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Bioinformatics (Oxford, England) Jun 2024World Health Organization estimates that there were over 10 million cases of tuberculosis (TB) worldwide in 2019, resulting in over 1.4 million deaths, with a worrisome...
MOTIVATION
World Health Organization estimates that there were over 10 million cases of tuberculosis (TB) worldwide in 2019, resulting in over 1.4 million deaths, with a worrisome increasing trend yearly. The disease is caused by Mycobacterium tuberculosis (MTB) through airborne transmission. Treatment of TB is estimated to be 85% successful, however, this drops to 57% if MTB exhibits multiple antimicrobial resistance (AMR), for which fewer treatment options are available.
RESULTS
We develop a robust machine-learning classifier using both linear and nonlinear models (i.e. LASSO logistic regression (LR) and random forests (RF)) to predict the phenotypic resistance of Mycobacterium tuberculosis (MTB) for a broad range of antibiotic drugs. We use data from the CRyPTIC consortium to train our classifier, which consists of whole genome sequencing and antibiotic susceptibility testing (AST) phenotypic data for 13 different antibiotics. To train our model, we assemble the sequence data into genomic contigs, identify all unique 31-mers in the set of contigs, and build a feature matrix M, where M[i, j] is equal to the number of times the ith 31-mer occurs in the jth genome. Due to the size of this feature matrix (over 350 million unique 31-mers), we build and use a sparse matrix representation. Our method, which we refer to as MTB++, leverages compact data structures and iterative methods to allow for the screening of all the 31-mers in the development of both LASSO LR and RF. MTB++ is able to achieve high discrimination (F-1 >80%) for the first-line antibiotics. Moreover, MTB++ had the highest F-1 score in all but three classes and was the most comprehensive since it had an F-1 score >75% in all but four (rare) antibiotic drugs. We use our feature selection to contextualize the 31-mers that are used for the prediction of phenotypic resistance, leading to some insights about sequence similarity to genes in MEGARes. Lastly, we give an estimate of the amount of data that is needed in order to provide accurate predictions.
AVAILABILITY
The models and source code are publicly available on Github at https://github.com/M-Serajian/MTB-Pipeline.
PubMed: 38940175
DOI: 10.1093/bioinformatics/btae243 -
The rapidly progressing and fatal outcome of rhombencephalitis by listeriosis in a 61-year-old male.Annals of Agricultural and... Jun 2024Listeria monocytogenes is a Gram-positive facultative anaerobic bacterium that is ubiquitous in the environment and can cause severe infections in immunocompromised...
Listeria monocytogenes is a Gram-positive facultative anaerobic bacterium that is ubiquitous in the environment and can cause severe infections in immunocompromised individuals, pregnant women, and newborns. Listeriosis can manifest as meningitis, encephalitis, or sepsis, and its diagnosis requires a high index of suspicion. The case is reported of a rare presentation of rhombencephalitis by listeriosis in a 61-year-old male who initially suffered from subacute gastric disturbances and fever. Neurological consultation showed abnormal functions of cranial nerves and meningeal signs were observed. MRI revealed a poorly demarcated focus of approximately 45 × 16 × 15mm, indicating possible inflammatory processes, necessitating a lumbar puncture. Assessment of the CSF indicated infection with the bacterium- Listeria Monocytogenes, with the final diagnosis of Listeriosis encephalitis. Despite antibiotic therapy of Ceftazidine and Ampicillin, the patient's condition deteriorated, followed by death.
Topics: Humans; Male; Listeriosis; Middle Aged; Fatal Outcome; Listeria monocytogenes; Encephalitis; Anti-Bacterial Agents; Rhombencephalon
PubMed: 38940119
DOI: 10.26444/aaem/178178 -
Annals of Agricultural and... Jun 2024As globalization and modernization continue to impact people's lives, a significant shift in lifestyle has taken place, resulting in a worldwide decrease in physical... (Review)
Review
INTRODUCTION AND OBJECTIVE
As globalization and modernization continue to impact people's lives, a significant shift in lifestyle has taken place, resulting in a worldwide decrease in physical activity and an increase in unhealthy eating patterns. Physical inactivity has become the fourth leading cause of death globally. The aim of this scoping review is to analyze the concept and development of integrating physical activity into healthcare (IPAHc), based on the principles of sports and exercise medicine (SEM) and exercise is medicine (EIM).
