bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenome-assembled genomes provide insight into the metabolic potential during early production of Hydraulic Fracturing Test Site 2 in the Delaware Basin
Authors: Stemple Brooke , Gulliver Djuna , Sarkar Preom , Tinker Kara , Bibby Kyle
Published: June 2024

Demand for natural gas continues to climb in the United States, having reached a record monthly high of 104.9 billion cubic feet per day (Bcf/d) in November 2023. Hydraulic fracturing, a technique used to extract natural gas and oil from deep underground reservoirs, involves injecting large volumes of fluid, proppant, and chemical additives into shale units. This is followed by a “shut-in” period, during which the fracture fluid remains pressurized in the well for several weeks. The microbial processes that occur within the reservoir during this shut-in period are not well understood; yet, these reactions may significantly impact the structural integrity and overall recovery of oil and gas from the well. To shed light on this critical phase, we conducted an analysis of both pre-shut-in material alongside production fluid collected throughout the initial production phase at the Hydraulic Fracturing Test Site 2 (HFTS 2) located in the prolific Wolfcamp formation within the Permian Delaware Basin of west Texas, USA. Specifically, we aimed to assess the microbial ecology and functional potential of the microbial community during this crucial time frame. Prior analysis of 16S rRNA sequencing data through the first 35 days of production revealed a strong selection for a Clostridia species corresponding to a significant decrease in microbial diversity. Here, we performed a metagenomic analysis of produced water sampled on Day 33 of production. This analysis yielded three high-quality metagenome-assembled genomes (MAGs), one of which was a Clostridia draft genome closely related to the recently classified Petromonas tenebris. This draft genome likely represents the dominant Clostridia species observed in our 16S rRNA profile. Annotation of the MAGs revealed the presence of genes involved in critical metabolic processes, including thiosulfate reduction, mixed acid fermentation, and biofilm formation. These findings suggest that this microbial community has the potential to contribute to well souring, biocorrosion, and biofouling within the reservoir. Our research provides unique insights into the early stages of production in one of the most prolific unconventional plays in the United States, with important implications for well management and energy recovery.
Omadacycline for the treatment of patients with Legionella pneumophila pneumonia after experiencing liver dysfunction: case series
Authors: Zhu Ani , Ma Qian , Liu Zhiyan
Published: June 2024

Introduction

Antibiotics frequently induce abnormal liver function. Omadacycline is a novel aminomethylcycline antibiotic, which shows potent activity against Gram-positive and Gram-negative aerobic, anaerobic, and atypical (including Legionella pneumophila) bacteria. Of note, omadacycline is tolerable in most patients with liver impairment. However, evidence regarding the application of omadacycline in patients with Legionella pneumophila pneumonia after experiencing liver dysfunction is scarce.

Methods

The current study reported 6 cases of patients with Legionella pneumophila pneumonia receiving omadacycline as subsequent antibiotics after experiencing liver dysfunction.

Results

These 6 cases were admitted to the hospital for pneumonia and received antibiotic therapy, including piperacillin-tazobactam, imipenem, meropenem, and moxifloxacin. After receiving these antibiotics, increased liver enzymes were noted. Although hepatoprotective therapy (such as magnesium isoglycyrrhizinate and glutathione) was given, the liver function was still abnormal. According to metagenomic next-generation sequencing, these patients were diagnosed with Legionella pneumophila pneumonia. Considering the abnormal liver function, the antibiotic therapy was switched to omadacycline-containing antibiotic therapy. After that, liver function was improved, and the infection was ameliorated. Ultimately, all patients discharged from the hospital, including 2 patients who achieved complete clinical symptomatic improvement and 4 patients who achieved partial clinical symptomatic improvement.

Discussion

This study emphasizes the successful treatment of switching to omadacycline after experiencing abnormal liver function in patients with Legionella pneumophila pneumonia. This study suggests that omadacycline may serve as an optional antibiotic for patients with Legionella pneumophila pneumonia, especially when occurring liver dysfunction. However, more clinical studies are required to validate our findings.
Longitudinal microbiome investigation throughout prion disease course reveals pre- and symptomatic compositional perturbations linked to short-chain fatty acid metabolism and cognitive impairment in mice
Authors: Losa Marco , Morsy Yasser , Emmenegger Marc , Manz Salomon M. , Schwarz Petra , Aguzzi Adriano , Scharl Michael
Published: June 2024

Commensal intestinal bacteria shape our microbiome and have decisive roles in preserving host metabolic and immune homeostasis. They conspicuously impact disease development and progression, including amyloid-beta (Aβ) and alpha (α)-synuclein pathology in neurodegenerative diseases, conveying the importance of the brain–gut–microbiome axis in such conditions. However, little is known about the longitudinal microbiome landscape and its potential clinical implications in other protein misfolding disorders, such as prion disease. We investigated the microbiome architecture throughout prion disease course in mice. Fecal specimens were assessed by 16S ribosomal RNA sequencing. We report a temporal microbiome signature in prion disease and uncovered alterations in Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae, and Muribaculaceae family members in this disease. Moreover, we determined the enrichment of Bilophila, a microorganism connected to cognitive impairment, long before the clinical manifestation of disease symptoms. Based on temporal microbial abundances, several associated metabolic pathways and resulting metabolites, including short-chain fatty acids, were linked to the disease. We propose that neuroinflammatory processes relate to perturbations of the intestinal microbiome and metabolic state by an interorgan brain–gut crosstalk. Furthermore, we describe biomarkers possibly suitable for early disease diagnostics and anti-prion therapy monitoring. While our study is confined to prion disease, our discoveries might be of equivalent relevance in other proteinopathies and central nervous system pathologies.
Utilization of Ningxiang pig milk oligosaccharides by Akkermansia muciniphila in vitro fermentation: enhancing neonatal piglet survival
Authors: Zhang Longlin , Wu Zichen , Kang Meng , Wang Jing , Tan Bie
Published: June 2024

