In Vitro Assessment of Newer Colistin-Sparing Antimicrobial Agents for Clinical Isolates of Carbapenem-Resistant Organisms.

OBJECTIVES: Carbapenem-resistant organisms (CROs) are a significant public health threat globally, particularly in countries like India with high antibiotic resistance rates. The current study investigates the prevalence of CROs, detects resistance mechanisms using phenotypic methods and assesses the efficacy of newer antibiotics against CROs. METHODS: A prospective study conducted at a tertiary care hospital in India during 2021-23. Clinical specimens were processed and bacterial identification was performed using MALDI-TOF mass spectrometry followed by antimicrobial susceptibility testing using CLSI guidelines against a plethora of newer antibiotics for CROs. Carbapenemase production was detected using phenotypic methods, and the presence of the mcr-1 gene was assessed by real-time PCR. RESULTS: During the study period, predominantly (70%) Gram-negative bacteria were isolated; amongst which 5692 strains were carbapenem-resistant, wherein resistance to different carbapenems ranged from 34.1%-79%. Majority of the carbapenemase producers were metallo-ß-lactamases (MBL) producers (75%). Colistin resistance was noted in 5.4% of selected carbapenem-resistant isolates. Among newer antibiotics, cefiderocol demonstrated the lowest resistance rates (0-14%), while resistance to newer ß-lactam/ß-lactamase inhibitor combinations was very high in carbapenem-resistant isolates. Fosfomycin, minocycline and tigecycline, each showing variable efficacy depending on the site of infection. Moreover, newer ß-lactam/ß-lactamase inhibitor combinations offer restricted benefits due to widespread prevalence of MBL in the region. CONCLUSION: The escalating prevalence of CROs in India underscores the urgency for alternative treatment options beyond colistin. Hence, highlighting the critical importance of developing effective strategies to combat carbapenem resistance.

Patient and Health Care Professional Perceptions of the Experience and Impact of Symptoms of Moderate-to-Severe Crohn's Disease in US and Europe: Results from the Cross-Sectional CONFIDE Study.

BACKGROUND: Crohn's disease (CD) significantly affects patients' health-related quality of life and well-being. AIMS: Communicating Needs and Features of IBD Experiences (CONFIDE) survey explores the experience and impact of moderate-to-severe CD symptoms on patients' lives and identifies communication gaps between patients and health care professionals (HCPs). METHODS: Online, quantitative, cross-sectional surveys of patients, and HCPs were conducted in the United States (US), Europe (France, Germany, Italy, Spain, United Kingdom), and Japan. Criteria based on previous treatment, steroid use, and/or hospitalization defined moderate-to-severe CD. US and Europe data are presented as descriptive statistics. RESULTS: Surveys were completed by 215 US and 547 European patients and 200 US and 503 European HCPs. In both patient groups, top three symptoms currently (past month) experienced were diarrhea, bowel urgency, and increased stool frequency, with more than one-third patients wearing diaper/pad/protection at least once a week in past 3 months due to fear of bowel urgency-related accidents. HCPs ranked diarrhea, blood in stool, and increased stool frequency as the most common symptoms. Although 34.0% US and 27.2% European HCPs ranked bowel urgency among the top five symptoms affecting patient lives, only 12.0% US and 10.9% European HCPs ranked it among top three most impactful symptoms on treatment decisions. CONCLUSION: Bowel urgency is common and impactful among patients with CD in the US and Europe. Differences in patient and HCP perceptions of experiences and impacts of bowel urgency exist, with HCPs underestimating its burden. Proactive communication between HCPs and patients in clinical settings is crucial for improving health outcomes in patients with CD.

Possible impact of revisions in disc diffusion breakpoints for aminoglycosides and piperacillin/tazobactam in the 33rd edition of CLSI M100 document on clinical reporting and use in Indian settings with low susceptibility.

