Artificial intelligence as a proficient tool in detecting pulmonary tuberculosis in massive population screening programs: a case study in Chennai, India.

Objective: To evaluate the performance of Genki, a computer-aided detection (CADe) software, in detecting tuberculosis (TB) using chest radiography in a mobile TB screening program in Chennai, India.

Materials And Methods: Genki, an AI-based CADe software, was employed in four mobile diagnostic units in remote areas of Chennai, India for screening TB. Patients from remote areas of Chennai who visited the vans and registered in the screening program underwent chest radiography, and the acquired X-ray scans were analyzed using Genki, which provided an assessment of each scan as either "TB suggestive" or "TB not suggestive".

Age associated susceptibility to SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still an ongoing global health crisis. Clinical data indicate that the case fatality rate (CFR) is age dependent, with a higher CFR percentage in the elderly population. We compared the pathogenesis of SARS-CoV-2 in young and aged K18-hACE2 transgenic mice.

Aerosolized sulfated hyaluronan derivatives prolong the survival of K18 ACE2 mice infected with a lethal dose of SARS-CoV-2.

Despite several vaccines that are currently approved for human use to control the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent medical need for therapeutic and prophylactic options. SARS-CoV-2 binding and entry in human cells involves interactions of its spike (S) protein with several host cell surface factors, including heparan sulfate proteoglycans (HSPGs), transmembrane protease serine 2 (TMPRSS2), and angiotensin-converting enzyme 2 (ACE2). In this paper we investigated the potential of sulphated Hyaluronic Acid (sHA), a HSPG mimicking polymer, to inhibit the binding of SARS-CoV-2 S protein to human ACE2 receptor.

Aid or Antagonize: Nuclear Long Noncoding RNAs Regulate Host Responses and Outcomes of Viral Infections.

Long noncoding RNAs (lncRNAs) are transcripts measuring >200 bp in length and devoid of protein-coding potential. LncRNAs exceed the number of protein-coding mRNAs and regulate cellular, developmental, and immune pathways through diverse molecular mechanisms. In recent years, lncRNAs have emerged as epigenetic regulators with prominent roles in health and disease.

Validation of a Deep Learning Model for Detecting Chest Pathologies from Digital Chest Radiographs.

Manual interpretation of chest radiographs is a challenging task and is prone to errors. An automated system capable of categorizing chest radiographs based on the pathologies identified could aid in the timely and efficient diagnosis of chest pathologies. For this retrospective study, 4476 chest radiographs were collected between January and April 2021 from two tertiary care hospitals.

Levels of Autonomous Radiology.

Radiology, being one of the younger disciplines of medicine with a history of just over a century, has witnessed tremendous technological advancements and has revolutionized the way we practice medicine today. In the last few decades, medical imaging modalities have generated seismic amounts of medical data. The development and adoption of artificial intelligence applications using this data will lead to the next phase of evolution in radiology.

A deep learning approach for automated diagnosis of pulmonary embolism on computed tomographic pulmonary angiography.

Background: Computed tomographic pulmonary angiography (CTPA) is the diagnostic standard for confirming pulmonary embolism (PE). Since PE is a life-threatening condition, early diagnosis and treatment are critical to avoid PE-associated morbidity and mortality. However, PE remains subject to misdiagnosis.

Observer performance evaluation of the feasibility of a deep learning model to detect cardiomegaly on chest radiographs.

Background: Cardiothoracic ratio (CTR) is the ratio of the diameter of the heart to the diameter of the thorax. An abnormal CTR (>0.55) is often an indicator of an underlying pathological condition.

Evaluating the Association Between Comorbidities and COVID-19 Severity Scoring on Chest CT Examinations Between the Two Waves of COVID-19: An Imaging Study Using Artificial Intelligence.

Background Coronavirus disease 2019 (COVID-19) has accounted for over 352 million cases and five million deaths globally. Although it affects populations across all nations, developing or transitional, of all genders and ages, the extent of the specific involvement is not very well known. This study aimed to analyze and determine how different were the first and second waves of the COVID-19 pandemic by assessing computed tomography severity scores (CT-SS).

Localization of infection in neonatal rhesus macaques after oral viral challenge.

Vertical transmission of human immunodeficiency virus (HIV) can occur in utero, during delivery, and through breastfeeding. We utilized Positron Emission Tomography (PET) imaging coupled with fluorescent microscopy of 64Cu-labeled photoactivatable-GFP-HIV (PA-GFP-BaL) to determine how HIV virions distribute and localize in neonatal rhesus macaques two and four hours after oral viral challenge. Our results show that by four hours after oral viral exposure, HIV virions localize to and penetrate the rectal mucosa.

6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro.

The emergence of SARS-CoV-2 has led to a global health crisis that, in addition to vaccines and immunomodulatory therapies, calls for the identification of antiviral therapeutics. The papain-like protease (PLpro) activity of nsp3 is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG), an orally available and widely available generic drug, inhibits SARS-CoV-2 replication in Vero-E6 cells with an EC50 of approximately 2 μM.

Efficient Inhibition of HIV Using CRISPR/Cas13d Nuclease System.

Recently discovered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas13 proteins are programmable RNA-guided ribonucleases that target single-stranded RNA (ssRNA). CRISPR/Cas13-mediated RNA targeting has emerged as a powerful tool for detecting and eliminating RNA viruses. Here, we demonstrate the effectiveness of CRISPR/Cas13d to inhibit HIV-1 replication.

Real-world analysis of artificial intelligence in musculoskeletal trauma.

