bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of haemosporidia in Asian Glossy Starling with discovery of misbinding of Haemoproteus-specific primer to Plasmodium genera in Sarawak, Malaysian Borneo
Authors: Noni Vaenessa , Tan Cheng Siang
Published: April 2023

Background

Plasmodium, Haemoproteus and Leucocytozoon are three mainly studied blood parasites known to cause malarial and pseudomalarial infections in avian worldwide. Although Sarawak is a biodiversity hotspot, molecular data on blood parasite diversity in birds are absent. The objective of the study is to determine the prevalence of blood parasite in Asian Glossy Starlings (AGS), an urban bird with high population density in Sarawak and to elucidate the phylogenetic relationship with other blood parasite.

Methods

Twenty-nine carcasses of juvenile AGS that were succumbed to death due to window collision were collected around the vicinity of Universiti Malaysia Sarawak. Nested-multiplex and nested PCR targeting the Cytochrome B gene were used to detect Plasmodium and Haemoproteus, and Leucocytozoon respectively. Two primer sets were used for Haemoproteus detection to increase detection sensitivity, with one being a genus-specific primer.

Results

Fourteen samples (prevalence rate: 48.28%) were found positive for avian Plasmodium. Phylogenetic analysis divided our sequences into five lineages, pFANTAIL01, pCOLL4, pACCBAD01, pALPSIS01 and pALPSIS02, with two lineages being novel. No Haemoproteus and Leucocytozoon was found in this study. However, Haemoproteus-specific primer used amplified our Plasmodium samples, making the primer non-specific to Haemoproteus only.

Conclusion

This is the first blood parasite detection study on AGS using carcasses and blood clot as sample source in Sarawak. Due to the scarcity of longer sequences from regions with high genetic plasticity, usage of genus-specific primers should be validated with sequencing to ensure correct prevalence interpretation.
Basement membrane-related regulators for prediction of prognoses and responses to diverse therapies in hepatocellular carcinoma
Authors: Ding Ruili , Zhao Chuanbing , Jing Yixin , Chen Rong , Meng Qingtao
Published: April 2023

Background

Hepatocellular carcinoma (HCC) remains a global health threat. Finding a novel biomarker for assessing the prognosis and new therapeutic targets is vital to treating this patient population. Our study aimed to explore the contribution of basement membrane-related regulators (BMR) to prognostic assessment and therapeutic response prediction in HCC.

Material and methods

The RNA sequencing and clinical information of HCC were downloaded from TCGA-LIHC, ICGC-JP, GSE14520, GSE104580, and CCLE datasets. The BMR signature was created by the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and used to separate HCC patients into low- and high-risk groups. We conducted analyses using various R 4.1.3 software packages to compare prognoses and responses to immunotherapy, transcatheter arterial chemoembolization (TACE), and chemotherapeutic drugs between the groups. Additionally, stemness indices, molecular functions, and somatic mutation analyses were further explored in these subgroups.

Results

The BMR signature included 3 basement membrane-related genes (CTSA, P3H1, and ADAM9). We revealed that BMR signature was an independent risk contributor to poor prognosis in HCC, and high-risk group patients presented shorter overall survival. We discovered that patients in the high-risk group might be responsive to immunotherapy, while patients in the low-risk group may be susceptible to TACE therapy. Over 300 agents were screened to identify effective drugs for the two subgroups.

Conclusion

Overall, basement membrane-related regulators represent novel biomarkers in HCC for assessing prognosis, response to immunotherapy, the effectiveness of TACE therapy, and drug susceptibility.
Long- and very long-chain ceramides are predictors of acute kidney injury in patients with acute coronary syndrome: the PEACP study
Authors: Liang Lianjing , Li Dongze , Zeng Rui , Zhang Haihong , Lv Lin , Wei Wei , Wan Zhi
Published: April 2023

Background

Acute kidney injury (AKI) can be caused by multiple factors/events, including acute coronary syndrome (ACS). Ceramides are involved in atherosclerosis progression, cardiovascular events, and renal damage. Almost no studies have been conducted on the relationship between ceramide concentrations and AKI events. Therefore, we evaluated the association between plasma ceramide level at admission and AKI in patients with ACS undergoing percutaneous coronary intervention.

Methods

We enrolled 842 ACS patients from the Prospective Multicenter Study for Early Evaluation of Acute Chest Pain. AKI was defined using the criteria from the 2012 Kidney Disease: Improving Global Outcomes. Eleven C16–C26 ceramides were measured using the high-performance liquid chromatography interfaced to tandem mass spectrometer procedure. Logistic regression models were used to evaluate relationships between ceramides and AKI risk. The area under the receiver operating characteristic curves (AUC) was used to evaluate differences between ceramides.

Results

Overall, 139 (16.5%) patients developed AKI during hospitalisation. Patients who developed AKI had higher levels of Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/21:0), Cer(d18:1/24:1), and Cer(d18:1/24:2) than patients who did not (P < 0.05). In risk-factor adjusted logistic regression models, these ceramides were independently associated with AKI risk (P < 0.05). Cer(d18:1/24:2) had the highest odds ratio of 3.503 (Q4 vs. Q1, 95% confidence interval: 1.743–7.040, P < 0.001). Ceramides had AUCs of 0.581–0.661 (P < 0.001) for AKI. Each ceramide combined with the Mehran risk score (AUC: 0.780) had AUCs of 0.802–0.808, greater than the Mehran risk score alone.

