bluuebunny/crossref_metadata_2025_split huggingface dataset:
ENPP2 promotes progression and lipid accumulation via AMPK/SREBP1/FAS pathway in chronic lymphocytic leukemia
Authors: Lu Liyan , Hu Xinting , Han Yang , Wang Hua , Tian Zheng , Zhang Ya , Wang Xin 
Published: December 2024

Abstract
Background
Disorders of lipid metabolism are critical factors in the progression of chronic lymphocytic leukemia (CLL). However, the characteristics of lipid metabolism and related regulatory mechanisms of CLL remain unclear.

Methods
Hence, we identified altered metabolites and aberrant lipid metabolism pathways in patients with CLL by ultra-high-performance liquid chromatography-mass spectrometry-based non-targeted lipidomics. A combination of transcriptomics and lipidomics was used to mine relevant target molecule and downstream signaling pathway. In vitro cellular assays, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, fluorescent staining, RNA sequencing, and coimmunoprecipitation were used to monitor the molecular levels as well as to explore the underlying mechanisms.

Results
Significant differences in the content of 52 lipid species were identified in CLL samples and healthy controls. Functional analysis revealed that alterations in glycerolipid metabolism, glycerophospholipid metabolism, sphingolipid metabolism, and metabolic pathways had the greatest impact on CLL. On the basis of the area under the curve value, a combination of three metabolites (phosphatidylcholine O-24:2_18:2, phosphatidylcholine O-35:3, and lysophosphatidylcholine 34:3) potentially served as a biomarker for the diagnosis of CLL. Furthermore, utilizing integrated lipidomic, transcriptomic, and molecular studies, we reveal that ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) plays a crucial role in regulating oncogenic lipogenesis. ENPP2 expression was significantly elevated in patients with CLL compared with normal cells and was validated in an independent cohort. Moreover, ENPP2 knockdown and targeted inhibitor PF-8380 treatment exerted an antitumor effect by regulating cell viability, proliferation, apoptosis, cell cycle, and enhanced the drug sensitivity to ibrutinib. Mechanistically, ENPP2 inhibited AMP-activated protein kinase (AMPK) phosphorylation and promoted lipogenesis through the sterol regulatory element-binding transcription factor 1 (SREBP-1)/fatty acid synthase (FAS) signaling pathway to promote lipogenesis.

Conclusions
Taken together, our findings unravel the lipid metabolism characteristics of CLL. Moreover, we demonstrate a previously unidentified role and mechanism of ENPP2 in regulation of lipid metabolism, providing a novel therapeutic target for CLL treatment.
Transgenic tomato strategies targeting whitefly eggs from apoplastic or ovary-directed proteins
Authors: Thompson Natalie S. , Anwar Aliya Fathima , Krum David , Ream Michael , Shouse Eva , Weston Zachary , Chen Yun-Ru , Sam Aisa , Deguchi Michihito , Kariuki Samwel M. , Rudrabhatla Sairam V. , Curtis Wayne R. 
Published: December 2024

Abstract
Background
Transgenic plants expressing proteins that target the eggs of the ubiquitous plant pest Bemisia tabaci (whitefly) could be an effective insecticide strategy. Two approaches for protein delivery are assessed using the mCherry reporter gene in transgenic tomato plants, while accommodating autofluorescence in both the plant, phloem-feeding whitefly and pedicle-attached eggs.

Results
Both transgenic strategies were segregated to homozygous genotype using digital PCR. The first strategy uses a glycotransferase secretion signal peptide. Despite bright apoplastic accumulation, mCherry is not evident in the eggs. The second strategy targets in vivo whitefly eggs, where the mCherry transgene was fused to a protein transduction domain (PTD) to facilitate uptake into the whitefly hemolymph as well as a synthetic vitellogenin ovary-targeting sequence. Phloem-specific expression of the mCherry fusion is achieved from a Commelina viral promoter. Accumulation was not sufficient to be observed in females feeding on these ovary-targeting plants nor in their eggs subsequently laid on non-transgenic plants. Egg protection may be mediated by protease activity which is observed in macerated eggs.

