Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease.

Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.

SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity.

Succinate is a signaling metabolite sensed extracellularly by succinate receptor 1 (SUNCR1). The accumulation of succinate in macrophages is known to activate a pro-inflammatory program; however, the contribution of SUCNR1 to macrophage phenotype and function has remained unclear. Here we found that activation of SUCNR1 had a critical role in the anti-inflammatory responses in macrophages. Myeloid-specific deficiency in SUCNR1 promoted a local pro-inflammatory phenotype, disrupted glucose homeostasis in mice fed a normal chow diet, exacerbated the metabolic consequences of diet-induced obesity and impaired adipose-tissue browning in response to cold exposure. Activation of SUCNR1 promoted an anti-inflammatory phenotype in macrophages and boosted the response of these cells to type 2 cytokines, including interleukin-4. Succinate decreased the expression of inflammatory markers in adipose tissue from lean human subjects but not that from obese subjects, who had lower expression of SUCNR1 in adipose-tissue-resident macrophages. Our findings highlight the importance of succinate-SUCNR1 signaling in determining macrophage polarization and assign a role to succinate in limiting inflammation.

RegulonDB v12.0: a comprehensive resource of transcriptional regulation in E. coli K-12.

RegulonDB is a database that contains the most comprehensive corpus of knowledge of the regulation of transcription initiation of Escherichia coli K-12, including data from both classical molecular biology and high-throughput methodologies. Here, we describe biological advances since our last NAR paper of 2019. We explain the changes to satisfy FAIR requirements. We also present a full reconstruction of the RegulonDB computational infrastructure, which has significantly improved data storage, retrieval and accessibility and thus supports a more intuitive and user-friendly experience. The integration of graphical tools provides clear visual representations of genetic regulation data, facilitating data interpretation and knowledge integration. RegulonDB version 12.0 can be accessed at https://regulondb.ccg.unam.mx.

United States-Based Colorectal Cancer Surgical Trials Lack Representation and Adequate Reporting of Racially and Ethnically Diverse Participants: Systematic Review and Regression Analysis.

BACKGROUND: Despite the established National Institute of Health Revitalization Act, which aims to include ethnic and racial minority representation in surgical trials, racial and ethnic enrollment disparities persist. OBJECTIVE: To assess the proportion of patients from minority races and ethnicities that are included in colorectal cancer surgical trials and reporting characteristics. DATA SOURCES: Search was performed using MEDLINE (Ovid), Embase, Web of Science, and Cochrane Central. STUDY SELECTION: Inclusion criteria included 1) trials performed in the United States between January 1, 2000, and May 30, 2022; 2) patients with colorectal cancer diagnosis; and 3) surgical intervention, technique, or postoperative outcome. Trials evaluating chemotherapy, radiotherapy, or other nonsurgical interventions were excluded. INTERVENTIONS: Pooled proportion and regression analysis was performed to identify the proportion of patients by race and ethnicity included in surgical trials and the association of year of publication and funding source. MAIN OUTCOME MEASURES: Proportion of trials reporting race and ethnicity and proportion of participants by race and ethnicity included in surgical trials. RESULTS: We screened 10,673 unique publications, of which 80 were examined in full text. Fifteen studies met our inclusion criteria. Ten (66.7%) trials did not report race, 3 reported races as a proportion of White participants only, and 3 reported 3 or more races. There was no description of ethnicity in 11 (73.3%) trials, with 2 describing "non-Caucasian" as ethnicity and 2 describing only Hispanic ethnicity. Pooled proportion of White participants was 81.3%, of Black participants was 6.2%, of Asian participants was 3.6%, and of Hispanic participants was 3.5%. LIMITATIONS: A small number of studies was identified that reported racial or ethnic characteristics of their participants. CONCLUSIONS: Both race and ethnicity are severely underreported in colorectal cancer surgical trials. To improve outcomes and ensure the inclusion of vulnerable populations in innovative technologies and novel treatments, reporting must be closely monitored.

Association of Metabolic Derangement and Postoperative Outcomes in Hernia Repair With Component Separation: A Propensity Score-matched Nationwide Analysis.