Conclusion

Long-chain and very-long-chain ceramide levels may help determine the high AKI risk beyond traditional assessments.
Enhanced supply of acetyl-CoA by exogenous pantothenate kinase promotes synthesis of poly(3-hydroxybutyrate)
Authors: Kudo Hirotaka , Ono Sho , Abe Kenta , Matsuda Mami , Hasunuma Tomohisa , Nishizawa Tomoyasu , Asayama Munehiko , Nishihara Hirofumi , Chohnan Shigeru
Published: April 2023

Background

Coenzyme A (CoA) is a carrier of acyl groups. This cofactor is synthesized from pantothenic acid in five steps. The phosphorylation of pantothenate is catalyzed by pantothenate kinase (CoaA), which is a key step in the CoA biosynthetic pathway. To determine whether the enhancement of the CoA biosynthetic pathway is effective for producing useful substances, the effect of elevated acetyl-CoA levels resulting from the introduction of the exogenous coaA gene on poly(3-hydroxybutyrate) [P(3HB)] synthesis was determined in Escherichia coli, which express the genes necessary for cyanobacterial polyhydroxyalkanoate synthesis (phaABEC).

Results

E. coli containing the coaA gene in addition to the pha genes accumulated more P(3HB) compared with the transformant containing the pha genes alone. P(3HB) production was enhanced by precursor addition, with P(3HB) content increasing from 18.4% (w/w) to 29.0% in the presence of 0.5 mM pantothenate and 16.3%–28.2% by adding 0.5 mM β-alanine. Strains expressing the exogenous coaA in the presence of precursors contained acetyl-CoA in excess of 1 nmol/mg of dry cell wt, which promoted the reaction toward P(3HB) formation. The amount of acetate exported into the medium was three times lower in the cells carrying exogenous coaA and pha genes than in the cells carrying pha genes alone. This was attributed to significantly enlarging the intracellular pool size of CoA, which is the recipient of acetic acid and is advantageous for microbial production of value-added materials.

Conclusions

Enhancing the CoA biosynthetic pathway with exogenous CoaA was effective at increasing P(3HB) production. Supplementing the medium with pantothenate facilitated the accumulation of P(3HB). β-Alanine was able to replace the efficacy of adding pantothenate.
Profile of health care workers in a context of instability: a cross-sectional study of four rural health zones in eastern DR Congo (lessons learned)
Authors: Mushagalusa Charles Ruhangaza , Mayeri Daniel Garhalangwanamuntu , Kasongo Bertin , Cikomola Aimé , Makali Sammuel Lwamushi , Ngaboyeka Amani , Chishagala Lili , Mwembo Albert , Mukalay Abdon , Bisimwa Ghislain Balaluka
Published: April 2023

Background

The crisis in human resources for health is observed worldwide, particularly in sub-Saharan Africa. Many studies have demonstrated the importance of human resources for health as a major pillar for the proper functioning of the health system, especially in fragile and conflict-affected contexts such as DR Congo. However, the aspects relating to human resources profile in relation to the level of performance of the health districts in a particular context of conflicts and multiform crises have not yet been described.

Objective

This study aims to describe the profile of staff working in rural health districts in a context of crisis and conflicts.

Methods

A cross-sectional study was carried out from May 15, 2017 to May 30, 2019 on 1090 health care workers (HCW) exhaustively chosen from four health districts in Eastern Democratic Republic of Congo (Idjwi, Katana, Mulungu and Walungu). Data were collected using a survey questionnaire. The Chi2 test was used for comparison of proportions and the Kruskal–Wallis test for medians. As measures of association, we calculated the odds ratios (OR) along with their 95% confidence interval. The α-error cut-off was set at 5%.

Results

In all the health districts the number of medical doctors was very insufficient with an average of 0.35 medical doctors per 10,000 inhabitants. However, the number of nurses was sufficient, with an average of 3 nurses per 5000 inhabitants; the nursing / medical staff (47%) were less represented than the administrative staff (53%). The median (Min–Max) age of all HCW was 46 (20–84) years and 32% of them were female. This was the same for the registration of staff in the civil service (obtaining a registration number). The mechanism of remuneration and payment of benefits, although a national responsibility, also suffered more in unstable districts. Twenty-one percent of the HCW had a monthly income of 151USD and above in the stable district; 9.2% in the intermediate and 0.9% in the unstable districts. Ninety-six percent of HCW do not receive Government’ salary and 64% of them do not receive the Government bonus.

Conclusion

The context of instability compromises the performance of the health system by depriving it of competent personnel. This is the consequence of the weakening of the mechanisms for implementing the practices and policies related to its management. DR Congo authorities should develop incentive mechanisms to motivate young and trained HCW to work in unstable and intermediate health districts by improving their living and working conditions.
Quantitative assessments of finger individuation with an instrumented glove
Authors: Conway Brian J. , Taquet Léon , Boerger Timothy F. , Young Sarah C. , Krucoff Kate B. , Schmit Brian D. , Krucoff Max O.
Published: April 2023

Background

In clinical and research settings, hand dexterity is often assessed as finger individuation, or the ability to move one finger at a time. Despite its clinical importance, there is currently no standardized, sufficiently sensitive, or fully objective platform for these evaluations.