REVIEW METHODS
A systematic search was conducted of relevant published studies with full text using PubMed, Scopus, Web of Science, Academic Search Ultimate, Medline, and SPORTDiscus, via the EBSCO search platform.
BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE
Twenty-nine studies met the inclusion criteria. The integration pathway centres around physical activity consultation and/or referral, and information technology which has been extensively utilized in IPAHc, including websites, electronic medical records, social media, wearable devices, mobile software, and referral tools. SEM and EIM face numerous implementation challenges, such as time constraints, education/training, resources, and tools.
SUMMARY
The concept of IPAHc involves the integration of Physical Activity Vital Signs (PAVS) into electronic medical records to evaluate the physical activity levels of the general population. This can assist individuals in achieving fitness goals, preventing diseases, treating existing illnesses, and undergoing rehabilitation. IPAHc has been in development for many years and is now being explored in practice. Despite the widespread use of information technology in this integration process, a number of challenges still need addressing.
PubMed: 38940098
DOI: 10.26444/aaem/183778 -
Journal of Integrative Neuroscience Jun 2024Excessively high or synchronized neuronal activity in the brain is the underlying cause of epilepsy, a condition of the central nervous system. Epilepsy is caused mostly... (Review)
Review
Excessively high or synchronized neuronal activity in the brain is the underlying cause of epilepsy, a condition of the central nervous system. Epilepsy is caused mostly by an imbalance in the activity of inhibitory and excitatory neural networks. Recurrent or prolonged seizures lead to neuronal death, which in turn promotes epileptogenesis and epileptic seizures. Ferrous ion-mediated cell death is known as ferroptosis, which is due to the accumulation of lipid peroxidation products resulting from compromise of the glutathione (GSH)-dependent antioxidant system. The pathophysiology of epilepsy has been linked to anomalies in the glutathione peroxidase 4 (GPX4)/GSH redox pathway, lipid peroxidation, and iron metabolism. Studies have shown that inhibiting ferroptosis may alleviate cognitive impairment and decrease seizures, indicating that it is neuroprotective. With the hope of aiding the development of more novel approaches for the management of epilepsy, this research aimed to examine the role of ferroptosis in this disease.
PubMed: 38940095
DOI: 10.31083/j.jin2306113 -
International Journal of Gynaecology... Jun 2024To determine the trend in adolescent maternal deaths and deliveries over a period of 5 years and 9 months (July 2014-March 2020) at the Ekurhuleni Health District in...
OBJECTIVE
To determine the trend in adolescent maternal deaths and deliveries over a period of 5 years and 9 months (July 2014-March 2020) at the Ekurhuleni Health District in South Africa.
METHODS
The present study was a retrospective review and secondary data analysis using data from the District Health Information System and clinical oversight data from the District Clinical Specialist Team. The study population was adolescent pregnant women aged 10-19 years who died at health facilities. Descriptive and inferential statistics were used for analysis.
RESULTS
There was a total of 12 559 adolescent deliveries. Adolescent birth rate was lower than that of sub-Saharan Africa. Adolescent deaths (n = 37) contributed to around 8% of the total maternal deaths. Deliveries (97%) and deaths (98%) were most common among women aged 15-19 years. Six (16%) women had a repeat pregnancy. A total of 21 (57%) had booked for antenatal care. There were few antenatal visits (mean 4 ± SD 2.1). The main three causes of death were hypertension (35%) followed by hemorrhage (24%) and suicide (14%). Postpartum deaths (62%) were significantly (chi-square test, P = 0.02) higher than antepartum deaths (38%). The majority (73%) of newborns were born alive which was significantly (chi-square test, P = 0.002) higher than those which were stillborn (27%).
CONCLUSION
The main challenges were the high number of adolescent deliveries, repeat pregnancies, and preventable causes of death. Multidisciplinary collaboration involving obstetricians, midwives, pediatricians, school health services, social workers and psychologists is indispensable for comprehensive management, prioritizing pregnancy prevention among this vulnerable group.
