation parameters and nutrient degradability with two different approaches using rumen fluid from lactating Holstein dairy cows. In Exp. 1, three doses of a DFM containing Lactobacillus animalis and Propionibacterium freudenreichii (PRO-A) at doses of 3.9 × 106, 7.8 × 106, and 11.7 × 106 CFU or a DFM containing PRO-A, Bacillus subtilis, and B. licheniformis (PRO-B) at doses of 15.2 × 106, 30.4 × 106, and 45.6 × 106 CFU were incubated using corn silage as substrate and pooled rumen fluid from three-rumen fistulated lactating Holstein cows. Dry matter and NDF degradability, gas production, and rumen pH were measured over a 24-h period. In Exp. 2, three ruminally cannulated multiparous cows (165 ± 63 DIM) were used in a 3 × 3 Latin square design. Each experimental period was of 28 d. All cows received a corn silage-based TMR (basal diet), and were assigned to: 1) Control (CON), 2) PRO-A: Basal diet top-dressed with PRO-A at 3 × 109 CFU/day, and 3) PRO-B: Basal diet top-dressed with PRO-B at 11.8 × 109 CFU/day. An ex vivo study (Exp. 2) was conducted using rumen fluid collected during wk 4 of each experimental period from experimental animals. Treatments included: CON, PRO-A, PRO-B, each of which utilized rumen fluid from donor cows given respective treatments. Another set of rumen fluid from PRO-A and PRO-B cows were dosed with additional dose of respective DFM, resulting in two more treatments (PRO-A+ and PRO-B+). In Exp. 1, linear effects (P = 0.03) were observed on in vitro NDF degradability following DFM incubation. In Exp. 2, no treatment effects were observed on DM and NDF digestibility. In summary, DFM increased DM and NDF degradability in vitro using rumen fluid from cows not exposed to DFM; however, no effects were observed under ex vivo experimental conditions when rumen fluid was collected from cows consuming DFM.
Nanoliposomal system for augmented antibacterial and antiproliferative efficacy of Melissa officinalis L. extract
Authors: Nizam Nagihan , Taner Gokce , Cagal Munevver Muge
Published: December 2024

Objective

This study focused on the nanoliposomal encapsulation of bioactive compounds extracted from Melissa officinalis L. (ME) using ethanol as a strategy to improve the antibacterial activity, anticytotoxic, and antiproliferative properties.

Methods

Nanoliposomes loaded with ME (MEL) were characterized for total phenolic content, particle size, polydispersity, and encapsulation efficiency. The minimum inhibitory concentration (MIC) values for MEL and ME were determined to evaluate antibacterial activity. To examine the toxicity profiles of ME and MEL, tests were conducted on the A549 and BEAS-2B cell lines using the MTT assay. Furthermore, an in vitro sctrach assay was conducted to evaluate the antiproliferative effects of ME and MEL on A549 cells.

Results

Nanoliposomes presented entrapment efficiency higher than 80%, nanometric particle size, and narrow polydispersity. The MIC values for MEL and ME were observed as 93.75 μg/μL against E. coli. MIC values for MEL and ME were achieved as 4.68 μg/μL and 9.375 μg/mL against S. aureus, respectively. The IC50 values for ME were determined to be 1.13 mg/mL and 0.806 mg/mL, while the IC50 values for MEL were found to be 3.5 mg/mL and 0.868 mg/mL on A549 and BEAS-2B cell lines, respectively. Additionally, The MEL showed an antiproliferative effect against A549 cells at 500 μg/mL concentration.

