Multiobjective Binary Differential Approach with Parameter Tuning for Discovering Business Process Models: MoD-ProM.

Process discovery approaches analyze the business data to automatically uncover structured information, known as a process model. The quality of a process model is measured using quality dimensions, completeness (replay fitness), preciseness, simplicity, and generalization. Traditional process discovery algorithms usually output a single process model. A single model may not accurately capture the observed behavior and overfit the training data. We have formed the process discovery problem in a multiobjective framework that yields several candidate solutions for the end user who can pick a suitable model based on the local environmental constraints (possibly varying). We consider the Binary Differential Evolution approach in a multiobjective framework for the task of process discovery. The proposed method employs dichotomous crossover/mutation operators. The parameters are tuned using grey relational analysis combined with the Taguchi approach. We have compared the proposed approach with the well-known single-objective algorithms and state-of-the-art multiobjective evolutionary algorithm-Nondominated Sorting Genetic Algorithm (NSGA-II). Additional comparison via computing a weighted average of the quality dimensions is also undertaken. Results show that the proposed algorithm is computationally efficient and produces diversified candidate solutions that score high on the fitness functions. It is shown that the process models generated by the proposed approach are superior to or at least as good as those generated by the state-of-the-art algorithms.

Adjuvant endobiliary radio-frequency ablation combined with self-expandable biliary metal stents for unresectable malignant hilar strictures: A pragmatic comparative study.

INTRODUCTION: The role of endo-biliary radio-frequency ablation (EB-RFA) in treating malignant biliary strictures remains a subject of controversy. This study aims to assess the efficacy and safety of EB-RFA in conjunction with self-expandable metal stents (SEMS) compared to SEMS alone. METHODS: This single-center prospective pragmatic comparative study, conducted between June 2021 and November 2022, involved 23 patients undergoing EB-RFA plus SEMS and 48 patients undergoing SEMS for unresectable malignant hilar obstruction. The study evaluated overall survival, stent patency and adverse events. RESULTS: Seventy-one patients (mean age [SD], 57.8 [11.2] years; 73.2% men) were enrolled. The clinical success rates did not significantly differ between the two groups (78.3% in EB-RFA and 66.6% in SEMS; p 0.316). The median (95% CI) overall survival was 155 (79.87-230.13) days in the EB-RFA group, contrasting with 86.0 (78.06-123.94) days in the SEMS group (p 0.020). The presence of carcinoma gallbladder (p 0.035; HR 0.55; 95% CI 0.32-0.96) and EB-RFA (p 0.047; HR 1.88; 95% CI 1.01-3.49) independently predicted overall survival. Median (95% CI) stent patency was 143.0 (95% CI, 61.61-224.39) days in the EB-RFA group compared to 78.0 (95% CI, 32.74-123.26) days in the SEMS group (p 0.019). The presence of carcinoma gallbladder (p 0.046, HR 0.60; 95% CI, 0.36-0.99), EB-RFA (p 0.023; HR 1.92; 95% CI, 1.10-3.36) and chemotherapy (p 0.017, HR 1.91; 95% CI, 1.12-3.26) independently predicted longer stent patency. There was no difference in procedure-related adverse events in both groups. CONCLUSION: EB-RFA with SEMS placement proves to be a safe and effective technique for palliative biliary decompression in patients with malignant biliary strictures, demonstrating superior overall survival and stent patency compared to SEMS alone. Further confirmation through multi-center trials is warranted. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT05320328).

CSUID - Comprehensive synthetic underwater image dataset.

The underwater environment is characterized by complex light traversal, encompassing effects such as color loss, contrast loss, water distortion, backscatter, light attenuation, and color cast, which vary depending on water purity, depth, and other factors. The dataset presented in this paper is prepared with 100 ground-truth images and 1,50,000 synthetic underwater images. This dataset approximates the effects of underwater environment with implementable combinations of color cast, blurring, low-light, and contrast reduction. These effects and their combinations, with different severity levels are applied to each ground-truth image to generate as many as 150 synthetic underwater images. In addition to the dataset of 1,50,100 images, a comprehensive set of 21 focus metrics, including the average contrast measure operator, Brenner's gradient-based metric, and many others, are calculated for each image.

