bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of therapeutic effect and prognostic value of 18F-FDG PET/CT in different treatment nodes of DLBCL patients
Authors: Zhao Wenyu , Wu Xiaodong , Huang Shuo , Wang Hui , Fu Hongliang
Published: February 2024

Background

In the present study, we aimed to investigate the role of baseline (B), interim (I) and end-of-treatment (Eot) 18F-FDG PET/CT in assessing the prognosis of diffuse large B cell lymphoma (DLBCL), so as to identify patients who need intensive treatment at an early stage.

Methods

A total of 127 DLBCL patients (62 men; 65 women; median age 62 years) were retrospectively analyzed in this study. Baseline (n = 127), interim (n = 127, after 3–4 cycles) and end-of-treatment (n = 53, after 6–8 cycles) PET/CT images were re-evaluated; semi-quantitative parameters such as maximum standardized uptake value of lesion-to-liver ratio (SUVmax(LLR)) and lesion-to-mediastinum ratio (SUVmax(LMR)), total metabolic tumor volume (TMTV) and total metabolic tumor volume (TLG) were recorded. ΔTLG1 was the change of interim relative to baseline TLG (I to B), ΔTLG2 (Eot to B). ΔSUVmax and ΔTMTV were the same algorithm. The visual Deauville 5-point scale (D-5PS) has been adopted as the major criterion for PET evaluation. Visual analysis (VA) and semi-quantitative parameters were assessed for the ability to predict progression-free survival (PFS) and overall survival (OS) by using Kaplan–Meier method, cox regression and logistic regression analysis. When visual and semi-quantitative analysis are combined, the result is only positive if both are positive.

Results

At a median follow-up of 34 months, the median PFS and OS were 20 and 32 months. The survival curve analysis showed that advanced stage and IPI score with poor prognosis, ΔSUVmax(LLR)1 < 89.2%, ΔTMTV1 < 91.8% and ΔTLG1 < 98.8%, ΔSUVmax(LLR)2 < 86.4% were significantly related to the shortening of PFS in patient (p < 0.05). ΔSUVmax(LLR)1 < 83.2% and ΔTLG1 < 97.6% were significantly correlated with the shortening of OS in patients (p < 0.05). Visual analysis showed that incomplete metabolic remission at I-PET and Eot-PET increased the risk of progress and death. In terms of predicting recurrence by I-PET, the combination of visual and semi-quantitative parameters showed higher positive predictive value (PPV) and specificity than a single index.

Conclusion

Three to four cycles of R-CHOP treatment may be a time point for early prediction of early recurrence/refractory (R/R) patients and active preemptive treatment. Combined visual analysis with semi-quantitative parameters of 18F-FDG PET/CT at interim can improve prognostic accuracy and may allow for more precise screening of patients requiring early intensive therapy.
Supplementation of vitamin E or a botanical extract as antioxidants to improve growth performance and health of growing pigs housed under thermoneutral or heat-stressed conditions
Authors: Silva-Guillen Ysenia V. , Arellano Consuelo , Wiegert Jeffrey , Boyd R. Dean , Martínez Gabriela E. , van Heugten Eric
Published: February 2024

Background

Heat stress has severe negative consequences on performance and health of pigs, leading to significant economic losses. The objective of this study was to investigate the effects of supplemental vitamin E and a botanical extract in feed or drinking water on growth performance, intestinal health, and oxidative and immune status in growing pigs housed under heat stress conditions.

Methods

Duplicate experiments were conducted, each using 64 crossbred pigs with an initial body weight of 50.7 ± 3.8 and 43.9 ± 3.6 kg and age of 13-week and 12-week, respectively. Pigs (n = 128) were housed individually and assigned within weight blocks and sex to a 2 × 4 factorial arrangement consisting of 2 environments (thermo-neutral (21.2 °C) or heat-stressed (30.9 °C)) and 4 supplementation treatments (control diet; control + 100 IU/L of D-α-tocopherol in water; control + 200 IU/kg of DL-α-tocopheryl-acetate in feed; or control + 400 mg/kg of a botanical extract in feed).

Results

Heat stress for 28 d reduced (P ≤ 0.001) final body weight, average daily gain, and average daily feed intake (−7.4 kg, −26.7%, and −25.4%, respectively) but no effects of supplementation were detected (P> 0.05). Serum vitamin E increased (P < 0.001) with vitamin E supplementation in water and in feed (1.64 vs. 3.59 and 1.64 vs. 3.24), but not for the botanical extract (1.64 vs. 1.67 mg/kg) and was greater when supplemented in water vs. feed (P = 0.002). Liver vitamin E increased (P < 0.001) with vitamin E supplementations in water (3.9 vs. 31.8) and feed (3.9 vs. 18.0), but not with the botanical extract (3.9 vs. 4.9 mg/kg). Serum malondialdehyde was reduced with heat stress on d 2, but increased on d 28 (interaction,P < 0.001), and was greater (P < 0.05) for antioxidant supplementation compared to control. Cellular proliferation was reduced (P = 0.037) in the jejunum under heat stress, but increased in the ileum when vitamin E was supplemented in feed and water under heat stress (interaction,P = 0.04). Tumor necrosis factor-α in jejunum and ileum mucosa decreased by heat stress (P < 0.05) and was reduced by vitamin E supplementations under heat stress (interaction,P < 0.001).

