The development of brain metastases in patients with different therapeutic strategies for metastatic renal cell cancer.

A diagnosis of brain metastasis (BM) significantly affects quality of life in patients with metastatic renal cell cancer (mRCC). Although systemic treatments have shown efficacy in mRCC, active surveillance (AS) is still commonly used in clinical practice. In this single-center cohort study, we assessed the impact of different initial treatment strategies for metastatic RCC (mRCC) on the development of BM. All consecutive patients diagnosed with mRCC between 2011 and 2022 were included at the Erasmus MC Cancer Institute, the Netherlands, and a subgroup of patients with BM was selected. In total, 381 patients with mRCC (ECM, BM, or both) were identified. Forty-six patients had BM of whom 39 had metachronous BM (diagnosed ≥1 month after ECM). Twenty-five (64.1%) of these 39 patients with metachronous BM had received prior systemic treatment for ECM and 14 (35.9%) patients were treatment naive at BM diagnosis. The median BM-free survival since ECM diagnosis was significantly longer (p = .02) in previously treated patients (29.0 [IQR 12.6-57.0] months) compared to treatment naive patients (6.8 [IQR 1.0-7.0] months). In conclusion, patients with mRCC who received systemic treatment for ECM prior to BM diagnosis had a longer BM-free survival as compared to treatment naïve patients. These results emphasize the need for careful evaluation of treatment strategies, and especially AS, for patients with mRCC.

Catheter Tip-Associated Mass With Continuous Infusion of Sufentanil for Persistent Spinal Pain Syndrome Type 2: A Case Report Including Histopathologic Examination and Review of the Associated Basic and Clinical Research.

OBJECTIVES: Intrathecal opioids delivered by implanted pumps are used to treat malignant or nonmalignant chronic pain. In this study, we 1) review a case in which intrathecal infusions of sufentanil along with other adjuvants were used and after an extended period led to an intrathecal mass and 2) compared and contrasted the potential mechanisms for these phenomena. MATERIALS AND METHODS: A woman aged 66 years with a history of scoliosis and multiple spine surgeries was treated with an implantable drug delivery system for treating persistent pain after laminectomy. The patient received intrathecal medication comprising sufentanil, bupivacaine, and clonidine. RESULTS: Intrathecal therapy over approximately ten years served to reduce pain and improve function over the treatment period. After the extended treatment interval, the patient developed an intrathecal mass that was associated with impairment. The mass was surgically removed. Systematic histopathology revealed the space-occupying mass to largely comprise fibroblasts and some inflammatory cells embedded in a collagen mass located proximally to the catheter tip. CONCLUSIONS: To our knowledge, this is the first published case report of sufentanil causing this complication. The science and mechanism of intrathecal catheter tip-associated mass formation and associated clinical research correlates are reviewed in detail, and explanations for this phenomenon are proposed based on histochemical analysis of the patient's pathology findings.

Reevaluation of Sensitivity of Monilinia fructicola Isolates to the DMI Fungicide Propiconazole in the Southeastern United States and Investigation of the Genetic Element Mona.

Sterol demethylation inhibitor (DMI) fungicides continue to be essential components for the control of brown rot of peach caused by Monilinia fructicola in the United States and worldwide. In the southeastern United States, resistance to DMIs had been associated with overexpression of the cytochrome P450 14α-demethylase gene MfCYP51 as well as the genetic element Mona, a 65 bp in length nucleotide sequence located upstream of MfCYP51 in resistant isolates. About 20 years after the first survey, we reevaluated sensitivity of M. fructicola from South Carolina and Georgia to propiconazole and also evaluated isolates from Alabama for the first time. A total of 238 M. fructicola isolates were collected from various commercial and two experimental orchards, and sensitivity to propiconazole was determined based on a discriminatory dose of 0.3 µg/ml. Results indicated 16.2, 89.2, and 72.4% of isolates from Alabama, Georgia, and South Carolina, respectively, were resistant to propiconazole. The detection of resistance in Alabama is the first report for the state. All resistant isolates contained Mona, but it was absent from most sensitive isolates. It was unclear if the resistance frequency had increased in South Carolina and Georgia. However, the resistance levels (as assessed by the isolate frequency in discriminatory dose-based relative growth categories) did not change notably, and no evidence of other resistance genotypes was found. Analysis of the upstream MfCYP51 gene region in the resistant isolate CF010 revealed an insertion sequence described for the first time in this report. Our study suggests that current fungicide spray programs have been effective against increasing resistance levels in populations of M. fructicola and suppressing development of new resistant genotypes of the pathogen.

