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BACKGROUND: The preterm infants are at risk of cerebellar injury and the risk factors for necrotizing enterocolitis (NEC) associated cerebellar injury are not fully understood. AIM: Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC). METHODS: Retrospective study compared clinical/pathological information between surgical NEC infants with and those without cerebellar injury detected on brain MRI obtained at term equivalent age. Cerebellar Injury patterns that we identified on MRI brain were cerebellar hemorrhage, siderosis and/or cerebellar volume loss. RESULTS: Cerebellar injury (21/65, 32.3%) in preterm infants with NEC was associated with patent ductus arteriosus (PDA) (18/21(85.7%) vs. 25/44(56.8%); p = 0.021), blood culture positive sepsis (13/21 (61.9%) vs. 11/44 (25%); p = 0.004) following NEC, predominantly grew gram positive bacteria (9/21(42.9%) vs. 4/44(9.1%); p = 0.001), greater red cell transfusion, higher rates of cholestasis following NEC and differences in intestinal histopathology (more hemorrhagic and reparative lesions) on univariate analysis. Those with cerebellar injury had higher grade white matter injury (14/21 (66.7%) vs. 4/44(9.1%) p = 0.0005) and higher-grade ROP (70.6% vs. 38.5%; p = 0.027) than those without cerebellar injury. On multilogistic regression, the positive blood culture sepsis (OR 3.9, CI 1.1–13.7, p = 0.03), PDA (OR 4.5, CI 1.0–19.9, p = 0.04) and severe intestinal pathological hemorrhage (grade 3-4) (OR 16.9, CI 2.1–135.5, p = 0.007) were independently associated with higher risk of cerebellar injury. CONCLUSION: Preterm infants with surgical NEC with positive blood culture sepsis, PDA, and severe intestinal hemorrhagic lesions (grade 3-4) appear at greater risk for cerebellar injury. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fifth most prevalent form of cancer worldwide. CagA - positive Helicobacter pylori infects more than 60% of the human population. Moreover, chronic infection of CagA-positive H. pylori can directly affect GC incidence. In the current study, we have repurposed FDA-approved antibiotics that are viable alternatives to current regimens and can potentially be used as combination therapy against the CagA of H. pylori. The 100 FDA-approved gram negative antibiotics were screened against CagA protein using the AutoDock 4.2 tool. Further, top nine compounds were selected based on higher binding affinity with CagA. The trajectory analysis of MD simulations reflected that binding of these drugs with CagA stabilizes the system. Nonetheless, atomic density map and principal component analysis also support the notion of stable binding of antibiotics to the protein. The residues ASP96, GLN100, PRO184, and THR185 of compound cefpiramide, doxycycline, delafloxacin, metacycline, oxytetracycline, and ertapenem were involved in the binding with CagA protein. These residues are crucial for the CagA that aids in entry or pathogenesis of the bacterium. The screened FDA-approved antibiotics have a potential druggability to inhibit CagA and reduce the progression of H. pylori borne diseases. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to determine the clinical and histopathological factors associated with intestinal hemorrhage and its correlation with clinical outcomes in neonates with surgical necrotizing enterocolitis (NEC). METHODS: A retrospective study compared clinical and histopathology information in neonates following surgical NEC with severe hemorrhage and those with mild/moderate hemorrhagic lesions seen on resected intestine pathology. RESULTS: The infants with severe hemorrhage (Grade 3-4, 81/148, 54.7%) had significantly lower exposure to antenatal steroids (52.5 % vs 76.9 %; p = 0.004), had higher gestational age (28.5 weeks [7.14] vs. 26.58 [2.90]; p = 0.034), lost more bowel length (p = 0.045), had higher CRP levels at 2 weeks (p = 0.035), and had less intestinal failure ([30.3 % vs 52.5 %]; p = 0.014) than mild/moderate (Grade 0–2, 67/148, 45.2%) hemorrhage group. Those with severe hemorrhage had significantly higher mean inflammation score (2.67 [0.94] vs. 1.63 [0.92]; p = <0.001), higher necrosis scores (1.95 [1.28] vs. 1.49 [1.35]; p = 0.037), higher neovascularization (p = 0.01), higher fibroblasts (p = 0.023) and higher lymphocyte percentages up to 48 hours (p < 0.05) following NEC than mild/ moderate hemorrhage group. On multivariable regression, less exposure to antenatal steroids (OR 0.18 [95% CI 0.05–0.58]; p = 0.005), higher inflammation (OR 3.7 [95% CI 2.09–7.32]; p = 0.001), and lymphocyte count on the day of onset/24 hours following NEC (OR 1.06 [95% CI 1.02–1.11]; p = 0.005) were independently associated with a higher odd of severe intestinal hemorrhage. CONCLUSION: The surgical NEC infants with intestinal hemorrhage were less likely to have antenatal steroid exposure but had higher inflammation grade and lymphocyte counts following NEC onset on multivariable regression modeling. [ABSTRACT FROM AUTHOR]

BACKGROUND: To determine the clinical implications and gestation age-specific diagnostic predictability of pneumatosis in preterm infants with necrotizing enterocolitis (NEC). METHODS: A retrospective study on abdominal radiographs comparing clinical and radiological information in infants with and without pneumatosis. RESULT: Our findings disproved our hypothesis. Pneumatosis was seen more frequently in infants with higher gestational age [28.4 (26.1–32.4) vs. 26.4 (24.3–29) weeks; p < 0.001] and birth weight [1110 (762–1768) vs. 770 (645–1022) grams; p < 0.001] and were more likely delivered vaginally (39.1% vs. 21.7%, p = 0.01). Portal venous gas was seen frequently on radiographs (10.3% vs. 0%, p < 0.001), but not pneumoperitoneum (20.7% vs. 36.7%, p = 0.02). Infants with pneumatosis frequently developed acute kidney injury, with higher serum creatinine (16.5% vs. 4.5%, p = 0.02) and frequent oliguria (12.9% vs. 2.7 %; p = 0.043) and had higher C-reactive protein levels at 24 and 96 hours (p < 0.002). Receiver operating curves for pneumatosis showed GA >28 weeks and birth weight > 1000 gm to have a sensitivity of 58.6% and specificity of 72.5%. CONCLUSION: Contrary to our hypothesis, infants who developed pneumatosis during NEC were more mature with a higher gestational age and birth weight than those who did not. [ABSTRACT FROM AUTHOR]

In order to assess the energy efficiency of building activities in real-time, this research offers a data-driven methodology. Efficiently managing building energy usage while minimizing negative effects on the environment is the focus of this study. Using a large dataset that includes efficiency ratings obtained from sophisticated analytics and continuous monitoring, as well as specific energy consumption (SEC) measurements, our study reveals intricate patterns in energy use. Reducing energy consumption by 15% during peak hours is possible with the use of predictive modeling tools, which show the possibility of proactive actions. With dynamic modifications resulting in a 20% reduction in total energy use, there are substantial benefits to implementing adaptive techniques based on real-time data. The method’s dependability is confirmed by comparing it to industry-standard standards, which highlights how strong the real-time evaluation system is. Building managers may benefit greatly from this research’s findings on energy efficiency, which will help to create more sustainable and financially feasible building systems.

