Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined Systemic and Hepatic Artery Infusion Pump Chemo-Therapy as a Liver-Directed Therapy for Colorectal Liver Metastasis-Review of Literature and Case Discussion

Simple Summary Liver metastasis is a major therapeutic challenge and common cause of death for patients with colorectal cancer. While systemic treatment especially chemotherapy remains the mainstay of treatment, selected patients with liver-only metastasis may further benefit from liver-directed therapies. Direct infusion of chemotherapy into the liver metastases via an implantable hepatic arterial infusion pump (HAIP) is potentially an effective way to improve treatment response and survival in selected patients. Here, we reviewed the literature utilizing HAIP as a liver-directed modality alone and in combination with systemic chemotherapy. We discussed two cases who were successfully treated with this combinatorial approach and achieved remission or prolongation of disease control. We discussed the limitations, toxicities of combined systemic and HAIP modalities. Lastly, we provided insights on the use of HAIP in the modern era of systemic treatment for colorectal cancer patients with liver metastasis. Abstract Colorectal cancer (CRC) is the third most prevalent malignancy and the second most common cause of death in the US. Liver is the most common site of colorectal metastases. About 13% of patients with colorectal cancer have liver metastasis on initial presentation and 50% develop them during the disease course. Although systemic chemotherapy and immunotherapy are the mainstay treatment for patients with metastatic disease, for selected patients with predominant liver metastasis, liver-directed approaches may provide prolonged disease control when combined with systemic treatments. Hepatic artery infusion pump (HAIP) chemotherapy is an approach which allows direct infusion of chemotherapeutic into the liver and is especially useful in the setting of multifocal liver metastases. When combined with systemic chemotherapy, HAIP improves the response rate, provides more durable disease control, and in some patients leads to successful resection. To ensure safety, use of HAIP requires multidisciplinary collaboration between interventional radiologists, medical oncologists, hepatobiliary surgeons and treatment nurses. Here, we review the benefits and potential risks with this approach and provide our single institution experience on two CRC patients successfully treated with HAIP in combination with systemic chemotherapy. We provide our recommendations in adopting this technique in the current era for patient with colorectal liver metastases.
Small Bait Traps May Not Accurately Reflect the Composition of Necrophagous Diptera Associated to Remains

Simple Summary Fly families such as Calliphoridae and Muscidae contribute to the decomposition of cadavers and play an important role in courtroom proceedings, in part because of the clues they provide to help determine the time of death. In forensic entomology studies, they are often sampled using small bait traps containing a small amount of decomposing animal tissue. To determine whether the fly assemblages recovered by small bait traps are similar to those found on whole remains, we simultaneously documented the flies found on domestic pig carcasses and within small traps baited with pork liver. Results indicated that the fly assemblages found in the small bait traps and on the carcasses were different and reinforced the fact that caution should be exercised when data obtained from small bait traps are used in court. Abstract Small bait traps are beginning to emerge in forensic entomology as a new approach to sample early-colonizing necrophagous Diptera species while reducing the investment in time and energy in obtaining information. To test the hypothesis conveyed by the literature that these traps can be a substitute for whole carcasses, we simultaneously documented the Diptera assemblages visiting and colonizing domestic pig carcasses and small traps baited with pork liver. Results indicated that Diptera species occurrence and assemblage composition in the small bait traps and on the carcasses differed, while they were similar when comparing only the pig carcasses. These results are in agreement with the literature that examined insect colonization of other decaying substrates. Although small bait traps can be useful tools to document the communities of necrophagous Diptera in a given area, we stress that caution must be exercised when extending the data obtained by these traps to courtroom proceedings.
Complications of Poly-l-Lactic Acid and Polyglycolic Acid (PLLA/PGA) Osteosynthesis Systems for Maxillofacial Surgery: A Retrospective Clinical Investigation

Two second-generation PLLA/PGA bioresorbable osteosynthetic plate systems for oral and maxillofacial surgery are available in Japan. The two systems have different PLLA-PGA component ratios (RapidSorb®, 85:15; Lactosorb®, 82:18) and plate and screw shapes. We conducted a retrospective study to compare our clinical evaluation and examine the incidence of postoperative complications between the two plate systems. A retrospective survey was conducted in 148 patients (midfacial fracture/trauma (68.2%) and dentofacial deformity patients (31.8%); males (54.7%); median age, 37.5 years) treated using maxillofacial osteosynthetic plate systems. The complications included plate exposure (7.4%), infection, (2.7%), and plate breakage (0.7%). Multivariate logistic regression analysis showed a significant correlation between sex (female), plate system (Lactosorb®), number of plates, and pyriform aperture and periorbital sites of plate placement (p < 0.05). Additionally, the propensity score-adjusted model showed a significant correlation between Lactosorb® and postoperative complications (odds ratio 1.007 (95% confidence interval, 1.001–1.055), p < 0.01). However, the two plate systems showed a low incidence rate of complications, and the plate integration and survivability were similar using 2.0-mm or 1.5-mm resorbable plate regardless of the plate system. Our findings suggest that female sex and a greater number of plates are risk factors for postoperative complications, whereas pyriform aperture and periorbital plate placements reduce the risk.
Influence of Micronutrient Intake, Sociodemographic, and Behavioral Factors on Periodontal Status of Adults Assisted by a Public Health Care System in Brazil: A Cross-Sectional Multivariate Analysis

