bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanization slows the rapid movement of fungal necromass carbon and nitrogen into both bacterial and fungal decomposer communities and soils
Authors: Maillard François , Michaud Talia J. , See Craig R. , DeLancey Lang C. , Blazewicz Steven J. , Kimbrel Jeffrey A. , Pett-Ridge Jennifer , Kennedy Peter G. 
Published: June 2023

ABSTRACT

Microbial necromass contributes significantly to both soil carbon (C) persistence and ecosystem nitrogen (N) availability, but quantitative estimates of C and N movement from necromass into soils and decomposer communities are lacking. Additionally, while melanin is known to slow fungal necromass decomposition, how it influences microbial C and N acquisition as well as elemental release into soils remains unclear. Here, we tracked decomposition of isotopically labeled low and high melanin fungal necromass and measured
13
C and
15
N accumulation in surrounding soils and microbial communities over 77 d in a temperate forest in Minnesota, USA. Mass loss was significantly higher from low melanin necromass, corresponding with greater
13
C and
15
N soil inputs. A taxonomically and functionally diverse array of bacteria and fungi was enriched in
13
C and/or
15
N at all sampling points, with enrichment being consistently higher on low melanin necromass and earlier in decomposition. Similar patterns of preferential C and N enrichment of many bacterial and fungal genera early in decomposition suggest that both microbial groups co-contribute to the rapid assimilation of resource-rich soil organic matter inputs. While overall richness of taxa enriched in C was higher than in N for both bacteria and fungi, there was a significant positive relationship between C and N in co-enriched taxa. Collectively, our results demonstrate that melanization acts as a key ecological trait mediating not only fungal necromass decomposition rate but also necromass C and N release and that both elements are rapidly co-utilized by diverse bacterial and fungal decomposers in natural settings.

IMPORTANCE
Recent studies indicate that microbial dead cells, particularly those of fungi, play an important role in long-term carbon persistence in soils. Despite this growing recognition, how the resources within dead fungal cells (also known as fungal necromass) move into decomposer communities and soils are poorly quantified, particularly in studies based in natural environments. In this study, we found that the contribution of fungal necromass to soil carbon and nitrogen availability was slowed by the amount of melanin present in fungal cell walls. Further, despite the overall rapid acquisition of carbon and nitrogen from necromass by a diverse range of both bacteria and fungi, melanization also slowed microbial uptake of both elements. Collectively, our results indicate that melanization acts as a key ecological trait mediating not only fungal necromass decomposition rate, but also necromass carbon and nitrogen release into soil as well as microbial resource acquisition.
Effects of size at birth on health, growth and developmental outcomes in children up to age 18: an umbrella review
Authors: Jamaluddine Zeina , Sharara Eman , Helou Vanessa , El Rashidi Nadine , Safadi Gloria , El-Helou Nehmat , Ghattas Hala , Sato Miho , Blencowe Hannah , Campbell Oona M R 
Published: June 2023

BackgroundSize at birth, an indicator of intrauterine growth, has been studied extensively in relation to subsequent health, growth and developmental outcomes. Our umbrella review synthesises evidence from systematic reviews and meta-analyses on the effects of size at birth on subsequent health, growth and development in children and adolescents up to age 18, and identifies gaps.MethodsWe searched five databases from inception to mid-July 2021 to identify eligible systematic reviews and meta-analyses. For each meta-analysis, we extracted data on the exposures and outcomes measured and the strength of the association.FindingsWe screened 16 641 articles and identified 302 systematic reviews. The literature operationalised size at birth (birth weight and/or gestation) in 12 ways. There were 1041 meta-analyses of associations between size at birth and 67 outcomes. Thirteen outcomes had no meta-analysis.Small size at birth was examined for 50 outcomes and was associated with over half of these (32 of 50); continuous/post-term/large size at birth was examined for 35 outcomes and was consistently associated with 11 of the 35 outcomes. Seventy-three meta-analyses (in 11 reviews) compared risks by size for gestational age (GA), stratified by preterm and term. Prematurity mechanisms were the key aetiologies linked to mortality and cognitive development, while intrauterine growth restriction (IUGR), manifesting as small for GA, was primarily linked to underweight and stunting.InterpretationFuture reviews should use methodologically sound comparators to further understand aetiological mechanisms linking IUGR and prematurity to subsequent outcomes. Future research should focus on understudied exposures (large size at birth and size at birth stratified by gestation), gaps in outcomes (specifically those without reviews or meta-analysis and stratified by age group of children) and neglected populations.PROSPERO registration numberCRD42021268843.
Detecting the corneal neovascularisation area using artificial intelligence
Authors: Mergen Burak , Safi Tarek , Nadig Matthias , Bhattrai Gopal , Daas Loay , Alexandersson Jan , Seitz Berthold 
Published: June 2023

