bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contextual factors affecting integration of eye health into school health programme in Zanzibar: a qualitative health system research
Authors: Chan Ving Fai , Yard Elodie , Mashayo Eden , Mulewa Damaris , Drake Lesley , Omar Fatma 
Published: December 2023

Abstract
Background
Short-term school eye health programmes supported by external funders have sustainability issues. This study aimed to understand the contextual factors affecting integrating eye health into the school health programme.

Methods
We elicited responses from 83 respondents, purposefully selected from the Ministry of Health (n = 7), Ministry of Education and Vocational Training (n = 7), hospitals/eye centres (n = 5), master trainers (4) and schools (n = 60) who participated in in-depth interviews. Their responses were analysed and grouped into contextual factors according to the WHO Consolidated Framework for Implementation Research: stakeholders/political, institutional, physical, cultural, delivery system and others. Themes were then generated, and quotations were presented to illustrate the findings.

Results
The six contextual factors affecting the integration of eye health into the school eye health programme were i) Stakeholders/political (Good ministry coordination, defined departmental roles and resource mobilisation from multiple stakeholders; Good stakeholder synergies and address current gaps); ii) Institutional (Institutional coordination and adequate clinic space; Securing human and financial resources; Strategic advocacy for institutional resources); iii) Physical (Long travel distance to service points); vi) Cultural (low eye health awareness among parents, teachers and children); iv) Delivery system (Practical approach to increase screening coverage using teachers as screeners; Balance teachers’ workload, increase screening sensitivity and follow up and; v) Others (Comprehensive training material and effective training delivery; Improved curriculum, teacher selection and supervision and incentives).

Conclusion
Integrated school eye health delivery is generally well-received by stakeholders in Zanzibar, with the caveat that investment is required to address the six contextual factors identified in the study.
Prognostic implications of obstructive sleep apnea in patients with acute coronary syndrome stratified by homocysteine level: a prospective cohort study
Authors: Chen Xiuhuan , Zhen Lei , Ai Hui , Que Bin , Fan Jingyao , Wang Xiao , Yan Yan , Li Siyi , Zhang Zekun , Zhou Yun , Gong Wei , Nie Shaoping 
Published: December 2023

Abstract
Background
Sporadic studies have examined the impact of OSA on ACS patients by homocysteine (Hcy) level. This study attempted to comprehensively evaluate the effects of the interaction between Hcy and OSA on long-term cardiovascular outcomes in ACS patients.

Methods
In this prospective, large-scale cohort study, 2160 patients admitted for ACS were recruited to undergo overnight sleep monitoring. OSA was diagnosed when apnea–hypopnea index ≥ 15 events/h. Patients with normohomocysteinemia (NHcy) were defined as having serum Hcy ≤ 15 μmol/L, and the others had hyperhomocysteinemia (HHcy). The primary endpoint was major adverse cerebrocardiovascular event (MACCE), a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization and hospitalization for unstable angina and heart failure.

Results
A total of 1553 eligible ACS patients (average age: 56.3 ± 10.5 years) were enrolled, among which 819 (52.7%) had OSA, and 988 (63.6%) were with NHcy. OSA did not significantly affect the level of Hcy. During a median follow-up of 2.9 (1.6, 3.5) years, after adjustment for clinical confounders, OSA was associated with increased risk for MACCE occurrence versus non-OSA ones in ACS patients with NHcy (adjusted hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.02–1.83, P = 0.039), but not in those with HHcy (adjusted HR = 0.92, 95%CI 0.62–1.36, P = 0.668). There was an absence of interaction between homocysteine level and OSA in relation to MACCE (interaction P = 0.106).

