bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the ferroptosis-related long non-coding RNAs signature to improve the prognosis prediction and immunotherapy response in patients with NSCLC
Authors: Li Meng , Zhang Yanpeng , Fan Meng , Ren Hui , Chen Mingwei , Shi Puyu 
Published: December 2021

AbstractBackgroundNon-small cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with an unfavorable prognosis. Ferroptosis is involved in the development of multiple cancers. Whereas, the prognostic value of ferroptosis-related lncRNAs in NSCLC remains uncertain.MethodsGene expression profiles and clinical information of NSCLC were retrieved from the TCGA database. Ferroptosis-related genes (FRGs) were explored in the FerrDb database and previous studies, ferroptosis-related lncRNAs (FRGs-lncRNAs) were identified by the correlation analysis and the LncTarD database. The differentially expressed FRGs-lncRNAs were screened and FRGs-lncRNAs associated with the prognosis were explored by univariate Cox regression analysis and Kaplan–Meier survival analysis. Then, an FRGs-lncRNAs signature was constructed and verified by the Lasso-penalized Cox analysis. Finally, the potential correlation between risk score, immune checkpoint genes, and chemotherapeutic sensitivity was further investigated.Results129 lncRNAs with a potential regulatory relationship with 59 differentially expressed FRGs were found in NSCLC, of which 10 were related to the prognosis of NSCLC (P < 0.05). 9 prognostic-related FRGs-lncRNAs were used to construct the prognostic model and stratify NSCLC patients into high- and low-risk groups. A worse outcome was found in patients with high risk (P < 0.05). Moreover, a good predictive capacity of this signature in predicting NSCLC prognosis was confirmed. Additionally, 45 immune checkpoint genes and 4 chemotherapeutics drugs for NSCLC were identified to be correlated with the risk score.ConclusionA novel FRGs-lncRNAs signature was successfully constructed, which may contribute to improving the management strategies of NSCLC.
Changes over time in inflammatory and structural lesions at the sacroiliac joint in children with spondyloarthritis exposed and unexposed to tumor necrosis factor inhibitor
Authors: Brandon Timothy G. , Xiao Rui , Peterson Rosemary G. , Chauvin Nancy A. , Francavilla Michael L. , Biko David M. , Rumsey Dax G. , Stoll Matthew L. , Weiss Pamela F. 
Published: December 2021

Abstract
Background
The objective of this work was to describe magnetic resonance imaging (MRI) changes over time in inflammatory and structural lesions at the sacroiliac joint (SIJ) in children with spondyloarthritis (SpA) exposed and unexposed to tumor necrosis factor inhibitor (TNFi).

Methods
This was a retrospective, multicenter study of SpA patients with suspected or confirmed sacroiliitis who underwent at ≥2 pelvic MRI scans. Images were reviewed independently by 3 radiologists and scored for inflammatory and structural changes using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ inflammation score (SIS) and structural score (SSS). Longitudinal, quantitative changes in patient MRI scans were measured using descriptive statistics and stratified by TNFi exposure. We used an average treatment effects (ATE) regression model to explore the average effect of TNFi exposure over time on inflammatory and structural lesions, adjusting for baseline lesion scores.

Results
Forty-six subjects were evaluated using the SIS (n = 45) and SSS (n = 18). Median age at baseline imaging was 13.6 years, 63% were male and 71% were white. Twenty-three subjects (50%) were TNFi exposed between MRI studies. The median change in SIS in TNFi exposed and unexposed subjects with a baseline SIS ≥0 was − 20.7 and − 14.3, respectively (p = 0.09). Eleven (85%) TNFi exposed and 8 (89%) unexposed subjects with a baseline SIS ≥0 met the SIS minimal clinically important difference (MCID; ≥2.5). Using the ATE model adjusted for baseline SIS, the average effect of TNFi on SIS in patients with a baseline SIS ≥2 was − 14.5 (p < 0.01). Unadjusted erosion change score was significantly worse in TNFi unexposed versus exposed subjects (p = 0.03) but in the ATE model the effect of TNFi was not significant.

Conclusion
This study quantitatively describes how lesions in the SIJs on MRI change over time in patients exposed to TNFi versus unexposed. Follow-up imaging in TNFi exposed patients showed greater improvement than the unexposed group by most metrics, some of which reached statistical significance. Surprisingly, a majority of TNFi unexposed children with a baseline SIS≥2 met the SIS MCID. Additional studies assessing the short and long-term effects of TNFi on inflammatory and structural changes in juvenile SpA are needed.
Downregulating expression of OPTN elevates neuroinflammation via AIM2 inflammasome- and RIPK1-activating mechanisms in APP/PS1 transgenic mice
Authors: Cao Long-Long , Guan Pei-Pei , Zhang Shen-Qing , Yang Yi , Huang Xue-Shi , Wang Pu 
Published: December 2021