Conclusion

All experimental findings unequivocally demonstrate that the novel nanoliposomal system has effectively augmented the antibacterial activities and antiproliferative effects of ME. The initial findings indicate that nanoliposomes could effectively serve as carriers for ME in pharmaceutical applications.
Impact of micro-nano plastics in daily life on human health: toxicological evaluation from the perspective of normal tissue cells and organoids
Authors: Wang Jie , Xie Lan-Gui , Wu Xian-Fu , Zhao Zong-Ge , Lu Yong , Sun Hui-Min
Published: December 2024

Plastics are the most frequently used materials in people’s daily life, and the primary and secondary microplastics generated from them may harm the health of adults. This paper focuses on the summary of the existence of microplastics in many objects most closely related to people in daily life, the toxicological influences it causes in cultured human normal cells and organoids, and the prospects for future research directions. Micro- and nano-plastics (MNPs) are found in almost all of our everyday products, such as food, drink, and daily necessities, etc. It can enter the digestive tract, respiratory system, and body fluids of the human body, and at lower or equal environment concentrations exhibits obvious cytotoxicity and genotoxicity toward cells and organoids, probably becoming a kind of toxin affecting human health. In addition, due to MNPs can be transferred from the placenta to the embryo, long-term growth-tracking studies of newborns should be done vitally. Besides, due to their wide usability in daily products and the ability to penetrate cytomembranes, the toxicological effects of polyethylene and polypropylene nanoplastic particles equal to or lower than environmental (normal exposure to human body) concentrations are recommended to be studied on human health in the future. Finally, for those individuals who carry MNPs, long-term health evaluation must be performed.
Predicting the molecular mechanisms of cardiovascular toxicity induced by per- and polyfluoroalkyl substances: an In Silico network toxicology perspective
Authors: Karakuş Fuat , Kuzu Burak
Published: December 2024

Background: Per- and polyfluoroalkyl substances (PFAS) are human-made chemicals that accumulate in the human body and the environment over time. Humans are primarily exposed to PFAS through drinking water, food, consumer products, and dust. These exposures can have many adverse health effects, including cardiovascular diseases (CVDs) and factors contributing to CVDs. This study identified the molecular mechanisms of CVDs caused by PFAS. Methods: For this purpose, various computational tools, such as the Comparative Toxicogenomic Database, ShinyGO, ChEA3, MIENTURNET, GeneMANIA, STRING, and Cytoscape, were used to conduct in silico analyses. Results: The results showed that 10 genes were common between PFAS and CVDs, and among these common genes, the PPAR signaling pathway, fatty acid metabolic processes, and lipid binding were the most significantly associated gene ontology terms. Among the top 10 transcription factors (TFs) related to these common genes, peroxisome proliferator-activated receptor gamma and androgen receptor were the most prominent. Additionally, hsa-miR-130b-3p, hsa-miR-130a-3p, and hsa-miR-129-5p were featured microRNAs involved in PFAS-induced CVDs. Finally, PPARA and PPARG were identified as core genes involved in PFAS-induced CVDs. Conclusion: These findings may contribute to a better understanding of the molecular mechanisms and reveal new potential targets in PFAS-induced CVDs.
Outcomes of HIV-infected children on antiretroviral therapy for at least 10 years at the Essos Hospital Centre, Cameroon: contributing to the elimination of paediatric AIDS in tropical settings
Authors: Njom Nlend Anne Esther , Fokam Joseph , Mekoui Suzanne , Epée Ngoué Jeannette , Nga Motaze Annie Carole , Colizzi Vittorio , Perno Carlo-Federico , Ndjolo Alexis , Halle-Ekane Gregory-Edie , Sandie Arsene
Published: December 2024