The lack of access to a balanced diet, rich in vitamins and minerals, can predispose people to inflammatory diseases such as obesity, diabetes mellitus, and periodontitis. We aimed to evaluate the relationship between micronutrient intake, sociodemographic behavioral characteristics, and periodontal health in adults assisted by a public health care system. Participants (n = 450) answered a food frequency questionnaire and were submitted to anthropometric and oral clinical examinations. Principal component analysis was used to summarize the number of components emerging from 17-micronutrient intake. Subsequently, cluster analysis was employed. The prevalence of at least one periodontal pocket ≥ 4 mm was 67.4%. Three clusters were identified according to periodontal status. Cluster 1 “poor periodontal status” was characterized by older individuals (n = 202; 85% females) with poor periodontal status, lower education level, mainly smokers with non-transmissible chronic diseases (NTCD), with lower energy, omega-3, fiber, Zn, K, Cu, and vitamin C intake. Cluster 3 “healthy periodontal status” included younger individuals (n = 54) with the healthiest periodontal status, a higher education level, without NTCD, and with higher energy, omega-3, fiber, Zn, calcium, retinol, and riboflavin intake. Cluster 2 was labeled as “intermediate periodontal status”. Micronutrient ingestion was associated with periodontal status and may be considered in health promotion actions for low-income populations.
A Tryptophan ‘Gate’ in the CRISPR-Cas3 Nuclease Controls ssDNA Entry into the Nuclease Site, That When Removed Results in Nuclease Hyperactivity

Cas3 is a ssDNA-targeting nuclease-helicase essential for class 1 prokaryotic CRISPR immunity systems, which has been utilized for genome editing in human cells. Cas3-DNA crystal structures show that ssDNA follows a pathway from helicase domains into a HD-nuclease active site, requiring protein conformational flexibility during DNA translocation. In genetic studies, we had noted that the efficacy of Cas3 in CRISPR immunity was drastically reduced when temperature was increased from 30 °C to 37 °C, caused by an unknown mechanism. Here, using E. coli Cas3 proteins, we show that reduced nuclease activity at higher temperature corresponds with measurable changes in protein structure. This effect of temperature on Cas3 was alleviated by changing a single highly conserved tryptophan residue (Trp-406) into an alanine. This Cas3W406A protein is a hyperactive nuclease that functions independently from temperature and from the interference effector module Cascade. Trp-406 is situated at the interface of Cas3 HD and RecA1 domains that is important for maneuvering DNA into the nuclease active site. Molecular dynamics simulations based on the experimental data showed temperature-induced changes in positioning of Trp-406 that either blocked or cleared the ssDNA pathway. We propose that Trp-406 forms a ‘gate’ for controlling Cas3 nuclease activity via access of ssDNA to the nuclease active site. The effect of temperature in these experiments may indicate allosteric control of Cas3 nuclease activity caused by changes in protein conformations. The hyperactive Cas3W406A protein may offer improved Cas3-based genetic editing in human cells.
Effect of Extract and Synthesized Derivatives of Isolated Compound from Symplocos chinensis f. Pilosa Ohwi on Neuropathic Pain in Mice

Neuropathic pain is described as the “most terrible of all tortures that a nerve wound may inflict. ” The aim of the present study was to demonstrate the antinociceptive effect of Symplocos chinensis f. pilosa Ohwiwaterextract (SCW) and synthesized derivatives of the isolated compound. The antinociceptive effect was tested using the acetic acid‐induced writhing and 5% formalin tests. Antinociceptive effects on neuropathic pain were evaluated using the von Frey test with chronic constriction injury (CCI) and surgical nerve ligation (SNI) models and tail‐flick test with a vincristine‐induced pain model. An Ames test was also conducted. 5‐hydroxymethylfurfural (5‐HMF) was isolated and derivatives were synthesized with various acid groups. Among the plant water extracts, SCW showed significantly effective activity. Additionally, SCW presented antinociceptive effects in the neuropathic pain models. The SCW water fraction resulted in fewer writhes than the other fractions, and isolated 5‐HMF was identified as an effective compound. Because 5‐HMF revealed a positive response in the Ames test, derivatives were synthesized. Among the synthesized derivations, 5‐succinoxymethylfurfural (5‐SMF) showed the best effect in the neuropathic pain model. Our data suggest that SCW and the synthesized compound, 5‐SMF, possess effective antinociceptive activity against neuropathic pain.
The Cohabitation of Humans and Urban Cats in the Anthropocene: The Clash of Welfare Concepts