AbstractBackgroundNeuroinflammation is thought to be a cause of Alzheimer’s disease (AD), which is partly caused by inadequate mitophagy. As a receptor of mitophagy, we aimed to reveal the regulatory roles of optineurin (OPTN) on neuroinflammation in the pathogenesis of AD.MethodsBV2 cells and APP/PS1 transgenic (Tg) mice were used as in vitro and in vivo experimental models to determine the regulatory roles of OPTN in neuroinflammation of AD. Sophisticated molecular technologies including quantitative (q) RT-PCR, western blot, enzyme linked immunosorbent assay (ELISA), co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were employed to reveal the inherent mechanisms.ResultsAs a consequence, key roles of OPTN in regulating neuroinflammation were identified by depressing the activity of absent in melanoma 2 (AIM2) inflammasomes and receptor interacting serine/threonine kinase 1 (RIPK1)-mediated NF-κB inflammatory mechanisms. In detail, we found that expression of OPTN was downregulated, which resulted in activation of AIM2 inflammasomes due to a deficiency in mitophagy in APP/PS1 Tg mice. By ectopic expression, OPTN blocks the effects of Aβ oligomer (Aβo) on activating AIM2 inflammasomes by inhibiting mRNA expression of AIM2 and apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), leading to a reduction in the active form of caspase-1 and interleukin (IL)-1β in microglial cells. Moreover, RIPK1 was also found to be negatively regulated by OPTN via ubiquitin protease hydrolysis, resulting in the synthesis of IL-1β by activating the transcriptional activity of NF-κB in BV2 cells. As an E3 ligase, the UBAN domain of OPTN binds to the death domain (DD) of RIPK1 to facilitate its ubiquitination. Based on these observations, ectopically expressed OPTN in APP/PS1 Tg mice deactivated microglial cells and astrocytes via the AIM2 inflammasome and RIPK-dependent NF-κB pathways, leading to reduce neuroinflammation.ConclusionsThese results suggest that OPTN can alleviate neuroinflammation through AIM2 and RIPK1 pathways, suggesting that OPTN deficiency may be a potential factor leading to the occurrence of AD.
The impact of natural disasters on the spread of COVID-19: a geospatial, agent-based epidemiology model
Authors: de Vries Maximillian Van Wyk , Rambabu Lekaashree 
Published: December 2021

Abstract
Background
Natural disasters and infectious diseases result in widespread disruption to human health and livelihood. At the scale of a global pandemic, the co-occurrence of natural disasters is inevitable. However, the impact of natural disasters on the spread of COVID-19 has not been extensively evaluated through epidemiological modelling.

Methods
We create an agent-based epidemiology model based on COVID-19 clinical, epidemiological, and geographic data. We first model 35 scenarios with varying natural disaster timing and duration for a COVID-19 outbreak in a theoretical region. We then evaluate the potential effect of an eruption of Vesuvius volcano on the spread of COVID-19 in Campania, Italy.

Results
In a majority of cases, the occurrence of a natural disaster increases the number of disease related fatalities. For a natural disaster fifty days after infection onset, the median increase in fatalities is 2, 59, and 180% for a 2, 14, and 31-day long natural disaster respectively, when compared to the no natural disaster scenario. For the Campania case, the median increase in fatalities is 1.1 and 2.4 additional fatalities per 100,000 for eruptions on day 1 and 100 respectively, and 60.0 additional fatalities per 100,000 for an eruption close to the peak in infections (day 50).

Conclusion
Our results show that the occurrence of a natural disaster in most cases leads to an increase in infection related fatalities, with wide variance in possible outcomes depending on the timing of the natural disaster relative to the peak in infections and the duration of the natural disaster.
Transforming social norms to improve girl-child health and well-being: a realist evaluation of the Girls’ Holistic Development program in rural Senegal
Authors: Kohli Anjalee , Shaw Bryan , Guntzberger Mathilde , Aubel Judi , Coulibaly Mamadou , Igras Susan 
Published: December 2021

Abstract
Background
Early adolescence is a critical period where social norms, attitudes, and behaviors around gender equality form. Social norms influence adolescent choices and behaviors and are reinforced by caregivers and community members, affecting girls’ reproductive health and educational opportunities. Understanding how to shift these often-interconnected norms to delay child marriage, pregnancy and keep girls in school requires understanding of the structure and dynamics of family and community systems. The Senegalese and American non-governmental organization, the Grandmothers Project—Change through Culture, seeks to address these intertwined factors through innovative community change strategies that build on the specific structure and values of West African collectivist cultures.