PURPOSE: The study explores the impact of significant interpretative breakpoint changes for aminoglycosides and piperacillin-tazobactam in Enterobacterales and Pseudomonas aeruginosa, considering PK/PD, clinical data, and susceptibility on clinical reporting and use. PROCEDURE: Between January 2021 and June 2023, a total of 189,583 samples were processed for bacterial pathogens and antimicrobial susceptibility testing was performed using disc diffusion method/VITEK® 2 Compact system/broth microdilution. WHONET software was utilised to capture and analyse the changes in the interpretation of disc diffusion method, following updates to CLSI M100 documents in comparison to previous editions. Antimicrobial consumption data was collected and interpreted as DDD/100 bed days using AMC tool software. Here, we present data for 13,615 members of Order Enterobacterales and 1793 Pseudomonas aeruginosa isolates. FINDING: Enterobacterales exhibited a significant susceptibility drop of 14.7% for gentamicin and 21.7% for amikacin. Pseudomonas aeruginosa showed an increase in isolates with intermediate tobramycin susceptibility, from 0.6% to 29.7%, with relatively minor changes in piperacillin-tazobactam interpretation. CONCLUSION: The changes indicate a shift toward increased 'resistance' and 'intermediate susceptibility' for these antibiotics, emphasizing the need for cautious use and leveraging PK/PD knowledge for improved antibiotic utilization, patient outcomes, and antimicrobial stewardship.

Quality assurance of SARS-CoV-2 testing laboratories during the pandemic period in India - An experience from a designated provider laboratory.

PURPOSE: Indian Council of Medical Research (ICMR) initiated an Inter-Laboratory Quality Control testing (ILQC) program for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. Under this program, SARS-CoV-2 testing laboratories across the country submit specimens to the assigned State Quality Control (SQCs) laboratories for ILQC testing. This study aimed to investigate the performance of public and private SARS-CoV-2 testing laboratories in Delhi and highlights the country's effort in ramping up testing facility with close monitoring of the quality of Covid-19 testing results. METHODS: In the present study, two-years of SARS-CoV-2 testing data is included. During July 2020 through February 2022, a total of 1791 anonymised specimens were received from 56 public and private laboratories. These specimens were processed by reverse transcriptase - polymerase chain reaction (RT-PCR) tests as per National Institute of Virology (NIV) protocol and the results were uploaded on the ICMR quality control/quality assurance (QC/QA) portal without directly conveying the results to respective participating laboratories. This portal generated a final report stating concordance and intimate results to individual laboratories. RESULTS: Among the 1791 specimens, 25 were rejected and the remaining 1766 were tested. Among these specimens 1691 (95.75%) revealed concordance, and 75 (4.24%) were discordant. A total of 29 laboratories had 100% concordance, 21 laboratories had over 90% concordance and six laboratories had over 80% concordance. CONCLUSIONS: The study demonstrates that the establishment of an inter-laboratory comparison program for SARS-CoV-2 testing helped in monitoring quality of SARS-CoV-2 testing in the country.

Paeniclostridium sordellii causing liver abscess: A rare case report in India.

Paeniclostridium sordellii, an anaerobic bacterium, causes hepatic infections in alcoholics and post-surgery (liver transplantation). While liver and brain abscesses are rare, drainage procedures and targeted antibiotic therapy assisted by early microbiological diagnosis have reduced mortality rates. We report a rare case of pyogenic liver abscess caused by Paeniclostridium sordellii in India, the early diagnosis of which has led to life saving outcome for the patient. Hence, the microbiological diagnosis and comprehensive medical-surgical treatment are vital for preventing mortality in Paeniclostridium sordellii infections.

Patient Perspectives of Bowel Urgency and Bowel Urgency-Related Accidents in Ulcerative Colitis and Crohn's Disease.

