bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial-targeting Mn3O4/UIO-TPP nanozyme scavenge ROS to restore mitochondrial function for osteoarthritis therapy
Authors: Zhang Shengqing , Cai Jinhong , Yao Yi , Huang Lanli , Zheng Li , Zhao Jinmin
Published: September 2023

Excessive reactive oxygen species (ROS)-induced mitochondrial damage has impact on osteoarthritis (OA). Nanozyme mimics as natural enzyme alternatives to scavenge excessive ROS has offered a promising strategy for OA therapy. Herein, we reported a novel mitochondrial-targeting Mn3O4/UIO-TPP nanozyme using metal-organic frameworks with loaded Mn3O4 as the enzyme-like active core combining mitochondria-targeting triphenylphosphine (TPP) groups to serve as ROS scavengers for therapy of OA. With sequential catalysis of superoxide dismutase-like, catalase (CAT)-like, and hydroxyl radical (·OH) scavenging potentials, the nanozyme can target mitochondria by crossing subcellular barriers to effectively eliminate ROS to restore mitochondrial function and inhibit inflammation and chondrocyte apoptosis. It also has favorable biocompatibility and biosafety. Based on anterior cruciate ligament transection-induced OA joint models, this mitochondrial-targeting nanozyme effectively mitigated the inflammatory response with the Pelletier score reduction of 49.9% after 8-week therapy. This study offers a prospective approach to the design of nanomedicines for ROS-related diseases.
Imaging of Fetal Head and Neck Masses: A Systematic and Anatomic Approach
Authors: Vaughn Jennifer A. , Goncalves Luis F. , Cornejo Patricia
Published: September 2023

Congenital neck masses are rare lesions typically encountered during second-trimester anatomy ultrasound. Accurate diagnosis is crucial to appropriate ante- and perinatal management though imaging characterization remains a challenge. Ultrasound and MRI play complementary roles in the diagnosis of prenatal head and neck masses now facilitated by the increased availability of fetal MRI, technologic advancements in both imaging modalities and large tertiary referral centers with specialized care teams. As in both adult and pediatric head and neck imaging, a solid understanding of the neck anatomic spaces is a requisite to formulate a focused differential diagnosis. In this review, the more common fetal neck masses in four anatomic locations are presented. Unlike the wide spectrum of potential pathologies encountered in children, fetal neck masses can be categorized into three major groups: tumors, vascular malformations, and congenital lesions. Using an anatomic and systematic approach, the radiologist can narrow the differential diagnosis into a single or a limited list of possibilities. This article provides a focused review of the more common fetal head and neck pathologies, emphasizing their location and imaging characteristics. Based on these features, a reasonable differential diagnosis can be formulated and applied to prenatal counseling, delivery management, and postnatal treatment.
Higher ultra-processed food intake was positively associated with odds of NAFLD in both US adolescents and adults: A national survey
Authors: Zhao Longgang , Zhang Xinyuan , Martinez Steele Euridice , Lo Chun-Han , Zhang Fang Fang , Zhang Xuehong
Published: September 2023

Background:

The effect of ultra-processed foods (UPF) on NAFLD remains unclear. Related evidence for adult NAFLD is limited and no study has yet evaluated UPF’s impact on NAFLD in adolescence.

Methods:

We used data from the National Health and Nutrition Examination Survey (2017-2018) with 806 adolescents and 2734 adults. UPF intake was estimated using dietary data from two 24-hour dietary recalls. NAFLD was defined by transient elastography. Logistic regression was used to estimate the multivariable OR and 95% CI for associations between UPF and NAFLD with survey weight adjustments.

Results:

The mean UPF intake was 812 g/d in adolescents and 823 g/d in adults. A total of 12.4% of the adolescents and 35.6% of the adults had NAFLD. Higher UPF intake was associated with higher odds of NAFLD in both adolescents (OR Quintile 5 vs. Quartile 1 = 2.34, 95% CI, 1.01, 5.41; p

trend
= 0.15) and adults (OR Quintile 5 vs. Quintile 1 = 1.72, 95% CI, 1.01, 2.93; p

trend
= 0.002). In adults, ~68% and 71% of the association between UPF intake and NAFLD was mediated by body mass index and waist circumference (all p-values < 0.001), respectively. The results were similar for adolescents but not statistically significant. A higher UPF intake was associated with lower levels of serum albumin and higher levels of C-reactive protein in adults.

Conclusions:

Higher UPF intake was linked to higher NAFLD odds in both adolescents and adults, mainly because of elevated body fatness. If confirmed, reducing UPF intake may help prevent NAFLD in both adolescents and adults.
Anisometropia and Amblyopia Outcomes in Early Versus Late Resolution of Congenital Nasolacrimal Duct Obstruction in Older Infants
Authors: Sims Deion T. , Gillette Thomas B. , Lam Jocelyn G. , Liu Darren , Lee Calvin , Ding Leona , Tarczy-Hornoch Kristina , Cabrera Michelle T.
Published: September 2023

Purpose:

Congenital nasolacrimal duct obstruction is a known risk factor for amblyopia and anisometropia. The purpose of this study was to investigate whether the rate of anisometropia and amblyopia development differed based on the age at CNLDO resolution in older infants.