Conclusions

The addition of the antioxidants in feed or in drinking water did not alleviate the negative impact of heat stress on feed intake and growth rate of growing pigs.
Quantitative calibration of Tb-161 SPECT/CT in view of personalised dosimetry assessment studies
Authors: McIntosh Lachlan , Jackson Price , Emmerson Brittany , Buteau James P. , Alipour Ramin , Kong Grace , Hofman Michael S.
Published: February 2024

Background

Terbium-161 (161Tb)-based radionuclide therapy poses an alternative to current Lutetium-177 (177Lu) approaches with the additional benefit of secondary Auger and conversion electron emissions capable of delivering high doses of localised damage to micro-metastases including single cells. Quantitative single-photon emission computed tomography, paired with computed tomography (SPECT/CT), enables quantitative measurement from post-therapy imaging. In view of dosimetry extrapolations, a Tb-161 sensitivity SPECT/CT camera calibration was performed using a method previously validated for 177Lu.

Methods

Serial imaging of a NEMA/IEC body phantom with Tb-161 was performed on SPECT/CT with low-energy high-resolution collimators employing a photopeak of 75 keV with a 20% width. Quantitative stability and recovery coefficients were investigated over a sequence of 19 scans with buffered 161Tb solution at total phantom activity ranging from 70 to 4990 MBq.

Results

Sphere recovery coefficients were 0.60 ± 0.05, 0.52 ± 0.07, 0.45 ± 0.07, 0.39 ± 0.07, 0.28 ± 0.08, and 0.20 ± 0.08 for spheres 37, 28, 22, 17, 13, and 10mm, respectively, when considered across all activity and scan durations with dual-energy window scatter correction. Whole-field reconstructed sensitivity was calculated as 1.42E−5 counts per decay. Qualitatively, images exhibited no visual artefacts and were comparable to 177Lu SPECT/CT.

Conclusions

Quantitative SPECT/CT of 161Tb is feasible over a range of activities enabling dosimetry analogous to 177Lu whilst also producing suitable imaging for clinical review. This has been incorporated into a prospective trial of 161Tb-PSMA for men with metastatic prostate cancer.
Prevention of umbilical outpouchings and mortality in pigs: Meloxicam, tying, cutting, and chlorhexidine versus amoxicillin or no treatment? A clinical field trial
Authors: Hansen Marie-Louise , Larsen Inge , Jensen Tina Birk , Kristensen Charlotte Sonne , Pedersen Ken Steen
Published: February 2024

Background

Umbilical outpouchings (UOs) are common in Danish pigs. Neonatal antibiotics are therefore used with the hope of reducing umbilical infections and subsequently UOs. However, the effect of neonatal antibiotics on preventing UO has been the subject of mixed conclusions, and secondly, treating all animals with antibiotics might exacerbate the development of antimicrobial resistance.

This study analysed the effects of different treatments on the prevalence of umbilical outpouchings and mortality from birth to nursery unit. All treatment was on the day of birth. The groups were: a negative control group, an antibiotic group receiving amoxicillin, and an experimental group where the piglets had their umbilical cord disinfected with chlorhexidine, followed by tying and clipping, and lastly, injection with meloxicam. The pigs were examined six weeks after weaning, and all pigs that died during the study were autopsied.

Results

There were 5494 pigs divided across the three groups. There were no statistically significant differences in UO prevalence between the groups: control 3.9%, antibiotic 4.2%, and experimental 4.0% (p = 0.87). The only variable affecting the prevalence of UOs in this study was sex with females being at higher risk. There were no statistically significant differences in mortality between the groups from birth until departure from the nursery unit: control 22.9%, antibiotic 21%, and experimental 21.4% (p = 0.33). The variables affecting mortality were sex, intrauterine growth restriction (IUGR), birth weight, and cross fostering. Males had higher odds of dying, as had piglets recorded with some degree of IUGR. Also, low birth weight increased the odds of dying for all weight quartiles compared to the fourth (the heaviest piglets > 1.6 kg), as well as cross fostering increased the odds ratio of dying.