This paper focuses on the optimal scheduling of the load frequency control (LFC) of a two-area thermal power system (TATPS) under load perturbations. For obtaining optimal LFC performance, presenting the three-degree-of-freedom proportional-integral-derivative controller (3DOFPID) as regulator. However, for the effective functioning of the 3DOFPID regulator, the water cycle algorithm (WCA) is enforced for the location of the suitable parametric values. Moreover, the TATPS is operated with the GRC structures of the open loop and closed loop individually to demonstrate the most effective model for optimal operation. Simulation results showcased that the closed-loop GRC structure dominates open-loop modeling in obtaining the optimal LFC. Further, the closed-loop GRC model for the robust performance of thermal units is validated by testing its performance under varying loads and jtluncertainty in the tie-line parameter.

The dynamic stability of the realistic two-area multi-source (TAMS) power system is appraised under the control of various fractional order controllers (FOC) in present work. Initially, the area-1 of TAMS is subjugated with 10% step load disturbance (SLD), and its dynamic variations are comparatively analyzed under the performances of FOPI, FOPID, and tilt-integral-derivative-filter (TIDF) controllers individually. Moreover, the controllers are individually optimized with the fruit fly algorithm (FFA), and the simulation results demonstrated that the TAMS power system stability is effectively controlled with the TIDF controller. Taken the communication time delays (CTDs) with TAMS to bring the investigative analysis near to the real-time environment, and its significant impact on the system stability is showcased. Further, the two areas are integrated with the battery energy storage (BES), and the Thyristor-controlled phase shifter (TCPS) is placed with the tie-line to enforce them as the territory control approach. Simulation analysis revealed an enhancement in TAMS system behavior with the deployment of the BES-TCPS strategy.

Regulating the dynamical nature of the interconnected power system (IPS) due to fluctuating electric power demands is a crucial part of assessing its stability. The power demands on the IPS are continuous and require automatic actions to mitigate their subsequent impact. Thus, this work suggested the proportional-integral-derivative (PID) controller as the load frequency control (LFC) regulator using the robust optimization of the water cycle algorithm (WCA). The performance of the WCA tubed PID is tested on the two-area hydrothermal (TAHT) system, and the supremacy of the WCA is demonstrated with the Sooty tern algorithm (STA) and the grey wolf optimization (GWO) performance. Further, the TAHT is integrated with the HVDC line to attain further stability. The simulation analysis confirmed the enrichment in the TAHT performance with the HVDC line incorporation. Furthermore, the TAHT system is subjugated by the loading uncertainty under the suggested regulator. The investigation confirmed the robustness of the WCA-tuned PID performance.

It is now a well-accepted notion that each new experimental design requires proper evaluation of internal control genes (ICGs) for accurate normalization of expression data. In riverine buffaloes, till date no appropriate ICG has been reported for studying transcriptional response under any of the physiological stressful condition. The objective here was to test 16 well-known reference genes from different functional categories that could serve as suitable ICG during heat stress studies in buffalo mammary tissue. Briefly, the mammary explants were exposed to 45°C for 1 h and subsequently allowed to recover at 37°C for different time points (2-24 h). Three software programs, geNorm, Normfinder and BestKeeper, were used to measure gene transcript stability. RPL22 was excluded because of weak amplification and unacceptable PCR efficiency. Except GAPDH, all other genes showed expression stability within the acceptable range (<1.5). RPL4, B2M, RPS23 and EEF1A1 genes were found to be most stably expressed while GAPDH and ACTB showed least stability. The BestKeeper analysis identified high correlation for RPL4 ( r = 0.953) and EEF1A1 ( r = 0.914) with BestKeeper index. Based on the present findings, it could be suggested that geometric average of RPL4, B2M, RPS23 and EEF1A1 would provide accurate normalization to transcriptional data of buffalo mammary explant in response to heat stress. [ABSTRACT FROM AUTHOR]

We assessed the suitability of 9 internal control genes (ICG) in milk somatic cells of lactating cows to find suitable reference genes for use in quantitative PCR (qPCR). Eighteen multiparous lactating Sahiwal cows were used, 6 in each of 3 lactation stages: early (25 ± 5 d in milk), mid (160 ± 15 d in milk), and late (275 ± 25 d in milk) lactation. Nine candidate reference genes [glyceraldehyde 3-phosphate dehydrogenase (GAPDH), protein phosphatase 1 regulatory subunit 11 (PPP1R11), β-actin (ACTB), β-2 microglobulin (B2M), 40S ribosomal protein S15a (RPS15A), ubiquitously expressed transcript (UXT), mitochondrial GTPase 1 (MTG1), 18S rRNA (RN18S1), and ubiquitin (UBC)] were evaluated. Three genes, β-casein (CSN2), lactoferrin (LTF), and cathelicidin (CAMP) were chosen as target genes. Very high amplification was observed in 7 ICG and very low level amplification was observed in 2 ICG (UXT and MTG1). Thus, UXT and MTG1 were excluded from further analysis. The qPCR data were analyzed by 2 software packages, ge- Norm and NormFinder, to determine suitable reference genes, based on their stability and expression. Overall, PPP1R11, ACTB, UBC, and GAPDH were stably expressed among all candidate reference genes. Therefore, these genes could be used as ICG for normalization of qPCR data in milk somatic cells through lactation. [ABSTRACT FROM AUTHOR]