Methods:

This retrospective chart review at a single tertiary children’s hospital from 2007 to 2017 compared early versus late spontaneous resolution (cutoff 12 months) and intervention (cutoff 15 months) groups presenting at ≥9 months of age, comparing visual outcomes, including anisometropia (≥1 D of sphere or cylinder) and amblyopia (≥2 levels difference in Teller acuity or optotype testing). Parents/guardians were contacted by phone for missing data on spontaneous resolution or intervention status.

Results:

A total of 462 patients were included (152 early; 310 late group). The early group presented at a median age of 12.0 (interquartile range: 10.0, 13.0) months, while the late group presented at 21.0 (interquartile range: 15.0, 32.0) months. Unilateral disease occurred in 62% and 59%, respectively. Anisometropia was seen in (12/102) 12% of early versus (25/243) 10% of late patients (p = 0.686, 95% CI: –0.059, 0.088), and amblyopia in (4/131) 3% of early versus (14/286) 5% of late patients (p = 0.322, 95% CI: –0.061, 0.018). In patients presenting <24 months without undergoing surgery, spontaneous resolution occurred in 76% between 12 and 24 months (n = 41).

Conclusions:

Anisometropia and amblyopia rates did not significantly differ between early and delayed intervention for congenital nasolacrimal duct obstruction in this retrospective cohort presenting beyond 9 months of age to a children’s hospital. This study found frequent late spontaneous resolution.
Primary Renal Neuroendocrine Tumor Causing Zollinger-Ellison Syndrome
Authors: Faber Lauren S. , Lokke Amanda , Zilavy Andrew , Kaplan Damara , Davis Michael S.
Published: September 2023

Primary renal neuroendocrine tumor causing Zollinger-Ellison syndrome, also known as renal gastrinoma, has only been reported twice in the literature and in both cases was treated with radical nephrectomy. Here we report the first case of renal gastrinoma successfully treated with renal preservation partial nephrectomy.
Practical Strategies for Addressing Video Visit Access Barriers in Urology
Authors: Rasheed Husain Abizer , Hazelrigg Olivia , Rasmussen Patrick Magnus , Raja Hamza Mustafa , Blazek Mary C. , Chen Julia , Ellimoottil Chad
Published: September 2023

Purpose:

Since March 2020, telehealth has been a major part of health care delivery. Observational studies have shown that seniors, minorities, low-income Americans, and rural Americans have proportionally greater challenges in accessing telehealth compared with their counterparts. However, strategies to overcome these challenges have not been fully addressed. The objective of this study was to understand in greater detail the challenges patients face with video visits and introduce specific strategies to address these problems.

Methods:

We collected data on the technical barriers faced by patients through phone calls from a medical student-run volunteer program that assisted patients with telehealth visits through an electronic health record referral system.

Results:

Our study identified 4 main issues faced by patients that prevent successful video visits: (1) completion of registration steps, (2) familiarity with accessing and using video conferencing software, (3) attainment of proxy access for parents of a pediatric patient, and (4) resolution of miscellaneous technical queries. We addressed these issues through a structured workflow algorithm, which provided patients with an opportunity to receive a live walk-through of the steps for registering for a video visit, practice with video conferencing software, and guidance to resources and answers to any issues in the process.

Conclusion:

This study provides practical guidance for overcoming the challenges that patients face with video visits. These strategies can be used in any urology practice to improve video visit adoption and telehealth access in patient populations where challenges may exist.
Risk factors for death in hospitalized COVID-19 patients in Africa: A systematic review and meta-analysis
Authors: Riziki Ghislain Manimani , Muzumbukilwa Willy Tambwe , Magula Nombulelo
Published: September 2023

Background:

The coronavirus disease 2019 has quickly spread worldwide since it first appeared in Wuhan, China, in late 2019. The most affected country in Africa was South Africa. This study aimed to identify the risk factors for death in hospitalized COVID-19 patients in Africa.

Methods:

We conducted a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We searched articles from the following database: PubMed, Embase, Cochrane Library, Medline, and COVID-19 Research Database. We used Google Scholar for gray literature. The language used in this article was English. The last search was conducted on January 15, 2023. Pooled HRs, or ORs, and 95% confidence intervals, were calculated separately to identify the risk factors for death in hospitalized COVID-19 patients. Heterogeneity was assessed by Cochran’s Q statistic and the I
2 test. The Egger test was used to assess publication bias. Subgroup analysis was performed to determine the source of heterogeneity. Data analysis was performed using Stata version 17. A P value < .05 was considered significant.

Results:

A total of 16,600 articles were obtained from the database search; finally, 16 articles met the inclusion criteria and were eligible for data extraction. The analysis revealed that the pooled prevalence of mortality in hospitalized COVID-19 patients was 13.9%. Advanced age was a significant risk factor for death in hospitalized COVID-19 patients, with the pooled coronavirus mortality HR and OR being 3.73 (95% CI: 2.27–5.19) and 1.04 (95% CI: 1.02–1.06), respectively. In addition, male gender (pOR 1.23; 95% CI: 1.07–1.40), patients with diabetes mellitus (DM) (pOR 1.26; 95% CI: 1.01–1.51), hypertension (HTN) (pOR 1.56; 95% CI: 1.27–1.85), chronic kidney disease (CKD) (pHR 5.43; 95% CI: 0.18–10.67), severe or critical conditions (pOR 9.04; 95% CI: 3.14–14.94) had a significantly increased risk of coronavirus-related mortality. The main limitations of the present study stem from the predominant use of published studies, which could introduce publication bias.