Methods

Here we developed two novel individuation scores and tested them against a previously developed score using a commercially available instrumented glove and data collected from 20 healthy adults. Participants performed individuation for each finger of each hand as well as whole hand open-close at two study visits separated by several weeks. Using the three individuation scores, intra-class correlation coefficients (ICC) and minimal detectable changes (MDC) were calculated. Individuation scores were further correlated with subjective assessments to assess validity.

Results

We found that each score emphasized different aspects of individuation performance while generating scores on the same scale (0 [poor] to 1 [ideal]). These scores were repeatable, but the quality of the metrics varied by both equation and finger of interest. For example, index finger intra-class correlation coefficients (ICC’s) were 0.90 (< 0.0001), 0.77 (< 0.001), and 0.83 (p < 0.0001), while pinky finger ICC’s were 0.96 (p < 0.0001), 0.88 (p < 0.0001), and 0.81 (p < 0.001) for each score. Similarly, MDCs also varied by both finger and equation. In particular, thumb MDCs were 0.068, 0.14, and 0.045, while index MDCs were 0.041, 0.066, and 0.078. Furthermore, objective measurements correlated with subjective assessments of finger individuation quality for all three equations (ρ = − 0.45, p < 0.0001; ρ = − 0.53, p < 0.0001; ρ = − 0.40, p < 0.0001).

Conclusions

Here we provide a set of normative values for three separate finger individuation scores in healthy adults with a commercially available instrumented glove. Each score emphasizes a different aspect of finger individuation performance and may be more uniquely applicable to certain clinical scenarios. We hope for this platform to be used within and across centers wishing to share objective data in the physiological study of hand dexterity. In sum, this work represents the first healthy participant data set for this platform and may inform future translational applications into motor physiology and rehabilitation labs, orthopedic hand and neurosurgery clinics, and even operating rooms.
Prenatal PM2.5 exposure impairs spatial learning and memory in male mice offspring: from transcriptional regulation to neuronal morphogenesis
Authors: Hou Yanwen , Yan Wei , Guo Lin , Li Guangke , Sang Nan
Published: April 2023

Background

As one of the environmental risk factors for human health, atmospheric fine particulate matter (PM2.5) contributes to cognitive deterioration in addition to respiratory and cardiovascular injuries. Recently, increasing evidence implicates that PM2.5 inhalation can affect neurological functions in offspring, but the sex-specific outcomes and the underlying biological processes are largely unknown.

Objectives

To observe the influence of prenatal PM2.5 exposure on cognitive performance in offspring, to elucidate the neuronal morphological alterations and possible transcriptional regulation based on mRNA-sequencing (mRNA-Seq) data after birth, and to determine the key components of PM2.5 contributing to the adverse effects.

Methods

Pregnant C57BL/6J mice were exposed to sterile saline or PM2.5 suspension. Morris water maze test was used to assess the cognitive function in weanling offspring. Microscopic observation was applied to detect neuronal morphogenesis in vivo and in vitro. The cortex tissues from male offspring were collected on postnatal days (PNDs) 1, 7, and 21 for mRNA-Seq analysis. The organic and inorganic components of PM2.5 were separated to assess their contributions using primary cultured neurons.

Results

Prenatal PM2.5 exposure impaired spatial learning and memory in weanling male mice, but not female mice. The sex-specific outcomes were associated with mRNA expression profiles of the cortex during postnatal critical windows, and the annotations in Gene Ontology (GO) of differentially expressed genes (DEGs) revealed that the exposure persistently disrupted the expression of genes involved in neuronal features in male offspring. Consistently, axonal growth impairment and dendritic complexity reduction were observed. Importantly, Homeobox A5 (Hoxa5), a critical transcription factor regulating all of the neuronal morphogenesis-associated hub genes on PNDs 1, 7, and 21, significantly decreased in the cortex of male offspring following PM2.5 exposure. In addition, both inorganic and organic components were harmful to axonal and dendritic growth, with organic components exhibiting stronger inhibition than inorganic ones.

Conclusion

Prenatal PM2.5 exposure affected spatial learning and memory in male mice by disrupting Hoxa5-mediated neuronal morphogenesis, and the organic components, including polycyclic aromatic hydrocarbons (PAHs), posed more adverse effects than the inorganic components.
Balancing the risks and benefits of antibiotic use in a globalized world: the ethics of antimicrobial resistance
Authors: Adebisi Yusuff Adebayo
Published: April 2023

Antimicrobial resistance (AMR) is a “silent pandemic” that threatens the efficacy of antibiotics and other antimicrobials. It is imperative to take into account the ethical implications of how these resources are used and distributed as the world deals with this silent pandemic. This commentary discusses the ethical considerations surrounding the use and distribution of antibiotics in the age of resistance, including issues of equity and access, responsibility for antimicrobial stewardship, the environmental impact of antibiotic use, and the development and promotion of these drugs. The ethical implications of unequal access to antibiotics and the role of social determinants of health in shaping this access are considered, as well as the globalization of AMR and the need for multiple stakeholders to be involved in addressing this issue. The opportunities of antimicrobial stewardship programmes for optimising antibiotic use and reducing the emergence and spread of resistant bacteria, as well as the ethical implications of implementing such programmes, are examined. The potential environmental outcomes of antibiotic use and the ethical implications of these impacts are also discussed, as well as the role of the pharmaceutical industry in the development and promotion of these drugs, the potential conflicts of interest that may arise and the ethical dimension of resource transfer from Global North to Global South. This paper emphasises the significance of a holistic strategy to AMR that considers these ethical components, as well as the importance of preserving antibiotic efficacy for future generations.
Machine learning in TCM with natural products and molecules: current status and future perspectives
Authors: Ma Suya , Liu Jinlei , Li Wenhua , Liu Yongmei , Hui Xiaoshan , Qu Peirong , Jiang Zhilin , Li Jun , Wang Jie
Published: April 2023