We report the development and validation of a method of analysis for nitrogen containing compounds using high-performance liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS/ MS). This LC/MS-MS procedure has been developed for quantitation of the analyte in rat plasma. The analyte and internal standard were isolated from the plasma matrix using deproteination with perchloric acid as the sole sample preparation involved prior to LC-MS/MS analysis. Analysis time of less than 2 minutes was achieved. The derivatization steps required for typical gas-chromatography/mass spectrometry (GC/MS) analyses are eliminated. The validation parameters such as specificity (selectivity), limit of quantitation, linearity, precision, accuracy, ruggedness, stability and system suitability were evaluated for this method. The results showed freedom from interference from other analytes. Retention time precision was less than 2% RSD for analyte and internal standard. The limit of quantitation (LOQ) was 2 &mu:g/L with 9% RSD. For calibration standard curves, an average linear response for three days validation (R[SUP-2] = 0.998) over the range 2 to 2000 μg/L was obtained. The interday precision % RSDs were 7.5, 4.6 and 4.1 for 6, 60 and 600 μg/L, respectively. Analysis accuracy was assessed by spiking actual rat plasma samples with analyte. The spike levels were 3 and 300 μg/L, with recoveries of 87% and 88% respectively. [ABSTRACT FROM AUTHOR]

Background: Of the 80 million forced displaced persons worldwide, women and children bear greater morbidity and mortality, especially in conflict-affected regions. This is due to disruption in health service provision, breakdown of social institutions and increase in sexual and gender-based violence. Reproductive health (RH) service delivery as part of humanitarian health cluster services is outlined in the Minimum Initial Service Package (MISP). This study explores the challenges of delivering RH services to forced-displaced populations, focussing on field level stakeholders in humanitarian settings. Methods: Qualitative semi-structured interviews were conducted with stakeholders from non-governmental and United Nations agencies involved in delivering RH services to conflict-affected populations. Additionally, a scoping review, using the Arksey and O’Malley framework, of the literature was also conducted reviewing challenges of delivering RH programmes to women in forced displaced populations. An inductive and deductive thematic approach was used in data analysis. Results: Eleven key informants (KIs) were interviewed from six conflict-affected countries including Syria, Afghanistan and Libya. Main emerging themes were: 1. Poor awareness of international guidelines (including the MISP) 2. Service provision barriers including lack of human resources 3. Attitudes towards SRH and women’s rights 4. Disruption of health services due to COVID-19. Conclusions: This study has highlighted the main challenges that the humanitarian actors delivering RH programmes in conflictaffected settings face. Implementation of international guidelines remains a key barrier. Key policy recommendations would be to standardise training for all RH providers, prioritise training in the MISP and address cultural attitudes towards RH. Further research exploring the use of WHO’s essential medicines for RH and the long-term impact of COVID-19 on forced displaced females needs to be conducted. Key messages: Providing basic essential reproductive health services to conflict affected populations remains a challenge, including implementation of standardised international guidance through the MISP. One key policy recommendation would be to prioritise training in MISP for conflict-affected humanitarian settings to ensure it is offered as part of the essential package. [ABSTRACT FROM AUTHOR]

Mitosis in early embryos often proceeds at a rapid pace, but how this pace is achieved is not understood. Here, we show that cyclin B3 is the dominant driver of rapid embryonic mitoses in the C. elegans embryo. Cyclins B1 and B2 support slow mitosis (NEBD to anaphase ∼600 s), but the presence of cyclin B3 dominantly drives the approximately threefold faster mitosis observed in wildtype. Multiple mitotic events are slowed down in cyclin B1 and B2-driven mitosis, and cyclin B3-associated Cdk1 H1 kinase activity is ∼25-fold more active than cyclin B1-associated Cdk1. Addition of cyclin B1 to fast cyclin B3-only mitosis introduces an ∼60-s delay between completion of chromosome alignment and anaphase onset; this delay, which is important for segregation fidelity, is dependent on inhibitory phosphorylation of the anaphase activator Cdc20. Thus, cyclin B3 dominance, coupled to a cyclin B1-dependent delay that acts via Cdc20 phosphorylation, sets the rapid pace and ensures mitotic fidelity in the early C. elegans embryo., (© 2024 Lara-Gonzalez et al.)

Helicobacter pylori and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that H. pylori and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis. Herein, we investigated the potential of Withania somnifera root extract (WSE) as a possible chemotherapeutic agent against host oncoprotein Gankyrin whose expression was altered by H. pylori and EBV-associated modified cellular milieu. The results show that WSE does not have any inhibitory effect on H. pylori and EBV-associated gene transcripts except for the lmps ( lmp1 , lmp2a, and lmp2B ). Moreover, the WSE exert their anticancer activity via host cellular response and decreased the expression of cell-migratory ( mmp3 and mmp7 ); cell-cycle regulator ( pcna ); antiapoptotic gene ( bcl2 ); increased the expression of the proapoptotic gene ( apaf1 and bax ); and tumor suppressor ( p53 , prb, and pten ). Knockdown of Gankyrin followed by the treatment of WSE also decreases the expression of TNF-ɑ, Akt, and elevated the expression of NFkB, PARP, Casp3, and Casp9. WSE also reduces cell migration, and genomic instability and forced the cells to commit programmed cell death. Moreover, molecular simulation studies revealed that out of eight active compounds of WSE, only four compounds such as withaferin A (WFA), withanoside IV (WA4), withanolide B (WNB), and withanolide D (WND) showed direct stable interaction with Gankyrin. This article reports for the first time that treatment of WSE decreased the cancerous properties through host cellular response modulation in gastric epithelial cells coinfected with H. pylori and EBV.Communicated by Ramaswamy H. Sarma.