Akkermansia muciniphila (A. muciniphila), an intestinal symbiont residing in the mucosal layer, shows promise as a probiotic. Our previous study found that the abundance of A. muciniphila was significantly higher in Ningxiang suckling piglets compared to other breeds, suggesting that early breast milk may play a crucial role. This study examines A. muciniphila’s ability to utilize Ningxiang pig milk oligosaccharides. We discovered that A. muciniphila can thrive on both Ningxiang pig colostrum and purified pig milk oligosaccharides. Genetic analysis has shown that A. muciniphila harbors essential glycan-degrading enzymes, enabling it to effectively break down a broad spectrum of oligosaccharides. Our findings demonstrate that A. muciniphila can degrade pig milk oligosaccharides structures such as 3′-FL, 3′-SL, LNT, and LNnT, producing short-chain fatty acids in the process. The hydrolysis of these host-derived glycan structures enhances A. muciniphila’s symbiotic interactions with other beneficial gut bacteria, contributing to a dynamic microbial ecological network. The capability of A. muciniphila to utilize pig milk oligosaccharides allows it to establish itself in the intestines of newborn piglets, effectively colonizing the mucosal layer early in life. This early colonization is key in supporting both mucosal and metabolic health, which is critical for enhancing piglet survival during lactation.
Serum 25-hydroxyvitamin D level and erectile dysfunction: a causal relationship? Findings from a two-sample Mendelian randomization study
Authors: Sun Hengchang , Shen Gang , Dong Huimin , Shang Mei , Zhou Wenying , Wang Lingling , Li Zhaoxia , Gong Jiao , Hu Bo
Published: June 2024

Background

Serum 25-hydroxyvitamin D level is associated with erectile dysfunction (ED) in observational studies. However, whether there is a causal association between them remains uncertain.

Objective

Conduct a two-sample Mendelian randomization (MR) analysis to investigate the causal effect between serum 25-hydroxyvitamin D level and ED risk.

Method

Genome-wide association study (GWAS) data of serum 25-hydroxyvitamin D levels comprising 6,896,093 single nucleotide polymorphisms (SNP) from 496,949 people of European ancestry were regarded as exposure for the MR analysis. Additional GWAS data involving 9,310,196 SNPs of 6,175 European ED cases and 217,630 controls were used as outcome data. The MR-Egger, inverse variance weighted (IVW) method, weighted median, simple mode, and weighted mode were employed to evaluate causal effects, among which IVW was the primary MR analysis method. The stability of the MR analysis results was confirmed by a heterogeneity test, a horizontal pleiotropy test, and the leave-one-out method.

Result

There were 103 SNPs utilized as instrumental variables (p < 5 × 10−8). The results of MR analysis showed no causal effects of serum 25(OH) D concentration on ED risks (IVW; OR = 0.9516, 95% CI = 0.7994 to 1.1328, p = 0.5772). There was no heterogeneity and pleiotropy in the statistical models.

Conclusion

The present MR study did not support a causal association for genetically predicted serum 25-hydroxyvitamin D concentration in the risk of ED in individuals of European descent.
Mechanistic insight into the mode of inhibition of dietary flavonoids; targeting macrophage migration inhibitory factor
Authors: Siddiqui Ali Raza , Mushtaq Mamona , Sardar Madiha , Atta Lubna , Nur-e-Alam Mohammad , Ahmad Aftab , Ul-Haq Zaheer
Published: June 2024

Introduction: The Macrophage Migration Inhibitory Factor (MIF), a key pro-inflammatory mediator, is responsible for modulating immune responses. An array of inflammatory and autoimmune diseases has been linked to the dysregulated activity of MIF. The significance in physiological as well as pathophysiological phenomena underscores the potential of MIF as an attractive target with pharmacological relevance. Extensive research in past has uncovered a number of inhibitors, while the ISO-1, or (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester being recognized as a benchmark standard so far. Recent work by Yang and coworkers identified five promising dietary flavonoids, with superior activity compared to the standard ISO-1. Nevertheless, the exact atomic-level inhibitory mechanism is still elusive.

Methods: To improve the dynamic research, and rigorously characterize, and compare molecular signatures of MIF complexes with ISO-1 and flavonoids, principal component analysis (PCA) was linked with molecular dynamics (MD) simulations and binding free energy calculations.

Results: The results suggest that by blocking the tautomerase site these small molecule inhibitors could modify the MIF activity by disrupting the intrinsic dynamics in particular functional areas. The stability matrices revealed the average deviation values ranging from 0.27–0.32 nm while the residue level fluctuations indicated that binding of the selected flavonoids confer enhanced stability relative to the ISO-1. Furthermore, the gyration values extracted from the simulated trajectories were found in the range of 1.80–1.83 nm.