AimsTo create and assess the performance of an artificial intelligence-based image analysis tool for the measurement and quantification of the corneal neovascularisation (CoNV) area.MethodsSlit lamp images of patients with CoNV were exported from the electronic medical records and included in the study. An experienced ophthalmologist made manual annotations of the CoNV areas, which were then used to create, train and evaluate an automated image analysis tool that uses deep learning to segment and detect CoNV areas. A pretrained neural network (U-Net) was used and fine-tuned on the annotated images. Sixfold cross-validation was used to evaluate the performance of the algorithm on each subset of 20 images. The main metric for our evaluation was intersection over union (IoU).ResultsThe slit lamp images of 120 eyes of 120 patients with CoNV were included in the analysis. Detections of the total corneal area achieved IoU between 90.0% and 95.5% in each fold and those of the non-vascularised area achieved IoU between 76.6% and 82.2%. The specificity for the detection was between 96.4% and 98.6% for the total corneal area and 96.6% and 98.0% for the non-vascularised area.ConclusionThe proposed algorithm showed a high accuracy compared with the measurement made by an ophthalmologist. The study suggests that an automated tool using artificial intelligence may be used for the calculation of the CoNV area from the slit-lamp images of patients with CoNV.
Network pharmacology and biochemical experiments reveal the antiapoptotic mechanism of huperzine A for treating diabetic retinopathy
Authors: Zhang Ying , Huang Wunan , Tian Qing , Bai Guannan , Wu Wei , Yin Houfa , Hu Lidan , Chen Xiangjun 
Published: June 2023

Background/aims
Diabetic retinopathy is the most common eye disease that causes blindness in the working population. Neurodegeneration is the early sign of diabetic retinopathy, but no drug has been approved for delaying or reversing retinal neurodegeneration. Huperzine A, a natural alkaloid isolated from Huperzia serrata, displays neuroprotective and antiapoptotic effects in treating neurodegenerative disorders. Our study aims to investigate the effect of huperzine A in preventing retinal neurodegeneration of diabetic retinopathy and its possible mechanism.

Methods
Diabetic retinopathy model was induced by streptozotocin. H&E staining, optical coherence tomography, immunofluorescence staining and angiogenic factors were used to determine the degree of retinal pathological injury. The possible molecular mechanism was unrevealed by network pharmacology analysis and further validated by biochemical experiments.

Results
In our study, we demonstrated that huperzine A has a protective effect on the diabetes retina in a diabetic rat model. Based on the network pharmacology analysis and biochemical studies, huperzine A may treat diabetic retinopathy via key target HSP27 and apoptosis-related pathways. Huperzine A may modulate the phosphorylation of HSP27 and activate the antiapoptotic signalling pathway.

Conclusion
Our findings revealed that huperzine A might be a potential therapeutic drug to prevent diabetic retinopathy. It is the first-time combining network pharmacology analysis with biochemical studies to explore the mechanism of huperzine A in preventing diabetic retinopathy.
Drug interventions for prevention of COVID-19 progression to severe disease in outpatients: a systematic review with meta-analyses and trial sequential analyses (The LIVING Project)
Authors: Petersen Johanne Juul , Jørgensen Caroline Kamp , Faltermeier Pascal , Siddiqui Faiza , Feinberg Joshua , Nielsen Emil Eik , Torp Kristensen Andreas , Juul Sophie , Holgersson Johan , Nielsen Niklas , Bentzer Peter , Thabane Lehana , Kwasi Korang Steven , Klingenberg Sarah , Gluud Christian , Jakobsen Janus C 
Published: June 2023

