bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved detection of clinically relevant fusion transcripts in cancer by machine learning classification
Authors: Hafstað Völundur , Häkkinen Jari , Larsson Malin , Staaf Johan , Vallon-Christersson Johan , Persson Helena 
Published: December 2023

Abstract
Background
Genomic rearrangements in cancer cells can create fusion genes that encode chimeric proteins or alter the expression of coding and non-coding RNAs. In some cancer types, fusions involving specific kinases are used as targets for therapy. Fusion genes can be detected by whole genome sequencing (WGS) and targeted fusion panels, but RNA sequencing (RNA-Seq) has the advantageous capability of broadly detecting expressed fusion transcripts.

Results
We developed a pipeline for validation of fusion transcripts identified in RNA-Seq data using matched WGS data from The Cancer Genome Atlas (TCGA) and applied it to 910 tumors from 11 different cancer types. This resulted in 4237 validated gene fusions, 3049 of them with at least one identified genomic breakpoint. Utilizing validated fusions as true positive events, we trained a machine learning classifier to predict true and false positive fusion transcripts from RNA-Seq data. The final precision and recall metrics of the classifier were 0.74 and 0.71, respectively, in an independent dataset of 249 breast tumors. Application of this classifier to all samples with RNA-Seq data from these cancer types vastly extended the number of likely true positive fusion transcripts and identified many potentially targetable kinase fusions. Further analysis of the validated gene fusions suggested that many are created by intrachromosomal amplification events with microhomology-mediated non-homologous end-joining.

Conclusions
A classifier trained on validated fusion events increased the accuracy of fusion transcript identification in samples without WGS data. This allowed the analysis to be extended to all samples with RNA-Seq data, facilitating studies of tumor biology and increasing the number of detected kinase fusions. Machine learning could thus be used in identification of clinically relevant fusion events for targeted therapy. The large dataset of validated gene fusions generated here presents a useful resource for development and evaluation of fusion transcript detection algorithms.
Overexpression of PavbHLH28 from Prunus avium enhances tolerance to cold stress in transgenic Arabidopsis
Authors: Cao Xuejiao , Wen Zhuang , Shen Tianjiao , Cai Xiaowei , Hou Qiandong , Shang Chunqiong , Qiao Guang 
Published: December 2023

Abstract
Background
The basic helix-loop-helix (bHLH) gene family is one of plants’ largest transcription factor families. It plays an important role in regulating plant growth and abiotic stress response.

Results
In this study, we determined that the PavbHLH28 gene participated in cold resistance. The PavbHLH28 gene was located in the nucleus and could be induced by low temperature. Under the treatment of ABA, PEG, and GA3, the transcript level of PavbHLH28 was affected. At low temperature, overexpression of the PavbHLH28 gene enhanced the cold resistance of plants with higher proline content, lower electrolyte leakage (EL) and malondialdehyde (MDA) content. Compared with the WT plants, the transgenic plants accumulated fewer reactive oxygen species (ROS), and the activity and expression levels of antioxidant enzymes were significantly increased. The expression of proline synthesis enzyme genes was up-regulated, and the transcripts levels of degradation genes were significantly down-regulated. The transcripts abundance of the cold stressed-related genes in the C-repeat binding factor (CBF) pathway was not significantly different between WT plants and transgenic plants after cold stress. Moreover, the PavbHLH28 could directly bind to the POD2 gene promoter and promote its gene expression.

Conclusions
Overall, PavbHLH28 enhanced the cold resistance of transgenic plants through a CBF-independent pathway, which may be partly related to ROS scavenging.
A virtual mother-infant postpartum psychotherapy group for mothers with a history of adverse childhood experiences: open-label feasibility study
Authors: Wright Elisabeth , Martinovic Jovana , de Camps Meschino Diane , Barker Lucy C , Philipp Diane A , Israel Aliza , Hussain-Shamsy Neesha , Mukerji Geetha , Wang Vivienne , Chatterjee Antara , Vigod Simone N 
Published: December 2023

Abstract
Objectives
Mothers with a history of adverse childhood experiences (ACE) are at elevated risk for postpartum mental illness and impairment in the mother-infant relationship. Interventions attending to maternal-infant interactions may improve outcomes for these parents and their children, but barriers to accessing in-person postpartum care limit uptake. We adapted a postpartum psychotherapy group for mothers with mental illness (e.g., mood, anxiety, trauma-related disorders) and ACE for live video-based delivery, and evaluated feasibility, acceptability, and preliminary efficacy in an open-label pilot study.