Discussion: Although all the tested flavonoids demonstrated remarkable results, the one obtained for the potent inhibitors, particularly Morin and Amentoflavone exhibited a good correlation with biological activity. The PCA results featured relatively less variance and constricted conformational landscape than others. The stable ensembles and reduced variation in turns might be the possible reasons for their outstanding performance documented previously. The results from the present exploration provide a comprehensive understanding of the molecular complexes formed by flavonoids and MIF, shedding light on their potential roles and impacts. Future studies on MIF inhibitors may benefit from the knowledge gathered from this investigation.
A specific olfactory bulb interneuron subtype Tpbg/5T4 generated at embryonic and neonatal stages
Authors: Tsuboi Akio
Published: June 2024

Various mammals have shown that sensory stimulation plays a crucial role in regulating the development of diverse structures, such as the olfactory bulb (OB), cerebral cortex, hippocampus, and retina. In the OB, the dendritic development of excitatory projection neurons like mitral/tufted cells is influenced by olfactory experiences. Odor stimulation is also essential for the dendritic development of inhibitory OB interneurons, such as granule and periglomerular cells, which are continuously produced in the ventricular-subventricular zone throughout life. Based on the morphological and molecular features, OB interneurons are classified into several subtypes. The role for each interneuron subtype in the control of olfactory behavior remains poorly understood due to lack of each specific marker. Among the several OB interneuron subtypes, a specific granule cell subtype, which expresses the oncofetal trophoblast glycoprotein (Tpbg or 5T4) gene, has been reported to be required for odor detection and discrimination behavior. This review will primarily focus on elucidating the contribution of different granule cell subtypes, including the Tpbg/5T4 subtype, to olfactory processing and behavior during the embryonic and adult stages.
Extended tests for evaluating post-traumatic brain injury deficits in resource-limited settings: methods and pilot study data
Authors: Semework Mulugeta , Laeke Tsegazeab , Aklilu Abenezer Tirsit , Tadele Abraham , Ashagre Yordanos , Teklewold Peter , Kolias Angelos G. , Hutchinson Peter , Balcha Abel , Yohannes Dagnachew , Hassen Getaw Worku
Published: June 2024

Introduction

Traumatic brain injury (TBI) is one of the leading causes of all injury-related deaths and disabilities in the world, especially in low to middle-income countries (LMICs) which also suffer from lower levels of funding for all levels of the health care system for patients suffering from TBI. These patients do not generally get comprehensive diagnostic workup, monitoring, or treatment, and return to work too quickly, often with undiagnosed post-traumatic deficits which in turn can lead to subsequent incidents of physical harm.

Methods

Here, we share methods and results from our research project to establish innovative, simple, and scientifically based practices that dramatically leverage technology and validated testing strategies to identify post-TBI deficits quickly and accurately, to circumvent economic realities on the ground in LMICs. We utilized paper tests such as the Montreal cognitive assessment (MoCA), line-bisection, and Bell’s test. Furthermore, we combined modifications of neuroscience computer tasks to aid in assessing peripheral vision, memory, and analytical accuracies. Data from seventy-one subjects (51 patients and 20 controls, 15 females and 56 males) from 4 hospitals in Ethiopia are presented. The traumatic brain injury group consists of 17 mild, 28 moderate, and 8 severe patients (based on the initial Glasgow Comma Score). Controls are age and education-matched subjects (no known history of TBI, brain lesions, or spatial neglect symptoms).

Results

We found these neurophysiological methods can: 1) be implemented in LMICs and 2) test impairments caused by TBI, which generally affect brain processing speed, memory, and both executive and cognitive controls.

Discussion

The main findings indicate that these examinations can identify several deficits, especially the MoCA test. These tests show great promise to assist in the evaluation of TBI patients and support the establishment of dedicated rehabilitation centers. Our next steps will be expansion of the cohort size and application of the tests to other settings.
Abnormal brain spontaneous neural activity in neuromyelitis optica spectrum disorder with neuropathic pain
Authors: Wang Gendi , Chen Xiang , Wang Xiaoyuan , Duan Yinghui , Gao Hanqing , Ji Xiaopei , Zhu Yunfei , Xiang Xuanyi , Ma Hairong , Li Yonggang , Xue Qun
Published: June 2024

Background

Neuropathic pain is one of the most common symptoms in neuromyelitis optica spectrum disorder (NMOSD). Notwithstanding, its underlying mechanism remains obscure.

Methods

The amplitude of low-frequency fluctuations (ALFF) metric was employed to investigate spontaneous neural activity alterations via resting-state functional magnetic resonance imaging (rs-MRI) data from a 3.0 T MRI scanner, in a sample of 26 patients diagnosed with NMOSD with neuropathic pain (NMOSD-WNP), 20 patients with NMOSD but without neuropathic pain (NMOSD-WoNP), and 38 healthy control (HC) subjects matched for age and sex without the comorbidity of depressive or anxious symptoms.