Traditional Chinese medicine (TCM) has been practiced for thousands of years with clinical efficacy. Natural products and their effective agents such as artemisinin and paclitaxel have saved millions of lives worldwide. Artificial intelligence is being increasingly deployed in TCM. By summarizing the principles and processes of deep learning and traditional machine learning algorithms, analyzing the application of machine learning in TCM, reviewing the results of previous studies, this study proposed a promising future perspective based on the combination of machine learning, TCM theory, chemical compositions of natural products, and computational simulations based on molecules and chemical compositions. In the first place, machine learning will be utilized in the effective chemical components of natural products to target the pathological molecules of the disease which could achieve the purpose of screening the natural products on the basis of the pathological mechanisms they target. In this approach, computational simulations will be used for processing the data for effective chemical components, generating datasets for analyzing features. In the next step, machine learning will be used to analyze the datasets on the basis of TCM theories such as the superposition of syndrome elements. Finally, interdisciplinary natural product-syndrome research will be established by unifying the results of the two steps outlined above, potentially realizing an intelligent artificial intelligence diagnosis and treatment model based on the effective chemical components of natural products under the guidance of TCM theory. This perspective outlines an innovative application of machine learning in the clinical practice of TCM based on the investigation of chemical molecules under the guidance of TCM theory.
Toward patient-centered treatment goals for duchenne muscular dystrophy: insights from the “Your Voice” study
Authors: Schwartz Carolyn E. , Jackson Skyler , Valentine James , Miller Natalie , Lowes Linda , Edwards Danielle , McSherry Christine , Savva Dimitrios , Lowe Alex , McSherry Jordan , Engel Patti
Published: April 2023

Background

Patient-centered research has emerged as critically important for understanding the impact of treatments on key stakeholders. The subjective experience of quality of life (QOL) is increasingly recognized as fundamental to delineating treatment goals. The present study utilized content analysis of qualitative data and quantitative analysis to highlight important domains of disease burden and underlying reasons for their importance, and to characterize goals for new treatments for Duchenne Muscular Dystrophy (DMD).

Results

The study sample reflected the perspectives of DMD patients and caregivers representing ambulatory, transitional, and non-ambulatory stages of disability progression (n = 20 per category). Open-ended interviews were content-analyzed and non-parametric statistical tests were used to compare ambulation groups. As patients progressed in disability, the noted DMD burdens reflected some differences in functional areas. While daily functioning and sports/recreation remained the most important priority areas across ambulation groups, “health” became less prominent as the disability progressed from ambulatory to transitional to non-ambulatory phases of disability; whereas relationships became more prominent as one progressed to the non-ambulatory phase from the ambulatory or transitional phases (Kruskall Wallis H = 12.24 and 5.28, p = 0.002 and 0.02, respectively). When asked why their burdens were important to them and how it impacted their or their child’s life, self-esteem/confidence was most important for ambulatory patients, and became less prominent for patients in the transitional and non-ambulatory phases of disability (Kruskall Wallis H = 9.46, p = 0.009). In contrast, independence was less important for ambulatory patients, and became increasing prominent for patients in the transitional and non-ambulatory phases of disability (Kruskall Wallis H = 7.35, p = 0.025). Emotional functioning was most prominent for all ambulation groups on their best and worst days. Goals for new DMD treatments focused on functional goals, general QOL goals, and concerns about safety, ease of use, and effectiveness.

Conclusion

This study provides useful information about treatment goals for DMD from the perspective of patients and their caregivers. It highlights some consistent values across the disability trajectory, as well as introducing an evolution of priorities as the person with DMD becomes more disabled. Results provide a roadmap for patient-centered DMD drug development.
Association between one-session bilateral whole-lung lavage and periprocedural complications in patients with pulmonary alveolar proteinosis: a retrospective cohort study
Authors: Xu Xiaohan , Qiu Huanrong , Chen Fei , Zhang Yuelun , Tian Xinlun , Liu Yongjian , Wang Ping , Zhu Bo , Huang Yuguang
Published: April 2023

Background

Whole lung lavage (WLL) has been recognized as the most effective therapy of severe pulmonary alveolar proteinosis (PAP). Most centers perform the lavage of each lung in two sessions under general anesthesia at an interval of several days to weeks. Compared with two-session WLL, one-session bilateral sequential WLL only requires general anesthesia once. However, the safety of one-session WLL in PAP patients has not been assessed by large cohort studies. In this study, we aimed to investigate the association between the mode of WLL procedure (one-session or two-session) and the risk of periprocedural complications in PAP patients.