Circadian clock- and temperature-associated genes contribute to overall genomic differentiation along elevation in lichenized fungi.

Circadian regulation is linked to local environmental adaptation, and many species with broad climatic niches display variation in circadian genes. Here, we hypothesize that lichenizing fungi occupying different climate zones tune their metabolism to local environmental conditions with the help of their circadian systems. We study two species of the genus Umbilicaria occupying similar climatic niches (Mediterranean and the cold temperate) in different continents. Using homology to Neurospora crassa genes, we identify gene sets associated with circadian rhythms (11 core, 39 peripheral genes) as well as temperature response (37 genes). Nucleotide diversity of these genes is significantly correlated with mean annual temperature, minimum temperature of the coldest month and mean temperature of the coldest quarter. Furthermore, we identify altitudinal clines in allele frequencies in several non-synonymous substitutions in core clock components, for example, white collar-like, frh-like and various ccg-like genes. A dN/dS approach revealed a few significant peripheral clock- and temperature-associated genes (e.g. ras-1-like, gna-1-like) that may play a role in fine-tuning the circadian clock and temperature-response machinery. An analysis of allele frequency changes demonstrated the strongest evidence for differentiation above the genomic background in the clock-associated genes in U. pustulata. These results highlight the likely relevance of the circadian clock in environmental adaptation, particularly frost tolerance, of lichens. Whether or not the fungal clock modulates the symbiotic interaction within the lichen consortium remains to be investigated. We corroborate the finding of genetic variation in clock components along altitude-not only latitude-as has been reported in other species.

Pericentromeric recombination suppression and the 'large X effect' in plants.

X chromosome was reported to be a major contributor to isolation between closely related species-the 'large X' effect (LXE). The causes of LXE are not clear, but the leading theory is that it is caused by recessive species incompatibilities exposed in the phenotype due to the hemizygosity of X-linked genes in the heterogametic sex. However, the LXE was also reported in species with relatively recently evolved sex chromosomes where Y chromosome is not completely degenerate and X-linked genes are not hemizygous, such as the plant Silene latifolia. Recent genome sequencing and detailed genetic mapping in this species revealed a massive (> 330 Mb) non- or rarely-recombining pericentromeric region on the X chromosome (Xpr) that comprises ~ 90% of the chromosome and over 13% of the entire genome. If any of the Xpr genes are involved in species incompatibilities, this would oppose interspecific gene flow for other genes tightly linked in the Xpr. Here we test the hypothesis that the previously reported LXE in S. latifolia is caused by the lack of recombination on most of the X chromosome. Based on genome-wide analysis of DNA polymorphism and gene expression in S. latifolia and its close cross-compatible relative S. dioica, we report that the rarely-recombining regions represent a significant barrier for interspecific gene flow. We found little evidence for any additional factors contributing to the LXE, suggesting that extensive pericentromeric recombination suppression on the X-chromosome is the major if not the only cause of the LXE in S. latifolia and S. dioica.

Low frequency of resistance to thiophanate-methyl in Monilinia fructicola populations from southeastern United States peach orchards.

Methyl benzimidazole carbamate (MBC) fungicides were once widely used for brown rot (Monilinia fructicola) control of peach (Prunus persica (L.) Batsch) in the southeastern US, but their use was substantially reduced and often eliminated due to widespread resistance. In this study, 233 M. fructicola isolates were collected from major peach production areas in Alabama, Georgia, and South Carolina, and sensitivity to thiophanate-methyl was examined. Isolates were also collected from one organic and two experimental peach orchards. A discriminatory dose of 1 µg/ml was used to distinguish sensitive (S) and moderately sensitive (S-LR) isolates from low resistant phenotypes, while 50 and 500 µg/ml thiophanate-methyl concentrations were used to determine high resistant (HR) phenotypes. Sequence analyses were performed to identify mutations in the ß-tubulin target gene and detached fruit assays were performed to determine the efficacy of a commercial product against isolates representing each phenotype. Results indicated 55.7%, 63.5%, and 75.9% of isolates from Alabama, Georgia, and South Carolina, respectively, were S to thiophanate-methyl; 44.3%, 36.5%, and 21.4% were S-LR; no isolates were LR; and only 3 isolates (1.3%) from South Carolina were HR. No mutations in S or S-LR isolates were found, but HR isolates revealed the E198A mutation, an amino acid change of glutamic acid to alanine conferring high resistance. The high label rate of a commercial product containing thiophanate-methyl controlled brown rot caused by S and S-LR isolates in detached fruit studies but was ineffective against HR isolates. The combinations of thiophanate-methyl with azoxystrobin or isofetamid, when mixed together and applied in an experimental orchard 14 days preharvest, significantly reduced brown rot incidence on pre and postharvest commercially ripe fruit and efficacy was comparable to that of a grower standard fungicide. These results indicate that thiophanate-methyl may again be useful to peach growers in the southeastern US for brown rot and fungicide resistance management.