Results

It was observed that patients with NMOSD-WNP displayed a significant ALFF decrease in the left amygdala and right anterior insula, relative to both patients with NMOSD-WoNP and HC subjects. Furthermore, ALFF values in the left amygdala were negatively correlated with the scores of the Douleur Neuropathique en 4 Questions and McGill Pain Questionnaire (both sensory and affective descriptors) in patients with NMOSD-WNP. Additionally, there were negative correlations between the ALFF values in the right anterior insula and the duration of pain and the number of relapses in patients with NMOSD-WNP.

Conclusion

The present study characterizes spontaneous neural activity changes in brain regions associated with sensory and affective processing of pain and its modulation, which underscore the central aspects in patients with NMOSD-WNP. These findings might contribute to a better understanding of the pathophysiologic basis of neuropathic pain in NMOSD.
Combination of static and dynamic neural imaging features to distinguish sensorineural hearing loss: a machine learning study
Authors: Wu Yuanqing , Yao Jun , Xu Xiao-Min , Zhou Lei-Lei , Salvi Richard , Ding Shaohua , Gao Xia
Published: June 2024

Purpose

Sensorineural hearing loss (SNHL) is the most common form of sensory deprivation and is often unrecognized by patients, inducing not only auditory but also nonauditory symptoms. Data-driven classifier modeling with the combination of neural static and dynamic imaging features could be effectively used to classify SNHL individuals and healthy controls (HCs).

Methods

We conducted hearing evaluation, neurological scale tests and resting-state MRI on 110 SNHL patients and 106 HCs. A total of 1,267 static and dynamic imaging characteristics were extracted from MRI data, and three methods of feature selection were computed, including the Spearman rank correlation test, least absolute shrinkage and selection operator (LASSO) and t test as well as LASSO. Linear, polynomial, radial basis functional kernel (RBF) and sigmoid support vector machine (SVM) models were chosen as the classifiers with fivefold cross-validation. The receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity and accuracy were calculated for each model.

Results

SNHL subjects had higher hearing thresholds in each frequency, as well as worse performance in cognitive and emotional evaluations, than HCs. After comparison, the selected brain regions using LASSO based on static and dynamic features were consistent with the between-group analysis, including auditory and nonauditory areas. The subsequent AUCs of the four SVM models (linear, polynomial, RBF and sigmoid) were as follows: 0.8075, 0.7340, 0.8462 and 0.8562. The RBF and sigmoid SVM had relatively higher accuracy, sensitivity and specificity.

Conclusion

Our research raised attention to static and dynamic alterations underlying hearing deprivation. Machine learning-based models may provide several useful biomarkers for the classification and diagnosis of SNHL.
Bringing nutritional ketosis to the table as an option for healing the pediatric brain
Authors: Gertler Tracy S. , Blackford Robyn
Published: June 2024

Our core premise is that personalized variations of a ketogenic diet are likely to benefit pediatric patients with neuropsychiatric symptoms across multiple domains. Although pediatric epilepsy is currently a well-accepted indication for a strict ketogenic diet, there is a dearth of knowledge and therefore clinical guidelines upon which to recommend nutritional ketosis for pervasive pediatric conditions such as autism spectrum disorder and ADHD, even when comorbid epilepsy is present. However, there are published cohort studies and current clinical trials implementing medical ketogenic therapies for cognitive impairment, psychiatric comorbidities, motor disability, and even neuroinflammation. As holistic practitioners, it is imperative that we consider the health of a child in its entirety - and additionally offer the ketogenic diet as a therapeutic option when it may be synergistic in treating extra-neurologic diseases such as obesity. While there are uniquely pediatric potential adverse side effects such as linear growth deceleration and micronutrient deficiencies, previous trials in epilepsy and our center’s experience have already proven the ketogenic diet to be a low-risk intervention when optimized with appropriate patient monitoring and support.
Societal impacts of marine nitrogen pollution: rapid evidence assessment and future research
Authors: Rendon Olivia Raquel , Arnull Jessica , Beaumont Nicola J. , Wilson A. Meriwether W. , Painter Stuart C. , Shadiya Fathmath
Published: June 2024

Nitrogen pollution is a global problem and to effectively mitigate the effects we need to understand both the ecological and societal impacts. Coral reefs are of particular concern, as they are a critical source of livelihoods, culture, and wellbeing for hundreds of millions of people. Yet they are rapidly declining due to numerous pressures, with nitrogen pollution identified as a top-ranked non-climatic pressure. A Rapid Evidence Assessment was carried out to understand the societal impacts derived from marine nitrogen pollution on coral reefs. The results highlight key research evidence gaps, such as unclear reporting of nitrogen pollution, not distinguishing impacts from nitrogen and other stressors, non-quantification of nitrogen-specific marine and societal impacts, unstudied global regions with high nitrogen pressure, and the need for greater awareness on marine nitrogen pollution. Future research questions are proposed to allow better understanding on how tropical coastal societies are being impacted by marine nitrogen pollution.
Non-invasive intracranial pressure monitoring for high-grade gliomas patients treated with radiotherapy: results of the GMaPIC trial
Authors: Casile Mélanie , Thivat Emilie , Giraudet Fabrice , Ginzac Angeline , Molnar Ioana , Biau Julian , Brehant Julien , Lourenco Blandine , Avan Paul , Durando Xavier
Published: June 2024

Introduction

Patients with high-grade gliomas are at risk of developing increased intracranial hypertension (ICHT) in relation to the increase in volume of their tumor. ICP change cannot be measured by invasive method but can be estimated by using routine clinical signs, in combination with a standard imaging method, magnetic resonance imaging (MRI). A non-invasive monitoring of ICP could be of interest in high-grade glioma, in particular after radiotherapy treatment with as major side effect a cerebral oedema.

