Search Results (389)

Antimicrobial peptides (AMPs) provide a robust alternative to conventional antibiotics, combating escalating microbial resistance through their diverse functions and broad pathogen-targeting abilities. While current deep learning technologies enhance AMP generation, they face challenges in developing multifunctional AMPs due to intricate amino acid interdependencies and limited consideration of diverse functional activities. To overcome this challenge, we introduce a novel de novo multifunctional AMP design framework that enhances a Feedback Generative Adversarial Network (FBGAN) by integrating a global quantitative AMP activity regression module and a multifunctional-attribute integrated prediction module. This integrated approach not only facilitates the automated generation of potential AMP candidates, but also optimizes the network’s ability to assess their multifunctionality. Initially, by integrating an effective pre-trained regression and classification model with feedback-loop mechanisms, our model can not only identify potential valid AMP candidates, but also optimizes computational predictions of Minimum Inhibitory Concentration (MIC) values. Subsequently, we employ a combinatorial predictor to simultaneously identify and predict five multifunctional AMP bioactivities, enabling the generation of multifunctional AMPs. The experimental results demonstrate the efficiency of generating AMPs with multiple enhanced antimicrobial properties, indicating that our work can provide a valuable reference for combating multi-drug-resistant infections. Full article

The concept of “more is better” has long dominated cancer treatment, emphasizing aggressive therapies despite their toxicity. However, the rise of personalized medicine has fostered treatment de-escalation strategies aimed at minimizing toxicity, improving quality of life, and reducing costs. This position paper highlights key applications of de-escalation in medical oncology, with a primary focus on breast cancer and notable examples in colorectal, head and neck, ovarian, lung, and prostate cancers. Various approaches, including dose reduction, treatment duration shortening, and regimen optimization, have demonstrated efficacy without compromising clinical outcomes. Advances in molecular diagnostics, such as Oncotype Dx in breast cancer and circulating tumor DNA (ctDNA) analysis in colorectal cancer, have facilitated patient selection for de-escalation. While these strategies present promising results, challenges remain, particularly in balancing treatment intensity with oncologic control. The review underscores the need for further prospective trials to refine de-escalation approaches and ensure their safe integration into standard oncologic care. Full article

Despite being a rare malignancy, there have been several changes in the management paradigm for vulvar cancer. This review of the literature was undertaken to highlight key areas of treatment innovation and progress, including efforts to de-escalate morbid surgical resection as well as perform dose escalation of radiotherapy and incorporation of modern systemic agents to achieve better oncologic outcomes. There is still much debate regarding key high-risk pathology features and their corresponding prognostic significance and indications for adjuvant treatments. However, we are also developing a more nuanced understanding of the importance of precursor lesions and resultant subtypes of vulvar cancer, which suggests that there are more subtypes beyond the umbrella distinction of HPV status. Moving forward, we anticipate there will be an increasing number of trials investigating the triaging of management recommendations based on risk. Full article

Conventional chemotherapy continues to form the backbone of treatment for many pediatric central nervous system (CNS) tumors. Advances have been made especially in the molecular underpinning of certain pediatric CNS tumors, allowing for advancement and consideration in incorporating this molecular information in molecular targeted therapy or appropriate de-escalation or escalation of therapy. In very young children with embryonal CNS tumors, intensive high-dose chemotherapy approaches have been used with varied increased survival in medulloblastoma, atypical teratoid rhabdoid tumor (ATRT), and rare embryonal subtypes, but there are certain molecular risk groups that require new therapies, such as the ATRT MYC subtype. Some CNS tumors remain resistant or refractory to conventional chemotherapy, especially in relapsed disease. Strategies to explore combination therapies with chemotherapy, novel agents, and novel approaches are needed to improve survival in this population in the future. Full article

Background: Kawasaki disease (KD) is a systemic vasculitis and the leading cause of acquired heart disease in children. Early identification of coronary artery abnormalities (CAAs) is crucial to guide treatment and improve outcomes. While transthoracic 2D echocardiography (TTE) remains the first-line imaging modality, it has limitations, particularly in visualizing distal coronary artery segments and detecting thrombi. Computed tomography coronary angiography (CTCA) offers enhanced visualization, but its role at initial presentation of KD remains underexplored. Methods: We reviewed the records of 71 children with KD who underwent CTCA at their initial presentation at a tertiary center between November 2013 and December 2024. The CTCA findings were compared with those of TTE. CTCA was performed after stabilization using radiation-minimized protocols. Results: Of 71 patients, 62 had CAAs on baseline TTE. CTCA confirmed CAAs in 39 patients, identified additional lesions in 23, and detected distal aneurysms and coronary branch involvement missed by TTE. In 20 patients with initially abnormal TTE, CTCA demonstrated normal coronaries, facilitating treatment de-escalation. CTCA identified coronary thrombi missed on TTE in two patients and congenital coronary anomalies in three patients. CTCA findings led to modification of therapy in multiple cases. Conclusions: CTCA is a valuable adjunct to TTE in evaluating coronary artery involvement at the time of initial presentation of children with KD. Given its superior visualization of the entire length of coronary arteries, CTCA has a vital role in therapeutic decision-making in KD. Full article

