bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intronic small nucleolar RNAs regulate host gene splicing through base pairing with their adjacent intronic sequences
Authors: Bergeron Danny , Faucher-Giguère Laurence , Emmerichs Ann-Kathrin , Choquet Karine , Song Kristina Sungeun , Deschamps-Francoeur Gabrielle , Fafard-Couture Étienne , Rivera Andrea , Couture Sonia , Churchman L. Stirling , Heyd Florian , Abou Elela Sherif , Scott Michelle S. 
Published: July 2023

Abstract
Background
Small nucleolar RNAs (snoRNAs) are abundant noncoding RNAs best known for their involvement in ribosomal RNA maturation. In mammals, most expressed snoRNAs are embedded in introns of longer genes and produced through transcription and splicing of their host. Intronic snoRNAs were long viewed as inert passengers with little effect on host expression. However, a recent study reported a snoRNA influencing the splicing and ultimate output of its host gene. Overall, the general contribution of intronic snoRNAs to host expression remains unclear.

Results
Computational analysis of large-scale human RNA-RNA interaction datasets indicates that 30% of detected snoRNAs interact with their host transcripts. Many snoRNA-host duplexes are located near alternatively spliced exons and display high sequence conservation suggesting a possible role in splicing regulation. The study of the model SNORD2-EIF4A2 duplex indicates that the snoRNA interaction with the host intronic sequence conceals the branch point leading to decreased inclusion of the adjacent alternative exon. Extended SNORD2 sequence containing the interacting intronic region accumulates in sequencing datasets in a cell-type-specific manner. Antisense oligonucleotides and mutations that disrupt the formation of the snoRNA-intron structure promote the splicing of the alternative exon, shifting the EIF4A2 transcript ratio away from nonsense-mediated decay.

Conclusions
Many snoRNAs form RNA duplexes near alternative exons of their host transcripts, placing them in optimal positions to control host output as shown for the SNORD2-EIF4A2 model system. Overall, our study supports a more widespread role for intronic snoRNAs in the regulation of their host transcript maturation.
Starting a conversation about estimands with public partners involved in clinical trials: a co-developed tool
Authors: Cro Suzie , Kahan Brennan C , Patel Akshaykumar , Henley Ania , C Joanna , Hellyer Paul , Kumar Manos , Rahman Yasmin , Goulão Beatriz 
Published: July 2023

Abstract
Background
Clinical trials aim to draw conclusions about the effects of treatments, but a trial can address many different potential questions. For example, does the treatment work well for patients who take it as prescribed? Or does it work regardless of whether patients take it exactly as prescribed? Since different questions can lead to different conclusions on treatment benefit, it is important to clearly understand what treatment effect a trial aims to investigate—this is called the ‘estimand’. Using estimands helps to ensure trials are designed and analysed to answer the questions of interest to different stakeholders, including patients and public. However, there is uncertainty about whether patients and public would like to be involved in defining estimands and how to do so. Public partners are patients and/or members of the public who are part of, or advise, the research team. We aimed to (i) co-develop a tool with public partners that helps explain what an estimand is and (ii) explore public partner’s perspectives on the importance of discussing estimands during trial design.

Methods
An online consultation meeting was held with 5 public partners of mixed age, gender and ethnicities, from various regions of the UK. Public partner opinions were collected and a practical tool describing estimands, drafted before the meeting by the research team, was developed. Afterwards, the tool was refined, and additional feedback sought via email.

Results
Public partners want to be involved in estimand discussions. They found an introductory tool, to be presented and described to them by a researcher, helpful for starting a discussion about estimands in a trial design context. They recommended storytelling, analogies and visual aids within the tool. Four topics related to public partners’ involvement in defining estimands were identified: (i) the importance of addressing questions that are relevant to patients and public in trials, (ii) involving public partners early on, (iii) a need for education and communication for all stakeholders and (iv) public partners and researchers working together.