Patients and Methods

This prospective clinical study aimed to compare the ICP changes (estimated by a non-invasive method based upon distortion product otoacoustic emissions (DPOAE) monitoring) with volume changes observed on MRI in patients with high-grade gliomas treated with radiotherapy. DPOAE measurements were performed one month after the end of radiotherapy and then every 3 months for one year. At each visit, the patient also underwent MRI as well as an evaluation of clinical signs.

Results

The variation in the estimate of intracranial pressure readout measured at each follow-up visit (in absolute value with respect to the baseline measurements) was significantly associated with the variation of T2/FLAIR volume (n=125; p<0.001) with a cut off value of change ICP readout of 40.2 degrees (e.i. an estimated change of 16 mm Hg).

Discussion

The GMaPIC trial confirm the hypothesis that the ICP change estimated by DPOAEs measurement using a non-invasive medical device is correlated with the change of the tumor or edema in high grade glioma after radiotherapy. The device could thus become an easy-to-use and non-invasive intracranial pressure monitoring tool for these patients.

Clinical Trial Registration

Clinicaltrials.gov, identifier (NCT02520492)
Comparative analysis of plan quality and delivery efficiency: ZAP-X vs. CyberKnife for brain metastases treatment
Authors: Niu Ying , Rashid Abdul , Lee Jui-min , Carrasquilla Michael , Conroy Dylan R. , Collins Brian T. , Satinsky Andrew , Unger Keith R. , Pang Dalong
Published: June 2024

Purpose/Objectives

ZAP-X, a novel and dedicated radiosurgery (SRS) system, has recently emerged, while CyberKnife has solidified its position as a versatile solution for SRS and stereotactic body radiation therapy over the past two decades. This study aims to compare the dosimetric performance and delivery efficiency of ZAP-X and CyberKnife in treating brain metastases of varying target sizes, employing circular collimation.

Methods and materials

Twenty-three patients, encompassing a total of 47 brain metastases, were included in the creation of comparative plans of ZAP-X and CyberKnife for analysis. The comparative plans were generated to achieve identical prescription doses for the targets, while adhering to the same dose constraints for organs at risk (OAR). The prescription isodose percentage was optimized within the range of 97–100% for each plan to ensure effective target-volume coverage. To assess plan quality, indices such as conformity, homogeneity, and gradient (CI, HI, and GI) were computed, along with the reporting of total brain volumes receiving 12Gy and 10Gy. Estimated treatment time and monitor units (MUs) were compared between the two modalities in evaluating delivery efficiency.

Results

Overall, CyberKnife achieved better CI and HI, while ZAP-X exhibited better GI and a smaller irradiated volume for the normal brain. The superiority of CyberKnife’s plan conformity was more pronounced for target size less than 1 cc and greater than 10 cc. Conversely, the advantage of ZAP-X’s plan dose gradient was more notable for target sizes under 10 cc. The homogeneity of ZAP-X plans, employing multiple isocenters, displayed a strong correlation with the target’s shape and the planner’s experience in placing isocenters. Generally, the estimated treatment time was similar between the two modalities, and the delivery efficiency was significantly impacted by the chosen collimation sizes for both modalities.

Conclusion

This study demonstrates that, within the range of target sizes within the patient cohort, plans generated by ZAP-X and CyberKnife exhibit comparable plan quality and delivery efficiency. At present, with the current platform of the two modalities, CyberKnife outperforms ZAP-X in terms of conformity and homogeneity, while ZAP-X tends to produce plans with a more rapid dose falloff.
Revitalizing oral cancer research: Crispr-Cas9 technology the promise of genetic editing
Authors: S. V. Sowmya , Augustine Dominic , Mushtaq Shazia , Baeshen Hosam Ali , Ashi Heba , Hassan Reem Nabil , Alshahrani Mohammed , Patil Shankargouda
Published: June 2024

This review presents an in-depth analysis of the immense potential of CRISPR-Cas9 technology in revolutionizing oral cancer research. It underscores the inherent limitations of conventional treatments while emphasizing the pressing need for groundbreaking approaches. The unparalleled capability of CRISPR-Cas9 to precisely target and modify specific genes involved in cancer progression heralds a new era in therapeutic intervention. Employing genome-wide CRISPR screens, vulnerabilities in oral cancer cells can be identified, thereby unravelling promising targets for therapeutic interventions. In the realm of oral cancer, the disruptive power of CRISPR-Cas9 manifests through its capacity to perturb genes that are intricately associated with drug resistance, consequently augmenting the efficacy of chemotherapy. To address the challenges that arise, this review diligently examines pertinent issues such as off-target effects, efficient delivery mechanisms, and the ethical considerations surrounding germline editing. Through precise gene editing, facilitated by CRISPR/Cas9, it becomes possible to overcome drug resistance by rectifying mutations, thereby enhancing the efficacy of personalized treatment strategies. This review delves into the prospects of CRISPR-Cas9, illuminating its potential applications in the domains of medicine, agriculture, and biotechnology. It is paramount to emphasize the necessity of ongoing research endeavors and the imperative to develop targeted therapies tailored specifically for oral cancer. By embracing this comprehensive overview, we can pave the way for ground-breaking treatments that instill renewed hope for enhanced outcomes in individuals afflicted by oral cancer.
Assessment of the quality of interdisciplinary communication (CritCom): evaluation and refinement of a center summary report
Authors: Counts Lara , Rivera Jocelyn , Wiphatphumiprates Parima , Puerto-Torres Maria , Prewitt Kim , Luke Douglas A. , Graetz Dylan E. , Malone Sara , Agulnik Asya
Published: June 2024