Conclusions
mCherry proved an effective reporter for the desired tissue-specific expression in tomato, but insufficiently sensitive to allow for localization in feeding whiteflies or their eggs. Segregated homozygous transgenic tomato lines were important for drawing these conclusions. The implications of these observations to possible pest-control strategies including preliminary expression of analogous chitinase constructs are discussed.
Self-monitoring of blood pressure following a stroke or transient ischaemic attack (TASMIN5S): a randomised controlled trial
Authors: McManus R. J. , Smith A. , Temple E. , Yu L. M. , Allen J. , Doogue R. , Ford G. A. , Glynn L. , Guthrie B. , Hall P. , Hinton L. , Hobbs F. D. R. , Mant J. , McKinstry B. , Mead G. , Morton K. , Rai T. , Rice C. , Roman C. , Stoddart A. , Tarassenko L. , Velardo C. , Williams M. , Yardley L. ,   on behalf of the TASMIN5S investigators
Published: December 2024

Abstract
Background
Blood pressure (BP) control following stroke is important but currently sub-optimal. This trial aimed to determine whether self-monitoring of hypertension with telemonitoring and a treatment escalation protocol, results in lower BP than usual care in people with previous stroke or transient ischaemic attack (TIA).

Methods
Unblinded randomised controlled trial, comparing a BP telemonitoring-based intervention with control (usual care) for hypertension management in 12 primary care practices in England. People with previous stroke or TIA with clinic systolic BP 130–180 mmHg, taking ≤ 3 antihypertensive medications and on stable treatment for at least four weeks were randomised 1:1 using secure online system to intervention or control. The BP:Together intervention comprised self-monitoring of blood pressure with a digital behavioural intervention which supported telemonitoring of self-monitored BP with feedback to clinicians and patients regarding medication titration. The planned primary outcome was difference in clinic measured systolic BP 12 months from randomisation but was not available following early study termination due to withdrawal of funding during the COVID-19 pandemic. Instead, in addition to pre-randomised data, routinely recorded BP was extracted from electronic patient records both pre- and post-randomisation and presented descriptively only. An intention to treat approach was taken.

Results
From 650 postal invitations, 129 (20%) responded, of whom 95 people had been screened for eligibility prior to the pandemic (November 2019-March 2020) and 55 (58%) were randomised. Pre-randomisation routinely recorded mean BP was 145/78 mmHg in the control (n = 26) and 145/79 mmHg in the self-monitoring (n = 21) groups. Post-randomisation mean BP was 134/73 mmHg in the control (n = 19) and 130/75 mmHg in the self-monitoring (n = 25) groups. Participants randomised to self-monitoring used the intervention for ≥ 7 months in 25/27 (93%) of cases.

Conclusions
Recruitment of people with stroke/TIA to a trial comparing a BP self-monitoring and digital behavioural intervention to usual care was feasible prior to the COVID-19 pandemic and the vast majority of those randomised to intervention used it while the trial was running. Routinely recorded blood pressure control improved in both groups. Digital interventions including self-monitoring are feasible for people with stroke/TIA and should be definitively evaluated in future trials.

Trial registration
ISRCTN57946500 06/09/2019 Prospective.
Early response of anti-vascular endothelial growth factor (anti-VEGF) in diabetic macular edema (DME) management: microperimetry and optical coherence tomography (OCT) findings: a pilot study at national eye center of third world country
Authors: Ihsan Grimaldi , Kwartika Ameliza , Widyanatha Made Indra , Virgana Rova , Iskandar Erwin , Kartasasmita Arief Sjamsulaksan 
Published: December 2024

Abstract
Purpose
To evaluate early response of retinal sensitivity (RS) and retinal morphology in diabetic macular edema (DME) patients after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment.

Methods
Sixteen eyes of 12 DME patients were included in this study conducted prospectively. All eyes underwent functional and morphologic examination of the macular area using microperimetry and optical coherence tomography (OCT) before and after intravitreal anti-VEGF injection. To determine significant differences between the values, paired t test was used. A correlation between CMT and RS was made using Spearman’s test.