ObjectivesTo assess the effects of interventions authorised by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA) for prevention of COVID-19 progression to severe disease in outpatients.SettingOutpatient treatment.ParticipantsParticipants with a diagnosis of COVID-19 and the associated SARS-CoV-2 virus irrespective of age, sex and comorbidities.InterventionsDrug interventions authorised by EMA or FDA.Primary outcome measuresPrimary outcomes were all-cause mortality and serious adverse events.ResultsWe included 17 clinical trials randomising 16 257 participants to 8 different interventions authorised by EMA or FDA. 15/17 of the included trials (88.2%) were assessed at high risk of bias. Only molnupiravir and ritonavir-boosted nirmatrelvir seemed to improve both our primary outcomes. Meta-analyses showed that molnupiravir reduced the risk of death (relative risk (RR) 0.11, 95% CI 0.02 to 0.64; p=0.0145, 2 trials; very low certainty of evidence) and serious adverse events (RR 0.63, 95% CI 0.47 to 0.84; p=0.0018, 5 trials; very low certainty of evidence). Fisher’s exact test showed that ritonavir-boosted nirmatrelvir reduced the risk of death (p=0.0002, 1 trial; very low certainty of evidence) and serious adverse events (p<0.0001, 1 trial; very low certainty of evidence) in 1 trial including 2246 patients, while another trial including 1140 patients reported 0 deaths in both groups.ConclusionsThe certainty of the evidence was very low, but, from the results of this study, molnupiravir showed the most consistent benefit and ranked highest among the approved interventions for prevention of COVID-19 progression to severe disease in outpatients. The lack of certain evidence should be considered when treating patients with COVID-19 for prevention of disease progression.PROSPERO registration numberCRD42020178787.
Risk of myocarditis and pericarditis in mRNA COVID-19-vaccinated and unvaccinated populations: a systematic review and meta-analysis
Authors: Alami Abdallah , Krewski Daniel , Farhat Nawal , Mattison Donald , Wilson Kumanan , Gravel Christopher A , Farrell Patrick J , Crispo James A G , Haddad Nisrine , Perez-Lloret Santiago , Villeneuve Paul J 
Published: June 2023

ObjectiveTo summarise the available evidence on the risk of myocarditis and/or pericarditis following mRNA COVID-19 vaccination, compared with the risk among unvaccinated individuals in the absence of COVID-19 infection.DesignSystematic review and meta-analysis.Data sourcesElectronic databases (Medline, Embase, Web of Science and WHO Global Literature on Coronavirus Disease), preprint repositories (medRxiv and bioRxiv), reference lists and grey literature were searched from 1 December 2020 until 31 October 2022.Study selectionEpidemiological studies of individuals of any age who received at least one dose of an mRNA COVID-19 vaccine, reported a risk of myo/pericarditis and compared the risk of myo/pericarditis to individuals who did not receive any dose of an mRNA COVID-19 vaccine.Data extraction and synthesisTwo reviewers independently conducted screening and data extraction. The rate of myo/pericarditis among vaccinated and unvaccinated groups was recorded, and the rate ratios were calculated. Additionally, the total number of individuals, case ascertainment criteria, percentage of males and history of SARS-CoV-2 infection were extracted for each study. Meta-analysis was done using a random-effects model.ResultsSeven studies met the inclusion criteria, of which six were included in the quantitative synthesis. Our meta-analysis indicates that within 30-day follow-up period, vaccinated individuals were twice as likely to develop myo/pericarditis in the absence of SARS-CoV-2 infection compared to unvaccinated individuals, with a rate ratio of 2.05 (95% CI 1.49–2.82).ConclusionAlthough the absolute number of observed myo/pericarditis cases remains quite low, a higher risk was detected in those who received mRNA COVID-19 vaccinations compared with unvaccinated individuals in the absence of SARS-CoV-2 infection. Given the effectiveness of mRNA COVID-19 vaccines in preventing severe illnesses, hospitalisations and deaths, future research should focus on accurately determining the rates of myo/pericarditis linked to mRNA COVID-19 vaccines, understanding the biological mechanisms behind these rare cardiac events and identifying those most at risk.
Socioeconomic inequalities in cervical precancer screening among women in Ethiopia, Malawi, Rwanda, Tanzania, Zambia and Zimbabwe: analysis of Population-Based HIV Impact Assessment surveys
Authors: Chipanta David , Kapambwe Sharon , Nyondo-Mipando Alinane Linda , Pascoe Margaret , Amo-Agyei Silas , Bohlius Julia , Estill Janne , Keiser Olivia 
Published: June 2023

