An Integrated Framework for Infectious Disease Control Using Mathematical Modeling and Deep Learning.

Infectious diseases are a major global public health concern. Precise modeling and prediction methods are essential to develop effective strategies for disease control. However, data imbalance and the presence of noise and intensity inhomogeneity make disease detection more challenging.

Knockdown resistance mutations in Phlebotomus argentipes sand flies in Bihar, India.

Background: Vector control based on indoor residual spraying (IRS) is one of the main components of the visceral leishmaniasis (VL) elimination programme in India. Dichlorodiphenyltrichloroethane (DDT) was used for IRS until 2015 and was later replaced by the synthetic pyrethroid alpha-cypermethrin. Both classes of insecticides share the same target site, the voltage-gated sodium channel (Vgsc).

Mevalonate kinase of Leishmania donovani promotes its survival and plays a pivotal role in pathogenesis.

The infectivity of Leishmania is determined by its ability to invade and evade host and its thriving capacity within the macrophage. Our study revealed the role of Leishmania donovani mevalonate kinase (MVK), an enzyme of mevalonate pathway in visceral leishmaniasis pathogenesis. Peritoneal exudate cells (PEC)-derived macrophages from BALB/c mice were infected with wild type (WT), MVK over expressing (MVK OE) and knockdown (KD) parasites and MVK OE parasites were found to be more infective than WT and MVK KD parasites.

A phase II, non-comparative randomised trial of two treatments involving liposomal amphotericin B and miltefosine for post-kala-azar dermal leishmaniasis in India and Bangladesh.

Background: In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF.

Heterogeneous identity, stiffness and growth characterise the shoot apex of Arabidopsis stem cell mutants.

Stem cell homeostasis in the shoot apical meristem involves a core regulatory feedback loop between the signalling peptide CLAVATA3 (CLV3), produced in stem cells, and the transcription factor WUSCHEL, expressed in the underlying organising centre. clv3 mutant meristems display massive overgrowth, which is thought to be caused by stem cell overproliferation, although it is unknown how uncontrolled stem cell divisions lead to this altered morphology. Here, we reveal local buckling defects in mutant meristems, and use analytical models to show how mechanical properties and growth rates may contribute to the phenotype.

Skin pharmacokinetics of miltefosine in the treatment of post-kala-azar dermal leishmaniasis in South Asia.

Introduction: Post-kala-azar dermal leishmaniasis (PKDL) arises as a dermal complication following a visceral leishmaniasis (VL) infection. Current treatment options for PKDL are unsatisfactory, and there is a knowledge gap regarding the distribution of antileishmanial compounds within human skin. The present study investigated the skin distribution of miltefosine in PKDL patients, with the aim to improve the understanding of the pharmacokinetics at the skin target site in PKDL.

ACDSSNet: Atrous Convolution-Based Deep Semantic Segmentation Network for Efficient Detection of Sickle Cell Anemia.

In medical image processing, semantic segmentation plays an important role since, in most applications, it is required to find the exact location of the anomaly. It is tough than the segmentation or classification task since in this task class-belongingness of each pixel is predicted. The presence of noise, and variations of viewpoint, shape, and size of cells make it more challenging.

Leishmania donovani mevalonate kinase regulates host actin for inducing phagocytosis.

Despite the well-established role of macrophages in phagocytosing Leishmania, the contribution of the parasite to this process is not well understood. Present study provides insights into the mechanism underlying the MVK-induced entry of L. donovani and improve our knowledge of host-pathogen interactions.

Leishmania antigens activated CD4 T cells expressing CD200R receptors are the prime IL-10 producing phenotype and an important determinant of visceral leishmaniasis pathogenesis.

The excessive production of IL-10, an anti-inflammatory cytokine, by Leishmania antigen-activated T cells is supposed to be a key player in the onset and progression of visceral leishmaniasis (VL). The IL-10-producing sources in VL remain unidentified and uncharacterized. In this study, we reveal that antigen-activated CD4 T cells, i.