Helicobacter pylori is a pathogenic bacterium that causes gastritis and gastric carcinoma. Besides gastric complications its potential link with gut-brain axis disruption and neurological disorders has also been reported. The current study investigated the plausible role and its associated molecular mechanism underlying H. pylori mediated gut-brain axis disruption and neuroinflammation leading to neurological modalities like Alzheimer's disease (AD). We have chosen the antimicrobial resistant and susceptible H. pylori strains on the basis of broth dilution method. We have observed the increased inflammatory response exerted by H. pylori strains in the gastric as well as in the neuronal compartment after treatment with Helicobacter pylori derived condition media (HPCM). Further, elevated expression of STAT1, STAT3, and AD-associated proteins- APP and APOE4 was monitored in HPCM-treated neuronal and neuron-astrocyte co-cultured cells. Excessive ROS generation has been found in these cells. The HPCM treatment to LN229 causes astrogliosis, evidenced by increased glial fibrillary acidic protein. Our results indicate the association of STAT3 as an important regulator in the H. pylori- mediated pathogenesis in neuronal cells. Notably, the inhibition of STAT3 by its specific inhibitor, BP-1-102, reduced the expression of pSTAT3 and AD markers in neuronal compartment induced by HPCM. Thus, our study demonstrates that H. pylori infection exacerbates inflammation in AGS cells and modulates the activity of STAT3 regulatory molecules. H. pylori secretome could affect neurological compartments by promoting STAT3 activation and inducing the expression of AD-associated signature markers. Further, pSTAT-3 inhibition mitigates the H. pylori associated neuroinflammation and amyloid pathology.

Objective: The aim of the study is to determine clinical correlates of moderate to severe bronchopulmonary dysplasia (BPD) in preterm infants following surgical necrotizing enterocolitis (NEC)., Study Design: This is a retrospective, single-center cohort study comparing patients with moderate to severe BPD to patients with non/mild BPD among surgical NEC infants. BPD was defined by NIH 2001 consensus definition., Results: Of 92 consecutive neonates with surgical NEC, 77% (71/92) had moderate/severe BPD and 22% (21/92) had non/mild BPD. The patent ductus arteriosus (PDA) was significantly higher in those developing moderate/severe BPD (67.6% [48/71]) than non/mild BPD (28.6% [6/21]; p  = 0.001). Postoperatively, infants with moderate/severe BPD had more severe acute kidney injury (AKI; 67.6 [48/71] vs. 28.6% [6/21]; p  = 0.001), were intubated longer (40.5 [interquartile (IQR): 12, 59] vs. 6 days [IQR: 2, 13]; p <0.001), received more parenteral nutrition (109 [IQR: 77, 147] vs. 55 days [IQR: 19, 70]; p <0.001), developed higher surgical morbidity (46.5 [33/71] vs. 14.3% [3/21]; p  = 0.008), had more intestinal failure (62.5 vs. 13.3%; p <0.001), required a longer hospital stay (161 [IQR: 112, 186] vs. 64 days [IQR: 20, 91]; p <0.001), and were more likely to need home oxygen. In a multivariable analysis, lower birth weight (OR = 0.3, [95% confidence interval (CI): 0.1-0.5]; p  = 0.001), PDA (OR = 10.3, [95% CI: 1.6-65.4]; p  = 0.014), and longer parenteral nutritional days (OR = 8.8; [95% CI: 2.0-43.0]; p  = 0.005) were significantly and independently associated with higher odds of moderate/severe versus non-/mild BPD., Conclusion: Development of moderate/severe BPD occurred in the majority of preterm infants with surgical NEC in this consecutive series. Preterm infants with moderate/severe BPD were more likely to have a PDA before NEC. Development of moderate/severe BPD was associated with significantly greater burden and duration of postoperative morbidity following surgical NEC. Identifying surgical NEC infants at increased risk of moderate/severe BPD and developing lung protection strategies may improve surgical NEC outcomes., Key Points: · Three-fourths of preterm infants experienced severe lung injury following surgical NEC.. · The infants with severe moderate/severe BPD were most likely associated with greater duration of postoperative morbidity.. · There is need to understand and develop lung protective strategies in infants with surgical NEC.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Gastroenteritis is a common cause of morbidity and mortality globally. Its cause encompasses a spectrum of agents, including viruses, bacteria, parasites, toxins, and drugs. Viruses account for a considerable portion of gastroenteritis cases across all age groups, typically presenting with symptoms like nausea, vomiting, diarrhea, dehydration, anorexia, and weight loss. While sporadic cases occur, viral gastroenteritis is more frequently observed in outbreaks within closely knit communities such as daycare facilities, nursing homes, and cruise ships. Therefore, it becomes necessary to determine when healthcare providers should consider this condition in their differential diagnosis and to develop the most effective strategy to confirm the diagnosis., Methods: De-identified data of patients with gastroenteritis were collected over a five-year period utilizing the Patient Cohort Explorer, an electronic health record at the University of Mississippi Medical Center. Confirmatory laboratory tests employed the BioFire® FilmArray® multiplex polymerase chain reaction for gastrointestinal pathogens. Out of the 22 most common agents associated with gastroenteritis, only viral pathogens, specifically adenovirus, astrovirus, norovirus, rotavirus, and sapovirus, were included in the analysis. When available, histopathology was reviewed., Results: Among the various causes of gastroenteritis, both infectious and non-infectious, our findings revealed that 25.46% of the cases were linked to viral pathogens. This included a significantly higher percentage of pediatric patients (72.73%) when compared to adults (27.07%), with a p-value of 0.015. Norovirus genogroups I and II emerged as the most frequently detected viruses across all age groups, with a significant prevalence among adults. No discernible gender-based differences were observed. The histopathological findings included inflammation, ulceration, erosion, architectural distortion, and the pathognomonic viral inclusion bodies associated with adenovirus., Conclusion: Our comprehensive analysis of viral gastroenteritis cases highlights the substantial burden of this condition, particularly among pediatric patients. Norovirus emerges as a prevalent culprit which emphasizes the importance of vigilant surveillance and timely diagnosis, especially in settings where outbreaks are common., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Dr. Robert T. Brodell declare(s) stock/stock options and Principal investigator for clinical trials from University of Mississippi Medical Center. Dr. Brodell is a principal investigator for clinical trials (Novartis and Sanofi) and the CorEvitas Psoriasis Registry and owns stock in Veradermics, Inc. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sharma et al.)