BACKGROUND: Bowel urgency is bothersome in patients with ulcerative colitis (UC) or Crohn's disease (CD) and impacts their well-being but remains underappreciated in clinical trials and during patient-healthcare provider interactions. This study explored the experiences of bowel urgency and bowel urgency-related accidents to identify the concepts most relevant and important to patients. METHODS: Adults with a diagnosis of moderate-to-severe UC or CD for ≥6 months and experience of bowel urgency in the past 6 months were included. Qualitative, semi-structured interviews were conducted via telephonic/Web-enabled teleconference. Interview transcripts were coded and analyzed in ATLAS.ti 9 using a systematic thematic analysis. RESULTS: In total, 30 participants with UC or CD (n = 15 each) (mean age 52 and 50 years, respectively) participated in the interviews. The majority of participants were receiving biologic and/or conventional therapy (80% and 87%, respectively). Most participants with UC (87%) and all with CD experienced bowel urgency-related accidents. The most frequently reported symptoms co-occurring with bowel urgency were abdominal pain, fatigue, and abdominal cramping. Abdominal pain and abdominal cramping were the most bothersome co-occurring symptoms of bowel urgency and bowel urgency-related accidents. In both groups, participants reported decreased frequency of bowel urgency and not wanting to experience bowel urgency-related accidents at all as a meaningful improvement. CONCLUSIONS: Participants with UC or CD expressed bowel urgency and bowel urgency-related accidents to be bothersome and impactful on their daily lives despite use of biologic and/or conventional therapy. These findings underscore the need for development of patient-reported outcome measures to assess bowel urgency in clinical settings.

Bowel urgency and bowel urgency-related accidents are accompanied by several bothersome symptoms and considerably impact patients' quality of life, highlighting the need to develop a patient-reported outcome measure for assessing and addressing bowel urgency in clinical settings.

Approach towards surveillance-based diagnosis of acute respiratory illness in India: Expert recommendations.

BACKGROUND: Emerging infectious diseases, often zoonotic, demand a collaborative "One-Health" surveillance approach due to human activities. The need for standardized diagnostic and surveillance algorithms is emphasized to address the difficulty in clinical differentiation and curb antimicrobial resistance. OBJECTIVE: The present recommendations are comprehensive diagnostic and surveillance algorithm for ARIs, developed by the Indian Council of Medical Research (ICMR), which aims to enhance early detection and treatment with improved surveillance. This algorithm shall be serving as a blueprint for respiratory infections landscape in the country and early detection of surge of respiratory infections in the country. CONTENT: The ICMR has risen up to the threat of emerging and re-emerging infections. Here, we seek to recommend a structured approach for diagnosing respiratory illnesses. The recommendations emphasize the significance of prioritizing respiratory pathogens based on factors such as the frequency of occurrence (seasonal or geographical), disease severity, ease of diagnosis and public health importance. The proposed surveillance-based diagnostic algorithm for ARI relies on a combination of gold-standard conventional methods, innovative serological and molecular techniques, as well as radiological approaches, which collectively contribute to the detection of various causative agents. The diagnostic part of the integrated algorithm can be dealt at the local microbiology laboratory of the healthcare facility with the few positive and negative specimens shipped to linked viral disease research laboratories (VRDLs) and other ICMR designated laboratories for genome characterisation, cluster identification and identification of novel agents.

Blood borne infections and Hepatitis B virus immunization levels among medical students in India.