Communication failures among clinicians in the ICU (intensive care unit) often lead to worse patient outcomes. CritCom is a bilingual (English and Spanish) tool to evaluate the quality of interdisciplinary communication around patient deterioration for pediatric oncology patients. The use of reports, such as the CritCom report, as dissemination methods lead to quicker knowledge translation and implementation of research findings into policy. Nurses and physicians at participating centers who care for patients at risk of deterioration completed the CritCom survey and center-specific reports were generated to communicate CritCom results. Focus groups were conducted with clinicians receiving CritCom reports in both English and Spanish to evaluate report clarity and usability. Participants found the reports to be useful and described the writing and design as clear and specific. Participants provided feedback to improve report design and requested actionable steps to improve communication at their center. Feedback illustrated that the report was easy to interpret and a useful way to disseminate information. Participants noted the utility of the report, illustrating that the use of reports can be a useful method to disseminate research findings back to participants in a way that is applicable to the local context. Communicating research findings through reports can minimize the significant time lag in knowledge translation and provide participants with actionable steps to implement in their setting.
Intrahepatic cholangiocarcinoma detected on 18F-PSMA-1007 PET/MR imaging in a prostate cancer patient: a case report and literature review
Authors: Sun Yu , Wang Haiyan , Yang Yihong , You Zhiwen , Zhao Jun
Published: June 2024

Radionuclide probes-targeted prostate-specific membrane antigen (PSMA) is used in diagnosis and treatment of prostate cancer (PCa). Recent studies have shown that PSMA is expressed in the tumor neovascular endothelium, such as in malignant liver tumors. We report a case of PCa with incidental intrahepatic cholangiocarcinoma (ICC) detection using 18F-PSMA-1007 and 18F-fluorodeoxyglucose (FDG) positron emission topography (PET)/MRI.18F-PSMA-1007 PET/MRI of our patient with PCa showed that one liver lesion had high PSMA uptake. 18F-FDG PET/MRI revealed minimal FDG uptake in the liver lesion. Histopathological examination revealed that the liver lesion was moderately to poorly differentiated cholangiocarcinoma. Our studies, along with others, demonstrated that malignant liver tumors, such as ICC, hepatocellular carcinoma (HCC), and combined hepatocellular-cholangiocarcinoma (CHC), and benign lesions, such as benign liver hemangioma, focal nodular hyperplasia, focal inflammation and steatosis, vascular malformation, and fatty sparing, exhibited elevated PSMA uptake. Moreover, PSMA-PET was superior to FDG-PET in detecting ICC and HCC, indicating that PSMA-PET may be used as alternative staging and to identify patients for PSMA-targeted therapy.
Cancer fusion transcripts with human non-coding RNAs
Authors: Mohammad Tharaa , Zolotovskaia Marianna A. , Suntsova Maria V. , Buzdin Anton A.
Published: June 2024

Cancer chimeric, or fusion, transcripts are thought to most frequently appear due to chromosomal aberrations that combine moieties of unrelated normal genes. When being expressed, this results in chimeric RNAs having upstream and downstream parts relatively to the breakpoint position for the 5’- and 3’-fusion components, respectively. As many other types of cancer mutations, fusion genes can be of either driver or passenger type. The driver fusions may have pivotal roles in malignisation by regulating survival, growth, and proliferation of tumor cells, whereas the passenger fusions most likely have no specific function in cancer. The majority of research on fusion gene formation events is concentrated on identifying fusion proteins through chimeric transcripts. However, contemporary studies evidence that fusion events involving non-coding RNA (ncRNA) genes may also have strong oncogenic potential. In this review we highlight most frequent classes of ncRNAs fusions and summarize current understanding of their functional roles. In many cases, cancer ncRNA fusion can result in altered concentration of the non-coding RNA itself, or it can promote protein expression from the protein-coding fusion moiety. Differential splicing, in turn, can enrich the repertoire of cancer chimeric transcripts, e.g. as observed for the fusions of circular RNAs and long non-coding RNAs. These and other ncRNA fusions are being increasingly recognized as cancer biomarkers and even potential therapeutic targets. Finally, we discuss the use of ncRNA fusion genes in the context of cancer detection and therapy.
Time, cause of early neonatal death, and its predictors among neonates admitted to neonatal intensive care units at Bahir Dar City public hospitals, northwest Ethiopia: a prospective follow-up study
Authors: Gessesse Abraham Dessie , Belete Minyichil Birhanu , Tadesse Fikir
Published: June 2024

Background

Globally, 75% of neonatal deaths occur during the first weeks of life and more than 43% of deaths are covered by sub-Saharan Africa. Health-related policymakers and decision-makers need to use evidence-based treatments to reduce the time to early neonatal death and associated predictors. However, there are limited studies on median survival time, cause, incidence, and predictors in the study area as well as the country. Therefore, the aim of the present study was to assess time, the cause of early neonatal death, and its predictors among neonates admitted to neonatal intensive care units at Bahir Dar City public hospitals in northwest Ethiopia.

