Deep learning for NAD/NADP cofactor prediction and engineering using transformer attention analysis in enzymes.

Understanding and manipulating the cofactor preferences of NAD(P)-dependent oxidoreductases, the most widely distributed enzyme group in nature, is increasingly crucial in bioengineering. However, large-scale identification of the cofactor preferences and the design of mutants to switch cofactor specificity remain as complex tasks. Here, we introduce DISCODE (Deep learning-based Iterative pipeline to analyze Specificity of COfactors and to Design Enzyme), a novel transformer-based deep learning model to predict NAD(P) cofactor preferences.

An Optimized Method for Reconstruction of Transcriptional Regulatory Networks in Bacteria Using ChIP-exo and RNA-seq Datasets.

Transcriptional regulatory networks (TRNs) in bacteria are crucial for elucidating the mechanisms that regulate gene expression and cellular responses to environmental stimuli. These networks delineate the interactions between transcription factors (TFs) and their target genes, thereby uncovering the regulatory processes that modulate gene expression under varying environmental conditions. Analyzing TRNs offers valuable insights into bacterial adaptation, stress responses, and metabolic optimization from an evolutionary standpoint.

Unveiling the novel regulatory roles of RpoD-family sigma factors in Salmonella Typhimurium heat shock response through systems biology approaches.

Three RpoD-family sigma factors, RpoD, RpoS, and RpoH, play critical roles in transcriptional regulation in Salmonella enterica serovar Typhimurium under heat shock conditions. However, the genome-wide regulatory mechanisms of these sigma factors in response to heat stress have remained elusive. In this study, we comprehensively identified 2,319, 2,226, and 213 genome-wide binding sites for RpoD, RpoS, and RpoH, respectively, under sublethal heat shock conditions (42°C).

Thermomechanical and Structural Analysis of WO Array for Optimized Photoelectrochemical Chloride Oxidation Performance.

Understanding the crystal structure of WO is essential for optimizing its photoelectrochemical performance. This study comprehensively analyzes the structural characteristics of WO during synthesis and investigates their correlation with photoelectrochemical activity. Structural analysis, incorporating annealing procedure and WO thickness, identifies a blend of hexagonal, monoclinic, and orthorhombic phases within WO array.

Use of acetate as substrate for sustainable production of homoserine and threonine by Escherichia coli W3110: A modular metabolic engineering approach.

Acetate, a promising yet underutilized carbon source for biological production, was explored for the efficient production of homoserine and threonine in Escherichia coli W. A modular metabolic engineering approach revealed the crucial roles of both acetate assimilation pathways (AckA/Pta and Acs), optimized TCA cycle flux and glyoxylate shunt activity, and enhanced CoA availability, mediated by increased pantothenate kinase activity, for efficient homoserine production. The engineered strain W-H22/pM2/pR1P exhibited a high acetate assimilation rate (5.

Neoadjuvant chemotherapy is associated with improved disease-free survival in pancreatic cancer patients undergoing pancreaticoduodenectomy with vascular resection.

Background And Objectives: Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown.

Experimental promoter identification of a foodborne pathogen subsp. serovar Typhimurium with near single base-pair resolution.

serovar Typhimurium ( Typhimurium) is a common foodborne pathogen which is frequently used as the reference strain for . Investigating the sigma factor network and protomers is crucial to understand the genomic and transcriptomic properties of the bacterium. Its promoters were identified using various methods such as dRNA-seq, ChIP-chip, or ChIP-Seq.

Sarcoma in patients with Lynch syndrome and response to immunotherapy.

Background: Lynch syndrome (LS) is an autosomal dominant genetic predisposition to multiple malignancies and is characterized by deficient DNA mismatch repair. Increased incidence of sarcomas is not formally ascribed to LS; however, increasing evidence suggests a preponderance of these malignancies in affected families. Sarcomas typically possess a low tumor mutational burden and incite a poor immune infiltrate, thereby rendering them poorly responsive to immunotherapy.

Blanket antimicrobial resistance gene database with structural information, BOARDS, provides insights on historical landscape of resistance prevalence and effects of mutations in enzyme structure.

Antimicrobial resistance (AMR) in pathogenic bacteria poses a significant threat to public health, yet there is still a need for development in the tools to deeply understand AMR genes based on genetic or structural information. In this study, we present an interactive web database named Blanket Overarching Antimicrobial-Resistance gene Database with Structural information (BOARDS, sbml.unist.

Posterior canal benign paroxysmal positional vertigo with long duration: Heavy or light cupula?

Objective: To investigate the characteristics of positional nystagmus in posterior semicircular canal (PSCC) benign paroxysmal positional vertigo (BPPV) patients with longer durations, and to discuss the possible underlying mechanism of this nystagmus.

Methods: We conducted a retrospective review, and enrolled 118 consecutive patients with unilateral PSCC BPPV. The duration of nystagmus during a Dix-Hallpike test was classified into short (<1 min) and long (≥1 min) durations.

Surgical and Endoscopic Resection of Duodenal Neuroendocrine Tumors Have Similar Disease-Specific Survival Outcome.