Methods

In this single-center retrospective cohort study, we included adult patients who were diagnosed as PAP and had undergone WLL procedures under general anesthesia from 2000 to 2022. Patients requiring extra-corporeal oxygenation during WLL were excluded. Since some patients received multiple WLL procedures, we considered each procedure in one-session or two-session group as a unique unit in our analysis. The primary outcome was the occurrence of any complications during hospitalization, including termination of WLL procedure due to fluid leakage or refractory hypoxemia, bronchospasm, delayed endotracheal extubation, cardiovascular event, pneumothorax, and fever.

Results

We included a total of 175 WLL procedures (118 patients), with 48 in the two-session group and 127 in the one-session group. Periprocedural complications occurred in 17 (35.4%) and 39 (30.7%) procedures in the two-session and the one-session groups, respectively. The risk of periprocedural complications did not differ significantly between groups, after adjusting the unbalanced confounders in a multivariable model (odds ratio 0.95, 95% confidence interval 0.34 to 2.69, P 0.929) or by inverse probability of treatment weighting (odds ratio 0.70, 95% confidence interval 0.30 to 1.54, P 0.379). Compared with the two-session WLL group, the one-session WLL group had a shorter postprocedural length of hospitalization and comparable decrease in alveolar-arterial oxygen tension gradient from baseline.

Conclusions

One-session bilateral WLL was not associated with an increased risk of periprocedural complications compared with two-session WLL in PAP patients. Experienced physicians may consider performing one-session WLL in view of the comparable safety and efficacy and potential advantages of saving time.
The global prevalence of ADHD in children and adolescents: a systematic review and meta-analysis
Authors: Salari Nader , Ghasemi Hooman , Abdoli Nasrin , Rahmani Adibeh , Shiri Mohammad Hossain , Hashemian Amir Hossein , Akbari Hakimeh , Mohammadi Masoud
Published: April 2023

Background

Attention-Deficit / Hyperactivity Disorder is a developmental neurological disorder that has three basic characteristics: Attention Deficit, Hyperactivity, and impulsivity. This study aimed to investigate the prevalence of ADHD in children and adolescents.

Methods

This investigation was carried out using the meta-analysis method under PRISMA guidelines. Until October 2020, the articles were gathered by scanning PubMed, Scopus, WOS, and Science Direct databases. The second version of Comprehensive Meta-Analysis software was used to run analyses after extracting data from chosen papers. At a significance level of 0.05, the I2 test was used to analyze study heterogeneity, and the Egger test was used to assess publication bias.

Results

This analysis includes 61 cross-sectional research, with 53 research used to determine the prevalence of ADHD in children, 7.6% of 96,907 children aged 3 to 12 years had ADHD (95% confidence interval: 6.1–9.4%), and 5.6% of teenagers aged 12 to 18 years have ADHD (95% confidence interval: 4.8-7%). The prevalence of ADHD in children and adolescents according to the DSM-V criterion is also higher than previous diagnostic criteria, according to studies.

Conclusion

The findings of this study based on meta-analysis show the high prevalence of attention deficit hyperactivity disorder (ADHD). The findings of this study demonstrate the importance of management and policy in the treatment and control of ADHD in children and adolescents.
Major adverse cardiovascular events are associated with necroptosis during severe COVID-19
Authors: Wiscovitch-Russo Rosana , Ibáñez-Prada Elsa D. , Serrano-Mayorga Cristian C. , Sievers Benjamin L. , Engelbride Maeve A. , Padmanabhan Surya , Tan Gene S. , Vashee Sanjay , Bustos Ingrid G. , Pachecho Carlos , Mendez Lina , Dube Peter H. , Singh Harinder , Reyes Luis Felipe , Gonzalez-Juarbe Norberto
Published: April 2023

Background

The mechanisms used by SARS-CoV-2 to induce major adverse cardiac events (MACE) are unknown. Thus, we aimed to determine if SARS-CoV-2 can induce necrotic cell death to promote MACE in patients with severe COVID-19.

Methods

This observational prospective cohort study includes experiments with hamsters and human samples from patients with severe COVID-19. Cytokines and serum biomarkers were analysed in human serum. Cardiac transcriptome analyses were performed in hamsters' hearts.

Results

From a cohort of 70 patients, MACE was documented in 26% (18/70). Those who developed MACE had higher Log copies/mL of SARS-CoV-2, troponin-I, and pro-BNP in serum. Also, the elevation of IP-10 and a major decrease in levels of IL-17ɑ, IL-6, and IL-1rɑ were observed. No differences were found in the ability of serum antibodies to neutralise viral spike proteins in pseudoviruses from variants of concern. In hamster models, we found a stark increase in viral titters in the hearts 4 days post-infection. The cardiac transcriptome evaluation resulted in the differential expression of ~ 9% of the total transcripts. Analysis of transcriptional changes in the effectors of necroptosis (mixed lineage kinase domain-like, MLKL) and pyroptosis (gasdermin D) showed necroptosis, but not pyroptosis, to be elevated. An active form of MLKL (phosphorylated MLKL, pMLKL) was elevated in hamster hearts and, most importantly, in the serum of MACE patients.

Conclusion

SARS-CoV-2 identification in the systemic circulation is associated with MACE and necroptosis activity. The increased pMLKL and Troponin-I indicated the occurrence of necroptosis in the heart and suggested necroptosis effectors could serve as biomarkers and/or therapeutic targets.