INTRODUCTION: Metabolic syndrome (MetS) is characterized by cardiometabolic abnormalities such as hypertension, obesity, diabetes, or dyslipidemia. This study aims to evaluate the association of MetS on the postoperative outcomes of ventral, umbilical, and epigastric hernia repair using component separation. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to identify patients who underwent ventral, umbilical, and epigastric hernia repair with component separation between 2015 and 2021. MetS status was defined as patients receiving medical treatment for diabetes mellitus and hypertension, with a body mass index greater than 30 kg/m2. Propensity matching was performed to generate two balanced cohorts with and without MetS. T-tests and Fisher's Exact tests assessed group differences. Logistic regression models evaluated complications between the groups. RESULTS: After propensity score matching, 3930 patients were included in the analysis, with 1965 in each group (MetS versus non-MetS). Significant differences were observed in the severity and clinical presentation of hernias between the groups. The MetS cohort had higher rates of incarcerated hernia (39.1% versus 33.2%; P < 0.001), and recurrent ventral hernia (42.7% versus 36.5%; P < 0.001) compared to the non-MetS cohort. The MetS group demonstrated significantly increased rates of renal insufficiency (P = 0.026), unplanned intubation (P = 0.003), cardiac arrest (P = 0.005), and reoperation rates (P = 0.002) than the non-MetS cohort. Logistic regression models demonstrated higher likelihood of postoperative complications in the MetS group, including mild systemic complications (OR 1.25; 95%CI 1.030-1.518; P = 0.024), severe systemic complications (OR 1.63; 95%CI 1.248-2.120; P < 0.001), and reoperation (OR 1.47; 95%CI 1.158-1.866; P = 0.002). There were no significant differences in the rates of 30-d wound complications between groups. CONCLUSIONS: The presence of metabolic derangement appears to be associated with adverse postoperative medical outcomes and increased reoperation rates after hernia repair with component separation. These findings highlight the importance of optimizing preoperative comorbidities as surgeons counsel patients with MetS.

Monocyte distribution width (MDW): study of reference values in blood donors.

OBJECTIVES: Monocyte distribution width (MDW) is a new biomarker used as an early indicator of sepsis (ESId). It is often aids in the identification of patients who may develop sepsis. This study aims to establish the MDW reference interval (RI) within the healthy population of blood donors using EDTA-K2 as anticoagulant. Many hospitals use this biomarker as a means of identifying patients who present to the hospital with sepsis. METHODS: A total of 274 samples obtained from healthy donors were analyzed. MDW measurements were taken within 2 h post-extraction. The RI was estimated using various statistical methodologies, including the recommended CLSI EP28-A3c guideline, non-parametric and robust methods, along with the Harrell-Davis bootstrap method applied to the entire sample. RESULTS: The RI estimated through non-parametric method was 14.77 CI90 % (14.36-14.97)-21.13 CI90 % (20.89-21.68); RI using the robust method was 15.64-19.05 and RI using the Harrell-Davis bootstrap method was 14.73 CI90 % (14.53-14.92)-21.14 CI90 % (20.88-21.40). CONCLUSIONS: Based on clinical applicability, we recommend utilizing the RI derived from the non-parametric method, aligning with the CLSI recommendations. Furthermore, we consider that our results can be taken as a reference in other laboratories that serve a population similar to our study cohort.

Women in Plastic Surgery Innovation: A 10-Year Review of Gender Representation in Mammary Device Patents.