Bacillus subtilis ZB423: 90-Day repeat dose oral (gavage) toxicity study in Wistar rats.

The novel genetically modified probiotic Bacillus subtilis ZB423 was assessed in a 90-day repeated-dose oral toxicity study adhering to Good Laboratory Practice (GLP) and Organization for Economic Cooperation and Development (OECD) guidelines. Spray-dried spores at a concentration of 1.1E12 CFU/g were administered at doses of 130, 260, and 519 mg/kg body weight/day correlating to 1.43 × 1011, 2.86 × 1011, and 5.71 × 1011 CFU/kg/day, respectively, by oral gavage to Wistar rats for a period of 90 consecutive days. Results showed no toxicologically relevant findings for B. subtilis ZB423 from measured parameters. The no observed adverse effect level (NOAEL) of B. subtilis ZB423 is 519 mg/kg body weight/day corresponding to 5.71 × 1011 CFU/kg/day for lyophilized B. subtilis ZB423 spores under the test conditions employed.

Precise jaw relation recorder: An innovative device for prosthodontic rehabilitation.

BACKGROUND: The orchestration of jaw relations in edentulous scenarios poses a significant challenge, demanding acumen, and expertise from the clinician. A myriad of devices, substances, and methodologies are employed to gauge the transverse, vertical, and horizontal spectrums of jaw relations. Traditionally, a synthesis of assorted devices and techniques has been requisitioned to chronicle the spatial dynamics between the maxilla and mandible. Yet, the absence of a solitary apparatus capable of concurrently documenting the triad of jaw relations has been a notable lacuna in prosthodontic rehabilitation. PURPOSE: This discourse expounds on an innovative contrivance, termed the Precise Jaw Relation Recorder. This pioneering instrument is adept at capturing the tripartite jaw relation processes: the occlusal plane's alignment in parallelism to the ala-tragus line, the vertical dimension at repose, and the occlusion as well as the centric relation. The device's strategic utility lies in its ability to facilitate the creation of prostheses that are not only functionally superior but also aesthetically more pleasing. CONCLUSION: Its implementation is a stride toward refining the accuracy of prosthodontic outcomes, thereby elevating the standard of patient care in dental practice.

Computational prediction of crucial genes involved in gonorrhea infection and neoplastic cell transformation: A multiomics approach.

Neisseria gonorrheae, the causative agent of genitourinary infections, has been associated with asymptomatic or recurrent infections and has the potential to form biofilms and induce inflammation and cell transformation. Herein, we aimed to use computational analysis to predict novel associations between chronic inflammation caused by gonorrhea infection and neoplastic transformation. Prioritization and gene enrichment strategies based on virulence and resistance genes utilizing essential genes from the DEG and PANTHER databases, respectively, were performed. Using the STRING database, protein‒protein interaction networks were constructed with 55 nodes of bacterial proteins and 72 nodes of proteins involved in the host immune response. MCODE and cytoHubba were used to identify 12 bacterial hub proteins (murA, murB, murC, murD, murE, purN, purL, thyA, uvrB, kdsB, lpxC, and ftsH) and 19 human hub proteins, of which TNF, STAT3 and AKT1 had high significance. The PPI networks are based on the connectivity degree (K), betweenness centrality (BC), and closeness centrality (CC) values. Hub genes are vital for cell survival and growth, and their significance as potential drug targets is discussed. This computational study provides a comprehensive understanding of inflammation and carcinogenesis pathways that are activated during gonorrhea infection.

Estimation of Titanium Levels in Blood Following Reconstruction of Post-Craniotomy Defect by Titanium Mesh Using Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES).