Musculoskeletal trauma accounts for a large percentage of emergency room visits and is amongst the top causes of unscheduled patient visits to the emergency room. Musculoskeletal trauma results in expenditure of billions of dollars and protracted losses of quality-adjusted life years. New and innovative methods are needed to minimise the impact by ensuring quick and accurate assessment.

Key Technology Considerations in Developing and Deploying Machine Learning Models in Clinical Radiology Practice.

The use of machine learning to develop intelligent software tools for the interpretation of radiology images has gained widespread attention in recent years. The development, deployment, and eventual adoption of these models in clinical practice, however, remains fraught with challenges. In this paper, we propose a list of key considerations that machine learning researchers must recognize and address to make their models accurate, robust, and usable in practice.

Mapping functional humoral correlates of protection against malaria challenge following RTS,S/AS01 vaccination.

Vaccine development has the potential to be accelerated by coupling tools such as systems immunology analyses and controlled human infection models to define the protective efficacy of prospective immunogens without expensive and slow phase 2b/3 vaccine studies. Among human challenge models, controlled human malaria infection trials have long been used to evaluate candidate vaccines, and RTS,S/AS01 is the most advanced malaria vaccine candidate, reproducibly demonstrating 40 to 80% protection in human challenge studies in malaria-naïve individuals. Although antibodies are critical for protection after RTS,S/AS01 vaccination, antibody concentrations are inconsistently associated with protection across studies, and the precise mechanism(s) by which vaccine-induced antibodies provide protection remains enigmatic.

Author Correction: CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome.

Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted in a corresponding change in CCR5 expression on CD4 T cells.

Lymphocytes upregulate CD36 in adipose tissue and liver.

CD36 is a multifunctional scavenger receptor and lipid transporter implicated in metabolic and inflammatory pathologies, as well as cancer progression. CD36 is known to be expressed by adipocytes and monocytes/macrophages, but its expression by T cells is not clearly established. We found that CD4 and CD8 T cells in adipose tissue and liver of humans, monkeys, and mice upregulated CD36 expression (ranging from ~5-40% CD36+), whereas little to no CD36 was expressed by T cells in blood, spleen, and lymph nodes.

DNA Vaccine-Induced Long-Lasting Cytotoxic T Cells Targeting Conserved Elements of Human Immunodeficiency Virus Gag Are Boosted Upon DNA or Recombinant Modified Vaccinia Ankara Vaccination.

DNA-based vaccines able to induce efficient cytotoxic T-cell responses targeting conserved elements (CE) of human immunodeficiency virus type 1 (HIV-1) Gag have been developed. These CE were selected by stringent conservation, the ability to induce T-cell responses with broad human leukocyte antigen coverage, and the association between recognition of CE epitopes and viral control in HIV-infected individuals. Based on homology to HIV, a simian immunodeficiency virus p27 CE DNA vaccine has also been developed.

Anti-HIV IgM protects against mucosal SHIV transmission.

Objective: Worldwide, most new HIV infections occur through mucosal exposure. Immunoglobulin M (IgM) is the first antibody class generated in response to infectious agents; IgM is present in the systemic circulation and in mucosal fluids as secretory IgM. We sought to investigate for the first time the role of IgM in preventing AIDS virus acquisition in vivo.

Mucosal IgA Responses: Damaged in Established HIV Infection-Yet, Effective Weapon against HIV Transmission.

HIV infection not only destroys CD4 T cells but also inflicts serious damage to the B-cell compartment, such as lymphadenopathy, destruction of normal B-cell follicle architecture, polyclonal hypergammaglobulinemia, increased apoptosis of B cells, and irreversible loss of memory B-cell responses with advanced HIV disease. Subepithelial B cells and plasma cells are also affected, which results in loss of mucosal IgG and IgA antibodies. This leaves the mucosal barrier vulnerable to bacterial translocation.

Posttranscriptional Regulation of HLA-A Protein Expression by Alternative Polyadenylation Signals Involving the RNA-Binding Protein Syncrip.

Genomic variation in the untranslated region (UTR) has been shown to influence HLA class I expression level and associate with disease outcomes. Sequencing of the 3'UTR of common alleles indicated the presence of two polyadenylation signals (PAS). The proximal PAS is conserved, whereas the distal PAS is disrupted within certain alleles by sequence variants.

DNA Prime-Boost Vaccine Regimen To Increase Breadth, Magnitude, and Cytotoxicity of the Cellular Immune Responses to Subdominant Gag Epitopes of Simian Immunodeficiency Virus and HIV.

HIV sequence diversity and the propensity of eliciting immunodominant responses targeting variable regions of the HIV proteome are hurdles in the development of an effective AIDS vaccine. An HIV-derived conserved element (CE) p24 plasmid DNA (pDNA) vaccine is able to redirect immunodominant responses to otherwise subdominant and often more vulnerable viral targets. By homology to the HIV immunogen, seven CE were identified in SIV p27 Analysis of 31 rhesus macaques vaccinated with full-length SIV gag pDNA showed inefficient induction (58% response rate) of cellular responses targeting these CE.

Dose-dependent inhibition of Gag cellular immunity by Env in SIV/HIV DNA vaccinated macaques.

The induction of a balanced immune response targeting the major structural proteins, Gag and Env of HIV, is important for the development of an efficacious vaccine. The use of DNA plasmids expressing different antigens offers the opportunity to test in a controlled manner the influence of different vaccine components on the magnitude and distribution of the vaccine-induced cellular and humoral immune responses. Here, we show that increasing amounts of env DNA results in greatly enhanced Env antibody titers without significantly affecting the levels of anti-Env cellular immune responses.

A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques.

Background: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs.

Methods: To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1.