BACKGROUND: This study aims to pioneer in evaluating women's representation in plastic surgery innovations, focusing on mammary prosthesis devices' inventorship. Despite growing gender parity in the field, women's involvement in innovation remains underexplored. This is especially crucial, as the predominant recipients of these innovative technologies are women, urging a necessity for broader female engagement in pioneering surgical advancements. METHOD: Patents under the "A61F2/12: Mammary prostheses and implants" classification between the dates January 1, 2011, to December 31, 2020, were identified using Google Patents Advanced. Inclusion criteria included patents (not designs) in English and applications (not grants), with no litigation limitations. Data collected included ID, title, assignee (categorized as industry, academic, private, individual), inventors, and dates (priority, filing, and publication). Sex of inventors was identified with the literature validated gender API, with manual resolution of unresolved genders or with ga_accuracy scores of less than 75%. Data were analyzed using 2-tailed Student t tests, χ2 analysis, and Pearson correlation coefficient (significance set at P ≤ 0.05). RESULTS: Of the more than 130,000 plastic surgery patents in English identified between the 10-year period, 1355 were classified as A61F2/12. A total of 374 unique patents were included for analysis (841 duplicates were removed, and 140 patents were excluded because of non-English character author names). There was a significant increase in patents over the decade (from 15 in 2011 to 88 in 2020, R2 = 0.74, P < 0.05), with a decrease in number of inventors per patent (R2 = 0.12, P < 0.05). Of the 1102 total inventors, 138 were female (11.2%), with a 4-fold increase in representation over the decade (R2 = 0.58, P < 0.05), including increase in patents filed with a woman first inventor (0%-14.8%). Women were equally likely to be first 3 inventors versus middle to last inventors (12.8% vs 11.1%, respectively). CONCLUSIONS: Over a decade, mammary device innovations rose significantly. Although women inventors' representation improved, it remains disproportionate compared with women in residency/practice. Hence, interventions should aim to align inventor representation with training ratios, through institutional optimization, reducing gender segmentation, and enhancing funding opportunities.

The value of microvascular breast reconstruction: Cost equivalence of TRAM and DIEP flaps implications in the era of CMS reforms.

BACKGROUND: Recent CMS billing changes have raised concerns about insurance coverage for deep inferior epigastric perforator (DIEP) flap breast reconstruction. This study compared the costs and utilization of transverse rectus abdominis myocutaneous (TRAM), DIEP, and latissimus dorsi (LD) flaps in breast reconstruction. METHOD: The study utilized the National Inpatient Sample database to identify female patients who underwent DIEP, TRAM, and LD flap procedures from 2016 to 2019. Key data such as patient demographics, length of stay, complications, and costs (adjusted to 2021 USD) were analyzed, focusing on differences across the flap types. RESULTS: A total of 17,770 weighted patient encounters were identified, with the median age being 51. The majority underwent DIEP flaps (73.5%), followed by TRAM (14.2%) and LD (12.1%) flaps. The findings revealed that DIEP and TRAM flaps had a similar length of stay (LOS), while LD flaps typically had a shorter LOS. The total hospital charges to costs using cost-to-charge ratio were also comparable between DIEP and TRAM flaps, whereas LD flaps were significantly less expensive. Factors such as income quartile, primary payer of hospitalization, and geographic region significantly influenced flap choice. CONCLUSION: The study's results appear to contradict the prevailing notion that TRAM flaps are more cost-effective than DIEP flaps. The total hospital charges to costs using cost-to-charge ratio and hospital stays associated with TRAM and DIEP flaps were found to be similar. These findings suggest that changes in the insurance landscape, which may limit the use of DIEP flaps, could undermine patient autonomy while not necessarily reducing healthcare costs. Such policy shifts could favor less costly options like the LD flap, potentially altering the landscape of microvascular breast reconstruction.

From Case Reports to Molecular Insight: Examining the Outcomes and Underlying Mechanisms of Squamous Cell Carcinoma in Breast Implant Patients-A Systematic Review.

There is extensive coverage in the existing literature on implant-associated lymphomas like anaplastic large-cell lymphoma, but breast implant-associated squamous cell carcinoma (BIA-SCC) has received limited scholarly attention since its first case in 1992. Thus, this study aims to conduct a qualitative synthesis focused on the underexplored association between breast implants and BIA-SCC. A systematic review was conducted utilizing the PubMed, Web of Science, and Cochrane databases to identify all currently reported cases of BIA-SCC. Additionally, a literature review was performed to identify potential biochemical mechanisms that could lead to BIA-SCC. Studies were vetted for quality using the NIH quality assessment tool. From an initial pool of 246 papers, 11 met the quality criteria for inclusion, examining a total of 14 patients aged between 40 and 81 years. BIA-SCC was found in a diverse range of implants, including those with smooth and textured surfaces, as well as those filled with saline and silicone. The condition notably manifested a proclivity for aggressive clinical progression, as evidenced by a mortality rate approximating 21.4% within a post-diagnostic interval of six months. Our literature review reveals that chronic inflammation, driven by various external factors such as pathogens and implants, can initiate carcinogenesis through epigenetic modifications and immune system alterations. This includes effects from exosomes and macrophage polarization, showcasing potential pathways for the pathogenesis of BIA-SCC. The study highlights the pressing need for further investigation into BIA-SCC, a subject hitherto inadequately addressed in the academic sphere. This necessitates the urgency for early screening and intervention to improve postoperative outcomes. While the review is confined by its reliance on case reports and series, it serves as a valuable reference for future research endeavors.