Background: Duodenal neuroendocrine tumors (dNETs) are rare, and their management is not well-defined. National Comprehensive Cancer Network (NCCN) guidelines recommend surgical resection of large dNETs (> 2 cm) and endoscopic resection of small tumors (< 2 cm). We compared the survival outcomes between surgical and endoscopic resection in various dNET sizes.

Laparoscopic compared to open approach for distal gastrectomy may reduce pneumonia risk for patients with gastric cancer.

Background: Whether laparoscopic approach to gastrectomy for gastric cancer (GC) reduces the risk of pneumonia remains unknown. In this study, we compared pneumonia outcomes for patients with GC who underwent either laparoscopic gastrectomy (LG) or open gastrectomy (OG).

Methods: The ACS NSQIP database was queried to identify patients with GC who underwent LG or OG between Jan 2012 - Dec 2018.

Learning Curves in Establishing a New Minimally Invasive Pancreas Program.

Introduction: Robotic pancreaticoduodenectomy (rPD) is a complex operation with a reported learning curve of 80 cases. Two recent graduates of a formal robotic complex general surgical oncology training program have been performing rPD at our institution since 2016, which had no previous institutional experience with rPD.

Objective: To evaluate the learning curve associated with developing a new robotic pancreaticoduodenectomy (rPD) program by fellowship trained surgeons with institutional support.

MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell-intrinsic Amplification of Type I IFN Signaling.

Purpose: Stimulator of interferon genes (STING) agonists are currently in development for treatment of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Response rates to STING agonists alone have been promising yet modest, and combination therapies will likely be required to elicit their full potency. We sought to identify combination therapies and mechanisms that augment the tumor cell-intrinsic effect of therapeutically relevant STING agonists apart from their known effects on tumor immunity.

Histological subtypes of hepatocellular carcinoma: Their clinical and prognostic significance.

Assigning a hepatocellular carcinoma (HCC) to an appropriate subtype is important because this guarantees the diagnosis and treatment and allows decisions regarding the prognosis of the patient. HCC subtyping is usually based on the World Health Organization (WHO) classification and the 2019 fifth edition is the latest version. However, the WHO classification system is still in evolution and has limited clinical relevance.

Spontaneous Nystagmus in Patients With Posterior Semicircular Canal Benign Paroxysmal Positional Vertigo.

Objective: This study aimed to investigate the incidence of spontaneous nystagmus (SN) in posterior semicircular canal (PSCC) benign paroxysmal positional vertigo (BPPV) and its effect on treatment outcomes.

Study Design: Retrospective case series.

Setting: Tertiary referral center.

B7-H3 expression is associated with high PD-L1 expression in clear cell renal cell carcinoma and predicts poor prognosis.

Background: Clear cell Renal cell carcinoma (ccRCC) is an immunogenic tumor. B7 family members, such as CTLA-4, PD-1, and PD-L1, are the main components of immune checkpoints that regulate various immune responses. Specifically, B7-H3 regulates T cell-mediated immune responses against cancer.

Deep-learning optimized DEOCSU suite provides an iterable pipeline for accurate ChIP-exo peak calling.

Recognizing binding sites of DNA-binding proteins is a key factor for elucidating transcriptional regulation in organisms. ChIP-exo enables researchers to delineate genome-wide binding landscapes of DNA-binding proteins with near single base-pair resolution. However, the peak calling step hinders ChIP-exo application since the published algorithms tend to generate false-positive and false-negative predictions.

Model-driven experimental design workflow expands understanding of regulatory role of Nac in .

The establishment of experimental conditions for transcriptional regulator network (TRN) reconstruction in bacteria continues to be impeded by the limited knowledge of activating conditions for transcription factors (TFs). Here, we present a novel genome-scale model-driven workflow for designing experimental conditions, which optimally activate specific TFs. Our model-driven workflow was applied to elucidate transcriptional regulation under nitrogen limitation by Nac and NtrC, in .

Vestibular Schwannoma Presenting as Acute Vertigo Mimicking Vestibular Neuritis.

Vestibular schwannoma (VS) is commonly accompanied by hearing loss, tinnitus, and dizziness and tends to be chronically progressive in nature. We report a case of VS presenting as left vestibular neuritis (VN) in a previously healthy 57-year-old patient. Right-beating horizontal-torsional spontaneous nystagmus was observed, and the bedside head impulse test revealed a left catch-up saccade.

The stromal tumor-infiltrating lymphocytes, cancer stemness, epithelial-mesenchymal transition, and B7-H4 expression in ovarian serous carcinoma.

Background: B7-H4 is expressed in various types of cancers and its expression inversely correlates with the degree of tumor-infiltrating lymphocytes (TILs). Studies have shown the relationship between B7-H4, cancer stem cell (CSC) properties, and epithelial-mesenchymal transition (EMT) in various cancers. However, very few studies have investigated the relationship between B7-H4, TILs, cancer stemness, and EMT in epithelial ovarian cancer (EOC).