Simple Summary Current cultural shifts in Western countries have changed the position of the cat to a companion animal, and its traditional role as a pest controller is no longer recognized by city dwellers. In a growing number of theoretical and field studies, the hunting abilities of cats and their high fertility are perceived as environmental risks. Bringing together theoretical perspectives from human–animal studies, animal ethics, population ecology, and biosemiotics, I highlight the existence of two different ecological (and even cultural) communities inhabiting urban environments: the culture of feral cats and the humano–cat culture of pets. Arguments are given for the essential role of feral cats in the population dynamics of the species when a growing number of pet cats are routinely neutered. Whereas neutering is presented by animal shelters and veterinary institutions as a universal means for improving cat welfare, it is at odds with the psychobiological needs of cats as viewed by a laissez-faire approach. This leads us to the conclusion that instead of one type of management of free-roaming cats, individual solutions should be sought to achieve a balance between the welfare of cats, other species, and human cultures in diverse urban environments. Abstract Urban environments are inhabited by several types of feline populations, which we can differentiate as feral cats, free-roaming pets, and confined pets. Due to a shift in the cultural representation of cats from pest controllers to companion animals, cats living semi-independently of humans are perceived increasingly negatively, while the pet population has become the object of intense care. A regulative approach converges with a concern for welfare in the operation and educational campaigns of municipal shelters, which through their implementation of neutering policies have proven to be key players in the contemporary relation of urban cats and humans. The generally widespread notion of cat welfare associated with a secure life comes into tension with the fact that the psychobiological needs of feral cats are significantly different than those of pets. It becomes apparent that individual interactions between humans and cats in urban environments in the Anthropocene are increasingly influenced by the intervention of institutions that can be characterized as seeking to administer the wild.
Rheological and Textural Properties of Apple Pectin-Based Composite Formula with Xanthan Gum Modification for Preparation of Thickened Matrices with Dysphagia-Friendly Potential

Modifying the consistency of a given edible fluid matrix by incorporating food thickeners is a common nursing remedy for individuals with dysphagia when adequate water consumption is a concern. As apple pectin (AP) offers nutraceutical benefits, properly formulated apple pectin (AP)-based thickeners featuring xanthan gum (XG) can be superior candidates for preparation of dysphagia-friendly matrices (DFMs). Our recruited DFMs exhibit fluid-like behavior (loss modulus > storage modulus, G” > G’) at lower AP concentrations (2 and 5%, w/w); they turn into weak/critical gels (G’ ≈ G”) as the concentration becomes higher (9%). In contrast, XG-DFMs display gel-like attributes with G’ > G”, even at rather low concentrations (<1%) and become more resistant to sugar, Na+, and Ca2+ modifications. The composite matrix of AP1.8XG0. 2 (constraint at 2%) exhibits a confined viscosity of 278 ± 11.7 mPa∙s, which is considered a DFM, in comparison to only AP- or XG-thickened ones. The hardness measurements of XG0.6 and AP1.2XG0. 8 are 288.33 ± 7.506 and 302.00 ± 9.849 N/m2, respectively, which potentially represent a promising formulation base for future applications with DFMs; these textural values are not significantly different from a commercially available product (p > 0.05) for dysphagia nursing administrations.
Cell-Free DNA for the Management of Classical Hodgkin Lymphoma

Cell-free DNA (cfDNA) testing, is an emerging “liquid biopsy” tool for noninvasive lymphoma detection, and an increased amount of data are now available to use this technique with accuracy, especially in classical Hodgkin lymphoma (cHL). The advantages of cfDNA include simplicity of repeated blood sample acquisition over time; dynamic, noninvasive, and quantitative analysis; fast turnover time; reasonable cost; and established consistency with results from tumor genomic DNA. cfDNA analysis offers an easy method for genotyping the overall molecular landscape of pediatric and adult cHL and may help in cases of diagnostic difficulties between cHL and other lymphomas. cfDNA levels are correlated with clinical, prognostic, and metabolic features, and may serve as a therapeutic response evaluation tool and as a minimal residual disease (MRD) biomarker in complement to positron emission tomography (PET). Indeed, cfDNA real-time monitoring by fast high-throughput techniques enables the prompt detection of refractory disease or may help to address PET residual hypermetabolic situations during or at the end of treatment. The major recent works presented and described here demonstrated the clinically meaningful applicability of cfDNA testing in diagnostic and theranostic settings, but also in disease risk assessment, therapeutic molecular response, and monitoring of cHL treatments.
The Interaction of Human and Epstein–Barr Virus miRNAs with Multiple Sclerosis Risk Loci

Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines of evidence suggest that Epstein–Barr virus (EBV) infection may contribute to the development of MS. Here, we aimed to identify the potential contribution of EBV-encoded and host cellular miRNAs to MS pathogenesis. We identified differentially expressed host miRNAs in EBV infected B cells (LCLs) and putative host/EBV miRNA interactions with MS risk loci. We estimated the genotype effect of MS risk loci on the identified putative miRNA:mRNA interactions in silico. We found that the protective allele of MS risk SNP rs4808760 reduces the expression of hsa-mir-3188-3p. In addition, our analysis suggests that hsa-let-7b-5p may interact with ZC3HAV1 differently in LCLs compared to B cells. In vitro assays indicated that the protective allele of MS risk SNP rs10271373 increases ZC3HAV1 expression in LCLs, but not in B cells. The higher expression for the protective allele in LCLs is consistent with increased IFN response via ZC3HAV1 and so decreased immune evasion by EBV. Taken together, this provides evidence that EBV infection dysregulates the B cell miRNA machinery, including MS risk miRNAs, which may contribute to MS pathogenesis via interaction with MS risk genes either directly or indirectly.
Antimicrobial Effect and the Mechanism of Diallyl Trisulfide against Campylobacter jejuni

Campylobacter jejuni is an important foodborne pathogen causing campylobacteriosis. It can infect humans through the consumption of contaminated chicken products or via the direct handling of animals. Diallyl trisulfide (DATS) is a trisulfide compound from garlic extracts that has a potential antimicrobial effect on foodborne pathogens. This study investigated the antimicrobial activity of DATS on C. jejuni by evaluating the minimal inhibitory concentrations (MICs) of C. jejuni 81-168, and fourteen C. jejuni isolates from chicken carcasses. Thirteen of 14 C. jejuni isolates and 81-176 had MICs ≤ 32 μg/mL, while one isolate had MIC of 64 μg/mL. Scanning electron microscopy (SEM) analysis showed the disruption and shrink of C. jejuni bacterial cell membrane after the DATS treatment. A time-killing analysis further showed that DATS had a dose-dependent in vitro antimicrobial effect on C. jejuni during the 24 h treatment period. In addition, DATS also showed an antimicrobial effect in chicken through the decrease of C. jejuni colony count by 1.5 log CFU/g (cloacal sample) during the seven-day DATS treatment period. The transcriptional analysis of C. jejuni with 16 μg/mL (0.5× MIC) showed 210 differentially expression genes (DEGs), which were mainly related to the metabolism, bacterial membrane transporter system and the secretion system. Fourteen ABC transporter-related genes responsible for bacterial cell homeostasis and oxidative stress were downregulated, indicating that DATS could decrease the bacterial ability to against environmental stress. We further constructed five ABC transporter deletion mutants according to the RNA-seq analysis, and all five mutants proved less tolerant to the DATS treatment compared to the wild type by MIC test. This study elucidated the antimicrobial activity of DATS on C. jejuni and suggested that DATS could be used as a potential antimicrobial compound in the feed and food industry.
Therapeutic Potential of AAV1-Rheb(S16H) Transduction against Neurodegenerative Diseases

Neurotrophic factors (NTFs) are essential for cell growth, survival, synaptic plasticity, and maintenance of specific neuronal population in the central nervous system. Multiple studies have demonstrated that alterations in the levels and activities of NTFs are related to the pathology and symptoms of neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease. Hence, the key molecule that can regulate the expression of NTFs is an important target for gene therapy coupling adeno-associated virus vector (AAV) gene. We have previously reported that the Ras homolog protein enriched in brain (Rheb)–mammalian target of rapamycin complex 1 (mTORC1) axis plays a vital role in preventing neuronal death in the brain of AD and PD patients. AAV transduction using a constitutively active form of Rheb exerts a neuroprotective effect through the upregulation of NTFs, thereby promoting the neurotrophic interaction between astrocytes and neurons in AD conditions. These findings suggest the role of Rheb as an important regulator of the regulatory system of NTFs to treat neurodegenerative diseases. In this review, we present an overview of the role of Rheb in neurodegenerative diseases and summarize the therapeutic potential of AAV serotype 1 (AAV1)-Rheb(S16H) transduction in the treatment of neurodegenerative disorders, focusing on diseases, such as AD and PD.