Effects of leaf and stem maturation on nutritional value in Megathyrsus maximus.

BACKGROUND: Megathyrsus maximus is a forage grass native to Africa but widely cultivated in tropical and subtropical regions of the world where it is part of the grazing food chain. This study aimed to evaluate five M. maximus genotypes for the effect of maturity on their morpho-agronomic traits, nutritional composition and digestibility, and to correlate their leaf blade and stem anatomy with their nutritional value. RESULTS: The proportion of sclerenchyma tissues increased as maturity was reached, while lignin accumulation was differentiated between genotypes. Gatton Panic, Green Panic and Mutale genotypes maintained their acid detergent lignin (ADL) values for leaf blades in the three cuts evaluated. In sacco ruminal dry matter disappearance was lower in Green Panic genotype at the vegetative stage for stems, but not for leaf blades. Significant positive correlations were found between dry matter disappearance and mesophyll tissues, and the latter were negatively correlated with neutral detergent fiber (NDF) and ADL. CONCLUSION: Our results strongly indicate that cutting age and genotype affected the nutritional value of M. maximus leaf blades and stems, with a more pronounced loss of quality in stems than in leaf blades. We recommend increasing the frequency of grazing at early stage or anticipating the stage of stem elongation in Green Panic to produce forage with better nutritional value. © 2023 Society of Chemical Industry.

An Institutional Analysis of Early Postoperative Free Tissue Transfer Takeback Procedures.

BACKGROUND: Postoperative free tissue transfer reexploration procedures are relatively infrequent but associated with increased overall failure rates. This study examines the differences between flaps requiring takeback versus no takeback, as well as trends in reexploration techniques that may increase the odds of successful salvage. METHODS: A retrospective review was conducted on all free tissue transfers performed at our institution from 2011 to 2022. Patients who underwent flap reexploration within 30 days of the original procedure were compared with a randomly selected control group who underwent free flap procedures without reexploration (1:2 cases to controls). Univariate and multivariate logistic regression analyses were performed. RESULTS: From 1,213 free tissue transfers performed in the study period, 187 patients were included in the analysis. Of the total flaps performed, 62 (0.05%) required takeback, and 125 were randomly selected as a control group. Free flap indication, flap type, reconstruction location, and number of venous anastomoses differed significantly between the two groups. Among the reexplored flaps, 8 (4.3% of the total) had a subsequent failure while 54 (87.10%) were salvaged, with significant differences in cause of initial flap failure, affected vessel type, and salvage technique. CONCLUSION: Free tissue transfers least prone to reexploration involved breast reconstruction in patients without predisposition to hypercoagulability or reconstruction history. When takeback operations were required, salvage was more likely in those without microvascular compromise or with an isolated venous injury who required a single exploratory operation.

Postcolonoscopy colorectal cancer: Prevalence, categorization and root-cause analysis based on the World Endoscopic Organization system.