Methods
The Girls’ Holistic Development approach in rural Vélingara, Senegal posits that by increasing recognition, knowledge and empowerment of elder community women and reinforcing intergenerational communication and decision-making, community members including girls will support and advocate on behalf of girls’ interests and desires. We assessed the Girls Holistic Development approach using Realist Evaluation with a mixed-method, quasi-experimental design with a comparison population. We examined differences in intergenerational communication, decision-making and descriptive and injunctive norms related to early marriage, pregnancy and schooling.

Results
After 18 months, intergenerational communication was more likely, grandmothers felt more valued in their communities, adolescent girls felt more supported with improved agency, and norms were shifting to support delayed marriage and pregnancy and keeping girls in school. Grandmothers in intervention villages were statistically significantly more likely to be perceived as influential decision-makers by both VYA girls and caregivers for marriage and schooling decisions compared to girls and caregivers in comparison villages.

Conclusions
This realist evaluation demonstrated shift in social norms, particularly for VYA girls, in intervention villages favoring delaying girls’ marriage, preventing early pregnancy and keeping girls in school along with increased support for and action by grandmothers to support girls and their well-being related to these same outcomes. These shifts represent greater community social cohesion on girl-child issues. This research helps explain the linkage between social norms and girls’ reproductive health and education outcomes and demonstrates that normative shifts can lead to behavior change via collective community action mechanisms.
LPI-EnEDT: an ensemble framework with extra tree and decision tree classifiers for imbalanced lncRNA-protein interaction data classification
Authors: Peng Lihong , Yuan Ruya , Shen Ling , Gao Pengfei , Zhou Liqian 
Published: December 2021

Abstract
Background
Long noncoding RNAs (lncRNAs) have dense linkages with various biological processes. Identifying interacting lncRNA-protein pairs contributes to understand the functions and mechanisms of lncRNAs. Wet experiments are costly and time-consuming. Most computational methods failed to observe the imbalanced characterize of lncRNA-protein interaction (LPI) data. More importantly, they were measured based on a unique dataset, which produced the prediction bias.

Results
In this study, we develop an Ensemble framework (LPI-EnEDT) with Extra tree and Decision Tree classifiers to implement imbalanced LPI data classification. First, five LPI datasets are arranged. Second, lncRNAs and proteins are separately characterized based on Pyfeat and BioTriangle and concatenated as a vector to represent each lncRNA-protein pair. Finally, an ensemble framework with Extra tree and decision tree classifiers is developed to classify unlabeled lncRNA-protein pairs. The comparative experiments demonstrate that LPI-EnEDT outperforms four classical LPI prediction methods (LPI-BLS, LPI-CatBoost, LPI-SKF, and PLIPCOM) under cross validations on lncRNAs, proteins, and LPIs. The average AUC values on the five datasets are 0.8480, 0,7078, and 0.9066 under the three cross validations, respectively. The average AUPRs are 0.8175, 0.7265, and 0.8882, respectively. Case analyses suggest that there are underlying associations between HOTTIP and Q9Y6M1, NRON and Q15717.

Conclusions
Fusing diverse biological features of lncRNAs and proteins and exploiting an ensemble learning model with Extra tree and decision tree classifiers, this work focus on imbalanced LPI data classification as well as interaction information inference for a new lncRNA (or protein).
Dysregulated splicing factor SF3B1 unveils a dual therapeutic vulnerability to target pancreatic cancer cells and cancer stem cells with an anti-splicing drug
Authors: Alors-Perez Emilia , Blázquez-Encinas Ricardo , Alcalá Sonia , Viyuela-García Cristina , Pedraza-Arevalo Sergio , Herrero-Aguayo Vicente , Jiménez-Vacas Juan M. , Mafficini Andrea , Sánchez-Frías Marina E. , Cano María T. , Abollo-Jiménez Fernando , Marín-Sanz Juan A. , Cabezas-Sainz Pablo , Lawlor Rita T. , Luchini Claudio , Sánchez Laura , Sánchez-Hidalgo Juan M. , Ventura Sebastián , Martin-Hijano Laura , Gahete Manuel D. , Scarpa Aldo , Arjona-Sánchez Álvaro , Ibáñez-Costa Alejandro , Sainz Bruno , Luque Raúl M. , Castaño Justo P. 
Published: December 2021

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, requiring novel treatments to target both cancer cells and cancer stem cells (CSCs). Altered splicing is emerging as both a novel cancer hallmark and an attractive therapeutic target. The core splicing factor SF3B1 is heavily altered in cancer and can be inhibited by Pladienolide-B, but its actionability in PDAC is unknown. We explored the presence and role of SF3B1 in PDAC and interrogated its potential as an actionable target.

Methods
SF3B1 was analyzed in PDAC tissues, an RNA-seq dataset, and publicly available databases, examining associations with splicing alterations and key features/genes. Functional assays in PDAC cell lines and PDX-derived CSCs served to test Pladienolide-B treatment effects in vitro, and in vivo in zebrafish and mice.

