bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined pangenomics and transcriptomics reveals core and redundant virulence processes in a rapidly evolving fungal plant pathogen
Authors: Chen Hongxin , King Robert , Smith Dan , Bayon Carlos , Ashfield Tom , Torriani Stefano , Kanyuka Kostya , Hammond-Kosack Kim , Bieri Stephane , Rudd Jason 
Published: February 2023

Abstract
Background
Studying genomic variation in rapidly evolving pathogens potentially enables identification of genes supporting their “core biology”, being present, functional and expressed by all strains or “flexible biology”, varying between strains. Genes supporting flexible biology may be considered to be “accessory”, whilst the “core” gene set is likely to be important for common features of a pathogen species biology, including virulence on all host genotypes. The wheat-pathogenic fungus Zymoseptoria tritici represents one of the most rapidly evolving threats to global food security and was the focus of this study.

Results
We constructed a pangenome of 18 European field isolates, with 12 also subjected to RNAseq transcription profiling during infection. Combining this data, we predicted a “core” gene set comprising 9807 sequences which were (1) present in all isolates, (2) lacking inactivating polymorphisms and (3) expressed by all isolates. A large accessory genome, consisting of 45% of the total genes, was also defined. We classified genetic and genomic polymorphism at both chromosomal and individual gene scales. Proteins required for essential functions including virulence had lower-than average sequence variability amongst core genes. Both core and accessory genomes encoded many small, secreted candidate effector proteins that likely interact with plant immunity. Viral vector-mediated transient in planta overexpression of 88 candidates failed to identify any which induced leaf necrosis characteristic of disease. However, functional complementation of a non-pathogenic deletion mutant lacking five core genes demonstrated that full virulence was restored by re-introduction of the single gene exhibiting least sequence polymorphism and highest expression.

Conclusions
These data support the combined use of pangenomics and transcriptomics for defining genes which represent core, and potentially exploitable, weaknesses in rapidly evolving pathogens.
Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study
Authors: Øyri Linn K. L. , Christensen Jacob J. , Sebert Sylvain , Thoresen Magne , Michelsen Trond M. , Ulven Stine M. , Brekke Hilde K. , Retterstøl Kjetil , Brantsæter Anne Lise , Magnus Per , Bogsrud Martin P. , Holven Kirsten B. 
Published: February 2023

AbstractBackgroundNumerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent.MethodsThis parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age).ResultsHigher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99).ConclusionsMaternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.
Neonatal intensive care admission for term neonates and subsequent childhood mortality: a retrospective linkage study
Authors: Talisman Shahar , Guedalia Joshua , Farkash Rivka , Avitan Tehila , Srebnik Naama , Kasirer Yair , Schimmel Michael S. , Ghanem Donia , Unger Ron , Granovsky Sorina Grisaru 
Published: February 2023

Abstract

Background
Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The aim of this study was to study the association of the NICU admission of term neonates on the risk of long-term childhood mortality.

Methods
A single-center case–control retrospective study between 2005 and 2019, including all in-hospital ≥ 37 weeks’ gestation singleton live-born neonates. The center perinatal database was linked with the birth and death certificate registries of the Israeli Ministry of Internal Affairs. The primary aim of the study was to study the association between NICU admission and childhood mortality throughout a 15-year follow-up period.

Results
During the study period, 206,509 births were registered; 192,527 (93.22%) term neonates were included in the study; 5292 (2.75%) were admitted to NICU. Throughout the follow-up period, the mortality risk for term neonates admitted to the NICU remained elevated; hazard ratio (HR), 19.72 [14.66, 26.53], (p < 0.001). For all term neonates, the mortality rate was 0.16% (n = 311); 47.9% (n = 149) of those had records of a NICU admission. The mortality rate by time points (ratio1:10,0000 births) related to the age at death during the follow-up period was as follows: 29, up to 7 days; 20, 7–28 days; 37, 28 days to 6 months; 21, 6 months to 1 year; 19, 1–2 years; 9, 2–3 years; 10, 3–4 years; and 27, 4 years and more. Following the exclusion of congenital malformations and chromosomal abnormalities, NICU admission remained the most significant risk factor associated with mortality of the study population, HRs, 364.4 [145.3; 913.3] for mortality in the first 7 days of life; 19.6 [12.1; 32.0] for mortality from 28 days through 6 months of life and remained markedly elevated after age 4 years; HR, 7.1 [3.0; 17.0]. The mortality risk related to the NICU admission event, adjusted for admission diagnoses remained significant; HR = 8.21 [5.43; 12.4].