Results
Patients were evaluated at baseline, one week and one month after injection. The central macular thickness (CMT) decreased significantly from 449.33 ± 100.79 μm to 427.94 ± 85.76 μm to 357.93 ± 75.92 μm. The RS improved significantly from 7.94 ± 6.43 dB to 11.09 ± 7.42 dB at one week and to 14.22 ± 7.66 dB at one month after treatment. The CMT was significant negatively correlated to RS (r=-0.259, p = < 0.001), with decay of 0.025 dB for every 1 μm increase of CMT.

Conclusions
Retinal thickening due to DME can be adequately quantified using OCT, while microperimetry can offer information about retinal sensitivity in the exact location. Therefore, microperimetry can be a useful tool in predicting the functional outcome and determining the efficacy of anti-VEGF treatment for DME patients.
The effect of eye movement desensitization on neurocognitive functioning compared to retrieval-only in PTSD patients: a randomized controlled trial
Authors: Susanty Eka , Sijbrandij Marit , Srisayekti Wilis , Suparman Yusep , Huizink Anja C. 
Published: December 2024

Abstract
Background
There is robust evidence that posttraumatic stress disorder (PTSD) is associated with neurocognitive deficits, such as executive dysfunction or memory dysfunction. Eye Movement Desensitization and Reprocessing (EMDR) is an evidence-based treatment for PTSD, in which eye movements (EMs) are performed during traumatic memory retrieval. We examined whether Eye Movement Desensitization (EMD) improves neurocognitive functioning in PTSD patients, in comparison with a retrieval-only control condition without EMs.

Methods
Adult patients with PTSD (N = 91) were randomized into EMD (N = 47) or retrieval-only (N = 44). Data were collected at baseline (T0), one-week post-treatment (T1), one-month follow-up (T2), and at three-month follow-up (T3). Outcome measures were the California Verbal Learning Test (CVLT), the Trail Making Test (TMT), and the Digit Span Subtest of the Wechsler Adult Intelligence Scale fourth edition (WAIS-IV). We conducted linear mixed model to analyse the main outcomes.

Results
There was a main effect of time, indicating improvements for both the EMD and retrieval-only groups in CVLT scores, TMT A, TMT B and Digit Span score of WAIS-IV (Bonferroni-adjusted p’s < 0.001) from T0 to T3. There were no effects of group (p = .64) or group by time on CVLT total trial A (T3; p = .34), delay A (T3; p = .76), TMT A (T3; p = .61), TMT B (T3: p = .58), and Digit Span scores (T3; p = .78) of the WAIS-IV, indicating no significant differences between groups on any of the outcomes.

Conclusion
Comparing EMD and retrieval-only did not show evidence for additive effects of EMs on the treatment of PTSD in terms of improvements in neurocognitive functioning. Thus, treatments based on retrieval of traumatic memories may be used to improve neurocognitive functioning in patients with PTSD.

Clinical trial registration
The trial was registered 19/12/2017 at ClinicalTrials.gov, identifier [ISRCTN55239132].
A happy place to be in: how beliefs about living places influence depression in Chinese international student returnees
Authors: Jin Ruining , Yin Meiling , Shen Qiang , Le Tam-Tri 
Published: December 2024

Abstract
Background
The mental health of Chinese international student returnees is a critical concern impacting their well-being and successful reintegration into home society, especially in the post-COVID-19 era. This study examines how beliefs about changing living conditions, emigration intentions, and belief in fate influence depression levels among these returnees.

Methods
A cross-sectional survey collected data from 1,014 returnees through WeChat public groups. Depression levels were measured using the Patient Health Questionnaire-9 (PHQ-9), and Bayesian analysis with Markov Chain Monte Carlo (MCMC) algorithms was employed for statistical examination.

Findings
It was found that a stronger belief that changing one's living environment can bring happiness is associated with lower depression levels, highlighting the positive role of agency thinking in mental health. This association is moderated by emigration intentions and belief in fate. Specifically, among returnees who believe that changing living conditions enhances happiness, those with stronger intentions to emigrate from China exhibited lower depression levels, while those with a strong belief in fate showed higher depression levels.