AIMS: The World Endoscopy Organization (WEO) recommends that endoscopy units implement a process to identify postcolonoscopy colorectal cancer (PCCRC). The aims of this study were to assess the 3-year PCCRC rate and to perform root-cause analyses and categorization in accordance with the WEO recommendations. PATIENTS AND METHODS: Cases of colorectal cancers (CRCs) in a tertiary care center were retrospectively included from January 2018 to December 2019. The 3-year and 4-year PCCRC rates were calculated. A root-cause analysis and categorization of PCCRCs (interval and type A, B, C noninterval PCCRCs) were performed. The level of agreement between two expert endoscopists was assessed. RESULTS: A total of 530 cases of CRC were included. A total of 33 were deemed PCCRCs (age 75.8±9.5 years; 51.5% women). The 3-year and 4-year PCCRC rates were 3.4% and 4.7%, respectively. The level of agreement between the two endoscopists was acceptable either for the root-cause analysis (k=0.958) or for the categorization (k=0.76). The most plausible explanations of the PCCRCs were 8 "likely new PCCRCs", 1 (4%) "detected, not resected", 3 (12%) "detected, incomplete resection", 8 (32%) "missed lesion, inadequate examination", and 13 (52%) "missed lesion, adequate examination". Most PCCRCs were deemed noninterval Type C PCCRCs (N=17, 51.5%). CONCLUSION: WEO recommendations for root-cause analysis and categorization are useful to detect areas for improvement. Most PCCRCs were avoidable and were likely due to missed lesions during an otherwise adequate examination.

Pulmonary glycogen deficiency as a new potential cause of respiratory distress syndrome.

The glycogenin knockout mouse is a model of Glycogen Storage Disease type XV. These animals show high perinatal mortality (90%) due to respiratory failure. The lungs of glycogenin-deficient embryos and P0 mice have a lower glycogen content than that of wild-type counterparts. Embryonic lungs were found to have decreased levels of mature surfactant proteins SP-B and SP-C, together with incomplete processing of precursors. Furthermore, non-surviving pups showed collapsed sacculi, which may be linked to a significantly reduced amount of surfactant proteins. A similar pattern was observed in glycogen synthase1-deficient mice, which are devoid of glycogen in the lungs and are also affected by high perinatal mortality due to atelectasis. These results indicate that glycogen availability is a key factor for the burst of surfactant production required to ensure correct lung expansion at the establishment of air breathing. Our findings confirm that glycogen deficiency in lungs can cause respiratory distress syndrome and suggest that mutations in glycogenin and glycogen synthase 1 genes may underlie cases of idiopathic neonatal death.

Regulation of death receptor signaling by the autophagy protein TP53INP2.

TP53INP2 positively regulates autophagy by binding to Atg8 proteins. Here, we uncover a novel role of TP53INP2 in death-receptor signaling. TP53INP2 sensitizes cells to apoptosis induced by death receptor ligands. In keeping with this, TP53INP2 deficiency in cultured cells or mouse livers protects against death receptor-induced apoptosis. TP53INP2 binds caspase-8 and the ubiquitin ligase TRAF6, thereby promoting the ubiquitination and activation of caspase-8 by TRAF6. We have defined a TRAF6-interacting motif (TIM) and a ubiquitin-interacting motif in TP53INP2, enabling it to function as a scaffold bridging already ubiquitinated caspase-8 to TRAF6 for further polyubiquitination of caspase-8. Mutations of key TIM residues in TP53INP2 abrogate its interaction with TRAF6 and caspase-8, and subsequently reduce levels of death receptor-induced apoptosis. A screen of cancer cell lines showed that those with higher protein levels of TP53INP2 are more prone to TRAIL-induced apoptosis, making TP53INP2 a potential predictive marker of cancer cell responsiveness to TRAIL treatment. These findings uncover a novel mechanism for the regulation of caspase-8 ubiquitination and reveal TP53INP2 as an important regulator of the death receptor pathway.

Design of novel granulopoietic proteins by topological rescaffolding.

Computational protein design is rapidly becoming more powerful, and improving the accuracy of computational methods would greatly streamline protein engineering by eliminating the need for empirical optimization in the laboratory. In this work, we set out to design novel granulopoietic agents using a rescaffolding strategy with the goal of achieving simpler and more stable proteins. All of the 4 experimentally tested designs were folded, monomeric, and stable, while the 2 determined structures agreed with the design models within less than 2.5 Å. Despite the lack of significant topological or sequence similarity to their natural granulopoietic counterpart, 2 designs bound to the granulocyte colony-stimulating factor (G-CSF) receptor and exhibited potent, but delayed, in vitro proliferative activity in a G-CSF-dependent cell line. Interestingly, the designs also induced proliferation and differentiation of primary human hematopoietic stem cells into mature granulocytes, highlighting the utility of our approach to develop highly active therapeutic leads purely based on computational design.