Methods
We recruited adults with children (6–18 months) from a perinatal psychiatry program in Toronto, Canada. The intervention was a live video-based 12-week interactive psychotherapy group focused on maternal symptoms and maternal-infant relationships. The primary outcome was feasibility, including feasibility of recruitment and retention, fidelity of the intervention, and acceptability to patients and group providers. Maternal clinical outcomes were compared pre- to post-intervention, as secondary outcomes.

Results
We recruited 31 participants (mean age 36.5 years (SD 3.9)) into 6 groups; 93.6% (n = 29) completed post-group questionnaires, and n = 20 completed an optional post-group acceptability interview. Mean weekly group attendance was 83% (IQR 80–87); one participant (3.2%) dropped out. All group components were implemented as planned, except for dyadic exercises where facilitator observation of dyads was replaced with unobserved mother-infant exercises followed by in-group reflection. Participant acceptability was high (100% indicated the virtual group was easy to access, beneficial, and reduced barriers to care). Mean maternal depressive [Edinburgh Postnatal Depression Scale: 14.6 (SD 4.2) vs. 11.8 (SD 4.2), paired t, p = 0.005] and post-traumatic stress [Posttraumatic Stress Disorder Checklist for DSM-5: 35.5 (SD 19.0) vs. 27.1 (SD 16.7)], paired t, p = 0.01] symptoms were significantly lower post vs. pre-group. No differences were observed on mean measures of anxiety, emotion regulation or parenting stress.

Conclusions
Recruitment and retention met a priori feasibility criteria. There were significant pre- to post-group reductions in maternal depressive and post-traumatic symptoms, supporting proceeding to larger-scale implementation and evaluation of the intervention, with adaptation of dyadic exercises.
HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol
Authors: Arif Ambreen , Hasnain Aliya , Chaudhry Auj , Asim Muhammad , Shafqat Muhammad Nabeel , Altaf Abeer , Saba Noor , Kemos Polychronis , Ansari M. Azim , Barnes Eleanor , Metcalfe Chris , Vickerman Peter , Qureshi Huma , Hamid Saeed , Choudhry Asad Ali , Niaz Saad Khalid , Foster Graham R. , Choudhry Naheed 
Published: December 2023

Abstract
Background
Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization’s goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan.

Methods
This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection.

Conclusion
The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan.

Study registration
This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.
Political Economy of Non-Communicable Disease (NCD) prevention and control in Lebanon: identifying challenges and opportunities for policy change and care provision reforms
Authors: Bou-Orm Ibrahim R. , Loffreda Giulia , Diaconu Karin , Witter Sophie , deVos Pol 
Published: December 2023

AbstractIntroductionLebanon is a middle-income country facing substantial fragility features. Its health profile shows a high burden of NCD morbidity and mortality. This paper intends to analyse the political economy of NCD prevention and control in Lebanon.MethodsThis study adopted a literature-based case study research design using a problem-driven political economy analysis framework. A total of 94 peer-reviewed articles and documents from the grey literature published before June 2019 were retrieved and analysed.ResultsLebanon’s political instability and fragile governance negatively affect its capacity to adapt a Health-in-All-Policies approach to NCD prevention and enable the blocking of NCD prevention policies by opposed stakeholders. Recent economic crises limit the fiscal capacity to address health financing issues and resulting health inequities. NCD care provision is twisted by powerful stakeholders towards a hospital-centred model with a powerful private sector. Stakeholders like the MOPH, UN agencies, and NGOs have been pushing towards changing the existing care model towards a primary care model. An incremental reform has been adopted to strengthen a network of primary care centres, support them with health technologies and improve the quality of primary care services. Nevertheless, outpatient services that are covered by other public funds remain specialist-led without much institutional regulation.ConclusionOur study revealed a locked equilibrium in NCD prevention policymaking in Lebanon, but with an incremental progress in service delivery reforms towards a primary care model. Advocacy and close monitoring by policy entrepreneurs (such as civil society) could initiate and sustain the implementation of policy change and care model reforms.
The effectiveness of digital delivery versus group-based face-to-face delivery of the English National Health Service Type 2 Diabetes Prevention Programme: a non-inferiority retrospective cohort comparison study
Authors: Marsden Antonia M. , Hann Mark , Barron Emma , McGough Ben , Murray Elizabeth , Valabhji Jonathan , Cotterill Sarah 
Published: December 2023

Abstract
Background
Face-to-face group-based diabetes prevention programmes have been shown to be effective in many settings. Digital delivery may suit some patients, but research comparing the effectiveness of digital with face-to-face delivery is scarce. The aim was to assess if digital delivery of the English National Health Service Diabetes Prevention Programme (NHS DPP) is non-inferior to group-based face-to-face delivery in terms of weight change, and evaluate factors associated with differential change.