Implications
These results suggest that both agency and pathway thinking significantly affect the mental health of returnees. To support their well-being and reintegration, we recommend that policymakers create more diverse and inclusive environments within China that accommodate returnees' aspirations. Educational institutions should offer counseling services that bolster returnees' proactive strategies for achieving personal goals. Additionally, mental health interventions should address cultural beliefs, such as fatalism, which might hinder proactive coping mechanisms.
Implementation and evaluation of an optimized surgical clerkship teaching model utilizing ChatGPT
Authors: Huang Yi , Xu Bei-bei , Wang Xiu-yan , Luo Yun-cheng , Teng Miao-miao , Weng Xuejian 
Published: December 2024

Abstract
Objective
This study aims to explore the effect of an innovative teaching model incorporating ChatGPT on medical students’ learning outcomes, compliance with learning activities, and overall satisfaction with the learning process.

Methods
A cohort of 64 students participating in general surgery clerkships at Wenzhou People’s Hospital during the 2022–2023 academic year were randomly assigned into 4 groups, each comprising 16 students. Two of these groups were designated as the study group, where ChatGPT was employed as a supplementary educational tool. The remaining 2 groups served as control groups and used traditional multimedia-based learning methods. Outcomes, including learning effectiveness, compliance, and satisfaction, were evaluated using questionnaires and tests.

Results
The study groups exhibited significantly higher levels of compliance and satisfaction compared to the control groups. Specifically, the study groups exhibited significantly greater compliance in both pre-class preparation and post-class review activities (P < 0.05). During classroom teaching, Group 1 of the study group achieved significantly higher compliance than the control groups (P < 0.0001), while Group 2 of the study group showed significantly higher compliance than Group 1 (P < 0.001). In terms of seeking feedback and assistance, both Groups 1 and 2 of the study group had significantly higher compliance compared to Group 1 of the control group (P < 0.01, P < 0.001 respectively). Overall satisfaction was significantly higher in the study groups compared to the control groups (P < 0.0001), particularly with respect to course organization (P < 0.001, P < 0.05).

Conclusion
The incorporation of ChatGPT into the surgical clerkship teaching model substantially enhances learner compliance and satisfaction, offering notable advantages in educational effectiveness.
Helicopter emergency medical services demonstrate reduced time to emergency anaesthesia in an undifferentiated trauma population: a retrospective observational analysis across three major trauma networks
Authors: Heritage Daniel , Griggs Joanne , Barrett Jack , Clarke Scott , Carroll Rory , Lyon Richard , Bootland Duncan 
Published: December 2024

Abstract
Background
Early rapid sequence induction of anaesthesia (RSI) and tracheal intubation for patients with airway or ventilatory compromise following major trauma is recommended, with guidance suggesting a 45-min timeframe. Whilst on-scene RSI is recommended, the potential time benefit offered by Helicopter Emergency Medical Services (HEMS) has not been studied. We compared the time from 999/112 emergency call to delivery of RSI between patients intubated either in the Emergency Department or pre-hospital by HEMS.

Methods
A retrospective observational cohort study of major trauma patients in South-East England who received a pre-hospital RSI (PHRSI) or Emergency Department RSI (EDRSI) between 2 January 2018 and 24 September 2019. Data were extracted from the UK Trauma Audit and Research Network database. The primary outcome was the time from emergency call to delivery of RSI. Secondary outcomes included mortality at 30-days or hospital discharge, time from arrival of service at hospital or scene to RSI, time from emergency call to Computerised Tomography scan, and conveyance interval. Linear regression was used to model time to RSI in both groups.

Results
Of 378 eligible patients, 209 patients met inclusion criteria. 103 received a PHRSI and 106 received an EDRSI. Most patients were male (n = 171, 82%) and the median age was 48 years (IQR 28–65). 94% sustained a blunt injury mechanism and head was the most injured body region for both cohorts (n = 134, 64%). 63% (n = 67) of patients receiving a PHRSI were conveyed by helicopter. PHRSI was delivered significantly earlier with a median of 64 [IQR 51–75] minutes (95% CI, 60–68) compared with EDRSI with a median of 84 [IQR 68–113] minutes (95% CI, 76–94), p < 0.001).