Trial registration Not applicable.
satmut_utils: a simulation and variant calling package for multiplexed assays of variant effect
Authors: Hoskins Ian , Sun Song , Cote Atina , Roth Frederick P. , Cenik Can
Published: April 2023

The impact of millions of individual genetic variants on molecular phenotypes in coding sequences remains unknown. Multiplexed assays of variant effect (MAVEs) are scalable methods to annotate relevant variants, but existing software lacks standardization, requires cumbersome configuration, and does not scale to large targets. We present satmut_utils as a flexible solution for simulation and variant quantification. We then benchmark MAVE software using simulated and real MAVE data. We finally determine mRNA abundance for thousands of cystathionine beta-synthase variants using two experimental methods. The satmut_utils package enables high-performance analysis of MAVEs and reveals the capability of variants to alter mRNA abundance.
Delayed hypersensitivity reaction to cosmetic filler following two COVID-19 vaccinations and infection
Authors: Azzouz Safaa , Lanoue Derek , Champagne Katéri , Genest Genevieve
Published: April 2023

Background

With ongoing COVID-19 vaccination schedules and the popularity of cosmetic fillers, it is important to examine and record associated adverse reactions to a more general audience of health care professionals. Case reports exist in subspecialty journals outlining reactions after SARS-CoV-2 infection and vaccination. This is one of the first cases published in Canada, and it highlights priorities and challenges faced by physicians in assessing and managing patients presenting with adverse reactions post vaccination.

Case Presentation

We present a case of a 43 -year-old women with delayed type 4 hypersensitivity reaction to hyaluronic acid cosmetic filler triggered by COVID-19 mRNA vaccination. We outline the clinical presentation, diagnosis, complications, and treatment of a late inflammatory reaction to hyaluronic acid filler and highlight the treatment priorities for clinicians faced with similar presentations.

Conclusion

The differential diagnosis of delayed onset nodules formation post filler injection is broad and includes redistribution of fillers, inflammatory reaction to biofilm, and delayed hypersensitivity reaction. As result, in order to make the right diagnosis, administer the appropriate treatment and achieve great cosmetic results, we highly recommend seeking expert opinion from dermatologist, plastic surgeon and allergist immunologist in a timely manner.
Effects of multiple-dose intranasal oxytocin administration on social responsiveness in children with autism: a randomized, placebo-controlled trial
Authors: Daniels Nicky , Moerkerke Matthijs , Steyaert Jean , Bamps Annelies , Debbaut Edward , Prinsen Jellina , Tang Tiffany , Van der Donck Stephanie , Boets Bart , Alaerts Kaat
Published: April 2023

Background

Intranasal administration of oxytocin is increasingly explored as a new approach to facilitate social development and reduce disability associated with a diagnosis of autism spectrum disorder (ASD). The efficacy of multiple-dose oxytocin administration in children with ASD is, however, not well established.

Methods

A double-blind, randomized, placebo-controlled trial with parallel design explored the effects of a 4-week intranasal oxytocin administration (12 IU, twice daily) on parent-rated social responsiveness (Social Responsiveness Scale: SRS-2) in pre-pubertal school-aged children (aged 8–12 years, 61 boys, 16 girls). Secondary outcomes included a questionnaire-based assessment of repetitive behaviors, anxiety, and attachment. Effects of oxytocin were assessed immediately after the administration period and at a follow-up, 4 weeks after the last administration. The double-blind phase was followed by a 4-week single-blind phase during which all participants received intranasal oxytocin.

Results

In the double-blind phase, both the oxytocin and placebo group displayed significant pre-to-post-improvements in social responsiveness and secondary questionnaires, but improvements were not specific to the intranasal oxytocin. Notably, in the single-blind phase, participants who were first allocated to intranasal placebo and later changed to intranasal oxytocin displayed a significant improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. Participants receiving oxytocin in the first phase also showed a significant further improvement upon receiving a second course of oxytocin, but only at the 4-week follow-up. Further, exploratory moderator analyses indicated that children who received psychosocial trainings (3 or more sessions per month) along with oxytocin administration displayed a more pronounced improvement in social responsiveness.

Limitations

Future studies using larger cohorts and more explicitly controlled concurrent psychosocial trainings are warranted to further explore the preliminary moderator effects, also including understudied populations within the autism spectrum, such as children with co-occurring intellectual disabilities.

Conclusions

Four weeks of oxytocin administration did not induce treatment-specific improvements in social responsiveness in school-aged children with ASD. Future studies are warranted to further explore the clinical efficacy of oxytocin administration paired with targeted psychosocial trainings that stimulate socio-communicative behaviors.

Trial registration The trial was registered with the European Clinical Trial Registry (EudraCT 2018-000769-35) on June 7th, 2018 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000769-35/BE).
Fumarate hydratase-deficient renal cell carcinoma: a case report and review of the literature
Authors: Lv Yanting , Song Lide , Hu Mengjun
Published: April 2023

Background

Fumarate hydratase-deficient renal cell carcinoma is a rare pathological subtype that was defined by the World Health Organization (WHO 5th edition) in 2022. At present, only a few hundreds of cases have been reported worldwide, mainly in Europe and the United States. A case of a Chinese patient is reported here, along with a literature review.

