Fractionated stereotactic radiotherapy in craniopharyngiomas: A systematic review and single arm meta-analysis.

INTRODUCTION: Numerous studies have demonstrated Fractionated Stereotactic Radiotherapy's (FSRT) effectiveness in tumor control post-resection for craniopharyngiomas. Nevertheless, past literature has presented conflicting findings particularly regarding endocrine and visual function outcomes. This study aims to elucidate FSRT's efficacy and safety for this population. METHODS: Adhering to PRISMA, a systematic review and meta-analyses was conducted. Included studies had to report the effects of FSRT for treating craniopharyngiomas in a sample greater than four patients, addressing at least one of the outcomes of interest: improvement in visual acuity or field, new-onset hypopituitarism, effectiveness, and tumor progression. Relative risk with 95% confidence intervals were used to assess the outcomes. RESULTS: After retrieving a total of 1292 studies, 10 articles met the predefined criteria and thus were finally selected, amounting to a total of 256 patients. The improvement in visual acuity was estimated at 45% (95% CI: 6-83%), while the improvement in the visual field was 22% (95% CI: 0-51%). Regarding endocrine function, the new-onset hypopituitarism rate was found to be 5% (95% CI: 0-11%). Relative to FSRT effectiveness, the pooled estimate of the complete tumor response rate was 17% (95% CI: 4-30%), and the tumor progression rate was 7% (95% CI: 1-13%). Also, a 3-year progression-free survival rate of 98% (95% CI: 95-100%) was obtained. CONCLUSION: Despite limitations and risks, FSRT shows promise as a viable therapeutic option for craniopharyngiomas, offering notable benefits for visual functions and tumor control. Further research is required to better understand the associated risks, benefits, and clinical utility.

Beyond surgical resection: evaluating stereotactic brachytherapy iodine-125 for low-grade gliomas: a systematic review and meta-analysis.

Stereotactic Brachytherapy Iodine-125 (SBT I-125) has been investigated by some studies for the treatment of lowgrade gliomas. We performed a meta-analysis to assess the efficacy and safety of SBT I-125 Brachytherapy for treatment of patients with Low-Grade Gliomas. PubMed, Cochrane, Web of Science, and EMBASE databases were searched for randomized and observational studies. This systematic review and meta-analysis was conducted according to the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. We used relative risk (RR) with 95% confidence intervals and random effects model to compare the effects of I-125 SBT treatment on the interest outcomes. We evaluated heterogeneity using I2 statistics; we considered heterogeneity to be significant if the p-value was less than 0.05 and I2 was higher than 35%. We performed statistical analysis using the software R (version 4.2.3). A total of 20 studies with a cohort of 988 patients with low grade gliomas who received SBT I-125 as a treatment option. The pooled analysis evidenced: (1) Complication rate of 10% (95% CI: 7-12%; I² = 60%); (2) 5-year PFS of 66% (99% CI: 45-86%; I²= 98%); (3) 10-year PFS was 66% (99% CI: 45-86%; I²= 98%); (4) Malignant transformation rate of 26% (95% CI: 8-45%; I²=0); (5) Mortality of 33% (95% CI: 15-51%; I² = 0%). Our systematic review and meta-analysis of SBT I-125 for low-grade gliomas have revealed significant concerns regarding its safety and efficacy. Despite a proportion of patients remaining progression-free, elevated rates of complications and mortality cast doubt on the intervention's reliability. Future research should prioritize long-term follow-up studies, standardized protocols, and comparative effectiveness research.

Magnetic resonance-guided focused ultrasound ventral intermediate thalamotomy for Tremor-Dominant Parkinson's disease: a systematic review and meta-analysis.