Conclusions

This study found no significant differences in the prevalence of UOs and mortality following different treatments at birth. The study showed that the prevalence of UO and mortality was not reduced following the administration of amoxicillin or meloxicam in combination with disinfection and tying of the umbilical cord.
Co-producing an online patient public community research hub: a qualitative study exploring the perspectives of national institute for health research (NIHR) research champions in England
Authors: Hoverd Eleanor , Staniszewska Sophie , Dale Jeremy , Spencer Rachel , Devrell Anne , Khan Dena , Lamouline Carrol , Saleem Sanya , Smith Pam
Published: February 2024

Background

Patient and Public Involvement and Engagement (PPIE) should be embedded as part of researchers’ everyday practice. However, this can be challenging. Creating a digital presence for PPIE as part of Higher Education Institutes’ (HEIs) infrastructure may be one way of supporting this. This can support how information is made available to patients and members of the public, but relatively little is known about how HEIs can best do this. Our aim was to develop a university website for patients and members of the public to learn about ways to get actively involved in research and be able to access the results of health and social care research.

Methods

This project involved working as partners with five National Institute for Health and Care Research (NIHR) Research Champions. NIHR Research Champions are volunteers who raise awareness and share experiences about health and social care research. Content of a prototype Patient Public Community Research Hub website was co-produced with the Research Champions, and then 15 NIHR Research Champions from across England were asked for their views about the website.

Findings

The information collected told us that the Patient Public Community Research Hub was viewed as being beneficial for increasing visibility of PPIE opportunities and sharing the findings of studies though needs further work: to make the information more user-friendly; to improve the methods for directing people to the site and to create new ways of connecting with people. It provides a foundation for further co-development and evaluation. A set of recommendations has been developed that may be of benefit to other HEIs and organisations who are committed to working with patients and members of the public.
Is it harmful or helpful? Examining the causes and consequences of generative AI usage among university students
Authors: Abbas Muhammad , Jam Farooq Ahmed , Khan Tariq Iqbal
Published: February 2024

While the discussion on generative artificial intelligence, such as ChatGPT, is making waves in academia and the popular press, there is a need for more insight into the use of ChatGPT among students and the potential harmful or beneficial consequences associated with its usage. Using samples from two studies, the current research examined the causes and consequences of ChatGPT usage among university students. Study 1 developed and validated an eight-item scale to measure ChatGPT usage by conducting a survey among university students (N = 165). Study 2 used a three-wave time-lagged design to collect data from university students (N = 494) to further validate the scale and test the study’s hypotheses. Study 2 also examined the effects of academic workload, academic time pressure, sensitivity to rewards, and sensitivity to quality on ChatGPT usage. Study 2 further examined the effects of ChatGPT usage on students’ levels of procrastination, memory loss, and academic performance. Study 1 provided evidence for the validity and reliability of the ChatGPT usage scale. Furthermore, study 2 revealed that when students faced higher academic workload and time pressure, they were more likely to use ChatGPT. In contrast, students who were sensitive to rewards were less likely to use ChatGPT. Not surprisingly, use of ChatGPT was likely to develop tendencies for procrastination and memory loss and dampen the students’ academic performance. Finally, academic workload, time pressure, and sensitivity to rewards had indirect effects on students’ outcomes through ChatGPT usage.
Using 6-CIT, P300 encephalography, and pro-inflammation assessments for screening age-related cognitive decline and exploring associated risk factors in Egyptian elderly
Authors: Saleh Mai S. , Galal Asmaa F. , Sallam Sara F. , Mowaad Noha A. , Zeidan Hala M. , Hashish Adel , Elhabashy Hala R. , Heikal Ola A.
Published: February 2024

Background

The elderly population is suffering from many mental health problems that are aggravated as a matter of age and cognitive decline is a serious one of them. The aim of the present work is to screen the cognitive performance among a sample of Egyptian elderly volunteers and to investigate the associated risk factors.

Results

A sample of 88 elderly volunteers from both genders was enrolled in the study according to the specified eligibility criteria after signing the approval consent. Medical history and socio-demographic data were collected from all participants in addition to basic clinical examination. Cognitive performance was assessed using the 6-Item Cognitive Impairment Test (6-CIT) while the endogenous event-related potentials (ERP) was measured using P300. The inflammatory biomarkers; TNF-α and COX-2 levels were assessed in serum using ELISA technique in addition to gene expression of TNF-α, PPAR-γ and CD-36 exploration using qRT-PCR. About half (51%) of the sample under investigation showed cognitive problems with scores on the 6-CIT exceeding the normal level. TNF-α serum levels showed positive correlation with P300 latency and correlated negatively with P300 reaction time. Furthermore, serum COX-2 levels correlated positively with P300 reaction time and negatively with P300 amplitude.

Conclusion

The study population is showing early signs of cognitive decline that invites attention to the importance of spreading preventive measures against further deterioration. Inflammatory biomarkers under investigation and 6-CIT are suggested to be used in prediction of early stages of cognitive decline among the elderly population.
Inflammatory cytokines and their potential role in Sjogren’s syndrome risk: insights from a mendelian randomization study
Authors: Shi Wenbin , Xu Yuli , Zhang Anan , Jia Xiqun , Liu Shuhua , Hu Ziyang
Published: February 2024

Aim

This study aimed to investigate the causal impact of inflammatory cytokines on Sjogren’s Syndrome (SS) and to identify potential biomarkers for SS clinical management using Mendelian Randomization (MR).