Conclusions
We co-developed a tool for researchers and public partners to use to facilitate the involvement of public partners in estimand discussions.
Control of ticks and tick-borne diseases in Africa through improved diagnosis and utilisation of data on acaricide resistance
Authors: Bishop Richard P. , Githaka Naftaly W. , Bazarusanga Thomas , Bhushan Chandra , Biguezoton Abel , Vudriko Patrick , Muhanguzi Dennis , Tumwebaze Maria , Bosco Timbiira John , Shacklock Caryn , Kiama Josphat , Madder Maxime , Maritz-Olivier Christine , Zhao Weining , Maree Francois , Majekodunmi Ayodele O. , Halos Lenaig , Jongejan Frans , Evans Alec 
Published: July 2023

AbstractA meeting, sponsored by the Bill and Melinda Gates Foundation (BMGF) and organised by Clinglobal, was held at The International Livestock Research Institute (ILRI) in Nairobi, Kenya, from 19th – to 21st October 2022. The meeting assembled a unique group of experts on tick control in Africa. Academia, international agencies (FAO and ILRI), the private Animal Health sector and government veterinary services were represented. The significant outcomes included: (i) a shared commitment to standardisation and improvement of acaricide resistance bioassay protocols, particularly the widely used larval packet test (LPT); (ii) development of novel molecular assays for detecting acaricide resistance; (3) creation of platforms for disseminating acaricide resistance data to farmers, veterinary service providers and veterinary authorities to enable more rational evidence-based control of livestock ticks. Implementation of enhanced control will be facilitated by several recently established networks focused on control of parasites in Africa and globally, whose activities were presented at the meeting. These include a newly launched community of practice on management of livestock ticks, coordinated by FAO, an African module of the World Association for the Advancement of Veterinary Parasitology (WAAVP-AN) and the MAHABA (Managing Animal Health and Acaricides for a Better Africa) initiative of Elanco Animal Health.
Graphical Abstract
Impact of non-regional lymph node metastases accurately revealed on 18F-PSMA-1007 PET/CT in the clinical management of metastatic hormone-sensitive prostate cancer
Authors: Jiang Zhangdong , Fan Junjie , Gan Chaosheng , Dong Xiaoxin , Gao Guoqiang , Wang Zhuonan , He Dalin , Li Lei , Duan XiaoYi , Wu Kaijie 
Published: July 2023

Abstract
Background
Non-regional lymph node (NRLN) metastases has shown increasing importance in the prognosis evaluation and clinical management of primary metastatic hormone-sensitive prostate cancer (mHSPC). Hence, this study aimed to investigate the concordance rates between 18F-PSMA-1007 PET/CT and conventional imaging (CI) in revealing NRLN metastases, and explore the impact of NRLN metastases on the management of primary mHSPC.

Methods
The medical records of 224 patients with primary mHSPC were retrospectively reviewed, including 101 patients (45.1%) only received CI for TNM classification, 24 patients (10.7%) only received 18F-PSMA-1007 PET/CT, and 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI. Among patients who received 18F-PSMA-1007 PET/CT and CI before initial treatment, the concordance rates between 18F-PSMA-1007 PET/CT and CI were analyzed. The high-volume disease was defined as the presence of visceral metastases and/or ≥ 4 bone metastases (≥ 1 beyond the vertebral bodies or the pelvis) based on the findings of 18F-PSMA-1007 PET/CT and/or CI. The primary endpoint was progression-free survival (PFS), and Cox regression analyses were performed to explore independent predictors of PFS.

Results
A total of 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI, the concordance rate in revealing NRLN metastases between 18F-PSMA-1007 PET/CT and CI was only 61.62%, and Cohen’s kappa coefficient was as low as 0.092. Moreover, 18F-PSMA-1007 PET/CT detected an additional 37 of 94 (39.4%) patients with positive NRLNs who were negative on CI. Cox regression revealed that androgen deprivation therapy (ADT), N1, high-volume, NRLN and visceral metastases were associated with worse PFS (all P < 0.05) in 224 patients. Furthermore, in patients with low-volume disease, the median PFS of patients with NRLN metastases was significantly shorter than that of patients without NRLN metastases (19.5 vs. 27.5 months, P = 0.01), while the difference between patients with low-volume plus NRLN metastases and high-volume disease was not significant (19.5 vs. 16.9 months, P = 0.55). Moreover, early docetaxel chemotherapy significantly prolonged the PFS of these patients compared with ADT alone (20.7 vs. 12.3 months, P = 0.008).