Conclusion:

According to this study, advanced age, male gender, hypertension, diabetes mellitus, chronic kidney disease, and severe or critical condition were clinical risk factors associated with death outcomes in hospitalized COVID-19 patients in Africa.
Comparison of the analgesic effect of intrathecal morphine between laparoscopic and open living donor hepatectomy: Propensity score matching analysis
Authors: Kwon Ji-Hye , Ko Justin Sangwook , Kim Hyo Jin , Han Sangbin , Gwak Mi Sook , Kim Gaab Soo , Lee Seung Young , Wi Wongook
Published: September 2023

Laparoscopic donor hepatectomy is being increasingly adopted in transplant programs due to its numerous advantages. However, the role of intrathecal morphine (ITM) in laparoscopic donor hepatectomy has not been thoroughly investigated. This study aimed to compare the analgesic effects and safety of ITM between laparoscopic and open donor hepatectomy. This retrospective study included 742 donors who underwent hepatectomy with ITM between April 2007 and June 2019. Among them, 168 and 574 donors underwent laparoscopic hepatectomy (LH) and open hepatectomy (OH), respectively. Propensity score matching yielded two comparable groups of 168 donors each. The primary endpoint was the incidence of moderate-to-severe pain (maximum numerical rating scale [NRS] pain score ≥ 4) within 24 postoperative hours. The LH group had a significantly lower incidence of moderate-to-severe pain within 24 postoperative hours than the OH group (16.1% vs 64.3%,P< .001). Moreover, the cumulative rescue intravenous opioids (in morphine-equivalent dose) on postoperative day (POD) 1 was lower in the LH group than in the OH group (3.3 [0–8.3] mg vs 10 [3.3–17.3] mg;P< .001). There were no significant between-group differences in the incidence of respiratory depression (2.4% vs 0.6%;P= .371) and prescriptions for pruritus (14.3% vs 15.5%;P= .878). However, the prescriptions for postoperative nausea and vomiting (PONV) was significantly higher in the LH group than in the OH group (64.9% vs 41.7%;P< .001). The predictors of antiemetic agent prescription included the use of laparoscopic procedure (adjusted odds ratio [OR], 2.05; 95% confidence interval [CI], 1.11–3.79;P= .021) and female sex (adjusted OR, 5.63; 95% CI, 3.19–9.92;P< .001). Preoperative ITM administration resulted in a significantly lower incidence of moderate-to-severe pain within 24 postoperative hours after laparoscopic donor hepatectomy than after open donor hepatectomy.
Recurrence of pediatric intussusception: A nationwide population-based descriptive study in Taiwan
Authors: Chang Chao-Yang , Chen Yu-Ying , Lin Chih-Hsuan , Sheen Jiunn-Ming , Shih Wei-Tai , Chen Ko-Jung , Yang Yao-Hsu
Published: September 2023

Intussusception is frequently observed pediatric emergency that is often followed by recurrent intussusception after initial treatment. This study investigated the risk factors associated with recurrent intussusception in children aged ≤ 3 years. Between January 2007 and December 2015, a cohort study was conducted by linking the Taiwan Maternal and Child Health Database to the Birth Certificate Application database and the National Health Insurance Research Database in Taiwan. Patients aged ≤ 3 years with intussusception diagnosis and related treatment were included in our study. Multivariable logistic regression was used to analyze the risk factors associated with recurrent intussusception. In total, 5341 children with intussusception aged ≤ 3 years were enrolled in our cohort. The adjusted odds ratio (aOR) for recurrent intussusception in children aged 2 to 3 years was 0.62 (95% confidence interval [CI]: 0.47–0.82) compared with children aged < 1 year, and surgery decreased the risk of recurrent intussusception (aOR = 0.64, 95% CI: 0.46–0.88). Male patients had higher risk of recurrent intussusception than female patients had (aOR = 1.41, 95% CI: 1.13–1.75). Higher birth weight may increase the risk of recurrent intussusception, but this association was not statistically significant. Furthermore, gestational age did not seem to affect the risk of recurrent intussusception. Surgical treatment and delayed onset of intussusception are associated with a reduced risk of recurrent intussusception; males are associated with increased risk of recurrent intussusception. In addition, we suggest that in early infancy, patients who received non-surgical treatment as the initial treatment for intussusception should be closely followed up for potential recurrence of intussusception.
Nurses’ attitudes, knowledge, and practices concerning evidence-based practice: a descriptive cross-sectional study
Authors: Ibrahim Radhwan Hussein , Abdulghani Mohammad Faris , Abdullah Mohanned Khaleel , Mahmood Hanady Jabbar , Mohsen Ommar Akram , Jassim Raghad Saad
Published: September 2023

Background & Aim:

Evidence-based practice (EBP) is an essential approach to patient care that relies on the best available evidence to guide decision-making. However, there are several barriers to implementing EBP among nurses. This study aimed to investigate the attitudes, knowledge, and practices of nurses regarding EBP in patient care, as well as the obstacles they faced in its implementation.

