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Backgrounds: MUTYH-associated polyposis (MAP) is an autosomal recessive disease caused by biallelic pathogenic variants (PV) of the MUTYH gene. The aim of this study was to investigate the genetic causes of unexplained polyposis patients with monoallelic MUTYH PV. The analysis focused on 26 patients with suspected MAP, belonging to 23 families. Ten probands carried also one or more additional MUTYH variants of unknown significance., Methods: Based on variant type and on the collected clinical and molecular data, these variants were reinterpreted by applying the ACMG/AMP rules. Moreover, supplementary analyses were carried out to investigate the presence of other variants and copy number variations in the coding and promoter regions of MUTYH, as well as other polyposis genes (APC, NTHL1, POLE, POLD1, MSH3, RNF43, and MCM9)., Results: We reclassified 4 out of 10 MUTYH variants as pathogenic or likely pathogenic, thus supporting the diagnosis of MAP in only four cases. Two other patients belonging to the same family showed a previously undetected deletion of the APC gene promoter. No PVs were found in the other investigated genes. However, 6 out of the 18 remaining families are still interesting MAP candidates, due to the co-presence of a class 3 MUTYH variant that could be reinterpreted in the next future., Conclusion: Several efforts are necessary to fully elucidate the genetic etiology of suspected MAP patients, especially those with the most severe polyposis/tumor phenotype. Clinical data, tumor molecular profile, family history, and polyposis inheritance mode may guide variant interpretation and address supplementary studies., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Classification of variants in the BRCA1 and BRCA2 genes has a major impact on the clinical management of subjects at high risk for breast and ovarian cancer. The identification of a pathogenic variant allows for early detection/prevention strategies in healthy carriers as well as targeted treatments in patients affected by BRCA-associated tumors. The BRCA2 c.9227G>T p.(Gly3076Val) variant recurs in families from Northeast Italy and is rarely reported in international databases. This variant substitutes the evolutionary invariant glycine 3076 with a valine in the DNA binding domain of the BRCA2 protein, thus suggesting a high probability of pathogenicity. We analysed clinical and genealogic data of carriers from 15 breast/ovarian cancer families in whom no other pathogenic variants were detected. The variant was shown to co-segregate with breast and ovarian cancer in the most informative families. Combined segregation data led to a likelihood ratio of 81,527:1 of pathogenicity vs. neutrality. We conclude that c.9227G>T is a BRCA2 pathogenic variant that recurs in Northeast Italy. It can now be safely used for the predictive testing of healthy family members to guide preventive surgery and/or early tumor detection strategies, as well as for PARP inhibitors treatments in patients with BRCA2-associated tumors.

Background: Male breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. BRCA1 and BRCA2 mutations account for about 10% of all MBC cases. Thus, a fraction of MBC cases are expected to be due to genetic factors not yet identified. To further explain the genetic susceptibility for MBC, whole-exome sequencing (WES) and targeted gene sequencing were applied to high-risk, BRCA1/2 mutation-negative MBC cases., Methods: Germ-line DNA of 1 male and 2 female BRCA1/2 mutation-negative breast cancer (BC) cases from a pedigree showing a first-degree family history of MBC was analyzed with WES. Targeted gene sequencing for the validation of WES results was performed for 48 high-risk, BRCA1/2 mutation-negative MBC cases from an Italian multicenter study of MBC. A case-control series of 433 BRCA1/2 mutation-negative MBC and female breast cancer (FBC) cases and 849 male and female controls was included in the study., Results: WES in the family identified the partner and localizer of BRCA2 (PALB2) c.419delA truncating mutation carried by the proband, her father, and her paternal uncle (all affected with BC) and the N-acetyltransferase 1 (NAT1) c.97C>T nonsense mutation carried by the proband's maternal aunt. Targeted PALB2 sequencing detected the c.1984A>T nonsense mutation in 1 of the 48 BRCA1/2 mutation-negative MBC cases. NAT1 c.97C>T was not found in the case-control series., Conclusions: These results add strength to the evidence showing that PALB2 is involved in BC risk for both sexes and indicate that consideration should be given to clinical testing of PALB2 for BRCA1/2 mutation-negative families with multiple MBC and FBC cases. Cancer 2017;123:210-218. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