Evidence on long-term outcomes of children receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is of utmost importance to optimize current and future therapeutic strategies for HIV. We sought to ascertain the long-term responses among ART-experienced children and their potential implications. A retrospective, observational, facility-based cohort study was conducted among 136 ART-experienced children monitored for 10 years (2007–2017) at the Essos Hospital Centre in Yaoundé, Cameroon. Primary outcomes were good clinical response defined as the World Health Organization (WHO) clinical stage 1/2, immune restoration as CD4 >500 cells/mm3, viral suppression (VS) as viral load (VL) <1000, or viral undetectability as VL <40 copies/ml at the last follow-up and their predictors (P < .05). At ART initiation among the 90 eligible children, median (interquartile range) age was 29.5 (11–60) months, 53.3% were males, 34.5% were at WHO clinical stage 1/2, median-CD4 was 497 cells/mm3, and initial ART-regimens were mainly zidovudine-lamivudine-nevirapine (85.5%) and zidovudine-lamivudine-efavirenz (12.2%). After 10 years of follow-up, 36.7% were switched to protease-based ART regimens, those at WHO clinical stage 1/2 improved to 75.5%; median-CD4 increased to 854 cells/mm3; 83.3% achieved VS, while only 10% achieved viral undetectability. Following multivariate analysis, no predictor of VS or immune recovery was identified (P > .05). In this LMIC, long-term outcomes of children on ART appear encouraging, characterized by moderate VS rate and immune recovery. However, challenges in achieving viral undetectability indicate continuous viral replication and risks of drug resistance emergence that may jeopardize effectiveness of future paediatric ART strategies.
Rosthornin B alleviates inflammatory diseases via directly targeting NLRP3
Authors: Yang Yanqing , Liu Didi , Cao Hairuo , Lu Li , Zhang Wei , Liu Chenfei , Zeng Yao , Shang Feifei , Tao Ye , Zhao Bao , Wang Fengchao , Tang Tiantian , Deng Mengmeng
Published: December 2024

Aberrant activation of the NLRP3 inflammasome contributes to the evolution of diverse inflammatory diseases. Inhibition of the NLRP3 inflammasome has been proven to be an effective treatment strategy for NLRP3‐driven diseases. This study revealed that multiple natural diterpenes from Isodon plants can inhibit the NLRP3 inflammasome, among which Rosthornin B (Ros B) exhibited the best inhibitory effect, with an IC50 of 0.39 μM. Further study revealed that Ros B directly interacts with NLRP3, thereby restraining NEK7‐NLRP3 interaction and inhibiting NLRP3 inflammasome assembly and activation. Remarkably, Ros B had a significant therapeutic benefit in mouse models of NLRP3‐driven septic shock, peritonitis, and colitis. Our study has identified a series of natural diterpenes that target the NLRP3 inflammasome. These natural diterpenes, especially those with low IC50 values, may lead to the development of new drugs and potential clinical therapies for diseases driven by NLRP3 inflammasome activation.
Exploring combination therapy centered on targeted immunotherapy for advanced hepatocellular carcinoma: a beacon of hope
Authors: Wang Yanbin , Wu Yuqi , Zhang Hong , Wang Jing , Song Anping , Qiu Hong , Yuan Xianglin , Xiong Hua , Zou Yanmei
Published: December 2024

Hepatocellular carcinoma (HCC) is an aggressive malignancy that is highly prevalent worldwide. It is often diagnosed at an advanced stage, which poses challenges for curative treatment and leads to an unfavorable prognosis. The introduction of targeted therapy drugs, such as tyrosine kinase inhibitors, and immunotherapeutic drugs, including immune checkpoint inhibitors, has substantially improved the therapeutic effectiveness for advanced HCC. However, their efficacy remains suboptimal, owing to challenges related to patient responsiveness and drug resistance. To address these challenges, researchers have investigated combination therapies, including targeted immunotherapy, and triple therapies based on targeted immunotherapy, such as a combination of radiotherapy and targeted immunotherapy. In addition, they conducted a comprehensive investigation of potential new targets and drugs, yielding a series of significant findings. This review presents an outline of the treatment mechanisms and associated clinical research findings on mainstream targeted therapies, immunotherapies, and combination therapies. It also summarizes the current status of combination therapies for advanced HCC and anticipates future developments and trends in this field.
Survival time and prognostic factors in dogs diagnosed with haemangiosarcoma in UK first opinion practice
Authors: Taylor C. , Barry G.J. , O’Neill D.G. , Guillén A. , Pickard P. , Labadie J. , Brodbelt D.C.
Published: December 2024

Abstract

Visceral haemangiosarcoma is considered clinically aggressive in dogs, with perceived poor prognosis often leading to euthanasia at presentation. This study aimed to determine survival times and prognostic factors in dogs with haemangiosarcoma under first-opinion care.