BACKGROUND: Medical students are actively involved in direct patient care during their training and subsequent medical practice, making them susceptible to acquiring blood-borne pathogens, including HBV. This study aimed to assess the occurrence of blood-borne infections and the Hepatitis B immunization status among medical students. Furthermore, it sought to identify gaps in risk assessment for blood-borne pathogens among medical students at a Medical College in New Delhi. METHODS: The study included 108 medical students who participated in a blood donation camp. Blood samples collected from these individuals underwent testing for blood-borne pathogens in accordance with standard screening protocols at the blood bank. The quantitative estimation was performed for anti-HBs IgG using ELISA. RESULTS: All 108 participants were pursuing their undergraduate or postgraduate medical degrees. All students tested negative for HBsAg and HIV markers and showed no reactivity to Syphilis and Malaria. However, one student tested positive for HCV. Two postgraduate students had a history of needlestick injuries. Eighty-one (75%) students had received Hepatitis B vaccination. Among the vaccinated students, 34 (41.97%) were immunized before the age of five years, 22 (27.16%) after the age of five years, while 25 (30.86%) couldn't recall the exact age of their Hepatitis B vaccination. Protective anti-HBs titer of anti-Hepatitis B antibodies (>10 mIU/ml) were detected in 48.15% (52/108) of students. CONCLUSIONS: Over 50% of medical students did not possess sufficient immunity against HBV infection, putting them at a heightened risk of acquiring HBV during their active participation in patient care in the near future. It is imperative to establish a policy for routine anti-HBs titer assessment and ensure easy access to Hepatitis B immunization for medical students, thereby enhancing their protection against this infectious agent.

DNMT1 downregulation as well as its overexpression distinctly affect mostly overlapping genes implicated in schizophrenia, autism spectrum, epilepsy, and bipolar disorders.

Data on schizophrenia (SZ), epilepsy (EPD) and bipolar disorders (BPD) suggested an association of DNMT1 overexpression whereas certain variants of the gene were predicted to result in its increased expression in autism spectrum disorder (ASD). In addition, loss of DNMT1 in frontal cortex resulted in behavioral abnormalities in mice. Here we investigated the effects of increased as well as lack of DNMT1 expression using Dnmt1tet/tet neurons as a model for abnormal neurogenesis and 10,861 genes showing transcript level dysregulation in datasets from the four disorders. In case of overexpression, 3,211 (∼ 30%) genes were dysregulated, affecting pathways involved in neurogenesis, semaphorin signaling, ephrin receptor activity, etc. A disproportionately higher proportion of dysregulated genes were associated with epilepsy. When transcriptome data of Dnmt1tet/tet neurons treated with doxycycline that downregulated DNMT1 was used, 3,356 genes (∼31%) were dysregulated with a significant proportion involved in pathways similar to those in untreated cells. Both conditions resulted in ∼68% of dysregulated genes wherein a majority showed similar patterns of transcript level changes. Among the genes with transcripts returning to normal levels, ribosome assembly/biogenesis was most significant whereas in absence of DNMT1, a new set of 903 genes became dysregulated and are involved in similar pathways as mentioned above. These findings provide support for overexpression of DNMT1 as well as its downregulation as risk factor for the four disorders and that its levels within a tight range are essential for normal neurodevelopment/mental health.

Quality improvement initiative improves the empiric antibiotic prescribing practices in a tertiary care children's hospital in India.

INTRODUCTION: Infections are a common cause of paediatric morbidity. Antibiotics are vital in treating them. Erratic prescribing practices are an important cause for the development of antibiotic resistance. Our objective was to estimate the effectiveness of educational interventions to improve empirical antibiotic prescribing practices among paediatric trainees. We aimed to improve the compliance to antibiotic protocols and to sustain it over 6 months. METHODS: It is a time interrupted non-randomised trial conducted in a tertiary hospital in India. Initially, 200 admitted children were selected randomly. Their antibiotic prescriptions, adherence of prescriptions to the then existing antibiotics guidelines, course during hospital stay and the final outcome were noted. The existing antibiotic policy and its use were reviewed. It was then considered essential to prepare a fresh antibiotic policy based on national guidelines, local sensitivity patterns and with inputs from microbiologists. This was distributed to the residents through seminars, posters and cellphone friendly documents. Compliance to the policy was also tracked twice a week. The adherence to guideline was recorded in the subsequent 6 months. RESULTS: The adherence of empirical antibiotic prescriptions was 59% before intervention which improved to 72% in the first month, 90% in the second month, 86% and 78% in the third and sixth months, respectively. There was no significant difference in duration of stay and the outcome at discharge in the patients in adherent and non-adherent groups. CONCLUSION: Educational interventions and frequent monitoring improved antibiotic prescribing practices among residents with no negative impact on patient outcomes. Quality improvements need persistent reinforcement and frequent monitoring to be sustainable.