Conclusions
OSA was independently associated with worse prognosis in ACS patients with NHcy. Our study emphasized the necessity to identify potential presence of OSA in such a population.
Trial registration: ClinicalTrials.gov; Number: NCT03362385; URL: www.clinicaltrials.gov.
A novel minimally invasive fixation method for flail chest management in a Canine model: an animal research
Authors: Li Zhe , Zhu Weiwei , Zhang Bing , Zhang Yaxiao , Li Huixian , Lv Baolei , Zhen Qiang , Liu Lin , Liu Lijun , Wu Yanxin , Li Shujun 
Published: December 2023

AbstractBackgroundMultiple rib fractures can lead to flail chest with up to 35% mortality rate due to severe pulmonary complications. Current treatments of flail chest remain controversial. Studies have shown that surgical treatments can improve outcomes and reduce mortality, comparing to non-operative treatments. Current surgical fixation methods focus on stabilization of ribs on the outward facing side, and they require division of intercostal muscles. Damages to surrounding nerves and vessels may lead to chronic pain. This study tests a novel interior fixation method that minimizes neurovascular injuries.MethodsTwelve healthy canines were divided in two surgical operation groups for exterior and interior fixation using titanium metal plates. Osteotomy with oblique fractures was prepared under general anesthesia. Exterior fixation was performed in open surgery. Interior fixation was minimally invasive using custom made tools including a flexible shaft extension screwdriver, solid plate stand, guiding wire loop and metal plates with threaded holes.ResultsRespiratory and cardiovascular functions (RR, PO2, PCO2, SpO2, and HR) together with body temperature were measured before anesthesia and within 48 h after surgery. The difference in measurements was not statistically significant between the two groups before surgery withPvalues greater than 0.05. However, the interior group canines had better RR and PO2values starting from the 24th hour, and better PCO2, SpO2, and HR values starting from the 48thhour. It took longer operation time to complete the minimally invasive interior fixation surgery (Pvalue less than 0.001), but the total blood loss was less than the exterior fixation group (Pvalue less than 0.001). Results also showed that interior group canines suffered less pain, and they had quicker recovery in gastrointestinal and physical mobility.ConclusionsThe investigative interior fixation method was safe and effective in rib stabilization on a canine rib fracture model, comparing to the exterior fixation method. The interior fixation was minimally invasive, with less damages to tissues and nerves surrounding the ribs, leading to better postoperative outcomes.
Folate deficiency reduced aberrant level of DOT1L-mediated histone H3K79 methylation causes disruptive SHH gene expression involved in neural tube defects
Authors: Li Xue , Pei Pei , Shen Jinying , Yu Juan , Wang Fang , Wang Lei , Liu Changyun , Wang Shan 
Published: December 2023

Abstract
Background
Neural tube defects (NTDs) are one of the most severe congenital abnormalities characterized by failures of the neural tube to close during early embryogenesis. Maternal folate deficiency could impact the occurrence of NTDs, however, the mechanisms involved in the cause of NTDs are poorly defined.

Results
Here, we report that histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Interestingly, folate antagonist methotrexate treatment led to attenuation of H3K79me2 due to Dot1l, affecting Shh and Sufu genes regulation. Upon further analysis, we find that the genes Shh and Sufu are both downregulated in the brain tissues of mice and humans with NTDs. There was a positive correlation between the transcription levels of Shh, Sufu and the protein levels of DOT1L by Pearson correlation analysis.

Conclusion
Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.
O-GlcNAcylation: the sweet side of epigenetics
Authors: Dupas Thomas , Lauzier Benjamin , McGraw Serge 
Published: December 2023

AbstractHistones display a wide variety of post-translational modifications, including acetylation, methylation, and phosphorylation. These epigenetic modifications can influence chromatin structure and function without altering the DNA sequence. Histones can also undergo post-translational O-GlcNAcylation, a rather understudied modification that plays critical roles in almost all biological processes and is added and removed by O-linked N-acetylglucosamine transferase and O-GlcNAcase, respectively. This review provides a current overview of our knowledge of how O-GlcNAcylation impacts the histone code both directly and by regulating other chromatin modifying enzymes. This highlights the pivotal emerging role of O-GlcNAcylation as an essential epigenetic marker.
Microbiota promotes recruitment and pro-inflammatory response of caecal macrophages during E. tenella infection
Authors: Tomal F. , Sausset A. , Le Vern Y. , Sedano L. , Techer C. , Lacroix-Lamandé S. , Laurent F. , Silvestre A. , Bussière F. I. 
Published: December 2023