Conclusion
NRLN metastases could be accurately revealed by 18F-PSMA-1007 PET/CT, which should be considered a high-volume feature, especially concomitant with bone metastases. Furthermore, patients with low-volume plus NRLN metastases may be suitable for more intensive treatment, such as early docetaxel chemotherapy.
Gut microbiome modulates tacrolimus pharmacokinetics through the transcriptional regulation of ABCB1
Authors: Degraeve Alexandra L. , Haufroid Vincent , Loriot Axelle , Gatto Laurent , Andries Vanessa , Vereecke Lars , Elens Laure , Bindels Laure B. 
Published: July 2023

AbstractBackgroundFollowing solid organ transplantation, tacrolimus (TAC) is an essential drug in the immunosuppressive strategy. Its use constitutes a challenge due to its narrow therapeutic index and its high inter- and intra-pharmacokinetic (PK) variability. As the contribution of the gut microbiota to drug metabolism is now emerging, it might be explored as one of the factors explaining TAC PK variability. Herein, we explored the consequences of TAC administration on the gut microbiota composition. Reciprocally, we studied the contribution of the gut microbiota to TAC PK, using a combination of in vivo and in vitro models.ResultsTAC oral administration in mice resulted in compositional alterations of the gut microbiota, namely lower evenness and disturbance in the relative abundance of specific bacterial taxa. Compared to controls, mice with a lower intestinal microbial load due to antibiotics administration exhibit a 33% reduction in TAC whole blood exposure and a lower inter-individual variability. This reduction in TAC levels was strongly correlated with higher expression of the efflux transporterABCB1(also known as the p-glycoprotein (P-gp) or the multidrug resistance protein 1 (MDR1)) in the small intestine. Conventionalization of germ-free mice confirmed the ability of the gut microbiota to downregulateABCB1expression in a site-specific fashion. The functional inhibition of ABCB1 in vivo by zosuquidar formally established the implication of this efflux transporter in the modulation of TAC PK by the gut microbiota. Furthermore, we showed that polar bacterial metabolites could recapitulate the transcriptional regulation ofABCB1by the gut microbiota, without affecting its functionality. Finally, whole transcriptome analyses pinpointed, among others, the Constitutive Androstane Receptor (CAR) as a transcription factor likely to mediate the impact of the gut microbiota onABCB1transcriptional regulation.ConclusionsWe highlight for the first time how the modulation ofABCB1expression by bacterial metabolites results in changes in TAC PK, affecting not only blood levels but also the inter-individual variability. More broadly, considering the high number of drugs with unexplained PK variability transported by ABCB1, our work is of clinical importance and paves the way for incorporating the gut microbiota in prediction algorithms for dosage of such drugs.
Epidemiology of co-infections in pregnant women living with human immunodeficiency virus 1 in rural Gabon: a cross-sectional study
Authors: Davi Saskia Dede , Okwu Dearie Glory , Luetgehetmann Marc , Abba Frederique Mbang , Aepfelbacher Martin , Endamne Lillian Rene , Alabi Ayodele , Zoleko-Manego Rella , Mombo-Ngoma Ghyslain , Mahmoudou Saidou , Addo Marylyn Martina , Ramharter Michael , Mischlinger Johannes 
Published: July 2023

Abstract
Background
There is no recent epidemiological data on HIV infection in Gabon, particularly in pregnant women. To close this gap, an HIV-prevalence survey was conducted among Gabonese pregnant women, followed by a cross-sectional case–control study in which the prevalence of various co-infections was compared between HIV-positive and HIV-negative pregnant women.