Autoimmune encephalitis: A diagnostic enigma.

Autoimmune encephalitis with anti-NMDA (N-methyl-D-aspartate) receptor encephalitis is the most common type. This condition can be associated with underlying malignancy, making appropriate screening essential. Prompt identification and intervention of autoimmune encephalitis is essential for a successful outcome and full recovery from this serious and potentially fatal condition. Immunotherapy is typically used to suppress the immune response and reduce brain inflammation. The choice of therapy depends on the type and severity of autoimmune encephalitis, as well as the presence of an underlying tumour.

Data Augmentation for Medical Image Classification based on Gaussian Laplacian Pyramid Blending with a Similarity Measure.

Breast cancer is a devastating disease that affects women worldwide, and computer-aided algorithms have shown potential in automating cancer diagnosis. Recently Generative Artificial Intelligence (GenAI) opens new possibilities for addressing the challenges of labeled data scarcity and accurate prediction in critical applications. However, a lack of diversity, as well as unrealistic and unreliable data, have a detrimental impact on performance. Therefore, this study proposes an augmentation scheme to address the scarcity of labeled data and data imbalance in medical datasets. This approach integrates the concepts of the Gaussian-Laplacian pyramid and pyramid blending with similarity measures. In order to maintain the structural properties of images and capture inter-variability of patient images of the same category similarity-metric-based intermixing has been introduced. It helps to maintain the overall quality and integrity of the dataset. Subsequently, deep learning approach with significant modification, that leverages transfer learning through the usage of concatenated pre-trained models is applied to classify breast cancer histopathological images. The effectiveness of the proposal, including the impact of data augmentation, is demonstrated through a detailed analysis of three different medical datasets, showing significant performance improvement over baseline models. The proposal has the potential to contribute to the development of more accurate and reliable approach for breast cancer diagnosis.

Is Omicron really mild? - Comparative analysis of comorbidities and disease outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants.

PURPOSE: Multiple variants of SARS-CoV-2 from Alpha to Omicron have an estimated 6.1 million deaths globally till date. These variants have been found to vary in transmissibility and severity. The present study deals with comparison of morbidity and mortality with SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants. MATERIALS AND METHOD: An observational retrospective cohort study was conducted on a cohort of laboratory confirmed patients of SARS-CoV-2 diagnosed by qRT-PCR of nasopharyngeal swabs in periods; April-2021 and January-2022; that were sequenced and variants were recorded. Patients were invited for a telephonic interview after voluntary and informed consent was obtained from each participant wherein, the demographics, co-morbidities, oxygen requirement and mortality outcomes of the patients were enquired about. RESULTS: A total of 200 patients, with 100 from each period were included in the study. Major comorbidities in patients included hypertension, diabetes mellitus and pulmonary disease. Patients who succumbed to the Delta variant (26%) were higher as compared to the Omicron variant (10%); with the elderly (68 â€‹± â€‹9.7 â€‹years) having significant mortality during the Omicron variant. The mortality was increased in patients with comorbidities as with hypertension (53.8%, 70%), diabetes mellitus (26.9%, 40%), chronic pulmonary disease (30.8%, 20%), and smoking (15.4%, 40%) in the patients infected with both Delta and Omicron variants, respectively. CONCLUSION: The study concluded that the newer strains of SARS-CoV-2 have potential of high transmissibility and milder disease for the population by large, however, for patients with comorbidities have a higher proportion of adverse outcomes, irrespective of the variant.

Proportion of syphilis and hepatitis B and C virus infections among the Integrated Counselling and Testing Centre attendees of a tertiary care hospital.