INTRODUCTION: Tremor-dominant Parkinson's Disease (TDPD) has a slower neurological decline compared to other phenotypes of the disease, but significantly impacts daily activities and is often less responsive to standard medications. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) lesioning of the Ventral Intermediate (VIM) nucleus of the thalamus may alleviate symptoms for these patients. METHODS: A systematic review and meta-analysis of English-language studies from PubMed, Cochrane, and Embase were conducted, assessing the efficacy and safety of MRgFUS VIM thalamotomy in TDPD patients. Tremor scores were evaluated using the Clinical Scale Rating for Tremor and the Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRSIII). Neuropsychological outcomes were measured using the Parkinson Disease Questionnaire (PDQ) and the Montreal Cognitive Assessment. This analysis adhered to Cochrane and PRISMA guidelines. RESULTS: Thirteen studies with 211 patients were included. MDS-UPDRSIII scores showed significant improvement at 1, 6, and 12 months post-MRgFUS, respectively: (MD -8.92 points, 95% CI: -15.44 to -2.40, p < 0.01; MD -7.39 points, 95% CI: -11.47 to -3.30, p < 0.01; MD -10.66 points, 95% CI: -16.89 to -4.43, p < 0.01). PDQ scores at baseline compared to 6 months post-treatment also indicated a significant improvement (SMD - 0.86, 95% CI: -1.21 to -0.50, p < 0.01). Neurological adverse events were generally mild and transient, with gait instability and sensory deficits being the most common. CONCLUSION: This meta-analysis demonstrates significant improvements in tremor and neuropsychological outcomes following MRgFUS VIM thalamotomy in TDPD patients, with adverse events being typically mild and transient.

Challenges and limitations in meta-analyses of complications in neurosurgery: Systematic review with proposed approach and checklist to mitigate errors and improve the assessment of the real-world experience.

Meta-analyses are highly valued in medical science, yet accurately reporting complications in neurosurgical studies remains challenging. Examples include inconsistencies in defining and classifying complications and variations in reporting methods. This lack of reproducibility and comparability, along with other issues related to biases, hinders the ability of meta-analyses to yield significant advancements. This systematic review investigated the challenges and limitations inherent in meta-analyses of complications in neurosurgery. Based on the identified challenges and our group's experience, we developed a practical checklist to mitigate and avoid common errors in meta-analyses of complications in neurosurgery.We searched PubMed, Embase, and Web of Science for studies addressing challenges in assessing complications in neurosurgery. The main findings were qualitatively synthesized to identify common challenges and limitations. The proposed checklist was developed using a modified Delphi technique. Eleven studies were included, uncovering heterogeneity and a lack of standardization regarding the classification of complications in neurosurgery across various authors and institutions. They suggested solutions such as implementing a more uniform classification system. Additionally, the NeuroComp Meta-Analysis Checklist was developed, comprising 23 items divided into 5 domains, with a practical approach and suggestions on how to deal with the challenges when meta-analyzing.We identified numerous challenges and concerns when assessing complications in the neurosurgical field. The NeuroComp Meta-Analysis Checklist incorporated methodologies and approaches we utilized in several previously published meta-analyses. While we acknowledge that the proposal cannot solve all the issues involved in comparing and meta-analyzing complications in neurosurgery, it has the potential to enhance the informativeness of future meta-analyses and help authors mitigate common errors. Ultimately, this tool has the potential to contribute to the advancement of accumulating real-world evidence in neurosurgical science.

Efficacy and safety of microvascular decompression with or without partial sensory rhizotomy: a comprehensive meta-analysis and systematic review in treating trigeminal neuralgia.

Classical trigeminal neuralgia (TN), caused by vascular compression of the nerve root, is a severe cause of pain with a considerable impact on a patient's quality of life. While microvascular decompression (MVD) has lower recurrence rates when compared with partial sensory rhizotomy (PSR) alone, refractoriness can still be as high as 47%. We aimed to assess the efficacy and safety profile of MVD + PSR when compared to standalone MVD for TN. We searched Medline, Embase, and Web of Science following PRISMA guidelines. Eligible studies included those with ≥ 4 patients, in English, published between January 1980 and December 2023, comparing MVD vs. MVD + PSR for TN. Endpoints were pain cure, immediate post-operative pain improvement, long-term effectiveness, long-term recurrence, and complications (facial numbness, hearing loss, and intracranial bleeding). We pooled odds ratios (OR) with 95% confidence intervals with a random-effects model. I2 was used to assess heterogeneity, and sensitivity and Baujat analysis were conducted to address high heterogeneity. Eight studies were included, comprising a total of 1,338 patients, of whom 1,011 were treated with MVD and 327 with MVD + PSR. Pain cure analysis revealed a lower likelihood of pain cure in patients treated with MVD when compared to patients treated with MVD + PSR (OR = 0.30, 95% CI: 0.13 to 0.72). Immediate postoperative pain improvement assessment revealed a lower likelihood of improvement in the MVD group when compared with the MVD + PSR group (OR = 0.31, 95% CI: 0.10 to 0.95). Facial numbness assessment revealed a lower likelihood of occurrence in MVD alone when compared to MVD + PSR (OR = 0.08, 95% CI: 0.04 to 0.15). Long-term effectiveness, long-term recurrence, hearing loss, and intracranial bleeding analyses revealed no difference between both approaches. Our meta-analysis identified that MVD + PSR was superior to MVD for pain cure and immediate postoperative pain improvement for treating TN. However, MVD + PSR demonstrated a higher likelihood of facial numbness complications. Furthermore, identified that hearing loss and intracranial bleeding complications appear comparable between the two treatments, and no difference between long-term effectiveness and recurrence.