The production of rice husks, abundant agro-waste rich in biopolymers and minerals, already at a rate of 120 million tons/year, is expected to further increase to meet the demand of a growing world population. It is the most common use as fuel pollutes air, water, and soil. However, there is still a significant lack of methods for fractionation of all of its compounds. We are presenting here a biorefinery process based on successive extraction of extractives (xylose, lignin, cellulose, and silica) from rice husk through pre-extraction, hydrolysis, organosolv pulping, and demineralization while assessing the effect of these processes on the extracted biopolymers. The optimized conditions for pulping of hydrolyzed rice husks are 3% of FeCl3·6H2O as catalyst, a biomass/solvent ratio of 1:10 (m/v), and a 50% ethanol:water as cooking liquor treated in a reactor at 200 °C for 60 min. The conditions for demineralization of the pulp resulting from organosolv pulping are 10% of Na2CO3 as base, a biomass/solvent ratio of 1:15 (m/v), and treated in a reactor at 115 °C for 30 min. The properties of the lignin and cellulose recovered from hydrolyzed rice husk were almost identical to those of untreated rice husk. We successfully obtained lignin with a recovery of 47% and a purity of 94%, cellulose recovered after silica removal with only 1% ash and a purity of 82%, while also recovering silica. The recovery of lignin and cellulose, along with silica, offers an opportunity for further valorization while also proposing an alternative solution to rice husk disposal and implicated pollution. [ABSTRACT FROM AUTHOR]

This review explores the potential of biopolymers as sustainable alternatives to conventional plastics in food packaging. Biopolymers derived from plant or animal sources are crucial in extending food shelf life, minimizing degradation, and protecting against oxidative and microbial agents. Their physical and chemical properties, influenced by the raw materials used, determine their suitability for specific applications. Biopolymers have been successfully used in fruits, vegetables, meats, and dairy products, offering antimicrobial and antioxidant benefits. Consequently, they represent a functional and eco-friendly solution for the packaging industry, contributing to sustainability while maintaining product quality. [ABSTRACT FROM AUTHOR]

MUTYH variants are differently distributed in geographical areas of the world. In MUTYH-associated polyposis (MAP) patients from North-Eastern Italy, c.933+3A>C (IVS10+3A>C), a transversion causing an aberrant splicing process, accounts for nearly 1/5 of all mutations. The aim of this study was to verify whether its high frequency in North-Eastern Italy is due to a founder effect and to clarify its impact on MUTYH transcripts and protein. Haplotype analysis and age estimate performed on members of eleven Italian MAP families and cancer-free controls provided evidence that c.933+3A>C is a founder mutation originated about 83 generations ago. In addition, the Italian haplotype associated with the c.933+3A>C was also found in German families segregating the same mutation, indicating it had a common origin in Western Europe. Altogether c.933+3A>C and the two common Caucasian mutations p.Tyr179Cys and p.Gly396Asp represent about 60% of MUTYH alterations in MAP patients from North-Eastern Italy, suggesting the opportunity to perform targeted molecular screening for these variants in the diagnostic setting. Expression analyses performed on lymphoblastoid cell lines supported the notion that MUTYH c.933+3A>C alters splicing causing the synthesis of a non functional protein. However, some primary transcripts escape aberrant splicing, producing traces of full-length transcript and wild-type protein in a homozygote; this is in agreement with clinical findings that suggest a relatively mild phenotypic effect for this mutation. Overall, these data, that demonstrate a founder effect and further elucidate the splicing alterations caused by the MUTYH c.933+3A>C mutation, have important implications for genetic counseling and molecular diagnosis of MAP., (Copyright © 2012 UICC.)