Introduction: Human Immunodeficiency Virus (HIV) affects the immune system of the body, causing a breakdown in its normal defenses and leaving it vulnerable to a host of life-threatening diseases. High-risk behaviors and routes of transmission for sexually transmitted infections such as syphilis, hepatitis B and hepatitis C are identical with HIV. This study was conducted to assess the proportion of syphilis and hepatitis B and C virus infections in HIV-positive and HIV-negative individuals, and their association with socioeconomic and other factors in Integrated Counselling and Testing Centre (ICTC) attendees, and to determine the association of absolute CD4+ T-lymphocyte count with these co-infections in HIV-positive individuals. Materials and Methods: The study was conducted in the Department of Microbiology of a tertiary care hospital. It included 100 HIV-positive individuals and 100 matched HIV-negative controls attending the ICTC. HIV-positive patients on antiretroviral therapy and patients with history of current/past treatment for chronic hepatitis infection were excluded from the study. Blood samples were tested for HIV, syphilis, and hepatitis B and C infections. Results: The prevalence of syphilis, hepatitis B, and hepatitis C was observed in 3.5%, 2%, and 10% of patients, respectively. The frequency of hepatitis B virus (HBV) infection in HIV-positive and HIV-negative individuals was 1% and 3%, respectively. Hepatitis C virus (HCV) infection among HIV-positive and HIV-negative patients was 16% and 4%, respectively. Syphilis was seen in 7% of the HIV-infected patients. The mean CD4+ count for the HIV-positive patients with either syphilis, HBV, or HCV infections was 252 ± 137.5 cells/µl. Significant associations between HIV infection and education below high school, IV drug abuse, and multiple sexual partners were observed. Conclusions: The HIV-infected patients were observed to be at an increased risk of acquiring syphilis and HCV co-infections through the shared routes of transmission. Routine screening of these patients for concurrent syphilis and viral hepatitis may aid in prompt diagnosis and treatment with improved outcomes, which in turn may decrease the further spread of these infections.

Comparative Diagnostic of Cervical Tuberculous Lymphadenitis: PCR is a Fast, Efficient, and Improved Diagnostic Approach.

Methods: The study included 100 clinically suspected cases of TBLN. Fine needle aspirate (FNA) samples were processed for cytology staining and cultured on LJ & BACTEC 12B media. The biochemical tests were performed to identify the isolates at the species level. Additionally, for PCR, DNA was extracted and used for the diagnosis and identification of mycobacterial species. Results: Patients ranged from 2 to 45 years with a mean age of 24.96 ± 9.10 years. Out of 100 patients, 73% had clinical symptoms of weight loss, followed by fever (72%), anorexia (66%), and night sweats (58%). 24% of patients were found to be smear-positive after Ziehl-Neelsen (ZN) staining and statistically highly significant with PCR. On LJ medium 34% and on BACTEC radiometric 45% of samples were smearing positive. Overall, 48% of cases were PCR-positive for TBLN. When compared with culture, the sensitivity and specificity of PCR were 93.75% and 100%, respectively, which are higher than cytology. The true positive predictive value (PPV) and negative predictive value (NPV) were 83.3% and 61.5%, respectively. Conclusion: This study suggests that PCR is a rapid, sensitive, and specific tool for correct diagnosis of TBLN cases as compared to staining and culture which lead to the early and proper management of mycobacterial diseases.

Procalcitonin for Detecting Culture-Positive Sepsis in Neonates: A Prospective, Multicenter Study.