Enhancing the quality of evidence, comparability, and reproducibility in brain arteriovenous malformations treated with open surgery research: a systematic review and proposal of a reporting guideline for surgical and clinical outcomes.

Brain Arteriovenous Malformations (bAVMs) are rare but high-risk developmental anomalies of the vascular system. Microsurgery through craniotomy is believed to be the mainstay standard treatment for many grades of bAVMs. However, a significant challenge emerges in the existing body of clinical studies on open surgery for bAVMs: the lack of reproducibility and comparability. This study aims to assess the quality of studies reporting clinical and surgical outcomes for bAVMs treated by open surgery and develop a reporting guideline checklist focusing on essential elements to ensure comparability and reproducibility. This is a systematic literature review that followed the PRISMA guidelines with the search in Medline, Embase, and Web of Science databases, for studies published between January 1, 2018, and December 1, 2023. Included studies were scrutinized focusing on seven domains: (1) Assessment of How Studies Reported on the Baseline Characteristics of the Patient Sample; (2) Assessment and reporting on bAVMs grading, anatomical characteristics, and radiological aspects; (3) Angioarchitecture Assessment and Reporting; (4) Reporting on Pivotal Concepts Definitions; (5) Reporting on Neurosurgeon(s) and Staff Characteristics; (6) Reporting on Surgical Details; (7) Assessing and Reporting Clinical and Surgical Outcomes and AEs. A total of 47 studies comprising 5,884 patients were included. The scrutiny of the studies identified that the current literature in bAVM open surgery is deficient in many aspects, ranging from fundamental pieces of information of methodology to baseline characteristics of included patients and data reporting. Included studies demonstrated a lack of reproducibility that hinders building cumulative evidence. A bAVM Open Surgery Reporting Guideline with 65 items distributed across eight domains was developed and is proposed in this study aiming to address these shortcomings. This systematic review identified that the available literature regarding microsurgery for bAVM treatment, particularly in studies reporting clinical and surgical outcomes, lacks rigorous scientific methodology and quality in reporting. The proposed bAVM Open Surgery Reporting Guideline covers all essential aspects and is a potential solution to address these shortcomings and increase transparency, comparability, and reproducibility in this scenario. This proposal aims to advance the level of evidence and enhance knowledge regarding the Open Surgery treatment for bAVMs.

Optimizing radiotherapy strategies for skull base chordoma: a comprehensive meta-analysis and systematic review of treatment modalities and outcomes.

OBJECTIVE: In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor's location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC. METHODS: Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I2 statistics, and statistical significance was defined as p < 0.05. RESULTS: A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%-84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%-87%, 517 cases); in proton-based + carbon ion-based radiotherapy, 85% (82%-88%, 622 cases); and in a comparative analysis of proton-based and carbon ion-based therapy, there was an OR of 1.2 (95% CI 0.59-2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%-45%, 95 cases) for photon fractionated therapy; 35% (25%-45%, 85 cases) for stereotactic radiotherapy; 77% (50%-100%, 180 cases) for proton-based and carbon ion-based radiotherapy; and 74% (45%-100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion-based therapy, the overall estimated rates were 84% (78%-90%, 326 cases) and 75% (65%-85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion-based therapy, the 5-year LC rates were 76% (67%-86%, 259 cases) and 75% (59%-91%, 189 cases), respectively. CONCLUSIONS: The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.

AI-Driven Discovery of SARS-CoV-2 Main Protease Fragment-like Inhibitors with Antiviral Activity In Vitro.