In this study, the fabrication of magnetic hemicellulosic composite microspheres and the adsorption of copper ions are explored. The microspheres were prepared by the micro-emulsion technique, using Fe3O4 nanoparticles and hemicellulose extracted from wheat straw with the ionic liquid B[mim]Cl as a solvent. Fe3O4 nanoparticles, synthesized through coprecipitation, were evenly encapsulated within the hemicellulosic microspheres. The Fe3O4 nanoparticles measured 10–15 nm in size, while the microspheres had an average diameter of about 20 μm and displayed a saturation magnetization of 35.95 emu/g. The optimal conditions for copper adsorption by the microspheres were found to be a pH of 5.0, a temperature of 323 K, and an initial copper ion concentration of 80 mg/L, resulting in an adsorption capacity of 85.65 mg/g after 24 h. The adsorption kinetics followed a pseudo-second-order model, and the Langmuir isotherm suggested a monomolecular layer adsorption mechanism, with a theoretical maximum capacity of 149.25 mg/g. In summary, the magnetic hemicellulosic microspheres exhibited considerable adsorption potential and favorable recycling capabilities for copper ions. [ABSTRACT FROM AUTHOR]

This paper describes the effect of two different fillers derived from giant reed (Arundo donax L.), namely fibers and shredded aerial parts of the plant, on the thermal properties of polyethylene-based composites, as the analysis of dimensional stability of lignocellulose-based composites, and its relationship with their thermal diffusivity, has not yet been assessed in the literature. It has been found that the introduction of such materials resulted in a significant reduction of the coefficient of thermal expansion, particularly more important in the case of fibers, due to their higher aspect ratio; in particular, this coefficient is reduced to less than half for fibrous composites (from 1.6·10− 4 K− 1 to 6.1·10− 5 K− 1 or 3.5·10− 5 K− 1 for 20 and 40% loadings). This parameter also influences the thermal diffusivity of the final parts; the diffusivity of composites increases with the ratio of lignocellulosic filler used, particularly when using fibers, due to a better orientation of these fibers than the shredded material, which does not exhibit a fibrous shape. Composites with 20% share of the filler exhibited a thermal diffusivity increased by about 15% compared to neat polyethylene, while 40% loadings resulted in a 25% and 60% increase for ground and fibrous materials, respectively. These results provide additional features to lignocellulose-composites characterization, providing properties not usually mentioned in the literature to expand the knowledge about such composite materials beyond mechanical properties, providing a broader range of properties to offer a wider application area of such composites. Statement of Novelty Arundo donax L. is of great interest to biorefineries due to its fast growth and resistance to adverse environmental conditions. Most research on this plant species focuses on obtaining energy products or valuable chemicals, while very few are related to composite production, particularly on thermoplastic materials. The work found in the literature so far does not provide insights into the relationships between the types of filler (and their aspect ratio) and their thermal properties. Therefore, this work expands the knowledge on the thermal behavior of lignocellulose-polymer composites, supplementing the research, usually focused only on mechanical properties, in their characterization by correlative analysis of thermal influenced dimensional change with structure and thermal diffusivity. Determining the coefficient of thermal expansion (CTE) is a relevant parameter to assess the possibilities of using a material at high or low temperatures and evaluate the dimensional stability of a product during its service lifetime. On the other hand, thermal diffusivity brings together the capacity of a material to store thermal energy and distribute it throughout the material; that is, it relates heat capacity and thermal conductivity, which are also essential in using materials in market applications. Therefore, the work not only provides the results of thermal diffusivity and CTE of thermoplastic-reed composites but also correlates both parameters as a way to widen the range of application of plant-based composites in areas where dimensional stability (i.e., low thermal expansion) is required. [ABSTRACT FROM AUTHOR]

Rice straw is a relevant and potential feedstock for bioethanol production due to its abundance and availability around the globe. In this study, a fractional factorial design (FFD 25–1) was applied to simultaneously evaluate the influence of only alkaline and acid-alkaline pretreatment conditions in glucose release, considering the glucose release after 12 and 24 h of enzymatic hydrolysis as responses and predicting alternatives for the fractionation of rice straw components. Hydrolysis yields (HY) higher than 90% were achieved using low enzyme loads (8 FPU/g substrate) after only 24 h of hydrolysis under optimized pretreatment conditions. Simultaneous DOE optimization showed that the acid step is optional to achieve higher HY but can contribute to a more holistic use of the hemicellulose fraction. Also, it significantly increased the hydrolysis efficiency compared to untreated rice straw (HY = 18%). Enzymatic hydrolysis with a different type of enzymatic cocktail in the optimized conditions using higher solid contents resulted in high cellulose conversion (up to 85%), showing the robustness of the DOE optimization and its applicability as a starting point for optimizations using other types of enzymes. Chemical and morphological analyses were also carried out to understand the effect of the treatments, aiming to achieve pretreatment and hydrolysis processes more effective for lignocellulosic biorefineries. [ABSTRACT FROM AUTHOR]