Recent advancements in machine learning and deep learning-based breast cancer detection using mammograms.

Objective: Mammogram-based automatic breast cancer detection has a primary role in accurate cancer diagnosis and treatment planning to save valuable lives. Mammography is one basic yet efficient test for screening breast cancer. Very few comprehensive surveys have been presented to briefly analyze methods for detecting breast cancer with mammograms.

Adjuvantation of whole-killed Leishmania vaccine with anti-CD200 and anti-CD300a antibodies potentiates its efficacy and provides protection against wild-type parasites.

One of the major reasons behind the limited success of vaccine candidates against all forms of leishmaniasis is the inability of parasitic antigens to induce robust cell-mediated immunity and immunological memory. Here we find, for the first time, that the adjuvantation of whole-killed Leishmania vaccine (Leishvacc) with anti-CD200 and anti-CD300a antibodies enhances CD4 T cells mediated immunity in vaccinated mice and provides protection against wild-type parasites. The antibody adjuvantation, either alone or with a TLR4 agonist monophosphoryl A (MPL-A), induced the production of pro-inflammatory cytokines viz.

Comparison of collection methods for Phlebotomus argentipes sand flies to use in a molecular xenomonitoring system for the surveillance of visceral leishmaniasis.

Background: The kala-azar elimination programme has resulted in a significant reduction in visceral leishmaniasis (VL) cases across the Indian Subcontinent. To detect any resurgence of transmission, a sensitive cost-effective surveillance system is required. Molecular xenomonitoring (MX), detection of pathogen DNA/RNA in vectors, provides a proxy of human infection in the lymphatic filariasis elimination programme.

An Efficient Detection and Classification of Acute Leukemia Using Transfer Learning and Orthogonal Softmax Layer-Based Model.

For the early diagnosis of hematological disorders like blood cancer, microscopic analysis of blood cells is very important. Traditional deep CNNs lead to overfitting when it receives small medical image datasets such as ALLIDB1, ALLIDB2, and ASH. This paper proposes a new and effective model for classifying and detecting Acute Lymphoblastic Leukemia (ALL) or Acute Myelogenous Leukemia (AML) that delivers excellent performance in small medical datasets.

Concurrent Cervical and Anal High-Risk Human Papillomavirus Infection in Women Living With HIV: An Observational Case-Control Study.

Background: To evaluate the prevalence and correlates of concurrent uterine cervical and anal HR-HPV infections in women living with HIV (WLHIV).

Setting: A cross-sectional study was undertaken at a tertiary care hospital and linked ART center.

Methods: One hundred and forty-one WLHIV and 161 HIV-negative women were enrolled for cervical and anal cytology as well as HR-HPV testing using the HC2 method.

Impact of intensified control on visceral leishmaniasis in a highly-endemic district of Bihar, India: an interrupted time series analysis.

Visceral leishmaniasis (VL) is declining in India and the World Health Organization's (WHO) 2020 'elimination as a public health problem' target has nearly been achieved. Intensified combined interventions might help reach elimination, but their impact has not been assessed. WHO's Neglected Tropical Diseases 2021-2030 roadmap provides an opportunity to revisit VL control strategies.

Revealing a Novel Antigen Repressor of Differentiation Kinase 2 for Diagnosis of Human Visceral Leishmaniasis in India.

Visceral leishmaniasis (VL) is one of the major global health concerns due to its association with morbidity and mortality. All available diagnostic tools have been, until now, unable to provide a very specific and cost-effective mode of detection for VL globally. Therefore, the design of robust, specific, and commercially translatable diagnostic tests is urgently required.

AmBisome Monotherapy and Combination AmBisome-Miltefosine Therapy for the Treatment of Visceral Leishmaniasis in Patients Coinfected With Human Immunodeficiency Virus in India: A Randomized Open-Label, Parallel-Arm, Phase 3 Trial.

Background: Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian subcontinent.

Methods: This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India.