Introduction: Titanium and its alloys are the most popular choice of materials for the reconstruction of craniofacial defects. They have lighter weight and are nonferromagnetic, which makes them an advantage in cranial defect reconstruction. Although the formed oxide layer makes them corrosion-resistant, levels of titanium in blood have been seen in trace amounts. This is the first study as per authors' knowledge that a study of such kind has been conducted. Materials and methods: A pilot study was carried out at a tertiary level hospital, considering the inclusion and exclusion criteria in patients who were planned for the reconstruction of the residual defect using titanium mesh. Preoperative and 03- and 06-months postoperative blood samples were collected and analyzed for estimating the levels of titanium ions in blood by inductively coupled plasma-optical emission spectroscopy (ICP-OES). Results: Friedman's two-way analysis of variance by ranks was considered for testing of hypothesis summary, owing to the smaller sample size. The analysis suggested an increase in levels was minimal. Considering the asymptotic significances (two-tailed significance), a significance level was 0.050, which directed us to reject the null hypothesis. Pairwise comparison suggested the presence of negative values indicating steady increase in levels. Cluster analysis indicated that although minimal there is a cluster of difference in the values at all three stages. Continuous field information was used to determine the level with regard to the level of titanium at the three stages of study. Conclusion: The study revealed that the levels of titanium ions increase on prolonged contact with living tissues. The trace elements have to be analyzed at regular intervals. This first-of-the-time study if extended to larger sample size would reveal interesting facts.

Volumetric Analysis and Healing Ratio: Refining Prognostic Assessment in Maxillofacial Cysts Using Cone-Beam Computed Tomography.

Introduction: Volumetric analysis with imaging techniques provides clinicians with the capability to visualize the spatial extent of the lesions. CBCT offers images with minimal radiation, facilitating a detailed assessment of cystic dimension's relationships. This crucial information helps in formulating appropriate strategies, including excision, enucleation, or nonsurgical approaches. The "Healing ratio" emerges as a valuable technique for prognostic evaluation. Materials and Methods: This retrospective study focused on outpatient cases with, clinic-radiologically diagnosed cases of odontogenic keratocyst or radicular cysts. Preoperative CBCT was utilized for volumetric analysis through MIMIC Software. Subsequent analyses were performed at 24 and 48 weeks postoperatively. The healing ratio was calculated for further correlation. Results: A total of 21 cases were included in the study, with a mean age of 36.67 years with predominance of males (72.6%, n = 16). Healing ratio estimation revealed minimal or no association with age, gender, and location on point-biserial analysis. Noteworthy implications were observed concerning total cyst volume and the specific diagnosis of the cyst. Results suggested more favorable healing outcomes in smaller cysts and those diagnosed as radicular cysts. Discussion: Proficiency in deciphering three-dimensional CBCT images accurately demands specialized training. The crux of our study lies in the application of volumetric analysis, particularly the "Healing Ratio," as a robust means of evaluating prognoses in management. The Healing Ratio, derived from three-dimensional imaging techniques, offers a comprehensive insight into the spatial dynamics of cystic lesions. Our findings underscore its significance as the optimal technique for prognostic assessment in the context of cyst management. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-024-02168-7.

AI in ECG: Validating an ambulatory semiology labeller and predictor.

OBJECTIVES: Early prediction of epileptic seizures can help reduce morbidity and mortality. In this work, we explore using electrocardiographic (ECG) signal as input to a seizure prediction system and note that the performance can be improved by using selected signal processing techniques. METHODS: We used frequency domain analysis with a deep neural network backend for all our experiments in this work. We further analysed the effect of the proposed system for different seizure semiologies and prediction horizons. We explored refining the signal using signal processing to enhance the system's performance. RESULTS: Our final system using the Temple University Hospital's Seizure (TUHSZ) corpus gave an overall prediction accuracy of 84.02 %, sensitivity of 87.59 %, specificity of 81.9 %, and an area under the receiver operating characteristic curve (AUROC) of 0.9112. Notably, these results surpassed the state-of-the-art outcomes reported using the TUHSZ database; all findings are statistically significant. We also validated our study using the Siena scalp EEG database. Using the frequency domain data, our baseline system gave a performance of 75.17 %, 79.17 %, 70.04 % and 0.82 for prediction accuracy, sensitivity, specificity and AUROC, respectively. After selecting the optimal frequency band of 0.8-15 Hz, we obtained a performance of 80.49 %, 89.51 %, 75.23 % and 0.89 for prediction accuracy, sensitivity, specificity and AUROC, respectively which is an improvement of 5.32 %, 10.34 %, 5.19 % and 0.08 for prediction accuracy, sensitivity, specificity and AUROC, respectively. CONCLUSIONS: The seizure information in ECG is concentrated in a narrow frequency band. Identifying and selecting that band can help improve the performance of seizure detection and prediction. SIGNIFICANCE: EEG is susceptible to artefacts and is not preferred in a low-cost ambulatory device. ECG can be used in wearable devices (like chest bands) and is feasible for developing a low-cost ambulatory device for seizure prediction. Early seizure prediction can provide patients and clinicians with the required alert to take necessary precautions and prevent a fatality, significantly improving the patient's quality of life.