Background: Plastics are the most flexible products developed with a wide range of applications. They have been incorporated into almost every aspect of daily life due to their strength and low weight. However, widespread use and inadequate waste management have resulted in the accumulation of tiny plastic particles throughout the environment. Main text: Microplastics are found in oceans, rivers, sediments, sewers, soil, and agricultural products, even in table salts. Human beings are affected by microplastics through food ingestion and inhalation. Incorporated microplastics may accrue within the body and affect gastrointestinal, immune, endocrine, brain, and respiratory systems. It also interferes with the functions of major organs and causes chromosomal abnormalities. Conclusion: Addressing the issue of micro and nanoplastics requires interdisciplinary research, sustainable solutions, and improved waste management systems. The main focus of this review is to cover the harmful effects and impact of microplastics on human health and stress the need for combating strategies. [ABSTRACT FROM AUTHOR]

Purpose: Composting process can be accelerated by seeding microbial consortium into compost of plant residues and livestock manure mixture. The consortium could also be sourced from decomposing sawdust due to extensive microbial activity. This study investigated the effect of decomposing sawdust as an inoculant on the microbial and physicochemical properties of sawdust-chicken manure compost. Method: Decomposing sawdust collected at a depth of 0.6-1.2 m and a temperature between 40-48 °C was seeded into a sawdust-chicken manure mixture. The composting formulations used were, fresh sawdust + chicken manure (FSCM), fresh sawdust + decomposing sawdust (FSDS), and fresh sawdust + chicken manure + decomposing sawdust (FSCMDS). The composting process involved the use of pyramid piles (1.98 m × 1.89 m × 0.68 m). Physicochemical and microbial enzyme profiling, Scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and plant bioassays were carried out. Results: The compost formulations without inoculant exhibited higher microbial and enzyme activities throughout the composting process (lasting 37 days). High temperatures (45-59 °C) eliminates coliform bacteria after day 10, while thermophilic bacteria increased, with mesophilic bacteria dominating from the 25th day until maturation. The C/N ratio decreased to 12.62 and 15.04 in FSCM and FSCMDS, respectively, with reduced lignocellulosic composition and increased nutrients. The SEM analysis indicated disintegration of the feedstock while the FTIR spectra showed improvement in the aromatic content. Conclusion: Overall, the FSCM formulation had the greatest effect on compost qualities and Phaseolus vulgaris development. FSDS did not promote the composting process. Thus, composting sawdust and chicken manure alone was sufficient to achieve a desirable C/N ratio, nutrient level, efficient degradation, microbial population, compost sanitization and growth of Phaseolus vulgaris. [ABSTRACT FROM AUTHOR]

Aim: To investigate simultaneously UGT1A7, UGT1A9, ARP, SPINK and CFTR genes to verify whether genetic polymorphisms predispose to the development of pancreatic cancer (PC)., Methods: Genomic DNA of 61 pancreatic cancer patients and 105 healthy controls (HC) were analyzed. UGT1A7 genotyping was determined by PCR-RFLP analysis. Specific PCR and sequencing were used to analyze genetic variants of UGT1A9, ARP, SPINK1 and CFTR genes., Results: Four different alleles (*1: WT; *2: N129K and R131K; *3: N129K, R131K, and W208R; and *4: W208R) in UGT1A7 and three different alleles (*1: WT; *4: Y242X; and *5: D256N) in UGT1A9 were detected. All UGT1A polymorphisms were observed at similar frequency in PC patients and HC. Seven different alleles in ARP were found in PC patients and HC at similar frequency. The SPINK1 mutations N34S and P55S occurred in five PC patients with a prevalence (4.1%) not significantly different from that observed (2.0%) in HC. The only CFTR DeltaF508 mutation was recognized in three PC patients with a prevalence (4.9%) similar to HC., Conclusion: UGT1A7, UGT1A9, ARP, SPINK1 and CFTR gene polymorphisms are not associated with PC in Italian patients.