ObjectivesWe examined age, residence, education and wealth inequalities and their combinations on cervical precancer screening probabilities for women. We hypothesised that inequalities in screening favoured women who were older, lived in urban areas, were more educated and wealthier.DesignCross-sectional study using Population-Based HIV Impact Assessment data.SettingEthiopia, Malawi, Rwanda, Tanzania, Zambia and Zimbabwe. Differences in screening rates were analysed using multivariable logistic regressions, controlling for age, residence, education and wealth. Inequalities in screening probability were estimated using marginal effects models.ParticipantsWomen aged 25–49 years, reporting screening.Outcome measuresSelf-reported screening rates, and their inequalities in percentage points, with differences of 20%+ defined as high inequality, 5%–20% as medium, 0%–5% as low.ResultsThe sample size of participants ranged from 5882 in Ethiopia to 9186 in Tanzania. The screening rates were low in the surveyed countries, ranging from 3.5% (95% CI 3.1% to 4.0%) in Rwanda to 17.1% (95% CI 15.8% to 18.5%) and 17.4% (95% CI 16.1% to 18.8%) in Zambia and Zimbabwe. Inequalities in screening rates were low based on covariates. Combining the inequalities led to significant inequalities in screening probabilities between women living in rural areas aged 25–34 years, with a primary education level, from the lowest wealth quintile, and women living in urban areas aged 35–49 years, with the highest education level, from the highest wealth quintile, ranging from 4.4% in Rwanda to 44.6% in Zimbabwe.ConclusionsCervical precancer screening rates were inequitable and low. No country surveyed achieved one-third of the WHO’s target of screening 70% of eligible women by 2030. Combining inequalities led to high inequalities, preventing women who were younger, lived in rural areas, were uneducated, and from the lowest wealth quintile from screening. Governments should include and monitor equity in their cervical precancer screening programmes.
Cohort profile: radiotherapy dataset (RTDS) in England
Authors: Sandhu Sabrina , Sharpe Michael , Findlay Úna , Roe Catherine , Broggio John , Spencer Katie , Thackray Katherine 
Published: June 2023

PurposeThe purpose of the Radiotherapy Dataset (RTDS) is to collect consistent and comparable data across all providers of National Health Service (NHS)-funded radiotherapy and to provide intelligence for service planning, commissioning, clinical practice and research.ParticipantsThe RTDS is a mandated dataset requiring providers to collect and submit data monthly for patients treated in England. Data is available from 01 April 2009 to 2 months behind the calendar month.The National Disease Registration Service (NDRS) started receiving data from 01 April 2016. Prior to this, the National Clinical Analysis and Specialised Applications Team (NATCANSAT) were responsible for the RTDS. NDRS holds a copy of the NATCANSAT data for English NHS providers.The RTDS contains clinical information on the primary disease being treated, modality and intent of treatment, dose fractionation and hospital appointment details. Due to constraints in RTDS coding, linkage to the English National Cancer Registration dataset is beneficial.Findings to dateThe RTDS has been linked to the English National Cancer Registration and Systemic Anti-Cancer Therapy (SACT) datasets and to Hospital Episode Statistics (HES) to provide a more complete picture of the patient cancer pathway. Findings include a study to compare outcomes for patients treated with radical radiotherapy, an investigation of factors influencing 30-day mortality, assessing sociodemographic variation in the use of treatment and a study to assess the service impact of the COVID-19 pandemic. A range of other studies have been completed or are ongoing currently.Future plansThe RTDS can be used for a variety of functions including cancer epidemiological studies to investigate inequalities in treatment access; provide service planning intelligence; monitor clinical practice; and support clinical trial design and recruitment. Collection is to continue indefinitely, with regular updates to the data specification to enable capture of more detailed information on radiotherapy planning and delivery.
Children using a unilateral cochlear implant and contralateral hearing aid: bimodal hearing outcomes when one ear is outside the UK (NICE 2009) audiological criteria for cochlear implantation – a single site case–control study
Authors: Bruce Iain , Schaefer Simone , Kluk Karolina , Nichani Jaya , Odriscoll Martin , Rajai Azita , Sladen Mark 
Published: June 2023