Results
SF3B1 was overexpressed in human PDAC and associated with tumor grade and lymph-node involvement. SF3B1 levels closely associated with distinct splicing event profiles and expression of key PDAC players (KRAS, TP53). In PDAC cells, Pladienolide-B increased apoptosis and decreased multiple tumor-related features, including cell proliferation, migration, and colony/sphere formation, altering AKT and JNK signaling, and favoring proapoptotic splicing variants (BCL-XS/BCL-XL, KRASa/KRAS, Δ133TP53/TP53). Importantly, Pladienolide-B similarly impaired CSCs, reducing their stemness capacity and increasing their sensitivity to chemotherapy. Pladienolide-B also reduced PDAC/CSCs xenograft tumor growth in vivo in zebrafish and in mice.

Conclusion
SF3B1 overexpression represents a therapeutic vulnerability in PDAC, as altered splicing can be targeted with Pladienolide-B both in cancer cells and CSCs, paving the way for novel therapies for this lethal cancer.
A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol
Authors: Kuut T. A. , Müller F. , Aldenkamp A. , Assmann-Schuilwerve E. , Braamse A. , Geerlings S. E. , Gibney K. B. , Kanaan R. A. A. , Nieuwkerk P. , Olde Hartman T. C. , Pauëlsen D. , Prins M. , Slieker K. , Van Vugt M. , Bleeker-Rovers C. P. , Keijmel S. P. , Knoop H. 
Published: December 2021

Abstract
Background
Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2.

Method
The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2.

Discussion
This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms.

Trial registration
Netherlands Trial Register NL8947. Registered on 14 October 2020.
Managing solar retinopathy with suprachoroidal triamcinolone acetonide injection in a young girl: a case report
Authors: Marashi Ameen , Baba Marwa , Zazo Aya 
Published: December 2021

Abstract
Background
Solar retinopathy is a disease that causes photochemical toxicity in the retinal fovea tissues, leading to an acute decrease of vision.

Case presentation
This case report is an interventional case of an asymptomatic 17-year-old Caucasian female with a history of suddenly decreased vision due to solar retinopathy. The patient was managed with a custom-made needle injection of triamcinolone acetonide in the suprachoroidal space. Four months post suprachoroidal injection showed an anatomical and functional improvement in the ellipsoid zone layer through optical coherence tomography signal reappearance. In addition, the best-corrected visual acuity had improved from 0.1 to 1.0 on the Snellen chart with the disappearance of the scotoma. However, there was a mild increase in intraocular pressure after this procedure, controlled with topical hypertensive eye drops.

Conclusion
Suprachoroidal triamcinolone acetonide injection using a custom-made needle showed both functional and anatomical improvement of macular changes post-solar retinopathy, with acceptable safety outcomes in a young female.
Unacceptable failure of osteochondral glenoid allograft for biologic resurfacing of the glenoid
Authors: Familiari Filippo , Hochreiter Bettina , Gerber Christian 
Published: December 2021

Abstract
Purpose
Glenohumeral osteoarthritis (OA) represents a challenging problem in young, physically active patients. It was the purpose of this investigation to evaluate the results of a pilot study involving glenoid resurfacing with a glenoid allograft combined with a hemiarthroplasty on the humeral side.

Methods
Between April 2011 to November 2013, 5 patients (3 men, 2 women, mean age 46.4, range 35-57) with advanced OA of the glenohumeral joint, were treated with a humeral head replacement combined with replacement of the glenoid surface with an osteochondral, glenoid allograft.

Results
Overall, clinically, there was one excellent, one satisfactory and three poor results. Mean preoperative subjective shoulder value (SSV) was 34% (range: 20-50%) and preoperative relative Constant-Murley-Score (CSr) was 43 points (range: 29-64 points). Three patients with poor results had to be revised within the first three years. Their mean pre-revision SSV and CSr were 38% (range: 15-80%) and 36 points (range: 7-59 points) respectively. One patient was revised 9 years after the primary procedure with advanced glenoid erosion and pain and one patient has an ongoing satisfactory outcome without revision. Their SSVs were 60% and 83%, their CSr were 65 points and 91 points, 9 and 10 years after the primary procedure, respectively. Mean follow-up was 7 years (2-10 years) and mean time to revision was 4 years (range: 1-9 years).

Conclusion
The in-vivo pilot study of a previously established in-vitro technique of osteochondral glenoid allograft combined with humeral HA led to three early failures and only one really satisfactory clinical outcome which, however, was associated with advanced glenoid erosion. Osteochondral allograft glenoid resurfacing was associated with an unacceptable early failure rate and no results superior to those widely documented for HA or TSA, so that the procedure has been abandoned.

Level of evidence
Level IV, Case Series, Treatment Study.