Methods
Between 2018 and 2019, data for the HIV-prevalence survey were collected retrospectively in 21 Gabonese antenatal care centres (ANCs). Subsequently, for the prospective co-infection study, all HIV-positive pregnant women were recruited who frequented the ANC in Lambaréné and a comparator sub-sample of HIV-negative pregnant women was recruited; these activities were performed from February 2019 to February 2020. The mean number of co-infections was ascertained and compared between HIV-positive and HIV-negative women. Additionally, the odds for being co-infected with at least one co-infection was evaluated and compared between HIV-positive and HIV-negative women.

Results
HIV-positivity was 3.9% (646/16,417) among pregnant women. 183 pregnant women were recruited in the co-infection study. 63% of HIV-positive and 75% of HIV-negative pregnant women had at least one co-infection. There was a trend indicating that HIV-negative women were more often co-infected with sexually transmitted infections (STIs) than HIV-positive women [mean (standard deviation, SD): 2.59 (1.04) vs 2.16 (1.35), respectively; P = 0.056]; this was not the case for vector-borne infections [mean (SD): 0.47 (0.72) vs 0.43 (0.63), respectively; P = 0.59].

Conclusions
Counterintuitively, the crude odds for concomitant STIs was lower in HIV-positive than in HIV-negative women. The change of magnitude from the crude to adjusted OR is indicative for a differential sexual risk factor profile among HIV-positive and HIV-negative women in this population. This might potentially be explained by the availability of sexual health care counselling for HIV-positive women within the framework of the national HIV control programme, while no such similar overall service exists for HIV-negative women. This highlights the importance of easy access to sexual healthcare education programmes for all pregnant women irrespective of HIV status.
Pros & cons: impacts of social media on mental health
Authors: Zsila Ágnes , Reyes Marc Eric S. 
Published: July 2023

AbstractThe use of social media significantly impacts mental health. It can enhance connection, increase self-esteem, and improve a sense of belonging. But it can also lead to tremendous stress, pressure to compare oneself to others, and increased sadness and isolation. Mindful use is essential to social media consumption.
Examining the relationship between science motivational beliefs and science achievement in Emirati early adolescents through the lens of self-determination theory
Authors: Areepattamannil Shaljan , Khurma Othman Abu , Ali Nagla , Al Hakmani Rehab , Kadbey Hanadi 
Published: July 2023

Abstract
Background
A solid foundation in science is critical to students’ success in the 21st century workforce, especially in fields related to science, technology, engineering, and mathematics (STEM). Therefore, high-quality science education is critical to prepare students for the challenges of the future. However, Emirati students have consistently performed poorly on international standardized science assessments, suggesting that the underlying factors contributing to this trend need to be understood. Therefore, the present study examined the relationship between motivational beliefs in science (i.e., science self-concept and intrinsic and instrumental motivation to learn science) and science achievement in Emirati early adolescents using a self-determination theory framework.

Methods
A total of 7,915 Emirati eighth-grade students (Meanage = 13.61 years, SD = 0.53) participated in the 2019 Trends in International Mathematics and Science Study (TIMSS). The TIMSS 2019 assessment measured students’ motivational beliefs in science and their achievement in science. Path analysis and bootstrapping were used to examine the relationship between these variables and to test the mediating role of intrinsic and instrumental motivation to learn science in the relationship between science self-concept and science achievement.

Results
The results of the study indicate that science self-concept is positively related to both intrinsic and instrumental motivation to learn science and science achievement. Intrinsic motivation to learn science was significantly related to science achievement, whereas instrumental motivation was not. Moreover, intrinsic motivation to learn science alone significantly mediated the relationship between science self-concept and science achievement.

Conclusions
The study offers insights into the specific motivational beliefs associated with science achievement and highlights the importance of fostering positive science self-concept and intrinsic motivation in Emirati early adolescents. The study also suggests that interventions to promote positive science self-concept and intrinsic motivation to learn science may be particularly effective in improving science achievement in this population. These findings have important implications for educators and policymakers seeking to promote academic success and career opportunities for Emirati students in science.
The metabolic cost of inspiratory muscle training in mechanically ventilated patients in critical care
Authors: Jenkins Timothy O. , MacBean Vicky , Poulsen Mathias Krogh , Karbing Dan Stieper , Rees Stephen Edward , Patel Brijesh V. , Polkey Michael I. 
Published: July 2023

Abstract
Background
Diaphragmatic dysfunction is well documented in patients receiving mechanical ventilation. Inspiratory muscle training (IMT) has been used to facilitate weaning by strengthening the inspiratory muscles, yet the optimal approach remains uncertain. Whilst some data on the metabolic response to whole body exercise in critical care exist, the metabolic response to IMT in critical care is yet to be investigated. This study aimed to quantify the metabolic response to IMT in critical care and its relationship to physiological variables.