Case report

A 60-year-old Asian male who complained of hematuria for 20 days was admitted to the hospital. Contrast enhanced Computer Tomography showed that the volume of the right kidney was increased, with a patchy low-density shadow with infiltrative growth inside that had a significantly lower signal intensity than the renal cortex; thus, the possibility of collecting duct carcinoma or lymphoma, was considered. Enlarged perirenal and retroperitoneal lymph nodes were also seen, along with bilateral renal cysts. Eight years prior, ultrasonography had shown a complex renal cyst in the right kidney, and no treatment was administered at that time. Laparoscopic radical nephrectomy of the right kidney was performed this time, and the postoperative specimens were submitted for pathological examination. Because immunohistochemistry showed the loss of fumarate hydratase protein expression and the possibility of fumarate hydratase-deficient renal cell carcinoma was considered, corresponding molecular pathological tests were performed, and the results showed an FHp.R233H (arginine > histidine) germline mutation (inactivation mutation). The postoperative pathological diagnosis was fumarate hydratase-deficient renal cell carcinoma in the right kidney, T3aN1M0. The patient was treated with sunitinib, and bone and liver metastases developed half a year later. The treatment was then changed to axitinib and toripalimab. At present, the patient is in stable condition, and there has been no progression of the metastases.

Conclusion

Fumarate hydratase-deficient renal cell carcinoma is a very rare renal tumor that is defined on a molecular basis. It is highly malignant and metastasizes early. Therefore, fully understanding the disease, enabling detection and diagnosis and administering treatment are particularly important.
Outcomes of patient education in adult oncologic patients receiving oral anticancer agents: a systematic review protocol
Authors: Fonda Federico , Cedrone Sonja , Sartor Ivana , Cadorin Lucia
Published: April 2023

Background

A large variety of oral anticancer agents have become available and while at first glance these therapies appear to provide only benefits, patients have expressed their need for educational interventions and raised safety issues. Although both patients and providers have recognized patient education’s importance, and an interplay with safety has been acknowledged, no systematic reviews of the literature that summarize all of the current evidence related to patient education’s outcomes for patients who receive oral anticancer agents have been performed to date. Accordingly, this systematic review will attempt to fill the gap in the literature as well as to map (1) contents, (2) methodologies, (3) settings, (4) timing/duration, and (5) healthcare professionals involved.

Methods

This protocol is being reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic review will be performed. Studies that targeted eligible adult patients (≥ 18 years old) in hospital, outpatient, and home settings, and reported patient education’s outcomes for those taking oral anticancer agents will be included. Searches will be conducted in PubMed/MEDLINE, CINAHL, Embase, and Scopus, and gray literature will be also sought. Two researchers will screen the search results independently and blindly in two phases: (1) title/abstract screening and (2) full-text screening using the Rayyan AI platform. An electronic data extraction form will be implemented and piloted, and then, two trained data extractors will extract the data cooperatively. Thereafter, a quality appraisal will be conducted using the Critical Appraisal Tools from The Joanna Briggs Institute. The results will be analyzed, grouped, clustered into categories, and discussed until a consensus is reached. Emerging evidence will be synthesized narratively and reported in accordance with the synthesis without meta-analysis guidelines.

Discussion

The systematic review’s results will be relevant to (1) policymakers and management at an institutional level, and (2) for clinical practice, in an evidence-based paradigm, potentially leading to a quality improvement with respect to safety and patient satisfaction.

Systematic review registration

PROSPERO CRD42022341797
Estimated 24-Hour urinary sodium and potassium excretion in adults in the Northwest Region of Morocco, 2017
Authors: Idrissi Mohamed , Saeid Naima , Mounach Samir , Berri Hicham El , Al Jawaldah Ayoub , Rahhaoui Fadoua , Mouzouni Fatima-Zahra , Rami Anass , Benjeddou Kaoutar , Lahmam Houria , Benkirane Hasnae , Elmzibri Mohammed , Kari Khalid El , Bagri Abdallah , Aguenaou Hassan , Belakhel Latifa
Published: April 2023

Background

Excessive sodium (Na) and insufficient potassium (K) intake contribute to a high risk of cardiovascular events. Morocco lacks data on actual Na and K intake in adults. We estimated mean Na and K intake in a Moroccan population of adults residing in the Northwest region using 24-h urinary excretion and examined their association with blood pressure (BP).

Methods

A total of 371 adults from this region, who were recruited for the STEPs Survey Morocco 2017, completed demographic, anthropometric as well as BP data and provided a valid 24-h urine collection according to the standard World Health Organization (WHO) protocol. Multiple Linear Regression analysis was used to examine the association between 24-h urinary sodium (24-hUNa) and 24-h potassium excretion (24-hUK) with BP.

Results

Mean Na excretion was 2794 mg/day and mean K excretion was 1898 mg/day. Overall, only 114 (30.7%) adults met the WHO recommendation for Na intake (< 2000 mg/d) and 31 (8.4%) met the adequate level for K intake (⩾3510 mg/d). There was no association between 24-hUNa and 24-hUK with BP (P > 0.05 for all).