Background/aim: Hair-follicle keratinocytes contain high levels of cysteine, which is derived from methionine, rapidly proliferate, and form the hair shaft. The high proliferation rate of hair-follicle keratinocytes resembles that of aggressive cancer cells. In the present study, we determined the effect of a methionine-deficient diet on hair loss (alopecia) in mice with or without homocysteine supplementation., Materials and Methods: Mice were fed a normal rodent diet (2020X, ENVIGO) (Group 1); a methionine-choline-deficient diet (TD.90262, ENVIGO) (Group 2); a methionine-choline-deficient diet with a 10 mg/kg/day supply of homocysteine administered by intra-peritoneal (i.p.) injection for 2 weeks (Group 3). In Group 2, mice were fed a methionine-choline-deficient diet for an additional 2 weeks but with 10 mg/kg/day of i.p. l-homocysteine and the mice were observed for two additional weeks. Subsequently, the mice were fed a standard diet that included methionine. Hair loss was monitored by photography., Results: After 14 days, hair loss was observed in Group 2 mice on a methionine-restricted diet but not in Group 3 mice on the methionine-restricted diet which received i.p. homocysteine. In Group 2, at 2 weeks after methionine restriction, hair loss was not rescued by homocysteine supplementation. However, after restoration of methionine in the diet, hair growth resumed. Thus, after 2 weeks of methionine restriction, only methionine restored hair loss, not homocysteine., Conclusion: Hair maintenance requires methionine in the diet. Future experiments will determine the effects of methionine restriction on hair-follicle stem cells., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of borderline malignant potential. Nearly half of all IMTs have rearrangement of anaplastic lymphoma kinase (ALK) locus on chromosome 2p23 which can be treated with targeted therapy. Herein, we describe an unusual presentation of IMT involving an anatomical region rarely implicated in this disease process. A 15-year-old male patient came to the ER with dysphagia and coffee ground emesis. On esophagogastroscopy, a nodular luminal obstructing 30 × 50 mm mass in the lower esophagus was found, which was continuous with a large, partially circumferential gastric mass extending from the mid-body to the proximal antrum. Biopsies from esophageal and gastric masses revealed submucosal lesions composed of cytologically bland spindle and epithelioid cells, intermingled with inflammatory infiltrate, for which several immunohistochemical (IHC) stains were performed. The molecular study demonstrated ATIC::ALK fusion. Based on morphological, IHC, and molecular study findings, the diagnosis of ALK-positive IMT was rendered. Because surgical excision was deemed infeasible, the patient was started on ALK-inhibiting therapy with crizotinib. The patient responded well with no evidence of residual or recurrent disease on follow-up imaging or surveillance esophagogastroduodenoscopy. Crizotinib was ultimately discontinued after 10 months of therapy, and the patient continues to undergo surveillance imaging for monitoring of disease burden., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Organochlorine (OC) and organophosphorus (OP) pesticides such as chlorpyrifos (CPF) and endosulfan (ES) have been associated with a plethora of adverse health effects. Helicobacter pylori (H. pylori) infection can lead to gastrointestinal diseases by regulating several cellular processes. Thus, the current study focuses on the effect of the co-exposure to pesticides and H. pylori on gastric epithelial cells. We have used the in-silico approach to determine the interactive potential of pesticides and their metabolites with H. pylori-associated proteins. Further, various in-vitro methods depict the potential of ES in enhancing the virulence of H. pylori. Our results showed that ES along with H. pylori affects the mitochondrial dynamics, increases the transcript expression of mitochondrial fission genes, and lowers the mitochondrial membrane potential and biomass. They also promote inflammation and lower oxidative stress as predicted by ROS levels. Furthermore, co-exposure induces the multi-nucleated cells in gastric epithelial cells. In addition, ES along with H. pylori infection follows the extrinsic pathway for apoptotic signaling. H. pylori leads to the NF-κB activation which in turn advances the β-catenin expression. The expression was further enhanced in the co-exposure condition and even more prominent in co-exposure with ES-conditioned media. Thus, our study demonstrated that pesticide and their metabolites enhance the pathogenicity of H. pylori infection., Competing Interests: Declaration of competing interest Authors reports no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Outcomes of infants following surgical necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) categorized by the age of onset, interventions, and sex are not well defined., Methods: Retrospective comparison of infants categorized by age of onset (NEC at <10, 10-20, and >20 days) and SIP at <7 versus ≥7 days), sex, and intervention [Penrose Drain (PD) vs. laparotomy]., Results: A total of 114 infants had NEC and 37 had SIP. On multinomial logistic regression, infants with NEC/SIP onset >20 days had significantly lower odds of small bowel involvement (aOR = 0.07, 95% CI: 0.01-0.33, p = 0.001), higher necrosis (aOR = 3.59, 95% CI: 1.34-9.65, p = 0.012) and higher CRP (p = 0.004) than onset <10 days. Initial laparotomy was associated with more bowel loss (24.1 cm [12.3; 40.6] vs.12.1 [8.00; 23.2]; p = 0.001), small and large intestine involvement (47.1% vs 17.2%; p = 0.01), and ileocecal valve resection (42% vs. 19.4%; p = 0.036) than initial PD therapy. Females underwent fewer small bowel resections (52.3% vs 73.6%; p = 0.025) but had higher surgical morbidity (53.7% vs. 24.7%.; p = 0.001) than males., Conclusion: Clinical, radiological, and histopathological presentation and outcomes in preterm infants with surgical NEC/SIP are associated with age of disease onset, sex, and initial intervention., Impact: Neonates with surgical NEC onset >20 days had more severe necrosis, inflammation, kidney injury, and bowel loss than those with <10 days. Initial laparotomy was associated with later age onset, more bowel loss, and ileocecal valve resection compared to initial PD treatment, but not with differences in mortality or length of stay. Female sex was associated with lower maturity, more placental malperfusion, less often small bowel involvement, lower pre-NEC hematocrit as well as higher surgical morbidity than males. Whether the management of surgical NEC and SIP should differ by the age of onset requires further investigation., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Postpartum Depression Disorder (PPDD) is a prevalent mental health condition and results in severe depression and suicide attempts in the social community. Prompt actions are crucial in tackling PPDD, which requires a quick recognition and accurate analysis of the probability factors associated with this condition. This concern requires attention. The primary aim of our research is to investigate the feasibility of anticipating an individual's mental state by categorizing individuals with depression from those without depression using a dataset consisting of text along with audio recordings from patients diagnosed with PPDD. This research proposes a hybrid PPDD framework that combines Improved Bi-directional Long Short-Term Memory (IBi-LSTM) with Transfer Learning (TL) based on two Convolutional Neural Network (CNN) architectures, respectively CNN-text and CNN audio. In the proposed model, the CNN section efficiently utilizes TL to obtain crucial knowledge from text and audio characteristics, whereas the improved Bi-LSTM module combines written material and sound data to obtain intricate chronological interpersonal relationships. The proposed model incorporates an attention technique to augment the effectiveness of the Bi-LSTM scheme. An experimental analysis is conducted on the PPDD online textual and speech audio dataset collected from UCI. It includes textual features such as age, women's health tracks, medical histories, demographic information, daily life metrics, psychological evaluations, and 'speech records' of PPDD patients. Data pre-processing is applied to maintain the data integrity and achieve reliable model performance. The proposed model demonstrates a great performance in better precision, recall, accuracy, and F1-score over existing deep learning models, including VGG-16, Base-CNN, and CNN-LSTM. These metrics indicate the model's ability to differentiate among women at risk of PPDD vs. non-PPDD. In addition, the feature importance analysis demonstrates that specific risk factors substantially impact the prediction of PPDD. The findings of this research establish a basis for improved precision and promptness in assessing the risk of PPDD, which may ultimately result in earlier implementation of interventions and the establishment of support networks for women who are susceptible to PPDD., (© 2024. The Author(s).)