In vitro analysis of monomer leaching in modern dental materials: CAD milled, printed, traditional heat-processed, and auto-polymerizing denture base resins.

PURPOSE: Denture fabrication has shifted from traditional heat-processed and auto-polymerizing materials to computer-aided design and computer-aided manufacturing (CAD-CAM) milled and printed materials. The monomer in traditional materials can induce an allergic reaction in some patients. With the rise in the edentulous population and increasing demand for the fabrication of dentures, these newer materials should be studied for monomer leaching. The purpose of this study was to evaluate the ratio of residual monomer in materials being used for denture bases: CAD-milled polymethylmethacrylate (PMMA), printed denture base resin, heat-processed PMMA, and auto-polymerizing PMMA comparatively. MATERIALS AND METHODS: Milled, printed, heat-activated, and auto-polymerizing denture base specimens (n = 3 for each group, each test run three times) were fabricated according to manufacturer recommendations. Specimens were first immersed in deuterated chloroform (CDCl3), a deuterated organic solvent, to evaluate monomer leaching and to observe physical properties of the materials. NMR spectroscopy was used to evaluate the dissolution of materials and residual monomer to crosslinked polymer ratios at 1, 4, and 9 days. A second group of specimens was then immersed in deuterium oxide (D2O) to evaluate if the residual monomers would leach out of the system. The solution was then analyzed using nuclear magnetic resonance (NMR) spectroscopy for 1 month. The deuterated forms of chloroform (CDCl3) and water (D2O) were used to enable sample characterization by NMR. RESULTS: While the heat-processed, auto-polymerizing, and milled specimens possessed residual monomers, no significant monomer leaching was noted in the printed specimen, while immersed in CDCl3. Similarly, the printed specimen was most resistant to dissolution, as compared to the rest; dissolution of the specimen is indicative of little to no cross-linking. No detectable dissolution of monomer was seen when all specimens were immersed in D2O for up to 1 month. CONCLUSIONS: Residual monomers were not found in the printed denture material in this study in either CDCl3 or D2O, whereas CAD-milled and traditionally processed denture bases still have residual monomers within their respective systems when immersed in organic solvent. None of the specimens tested leached monomers into D2O.

Awareness of Oral Submucous Fibrosis among the Quid-Chewing South-Asian Expatriates in the United Arab Emirates.

Oral submucous fibrosis (OSF) is a chronic disorder prevalent in South and Southeast Asia and is mainly related to the habit of chewing betel quid. Although there are numerous South-Asian studies about OSF, there is no study that evaluates the awareness of OSF among expatriate populations of South-Asian origin. Evaluated the awareness of OSF among South-Asian expatriate patients reporting to a dental hospital in Sharjah. Prevalidated questionnaires were given to 150 expatriate patients of South-Asian origin with quid-chewing habit reporting to the teaching clinics of a dental hospital in the United Arab Emirates. Among the 150 patients, 103 responded to the questionnaire. Among the 103 respondents, 11.65% were aware of OSF. Respondents living in shared residency and labor camps had significantly (P = 0.43) lower awareness of OSF compared to respondents living with their families. The results of our study show that the awareness of OSF is lower among the respondents living in labor camps and shared residencies. The younger respondents had more awareness of OSMF and were more likely to quit the quid-chewing habit.