Methods

An institution-based prospective follow-up study design was conducted among 387 early neonates selected by systematic sampling between 22 February and 22 April 2023. Statistical software, Epi Data version 4.6 and Stata version 14, was used for entry and analysis, respectively. Proportional hazard assumption and model fitness were checked by the Schoenfeld residual test and the Cox-Snell residual test, respectively. Descriptive statistics, the Kaplan–Meier curve, and the life table were used to describe variables. The Cox regression analysis model was fitted to identify the predictors of early neonatal death.

Result

During the follow-up time, 59 (15.25%) early neonates died, with an incidence of 31.79 per 1,000 early neonate days [95% confidence interval (CI): 0.024–0.041]. The leading causes of early neonatal death were prematurity complications, asphyxia, sepsis, meconium aspiration syndrome, and necrotizing enterocolitis. The mean survival time was 2.72 days. Being born from a multigravida mother [adjusted hazard ratio (AHR) 4.34; 95% CI: 1.63–11.55], a grand multigravida mother (AHR 3.50; 95% CI: 1.12–10.95), respiratory distress syndrome (AHR 2.60; 95% CI: 1.03–6.58), birth asphyxia (AHR 7.51; 95% CI: 2.30–24.51), a small gestational age (AHR 2.05; 95% CI: 1.08–4.92), and being unable to exclusively breastfeed (AHR 3.46; 95% CI: 1.52–7.88) were significantly associated predictors for time to early neonatal death.

Conclusion and recommendations

The incidence of early neonatal death was high, and the mean survival time was 2.72 days. Gravidity, respiratory distress syndrome, birth asphyxia, and being unable to exclusively breastfeed were identified as predictors of early neonatal death. Therefore, future research will consist of long-term prospective follow-up studies at a multicenter, nationwide level.
Efficacy of five different traditional Chinese medicine injections in acute upper respiratory tract infection in children: a network meta-analysis and systematic review
Authors: Guo Xinyi , Liu Changxing , Zhao Qiong , Huang Sajiyue
Published: June 2024

Background

Acute upper respiratory tract infection (AURI) includes infections caused by a variety of pathogens and is one of the most common diseases in children. Traditional Chinese medicine (TCM) injections are widely used for treating AURI in clinical practice, but their efficacy is unclear because of the lack of clear evidence. In this study, a network meta-analysis (NMA) was used to evaluate the efficacy and safety of TCM injections in the treatment of AURI and to provide a reference for clinical treatment.

Methods

Eight databases were searched, namely, PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), the Wanfang database, and the Chinese Scientific Journal database (VIP). The search time period was from 1 January 2013 to 1 November 2023. Randomized controlled trials of herbal injections for treating AURI were searched. The Cochrane Risk of Bias 2.0 tool was used to assess the quality of these studies. Review Manager 5.4 and Stata 15.0 were used for the NMA.

Results

A total of 81 papers involving 11,736 patients were included. These involved five different TCM injections, namely, Xiyanping injection (XYPI), Qingkailing injection (QKLI), Reduning injection (RDNI), Yanhuning injection (YHNI), and Tanreqing injection (TRQI). QKLI was most effective in alleviating symptoms of fever and improving overall clinical effectiveness. TRQI was most effective in relieving cough symptoms. YHNI was most effective in alleviating sore throat, runny nose, and nasal congestion. The overall incidence of adverse effects of these herbal injections in the treatment of AURI was lower, and their safety profiles were better.

Conclusions

The herbal injections combined with ribavirin improved clinical outcomes, and were superior to ribavirin injection alone in alleviating clinical symptoms such as fever, cough, sore throat, runny nose, and nasal congestion, and have favorable safety profiles.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023484099, CRD42023484099.
Increased disease severity during COVID-19 related hospitalization in black non-hispanic, hispanic and medicaid-insured young children
Authors: Ochapa Monica Oyidu , McGrath Leah J. , Alfred Tamuno , Lopez Santiago M. C. , Nepal Rajeev M.
Published: June 2024

Background

The COVID-19 pandemic has disproportionately affected marginalized groups in the United States. Although most children have mild or asymptomatic COVID-19, some experience severe disease and long-term complications. However, few studies have examined health disparities in severe COVID-19 outcomes among US children.

Objective

To examine disparities in the clinical outcomes of infants and children aged <5 years hospitalized with COVID-19 by race/ethnicity and payer status.

Methods

Children aged <5 years hospitalized with an admission diagnosis of COVID-19 (April 2021-February 2023) were selected from the PINC AI™ Healthcare Database. Hospital outcomes included length of stay (LOS), intensive care unit (ICU) admission, oxygen supplementation, invasive mechanical ventilation (IMV), and prolonged duration of each outcome. Multivariable logistic regression models compared hospitalization outcomes by race/ethnicity and payer status.