Conclusions
NICU admission for term neonates is a pondering event for the risk of long-term childhood mortality. This group of term neonates may benefit from focused health care.
Association of intellectual disability with overall and type-specific cardiovascular diseases: a population-based cohort study in Denmark
Authors: Wang Hui , Lee Priscilla Ming Yi , Zhang Jun , Svendsen Katrine , Li Fei , Li Jiong 
Published: February 2023

Abstract
Background
Individuals with mental health problems have been shown to have an increased risk of cardiovascular disorder (CVD), but little is known about the risk of early-onset CVD among those with intellectual disability. We aimed to investigate the association between intellectual disability and subsequent CVD, taking into consideration the severity of intellectual disability and neurodevelopmental and neurologic comorbidity.

Methods
This population-based cohort study used individual-level linked data from Danish national health registries. Participants were all live-born singletons born in Denmark during 1978–2016 (n = 2,288,393). Follow-up began from birth and continued until the onset of CVD, death, emigration, or December 31, 2018, whichever came first. Clinical diagnosis of any CVD or type-specific CVDs was identified in the Danish National Patient Register. Time-varying Cox regression analyses were used to estimate the hazard ratio (HR) of intellectual disability associated with overall and type-specific CVDs.

Results
A total of 11,954 individuals received a diagnosis of intellectual disability (7434 males and 4520 females). During a median follow-up time of 18.5 years (interquartile range, 18.1 years), 652 individuals with intellectual disability (5.5%) received a diagnosis of CVD (incidence rate, 2.4 per 1000 person-years), compared with 78,088 (3.4%) CVD cases in individuals without intellectual disability (incidence rate, 1.9 per 1000 person-years), corresponding to a HR of 1.24 (95% CI, 1.15–1.34). Increased risks of CVD were similar in both childhood (HR, 1.24; 95% CI, 1.08–1.43) and early adulthood (HR, 1.25; 95% CI, 1.14–1.38). For type-specific CVDs, intellectual disability was significantly associated with cerebrovascular disease (HR, 2.50; 95% CI, 2.02–3.10), stroke (HR, 2.20; 95% CI, 1.69–2.86), heart failure (HR, 3.56; 95% CI, 2.37–5.35), hypertensive disease (HR, 1.30; 95% CI, 1.22–1.39), and deep vein thrombosis (HR, 2.10; 95% CI, 1.60–2.75). Stratified HRs of overall CVD were 1.14 (95% CI, 1.01–1.30) for borderline/mild intellectual disability, 1.25 (95% CI, 1.01–1.54) for moderate intellectual disability, and 1.91 (95% CI, 1.47–2.48) for severe/profound intellectual disability. After the exclusion of individuals with neurodevelopmental and neurologic comorbidity, intellectual disability remained significantly associated with increased risks of CVD.

Conclusions
Individuals with intellectual disability had increased risks of early-onset CVD, in particular, for cerebrovascular disease, stroke, heart failure, and deep vein thrombosis, and the risks also increased with the severity of intellectual disability. Our findings highlight the awareness of increased risks of CVD in intellectual disability patients.
Aspiration prevention surgeries: a review
Authors: Ueha Rumi , Magdayao Redentor B. , Koyama Misaki , Sato Taku , Goto Takao , Yamasoba Tatsuya 
Published: February 2023

AbstractBackgroundSevere dysphagia can cause intractable pneumonia and lead to life-threatening conditions. Intractable aspiration can occur despite medical management for aspiration prevention. Surgical intervention is indicated for intractable aspiration to prevent potentially life-threatening complications. Since the 1970s, several surgical treatments to prevent aspiration have been reported, and various aspiration prevention surgeries have been introduced, but little is known about them or their benefits. This is a review of the types of aspiration prevention surgery, with the aim of increasing aspiration prevention surgery awareness and their clinical outcomes among medical professionals, which will guide the choices of aspiration prevention surgeries for patients with intractable aspiration.Main bodyAspiration prevention surgeries can be categorized into three according to their approaches: removal of the larynx, altering the structure of the trachea, and closure of the larynx. Aspiration prevention surgeries to remove the larynx include total and central-part laryngectomy. Aspiration prevention surgeries to alter the structure of the trachea include tracheoesophageal diversion, laryngotracheal separation, and the tracheal flap method. Surgeries to close the larynx can be divided into supraglottic laryngeal closure, glottic laryngeal closure, and subglottic laryngeal closure. Aspiration prevention surgeries prevent aspiration and increase oral intake in 50–80% of patients. Most patients lose vocal function after aspiration prevention surgeries; however, some patients who have undergone total laryngectomy or laryngotracheal separation restored their speech function through tracheoesophageal puncture and use of voice prosthesis. Postoperative suture failure is frequent after epiglottic flap closure and total laryngectomy but rare after central-part laryngectomy, laryngotracheal separation, glottic closure, and subglottic closure. Furthermore, aspiration prevention surgeries improve the quality of life of patients and their caregivers by decreasing suctioning frequency.ConclusionsIn this review, we described the history and development of aspiration prevention surgeries. Medical professionals need to continually improve their knowledge and skills to facilitate appropriate aspiration prevention surgeries according to patient condition.
Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial
Authors: Chiarito Mauro , Sanz-Sanchez Jorge , Piccolo Raffaele , Condello Francesco , Liccardo Gaetano , Maurina Matteo , Avvedimento Marisa , Regazzoli Damiano , Pagnotta Paolo , Garcia-Garcia Hector M. , Mehran Roxana , Federici Massimo , Condorelli Gianluigi , Diez Gil Jose Luis , Reimers Bernhard , Ferrante Giuseppe , Stefanini Giulio 
Published: February 2023