Purpose: Many studies have evaluated the role of high levels of microsatellite instability (MSI) as a prognostic marker and predictor of the response to chemotherapy in colorectal cancer (CRC); however, the results are not conclusive. The aim of this study was to analyze the prognostic significance of high levels of MSI (MSI-H) in CRC patients in relation to fluorouracil-based chemotherapy., Experimental Design: In three different institutions, 1,263 patients with CRC were tested for the presence of MSI, and CRC-specific survival was then analyzed in relation to MSI status, chemotherapy, and other clinical and pathologic variables., Results: Two hundred and fifty-six tumors were MSI-H (20.3%): these were more frequently at a less advanced stage, right-sided, poorly differentiated, with mucinous phenotype, and expansive growth pattern than microsatellite stable carcinomas. Univariate and multivariate analyses of 5-year-specific survival revealed stage, tumor location, grade of differentiation, MSI, gender, and age as significant prognostic factors. The prognostic advantage of MSI tumors was particularly evident in stages II and III in which chemotherapy did not significantly affect the survival of MSI-H patients. Finally, we analyzed survival in MSI-H patients in relation to the presence of mismatch repair gene mutations. MSI-H patients with hereditary non-polyposis colorectal cancer showed a better prognosis as compared with sporadic MSI-H; however, in multivariate analysis, this difference disappeared., Conclusions: The type of genomic instability could influence the prognosis of CRC, in particular in stages II and III. Fluorouracil-based chemotherapy does not seem to improve survival among MSI-H patients. The survival benefit for patients with hereditary non-polyposis colorectal cancer is mainly determined by younger age and less advanced stage as compared with sporadic MSI-H counterpart.

A systematic search by Southern blot analysis in a cohort of 439 hereditary nonpolyposis colorectal cancer (HNPCC) families for genomic rearrangements in the main mismatch repair (MMR) genes, namely, MSH2, MLH1, MSH6, and PMS2, identified 48 genomic rearrangements causative of this inherited predisposition to colorectal cancer in 68 unrelated kindreds. Twenty-nine of the 48 rearrangements were found in MSH2, 13 in MLH1, 2 in MSH6, and 4 in PMS2. The vast majority were deletions, although one previously described large inversion, an intronic insertion, and a more complex rearrangement also were found. Twenty-four deletion breakpoints have been identified and sequenced in order to determine the underlying recombination mechanisms. Most fall within repetitive sequences, mainly Alu repeats, in agreement with the differential distribution of deletions between the MSH2 and MLH1 genes: the higher number and density of Alu repeats in MSH2 corresponded with a higher incidence of genomic rearrangement at this disease locus when compared with other MMR genes. Long interspersed nuclear element (LINE) repeats, relatively abundant in, for example, MLH1, did not seem to contribute to the genesis of the deletions, presumably because of their older evolutionary age and divergence among individual repeat units when compared with short interspersed nuclear element (SINE) repeats, including Alu repeats. Moreover, Southern blot analysis of the introns and the genomic regions flanking the MMR genes allowed us to detect 6 novel genomic rearrangements that left the coding region of the disease-causing gene intact. These rearrangements comprised 4 deletions upstream of the coding region of MSH2 (3 cases) and MSH6 (1 case), a 2-kb insertion in intron 7 of PMS2, and a small (459-bp) deletion in intron 13 of MLH1. The characterization of these genomic rearrangements underlines the importance of genomic deletions in the etiology of HNPCC and will facilitate the development of PCR-based tests for their detection in diagnostic laboratories.

Background: Gemcitabine has been recently recognized as standard treatment in advanced pancreatic cancer. To potentiate its single-agent activity we conducted a phase I-II study with the primary objective of establishing the maximum tolererated dose (MTD) of gemcitabine and continuous infusion 5-FU in patients with locally advanced or metastatic pancreatic cancer., Patients and Methods: Fifteen patients received a fired dose of 5-FU 200 mg/mq protracted infusion for six months. Gemcitabine was administered weekly for three out of four weeks for six cycles at escalating doses of 800 mg/mq to 1100 mg/mq., Results: MTD was established at 1000 mg/mq of gem citabine. Of the 11 evaluable patients, 7 patients had stable disease, 1 had partial response and 3 had progressive disease. Of the 14 patients evaluable at follow-up, median time to progression was 5 months. Median survival was 10 months., Conclusion: This study confirms the good tolerability of the combination, of gemcitabine with 5-FU.