Results

Among 10,190 children (mean age: 0.9 years, 56.5% male, 66.7% Medicaid-insured), race/ethnicity was distributed as follows: White non-Hispanic (35.1%), Hispanic (any or Unknown race; 28.3%), Black non-Hispanic (15.2%), Other race/ethnicity (8.9%) and Unknown (12.5%). Payer status varied by race/ethnicity. White non-Hispanic children had the highest proportion with commercial insurance (42.9%) while other racial/ethnic groups ranged between 13.8% to 26.1%. Black non-Hispanic children had the highest proportion with Medicaid (82.3%) followed by Hispanic children (76.9%). Black non-Hispanic children had higher odds of prolonged outcomes: LOS (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI]:1.05–1.38), ICU days (aOR = 1.44, 95% CI: 1.07–1.93), and IMV days (aOR = 1.80, 95% CI: 1.09–2.97) compared to White non-Hispanic children. Similar patterns were observed for Hispanic and children of Other race/ethnicity. Medicaid-insured and children with other insurance had higher odds of prolonged LOS and oxygen days than commercially insured patients.

Conclusion

There were disparities in clinical outcomes of COVID-19 by race/ethnicity and insurance type, particularly for prolonged-duration outcomes. Further research is required to fully comprehend the causes and consequences of these disparities and develop strategies to reduce them while ensuring equitable healthcare delivery.
Urethral multiplicity in boys: systematic review of case reports and case series from the last 15 years
Authors: Gozar Horea , Bara Zsolt , Kovacs Evelyn , Gozar Iulia , Derzsi Zoltan
Published: June 2024

Introduction

Urethral multiplicity is a rare congenital anomaly characterized by the presence of two or more urethral channels. It is more common in males and can cause double urinary stream, incontinence, obstruction, and recurrent urinary infections. Diagnosis is difficult due to diverse clinical manifestations. Implementing an evidence-based treatment plan is challenging due to the need for more concise and informative summary publications. Our paper provides a comprehensive review of the management of this pathology and might serve as a valuable resource for pediatric urologists and specialists in the field.

Methods

A comprehensive search in four electronic databases, PubMed®, PubMed Central® (PMC), Scopus, and Clarivate Analytics's Web of Science (WoS), was conducted to identify case reports and series published between 2008 and 2023 on urethral multiplicities. The quality of the articles was assessed using qualified instruments. Covidence® tool-guided synthesis was followed by individual patient data extraction. Further classifications and analysis were made using Microsoft Excel®.

Results

Out of the 90 papers included in the review, 62 were case presentations, and 28 were case series. We found 250 boys with urethral multiplicity. Based on Effman's classification, there were 38 cases of type I (15.3%), 21 type IIA1 (8.4%), 55 type IIA2 (22.1%), 91 type IIA2Y (36.5%), 4 type IIB (1.6%), and 6 type III (2.4%) urethral duplications. There were 19 cases of prepubic sinuses (7.6%), 9 triplications (3.6%), and 6 unknown forms (2.4%). We have provided data for each type, including clinical presentation, investigations, surgical management, and outcomes.

Conclusions

Urethral multiplicities are a rare and varied group of malformations that require high-quality imaging examination for successful management. Treatment is specific to each patient and may depend on the surgeon's preference or skill.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID = CRD42023471685, identifier (CRD42023471685).
An overview and single-arm meta-analysis of immune-mediated adverse events following COVID-19 vaccination
Authors: Yang Donghua , Tian Jinhui , Shen Caiyi , Li Qin
Published: June 2024

Background

We conducted an overview to assess immune adverse effects associated with the COVID-19 vaccine, guiding safer choices and providing evidence-based information to clinicians.

Methods

Forty-three studies on adverse effects of vaccines were reviewed from PubMed, Embase, and Web of Science. Single-arm meta-analyses estimated summary effects, incidence, presentation, etc. An overview using single-arm meta-analysis and reported the findings following the guidelines outlined in the ‘Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) specifically focusing on myocarditis and thrombosis. After screening 2,591 articles, 42 studies met the inclusion criteria. Methodological quality was evaluated using AMSTAR 2. Disagreements were resolved via consensus. Data analysis utilized a random-effects model in R software to estimate incidence rates of selected adverse events.

Results

After removing 1,198 duplicates and screening out irrelevant articles from a total of 2,591, we included 42 studies. Adverse reactions to vaccinations include myocarditis, thrombosis, skin reactions, GBS, etc. thrombosis and myocarditis are the most dangerous diseases associated with vaccination. Myocarditis occurred in 6% of Vector vaccine recipients, compared to 61% of mRNA vaccine recipients. Thrombosis was more common after Vector vaccination (91%) than after mRNA vaccination (9%). Furthermore, eight studies conducted anti-PF4 antibody tests and yielded a positivity rate of 67%. Meta-analysis showed that among all patients with Vaccine-induced Thrombotic Thrombocytopenia, cerebral venous sinus thrombosis occurred in 66%, and intracranial hemorrhage occurred in 43%. The rates of deep vein thrombosis and pulmonary thromboembolism in vaccinated patients were 13% and 23%, respectively, with a pooled case fatality rate of 30%.

Conclusion

The results of this overview indicate the majority of adverse reactions are self-limiting and require minimal intervention, while rare occurrences such as myocarditis and thrombosis pose a potentially fatal threat.