Abstract
Background
Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels.

Methods
In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality.

Results
142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3–2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3–2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR − 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43–150), no patients required hemodialysis and 2 patients died due to non-cardiac causes.

Conclusions
In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function.
Trial registration: The study was registered at Clinicaltrials.gov (NCT04766008).

Graphical Abstract
Effect of large-scale mass drug administration for malaria on mortality and morbidity in Angumu health zone, Ituri, Democratic Republic of Congo
Authors: Grout Lise , Katuala Givo Yves , Newport Trish , Mahamat Tom Adoum , Gitahi Priscillah , Mandagot Jean Jacques , Quere Michel , Wodon Sophie , Ciglenecki Iza , Bastard Mathieu , Baelongandi Francis , Tshulo Louis , Uluba Herman Jakisa , Sterk Esther , Gignoux Etienne 
Published: February 2023

Abstract
Background
Angumu health zone in Ituri, Democratic Republic of Congo, is a highly malaria-endemic area with an overburdened health system and hosting internally displaced persons (IDP). The World Health Organization recommends mass drug administration (MDA) for malaria in complex emergencies. Therefore, three MDA rounds were implemented by Ministry of Public Health and Médecins sans Frontières from September 2020 to January 2021 in four health areas selected for epidemiological (high malaria incidence) and logistic reasons. Reported mortality and morbidity were compared in locations where MDA has been performed and locations where it has not.

Methods
A non-randomized controlled population-based retrospective mortality survey was conducted in March 2021. Two-stage cluster sampling was used in villages; all IDP sites were surveyed with systematic random sampling. The main (mortality rates) and secondary (morbidity) outcomes were estimated and compared between locations where MDA had been conducted and where it had not, using mixed Poisson and binomial regression models respectively.

Results
Data was collected for 2554 households and 15470 individuals, of whom 721 died in the 18-month recall period. The under-five mortality rate (U5MR) decreased in the locations where MDA had been implemented from 2.32 [1.48–3.16] “before” the MDA to 1.10 [0.5–1.71] deaths/10,000 children under 5 years/day “after”, whereas it remained stable from 2.74 [2.08–3.40] to 2.67 [1.84–3.50] deaths/10,000 children/day in the same time periods in locations where MDA had not been implemented. The U5MR and malaria-specific mortality was significantly higher in non-MDA locations after MDA was implemented (aRR = 2.17 [1.36–3.49] and 2.60 [1.56–4.33], respectively, for all-cause and malaria-specific mortality among children  < 5 years). Morbidity (all age and  < 5 years, all cause or malaria-specific) appeared lower in MDA locations 2.5 months after last round: reported malaria-specific morbidity was 14.7% [11–18] and 25.0% [19–31] in villages and IDP sites where MDA had been implemented, while it was 30.4% [27–33] and 49.3% [45–54] in villages and IDP sites with no MDA.

Conclusions
Despite traditional limitations associated with non-randomized controlled retrospective surveys, the documented sharp decrease of under-5 mortality and morbidity shows that MDA has the potential to become an important malaria-control tool in emergency settings. Based on these results, new MDA rounds, along with indoor residual spraying campaigns, have been planned in the health zone in 2022. A set of surveys will be conducted before, during and after these rounds to confirm the effect observed in 2021 and assess its duration.
“It is like an umbrella covering you, yet it does not protect you from the rain”: a mixed methods study of insurance affordability, coverage, and financial protection in rural western Kenya
Authors: Maritim Beryl , Koon Adam D. , Kimaina Allan , Lagat Cornelius , Riungu Elvira , Laktabai Jeremiah , Ruhl Laura J. , Kibiwot Michael , Scanlon Michael L. , Goudge Jane 
Published: February 2023