Case of lead poisoning secondary to intake of herbal medicine for diabetes mellitus in a tertiary care hospital in Kerala.

Summary: Although most published cases of lead poisoning come from occupational exposures, some traditional remedies may also contain toxic amounts of lead. Here, we report the case of a 58-year-old female who presented with abdominal pain, generalized tiredness, and decreased food intake, with anemia and elevated levels of lead. The patient was found to be taking herbal capsules for diabetes prior to the presentation. This case highlights the need for increased awareness that some herbal remedies may contain potentially harmful levels of heavy metals, and people who use them are at risk of developing associated toxicities. Learning points: Individuals who support traditional medicine often incorrectly believe that herbal remedies for diabetes are free from side effects, leading them to favor these treatments over contemporary medications. Herbal medications are freely available online, even without a prescription. The accessibility of herbal medicines without prescriptions, coupled with the false belief in their lack of side effects, misleads educated individuals toward quackery treatments. Misinformation spread via social media exacerbates this issue. Heavy metals are present in toxic levels in the drugs, causing complications. Lead is the most common heavy metal found in such herbal medicines. Lead poisoning leads to anemia and other systemic complications which could have been fatal if not found in time.

Diagnostic accuracy of Dengue NS1 lateral flow immunoassay in comparison to reverse transcriptase polymerase chain reaction and enzyme linked Immunosorbent Assay.

The most widely used invitro diagnostic qualitative screening method for dengue virus infection is the lateral flow immunoassay technique. Testing of dengue non-structural antigen NS1 offers specificity in determining the active infection while testing of IgM and IgG helps in differentiating the primary and secondary dengue infections. The ELISA functions as the golden standard for dengue testing and PCR credits for the most accurate determination tool at the genetic level. The RT-PCR endorsed NS1 gene and in ELISA or LFIA NS1 antigen is used as the marker owing to the specificity and lesser chances of mutation effects. This study evaluated the performance of AG-Q Dengue NS1 LFIA kit in comparison with RT-PCR quantification cycle (Cq) Values and ELISA NS1 quantitation. The study also focused on differentiating the samples among dengue serotypes using the RealStar Dengue Type RT-PCR Kit 1.0. Dengue serotype 2 is the prominent viral strain in Kerala region succeeded by serotype 3 and 1 with a prevalence rate of 64 %, 20 % and 6 % respectively. Dengue serotype 4 was not reported during this study period. 10 % co-infection with DENV 1 & DENV 2 was also reported. The AG-Q Dengue NS1 kit stood as efficient in screening by providing positive results with samples having RT-PCR Cq values up to 43 and ELISA NS1 quantification minimum of 14 Panbio units.

Interim management of Pierre Robin sequence using a custom-made face mask.

Pierre Robin sequence poses a great challenge for anesthesiologists during laryngoscopy and intubation, making oxygenation and ventilation difficult. The role of early surgical intervention is recommended for the improvement of the airway and overall survival of the neonate. The situation becomes even more challenging, when the neonate may not be fit for such surgical interventions. The present case posed such a challenge to the team. To the authors' knowledge, the decision to use a face mask as an interim life-saving measure was considered for the first time. This provided a greater window of opportunity for further course of action, only to be later managed by distraction osteogenesis of the mandible. The unconventional use of orthopedic appliances for the management of threatened airways may provide the clinician with time, where further management may be carried out. The present article will explain such a procedure that was carried out as a life-saving measure.

Adverse outcomes in patients hospitalized with pneumonia at age 60 or more: A prospective multi-centric hospital-based study in India.

