"Nutrient-fungi-host" tripartite interaction in cancer progression.

The human microbiome exhibits a profound connection with the cancer development, progression, and therapeutic response, with particular emphasis on its components of the mycobiome, which are still in the early stages of research. In this review, we comprehensively summarize cancer-related symbiotic and pathogenic fungal genera. The intricate mechanisms through which fungi impact cancer as an integral member of both gut and tissue-resident microbiomes are further discussed. In addition, we shed light on the pivotal physiological roles of various nutrients, including cholesterol, carbohydrates, proteins and minerals, in facilitating the growth, reproduction, and invasive pathogenesis of the fungi. While our exploration of the interplay between nutrients and cancer, mediated by the mycobiome, is ongoing, the current findings have yet to yield conclusive results. Thus, delving into the relationship between nutrients and fungal pathogenesis in cancer development and progression would provide valuable insights into anticancer therapy and foster precision nutrition and individualized treatments that target fungi from bench to bedside.

Intraoperative ultrasound is valuable for detecting intracranial hematoma progression and decreasing mortality in traumatic brain injury.

BACKGROUND: Our aim was to explore the clinical benefit of intraoperative ultrasound in decompressive craniectomy (DC) for traumatic brain injury (TBI). METHODS: From January 1, 2018, through April 30, 2021, 54 patients who developed acute subdural hematoma (SDH) due to blunt injury and underwent DC with or without intraoperative ultrasound assistance were retrospectively included in our study. Logistic regression analyses were performed to compare the therapeutic efficacy in the two groups. RESULTS: In the ultrasound group (14 patients, 25.93%), intraoperative ultrasound was used for assisting hematoma removal and/or ventriculostomy during DC. In the control group (40 patients, 74.07%), ultrasound was not used during the operation and ventriculostomy was not performed. No statistically significant differences in age, sex, initial Glasgow Coma Scale (GCS) score, blood loss, postoperative intracranial pressure (ICP), duration of hyperosmolar therapy, or Glasgow Outcome Scale Extended (GOS-E) score 6 months after injury were observed. No mortality was recorded in the ultrasound group. The mortality rate in the control group during hospitalization was 25% (p < 0.05). CONCLUSIONS: Intraoperative ultrasound is helpful for intracranial hematoma removal and ventriculostomy with cerebrospinal fluid drainage and decreases mortality in experienced hands. The reason for higher mortality rate in the control group might result from poor hematoma clearance rate and poor postoperative intracranial pressure control. It is a useful tool for diagnosing and assisting with treatment in cases of TBI.

Neutrophil gelatinase-associated lipocalin partly reflects the dynamic changes of renal function among chronic hepatitis C patients receiving direct-acting antivirals.

BACKGROUND: Changes in renal function in chronic hepatitis C (CHC) patients receiving direct-acting antivirals (DAAs) are controversial. The evolution of neutrophil gelatinase-associated lipocalin (NGAL) in these patients remains unclear. METHODS: A total of 232 CHC patients receiving DAA at Dalin Tzu Chi Hospital from May 2016 to February 2019, were enrolled in this retrospective study. Grade 2/3 renal function deterioration, defined as a decrease in eGFR between 10% and 50% from baseline (BL) to 12 weeks after the end of treatment (P12), was investigated for its association with BL characteristics. The changes in renal function and NGAL levels were also analyzed at the SOF-base or nonSOF-base DAA. RESULTS: Sixty-two patients (26.7%) had grade 2/3 renal function deterioration at P12 after DAA therapy. Univariate analysis showed that it was associated with age (P = 0.038). Multivariate analysis indicated that age (OR = 1.033, 95% CI: 1.004-1.064, P = 0.027), sex (male; OR = 2.039, 95% CI: 1.093-3.804, P = 0.025), ACEI/ARB use (OR = 2.493, 95% CI: 1.016-6.119, P = 0.046), and BL NGAL (OR = 1.033, 95% CI: 1.001-1.067, P = 0.046) positively correlated with grade 2/3 renal function deterioration. Furthermore, eGFR was decreased (P = 0.009) and NGAL was increased (P = 0.004) from BL to P12 in CHC patients receiving SOF-based DAA. CONCLUSIONS: Of the CHC patients receiving DAA therapy, 26.7% had grade 2/3 renal function deterioration at P12, and it was associated with older age, gender being male, ACEI/ARB use, and higher BL NGAL levels. In addition, NGAL might be a biomarker of nephrotoxicity at P12 in patients receiving SOF-based DAA.