Risk factors associated to incisional hernia in stoma site after stoma closure: A systematic review and meta-analysis.

BACKGROUND: This study aims to identify which risk factors are associated with the appearance of an incisional hernia in a stoma site after its closure. This in the sake of identifying which patients would benefit from a preventative intervention and thus start implementing a cost-effective protocol for prophylactic mesh placement in high-risk patients. METHODS: A systematic review of PubMed, Cochrane library, and ScienceDirect was performed according to PRISMA guidelines. Studies reporting incidence, risk factors, and follow-up time for appearance of incisional hernia after stoma site closure were included. A fixed-effects and random effects models were used to calculate odds ratios' estimates and standardized mean values with their respective grouped 95% confidence interval. This to evaluate the association between possible risk factors and the appearance of incisional hernia after stoma site closure. RESULTS: Seventeen studies totaling 2899 patients were included. Incidence proportion between included studies was of 16.76% (CI95% 12.82; 21.62). Out of the evaluated factors higher BMI (p = 0.0001), presence of parastomal hernia (p = 0.0023), colostomy (p = 0,001), and end stoma (p = 0.0405) were associated with the appearance of incisional hernia in stoma site after stoma closure, while malignant disease (p = 0.0084) and rectum anterior resection (p = 0.0011) were found to be protective factors. CONCLUSIONS: Prophylactic mesh placement should be considered as an effective preventative intervention in high-risk patients (obese patients, patients with parastomal hernia, colostomy, and end stoma patients) with the goal of reducing incisional hernia rates in stoma site after closure while remaining cost-effective.

Laser-Assisted and Device-Assisted Filler Delivery: A Histologic Evaluation.

BACKGROUND: Lasers and devices are used to enhance transcutaneous delivery of fillers. However, little has been published on the histologic findings of this form of laser/device-assisted delivery to determine the optimal devices and fillers. OBJECTIVE: To objectively evaluate the histological effects of laser-assisted and device-assisted filler delivery. METHODS: Ex vivo human abdominoplasty skin samples were treated with fractional CO 2 laser (ECO 2 , 120 µm tip, 120 mJ), fractional radiofrequency microneedling (FRMN, Genius, 1.5 mm, 20 mJ/pin), and microneedling (2.0 mm). Immediately after poly- l -lactic acid (PLLA), hyaluronic acid gel, calcium hydroxylapatite, and black tissue marking dye were topically applied. After treatment, biopsies were collected for histologic evaluation. RESULTS: Histology revealed that PLLA and black dye were found in greatest abundance, hyaluronic acid was found to a lesser extent, and calcium hydroxylapatite was least found within channels created by fractional CO 2 laser. Microneedling was effective only at delivering black dye, whereas FRMN failed to show significant channel formation or delivery of the studied products. CONCLUSION: Among the devices and fillers studied, fractional CO 2 laser and PLLA proved to be the most effective combination for laser/device-assisted filler delivery. Neither microneedling nor FRMN was effective as devices to enhance filler delivery.

Dynamic Feature Dataset for Ransomware Detection Using Machine Learning Algorithms.

Ransomware-related cyber-attacks have been on the rise over the last decade, disturbing organizations considerably. Developing new and better ways to detect this type of malware is necessary. This research applies dynamic analysis and machine learning to identify the ever-evolving ransomware signatures using selected dynamic features. Since most of the attributes are shared by diverse ransomware-affected samples, our study can be used for detecting current and even new variants of the threat. This research has the following objectives: (1) Execute experiments with encryptor and locker ransomware combined with goodware to generate JSON files with dynamic parameters using a sandbox. (2) Analyze and select the most relevant and non-redundant dynamic features for identifying encryptor and locker ransomware from goodware. (3) Generate and make public a dynamic features dataset that includes these selected parameters for samples of different artifacts. (4) Apply the dynamic feature dataset to obtain models with machine learning algorithms. Five platforms, 20 ransomware, and 20 goodware artifacts were evaluated. The final feature dataset is composed of 2000 registers of 50 characteristics each. This dataset allows for a machine learning detection with a 10-fold cross-evaluation with an average accuracy superior to 0.99 for gradient boosted regression trees, random forest, and neural networks.