Phenylephrine, a potent sympathomimetic, induces mydriasis via iris dilator muscle contraction. Intracameral (IC) phenylephrine has been successfully used in cataract surgery for initial mydriasis, maintaining mydriasis, and management of intraoperative floppy-iris syndrome. Serious systemic adverse events (mainly cardiovascular) have been described with topical phenylephrine drops, but we found very little evidence of such adverse events associated with IC phenylephrine use. However, we suspect under-reporting of such adverse events, as they may instead be ascribed to anxiety, positioning, anesthesia, etc. Optimal dosage/concentrations for IC phenylephrine use in different purposes have not been fully studied. In the absence of robust evidence, we suggest that lower but effective IC phenylephrine concentrations are used: a lower concentration (0.31%), in conjunction with an anticholinergic and lidocaine, may be used for initial mydriasis. For management of intraoperative floppy-iris syndrome, 0.31% may be effective, though a higher concentration (1% to 1.25%) may be required., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

Objectives: The objective of this study is to analyze the association between TLR2 deletion (-196 to -174) and TLR1 743 A > G gene polymorphism with drug resistant tuberculosis (PTB, MDR-TB, and XDR-TB) in a population from Agra, Uttar Pradesh., Methods: The present case-control study included 101 pulmonary TB patients, 104 multidrug-resistant TB patients, 48 extremely drug-resistant TB patients, and 130 healthy and unrelated controls residing in the same locality. The genotyping method for TLR2 deletion (-196 to -174) was carried out by allele-specific polymerase chain reaction (PCR), and TLR1 743 A > G gene polymorphism was performed by hybridization probe chemistry in Roche Real-Time PCR. Genotype and allele frequencies were analyzed by the chi-square test. Cytokine levels were measured by ELISA and compared using Mann-Whitney and Kruskal-Wallis tests., Results: The frequency of heterozygous ( Ins/del ) genotypes for TLR2 (-196 to -174) polymorphism was predominant in XDR-TB patients (0.57), whereas heterozygous A/G genotype for TLR1 743 A > G single nucleotide polymorphism (SNP) was predominant in healthy controls (0.57) for TLR1 743 A > G gene polymorphism. The heterozygous genotype of TLR2 deletion polymorphism was found to be significantly higher in XDR-TB ( p  = 0.0001). TLR1 743 A > G SNP, AG genotypes were found to be significantly associated with healthy controls than PTB ( p  = 0.047). The level of serum cytokines (IL-6, TNF-α, and IFN-γ) was also found to be significantly different among TB patients and healthy controls., Conclusion: The findings suggested that in the present population, the heterozygous ( Ins/Del ) genotype and deletion allele of TLR2 deletion (-196 to -174) polymorphism are associated with the risk for the development of drug-resistant TB. Furthermore, for TLR1 743 A > G gene polymorphism, A/G genotype, and G allele are found associated with healthy controls, suggesting the protective role against TB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Varshney, Singh, Mohanty, Kumar, Varshney, Sinha and Barik.)

Background: The preterm infants are at risk of cerebellar injury and the risk factors for necrotizing enterocolitis (NEC) associated cerebellar injury are not fully understood., Aim: Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC)., Methods: Retrospective study compared clinical/pathological information between surgical NEC infants with and those without cerebellar injury detected on brain MRI obtained at term equivalent age. Cerebellar Injury patterns that we identified on MRI brain were cerebellar hemorrhage, siderosis and/or cerebellar volume loss., Results: Cerebellar injury (21/65, 32.3%) in preterm infants with NEC was associated with patent ductus arteriosus (PDA) (18/21(85.7%) vs. 25/44(56.8%); p = 0.021), blood culture positive sepsis (13/21 (61.9%) vs. 11/44 (25%); p = 0.004) following NEC, predominantly grew gram positive bacteria (9/21(42.9%) vs. 4/44(9.1%); p = 0.001), greater red cell transfusion, higher rates of cholestasis following NEC and differences in intestinal histopathology (more hemorrhagic and reparative lesions) on univariate analysis. Those with cerebellar injury had higher grade white matter injury (14/21 (66.7%) vs. 4/44(9.1%) p = 0.0005) and higher-grade ROP (70.6% vs. 38.5%; p = 0.027) than those without cerebellar injury.On multilogistic regression, the positive blood culture sepsis (OR 3.9, CI 1.1-13.7, p = 0.03), PDA (OR 4.5, CI 1.0-19.9, p = 0.04) and severe intestinal pathological hemorrhage (grade 3-4) (OR 16.9, CI 2.1-135.5, p = 0.007) were independently associated with higher risk of cerebellar injury., Conclusion: Preterm infants with surgical NEC with positive blood culture sepsis, PDA, and severe intestinal hemorrhagic lesions (grade 3-4) appear at greater risk for cerebellar injury.