INTRODUCTION: It is unclear if serum procalcitonin (PCT) estimated at sepsis suspicion can help detect culture-positive sepsis in neonates. We evaluated the diagnostic performance of PCT in culture-positive sepsis in neonates. METHODS: This was a prospective study (February 2016 to September 2020) conducted in four level-3 units in India. We enrolled neonates suspected of sepsis in the first 28 days of life. Neonates with birth weight <750 g, asphyxia, shock, and major malformations were excluded. Blood for PCT assay was drawn along with the blood culture at the time of suspicion of sepsis and before antibiotic initiation. The investigators labeled the neonates as having culture-positive sepsis or "no sepsis" based on the culture reports and clinical course. PCT assay was performed by electrochemiluminescence immunoassay, and the clinicians were masked to the PCT levels while assigning the label of sepsis. Primary outcomes were the sensitivity, specificity, and likelihood ratios to identify culture-positive sepsis. RESULTS: The mean birth weight (SD) and median gestation (IQR) were 2,113 (727) g and 36 (32-38) weeks, respectively. Of the 1,204 neonates with eligible cultures, 155 (12.9%) had culture-positive sepsis. Most (79.4%) were culture-positive within 72 h of birth. The sensitivity, specificity, and positive and negative likelihood ratios at 2 ng/mL PCT threshold were 52.3% (95% confidence interval: 44.1-60.3), 64.5% (60.7-68.1), 1.47 (1.23-1.76), and 0.74 (0.62-0.88), respectively. Adding PCT to assessing neonates with 12.9% pretest probability of sepsis generated posttest probabilities of 18% and 10% for positive and negative test results, respectively. CONCLUSION: Serum PCT did not reliably identify culture-positive sepsis in neonates.

Invasive fungal infections in hemato-oncology.

BACKGROUND: Patients with hematologic malignancies (HM) carries a significant risk of developing invasive fungal infection (IFI) and are associated with a high risk of attributable morbidity and mortality. OBJECTIVES: This review has highlighted the importance of diagnosis and management of invasive fungal infections in highly immunocompromised Hemato-Oncology patients. CONTENT: IFI continues to be a therapeutic issue in immunocompromised HM patients despite of many advancements in the field of fungal diagnosis and therapies. Non-specific and often overlapping signs and symptoms render fungal infections clinically undifferentiated from bacterial infections. Definite diagnosis requires microbiological diagnostic procedures in addition to imaging techniques. Many international committees have formulated definitions to aid in the diagnosis of IFI in immunocompromised patients and assigned 3 levels of probability to the diagnosis "proven," "probable," and "possible" IFI. Early specific risk-based antifungal strategies such as prophylaxis, pre-emptive and empirical therapies, are common practices in HM patients. For low-risk patients, fluconazole is recommended as primary prophylaxis, while, posaconazole and voriconazole are recommended for high-risk patients. Emerging antifungal-resistant IFIs and breakthrough fungal infections are the new threat to these heavily immunosuppressed patients. Antifungal agents such as azoles have variable pharmacokinetics leading to uncertainty in the drug dose-exposure relationship, especially in the initiation phase. TDM (therapeutic drug monitoring) of voriconazole is strongly recommended.

Artificial intelligence-based model for predicting the minimum inhibitory concentration of antibacterial peptides against ESKAPEE pathogens.

In response to environmental threats, pathogens make several changes in their genome, leading to antimicrobial resistance (AMR). Due to AMR, the pathogens do not respond to antibiotics. Amongst drug-resistant pathogens, the ESKAPEE group of bacteria poses a major threat to humans, and therefore World Health Organization has given them the highest priority status. Antibacterial peptides (ABPs) are a family of peptides found in nature that play a crucial role in the innate immune systems of organisms. These ABPs offer several advantages over widely used antibiotics. As a result, they have recently received a lot of attention as potential replacements for currently available antibiotics. But it is expensive and time-consuming to identify ABPs from natural sources. Thus, wet lab researchers employ various tools to screen promising ABPs rapidly. However, the main limitation of the existing tools is that they do not provide the minimum inhibitory concentration values against the ESKAPEE pathogens for the identified ABP. To address this, in the current work, we developed ESKAPEE-MICpred, a two-input model that utilizes transfer learning and ensemble learning techniques. The concept of ensemble learning was realized by combining the decisions provided by deep learning algorithms, whereas the concept of transfer learning was realized by utilizing pretrained amino acid embeddings. The proposed model has been deployed as a web server at https://eskapee-micpred.anvil.app/ to aid the scientific community.