Abstract
Background
Eimeria genus belongs to the apicomplexan parasite phylum and is responsible for coccidiosis, an intestinal disease with a major economic impact on poultry production. Eimeria tenella is one of the most virulent species in chickens. In a previous study, we showed a negative impact of caecal microbiota on the physiopathology of this infection. However, the mechanism by which microbiota leads to the physiopathology remained undetermined. Macrophages play a key role in inflammatory processes and their interaction with the microbiota during E. tenella infection have never been investigated. We therefore examined the impact of microbiota on macrophages during E. tenella infection. Macrophages were monitored in caecal tissues by immunofluorescence staining with KUL01 antibody in non-infected and infected germ-free and conventional chickens. Caecal cells were isolated, stained, analyzed and sorted to examine their gene expression using high-throughput qPCR.

Results
We demonstrated that microbiota was essential for caecal macrophage recruitment in E. tenella infection. Furthermore, microbiota promoted a pro-inflammatory transcriptomic profile of macrophages characterized by increased gene expression of NOS2, ACOD1, PTGS2, TNFα, IL1β, IL6, IL8L1, IL8L2 and CCL20 in infected chickens. Administration of caecal microbiota from conventional chickens to germ-free infected chickens partially restored macrophage recruitment and response.

Conclusions
Taken together, these results suggest that the microbiota enhances the physiopathology of this infection through macrophage recruitment and activation. Consequently, strategies involving modulation of the gut microbiota may lead to attenuation of the macrophage-mediated inflammatory response, thereby limiting the negative clinical outcome of the disease.
Effect of systemic atorvastatin on bone regeneration in critical-sized defects in hyperlipidemia: an experimental study
Authors: Öztürk Kübra , Kuzu Turan Emre , Ayrıkçil Semih , Gürgan Cem Abdulkadir , Önder Gözde Özge , Yay Arzu 
Published: December 2023

Abstract
Purpose
Hypocholesterolemic medications similar to atorvastatin are efficient in lowering blood lipid levels; however, compared to other medications in the statin family, their impact on bone metabolism is claimed to be insufficient. The impact of atorvastatin on bone regeneration in dental implantology in individuals with hyperlipidemia who received atorvastatin in the clinic is doubtful.

Methods
In the study, 16 male New Zealand rabbits of 6 months were used. All rabbits were fed a high-cholesterol diet for 8 weeks, and hyperlipidemia was created. It was confirmed that the total cholesterol level in rabbits was above 105 mg/dl. A critical-sized defect was created in the mandible. The defect was closed with xenograft and membrane. Oral 10 mg/kg atorvastatin was started in the experimental group, and no drug was administered in the control group. At 16th week, animals were sacrificed. For histomorphological examination, the new bone area, osteoclast, and osteoblast activities were evaluated.

Results
While new bone area (45,924 µm2, p < 0.001) and AP intensities (105.645 ± 16.727, p = 0.006) were higher in the atorvastatin group than in the control group, TRAP intensities in the control group (82.192 ± 5.346, p = 0.021) were higher than that in the atorvastatin group.

Conclusions
It has been found that high blood lipid levels will adversely affect bone graft healing and the use of systemic atorvastatin contributes to bone healing. Clinicians should pay attention to the selection of surgical materials, considering the importance of questioning drug use in their patients and the risks in cases of non-use.
Can intravitreal injections with higher volume cause higher intraocular eye pressure? Considerations for anti-complement injections in normal and glaucomatous eyes
Authors: Meyer Carsten H. , Melo Gustavo Barreto , Khanani Arshad M. 
Published: December 2023