Materials and methods

Leveraging GWAS summary data of inflammatory cytokines and SS, we executed the first two-sample MR analysis. Genetic variants from prior GWASs associated with circulating inflammatory cytokines served as instrumental variables (IVs). Data regarding cytokines were analyzed using the Olink Target-96 Inflammation panel, synthesizing data from 14,824 participants. GWAS summary statistics for SS were procured from the UK Biobank, focusing on samples of European ancestry. To discern the causal relationship between inflammatory cytokines and SS, several MR methodologies, including inverse variance weighted (IVW) and MR-Egger regression, were applied.

Results

After rigorous IV quality control, 91 cytokines were incorporated into the MR analysis. The IVW analysis identified 8 cytokines with a positive association to SS: Axin-1 (OR 2.56, 95% CI 1.07–6.10), T-cell surface glycoprotein CD5 (OR 1.81, 95% CI 1.08–3.02), CUDP1 (OR 1.61, 95% CI 1.00-2.58), CXCL10 (OR 1.92, 95% CI 1.25–2.95), IL-4 (OR 2.18, 95% CI 1.22–3.91), IL-7 (OR 2.35, 95% CI 1.27–4.33), MCP-2 (OR 1.27, 95% CI 1.05–1.54), and TNFRSF9 (OR 1.83, 95% CI 1.03–3.24), suggesting their potential in increasing SS risk.

Conclusion

Our study conducted through MR, identified various inflammatory cytokines associated with SS risk, validating some previous research results and offering some new potential biomarkers for SS. However, these findings necessitate further research for validation and exploration of their precise role in the onset and progression of SS.
Comparison of magnetic resonance elastography and diffusion-weighted imaging for differentiating benign and malignant liver lesions
Authors: Abdelgawad Mohammed Saied , Elseady Bassuoni Abdelaziz , ELabd Osama Lotfy , Kohla Mohamed Samy , Samea Mohamed El Sayed Abdel
Published: February 2024

Background

Imaging is a crucial diagnostic tool in focal liver lesions (FLLs) diagnosis. Without the need for an intravenous contrast agent, two such MRI methods that can distinguish between benign and malignant FLLs are diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE). The purpose of this study was to assess the utility of diffusion-weighted magnetic resonance imaging and magnetic resonance elastography in the identification and differentiation of benign and malignant hepatic focal lesions.

Methods

This cross-sectional study was carried out on ninety patients (with mean age 52 years) with hepatic focal lesions (29 benign and 61 malignant). Both MRE and DWI were performed on the patients. A modified gradient-echo sequence was used for MRE, and respiratory-triggered fat-suppressed single-shot echoplanar DW imaging (b = 0.800) was used for DWI. Maps of the apparent diffusion coefficient (ADC) and stiffness were produced. Regions of interest were placed over the FLLs on stiffness and ADC maps to get FLL ADC values and mean stiffness. Receiver operating curve (ROC) analysis was used to compare the roles of MRE and DWI in the differentiation of benign and malignant FLL.

Results

The ADC of FLLs and MRE stiffness exhibited strong negative correlation [(r: −0.559; p < 0.001)]. Compared to malignant FLLs, benign FLLs had much higher mean ADC values. However, compared to benign FLLs, malignant FLLs exhibited much greater mean stiffness. FNH has the lowest mean stiffness of all FLLs, at less than 2.22 kPa. Among FLLs, CCAs had the lowest mean ADC values and the highest mean stiffness. The results showed that the MRE and DWI cutoff values were > 4.23 and ≤ 1.43, respectively; the area under the curve (AUC) values were 0.991 and 0.894, and the sensitivity and specificity results were 96.7%, 93.1%, and 85.2%, 89.7%, respectively.

Conclusions

MRE was found to be more sensitive method for identifying benign and malignant hepatic focal lesions than DWI.
Development and characterization of niosomes loaded mucoadhesive biodegradable ocular inserts for extended release of pilocarpine HCl
Authors: Alotaibi Tamara Ahmad , Iyire Affiong , Assaf Shereen , Dahmash Eman Zmaily
Published: February 2024

Background

Pilocarpine HCl is a non-selective muscarinic receptor agonist that is prescribed for the treatment of glaucoma. The use of pilocarpine conventional eye drops is associated with several side effects, such as loss of visual acuity, and the need for several applications due to rapid drainage away via the nasolacrimal duct, especially for elderly people. Such adverse effects can lead to low patient compliance and poor clinical outcomes. Therefore, the aim of this project was to develop, optimise and characterise a biodegradable pilocarpine HCl ocular insert using niosomes as a drug delivery vehicle. To achieve that, various polymers such as hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), and a blend of both were investigated to prepare the ocular inserts using solvent casting technique. The niosomes of pilocarpine HCl were prepared using span-60 and cholesterol by thin film hydration method. The produced noisome-loaded ocular inserts were characterised using various analytical techniques, including Fourier Transform Infrared (FTIR), X-ray Diffractions (XRD), thermal analysis, particle size analysis, weight and content uniformity, surface pH and drug release profile, among others.