Immunogenicity and protective efficacy of an inactivated Newcastle disease virus vaccine encapsulated in poly-(lactic-co-glycolic acid) nanoparticles.

An immunization experiment was conducted in specific pathogen-free chickens with the inactivated Newcastle disease virus (NDV) vaccine encapsulated in the poly-(lactic-co-glycolic) acid (PLGA) nanoparticles (NP) to evaluate its immunogenicity and protective efficacy. The NDV vaccine was prepared by inactivating one virulent Indian strain of NDV belonging to Genotype VII by using beta-propiolactone. PLGA nanoparticles encapsulating inactivated NDV were prepared by the solvent evaporation method. Scanning electron microscopy and zeta sizer analysis revealed that the (PLGA+NDV) NP were spherical, with an average size of 300 nm, having a zeta potential of -6 mV. The encapsulation efficiency and loading efficiency were 72% and 2.4%, respectively. On immunization trial in chicken, the (PLGA+NDV) NP induced significantly (P < 0.0001) higher levels of HI and IgY antibodies with the peak HI titer of 28 and higher expression of IL-4 mRNA. The consistency of higher antibody levels suggests slow and pulsatile release of the antigens from the (PLGA+NDV) NP. The nano-NDV vaccine also induced cell mediated immunity with higher expression of IFN-γ indicating strong Th1 mediated immune responses in contrast to the commercial oil adjuvanted inactivated NDV vaccine. Further, the (PLGA+NDV) NP afforded 100% protection against the virulent NDV challenge. Our results suggested that PLGA NP have adjuvant potential on induction of humoral as well as Th1 biased cell mediated immune responses and also enhanced protective efficacy of the inactivated NDV vaccine. This study provides an insight for development of PLGA NP based inactivated NDV vaccine using the same genotype circulating in the field as well as for other avian diseases at exigencies.

EnDL-HemoLyt: Ensemble Deep Learning-based Tool for Identifying Therapeutic Peptides with Low Hemolytic Activity.

Low hemolytic therapeutic peptides have gained an edge over small molecule-based medicines. However, finding low hemolytic peptides in laboratory is time-consuming, costly and necessitates the use of mammalian red blood cells. Therefore, wet-lab researchers often perform in-silico prediction to select low hemolytic peptides before proceeding with in-vitro testing. The in-silico tools available for this purpose have following limitations: (i) They do not provide predictions for peptides having N/C terminal modifications. (ii) Data is food for AI; however, datasets used to create existing tools do not contain peptide data generated over past eight years. (iii) Performance of available tools is also low. Therefore, a novel framework has been proposed in current work. Proposed framework utilizes recent dataset and uses ensemble learning technique to combine the decisions produced by bidirectional long short-term memory, bidirectional temporal convolutional network, and 1-dimensional convolutional neural network deep learning algorithms. Deep learning algorithms are capable of extracting features themselves from data. However, instead of relying solely on deep learning-based features (DLF), handcrafted features (HCF) were also provided so that deep learning algorithms can learn features that are missing from HCF, and a better feature vector can be constructed by concatenating HCF and DLF. Additionally, ablation studies were carried out to understand the roles of an ensemble algorithm, HCF, and DLF in the proposed framework. Ablation studies found that the ensemble algorithm, HCF and DLF are crucial components of proposed framework, and there is a decrease in performance on eliminating any of them. Mean value of performance metrics, namely Acc, Sn, Pr, Fs, Sp, Ba, and Mcc obtained by proposed framework for test data is ≈ 87, 85, 86, 86, 88, 87, and 73, respectively. To aid scientific community, model developed from proposed framework has been deployed as a web server at https://endl-hemolyt.anvil.app/.