AbstractThe approval of Syfovre® (pegcetacoplan) and Iverzay® (avacincaptad pegol) for the treatment of geographic atrophy (GA) marks a significant advancement in retinal disease therapy, offering both complement 3 and complement 5 inhibitors. With this breakthrough, an increase in intravitreal injections (IVI) is expected to treat GA, raising questions about potential effects on intraocular pressure (IOP). This concern is exacerbated by the larger injection volume required for GA treatment, potentially impacting IOP. Previous studies have shown that IVI can lead to a temporary increase in IOP with a 0.05 ml injection. This transient elevation is challenging to manage with glaucoma drops, and a preventive approach, such as paracentesis immediately before IVIs, may be more effective. Despite concerns, clinical significance and long-term effects of IOP changes with a 0.05 ml injection remain uncertain. To address these concerns, routine evaluations including macular optical coherence tomography (OCT), fundus autofluorescence, IOP measurements, and retinal nerve fiber layer OCT before the first IVI with avacincaptad pegol and pegcetacoplan are recommended to detect potential changes early. Further research is needed to determine the extent to which IOP changes impact GA patients and whether cumulative effects occur with repeated IVIs, especially in those with additional eye conditions.
Identification of ceRNA-vsiRNA-mRNA network for exploring the mechanism underlying pathogenesis of sugarcane mosaic virus in resistant and susceptible maize inbred lines
Authors: Gao Xinran , Hao Kaiqiang , Du Zhichao , Zhang Sijia , Wang Zhiping , An Mengnan , Xia Zihao , Wu Yuanhua 
Published: December 2023

AbstractRNA silencing plays an important role in plant antiviral responses, which trigger the production of virus-derived small interfering RNAs (vsiRNAs). The competing endogenous RNA (ceRNA) hypothesis revealed a unique mechanism in which circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can interact with small RNAs to regulate the expression of corresponding target mRNAs. Sugarcane mosaic virus (SCMV) infection causes severe economic losses in maize (Zea mays L.) production worldwide. This study compared and analyzed characteristics of vsiRNAs derived from SCMV and their target genes in resistant (Chang7-2) and susceptible (Mo17) maize inbred lines through whole-transcriptome RNA sequencing and degradome sequencing. The results showed that 706 transcripts were targeted by 204 vsiRNAs, including 784 vsiRNA-target gene pairs. Furthermore, ceRNA networks of circRNA/lncRNA-vsiRNA-mRNA in response of maize to SCMV infection were obtained, including 3 differentially expressed (DE) circRNAs, 36 DElncRNAs, 105 vsiRNAs, and 342 DEmRNAs in Mo17 plants, and 3 DEcircRNAs, 35 DElncRNAs, 23 vsiRNAs, and 87 DEmRNAs in Chang7-2 plants. Our results also showed that the transcripts of ZmDCLs, ZmAGOs, and ZmRDRs were differentially accumulated in resistant and susceptible maize inbred lines after SCMV infection. These findings provide valuable insights into the relationship between SCMV-derived vsiRNAs and potential ceRNAs fine-tuning the SCMV-maize interaction and offer novel clues to reveal the mechanism underlying the pathogenesis of SCMV.
Delivery of nucleic acids using nanomaterials
Authors: Qin Yuyang , Ou Liyuan , Zha Lili , Zeng Yue , Li Ling 
Published: December 2023

AbstractThe increasing number of approved nucleic acid therapeutics demonstrates the potential for the prevention and treatment of a broad spectrum of diseases. This trend underscores the significant impact and promise of nucleic acid-based treatments in the field of medicine. Nevertheless, employing nucleic acids as therapeutics is challenging due to their susceptibility to degradation by nucleases and their unfavorable physicochemical characteristics that hinder delivery into cells. Appropriate vectors play a pivotal role in improving nucleic acid stability and delivering nucleic acids into specific cells. The maturation of delivery systems has led to breakthroughs in the development of therapeutics based on nucleic acids such as DNA, siRNA, and mRNA. Non-viral vectors have gained prominence among the myriad of nanomaterials due to low immunogenicity, ease of manufacturing, and simplicity of cost-effective, large-scale production. Here, we provide an overview of the recent advancements in nanomaterials for nucleic acid delivery. Specifically, we give a detailed introduction to the characteristics of polymers, lipids, and polymer-lipid hybrids, and provide comprehensive descriptions of their applications in nucleic acid delivery. Also, biological barriers, administration routes, and strategies for organ-selective delivery of nucleic acids are discussed. In summary, this review offers insights into the rational design of next-generation delivery vectors for nucleic acid delivery.
Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study
Authors: Pott Christiane , Jurinovic Vindi , Trotman Judith , Kehden Britta , Unterhalt Michael , Herold Michael , Jagt Richard van der , Janssens Ann , Kneba Michael , Mayer Jiri , Young Moya , Schmidt Christian , Knapp Andrea , Nielsen Tina , Brown Helen , Spielewoy Nathalie , Harbron Chris , Bottos Alessia , Mundt Kirsten , Marcus Robert , Hiddemann Wolfgang , Hoster Eva 
Published: December 2023