SARS-CoV-2 is the causative agent of COVID-19 and is responsible for the current global pandemic. The viral genome contains 5 major open reading frames of which the largest ORF1ab codes for two polyproteins, pp1ab and pp1a, which are subsequently cleaved into 16 nonstructural proteins (nsp) by two viral cysteine proteases encoded within the polyproteins. The main protease (Mpro, nsp5) cleaves the majority of the nsp's, making it essential for viral replication and has been successfully targeted for the development of antivirals. The first oral Mpro inhibitor, nirmatrelvir, was approved for treatment of COVID-19 in late December 2021 in combination with ritonavir as Paxlovid. Increasing the arsenal of antivirals and development of protease inhibitors and other antivirals with a varied mode of action remains a priority to reduce the likelihood for resistance emerging. Here, we report results from an artificial intelligence-driven approach followed by in vitro validation, allowing the identification of five fragment-like Mpro inhibitors with IC50 values ranging from 1.5 to 241 µM. The three most potent molecules (compounds 818, 737, and 183) were tested against SARS-CoV-2 by in vitro replication in Vero E6 and Calu-3 cells. Compound 818 was active in both cell models with an EC50 value comparable to its measured IC50 value. On the other hand, compounds 737 and 183 were only active in Calu-3, a preclinical model of respiratory cells, showing selective indexes twice as high as those for compound 818. We also show that our in silico methodology was successful in identifying both reversible and covalent inhibitors. For instance, compound 818 is a reversible chloromethylamide analogue of 8-methyl-γ-carboline, while compound 737 is an N-pyridyl-isatin that covalently inhibits Mpro. Given the small molecular weights of these fragments, their high binding efficiency in vitro and efficacy in blocking viral replication, these compounds represent good starting points for the development of potent lead molecules targeting the Mpro of SARS-CoV-2.

Enhancing meningioma resection: a comprehensive study on the safety and effectiveness of Onyx™ presurgical embolization.

Presurgical embolization (PE) has emerged as an interesting strategy to help turn brain tumor resection more amenable. This study aims to systematically review the safety and effectiveness of Onyx™ PE in meningioma resection. We followed Cochrane Collaboration and PRISMA for systematic review and meta-analysis, querying PUBMED, Cochrane Library, Web of Science, and Embase databases. Major complications were defined as other artery occlusion, visual deficits due to PE, or non temporary nerve damage, while minor included transitory conditions and others without clinical implications. A total of 186 patients were included, in which 120 were WHO grade I (80%), II (16%), and III (4%). Patient baseline characteristics and complications were distributed in groups without or with individual patient data analysis. Individual Patient Data Meta-Analysis (IPDMA) was performed on the last category, comprising 51 meningiomas that underwent Onyx™ PE. Among available data, 70%, 17%, and 13% were WHO grade I, II, and III, respectively. Considering all studies, tumor characteristics regarding grade underscored a certain homogeneity. Complications occurred at a rate of 9% (95% CI, 4 to 14%; I2 = 35%), with the rate of major complications significantly lower at only 1% (95% CI, 0 to 3%; I2 = 32%), whereas of minor complications was 7% (95% CI, 3 to 10%; I2 = 0%). Mean surgery blood loss was 668.7 (95% CI, 534.9 to 835.8; I2 = 0%) in IPDMA. Onyx™ PE is promising for safer surgical meningioma resection, despite limitations. Further studies are required to validate efficacy, enhance patient selection, and refine techniques.

CO2-plasma surface treatment of graphite sheet electrodes for detection of chloramphenicol, ciprofloxacin and sulphanilamide.

Graphite sheet (GS) electrodes are flexible and versatile substrates for sensing electrochemical; however, their use has been limited to incorporate (bio)chemical modifiers. Herein, we demonstrated that a cold (low temperature) CO2 plasma treatment of GS electrodes provides a substantial improvement of the electrochemical activity of these electrodes due to the increased structural defects on the GS surface as revealed by Raman spectroscopy (ID/IG ratio), and scanning electron microscopy images. XPS analyses confirmed the formation of oxygenated functional groups at the GS surface after the plasma treatment that are intrinsically related to the substantial increase in the electron transfer coefficient (K0 values increased from 1.46 × 10-6 to 2.09 × 10-3 cm s-1) and with reduction of the resistance to charge transfer (from 129.8 to 0.251 kΩ). The improved electrochemical activity of CO2-GS electrodes was checked for the detection of emerging contaminant species, such as chloramphenicol (CHL), ciprofloxacin (CIP) and sulphanilamide (SUL) antibiotics, at around + 0.15, + 1.10 and + 0.85 V (versus Ag/AgCl), respectively, by square wave voltammetry. Limit of detection values in the submicromolar range were achieved for CHL (0.08 µmol L-1), CIP (0.01 µmol L-1) and SFL (0.11 µmol L-1), which enabled the sensor to be successfully applied to natural waters and urine samples (recovery values from 85 to 119%). The CO2-GS electrode is highly stable and inexpensive ($0.09 each sensor) and can be easily inserted in portable 3D printed cells for environmental on-site analyses.