Results

The results indicated that drug-free ocular inserts of the two polymers (HPMC + PVA) were better than single polymer-based ocular inserts (HPMC or PVA alone). The formed niosomes demonstrated good entrapment efficiency of 49.7% ± 7.0, with an average particle size of 325.7 ± 3.5 nm. The FTIR analysis showed no interaction between the compositions of niosomes. Four optimal formulations with various co-polymer ratios and pilocarpine content were further evaluated. Pilocarpine-containing niosomes-loaded ocular inserts provided uniformity in pilocarpine content (89–96%), with 34.8% moisture content and an average pH of 7. The release profile of niosomes-loaded inserts demonstrated an initial burst release within 2 h ranging from 26.54% (T4) to 41.22% (T2), and continuous sustained release for the next 24 h (68.32 ± 5.11% (T4) to 82.11 ± 6.01% (T2)).

Conclusions

This work successfully optimised biodegradable ocular inserts containing slow-release pilocarpine HCl encapsulated in niosomes for the treatment of glaucoma without dose dumping, resulting in a user-friendly drug delivery system.

Graphical abstract
Impact of cluster farming on smallholder farmers teff commercialization in Ethiopia
Authors: Endalew Birara , Elias Asres , Yasunobu Kumi
Published: February 2024

Background

Cluster farming is an agricultural practice that involves organizing and grouping together farmers within a specific geographic area based on proximity of their farm plots to create synergies and economies of scale. In developing countries including Ethiopia cluster farming has gained prominence as a strategic initiative to foster commercialized agriculture and enhance the livelihoods of smallholder farmers by integrating their production within the broader value chain. In light of this, the government of Ethiopia plans to promote cluster farming throughout the country based on the best practices of the four cluster farming priority regions and 10 high-value commodities. Teff is one of the high-value commodities in the cluster farming priority regions. However, the impact of cluster farming on teff commercialization was not studied before.

Methods

We conducted this study to examine the impact of cluster farming on teff commercialization using nationally representative data collected by Agricultural Transformation Institute of Ethiopia. Then, we analyzed the data using descriptive and inferential statistics, commercialization index, and endogenous switching regression model.

Results

The result revealed that the mean teff commercialization of cluster farming participants was higher than non-participants in all the cluster farming priority regions of Ethiopia. Similarly, the model result indicated that cluster farming had a positive and significant impact on teff commercialization at p < 0.01.

Conclusion

The findings suggest that the promotion of cluster farming facilitates teff commercialization in Ethiopia. However, we recommend further studies using panel data collected from large samples to provide a longitudinal perspective on the impact of cluster farming on teff commercialization over time. The findings of these studies can offer comprehensive insights and concrete information that can inform policymakers to support and promote teff cluster farming in Ethiopia.
The First Etherization in England: New Research Regarding the Identity of the First Patient, Miss Lonsdale
Authors: Mather Laurence E. , Haridas Rajesh P.
Published: February 2024

On December 19, 1846, at the London home of Francis Boott, dentist James Robinson administered the vapor of diethyl ether to a young female patient named Miss Lonsdale. This was the earliest known attempt in England to provide painless operating conditions for a dental extraction, and it was successful. Many authors have since written much about Boott and Robinson, but scarcely anything is known about Miss Lonsdale. In contemporaneous accounts of the event, Robinson referred to his patient as a “young person” and a “young lady”; Boott, however, named her, suggesting that she was publicly recognizable. Our initial attempt to identify Miss Lonsdale was based on genealogical, United Kingdom Census, and other public records, using selection criteria based on age, name recognition, familial relationships, and London addresses. This produced 7 possible candidates from publicly recognizable families, though none was notable in her own right. Our second attempt was based primarily on contemporaneous newspaper records, among which were published 2 private letters in which Boott referred to Robinson’s patient as a “girl.” We found that “Miss Lonsdale” was the publicly recognizable name of 2 young stage-performing sisters, Adeline Lonsdale, a danseuse, and Annie Lonsdale, an actor-comedienne. Both subsequently emigrated to the United States where they were well-known stage performers. Accordingly, we suggest that both are highly probable candidates for that etherized patient, with the younger sister Adeline then more publicly recognizable. However, no records were found that directly associated any of the Miss Lonsdale candidates with that first dental anesthetic in England.
Depictions of “mental illness” in Greek criminal court rulings: Α discourse analysis
Authors: Mousourouli Eleni , Neztekidou Despina , Georgaca Eugenie
Published: February 2024