The human gut microbiota is a complex and dynamic community of microorganisms, that influence metabolic, neurodevelopmental, and immune pathways. Microbial dysbiosis, characterized by changes in microbial diversity and relative abundances, is implicated in the development of various chronic neurological and neurodegenerative disorders. These disorders are marked by the accumulation of pathological protein aggregates, leading to the progressive loss of neurons and behavioural functions. Dysregulations in protein-protein interaction networks and signalling complexes, critical for normal brain function, are common in neurological disorders but challenging to unravel, particularly at the neuron and synapse-specific levels. To advance therapeutic strategies, a deeper understanding of neuropathogenesis, especially during the progressive disease phase, is needed. Biomarkers play a crucial role in identifying disease pathophysiology and monitoring disease progression. Proteomics, a powerful technology, shows promise in accelerating biomarker discovery and aiding in the development of novel treatments. In this chapter, we provide an in-depth overview of how proteomic techniques, utilizing various biofluid samples from patients with neurological conditions and diverse animal models, have contributed valuable insights into the pathogenesis of numerous neurological disorders. We also discuss the current state of research, potential challenges, and future directions in proteomic approaches to unravel neuro-pathological conditions., (Copyright © 2024. Published by Elsevier Inc.)

Seed color is one of the key target traits of domestication and artificial selection in chickpeas due to its implications on consumer preference and market value. The complex seed color trait has been well dissected in several crop species; however, the genetic mechanism underlying seed color variation in chickpea remains poorly understood. Here, we employed an integrated genomics strategy involving QTL mapping, high-density mapping, map-based cloning, association analysis, and molecular haplotyping in an inter-specific RIL mapping population, association panel, wild accessions, and introgression lines (ILs) of Cicer gene pool. This delineated a MATE gene, CaMATE23, encoding a Transparent Testa (TT) and its natural allele (8-bp insertion) and haplotype underlying a major QTL governing seed color on chickpea chromosome 4. Signatures of selective sweep and a strong purifying selection reflected that CaMATE23, especially its 8-bp insertion natural allelic variant, underwent selection during chickpea domestication. Functional investigations revealed that the 8-bp insertion containing the third cis-regulatory RY-motif element in the CaMATE23 promoter is critical for enhanced binding of CaFUSCA3 transcription factor, a key regulator of seed development and flavonoid biosynthesis, thereby affecting CaMATE23 expression and proanthocyanidin (PA) accumulation in the seed coat to impart varied seed color in chickpea. Consequently, overexpression of CaMATE23 in Arabidopsis tt12 mutant partially restored the seed color phenotype to brown pigmentation, ascertaining its functional role in PA accumulation in the seed coat. These findings shed new light on the seed color regulation and evolutionary history, and highlight the transcriptional regulation of CaMATE23 by CaFUSCA3 in modulating seed color in chickpea. The functionally relevant InDel variation, natural allele, and haplotype from CaMATE23 are vital for translational genomic research, including marker-assisted breeding, for developing chickpea cultivars with desirable seed color that appeal to consumers and meet global market demand., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Competing Interests: H.L.B., N.V. and S.C-.G. deny any conflict of interest. R.S. participates in industry-sponsored clinical trials with a research contract awarded to the University of Mississippi Medical Center (UMMC) with R.S. as the site principal investigator and no salary support as well as no honoraria. He is also participating with Eli Lilly (SARS-CoV-2, baricitinib). The site opened for enrollment on March 8, 2023. He participated with JNJ (RSV, rilematovir), a study that was discontinued on March 1, 2022, the Eli Lilly study (SARS-CoV-2, LY3819253 and LY3832479), which was discontinued on January 3, 2022, and lastly, the MSD study (HIV, islatravir and doravirine), which was discontinued on December 6, 2022.

Racial disparities in maternal birth outcomes are substantial even when comparing women with similar levels of education. While racial differences in maternal death at birth or shortly afterward have attracted significant attention from researchers, non-fatal but potentially life-threatening pregnancy complications are 30-40 times more common than maternal deaths. Black women have the worst maternal health outcomes. Only recently have health researchers started to view structural racism rather than race as the critical factor underlying these persistent inequities. We discuss the economic framework that prevention scientists can use to convince policymakers to make sustainable investments in maternal health by expanding funding for doula care. While a few states allow Medicaid to fund doula services, most women at risk of poor maternal health outcomes arising from structural racism lack access to culturally sensitive caregivers during the pre-and post-partum periods as well as during birth. We provide a guide to how research in health services can be more readily translated to policy recommendations by describing two innovative ways that cost-benefit analysis can help direct private and public funding to support doula care for Black women and others at risk of poor birth outcomes., (© 2023. Society for Prevention Research.)

Soy protein isolate (SPI) has received widespread attention of the biomedical research community primarily due to its good biocompatibility, biodegradability, high availability and low cost. Herein, glutaraldehyde cross-linked microporous sponge-like SPI scaffolds were prepared using the cryogelation technique for tissue engineering applications. The prepared SPI scaffolds possess an interconnected porous structure with approximately 90% porosity and an average pore size in the range of 45-92 μm. The morphology, porosity, swelling capacity and degradation rate of the cryogels were found to be dependent on the concentration of polymer to crosslinking agent. All cryogels were found to be elastic and able to maintain physical integrity even after being compressed to one-fifth of their original length during cyclic compression analysis. These cryogels showed excellent mechanical properties, immediate water-triggered shape restoration and absorption speed. Furthermore, cryogels outperformed cotton and gauze in terms of blood clotting and blood cell adherence. The in vitro and in vivo studies demonstrated the potency of SPI scaffolds for skin tissue engineering applications. Our findings showed that crosslinking with glutaraldehyde had no detrimental effects on cell viability. In addition, an in vivo wound healing study in rats validated them as good potential wound dressing materials., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Brain tumors result from uncontrolled cell growth, potentially leading to fatal consequences if left untreated. While significant efforts have been made with some promising results, the segmentation and classification of brain tumors remain challenging due to their diverse locations, shapes, and sizes. In this study, we employ a combination of Discrete Wavelet Transform (DWT) and Principal Component Analysis (PCA) to enhance performance and streamline the medical image segmentation process. Proposed method using Otsu's segmentation method followed by PCA to identify the most informative features. Leveraging the grey-level co-occurrence matrix, we extract numerous valuable texture features. Subsequently, we apply a Support Vector Machine (SVM) with various kernels for classification. We evaluate the proposed method's performance using metrics such as accuracy, sensitivity, specificity, and the Dice Similarity Index coefficient. The experimental results validate the effectiveness of our approach, with recall rates of 86.9%, precision of 95.2%, F-measure of 90.9%, and overall accuracy. Simulation of the results shows improvements in both quality and accuracy compared to existing techniques. In results section, experimental Dice Similarity Index coefficient of 0.82 indicates a strong overlap between the machine-extracted tumor region and the manually delineated tumor region., (© 2023. The Author(s).)