Chemical Profile and Antimicrobial Activity of the Marine Diatom Chaetoceros muelleri.

Microalgae, due to its rapid growth, low nutritional requirements, and versatility of adaptation to different environmental conditions, has aroused the biotechnological interest, synthesizing novel molecules with antioxidant, anticoagulant, anti-inflammatory, antitumor, and antimicrobial activities. In this sense, we carried out the bioprospection of Chaetoceros muelleri, a marine diatom employed in aquaculture, as a candidate to the development of new drugs for the treatment of bacterial infections. The chemical profile of extracts in different solvents (hexane, chloroform, methylene chloride, ethyl acetate, methanol, and acetone) were analyzed by 1 H-NMR. The hexane extract was the most active against all bacteria species tested, including Mycobacterium tuberculosis, with a minimum inhibitory concentration of 100 µg/ml. Contrarily, the methanol extract was inactive against all tested microorganisms and, in addition, was the only one with IC50 >800 µg/mL, showing no cytotoxicity in VERO cell lines. All other extracts showed antibacterial potential and IC50 values varying between 267.58 and 142.47 µg/ml. The fact that C. muelleri is a microalga easily grown on bioreactors on a large scale may promote its biotechnological use, especially as scaffolds for the development of new compounds against bacterial species of clinical and public health interest.

Implementing ICHOM standard set for cataract surgery at IPO-Porto (Portugal): clinical outcomes, quality of life and costs.

BACKGROUND: This paper fills a gap in the applied research field, for a local context, by addressing the topics of describing cataract surgery' clinical outcomes; quality of life (QoL); and costs of the patients treated after the implementation of the ICHOM standard set. METHODS: This is a retrospective observational study using real-world data (RWD). We included all patients subjected to cataract surgery at the Portuguese Institute of oncology - Porto (IPO-Porto), Portugal, after 3 months follow up period completed between 5th June 2017 and 21st May 2018. The following inclusion criteria: corrected visual acuity of ≤ 6/10 or other significant visual disturbance due to lens opacity or the existence of a large anisometropia. A circuit was implemented based on the ICHOM standard for cataract, to measure clinical variables (e.g. visual acuity) and QoL (CATQUEST-9SF) before and after surgery, and cost of treatment. The results were explored by means of a paired-sample t-test, considering normality assumptions. RESULTS: Data refers to 268 patients (73 P25-P75:32-95 years old), regarding 374 eyes. The cataract surgery had a positive effect on visual acuity (p < 0.001), refraction (right and left cylinder; p < 0.001) and all QoL dimensions. The vast majority of patients, around 98%, reported improvements in QoL. Based on IPO-Porto administrative records, the direct cost of treating cataracts (per eye) is of 500€, representing a total cost of 187,000€ for the number of patients operated herein. CONCLUSION: This study reports the successful implementation of the ICHOM standard set for cataracts in a Portuguese institution and confirms that cataract surgery provides a rapid visual recovery, with excellent visual outcomes and minimal complications in most patients, while also having a positive impact on patients' quality of life.

Chemical, physical, and biological attributes in soils affected by deposition of iron ore tailings from the Fundão Dam failure.

Monitoring degraded areas is essential for evaluation of the quality of the rehabilitation process. In this study, we evaluate how the physical and chemical characteristics of the mixture of iron ore tailings with the soil have affected the soil microbial biomass and activity in areas along the Gualaxo do Norte River after the Fundão Dam disaster. Composite soil samples were collected from areas that were impacted (I) and not impacted (NI) by the tailings. The following attributes were evaluated: chemical element content; soil density, porosity, and texture; microbial biomass carbon; basal respiration; and enzyme activity and density of microbial groups (bacteria, actinobacteria, fungi, arbuscular mycorrhizae, phosphate solubilizers, cellulolytic microorganisms, nitrifiers, ammonifiers, and diazotrophs). According to result, the deposition of tailings increased the pH and the soil available P, Cr, Fe, and Mn content and reduced organic matter. The physical and biological attributes were negatively affected, with increases in the silt content and density of the soil, and reduction in macroporosity and in the microbial biomass and activity of the soil (respiration and enzymes) in the impacted area. However, the impacted areas exhibited greater densities of some microbial groups (cellulolytic microorganisms, nitrifiers, and diazotrophic bacteria). Modifications in the organic matter and silt content are the main attributes associated with deposition of the tailings that affected soil microbial biomass and microbial activity. This may affect erosive conditions and the functionality of the ecosystem, indicating an imbalance in this environment. In contrast, the higher density of some microbial groups in the impacted areas show the high rehabilitation potential of these areas.