Methods
The study included those recruited to the NHS DPP in 2017–2018. Individual-level data from a face-to-face cohort was compared to two cohorts on a digital pilot who (i) were offered no choice of delivery mode, or (ii) chose digital over face-to-face. Changes in weight at 6 and 12 months were analysed using mixed effects linear regression, having matched participants from the digital pilot to similar participants from face-to-face.

Results
Weight change on the digital pilot was non-inferior to face-to-face at both time points: it was similar in the comparison of those with no choice (difference in weight change: -0.284 kg [95% CI: -0.712, 0.144] at 6 months) and greater in digital when participants were offered a choice (-1.165 kg [95% CI: -1.841, -0.489]). Interactions between delivery mode and sex, ethnicity, age and deprivation were observed.

Conclusions
Digital delivery of the NHS DPP achieved weight loss at least as good as face-to-face. Patients who were offered a choice and opted for digital experienced better weight loss, compared to patients offered face-to-face only.
A novel de novo CLTC variant altering RNA splicing causes fetal developmental abnormalities
Authors: Cheng Chen , Yang Fan , Zhao Sheng , Chen Xinlin 
Published: December 2023

Abstract
Background
About 31 individuals with CLTC variants have been reported worldwide, and all reported individuals have motor and mental retardation. CLTC is known to lead to intellectual developmental disorder, autosomal dominant 56. Few studies are focusing on the prenatal stage of the disease.

Method
An ultrasound examination was performed to obtain the prenatal phenotype. Whole-exome sequencing was used to find the pathogenic variant. Multiple computational tools predicted the conservation and deleteriousness. Minigene assay and western blot were utilized to investigate the effect on splicing of mRNA and protein expression.

Result
Here we found a novel de novo variant of CLTC in a fetus. The fetus manifested bilateral choroid plexus cysts of the brain, hyperechogenic kidneys, and ventricular septal defect. A heterozygous variant c.3249 + 1G > C was identified in the fetus. This position was conserved and the variant was predicted to be deleterious. Minigene assay revealed the presence of a truncating transcript with the retention of intron 20. Western blot result showed the c.3249 + 1G > C variant elicited degradation of the protein.

Conclusion
To the best of our knowledge, our study identified a novel de novo variant of CLTC and provided the earliest clinical characteristic of the CLTC variant at the prenatal stage. The functional experiment suggested the variant caused the altering of the RNA splicing and the protein expression. We extended the mutational spectrum of CLTC and provided guidance on genetic counseling.
A novel mucosal bivalent vaccine of EV-A71/EV-D68 adjuvanted with polysaccharides from Ganoderma lucidum protects mice against EV-A71 and EV-D68 lethal challenge
Authors: Lin Yu-Li , Cheng Pei-Yun , Chin Chiao-Li , Chuang Kuan-Ting , Lin Jing-Yi , Chang Ning , Pan Chun-Kei , Lin Cheng-Sheng , Pan Siao-Cian , Chiang Bor-Luen 
Published: December 2023

Abstract
Background
Human enteroviruses A71 (EV-A71) and D68 (EV-D68) are the suspected causative agents of hand-foot-and-mouth disease, aseptic meningitis, encephalitis, acute flaccid myelitis, and acute flaccid paralysis in children. Until now, no cure nor mucosal vaccine existed for EV-A71 and EV-D68. Novel mucosal bivalent vaccines are highly important for preventing EV-A71 and EV-D68 infections.

Methods
In this study, formalin-inactivated EV-A71 and EV-D68 were used as antigens, while PS-G, a polysaccharide from Ganoderma lucidum, was used as an adjuvant. Natural polysaccharides have the characteristics of intrinsic immunomodulation, biocompatibility, low toxicity, and safety. Mice were immunized intranasally with PBS, EV-A71, EV-D68, or EV-A71 + EV-D68, with or without PS-G as an adjuvant.