Conclusion

Na intake was higher and K intake was lower than WHO recommendations in the study population. There was no association between estimated Na and K intake levels with BP in this population.
Interactions between rootstocks and compost influence the active rhizosphere bacterial communities in citrus
Authors: Castellano-Hinojosa Antonio , Albrecht Ute , Strauss Sarah L.
Published: April 2023

Background

While the rootstock genotype (belowground part of a plant) can impact rhizosphere microbial communities, few studies have examined the relationships between rootstock genotype-based recruitment of active rhizosphere bacterial communities and the availability of root nutrients for plant uptake. Rootstocks are developed to provide resistance to disease or tolerance of abiotic stresses, and compost application is a common practice to also control biotic and abiotic stresses in crops. In this field study, we examined: (i) the effect of four citrus rootstocks and/or compost application on the abundance, diversity, composition, and predicted functionality of active rhizosphere bacterial communities, and (ii) the relationships between active rhizosphere bacterial communities and root nutrient concentrations, with identification of bacterial taxa significantly correlated with changes in root nutrients in the rhizosphere.

Results

The rootstock genotype determined differences in the diversity of active rhizosphere bacterial communities and also impacted how compost altered the abundance, diversity, composition, and predicted functions of these active communities. Variations in the active bacterial rhizobiome were strongly linked to root nutrient cycling, and these interactions were root-nutrient- and rootstock-specific. Direct positive relationships between enriched taxa in treated soils and specific root nutrients were detected, and potentially important taxa for root nutrient uptake were identified. Significant differences in specific predicted functions were related to soil nutrient cycling (carbon, nitrogen, and tryptophan metabolisms) in the active bacterial rhizobiome among rootstocks, particularly in soils treated with compost.

Conclusions

This study illustrates that interactions between citrus rootstocks and compost can influence active rhizosphere bacterial communities, which impact root nutrient concentrations. In particular, the response of the rhizobiome bacterial abundance, diversity, and community composition to compost was determined by the rootstock. Specific bacterial taxa therefore appear to be driving changes in root nutrient concentrations in the active rhizobiome of different citrus rootstocks. Several potential functions of active bacterial rhizobiomes recruited by different citrus rootstocks did not appear to be redundant but rather rootstock-specific. Together, these findings have important agronomic implications as they indicate the potential for agricultural production systems to maximize benefits from rhizobiomes through the choice of selected rootstocks and the application of compost.
The identification, approaches to cleaning and removal of a lead-rich salt crust from the surface of an 18th century oil painting
Authors: Shah Nikita , Froment Emilie , Seymour Kate
Published: April 2023

A thin, grey surface layer was noticed after removing the varnish of an eighteenth century Dutch oil painting, by an unknown artist titled Vision of Saint Lutgard of Tongeren. This layer masked the paint layer almost entirely, casting a greyish veil that greatly influenced the painting’s appearance, colour, and saturation. Using scanning electron microscopy coupled with elemental analysis (SEM–EDX), this layer was identified as a lead-rich salt crust. The crust was a distinct layer on top of the paint layer, closely following the topography of the layer underneath but not embedded in it. The article discusses the possible theories behind the formation of this lead-rich salt crust by characterizing the painting’s material, past treatments, and environmental history. Furthermore, the article reports the decision-making process behind the removal of the crust, focusing specifically on the ethical and technical challenges of the cleaning treatment. Tests with different cleaning agents targeting separate components of the crust to remove it and different application techniques are described. The chelating agent Ethylenediaminetetraacetic acid (EDTA) was found to be the most effective in the removal of the crust and was chosen for its removal. The pH of the EDTA cleaning solution and its application had to be modified according to the colour of the paint the crust lay upon. Visual observations and analytical assessments using optical microscopy and SEM after cleaning indicate a successful reduction of the crust resulting in a significant improvement in the painting’s appearance.
Preoperative diagnosis of knee cartilage, meniscal, and ligament injuries by magnetic resonance imaging
Authors: Nakagawa Yasuaki , Mukai Shogo , Sakai Sayako , Nakamura Ryota , Takahashi Motoi , Nakagawa Shinnosuke
Published: April 2023

Purpose

The purpose of the study was to report on the current accuracy measures specific to 1.5‐Tesla MRI of the knee in the patient population prone to injuries of the anterior cruciate ligament (ACL), the menisci, and the articular cartilage.

Methods

We accrued patients between January 2018 through August 2021 who underwent a preoperative MRI and were diagnosed with an articular cartilage injury either due to unevenness of articular cartilage in T2‐weighted sequences or due to the irregularity of subchondral bone in T1‐weighted sequences. All patients were treated arthroscopically. Sensitivity, specificity, and accuracy were calculated for the detection of ACL, meniscus, and cartilage injuries. A P‐value of < 0.05 represented statistical significance.

Results

One‐hundred and forty‐seven cases which included 150 knee joints were enrolled in this study. The mean age at the time of surgery was 42.9 years‐old. The sensitivity in the diagnosis of ACL injuries was significantly greater than that in the diagnosis of cartilage injuries (P = 0.0083). The ratios of the equality of operative indication in 6 recipient sites were found to be between 90.0% and 96.0%. The diagnostic critical point was within a 1 cm in diameter.

Conclusion

The diagnostic sensitivity in cartilage injuries was significantly lower than ones of ACL and meniscal injuries. The ratios of the equality of operative indication was determined to be between 90.0% and 96.0%, if we consider the unevenness of articular cartilage or the irregularity of subchondral bone.

Level of evidence

Level III, Prospective diagnostic cohort study.