Methods and Materials:

A cross-sectional study was conducted among 250 nurses from XXX Teaching Hospital in XXXX using a convenience sampling method. Two questionnaires were administered to collect data on nurses’ EBP practices, knowledge, attitudes, and perceived difficulties. Descriptive statistics, Pearson correlations, and multivariate analysis of variance were used to analyze the collected data.

Results:

The study found that nurses had a moderate level of EBP utilization, moderate knowledge of EBP, and positive attitudes toward evidence-based practice. Lack of time was the most commonly reported obstacle, followed by lack of support from management and lack of access to relevant research. Nurses with positive attitudes and more knowledge about EBP were more likely to use it in their daily work. The study also revealed that nurses who had worked for more than 10 years perceived more barriers to implementing EBP than those who had worked for 10 years or less.

Conclusion:

The study recommends addressing the perceived barriers and promoting facilitators to improve the uptake and implementation of evidence-based practice among nurses in XXXX. This can be achieved by providing nurses with access to relevant research, encouraging supportive management, and promoting positive attitudes toward EBP. Moreover, the study highlights the importance of continuous education and training for nurses, especially those with more than 10 years of experience, to overcome the perceived barriers to EBP implementation.
Spontaneous widespread muscle hematoma complicated by pyomyositis in a case of dengue hemorrhagic fever: a case report from Nepal
Authors: Timilsina Binita , Suryabanshi Anil , Bhandari Aashna , Pokhrel Saroj , Chataut Chandra P.
Published: September 2023

Introduction and importance:

Most dengue infections are asymptomatic, and some of them develop haemorrhagic manifestations with or without shock. However, dengue can sometimes present with very rare complications like pyomyositis.

Case presentation:

A healthy 27-year-old male, presented with a 2-day fever, confirmed to be dengue through a positive non-structural protein 1 test. Despite initial symptomatic management, his condition worsened and he was hospitalized. Leucocyte and platelet counts dropped to the lowest value on the seventh day of illness, followed by the gradual development of chest pain, persistent fever, and severe limb pain. Radiographic evaluation revealed pleural effusion, and multiple intramuscular haematomas complicated by pyomyositis. Pleural effusion resolved on its own. Pyomyositis resolved with 6 weeks of appropriate antibiotics and aspiration of pus.

Clinical discussion:

Dengue infection, caused by a dengue virus transmitted through Aedes mosquitoes, is a significant public health concern in many parts of the world. Dengue haemorrhagic fever is a severe form of dengue infection characterized by vascular leakage, thrombocytopenia, and bleeding manifestations. Although musculoskeletal manifestations are common in dengue fever, the occurrence of multiple muscle haematomas and pyomyositis as complications of Dengue haemorrhagic fever is rare. Drainage or aspiration of pus combined with the antibiotics according to the pus culture and sensitivity report is the management strategy.

Conclusion:

Prolonged fever with severe musculoskeletal pain and focal tenderness on examination in a dengue patient, warrant radiographic testing (ultrasonography or MRI) considering the differentials of haematoma, myositis, or pyomyositis.
Artificial Intelligence Iterative Reconstruction in Computed Tomography Angiography: An Evaluation on Pulmonary Arteries and Aorta With Routine Dose Settings
Authors: Gong Huan , Peng Liying , Du Xiangdong , An Jiajia , Peng Rui , Guo Rui , Ma Xu , Xiong Sining , Ma Qin , Zhang Guozhi , Ma Jing
Published: September 2023

Objective

The objective of this study is to investigate whether a newly introduced deep learning–based iterative reconstruction algorithm, namely, the artificial intelligence iterative reconstruction (AIIR), has a clinical value in computed tomography angiography (CTA), especially for visualizing vascular structures and related lesions, with routine dose settings.

Methods

A total of 63 patients were retrospectively collected from the triple rule-out CTA examinations, where both pulmonary and aortic data were available for each patient and were taken as the example for investigation. The images were reconstructed using the filtered back projection (FBP), hybrid iterative reconstruction (HIR), and the AIIR. The visibility of vasculature and pulmonary emboli and the general image quality were assessed.

Results

Artificial intelligence iterative reconstruction resulted in significantly (P < 0.001) lower noise as well as higher signal-to-noise ratio and contrast-to-noise ratio compared with FBP and HIR. Besides, AIIR achieved the highest subjective scores on general image quality (P < 0.05). For the vasculature visibility, AIIR offered the best vessel conspicuity, especially for the small vessels (P < 0.05). Also, >90% of emboli on the AIIR images were graded as sharp (score 5), whereas <15% of emboli on FBP and HIR images were scored 5.

Conclusion

As demonstrated for pulmonary and aortic CTAs, AIIR improves the image quality and offers a better depiction for vascular structures compared with FBP and HIR. The visibility of the pulmonary emboli was also increased by AIIR.
Comparison of 18F-FDG and 68Ga-FAPI PET/CT in a Rare Renal Leiomyoma
Authors: Liu Yanggang , Zhang Shumao , Lan Lianjun , Chen Yue , Qiu Lin
Published: September 2023

Renal leiomyoma is a rare benign mesenchymal tumor of the kidney, which mainly originates from the renal capsule or pelvis. We described18F-FDG and68Ga-FAPI PET/CT findings in a case of renal leiomyoma. The PET/CT findings showed that the left renal leiomyoma demonstrated intensively increased68Ga-FAPI uptake, whereas only inhomogeneously slightly increased18F-FDG uptake. This case illustrates that68Ga-FAPI PET/CT may be an effective tool for detecting renal leiomyoma.
Cranial Nerve Palsies in the Setting of Arachnoid Cysts: A Case Series and Literature Review
Authors: Bison Henry S. , Janetos Timothy M. , Russell Eric J. , Volpe Nicholas J.
Published: September 2023

Background:

Arachnoid cysts (ACs) are benign lesions typically believed to not cause neurologic defects in the adult population and are most often found incidentally on imaging. We describe 2 patients with ACs potentially leading to isolated cranial nerve (CN) dysfunction.