Objective: This study aimed to assess the effect of antibiotic de-escalation on 30-day mortality, duration of intravenous (IV) antibiotic therapy and length of hospital stay (LOS) in severe community-acquired pneumonia (sCAP). Methods: We performed a retrospective analysis of prospectively collected data from a cohort of adults diagnosed with sCAP and microbiologically confirmed etiology between 1995 to 2022. Two distinct time points of the de-escalation were analyzed: 3 and 6 days post-admission, corresponding, respectively, to the availability of microbiological results and the median time to clinical stability. Inverse propensity score-weighted binary logistic regression was used to adjust for potential confounders. Results: A total of 398 consecutive cases of sCAP were analyzed. No significant differences were observed between the de-escalation and non-de-escalation groups in terms of age, sex, comorbidities, or severity-related variables (such as impaired consciousness, shock, respiratory failure, or multilobar pneumonia). Patients in the de-escalation group had lower rates of leukopenia, bacteremia and empyema, and less need for mechanical ventilation, with variations depending on the timing of de-escalation. After adjusting for confounding factors in an inverse propensity score-weighted analysis, de-escalation within 3 or 6 days after admission was not associated with increased mortality risk (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 0.29–7.4; p = 0.63, and aOR 0.57, 95% CI 0.14–2.31, p = 0.43, respectively). Similar findings were observed for prolonged LOS. However, antibiotic de-escalation was related to a lower risk of prolonged IV antibiotic. Conclusions: Antibiotic de-escalation in microbiologically confirmed sCAP did not negatively impact clinical outcomes, supporting the safety of this strategy for optimizing antibiotic use in this serious infection. Full article

Molecular methods allow for a rapid identification of the main causative agents of pneumonia along with the most frequent resistance genes. Prolonged broad-spectrum antibiotic therapy without microbiological evidence of infection drives antimicrobial resistance. We evaluated if the result provided by the molecular method is helpful for antimicrobial de-escalation. All respiratory samples collected and directly processed via Real-Time PCR from patients with suspected pneumonia, of whom clinical data were available, were included in this study. In 82 patients out of a total of 174 (47.1%), antimicrobial therapy was modified after the molecular test, and in 28/82 (34.1%), antimicrobial de-escalation was carried out. Among the 92 patients in whom therapy was not modified, 33 (35.9%) were did not receive any antimicrobial therapy before the molecular test and no antibiotics were prescribed after the test. Therefore, in 61 (28 + 33) out of the 174 (35%) patients, unnecessary antimicrobials were discontinued or avoided. The syndromic panel used at our institution can be of help in better choosing when empiric antibiotic de-escalation therapy could be feasible. Full article

Non-invasive ventilation (NIV) is a cornerstone in the management of acute and chronic respiratory failure, offering critical support without the risks of intubation. However, successful weaning from NIV remains a complex, high-stakes process. Poorly timed or improperly executed weaning significantly increases morbidity and mortality, yet current clinical practice often relies on subjective judgment rather than evidence-based protocols. This manuscript reviews the current landscape of NIV weaning, emphasizing structured approaches, objective monitoring, and predictors of weaning success or failure. It examines guideline-based indications, monitoring strategies, and various weaning techniques—gradual and abrupt—with evidence of their efficacy across different patient populations. Predictive tools such as the Rapid Shallow Breathing Index, Lung Ultrasound Score, Diaphragm Thickening Fraction, ROX index, and HACOR score are analyzed for their diagnostic value. Additionally, this review underscores the importance of care setting—ICU, step-down unit, or general ward—and how it influences outcomes. Finally, it highlights critical gaps in research, especially around weaning in non-ICU environments. By consolidating current evidence and identifying predictors and pitfalls, this article aims to support clinicians in making safe, timely, and patient-specific NIV weaning decisions. In the current literature, there are gaps regarding patient selection and lack of universal protocolization for initiation and de-escalation of NIV as the data has been scattered. This review aims to consolidate the relevant information to be utilized by clinicians throughout multiple levels of care in all hospital systems. Full article