PURPOSE We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968 ) trial. PATIENTS AND METHODS Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis. RESULTS MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; P < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; P < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% v 88.9%; P = .013) and at EOI (93.1% v 86.7%; P = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; P = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% v 16.0% in those receiving CHOP; P < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% v G-CHOP, 7.0%; R-CVP, 21.7% v G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse. CONCLUSION MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.
Four Additional Doses of PEG-L-Asparaginase During the Consolidation Phase in the AIEOP-BFM ALL 2009 Protocol Do Not Improve Outcome and Increase Toxicity in High-Risk ALL: Results of a Randomized Study
Authors: Conter Valentino , Valsecchi Maria Grazia , Cario Gunnar , Zimmermann Martin , Attarbaschi Andishe , Stary Jan , Niggli Felix , Dalla Pozza Luciano , Elitzur Sarah , Silvestri Daniela , Locatelli Franco , Möricke Anja , Engstler Gernot , Smisek Petr , Bodmer Nicole , Barbaric Draga , Izraeli Shai , Rizzari Carmelo , Boos Joachim , Buldini Barbara , Zucchetti Massimo , von Stackelberg Arend , Matteo Cristina , Lehrnbecher Thomas , Lanvers-Kaminsky Claudia , Cazzaniga Giovanni , Gruhn Bernd , Biondi Andrea , Schrappe Martin 
Published: December 2023

PURPOSE The AIEOP-BFM ALL 2009 protocol included, at the end of the induction phase, a randomized study of patients with high-risk (HR) ALL to investigate if an intensive exposure to pegylated L-asparaginase (PEG-ASNASE, 2,500 IU/sqm once a week × 4) on top of BFM consolidation phase IB allowed us to decrease minimal residual disease (MRD) and improve outcome. PATIENTS AND METHODS A total of 1,097 patients presented, from June 2010 to February 2017, with one or more of the following HR criteria: KMT2A::AFF1 rearrangement, hypodiploidy, prednisone poor response, poor bone marrow response at day 15 (Flow MRD ≥10%), or no complete remission (CR) at the end of induction. Of them, 809 (85.1%) were randomly assigned to receive (404) or not receive (405) four weekly doses of PEG-ASNASE. RESULTS By intention to treat (ITT) analysis, there was no significant difference in the proportion of patients with polimerase chain reaction MRD ≥5 × 10−4 at the end of phase IB in the experimental versus control arm (13.9% v 17.0%, P = .25). The 5-year event-free survival (median follow-up 6.3 years) by ITT in the experimental and control arms was 70.4% (2.3) versus 75.0% (2.2; P = .18), and the 5-year overall survival was 81.5% (2.0) versus 84.0% (1.9; P = .25), respectively. The corresponding 5-year cumulative incidence of death in CR was 9.5% (1.5) versus 5.7% (1.2; P = .08), and that of relapse was 17.7% (1.9) versus 17.2% (1.9), respectively ( P = .94). Adverse reactions in phase IB occurred in 22.2% and 8.9% of patients in the experimental and control arm, respectively ( P < .001). CONCLUSION Additional PEG-ASNASE in phase IB did not translate into a benefit for decreasing relapse incidence but was associated with higher toxicity. Further improvements with conventional chemotherapy might be difficult in the context of intensive treatment protocols.