Methods:

We describe 2 patients, 1 with a fourth nerve palsy and the other with a sixth nerve palsy found to have ACs on MRI brain imaging in locations that potentially caused a compressive CN palsy. We review previous literature of ACs presenting with CN III, IV, or VI palsy.

Results:

Patient 1 was a 62-year-old man who presented with a 22-year history of diplopia with strabismus examination consistent with a congenital CN IV palsy. Despite multiple surgeries, his CN IV palsy insidiously worsened. An AC in the posterior fossa with mass effect on the quadrigeminal plate and asymmetric atrophy of the right superior oblique was identified on imaging. Patient 2 was an 80-year-old man who presented with an 18-year history of diplopia and was found to have a left esotropia and abduction deficit consistent with complete CN VI palsy. An AC in the left cavernous sinus was identified on imaging. He underwent strabismus surgery with satisfactory resolution of diplopia. We identified a total of 18 previously published cases: 8 reports of CN III palsy, 4 reports of CN IV palsy, and 6 reports of CN VI palsy. Patient ages ranged from 1 to 67 with a median of 34.5. In 16/18 (89%) cases, the diagnosis of ACs was made within 1 year of symptom onset. Surgical removal of the AC was successful in resolving diplopia in 7/12 (58%) cases. In no case was strabismus surgery performed as primary treatment.

Conclusions:

Although ACs are typically congenital asymptomatic lesions, we present a case series of 2 patients with ACs in anatomic locations that potentially caused chronic, progressive, isolated CN palsies leading to strabismus. Our literature review revealed that most published cases detailing this clinical scenario resulted in neurosurgical fenestration of ACs with mixed results. Our cases represent 2 patients with AC-associated CN palsy treated with strabismus surgery.
Genomic characterization of respiratory syncytial virus genotypes circulating in the paediatric population of Sydney, NSW, Australia
Authors: Pangesti Krisna N. A. , Ansari Hifzur R. , Bayoumi Ali , Kesson Alison M. , Hill-Cawthorne Grant A. , Abd El Ghany Moataz
Published: September 2023

Respiratory syncytial virus (RSV), or human orthopneumovirus, is a major cause of acute lower respiratory infection (ALRI), particularly in young children, causing significant morbidity and mortality. We used pathogen genomics to characterize the population structure and genetic signatures of RSV isolates circulating in children in New South Wales between 2016 and 2018 and to understand the evolutionary dynamics of these strains in the context of publicly available RSV genomes from the region and globally. Whole-genome phylogenetic analysis demonstrated the co-circulation of a few major RSV clades in the paediatric population from Sydney. The whole-genome-based genotypes A23 (RSV-A ON1-like genotype) and B6 (RSV-B BA9-like genotype) were the predominant RSV-A and RSV-B genotypes circulating during the study period, respectively. These genotypes were characterized with high levels of diversity of predicted N- and O-linked glycosylation patterns in both the G and F glycoproteins. Interestingly, a novel 72-nucleotide triplication in the sequence that corresponds to the C-terminal region of the G gene was identified in four of the A23 genotype sequenced in this study. Consistently, the population dynamics analysis demonstrated a continuous increase in the effective population size of A23 and B6 genotypes globally. Further investigations including functional mapping of mutations and identifying the impact of sequence changes on virus fitness are highly required. This study highlights the potential impact of an integrated approach that uses WG-based phylogeny and studying selective pressure events in understanding the emergence and dissemination of RSV genotypes.
Flu-CNN: predicting host tropism of influenza A viruses via character-level convolutional networks
Authors: Luo Nan , Wang Xin , Wang Boqian , Meng Renjie , Zhao Yunxiang , Chai Zili , Jin Yuan , Yue Junjie , Hu Mingda , Chen Wei , Ren Hongguang
Published: September 2023

Throughout history, Influenza A viruses (IAVs) have caused significant harm and catastrophic pandemics. The presence of host barriers results in viral host tropism, where infected hosts are subject to strict restrictions due to the hindered spread of viruses across hosts. Therefore, the identification of host tropism of IAVs, particularly in humans, is crucial to preventing the cross-host transmission of avian viruses and their outbreaks in humans. Nevertheless, efficiently and effectively identifying host tropism, especially for early host susceptibility warnings based on viral genome sequences during outbreak onset, remains challenging. To address this challenge, we propose Flu-CNN, a deep neural network model based on classical character-level convolutional networks. By analyzing the genomic segments of IAVs, Flu-CNN can accurately identify the host tropism, with a particular focus on avian influenza viruses that may infect humans. According to our experimental evaluations, Flu-CNN achieved an accuracy of 99% in identifying virus hosts via only a single genomic segment, even for subtypes with a relatively small number of viral strains such as H5N1, H7N9, and H9N2. The superiority of Flu-CNN demonstrates its effectiveness in screening for critical amino acid mutations, which is important to host adaptation, and zoonotic risk prediction of viral strains. Flu-CNN is a valuable tool for identifying evolutionary characterization, monitoring potential outbreaks, and preventing epidemical spreads of IAVs, which contribute to the effective surveillance of influenza A viruses.
Relationship between sex biases in gene expression and sex biases in autism and Alzheimer’s disease
Authors: Fass Stuart B. , Mulvey Bernard , Yang Wei , Selmanovic Din , Chaturvedi Sneha , Tycksen Eric , Weiss Lauren A. , Dougherty Joseph D.
Published: September 2023

Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions. In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-seq datasets using both within-region and pan-regional frameworks. We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-cell data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case-control gene expression studies suggests a female molecular predisposition towards Alzheimer’s disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis. Finally, we provide region specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences.

Graphical Abstract
LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction
Authors: Peters Colin H , Singh Rohit K , Langley Avery A , Nichols William G , Ferris Hannah R , Jeffrey Danielle A , Proenza Catherine , Bankston John R
Published: September 2023

Lymphoid restricted membrane protein (LRMP) is a specific regulator of the hyperpolarization-activated cyclic nucleotide-sensitive isoform 4 (HCN4) channel. LRMP prevents cAMP-dependent potentiation of HCN4 but the interaction domains, mechanisms of action, and basis for isoform-specificity remain unknown. Here we identify the domains of LRMP essential for regulation. We show that LRMP acts by disrupting the intramolecular signal transduction between cyclic nucleotide binding and gating. And we demonstrate that multiple unique regions in HCN4 are required for LRMP isoform-specificity. Using patch clamp electrophysiology and Förster resonance energy transfer (FRET), we showed that the initial 227 residues of LRMP and the N-terminus of HCN4 are necessary for LRMP to interact with HCN4. We found that the HCN4 N-terminus and HCN4-specific residues in the C-linker are necessary for regulation of HCN4 by LRMP. And we demonstrate that LRMP-regulation can be conferred to HCN2 by addition of the HCN4 N-terminus along with mutation of 5 residues in the S5 region and C-linker to the cognate HCN4 residues. Taken together, these results suggest that LRMP inhibits HCN4 through an isoform-specific interaction involving the N-terminals of both proteins that prevents the transduction of cAMP binding into a change in channel gating via an HCN4-specific orientation of the N-terminus, C-linker, and S4-S5 linker.
Size-Correlated Polymorphisms in Phyllotaxis-Like Periodic and Symmetric Tentacle Arrangements in Hydrozoan Polyps
Authors: Sarper Safiye E. , Kitazawa Miho S. , Nakanishi Tamami , Fujimoto Koichi
Published: September 2023

Introduction

Periodic organ arrangements occur during growth and development and are widespread in animals and plants. In bilaterian animals, the organs can be interpreted as being periodically arranged along the two-dimensional space and defined by two body axes; on the other hand, in radially symmetrical animals and plants, organs are arranged in the three-dimensional space around the body axis and around plant stems, respectively. The principles of periodic organ arrangement have primarily been investigated in bilaterians; however, studies on this phenomenon in radially symmetrical animals are scarce.

Methods

In the present study, we combined live imaging, quantitative analysis, and mathematical modeling to elucidate periodic organ arrangement in a radially symmetrical animal,Coryne uchidai(Cnidaria, Hydrozoa).

Results

The polyps ofC. uchidaisimultaneously formed multiple tentacles to establish a regularly angled, ring-like arrangement with radial symmetry. Multiple rings periodically appeared throughout the body and mostly maintained symmetry. Furthermore, we observed polymorphisms in symmetry type, including tri-, tetra-, and pentaradial symmetries, as individual variations. Notably, the types of radial symmetry were positively correlated with polyp diameter, with a larger diameter in pentaradial polyps than in tetra- and triradial ones. Our mathematical model suggested the selection of size-correlated radial symmetry based on the activation-inhibition and positional information from the mouth of tentacle initiation.

Discussion

Our established quantification methods and mathematical model for tentacle arrangements are applicable to other radially symmetrical animals, and will reveal the widespread association between size-correlated symmetry and periodic arrangement principles.
Genetic evidence for T-wave area from 12-lead electrocardiograms to monitor cardiovascular diseases in patients taking diabetes medications
Authors: Qi Mengling , Zhang Haoyang , Xiu Xuehao , He Dan , Cooper David N. , Yang Yuanhao , Zhao Huiying
Published: September 2023

Aims

Many studies indicated use of diabetes medications can influence the electrocardiogram (ECG), which remains the simplest and fastest tool for assessing cardiac functions. However, few studies have explored the role of genetic factors in determining the relationship between the use of diabetes medications and ECG trace characteristics (ETC).

Methods

Genome-wide association studies (GWAS) were performed for 168 ETCs extracted from the 12-lead ECGs of 42,340 Europeans in the UK Biobank. The genetic correlations, causal relationships, and phenotypic relationships of these ETCs with medication usage, as well as the risk of cardiovascular diseases (CVDs), were estimated by linkage disequilibrium score regression (LDSC), Mendelian randomization (MR), and regression model, respectively.