The escalating heat flux densities in high-performance electronics necessitate superior thermal management. This study enhanced pool-boiling heat transfer, a method offering high heat removal capacity, by leveraging Binder Jetting 3D Printing (BJ3DP) to create complex porous copper structures without the need for chemical treatments. This approach enables a reliable utilization of phenomena like capillarity for improved performance. Three types of porous copper structures, namely Large Lattice, Small Lattice, and Staggered, were fabricated on pure copper substrates and tested via pool boiling of de-ionized and de-gassed water at atmospheric pressure. Compared to a plain polished copper surface, which exhibited a critical heat flux (CHF) of 782 kW/m² at a wall superheat of 18 K, the 3D-printed porous copper surfaces showed significantly improved heat transfer performance. The Staggered surface achieved a conventional CHF of 2342.4 kW/m² (a 199.7% enhancement) at a wall superheat of 24.6 K. Notably, the Large Lattice and Small Lattice structures demonstrated exceptionally stable boiling without reaching the typical catastrophic CHF within the experimental parameters. These geometries continued to increase in heat flux, reaching maximums of 2397.7 kW/m² (206.8% higher at a wall superheat of 55.6 K) and 2577.2 kW/m² (229.7% higher at a wall superheat of 39.5 K), respectively. Subsequently, a gradual decline in heat flux was observed with an increasing wall superheat, demonstrating an outstanding resistance to the boiling crisis. These improvements are attributed to the formation of distinct vapor–liquid pathways within the porous structures, which promotes the efficient rewetting of the heated surface through capillary action. This mechanism supports a highly efficient, self-sustaining boiling configuration, emphasizing the superior rewetting and vapor management capabilities of these 3D-printed porous structures, which extend the boundaries of sustained high heat flux performance. The porous surfaces also demonstrated a higher heat transfer coefficient (HTC), particularly at lower heat fluxes (≤750 kW/m²). High-speed digital camera visualization provided further insight into the boiling phenomenon. Overall, the findings demonstrate that these BJ3DP structured surfaces produce optimized vapor–liquid pathways and capillary-enhanced rewetting, offering significantly superior heat transfer performance compared to smooth surfaces and highlighting their potential for advanced thermal management. Full article

Background and Objectives: This study aimed to assess the prevalence of colistin prescriptions among patients with multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) infections admitted to a tertiary teaching hospital in Jordan. Additionally, the study evaluated the appropriateness of colistin prescriptions and assessed resistance levels of this strain. Materials and Methods: In this retrospective study, adult patients who were infected with MDR P. aeruginosa and were admitted to Jordan University Hospital between January 2018 and March 2024 were included. Data on demographics, clinical characteristics, sources of infection, antibiotic therapy, and clinical outcomes were collected. Results: Out of the 85 patients who met the inclusion criteria for having MDR P. aeruginosa, colistin was administered to 16 patients (18.8%). Notably, approximately two-thirds (68.7%) of the isolates from patients who received colistin were classified as extensively drug-resistant (XDR). Among the isolates, 15 out of 16 (93.8%) were resistant to both ciprofloxacin and imipenem. Among the patients requiring colistin, five (31.3%) discontinued therapy, while two (12.5%) remained on colistin despite the availability of safer alternatives. No significant difference was observed in 30-day all-cause mortality between patients treated with colistin (0%) and those who were not (4.3%, p = 1.00). Similarly, the incidence of acute kidney injury did not differ significantly between the colistin group (0%) and the non-colistin group (p = 1.00). No significant difference was found in the hospital stay between colistin-treated patients (median 10.5 days, IQR [5.0–14.0]) and those not treated with colistin (median 13.0 days, IQR [7.0–21.0]), (p = 0.22). Conclusions: This study demonstrated that colistin was selectively initiated in high-risk patients, particularly those with XDR P. aeruginosa. However, its inappropriate continuation despite safer alternatives, as well as its discontinuation when no other options existed, raise concerns about antibiotic de-escalation practices. Interestingly, no significant differences in mortality or acute kidney injury were observed between patients who were treated with colistin and those who were not. These findings emphasize the need for antimicrobial stewardship programs and highlight the importance of large-scale trials to evaluate colistin’s efficacy and safety in MDR infections. Full article