PubMed: 38940071
DOI: 10.1002/ijgo.15763 -
Frontiers in Bioscience (Landmark... Jun 2024The endoplasmic reticulum (ER) played an important role in the folding, assembly and post-translational modification of proteins. ER homeostasis could be disrupted by... (Review)
Review
The endoplasmic reticulum (ER) played an important role in the folding, assembly and post-translational modification of proteins. ER homeostasis could be disrupted by the accumulation of misfolded proteins, elevated reactive oxygen species (ROS) levels, and abnormal Ca2+ signaling, which was referred to ER stress (ERS). Ferroptosis was a unique programmed cell death model mediated by iron-dependent phospholipid peroxidation and multiple signaling pathways. The changes of mitochondrial structure, the damage of glutathione peroxidase 4 (GPX4) and excess accumulation of iron were the main characteristics of ferroptosis. ROS produced by ferroptosis can interfere with the activity of protein-folding enzymes, leading to the accumulation of large amounts of unfolded proteins, thus causing ERS. On the contrary, the increase of ERS level could promote ferroptosis by the accumulation of iron ion and lipid peroxide, the up-regulation of ferroptosis related genes. At present, the studies on the relationship between ferroptosis and ERS were one-sided and lack of in-depth studies on the interaction mechanism. This review aimed to explore the molecular mechanism of cross-talk between ferroptosis and ERS, and provide new strategies and targets for the treatment of liver diseases.
Topics: Ferroptosis; Humans; Endoplasmic Reticulum Stress; Liver Diseases; Reactive Oxygen Species; Animals; Signal Transduction; Iron; Lipid Peroxidation; Endoplasmic Reticulum
PubMed: 38940044
DOI: 10.31083/j.fbl2906221 -
Frontiers in Bioscience (Landmark... Jun 2024This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated...
BACKGROUND
This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth.
METHODS
The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between expression and its downstream genes was analyzed in a melanoma tissue array.
RESULTS
TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between expression and the expression of , , and . Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth.
CONCLUSIONS
TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.
Topics: Humans; Endoplasmic Reticulum Stress; Melanoma; Cell Line, Tumor; Cell Survival; Gene Expression Regulation, Neoplastic; Cell Death; Apoptosis; Cell Proliferation; Membrane Proteins
PubMed: 38940043
DOI: 10.31083/j.fbl2906233 -
Frontiers in Bioscience (Landmark... Jun 2024Gastric cancer (GC) is a leading cause of cancer-associated death worldwide. Its molecular mechanisms, especially concerning autophagy and various signaling pathways,...
BACKGROUND
Gastric cancer (GC) is a leading cause of cancer-associated death worldwide. Its molecular mechanisms, especially concerning autophagy and various signaling pathways, are not fully understood. Fatty Acid Binding Protein 6 () and RE1 Silencing Transcription Factor () emerge as potential key players in this context. This study sought to analyze the functional relationship of and concerning autophagy and their implications on the Akt/mTOR signaling pathway within GC cells.
METHODS
A comprehensive bioinformatics approach was used to identify key prognostic markers in GC. The effects of and on autophagy along with Akt/mTOR signaling pathways were analyzed by techniques including Western blotting (WB), flow cytometry, Transwell assay, dual luciferase reporter assay, and others.
RESULTS
was identified as overexpressed in GC, linked with poor prognosis. silencing reduces GC cell proliferation, induces S- and G2-phase arrest, and downregulates cyclins CDK2 and CDK4. It also inhibited GC cell invasion/migration and autophagy, effects that were counteracted by MG132. When combined with PI3K inhibitor LY294002c, knockdown showed synergistic anti-proliferative effects, modulating the Akt/mTOR pathway. Besides, the transcription factor has been shown to directly regulate expression, affecting autophagy and the Akt/mTOR signaling pathway in a -dependent manner.
CONCLUSIONS
positively regulates autophagy and negatively affects the Akt/mTOR signaling pathway in GC cells in a FABP6-dependent manner, providing valuable insights into regulatory networks involving and .