BACKGROUND: Limited data exists regarding risk factors for adverse outcomes in older adults hospitalized with Community-Acquired Pneumonia (CAP) in low- and middle-income countries such as India. This multisite study aimed to assess outcomes and associated risk factors among adults aged ≥60 years hospitalized with pneumonia. METHODS: Between December 2018 and March 2020, we enrolled ≥60-year-old adults admitted within 48 hours for CAP treatment across 16 public and private facilities in four sites. Clinical data and nasal/oropharyngeal specimens were collected by trained nurses and tested for influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) using the qPCR. Participants were evaluated regularly until discharge, as well as on the 7th and 30th days post-discharge. Outcomes included ICU admission and in-hospital or 30-day post-discharge mortality. A hierarchical framework for multivariable logistic regression and Cox proportional hazard models identified risk factors (e.g., demographics, clinical features, etiologic agents) associated with critical care or death. FINDINGS: Of 1,090 CAP patients, the median age was 69 years; 38.4% were female. Influenza viruses were detected in 12.3%, RSV in 2.2%, and ORV in 6.3% of participants. Critical care was required for 39.4%, with 9.9% in-hospital mortality and 5% 30-day post-discharge mortality. Only 41% of influenza CAP patients received antiviral treatment. Admission factors independently associated with ICU admission included respiratory rate >30/min, blood urea nitrogen>19mg/dl, altered sensorium, anemia, oxygen saturation <90%, prior cardiovascular diseases, chronic respiratory diseases, and private hospital admission. Diabetes, anemia, low oxygen saturation at admission, ICU admission, and mechanical ventilation were associated with 30-day mortality. CONCLUSION: High ICU admission and 30-day mortality rates were observed among older adults with pneumonia, with a significant proportion linked to influenza and RSV infections. Comprehensive guidelines for CAP prevention and management in older adults are needed, especially with the co-circulation of SARS-CoV-2.

A Monte Carlo simulation-based decision support system for radiation oncologists in the treatment of glioblastoma multiforme.

In the present research, we have developed a model-based crisp logic function statistical classifier decision support system supplemented with treatment planning systems for radiation oncologists in the treatment of glioblastoma multiforme (GBM). This system is based on Monte Carlo radiation transport simulation and it recreates visualization of treatment environments on mathematical anthropomorphic brain (MAB) phantoms. Energy deposition within tumour tissue and normal tissues are graded by quality audit factors which ensure planned dose delivery to tumour site thereby minimising damages to healthy tissues. The proposed novel methodology predicts tumour growth response to radiation therapy from a patient-specific medicine quality audit perspective. Validation of the study was achieved by recreating thirty-eight patient-specific mathematical anthropomorphic brain phantoms of treatment environments by taking into consideration density variation and composition of brain tissues. Dose computations accomplished through water phantom, tissue-equivalent head phantoms are neither cost-effective, nor patient-specific customized and is often less accurate. The above-highlighted drawbacks can be overcome by using open-source Electron Gamma Shower (EGSnrc) software and clinical case reports for MAB phantom synthesis which would result in accurate dosimetry with due consideration to the time factors. Considerable dose deviations occur at the tumour site for environments with intraventricular glioblastoma, haematoma, abscess, trapped air and cranial flaps leading to quality factors with a lower logic value of 0. Logic value of 1 depicts higher dose deposition within healthy tissues and also leptomeninges for majority of the environments which results in radiation-induced laceration.

Clinical Outcome and its Predictors in Children With Newly Diagnosed Immune Thrombocytopenia.

OBJECTIVE: To determine the predictors for chronic and/or persistent immune thrombocytopenia (ITP) among children with newly diagnosed ITP. METHODS: Ours was a mixed-design study (prospective: January 2020 to March 2022 and retrospective: January 2014 to December 2019), wherein we enrolled children, aged 1 month to 18 years presenting with newly diagnosed ITP. RESULTS: Of the 64 enrolled participants, 58 were followed up for atleast 1-year duration and 6 children were followed up for 3 to 12 months' duration. The median (IQR) age of the cohort was 8 (5, 11) years with a female preponderance (62.5%). Wet bleeding was seen in 56%; 6.25% developed intracranial bleeding. 67.2% (43/64) and 41.4% (24/58) children developed persistent and chronic ITP, respectively. Of the 34 children who achieved complete response at 12-months follow up, 21 (62%) achieved complete response by 3 months and the rest achieved complete response over the next 9 months. Development of overall response (complete or partial) at 3 and 12 months, was associated with a higher absolute lymphocyte count (ALC) at admission. The median ALC (×103/µL) at admission was 3.77 and 2.87 in children who had overall response and no response at 3 months, respectively (P = 0.03). The median ALC (×103/µL) at admission was 3.99 and 2.96 in children who had overall response and no response at 12 months, respectively (P = 0.04). Response rate was lesser in the treated group by approximately 10% compared to the non-treated group. CONCLUSION: The rate of chronicity and intracranial bleeding in our cohort is more than the reported rates in literature. Higher ALC was found to be associated with response.