Incidental Bystander or Essential Culprit: A Systematic Review of Bacterial Significance in the Pathogenesis of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a distinct subtype of T-cell non-Hodgkin lymphoma that arises in the context of prolonged exposure to textured breast implants. The intent of this manuscript is to explore whether the bacterial presence in biofilms on these implants is a mere incidental finding or plays a pivotal role in the pathogenesis of BIA-ALCL. Our goal is to delineate the extent of bacterial involvement, offering insights into potential underlying mechanisms, and establishing future research priorities aimed at resolving the remaining uncertainties surrounding this complex association. A comprehensive systematic review of several databases was performed. The search strategy was designed and conducted by an experienced librarian using controlled vocabulary with keywords. The electronic search identified 442 publications. After evaluation, six studies from 2015 to 2021 were included, encompassing 201 female patients aged 23 to 75. The diagnosis span post-implantation ranged from 53 to 135.6 months. Studies consistently found bacteria near breast implants in both BIA-ALCL cases and controls, with varied microbial findings. Both BIA-ALCL cases and controls exhibited the presence of specific bacteria, including Pseudomonas aeruginosa, Klebsiella oxytoca, Staphylococcus aureus, and Ralstonia spp., without any statistically significant differences between groups. The use of antiseptic and antimicrobial agents during implant insertion did not demonstrate any impact on reducing or altering the risk of developing BIA-ALCL. Our systematic review reveals that the current evidence is inadequate to link bacterial etiology as a central factor in the development of BIA-ALCL. The limitations in the existing data prevent a complete dismissal of the role of biofilms in its pathogenesis. The observed gap in knowledge underscores the need for more focused and comprehensive research, which should be structured in a multi-faceted approach. Initially, this involves the utilization of sophisticated genomic and proteomic methods. Following this, it is crucial to delve into the study of immunological reactions specifically induced by biofilms. Finally, this research should incorporate extended observational studies, meticulously tracking the evolution of biofilm development and its correlation with the emergence of BIA-ALCL. In light of the inconclusive nature of current findings, further investigation is not only justified but urgently needed to clarify these unresolved issues.

COVID-19 vaccination rate and willingness of an additional dose among inflammatory bowel disease patients receiving biologic therapy: Fearless and with desire.

Effective vaccines against the SARS-CoV-2 are already available and offer a promising action to control the COVID-19 pandemic. IBD patients on biological agents accept the vaccine as well as an additional dose if recommended. BACKGROUND: Vaccination against COVID-19 prevents its severe forms and associated mortality and offers a promising action to control this pandemic. In September 2021, an additional dose of vaccine was approved in patients with immunosuppression including IBD patients on biologic agents. We evaluated the vaccination rate and additional dose willingness in this group of at risk patients. METHODS: A single-center, cross-sectional study was performed among IBD patients on biologic agents and eligible for an additional dose of the COVID-19 vaccine. IBD clinical characteristics and type of vaccine and date of administration were checked in medical records. Acceptance was evaluated after telephone or face-to-face surveys in IBD patients. RESULTS: Out of a total of 344 patients, 269 patients (46.1% male; mean age 47±16 years; Crohn's disease 73.6%) were included. Only 15 (5.6%) patients refused the COVID-19 vaccine mainly (40%) for conviction (COVID-19 pandemic denial). 33.3% would re-consider after discussing with their doctor and/or receiving information on the adverse effects of the vaccine. Previous to the additional dose, the COVID-19 vaccination was present in 94.4% of patients (n=254). Adverse effects occurred in 53.9% of the cases, mainly pain in the arm (40%). Up to 94.1% of the patients agreed to an additional dose and 79.4% had already received the additional dose at the final time of the assessment. CONCLUSIONS: IBD patients on biological agents accept the vaccine as well as an additional dose if recommended. Physicians in charge of IBD units should provide information and confidence in the use of the vaccine in these IBD patients.