The recommended treatment for early-stage cervical cancer (FIGO 2018 stages IA–IB2 and selected IIA1) is surgery, followed by either observation or adjuvant therapy, based on individual risk factors. Surgical management has evolved from extensive radical procedures to more conservative strategies, allowing for fertility-preserving options in appropriately selected patients. In 2018, a landmark study (LACC trial) evaluated the surgical approach to radical hysterectomy, comparing open vs. minimally invasive surgery. The results demonstrated that minimally invasive surgery was associated with worse disease-free and overall survival, leading to guidelines changes that recommend the open radical hysterectomy as the new standard of care. More recently, results from the prospective randomized SHAPE trial demonstrated that in well-selected patients with low-risk early-stage cervical cancer, recurrence rates are comparable between simple hysterectomy and radical hysterectomy. An ongoing study, the CONTESSA trial, is evaluating the role of neoadjuvant chemotherapy in the setting of fertility preservation for lesions measuring 2–4 cm. In addition, ongoing studies are evaluating different surgical approaches for both simple hysterectomy (LASH trial) and radical hysterectomy (ROCC/GOG-3043 and RACC trials), with a focus on comparing oncologic outcomes. Attention has also turned to refining lymph node assessment. Sentinel lymph node biopsy has become a standard staging strategy with reduced morbidity. The SENTICOL I-II and SENTIX/ENGOT-Cx2 trials support its safety and diagnostic accuracy in early-stage disease. This article offers a comprehensive overview of recently published prospective trials that have shaped clinical practice in the management of early-stage cervical cancer. It focuses on surgical approaches and radicality, the role of sentinel lymph node mapping, and fertility-sparing treatments. The review further draws attention to ongoing investigations and novel studies that may influence future directions in the field. Full article

Background/Objectives: Antimicrobial stewardship programs (ASPs) optimize antimicrobial use, improving outcomes and reducing resistance. This study assessed the impact of a ward-specific ASP. Methods: A pre/post quasi-experimental study was conducted in an internal medicine ward at a tertiary hospital in Padua, Italy. During the intervention year (September 2023–August 2024), a multidisciplinary team (infectious disease consultants, pharmacists, microbiologists, nurses, and hygienists) held bi-weekly ward-based audits, reviewing antimicrobial prescriptions and performing bedside assessments. Therapy adjustments followed guidelines and local epidemiology. Educational sessions and infection prevention and control (IPC) protocols were also reinforced. Outcomes were compared to the previous year, considering patient characteristics. The primary outcome was antimicrobial consumption (DDD/100 patient days, DDD/100PD); secondary outcomes included cost savings, length of stay (LOS), and mortality. Results: Fifty audits assessed 1074 patients and 1401 antimicrobial treatments. Patient characteristics were similar. Antibiotic suspension or de-escalation occurred in 37.9% and 22% of patients, respectively. AWARE ACCESS class use increased (+17.5%), while carbapenem (−54.4%) and fluoroquinolone (−42.0%) use significantly declined (p < 0.05). IPC and microbiological culture guidance were provided in 12.1% of cases. Antimicrobial consumption dropped from 107.7 to 84.4 DDD/100PD (p < 0.05). No significant changes in LOS or mortality were observed. Antimicrobial costs fell by 48.8% (with EUR 57,100 saved). Conclusions: ASP reduced antimicrobial consumption, improved prescription quality, and cut costs without compromising patient outcomes. Multidisciplinary collaboration, audits, and education proved essential. Future studies should assess long-term resistance trends and integrate rapid diagnostics for enhanced stewardship. Full article