Topics: Humans; Stomach Neoplasms; TOR Serine-Threonine Kinases; Autophagy; Proto-Oncogene Proteins c-akt; Signal Transduction; Cell Line, Tumor; Fatty Acid-Binding Proteins; Cell Proliferation; Gene Expression Regulation, Neoplastic
PubMed: 38940038
DOI: 10.31083/j.fbl2906212 -
Frontiers in Bioscience (Landmark... Jun 2024Traumatic spinal cord injury (SCI) is a serious disease of the central nervous system. Aside from the limited intrinsic regenerative capacity of neurons, complex... (Review)
Review
Traumatic spinal cord injury (SCI) is a serious disease of the central nervous system. Aside from the limited intrinsic regenerative capacity of neurons, complex microenvironmental disturbances can also lead to further cellular damage and growth inhibition. Programmed cell death regulated by pyroptosis has an important role in the pathogenesis of SCI. While there has been a wealth of new knowledge regarding cellular pyroptosis, a detailed understanding of its role in SCI and possible therapeutic strategies is still lacking. This review summarizes current advances in the regulatory role of pyroptosis-regulated cell death and inflammasome components in the inhibitory microenvironment following SCI, as well as recent therapeutic advances.
Topics: Spinal Cord Injuries; Humans; Pyroptosis; Inflammasomes; Animals; Neurons
PubMed: 38940037
DOI: 10.31083/j.fbl2906210 -
Frontiers in Bioscience (Landmark... May 2024Lung cancer is the primary cause of cancer-related deaths, with one of the highest incidence and mortality rates of all malignant tumors. Dysregulated expression of...
BACKGROUND
Lung cancer is the primary cause of cancer-related deaths, with one of the highest incidence and mortality rates of all malignant tumors. Dysregulated expression of DEPDC1B has been reported to occur in various tumor types. However, the functional implications of this alteration in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we investigated the role and clinical significance of DEPDC1B in LUAD.
METHODS
The expression of DEPDC1B in LUAD and its relationship with prognosis were systematically evaluated in several publically available datasets. The effects of DEPDC1B knockdown on the proliferation and motility of LUAD cells were assessed using the JULI Stage Real-time Cell History Recorder, while the effect of knockdown on the cell cycle was studied by flow cytometry. Furthermore, RNA-Sequencing (RNA-Seq) analysis was conducted to identify the downstream target genes and pathways regulated by DEPDC1B. Correlations between the expression of DEPDC1B and immune cell infiltration, immunotherapy resistance, and chemoresistance were also examined. Additionally, molecular biological methods were used to explore the regulatory mechanism of B-Myb on DEPDC1B expression.
RESULTS
DEPDC1B was found to be upregulated in LUAD patients and this was associated with poor clinical outcomes. Knockdown of inhibited cell growth, migration and motility, as well as cell cycle progression. Knockdown also resulted in the down-regulation of several downstream genes, including , , and , as well as the inactivation of multiple critical pathways, such as the ERK and PI3K-AKT pathways. Analysis of the tumor immuno-environment in LUAD revealed that high DEPDC1B expression was associated with an abundance of activated CD4+ memory T cells, M0 macrophages, M1 macrophages, and CD8+ T cells. Moreover, these tumors responded poorly to immunotherapy. Analysis of chemo-drug sensitivity showed that LUADs with high DEPDC1B expression were more responsive to frontline chemotherapeutic drugs such as Vinorelbine, Cisplatin, and Etoposide. Additionally, mechanistic investigations revealed that DEPDC1B is a direct target gene of B-Myb, and that its knockdown attenuated the proliferation and motility effects of B-Myb.
CONCLUSIONS
In summary, our findings indicate that DEPDC1B is a critical regulator during the malignant progression of LUAD. DEPDC1B could therefore be a promising prognostic marker and therapeutic target in LUAD diagnosis and treatment.
Topics: Humans; Adenocarcinoma of Lung; GTPase-Activating Proteins; Lung Neoplasms; Cell Proliferation; Cell Movement; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Disease Progression; Cell Cycle Proteins; Prognosis; Drug Resistance, Neoplasm; Male; Gene Knockdown Techniques; Signal Transduction; Neoplasm Proteins; Trans-Activators
PubMed: 38940035
DOI: 10.31083/j.fbl2906204