AbstractCountries in Sub-Saharan Africa are increasingly adopting mandatory social health insurance programs. In Kenya, mandatory social health insurance is being implemented through the national health insurer, the National Hospital Insurance Fund (NHIF), but the level of coverage, affordability and financial risk protection provided by health insurance, especially for rural informal households, is unclear. This study provides as assessment of affordability of NHIF premiums, the need for financial risk protection, and the extent of financial protection provided by NHIF among rural informal workers in western Kenya.Methods We conducted a mixed methods study with a cross-sectional household survey (n = 1773), in-depth household interviews (n = 36), and 6 focus group discussions (FGDs) with community stakeholders in rural western Kenya. Health insurance status was self-reported and households were categorized into insured and uninsured. Using survey data, we calculated the affordability of health insurance (unaffordability was defined as the monthly premium being > 5% of total household expenditures), out of pocket expenditures (OOP) on healthcare and its impact on impoverishment, and incidence of catastrophic health expenditures (CHE). Logistic regression was used to assess household characteristics associated with CHE.Results Only 12% of households reported having health insurance and was unaffordable for the majority of households, both insured (60%) and uninsured (80%). Rural households spent an average of 12% of their household budget on OOP, with both insured and uninsured households reporting high OOP spending and similar levels of impoverishment due to OOP. Overall, 12% of households experienced CHE, with uninsured households more likely to experience CHE. Participants expressed concerns about value of health insurance given its cost, availability and quality of services, and financial protection relative to other social and economic household needs. Households resulted to borrowing, fundraising, taking short term loans and selling family assets to meet healthcare costs.Conclusion Health insurance coverage was low among rural informal sector households in western Kenya, with health insurance premiums being unaffordable to most households. Even among insured households, we found high levels of OOP and CHE. Our results suggest that significant reforms of NHIF and health system are required to provide adequate health services and financial risk protection for rural informal households in Kenya.
Smart nanoparticles and microbeads for interventional embolization therapy of liver cancer: state of the art
Authors: Wu Sitong , Fan Kevin , Yang Qi , Chen Zhao , Hou Yi , Zou Yinghua , Cai Weibo , Kang Lei 
Published: February 2023

AbstractThe process of transcatheter arterial chemoembolization is characterized by the ability to accurately deliver chemotherapy drugs with minimal systemic side effects and has become the standard treatment for unresectable intermediate hepatocellular carcinoma (HCC). However, this treatment option still has much room for improvement, one of which may be the introduction of nanomaterials, which exhibit unique functions and can be applied to in vivo tumor imaging and therapy. Several biodegradable and multifunctional nanomaterials and nanobeads have recently been developed and applied in the locoregional treatment of hepatocellular cancer. This review explores recent developments and findings in relation to micro-nano medicines in transarterial therapy for HCC, emerging strategies to improve the efficacy of delivering nano-based medicines, and expounding prospects for clinical applications of nanomaterials.
Visualization of SARS-CoV-2 particles in naso/oropharyngeal swabs by thin section electron microscopy
Authors: Laue Michael , Hoffmann Tobias , Michel Janine , Nitsche Andreas 
Published: February 2023

Abstract
Background
SARS-CoV-2 replicates efficiently in the upper airways of humans and produces high loads of virus RNA and, at least in the initial phase after infection, many infectious virus particles. Studying virus ultrastructure, such as particle integrity or presence of spike proteins, and effects on their host cells in patient samples is important to understand the pathogenicity of SARS-CoV-2.

Methods
Suspensions from swab samples with a high load of virus RNA (Ct < 20) were sedimented by desktop ultracentrifugation and prepared for thin section electron microscopy using a novel method which is described in detail. Embedding was performed in Epon or in LR White resin using standard or rapid protocols. Thin sections were examined using transmission electron microscopy.

Results
Virus particles could be regularly detected in the extracellular space, embedded in a background of heterogenous material (e.g. vesicles and needle-like crystals), and within ciliated cells. Morphology (i.e. shape, size, spike density) of virus particles in the swab samples was very similar to particle morphology in cell culture. However, in some of the samples the virus particles hardly revealed spikes. Infected ciliated cells occasionally showed replication organelles, such as double-membrane vesicles. The most common cells in all samples were keratinocytes from the mucosa and bacteria.

Conclusions
The new method allows the ultrastructural visualization and analysis of coronavirus particles and of infected host cells from easy to collect naso/oropharyngeal patient swab samples.