Ichthyosis fetalis in a cross-bred lamb.

BACKGROUND: Ichthyosis is a dermatological disease characterized by varying degrees of generalized hyperkeratosis and alopecia. Two congenital forms of ichthyosis are recognized in animals: fetalis (IF) and congenita. The disease occurs rarely in cattle, swine, dogs, chickens and a goat; it has not been reported in sheep. HYPOTHESIS/OBJECTIVES: To provide clinical, laboratory and pathological assessments of a case of IF in a cross-bred lamb. ANIMALS: A male cross-bred lamb. RESULTS: Physical examination revealed apathy, fever, ectropion and eclabium. Generalized thickening and scaling of the skin was noted; this was most severe on the face, ears, inner thighs, limbs and perineum. Deep fissures and wounds were present on the hind limbs and forelimbs. The lamb was monitored for 75 days. During this period, lesions progressed and occasionally obstructed the nostrils and increasingly made it difficult for the lamb to flex major limb joints. Postmortem findings included severe epidermal thickening, multiple subcutaneous abscesses, ectropion and corneal scars. Histological findings revealed diffuse orthokeratotic hyperkeratosis, follicular keratosis, irregular epidermal hyperplasia and atrophy of the sebaceous glands. Serum vitamin A concentration was within the normal range for the species. CONCLUSIONS AND CLINICAL IMPORTANCE: This case report describes a case of presumptive ichthyosis fetalis in a lamb. Greater awareness by practitioners is required for this disease to be included in the differential diagnosis of dermatopathies in this species.

Financial management, efficiency, and care quality: A systematic review in the context of Health 4.0.

This article investigates the intersection between innovation, Health 4.0, and financial management in the healthcare industry, emphasizing the importance of operational efficiency and quality of care. The study aims to analyze how financial management processes in healthcare relate to Health 4.0 and enhance care quality. It begins with a thorough theoretical grounding, proposing a framework that connects Health 4.0 with financial management practices. A systematic review of the literature was conducted, identifying trends, challenges, and opportunities in the financial management of Health 4.0. The results highlight selected articles on responsible innovation, Health 4.0 technologies, investments in health, hospital efficiency, performance forecasting, and high-cost patient management. These articles were clustered into "Data Analysis and Machine Learning in Healthcare" and "Health Management and Sustainability," providing a categorized understanding of the topics. The study reveals that Health 4.0 offers significant opportunities for process efficiency and cost reduction without compromising service quality. It highlights strategic advantages in addressing contemporary healthcare challenges by optimizing processes, improving financial projections, and incorporating advanced technologies efficiently. The successful implementation of Health 4.0 can lead to substantial improvements in service quality, adding value to patients and driving local economic development. This article offers valuable insights for healthcare professionals and managers, emphasizing the transformative potential of Health 4.0 and outlining strategies for its effective implementation. The clustering of articles provides a clearer understanding of current research in Health 4.0, contributing significantly to the field and guiding future research directions.

Electronic descriptors for dislocation deformation behavior and intrinsic ductility in bcc high-entropy alloys.

Controlling the balance between strength and damage tolerance in high-entropy alloys (HEAs) is central to their application as structural materials. Materials discovery efforts for HEAs are therefore impeded by an incomplete understanding of the chemical factors governing this balance. Through first-principles calculations, this study explores factors governing intrinsic ductility of a crucial subset of HEAs-those with a body-centered cubic (bcc) crystal structure. Analyses of three sets of bcc HEAs comprising nine different compositions reveal that alloy chemistry profoundly influences screw dislocation core structure, dislocation vibrational properties, and intrinsic ductility parameters derived from unstable stacking fault and surface energies. Key features in the electronic structure are identified that correlate with these properties: the fraction of occupied bonding states and bimodality of the d-orbital density of states. The findings enhance the fundamental understanding of the origins of intrinsic ductility and establish an electronic structure-based framework for computationally accelerated materials discovery and design.

Recent Advances on Targeting Proteases for Antiviral Development.