Methods
We conducted a prospective observational study on mechanically ventilated patients ventilated for ≥ 72 h and able to participate in IMT in a medical, surgical, and cardiothoracic intensive care unit. 76 measurements were taken on 26 patients performing IMT using an inspiratory threshold loading device at 4 cmH2O, and at 30, 50 and 80% of their negative inspiratory force (NIF). Oxygen consumption (VO2) was measured continuously using indirect calorimetry.

Results
First session mean (SD) VO2 was 276 (86) ml/min at baseline, significantly increasing to 321 (93) ml/min, 333 (92) ml/min, 351(101) ml/min and 388 (98) ml/min after IMT at 4 cmH2O and 30, 50 and 80% NIF, respectively (p = 0.003). Post hoc comparisons revealed significant differences in VO2 between baseline and 50% NIF and baseline and 80% NIF (p = 0.048 and p = 0.001, respectively). VO2 increased by 9.3 ml/min for every 1 cmH2O increase in inspiratory load from IMT. Every increase in P/F ratio of 1 decreased the intercept VO2 by 0.41 ml/min (CI − 0.58 to − 0.24 p < 0.001). NIF had a significant effect on the intercept and slope, with every 1 cmH2O increase in NIF increasing intercept VO2 by 3.28 ml/min (CI 1.98–4.59 p < 0.001) and decreasing the dose–response slope by 0.15 ml/min/cmH2O (CI − 0.24 to − 0.05 p = 0.002).

Conclusions
IMT causes a significant load-dependent increase in VO2. P/F ratio and NIF impact baseline VO2. The dose–response relationship of the applied respiratory load during IMT is modulated by respiratory strength. These data may offer a novel approach to prescription of IMT.

Take home message
The optimal approach to IMT in ICU is uncertain; we measured VO2 at different applied respiratory loads to assess whether VO2 increased proportionally with load and found VO2 increased by 9.3 ml/min for every 1 cmH2O increase in inspiratory load from IMT. Baseline NIF has a significant effect on the intercept and slope, participants with a higher baseline NIF have a higher resting VO2 but a less pronounced increase in VO2 as the inspiratory load increases; this may offer a novel approach to IMT prescription.
Trial registration ClinicalTrials.gov, registration number: NCT05101850. Registered on 28 September 2021, https://clinicaltrials.gov/ct2/show/NCT05101850
Adaptive H∞ event-triggered load frequency control in islanded microgirds with limited spinning reserve constraints
Authors: Zhang Yajian , Peng Chen 
Published: July 2023

AbstractUsing an islanded microgrid (MG) with large-scale integration of renewable energy is the most popular way of solving the reliable power supply problem for remote areas and critical electrical users. However, compared with traditional power systems, the limited spinning reserves and network communication bandwidth may cause weak frequency stability in the presence of stochastic renewable active outputs and load demand fluctuations. In this paper, an adaptive event-triggered control (ETC) strategy for a load frequency control (LFC) system in an islanded MG is proposed. First, a bounded adaptive event-triggered communication scheme is designed. This not only saves on network resources, but also ensures that the control center has a sensitive monitoring ability for the MG operating status when the frequency deviations have been effectively damped. Secondly, by fully considering the spinning reserve constraints and uncertain communication delays, the LFC system is described as a nonlinear model with saturation terms. Design criteria for ETC parameters are strictly deduced based on Lyapunov stability theory. Finally, an ETC parameter optimization algorithm based on random direction search is developed to reconcile the bandwidth occupancy and control performance. The effectiveness of the proposed method is verified in an MG test system.