IntroductionIn the new revised National Institute for Health & Care Excellence (NICE, TA566, 2019) guidelines for cochlear implantation (CI) have clearly stipulated that the hearing loss must be bilateral. Prior to this revision, children and young people (CYP) with asymmetrical thresholds have been considered for unilateral CI when one ear was in audiological criteria. Children with asymmetrical hearing loss represent an important cohort of potential CI candidates, who will continue to be prevented from benefiting from CI unless evidence is produced to support implantation and maximise subsequent benefit.The aim of this study is to evaluate the ‘real-life’ hearing performance in a group of children who have received a unilateral CI and who have hearing thresholds in the contralateral ear that are outside the current UK NICE 2019 audiological criteria for CI. The contralateral ear will be aided using a conventional hearing aid (HA). The outcomes from this ‘bimodal’ group will be compared with a group of children who have received bilateral CI, and a group of children using bilateral HA, to extend the current knowledge about the different performance levels between bilateral CI, bilateral HA and bimodal hearing in CYP.Methods and analysisThirty CYP aged 6–17 years old, 10 bimodal users, 10 bilateral HA users and 10 bilateral cochlear implant users will be subjected to a test battery consisting of: (1) spatial release from masking, (2) complex pitch direction discrimination, (3) melodic identification, (4) perception of prosodic features in speech and (5) TEN test. Subjects will be tested in their optimal device modality. Standard demographic and hearing health information will be collected. In the absence of comparable published data to power the study, sample size was determined on pragmatic grounds. Tests are exploratory and for hypothesis generating purposes. Therefore, the standard criterion of p<0.05 will be used.Ethics and disseminationThis has been approved by the Health Research Authority and NHS REC within the UK (22/EM/0104). Industry funding was secured via a competitive researcher-led grant application process. Trial results will be subject to publication according to the definition of the outcome presented in this protocol.
Method for estimation of apoptotic cell fraction of cytotherapy using in vivo fluorine-19 magnetic resonance: pilot study in a patient with head and neck carcinoma receiving tumor-infiltrating lymphocytes labeled with perfluorocarbon nanoemulsion
Authors: Ahrens Eric T , Helfer Brooke M , O’Hanlon Charles F , Lister Deanne R , Bykowski Julie L , Messer Karen , Leach Benjamin I , Chen Jiawen , Xu Hongyan , Daniels Gregory A , Cohen Ezra E W 
Published: June 2023

BackgroundAdoptive transfer of T cells is a burgeoning cancer therapeutic approach. However, the fate of the cells, once transferred, is most often unknown. We describe the first clinical experience with a non-invasive biomarker to assay the apoptotic cell fraction (ACF) after cell therapy infusion, tested in the setting of head and neck squamous cell carcinoma (HNSCC). A patient with HNSCC received autologous tumor-infiltrating lymphocytes (TILs) labeled with a perfluorocarbon (PFC) nanoemulsion cell tracer. Nanoemulsion, released from apoptotic cells, clears through the reticuloendothelial system, particularly the Kupffer cells of the liver, and fluorine-19 (19F) magnetic resonance spectroscopy (MRS) of the liver was used to non-invasively infer the ACF.MethodsAutologous TILs were isolated from a patient in their late 50s with relapsed, refractory human papillomavirus-mediated squamous cell carcinoma of the right tonsil, metastatic to the lung. A lung metastasis was resected for T cell harvest and expansion using a rapid expansion protocol. The expanded TILs were intracellularly labeled with PFC nanoemulsion tracer by coincubation in the final 24 hours of culture, followed by a wash step. At 22 days after intravenous infusion of TILs, quantitative single-voxel liver19F MRS was performed in vivo using a 3T MRI system. From these data, we model the apparent ACF of the initial cell inoculant.ResultsWe show that it is feasible to PFC-label ~7×1010TILs (F-TILs) in a single batch in a clinical cell processing facility, while maintaining >90% cell viability and standard flow cytometry-based release criteria for phenotype and function. Based on quantitative in vivo19F MRS measurements in the liver, we estimate that ~30% cell equivalents of adoptively transferred F-TILs have become apoptotic by 22 days post-transfer.ConclusionsSurvival of the primary cell therapy product is likely to vary per patient. A non-invasive assay of ACF over time could potentially provide insight into the mechanisms of response and non-response, informing future clinical studies. This information may be useful to developers of cytotherapies and clinicians as it opens an avenue to quantify cellular product survival and engraftment.