Results

The GWAS identified 124 independent single nucleotide polymorphisms (SNPs) that were study-wise and genome-wide significantly associated with at least one ETC. Regression model and LDSC identified significant phenotypic and genetic correlations of T-wave area in lead aVR (aVR_T-area) with usage of diabetes medications (ATC code: A10 drugs, and metformin), and the risks of ischemic heart disease (IHD) and coronary atherosclerosis (CA). MR analyses support a putative causal effect of the use of diabetes medications on decreasing aVR_T-area, and on increasing risk of IHD and CA.

Conclusion

Patients taking diabetes medications are prone to have decreased aVR_T-area and an increased risk of IHD and CA. The aVR_T-area is therefore a potential ECG marker for pre-clinical prediction of IHD and CA in patients taking diabetes medications.
Using Artificial Intelligence To Label Free-Text Operative And Ultrasound Reports For Grading Pediatric Appendicitis
Authors: Abu-Ashour Waseem , Emil Sherif , Poenaru Dan
Published: September 2023

Purpose

Data science approaches personalizing pediatric appendicitis management are hampered by small datasets and unstructured electronic medical records (EMR). Artificial intelligence (AI) chatbots based on large language models (LLMs) can structure free-text EMR data. Here we compare data extraction quality between ChatGPT-4 and human data collectors.

Methods

To train AI models to grade pediatric appendicitis preoperatively, several data collectors (medical students and research assistants) extracted detailed preoperative and operative data from 2100 children operated for acute appendicitis between 2014-2021. Collectors were trained and certified for the task based on satisfactory Kappa scores. ChatGPT-4 was prompted to structure free text from 103 random anonymized ultrasound and operative records in the dataset using the set variables and coding options, and to estimate the Pediatric Appendicitis Grade (PAG) from the operative report. A pediatric surgeon then adjudicated all data, identifying errors in each method.

Results

Within the 44 ultrasound (42.7%) and 32 operative reports (31.1%) discordant in at least one field, 98% of the errors were found in the manual data extraction. The PAG was erroneously assigned manually in 29 patients (28.2%), and by ChatGPT-4 in 3 (2.9%). Across datasets, the use of the AI chatbot was able to avoid misclassification in 59.2% of the records including both reports and extracted data approx. 100x faster than manually.

Conclusion

An AI chatbot significantly outperformed manual data extraction in accuracy for ultrasound and operative reports, and correctly assigned the PAG score. While wider validation is required and data safety concerns must be fully addressed, these novel AI tools show significant promise in improving the accuracy and efficiency of research data collection.

Highlights

1. What is known about this topic?

AI chatbots have several benefits and implications including healthcare uses.

2. What new information is contained in this article?

AI chatbot was proven to be more accurate when compared to human data extraction.
Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 synergistically enhances antibody evasion and ACE2 binding
Authors: Jian Fanchong , Feng Leilei , Yang Sijie , Yu Yuanling , Wang Lei , Song Weiliang , Yisimayi Ayijiang , Chen Xiaosu , Xu Yanli , Wang Peng , Yu Lingling , Wang Jing , Liu Lu , Niu Xiao , Wang Jing , Xiao Tianhe , An Ran , Wang Yao , Gu Qingqing , Shao Fei , Jin Ronghua , Shen Zhongyang , Wang Youchun , Wang Xiangxi , Cao Yunlong
Published: September 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants like EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. L455F and F456L evade Class 1 NAbs, reducing the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. The perturbed receptor-binding mode leads to the exceptional ACE2 binding and NAb evasion, as revealed by structural analyses. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.
Exploring Disease Model Mouse Using Knowledge Graphs: Combining Gene Expression, Orthology, and Disease Datasets
Authors: Kushida Tatsuya , de Farias Tarcisio Mendes , Sima Ana C. , Dessimoz Christophe , Chiba Hirokazu , Bastian Frederic B. , Masuya Hiroshi
Published: September 2023

Background

The RIKEN BRC develops and maintains the RIKEN BioResource MetaDatabase to help users explore appropriate target bioresources for their experiments and prepare precise and high-quality data infrastructures. The Swiss Institute of Bioinformatics develops two RDF datasets across multi species for the study of gene expression and orthology: Bgee and Orthologous MAtrix (OMA, an orthology database).

Methods

This study integrates the RIKEN BioResource knowledge graph with Resource Description Framework (RDF) datasets from Bgee, a gene expression database, the OMA, the DisGeNET, a human gene-disease association, Mouse Genome Informatics (MGI), UniProt, and four disease ontologies in the RIKEN BioResource MetaDatabase. Our aim is to explore which model organisms are most appropriate for specific medical science research applications, using SPARQL queries across the integrated datasets. More precisely, we attempt to explore disease-related genes, as well as anatomical parts where these genes are overexpressed and subsequently identify appropriate bioresource candidates available for specific disease research applications.

Results

We illustrate the above through two use cases targeting either Alzheimer’s disease or melanoma. We identified two Alzheimer’s disease-related genes that were overexpressed in the prefrontal cortex (APP and APOE) and 21 RIKEN bioresources predicted to be relevant to Alzheimer’s disease research. Furthermore, executing a transitive search for the Uberon terms by using the Property Paths function, we identified two melanoma-related genes (HRAS and PTEN), and eight anatomical parts in which these genes were overexpressed, such as the “skin of limb” as an example. Finally, we compared the performance of the federated SPARQL query via the remote Bgee SPARQL endpoint with the performance of a centralized SPARQL query using the Bgee dataset as part of the RIKEN BioResource MetaDatabase.