The present study investigates the constructions of people diagnosed with “mental illness” in Greek criminal court rulings. A Foucauldian discourse analysis approach was applied to criminal court rulings published from 2009 to 2018 to identify dominant discursive resources used to construct “mental illness”, as well as the functions performed by judicial discourse through the specific depictions of perpetrators and their crimes. Two main constructs emerged from the analysis. When constructing the unimputable “dangerous mental patient”, an intersection of biomedical and dangerousness discourses depicts the person as unpredictable, incapable of self-awareness, self-determination, and moral judgment. In the imputable “criminal personality” construction, the impact of “mental illness” on the committed crimes is relativized, since the criminal act is attributed to psychological characteristics of the individual, who is portrayed as deliberately violating the rules of socially acceptable behavior despite being capable of rational thinking and moral reasoning. The central issues that emerged include the pre-constructed categorization of the perpetrators into imputable or non-imputable, according to the determined degree of moral agency, and the selective utilization of biomedical discourse by the court, whereby it evaluates psychiatric expertise sometimes as objective evidence and others as unreliable opinion.
Effect of Centella asiatica ethanol extract on zebrafish larvae (Danio rerio) insomnia model through inhibition of Orexin, ERK, Akt and p38
Authors: Afif Zamroni , Eddy Santoso Mochammad Istiadjid , Nurdiana . , Khotimah Husnul , Satriotomo Irawan , Kurniawan Shahdevi Nandar , Sujuti Hidayat , Iskandar Dheka Sapti , Hakimah Annisatul
Published: February 2024

Background: Insomnia is difficulty initiating or maintaining sleep for at least three nights a week or more and lasting for at least 3 months. One of the molecules that play a role in the circadian rhythm of arousal system is hypocretin/orexin. Orexin activates the p38-MAPK signaling pathway and increases phosphorylated ERK1/2 levels. Centella asiatica (CA) has a role in the signal work of the MAPK/ERK, Akt, and p38 path in many various diseases. Methods: The research method used is true laboratory experimental. The research approach used was randomized control group post-test only. Zebrafish embryos aged 0-7 dpf were used in this study. The treatment group consisted of 5 groups: normal, insomnia, insomnia + 2.5 μg/mL CA, insomnia + 5 μg/mL CA, and insomnia + 10 μg/mL CA. The locomotor motion of zebrafish larvae was observed using Basler cameras on days five-, six- and seven-day post fertilization (dpf), then analyzed by using Western Blot method. Results: The results proved that exposure to CA extract was able to reduce the expression of orexin (91963 ± 9129) and p38 (117425 ± 6398) as an arousal trigger in the sleep-wake cycle, with the most optimal concentration of CA 5 μg/mL. Exposure to CA extract was also able to reduce the expression of ERK (94795 ± 30830) and Akt (60113.5 ± 27833.5) with an optimum concentration of CA 2.5 μg/mL. Conclusion: Exposure to CA extract was able to improve the sleep activity of zebrafish larvae insomnia model by extending the total inactivity time (cumulative duration) and shortening the duration of first sleep (latency to first) in light and dark phases through inhibition of orexin, ERK, p38, and Akt.
Behavioural change for Parkinson’s Disease: A randomised controlled feasibility study to promote physical activity and exercise adherence among people with Parkinson’s: study protocol
Authors: Ahern Leanne , Timmons Suzanne , Lamb Sarah E. , McCullagh Ruth
Published: February 2024

Background Parkinson’s is a common progressive neurological condition characterized by motor and non-motor deficits. Physical activity and exercise can improve health, but many people with Parkinson’s (PwP) have trouble reaching the recommended dosage. Our recent literature review found improvements in exercise adherence with behavioural change interventions, but it remains unclear which are most effective. Further qualitative research and patient and public involvement has informed a novel behavioural change intervention to be tested alongside an existing exercise program. Objective To examine the feasibility of behavioural change techniques delivered alongside an exercise programme to improve physical activity, function, and self-efficacy in PwP (and study procedures) to inform a future pilot RCT trial. Methods A parallel-arm single blinded randomised feasibility study. Twenty participants with Parkinson’s (Hoehn and Yahr stage 1-3) will be recruited from a physiotherapy primary-care waiting list. Following written consent, and baseline assessment, the participants will be randomly allocated to the intervention (n=10) or the control group (n=10). Both groups will receive usual care, which includes a weekly program of a multidisciplinary education, a supervised exercise class and a prescribed home exercise program. The intervention group will receive additional behavioural change techniques, targeting behaviour regulation, belief about capabilities and social influences. Class and home exercise adherence, behavioural component uptake and adherence, and negative events will be recorded. Outcomes will include enrolment and maintenance rates, physical function, falls, physical activity, and exercise self-efficacy measured pre- and post- the 12-week program (in-person). Surveys will be used to compare experiences and satisfaction between groups. Exit interviews will be completed with the intervention group only, exploring their experience of the behavioural change techniques. Discussion The results will help inform a future pilot RCT, based on the intervention acceptability, consent rate, maintenance, and protocol integrity. Trial Registration ClincialTrials.gov NCT06192628
JointTracker: Real-time inertial kinematic chain tracking with joint position estimation
Authors: Taetz Bertram , Lorenz Michael , Miezal Markus , Stricker Didier , Bleser-Taetz Gabriele
Published: February 2024