Efficient design of integrated sensing and communication systems can minimize signaling overhead by reducing the size and/or rate of feedback in reporting channel state information (CSI). To minimize the signaling overhead when performing sensing operations at the transmitter, this paper proposes a procedure to reduce the feedback rate. We consider a threshold-based sensing measurement and reporting procedure, such that the CSI is transmitted only if the channel variation exceeds a threshold. However, quantifying the channel variation, determining the threshold, and recovering sensing information with a lower feedback rate are still open problems. In this paper, we first quantify the channel variation by considering several metrics including the Euclidean distance, time-reversal resonating strength, and frequency-reversal resonating strength. We then design an algorithm to adaptively select a threshold, minimizing the feedback rate, while guaranteeing sufficient sensing accuracy by reconstructing high-quality signatures of human movement. To improve sensing accuracy with irregular channel measurements, we further propose two reconstruction schemes, which can be easily employed at the transmitter in case there is no feedback available from the receiver. Finally, the sensing performance of our scheme is extensively evaluated through real and synthetic channel measurements, considering channel estimation and synchronization errors. Our results show that the amount of feedback can be reduced by 50% while maintaining good sensing performance in terms of range and velocity estimations. Moreover, in contrast to other schemes, we show that the Euclidean distance metric is better able to capture various human movements with high channel variation values.

Self-assembled metal-ion cross-linked multifunctional hydrogels are gaining a lot of attention in the fields of biomedical and biocatalysis. Herein, we report a heat-triggered metallogel that was spontaneously formed by the self-assembly of adenosine 5'-monophosphate (AMP) and cobalt chloride, accompanied by a color transition depicting an octahedral to tetrahedral transition at high temperature. The hydrogel shows excellent stability in a wide pH window from 1 to 12. The metallogel is being exploited as a multienzyme mimic, exhibiting pH-responsive catalase and peroxidase activity. Whereas catalase mimicking activity was demonstrated by the hydrogel under neutral and basic conditions, it shows peroxidase mimicking activity in an acidic medium. The multifunctionality of the synthesized metallogel was further demonstrated by phenoxazinone synthase-like activities. Owing to its catalase-mimicking activity, the metallogel could effectively reduce the oxidative stress produced in cells due to excess hydrogen peroxide by degrading H 2 O 2 to O 2 and H 2 O under physiological conditions. The biocompatible metallogel could prevent cell apoptosis by scavenging reactive oxygen species. A green and simple synthetic strategy utilizing commonly available biomolecules makes this metallogel highly attractive for catalytic and biomedical applications.

Objective: To compare the clinical outcomes in preterm infants following surgical necrotizing enterocolitis (sNEC) and spontaneous intestinal perforation (SIP)., Methods: Retro-spective comparison of clinical information in preterm infants with sNEC and SIP admitted between January, 2013 and December 31, 2018. The clinical outcomes were compared in two groups, including postoperative and brain injury detected on brain magnetic resonance imaging (MRI) after clinical and histopathological confirmation of the SIP and the NEC diagnosis., Results: 114 infants had sNEC, and 37 had SIP. Infants with SIP had lower median gestational age [25.1 weeks (23.5, 27.1) vs 26.6 (24.4, 31.0), P=0.03], an earlier mean (SD) age of disease onset [10.1 (11.3) days vs 19.6 (17.9); P<0.001] and lower maternal chorioamnionitis on placental pathology [4 (23.5%) vs 22 (68.8%); P=0.007), received more often Penrose drain therapy (54% vs 33%; P=0.03), had less median (IQR) bowel length loss [3.3 cm (1.72, 4.38) vs 21.4 (9.55, 35.3); P=<0.001] and had more often intact ileocecal valve (91.4% vs 65.7%; P=0.006] compared to those with sNEC. In addition, those with sNEC had lower median (IQR) weight z scores at the time of discharge [-1.88 (-2.80, -1.09) vs -1.14 (-2.22, -0.44); P=0.036] than SIP. There were no significant differences in postoperative ileus, duration of parenteral nutrition, surgical morbidity, length of stay, mortality, white matter, and grey matter injury on brain MRI at term equivalent age in preterm infants with SIP and sNEC., Conclusion: In our cohort, preterm infants with SIP and sNEC did not show significant differences in postoperative morbidity and brain MRI abnormalities at term equivalent age. sNEC had lower discharge weight z scores. Larger prospective studies are needed for confirmation of these findings.

Cancer is a condition in which a few of the body's cells grow beyond its control and spread to other outward regions. Globally, gastric cancer (GC) is third most common cause of cancer-related mortality and the fourth most common kind of cancer. Persistent infection of VacA-positive Helicobacter pylori ( H. pylori ) modulates cellular physiology and leads to GC. About ∼70% of H. pylori are positive for vacuolating cytotoxin-A (VacA), and it infects ∼80-90% of world populations. Herein, for first time, we repurposed FDA-approved gram-negative antibiotics, which are feasible alternatives to existing regimens and may be used in combinatorial treatment against VacA-positive H. pylori . Out of 110 FDA-approved antibiotics, we retrieved 92 structures, which were screened against the VacA protein. Moreover, we determined that the top eight hit antibiotics viz ; cefpiramide, cefiderocol, eravacycline, doxycycline, ceftriaxone, enoxacin, tedizolid, and cefamandole show binding free energies of -9.1, -8.9, -8.1, -8.0, -7.9, -7.8, -7.8 and -7.8 Kcal/mol, respectively, with VacA protein. Finally, we performed 100 ns duplicate MD simulations on the top eight selected antibiotics showing strong VacA binding. Subsequently, five antibiotics, including cefiderocol, cefpiramide, doxycycline, enoxacin, and tedizolid show stable ligand protein distance and good binding affinity revealed by the MM-PBSA scheme. Among the five antibiotics cefiderocol act as the most potent inhibitor (-28.33 kcal/mol). Furthermore, we also identified the hotspot residue like Asn-506, Tyr-529, and Phe-483 which control the interaction. Concisely, we identified antibiotics that can be repurposed against VacA of H. pylori and explored their molecular mechanism of interaction with VacA.Communicated by Ramaswamy H. Sarma.