Dogs diagnosed with haemangiosarcoma in first-opinion practice in 2019 were identified in VetCompass electronic health records (EHRs) and manually examined to capture variables potentially associated with survival. Median survival time (MST) from diagnosis was calculated for the whole population and based on the primary tumour location. Binary logistic regression was used to explore differences between dogs that died on the day of diagnosis and those that survived ≥1 day. Cox proportional hazards modelling explored factors associated with time to death in dogs that survived ≥1 day.

Across all haemangiosarcoma cases (n=788), overall MST was 9.0 days (95%CI:5.0-15.0, range: 0-1789) and proportional 1-year survival was 12.0% (95%CI:9.7-15.0%). Dogs with splenic (MST=4.0 days, 95%CI 0.0-9.0) and cutaneous haemangiosarcoma (MST=119.0 days,95%CI:85.0-248.0) had MST greater than 0 days. Male sex and increasing tumour size were associated with increased hazard of death while cutaneous location and surgery were associated with reduced hazard of death.

A very short survival time was identified for haemangiosarcoma under first-opinion care. Although survival time was longest for cutaneous cases, the actualised prognosis was poor overall for haemangiosarcoma. This study provides valuable information for contextualised care and dialogues with clients in first-opinion practice.
Data-driven discovery of cell-type-directed network-correcting combination therapy for Alzheimer’s disease
Authors: Li Yaqiao , Serras Carlota Pereda , Blumenfeld Jessica , Xie Min , Hao Yanxia , Deng Elise , Chun You Young , Holtzman Julia , An Alice , Yoon Seo Yeon , Tang Xinyu , Rao Antara , Woldemariam Sarah , Tang Alice , Zhang Alex , Simms Jeffrey , Lo Iris , Oskotsky Tomiko , Keiser Michael J , Huang Yadong , Sirota Marina
Published: December 2024

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by heterogeneous molecular changes across diverse cell types, posing significant challenges for treatment development. To address this, we introduced a cell-type-specific, multi-target drug discovery strategy grounded in human data and real-world evidence. This approach integrates single-cell transcriptomics, drug perturbation databases, and clinical records. Using this framework, letrozole and irinotecan were identified as a potential combination therapy, each targeting AD-related gene expression changes in neurons and glial cells, respectively. In an AD mouse model, this combination therapy significantly improved memory function and reduced AD-related pathologies compared to vehicle and single-drug treatments. Single-nuclei transcriptomic analysis confirmed that the therapy reversed disease-associated gene networks in a cell-type-specific manner. These results highlight the promise of cell-type-directed combination therapies in addressing multifactorial diseases like AD and lay the groundwork for precision medicine tailored to patient-specific transcriptomic and clinical profiles.

Graphic Abstract
Tissue-Specific Cell Type Annotation with Supervised Representation Learning using Split Vector Quantization and Its Comparisons with Single-cell Foundation Models
Authors: Heryanto Yusri Dwi , Zhang Yao-zhong , Imoto Seiya
Published: December 2024