Conclusions

As a result, we demonstrated that the performance of the federated approach degraded. We concluded that we improved the degradation of the query performance of the federated approach from the BioResource MetaDatabase to the SIB by refining the transferred data through the subquery and enhancing the server specifications, that is optimizing the triple store query evaluation.
Tobacco Images Choice and Its Association with Craving and Dependence in Cigarette Smokers
Authors: Solinas Marcello , Chauvet Claudia , Lafay-Chebassier Claire , Vanderkam Paul , Barillot Lila , Moeller Scott J , Goldstein Rita Z , Noel Xavier , Jaafari Nematollah , Chatard Armand
Published: September 2023

Introduction: Increased salience of drug-related cues over non-drug reinforcers can drive drug use and contribute to tobacco use disorder (TUD). An important scientific and clinical goal is to effectively measure this elevated drug-seeking behavior in TUD. However, most TUD assessments rely on self-reported cravings and cigarette consumption, not providing an objective measure of the impact of drug-cues on biasing behavior towards drugs. The probabilistic image choice (PIC) task investigates the choice of viewing drug-related pictures as compared to other salient pictures (e.g., pleasant and unpleasant). This study aimed to develop and validate the PIC task for TUD and evaluate the associations between behavioral choice and tobacco craving, daily cigarette consumption, quit attempts and motivation to quit, and nicotine dependence (the Fagerstrom score). Methods: We recruited 468 smokers and 121 nonsmokers using the Prolific online platform. Participants performed the PIC task twice (at a one-month interval) and completed other measures relevant to TUD. Results: compared to nonsmokers, tobacco smokers selected to view significantly more tobacco images and less pleasant (non-drug reinforcer) images, a profile that remained stable at retest. Individual differences in choice of tobacco as compared to pleasant images on the PIC task were associated with craving but not with the other tobacco dependence measures, suggesting that the task may serve as a behavioral proxy measure of drug wanting rather than of cumulative nicotine exposure or physical dependence. Conclusions: these results suggest that the PIC task can be a valuable tool for objectively assessing craving-associated tobacco seeking in TUD.
Sex classification from functional brain connectivity: Generalization to multiple datasets
Authors: Wiersch Lisa , Friedrich Patrick , Hamdan Sami , Komeyer Vera , Hoffstaedter Felix , Patil Kaustubh R. , Eickhoff Simon B. , Weis Susanne
Published: September 2023

Machine learning (ML) approaches are increasingly being applied to neuroimaging data. Studies in neuroscience typically have to rely on a limited set of training data which may impair the generalizability of ML models. However, it is still unclear which kind of training sample is best suited to optimize generalization performance. In the present study, we systematically investigated the generalization performance of sex classification models trained on the parcelwise connectivity profile of either single samples or a compound sample containing data from four different datasets. Generalization performance was quantified in terms of mean across-sample classification accuracy and spatial consistency of accurately classifying parcels. Our results indicate that generalization performance of pwCs trained on single dataset samples is dependent on the specific test samples. Certain datasets seem to “match” in the sense that classifiers trained on a sample from one dataset achieved a high accuracy when tested on the respected other one and vice versa. The pwC trained on the compound sample demonstrated overall highest generalization performance for all test samples, including one derived from a dataset not included in building the training samples. Thus, our results indicate that a big and heterogenous training sample comprising data of multiple datasets is best suited to achieve generalizable results.
Apolipoprotein-based regulation of ganglioside metabolism upon secretase activity inhibition in iPSC-derived cerebral organoids
Authors: Jha Durga , Váňová Tereza , Bohačiaková Dáša , Spáčil Zdeněk
Published: September 2023

Beta and gamma-secretase inhibitors have been of pharmacological interest to reduce abeta (Aβ) formation and aggregation, one of the defining characteristics of Alzheimer’s disease (AD). Recent research indicates that Apolipoprotein E (ApoE), a genetic risk factor for AD, can regulate secretase activity. Secretase inhibitor-induced elevation of neuronal membrane lipids has been documented in 2D models. Due to their enhanced ability to reproduce AD-like pathology and ease of performing the experimental intervention, we utilized a 3D cerebral organoid model derived from human pluripotent stem cells generated from an AD patient. We treated cerebral organoids carrying ApoE3 and ApoE4 variants with beta and gamma-secretase inhibitors to determine if organoids could reproduce the differences observed in the 2D model and if the alteration in secretase activity could affect the regulation of neuronal lipids synthesis in an ApoE-dependent manner. Ganglioside profiling was accomplished using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) via selective reaction monitoring (SRM). The inhibitor administration elevated the levels of ganglioside and ceramide in ApoE4-derived organoids. Since gangliosides are known to enhance Aβ fibrillogenesis, our study implies that reduction in secretase activity affects neuronal membrane architecture that could eventually aggravate AD, particularly in patients with the ApoE4 isoform. In addition, the ability of organoids to replicate results from other experimental models demonstrates their potential to improve translatability significantly.