Synthesis, biological evaluation and molecular docking study of pyrimidine linked thiazolidinedione derivatives as potential antimicrobial and antitubercular agents.

The design and development of novel antimicrobial agents are highly desired to combat the emergence of medication resistance against microorganisms that cause infections. A series of new pyrimidine-linked thiazolidinedione derivatives (5a-j) were synthesized, characterized, and their antimicrobial properties assessed in the current investigation. Here, novel pyrimidine-linked thiazolidinedione compounds were designed using the molecular hybridization approach. Elemental and spectral techniques were used to determine the structures of the synthesized hybrids. The majority of compounds showed encouraging antibacterial properties. Among the active compounds, 5g, 5i, and 5j showed 1.85, 1.15, and 1.38 times the activity of streptomycin against S. aureus, respectively, with MIC values of 6.4, 10.3, and 8.6 µM. With MIC values of 10.8, 21.9, and 15.4 µM, respectively, the compounds 5g, 5i, and 5j showed 2.14, 1.05, and 1.50 times the activity of linezolid against the methicillin-resistant S. aureus (MRSA) strain. Furthermore, when compared to the reference medications, compounds 5g, 5i, and 5j demonstrated broad-range antimicrobial efficacy against all tested strains of bacteria and fungus. Out of all the compounds that were investigated, compounds 5g, 5i, and 5j showed noteworthy anti-tubercular activity. 5g is the most effective, 1.59 times more effective than reference drug isoniazid. To anticipate the binding manner, the synthesized potent compounds were subjected to molecular docking into the active binding site of MRSA and the mycobacterial membrane protein large 3 (MmpL3) protein. The compounds 5g, 5i, and 5j may eventually serve as lead compounds in the search for antimicrobial and anti-TB therapeutic agents.

Zinc solubilization and organic acid production by the entomopathogenic fungus, Metarhizium pingshaense sheds light on its key ecological role in the environment.

We report for the first-time higher zinc (Zn) solubilization efficiency and plant growth promotion by an entomopathogenic fungus (EPF), Metarhizium pingshaense IISR-EPF-14, which was earlier isolated from Conogethes punctiferalis, a pest of global importance. The Zn solubilizing efficiency of the fungus varied depending on the type of insoluble source of Zn used, which was observed to be 1.6 times higher in Zn3(PO4)2-amended media compared to ZnO media. In liquid media, there was a 6.2-fold increase in available Zn in ZnO-amended media, whereas a 20.2-fold increase in available Zn was recorded in Zn3(PO4)2 medium. We ascribe the production of various organic acids such as gluconic, keto-gluconic, oxalic, tartaric, malonic, succinic and formic acids, which in general, interact with insoluble Zn sources and make them soluble by forming metal cations and displacing anions as the major mechanism for Zn solubilization by M. pingshaense. However, the type and amount of organic acid produced in the media varied depending on the source of Zn used and the incubation period. Application of the fungus alone and in combination with insoluble Zn sources enhanced various plant growth parameters in rice and cardamom plants. Moreover, the uptake of Zn in rice plants was enhanced up to ~2.5-fold by fungal application. The fungus also exhibited various other plant growth-promoting traits, such as production of Indole-3-acetic acid, ammonia, siderophores, solubilization of mineral phosphate, and production of hydrolytic enzymes such as α-amylase, protease, and pectinase. Hence, apart from its use as a biological control agent, M. pingshaense has the potential to be used as a bio-fortifier to enhance the solubilization and uptake of Zn from nutrient poor soils under field conditions. Our findings shed light on the broader ecological role played by this fungus and widen its scope for utilization in sustainable agriculture.