In-field human motion capture (HMC) is drawing increasing attention due to the multitude of application areas. Plenty of research is currently invested in camera-based (markerless) HMC, with the advantage of no infrastructure being required on the body, and additional context information being available from the surroundings. However, the inherent drawbacks of camera-based approaches are the limited field of view and occlusions. In contrast, inertial HMC (IHMC) does not suffer from occlusions, thus being a promising approach for capturing human motion outside the laboratory. However, one major challenge of such methods is the necessity of spatial registration. Typically, during a predefined calibration sequence, the orientation and location of each inertial sensor are registered with respect to the underlying skeleton model. This work contributes to calibration-free IHMC, as it proposes a recursive estimator for the simultaneous online estimation of all sensor poses and joint positions of a kinematic chain model like the human skeleton. The full derivation from an optimization objective is provided. The approach can directly be applied to a synchronized data stream from a body-mounted inertial sensor network. Successful evaluations are demonstrated on noisy simulated data from a three-link chain, real lower-body walking data from 25 young, healthy persons, and walking data captured from a humanoid robot. The estimated and derived quantities, global and relative sensor orientations, joint positions, and segment lengths can be exploited for human motion analysis and anthropometric measurements, as well as in the context of hybrid markerless visual-inertial HMC.
Releasing synthetic data from the Avon Longitudinal Study of Parents and Children (ALSPAC): Guidelines and applied examples
Authors: Major-Smith Daniel , Kwong Alex S. F. , Timpson Nicholas J. , Heron Jon , Northstone Kate
Published: February 2024

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective birth cohort. Since its inception in the early 1990s, the study has collected over thirty years of data on approximately 15,000 mothers, their partners, and their offspring, resulting in over 100,000 phenotype variables to date. Maintaining data security and participant anonymity and confidentiality are key principles for the study, meaning that data access is restricted to bona fide researchers who must apply to use data, which is then shared on a project-by-project basis. Despite these legitimate reasons for restricting data access, this does run counter to emerging best scientific practices encouraging making data openly available to facilitate transparent and reproducible research. Given the rich nature of the resource, ALSPAC data are also a valuable educational tool, used for teaching a variety of methods, such as longitudinal modelling and approaches to modelling missing data. To support these efforts and to overcome the restrictions in place with the study’s data sharing policy, we discuss methods for generating and making openly available synthesised ALSPAC datasets; these synthesised datasets are modelled on the original ALSPAC data, thus maintaining variable distributions and relations among variables (including missing data) as closely as possible, while at the same time preserving participant anonymity and confidentiality. We discuss how ALSPAC data can be synthesised using the ‘synthpop’ package in the R statistical programming language (including an applied example), present a list of guidelines for researchers wishing to release such synthesised ALSPAC data to follow, and demonstrate how this approach can be used as an educational tool to illustrate longitudinal modelling methods.
Investigating light sensitivity in bipolar disorder (HELIOS-BD)
Authors: Roguski Amber , Needham Nicole , MacGillivray Tom , Martinovic Jasna , Dhillon Baljean , Riha Renata L. , Armstrong Lyle , Campbell Iain H. , Ferguson Amy , Hilgen Gerrit , Lako Majlinda , Ritter Philipp , Santhi Nayantara , von Schantz Malcolm , Spitschan Manuel , Smith Daniel J.
Published: February 2024

Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar disorder who are being treated with lithium have less pronounced light responses and attenuated retinal changes compared to individuals with bipolar disorder not being treated with lithium. This study represents a comprehensive investigation of visual and non-visual light responses in a large bipolar disorder population, with great translational potential for patient stratification and treatment innovation.
Injectable antibiotic use in India: public-private share in volume and cost
Authors: Fazaludeen Koya Shaffi , Ganesh Senthil , Klemperer Katherine , Yadav Prashant , McDonnell Anthony
Published: February 2024