Police officers work in high-stress environments that demand emotional resilience, interpersonal skills, and effective communication. Occupational stress can negatively impact their motivation, conflict resolution abilities, and professional effectiveness. Loving-Kindness Meditation (LKM), a mindfulness-based intervention focused on cultivating compassion and empathy, has shown promise in enhancing prosocial attitudes and emotional regulation. With the rise of short video platforms, digital interventions like video-guided LKM may offer accessible mental health support for law enforcement. This study examines the effects of short video app-guided LKM on police officers’ mindfulness, public service motivation (PSM), conflict resolution skills (CRSs), and communication skills (CSSs). It aims to determine whether LKM can enhance these psychological and professional competencies. A randomized controlled trial (RCT) was conducted with 110 active-duty police officers from a metropolitan police department in China, with 92 completing the study. Participants were randomly assigned to either the LKM group (n = 46) or the waitlist control group (n = 46). The intervention consisted of a 6-week short video app-guided LKM program with daily 10 min meditation sessions. Pre- and post-intervention assessments were conducted using several validated scales: the Mindfulness Attention Awareness Scale (MAAS), the Public Service Motivation Scale (PSM), the Conflict Resolution Styles Inventory (CRSI), and the Communication Competence Scale (CCS). A 2 (Group: LKM vs. Control) × 2 (Time: Pre vs. Post) mixed-design MANOVA was conducted to analyze the effects. Statistical analyses revealed significant group-by-time interaction effects for PSM (F(4,177) = 21.793, p < 0.001, η² = 0.108), CRS (F(4,177) = 20.920, p < 0.001, η² = 0.104), and CSS (F(4,177) = 49.095, p < 0.001, η² = 0.214), indicating improvements in these areas for LKM participants. However, no significant improvement was observed for mindfulness (F(4,177) = 2.850, p = 0.930, η² = 0.016). Short video app-guided LKM improves public service motivation, conflict resolution skills, and communication skills among police officers but does not significantly enhance mindfulness. These findings suggest that brief, digitally delivered compassion-focused programs can be seamlessly incorporated into routine in-service training to strengthen officers’ prosocial motivation, de-escalation competence, and public-facing communication, thereby fostering more constructive police–community interactions. Full article

Understanding how thermal variability affects marine ectotherms is essential for predicting species resilience under climate change. We investigated the physiological responses of juvenile Nodipecten subnodosus (lion’s paw scallop), offspring of two genetically distinct populations (Bahía de Los Ángeles and Laguna Ojo de Liebre), reared under common garden conditions and exposed to three temperature regimes: constant, regular oscillation, and stochastic variability. After 15 days of exposure, scallops underwent an acute hyperthermia challenge. We measured metabolic rates, scope for growth (SFG), tissue biochemical composition, and oxidative stress markers (SOD, CAT, GPx, TBARS). No significant differences were detected between populations for most traits, suggesting that phenotypic plasticity predominates over evolutionary divergence in thermal responses. However, the temperature regime significantly influenced metabolic, biochemical and oxidative stress markers, indicating that scallops in variable conditions compensated through improved energy balance and food assimilation but also showed higher oxidative stress compared to the constant regime. Following acute hyperthermic exposure, energy demand escalated, compensatory mechanisms were impaired, and scallops attained a state of physiological maintenance and survival under stress, irrespective of their population or prior thermal regime exposure. Full article

Background: Quality of life (QoL) is a critical indicator in assessing the success of oncological treatments for head and neck malignancies, reflecting their impact on physiological functions and psychosocial well-being beyond mere survival. Treatments (surgery, radiotherapy, chemotherapy) pose multiple functional and emotional challenges, and recent advancements underscore the necessity of evaluating post-treatment QoL. Objective: This literature review investigates the impact of oncological treatment on the QoL of patients with malignant head and neck cancers (oral, oropharyngeal, hypopharyngeal, laryngeal) and identifies factors influencing their QoL index. Methodology: Using a PICO framework, studies from PubMed Central were analyzed, selected based on inclusion (English publications, full text, PROM results) and exclusion criteria. The last research was conducted on 6 April 2025. From 231 identified studies, 49 were included after applying filters (MeSH: “Quality of Life,” “laryngeal cancer,” “oral cavity cancer,” etc.). Data were organized in Excel, and the methodology adhered to PRISMA standards. Results: Treatment Impact: Oncological treatments significantly affect QoL, with acute post-treatment declines in functions such as speech, swallowing, and emotional well-being (anxiety, depression). Partial recovery depends on rehabilitative interventions. Influencing Factors: Treatment type, disease stage, socioeconomic, and demographic contexts influence QoL. De-escalated treatments and prompt rehabilitation improve recovery, while complications like trismus, dysphagia, or persistent hearing issues reduce long-term QoL. Assessment Tools: Standardized PROM questionnaires (EORTC QLQ-C30, QLQ-H&N35, MDADI, HADS) highlighted QoL variations. Studies from Europe, North America, and Asia indicate regional differences in outcomes. Limitations: Retrospective designs, small sample sizes, and PROM variability limit generalizability. Multicentric studies with extended follow-up are recommended. Conclusions: Oncological treatments for head and neck malignancies have a complex impact on QoL, necessitating personalized and multidisciplinary strategies. De-escalated therapies, early rehabilitation, and continuous monitoring are essential for optimizing functional and psychosocial outcomes. Methodological gaps highlight the need for standardized research. Full article