Single-virion sequencing of lamivudine-treated HBV populations reveal population evolution dynamics and demographic history.

BACKGROUND: Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients - once before antiviral treatment and once after viral rebound due to resistance. RESULTS: With single-virion sequencing, we obtained 248-8796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently through PacBio SMRT and Illumina Pooled deep sequencing. CONCLUSIONS: Overall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance and host adaptation, allows differentiation between soft or hard selective sweeps, and may be useful in the reconstruction of intra-host viral population demographic history.

Giant serpentine aneurysm mimics cerebral arteriovenous malformation on angiography.

A serpentine aneurysm is defined as a thrombosed giant aneurysm with internal channel, which mimics a giant arteriovenous malformation on angiography. We report a case of serpentine aneurysm and its radiological characters.

Mutation analysis of DARPP-32 as a candidate gene for schizophrenia.

Dopamine- and cAMP-regulated phosphoprotein of relative molecular mass 32kDa (DARPP-32) plays a pivotal role in the signal transduction of several neurotransmitters and neuromodulators that are implicated in the pathophysiology of a variety of neuropsychiatric disorders. A postmortem study reported a significantly reduced DARPP-32 expression in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia, suggesting possible involvement of DARPP-32 in the pathophysiology of schizophrenia. Hence, DARPP-32 was considered as a candidate gene for schizophrenia in this study. We first systemically searched for mutations in the DARPP-32 gene in 50 Han Chinese patients with schizophrenia from Taiwan. Five molecular variants were identified, including a C-to-G substitution (g.-2036C>G) in the putative core promoter that obliterated a predictive AP-2 transcription factor binding site, a G deletion in the untranslated exon 2 (g.1238delG), a G-to-A and an A-to-G substitutions in intron 2 (IVS2+31G>A) and intron 6 (IVS6+32A>G), respectively, and a three-base pair deletion of AGA in exon 6 that resulted in deletion of a glutamate at codon 135 (E135del). Further SNP- and haplotype-based association study in 249 patients and 273 control subjects, however, did not detect association of these markers with schizophrenia. Hence, our results suggest that the reduced DARPP-32 protein in patients with schizophrenia is unlikely caused by mutations in the DARPP-32 gene itself and the DARPP-32 gene is also unlikely a major susceptibility gene for schizophrenia. Nevertheless, the identification of these molecular variants should help the study of gene regulation and structure-function relationship of DARPP-32, and the association study of DARPP-32 gene with other neuropsychiatric disorders.

Identification of molecular variants at the promoter region of the human alpha 7 neuronal nicotinic acetylcholine receptor subunit gene but lack of association with schizophrenia.

The human alpha7 neuronal nicotinic receptor subunit gene has been considered as a candidate gene for P50 sensory gating deficit in schizophrenic patients. Because P50 sensory gating deficit is a common neurophysiological dysfunction in patients with schizophrenia and schizophrenia spectrum disorders, it is conceivable to hypothesize that the human alpha7 neuronal nicotinic receptor subunit gene might be a susceptible gene for schizophrenia. Researchers have reported that mutations in the protein-coding sequences of the human alpha7 neuronal nicotinic receptor subunit gene are very rare. Therefore, we searched for mutations at the promoter region of the human alpha7 neuronal nicotinic receptor subunit gene and performed a genetic association study in 249 unrelated Han Chinese schizophrenic patients and 273 non-psychotic subjects from Taiwan. Two molecular variants were identified and designated g.-213G>A and g.-324A>G, respectively. The g.-213G>A variant was found to obliterate a putative NF-1 transcription factor binding site using computer analysis. One out of 249 patients was detected to be a heterozygote for this variant, but none of 273 control subjects was. The g.-324A>G variant was also very rare in both patients and control subjects, only one heterozygote of this variant was identified in 249 patients and 273 control subjects, respectively. Hence, in this study, we did not find mutations in the human alpha7 neuronal nicotinic receptor subunit gene that are associated with schizophrenia in our population.