Conclusion
Major trauma patients who had a pre-hospital RSI received this time-critical intervention sooner after their injury than those who received an emergency anaesthetic after conveyance to a specialist hospital. Patient outcome benefit of HEMS delivered early RSI should be explored.
The Rhipicephalus sanguineus group: updated list of species, geographical distribution, and vector competence
Authors: Dantas-Torres Filipe , de Sousa-Paula Lucas C. , Otranto Domenico 
Published: December 2024

AbstractThe Rhipicephalus sanguineus group is an assembly of species morphologically and phylogenetically related to Rhipicephalus sanguineus sensu stricto. The taxonomy and systematics of this species group have remained obscure for a long time, but extensive research conducted during the past two decades has closed many knowledge gaps. These research advancements culminated in the redescription of R. sanguineus sensu stricto, with subsequent revalidation of former synonyms (Rhipicephalus linnaei, Rhipicephalus rutilus, and Rhipicephalus secundus) and even the description of new species (Rhipicephalus afranicus and Rhipicephalus hibericus). With a much clearer picture of the taxonomy of these species, we present an updated list of species belonging to the R. sanguineus group, along with a review of their geographic distribution and vector role for various pathogens of animals and humans. We also identify knowledge gaps to be bridged in future studies.
Graphical abstract
The evolution of cephalic fins in manta rays and their relatives: functional evidence for initiation of domain splitting and modulation of the Wnt signaling pathway in the pectoral fin AER of the little skate
Authors: McFarland Emily P. , Crow Karen D. 
Published: December 2024

Abstract
Background
Batoids possess a unique body plan associated with a benthic lifestyle that includes dorsoventral compression and anteriorly expanded pectoral fins that fuse to the rostrum. The family Myliobatidae, including manta rays and their relatives, exhibit further modifications associated with invasion of the pelagic environment, and the evolution of underwater flight. Notably, the pectoral fins are split into two domains with independent functions that are optimized for feeding and oscillatory locomotion. Paired fin outgrowth is maintained during development by Wnt3, while domain splitting is accomplished by expression of the Wnt antagonist Dkk1, which is differentially expressed in the developing anterior pectoral fins of myliobatids, where cephalic fins separate from pectoral fins. We examine the evolution of this unique feature in the cownose ray (Rhinoptera bonasus), a member of the genus that is sister to Mobula.

Results
Here, we provide functional evidence that DKK1 is sufficient to initiate pectoral fin domain splitting. Agarose beads soaked in DKK1 protein were implanted in the pectoral fins of little skate (Leucoraja erinacea) embryos resulting in AER interruption. This disruption arrests fin ray outgrowth, resembling the myliobatid phenotype. In addition, fins that received DKK1 beads exhibit interruption of Axin2 expression, a downstream target of β-catenin-dependent Wnt signaling and a known AER marker. We demonstrate that Msx1 and Lhx2 are also associated with fin expansion at the AER. These results provide functional evidence for the underlying genetic pathway associated with the evolution of a novel paired fin/limb modification in manta rays and their relatives. We introduce the gas/brake pedal model for paired fin remodeling at the AER, which may have been co-opted from domain splitting in pelvic fins of cartilaginous fishes 370 million years earlier.

Conclusions
The pectoral fins of manta rays and their relatives represent a dramatic remodel of the ancestral batoid body plan. The premiere feature of this remodel is the cephalic fins, which evolved via domain splitting of the anterior pectoral fins through inhibition of fin ray outgrowth. Here, we functionally validate the role of Dkk1 in the evolution of this phenotype. We find that introduction of ectopic DKK1 is sufficient to recapitulate the myliobatid pectoral fin phenotype in an outgroup lacking cephalic fins via AER interruption and fin ray truncation. Additional gene expression data obtained via in situ hybridization suggests that cephalic fin development may have evolved as a co-option of the pathway specifying claspers as modifications to the pelvic fins, the only other known example of domain splitting in vertebrate appendages.