A new easy protocol to functionalize the middle layer of commercial surgical face masks (FMs) with Zn and Cu oxides is proposed in order to obtain antibacterial personal protective equipment. Zinc and copper oxides were synthesized embedded in a polydopamine (PDA) shell as potential antibacterial agents; they were analyzed by XRD and TEM, revealing, in all the cases, the formation of metal oxide nanoparticles (NPs). PDA is a natural polymer appreciated for its simple and rapid synthesis, biocompatibility, and high functionalization; it is used in this work as an organic matrix that, in addition to stabilizing NPs, also acts as a diluent in the functionalization step, decreasing the metal loading on the polypropylene (PP) surface. The functionalized middle layers of the FMs were characterized by SEM, XRD, FTIR, and TXRF and tested in their bacterial-growth-inhibiting effect against Klebsiella pneumoniae and Staphylococcus aureus. Among all functionalizing agents, Cu2O-doped-ZnO NPs enclosed in PDA shell, prepared by an ultrasound-assisted method, showed the best antibacterial effect, even at low metal loading, without changing the hydrophobicity of the FM. This approach offers a sustainable solution by prolonging FM lifespan and reducing material waste. [ABSTRACT FROM AUTHOR]

This study investigates the effectiveness of hydrothermal and alkaline pretreatment methods in enhancing the concentration of fermentable sugars derived from rice husk waste. After the pretreatments, enzymatic hydrolysis and fermentation processes were executed to evaluate the ethanol production from each pretreatment. Rice husk powder measuring ≤250 µm was used. For the alkaline pretreatment, sodium hydroxide (NaOH) was used at concentrations ranging from 0.5, 1 to 1.5% w/v. The efficacy of the hydrothermal pretreatment method was evaluated after 15, 30 and 45 min at 120 °C. The enzymatic hydrolysis process was performed over 144 h at 50 °C, pH 4.8 with an enzyme loading of 30 FPU (filter paper units). Fermentation was carried out at 37 °C using a strain of Saccharomyces cerevisiae Hansen 1883 (NCYC 366). Results indicated that the optimal conditions for alkaline pretreatment were observed at a 1.5% NaOH, while the best hydrothermal procedure was achieved at 120 °C and 45 min. The impact of these pretreatments was assessed based on the efficiency of enzymatic hydrolysis. The alkaline pretreatment resulted in 81.70% conversion of cellulose to glucose and 96.30% conversion of hemicellulose to xylose. In contrast, the hydrothermal pretreatment achieved 93% cellulose-to-glucose conversion and 83.35% hemicellulose-to-xylose conversion. The ethanol production registered ranged from 13 to 13.23 g·L−1, corresponding to a conversion factor of 0.43 for ethanol from fermentable sugars. [ABSTRACT FROM AUTHOR]

Rice husk is a valuable biomass that contains large amounts of amorphous silica. This study aims to present a simple combined thermal and chemical method of silica extraction from Iranian rice husk and to investigate the effect of operating conditions on the morphology of the obtained silica. The work also studied the effects of the extracted silica loading in two standard adhesion systems in the tire formulations, namely, rubber adhesion to resorcinol-formaldehyde-latex (RFL) coated polyester cords and rubber adhesion to brass-plated steel cords. The obtained amorphous silica showed different surface area in the range of 73 to 341 m2/g, which presented different rubber-cord adhesion values in rubber formulations. It was found that the pH of the precipitation step is the controlling factor of the silica surface area, which itself has a significant effect on the rubber-cord adhesion behavior. The decarbonization temperature of 700 ± 100 °C and the precipitation pH of 6 are favorable operating conditions for the production of amorphous silica, which is suitable for rubber-to-cord adhesion systems. [ABSTRACT FROM AUTHOR]