Results
The EV-A71 + EV-D68 bivalent vaccine generated considerable EV-A71- and EV-D68-specific IgG and IgA titres in the sera, nasal washes, saliva, bronchoalveolar lavage fluid, and feces. These antibodies neutralized EV-D68 and EV-A71 infectivity. They also cross-neutralized infections by different EV-D68 and EV-A71 sub-genotypes. Furthermore, compared with the PBS group, EV-A71 + EV-D68 + PS-G-vaccinated mice exhibited an increased number of EV-D68- and EV-A71-specific IgA- and IgG-producing cells. In addition, T-cell proliferative responses, and IFN-γ and IL-17 secretion in the spleen were substantially induced when PS-G was used as an adjuvant with EV-A71 + EV-D68. Finally, in vivo challenge experiments demonstrated that the immune sera induced by EV-A71 + EV-D68 + PS-G conferred protection in neonate mice against lethal EV-A71 and EV-D68 challenges as indicated by the increased survival rate and decreased clinical score and viral RNA tissue expression. Taken together, all EV-A71/EV-D68 + PS-G-immunized mice developed potent specific humoral, mucosal, and cellular immune responses to EV-D68 and EV-A71 and were protected against them.

Conclusions
These findings demonstrated that PS-G can be used as a potential adjuvant for EV-A71 and EV-D68 bivalent mucosal vaccines. Our results provide useful information for the further preclinical and clinical development of a mucosal bivalent enterovirus vaccine against both EV-A71 and EV-D68 infections.

Graphical Abstract
Rational design of NIR-II molecule-engineered nanoplatform for preoperative downstaging and imaging-guided surgery of orthotopic hepatic tumor
Authors: Pan Qi , Li Ke , Kang Xueqin , Li Kaixuan , Cheng Zihe , Wang Yafei , Xu Yuye , Li Lei , Li Na , Wu Guilong , Yang Sha , Qi Shuo , Chen Guodong , Tan Xiaofeng , Zhan Yonghua , Tang Li , Zhan Wenhua , Yang Qinglai 
Published: December 2023

AbstractOrthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core “S-D-A-D-S” NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.
Graphical Abstract
Prioritising and incentivising productivity within indicator-based approaches to Research Impact Assessment: a commentary
Authors: Deeming Simon , Hure Alexis , Attia John , Nilsson Michael , Searles Andrew 
Published: December 2023

AbstractResearch Impact Assessment (RIA) represents one of a suite of policies intended to improve the impact generated from investment in health and medical research (HMR). Positivist indicator-based approaches to RIA are widely implemented but increasingly criticised as theoretically problematic, unfair, and burdensome. This commentary proposes there are useful outcomes that emerge from the process of applying an indicator-based RIA framework, separate from those encapsulated in the metrics themselves. The aim for this commentary is to demonstrate how the act of conducting an indicator-based approach to RIA can serve to optimise the productive gains from the investment in HMR. Prior research found that the issues regarding RIA are less about the choice of indicators/metrics, and more about the discussions prompted and activities incentivised by the process. This insight provides an opportunity to utilise indicator-based methods to purposely optimise the research impact. An indicator-based RIA framework specifically designed to optimise research impacts should: focus on researchers and the research process, rather than institution-level measures; utilise a project level unit of analysis that provides control to researchers and supports collaboration and accountability; provide for prospective implementation of RIA and the prospective orientation of research; establish a line of sight to the ultimate anticipated beneficiaries and impacts; Include process metrics/indicators to acknowledge interim steps on the pathway to final impacts; integrate ‘next’ users and prioritise the utilisation of research outputs as a critical measure; Integrate and align the incentives for researchers/research projects arising from RIA, with those existing within the prevailing research system; integrate with existing peer-review processes; and, adopt a system-wide approach where incremental improvements in the probability of translation from individual research projects, yields higher impact across the whole funding portfolio.Optimisation of the impacts from HMR investment represents the primary purpose of Research Impact policy. The process of conducting an indicator-based approach to RIA, which engages the researcher during the inception and planning phase, can directly contribute to this goal through improvements in the probability that an individual project will generate interim impacts. The research project funding process represents a promising forum to integrate this approach within the existing research system.