Cell-type annotation in single-cell data involves identifying and labeling the cell types based on their gene expression profiles or molecular features. Recently, with advances in single-cell foundation models (FMs), unsupervised annotation and transfer learning with FMs have been explored for cell-type annotation tasks. However, because FMs are usually pre-trained in an unsupervised manner on data spanning a wide variety of tissues and cell types, their representations for specific tissues may lack specificity and become overly generalized. In this work, we propose a novel supervised representation learning method using split-vector-quantization, single-cell Vector-Quantization Classifier (scVQC). We evaluated scVQC against both supervised and unsupervised representation learning approaches, with a focus on foundation models pretrained on large-scale single-cell datasets, such as scBERT and scGPT. The experimental results highlight the importance of label supervision in cell-type annotation tasks and demonstrate that the learned codebook effectively profiles and distinguishes different cell types.
A global synthesis on land-cover changes in watersheds shaping freshwater detrital food webs
Authors: Oester Rebecca , Keck Francois , Moretti Marcelo , Altermatt Florian , Bruder Andreas , Ferreira Veronica
Published: December 2024

Anthropogenic land-cover changes are among the most pressing global threats to both aquatic and terrestrial ecosystems, jeopardising biodiversity and the critical connections between these systems. Resource flows and trophic interactions intricately link aquatic and terrestrial ecosystems, with terrestrial-derived detritus playing a foundational role in supporting aquatic food webs. These detrital inputs form essential cross-ecosystem linkages, underpinning key ecological processes and providing vital resources for aquatic communities. Yet, little research has focused on how land-cover changes cascade across this linkage. To better understand how land-cover changes in the watershed influence freshwater detrital food webs, we conducted a meta-analysis of field studies reporting the effects of vegetation changes on freshwater detrital consumers and organic matter decomposition. The results from 144 studies, reporting 1235 comparisons, showed that, overall, land-cover changes in the watershed vegetation, especially through harvest and land-use conversion, have negative effects on aquatic biodiversity and ecosystem processes. These vegetation changes reduced diversity, abundance, and biomass across multiple trophic levels in freshwater detrital food webs. Studies examining multiple organism groups most often observed negative responses across multiple trophic levels, suggesting that the land-cover changes negatively affected multiple detrital food web components simultaneously. Our results also show that outcomes of restoration of watershed vegetation were context-dependent, and no clear trend of improvement was visible. Therefore, conservation of natural riparian and catchment vegetation are key to maintain freshwater ecosystem processes and aquatic biodiversity worldwide, and more efficient and evidence-based restoration measures are urgently needed. As our global synthesis shows that direct human-induced alterations of vegetation type in watersheds have significant negative effects on freshwater detrital food webs, there is a pressing need to consider cross-ecosystem consequences of land-cover changes in conservation and ecosystem management.
Occurrence of the Humboldt Penguin (Spheniscus humboldti, Meyen, 1834) in El Ferrol Bay, Chimbote, Peru, and strategies for its conservation
Authors: Loayza-Aguilar Rómulo E. , Medina-Quezada Heillyn , Merino Fernando , Saldaña-Rojas Guillermo B. , Mendoza Sorayda , Olivos-Ramirez Gustavo E.
Published: December 2024

The Humboldt penguin is an emblematic species of the Humboldt ecosystem of Peru and Chile, declared as vulnerable in The IUCN Red List of Threatened Species in 2020. By 2023, its population was estimated around 9,900 pairs, which means a decrease of 93% of its population in 70 years. In response to a warning of its occurrence on the Guaneras Islands located in El Ferrol Bay (Chimbote, Peru), the objective of this study was to verify its presencein situ. Between October and November 2024, four expeditions were carried out on the leeward side of the Islote Peña Blanca (White Rock Islet), Isla Blanca (White Island), Isla Ferrol del Norte (Northern Ferrol Island), Isla Ferrol del Centro (Central Ferrol Island), and Isla Ferrol del Sur (Southern Ferrol Island). The presence of 149 individuals, 5 of them juveniles, and one chick accompanied by its parent, was verified on Northern Ferrol Island, Central Ferrol Island, and Southern Ferrol Island. It is estimated that the presence of these organisms is explained by the improvement of oceanographic conditions in this bay. Considering the high vulnerability of the species, the local community must articulate efforts to guarantee the establishment of its population in this particular habitat.