Viral proteases are an important target for drug development, since they can modulate vital pathways in viral replication, maturation, assembly and cell entry. With the (re)appearance of several new viruses responsible for causing diseases in humans, like the West Nile virus (WNV) and the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the mechanisms behind blocking viral protease's function is pivotal for the development of new antiviral drugs and therapeutical strategies. Apart from directly inhibiting the target protease, usually by targeting its active site, several new pathways have been explored to impair its activity, such as inducing protein aggregation, targeting allosteric sites or by inducing protein degradation by cellular proteasomes, which can be extremely valuable when considering the emerging drug-resistant strains. In this review, we aim to discuss the recent advances on a broad range of viral proteases inhibitors, therapies and molecular approaches for protein inactivation or degradation, giving an insight on different possible strategies against this important class of antiviral target.

Enhancing Oxygen Evolution Reaction Performance with rGO/CoNi-Prussian Blue-Derived Oxyhydroxide Nanocomposite Electrocatalyst: A Strategic Synthetic Approach.

Electrochemical water splitting is a promising approach in the development of renewable energy technologies, providing an alternative to fossil fuels. It has attracted considerable attention in recent years. The benchmark materials used in water splitting are precious metals that are expensive and scarce. Therefore, this work proposes a strategic electrochemical synthesis of a reduced graphene oxide and cobalt-nickel hexacyanoferrate (rGO/CoNiHCF)-derived composite (rGO/CoNiPBd-OOH) to achieve optimized OER performance. The optimum rGO/CoNiHCF was fabricated with the Co:Ni precursors in a 3:1 ratio with a ferricyanide solution of pH = 1.0. Using an alkaline electrochemical treatment, the well-distributed globular particles of CoNiHCF over rGO sheets were converted into layered frameworks of metallic (oxy)hydroxide species, giving the final rGO/CoNiPBd-OOH nanocomposite. This nanocomposite presented favorable kinetic activity resulting in a Tafel slope of 33 mV dec-1, while rGO, CoNiPBd-OOH, and RuO2 exhibited slopes of 80, 47, and 51 mV dec-1, respectively. Although the benchmark RuO2 electrocatalyst showed a lower overpotential (240 mV dec-1) at a current density of 10 mA cm-2, the rGO/CoNiPBd-OOH performed well with an overpotential of 346 mV, combined with superior stability compared to CoNiPBd-OOH and RuO2, maintaining a current density of 10 mA cm-2 for 15 h with an overpotential loss of 6.92%. This work successfully presents an "all-electrochemical" synthesis of a rGO/CoNiHCF-derived material with remarkable electrocatalytic activity for OER assisted by a strategic preparation methodology, which helped to understand the influence of synthetic parameters and choose their conditions to achieve the optimum OER performance.

Acquisition-invariant brain MRI segmentation with informative uncertainties.

Combining multi-site data can strengthen and uncover trends, but is a task that is marred by the influence of site-specific covariates that can bias the data and, therefore, any downstream analyses. Post-hoc multi-site correction methods exist but have strong assumptions that often do not hold in real-world scenarios. Algorithms should be designed in a way that can account for site-specific effects, such as those that arise from sequence parameter choices, and in instances where generalisation fails, should be able to identify such a failure by means of explicit uncertainty modelling. This body of work showcases such an algorithm that can become robust to the physics of acquisition in the context of segmentation tasks while simultaneously modelling uncertainty. We demonstrate that our method not only generalises to complete holdout datasets, preserving segmentation quality but does so while also accounting for site-specific sequence choices, which also allows it to perform as a harmonisation tool.

Generating multi-pathological and multi-modal images and labels for brain MRI.

The last few years have seen a boom in using generative models to augment real datasets, as synthetic data can effectively model real data distributions and provide privacy-preserving, shareable datasets that can be used to train deep learning models. However, most of these methods are 2D and provide synthetic datasets that come, at most, with categorical annotations. The generation of paired images and segmentation samples that can be used in downstream, supervised segmentation tasks remains fairly uncharted territory. This work proposes a two-stage generative model capable of producing 2D and 3D semantic label maps and corresponding multi-modal images. We use a latent diffusion model for label synthesis and a VAE-GAN for semantic image synthesis. Synthetic datasets provided by this model are shown to work in a wide variety of segmentation tasks, supporting small, real datasets or fully replacing them while maintaining good performance. We also demonstrate its ability to improve downstream performance on out-of-distribution data.