Background Consumption of injectable antibiotics is not widely studied, despite injectables constitute a major share of antibiotic cost. This study aimed to understand the share of oral and injectable antibiotic consumption and cost at the national level in India, and the public and private sector shares in the provision and cost of injectables in Kerala state. Methods We used the PharmaTrac private sector sales dataset and the Kerala Medical Services Corporation public sector procurement dataset. Using WHO Access, Watch, Reserve (AWaRe) and Anatomical Therapeutic Chemical (ATC) Classifications, we estimated the annual total and per-capita consumption, and the annual total, per defined daily dose (DDD), and per-capita spending on injectables. Results Although 94.9% of total antibiotics consumed at the national level were oral preparations, 35.8% of total spending were on injectables. In Kerala , around 33% of total antibiotic spending in the private sector were for injectables, compared to around 25% in the public sector. The public sector used fewer injectable antibiotic formulations (n=21) compared the private sector (n=69). The cost per DDD was significantly higher in the private sector as compared to the public sector. Despite only accounting for 6.3% of the cost share, the public sector provided 31.4% of injectables, indicating very high efficiency. Across both sectors, Watch group antibiotics were significantly more consumed and at a significantly higher cost than Access group antibiotics, for example in nearly double the quantity and at 1.75 times the price per DDD in the private sector. Reserve group antibiotics made up the lowest consumption share (0.61% in the private sector), but at the highest cost per DDD (over 16 times that of Access). Conclusions Public sector showed higher cost efficiency in antibiotic provisioning compared to private sector. Appropriate antibiotic use cannot be achieved through drug price control alone but requires extensive engagement with private providers through structured stewardship programs.
The genome sequence of the Straw Underwing, Thalpophila matura (Hufnagel, 1766)
Authors: Boyes Douglas , Skojec Chelsea , Kawahara Akito Y. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: February 2024

We present a genome assembly from an individual male Thalpophila matura (the Straw Underwing; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence is 520.4 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.52 kilobases in length. Gene annotation of this assembly on Ensembl identified 19,185 protein coding genes.
The genome sequence of the giant willow aphid, Tuberolachnus salignus (Gmelin, 1790)
Authors: Crowley Liam M. , McCulloch James , James Reuben ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: February 2024

We present a genome assembly from an individual female Tuberolachnus salignus (the giant willow aphid; Arthropoda; Insecta; Hemiptera; Aphididae). The genome sequence is 456.8 megabases in span. Most of the assembly is scaffolded into 10 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 22.43 kilobases in length.
The genome sequence of the Emperor moth, Saturnia pavonia (Linnaeus, 1758)
Authors: Crowley Liam M. , Baker Ellen , Holland Peter W. H. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: February 2024

We present a genome assembly from an individual male Saturnia pavonia (the Emperor moth; Arthropoda; Insecta; Lepidoptera; Saturniidae). The genome sequence is 489.9 megabases in span. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.29 kilobases in length. Gene annotation of this assembly on Ensembl identified 11,903 protein coding genes.
The genome sequence of a hoverfly, Merodon equestris (Fabricius, 1794)
Authors: Sivell Olga , Crowley Liam M. ,   Natural History Museum Genome Acquisition Lab,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: February 2024

We present a genome assembly from an individual female Merodon equestris (hoverfly; Arthropoda; Insecta; Diptera; Syrphidae). The genome sequence is 873.0 megabases in span. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 15.95 kilobases in length.
The genome sequence of the Large Nutmeg, Apamea anceps (Denis & Schiffermüller, 1775)
Authors: Holland Peter W.H. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: February 2024

We present a genome assembly from an individual male Apamea anceps (the Large Nutmeg; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence is 615.8 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.43 kilobases in length.
Phylogenetic signatures reveal multilevel selection and fitness costs in SARS-CoV-2
Authors: Bonetti Franceschi Vinicius , Volz Erik
Published: February 2024

Background Large-scale sequencing of SARS-CoV-2 has enabled the study of viral evolution during the COVID-19 pandemic. Some viral mutations may be advantageous to viral replication within hosts but detrimental to transmission, thus carrying a transient fitness advantage. By affecting the number of descendants, persistence times and growth rates of associated clades, these mutations generate localised imbalance in phylogenies. Quantifying these features in closely-related clades with and without recurring mutations can elucidate the tradeoffs between within-host replication and between-host transmission. Methods We implemented a novel phylogenetic clustering algorithm (mlscluster, https://github.com/mrc-ide/mlscluster) to systematically explore time-scaled phylogenies for mutations under transient/multilevel selection. We applied this method for a SARS-CoV-2 time-calibrated phylogeny with >1.2 million sequences from England, and characterised these recurrent mutations that may influence transmission fitness across PANGO-lineages and genomic regions using Poisson regressions and summary statistics. Results We found no major differences across two epidemic stages (before and after Omicron), PANGO-lineages, and genomic regions. However, spike, nucleocapsid, and ORF3a were proportionally more enriched for TFP-homoplasies than other proteins. We provide a catalog of SARS-CoV-2 sites under multilevel selection, which can guide experimental investigations within and beyond the spike protein. Conclusions This study highlights the existence of important tradeoffs between within-host replication and between-host transmission shaping the fitness landscape of SARS-CoV-2.