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial.

OBJECTIVE: This study aimed to assess the safety and effectiveness of a new charge-distributed multiphase stimulation paradigm during an extended spinal cord stimulation (SCS) trial. MATERIALS AND METHODS: This prospective, multicenter, randomized, single-blind, feasibility study included participants with chronic low back and/or leg pain and baseline numerical rating scale (NRS) for overall pain intensity ≥6. After a successful commercial SCS trial, participants were randomized to multiphase SCS therapy A (approximately 600-1500 Hz) or B (approximately 300-600 Hz), delivered via an investigational external pulse generator and existing leads during an 11-to-12-day testing period. Primary end points were mean NRS change from baseline to final in-office visit for each multiphase therapy and between therapies. Secondary end points included mean NRS change from end of commercial trial to final study visit and incidence of device-related adverse events (AEs). Additional measures included patient-reported outcomes collected at home through electronic watches and written diaries. Power usage was compared between multiphase and commercial therapies. RESULTS: A total of 122 participants initiated a commercial trial; 77 were randomized to a multiphase arm, and 65 completed the study. Reductions in mean NRS scores from baseline to final study visit were significant for multiphase therapy A and B (-4.3 and -4.7, respectively; both p < 0.0001). There was no statistically significant difference in mean NRS reduction or percent pain relief between multiphase therapies. In an additional analysis, 63.9% of participants reported greater pain relief with multiphase than with commercial SCS therapy in the at-home setting. On average, multiphase required less power than did commercial devices. One non-serious device-related AE was reported, and no infections occurred during the extended trial. CONCLUSIONS: Multiphase SCS effectively reduced pain in participants with chronic low back and/or leg pain during a trial, with no unanticipated device-related AEs reported. Future studies should evaluate long-term effectiveness of multiphase stimulation. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03594266.

The impact of vaping ethanol-containing electronic cigarette liquids on roadside impairment investigations.

Legal professionals and others have suggested that vaping electronic cigarettes (e-cigs) prior to or during ethanol breath testing may produce false positives. Preliminary breath tests (PBTs) and evidentiary breath tests (EBTs) measure ethanol in exhaled breath and standardized field sobriety tests (SFSTs) are used to assess impairment. Ethanol has been identified in e-cig liquids (e-liquids). Presented are a series of experiments designed to determine the mechanics of vaping ethanol using an e-cig and the effects of vaping ethanol on the SFSTs and breath tests used by law enforcement officers (LEO). Twelve participants (five females, age: 21-32 and seven males, age: 21-55), vaped either one or ten puffs of an e-liquid (0% or 20% ethanol). LEOs assessed impairment using SFSTs (12 and 42 min), PBTs (<1, 27, 32, 37 and 57 min) and EBTs (2, 29, 34, 39 and 59 min) post-vaping. A self-assessment test was administered post-vaping (22 and 52 min). Baseline responses for all measures were collected prior to vaping. Results demonstrated that ethanol in the e-liquids was aerosolized by e-cigs and produced particles that could reach the deep lung tissue based on mean-mass diameter. Ethanol was detected by PBT <3 min after participants vaped one (0.007-0.030 g/210 L) or ten puffs (013-0.074 g/210 L) of a 20% ethanol e-liquid. Ethanol was not detected by PBT at any subsequent time point. Ethanol was not detected by the EBT under any condition. Impairment was not indicated by the SFST. Some subjective effects were reported, but few statistically significant differences between conditions were indicated. A wait period prior to ethanol breath testing is not always mandated, depending on jurisdiction, or observed in all applications, such as workplace testing. The results demonstrate that a wait period must be employed to prevent vaping-related false-positive breath ethanol results.

The role of recombination landscape in species hybridisation and speciation.

It is now well recognised that closely related species can hybridize and exchange genetic material, which may promote or oppose adaptation and speciation. In some cases, interspecific hybridisation is very common, making it surprising that species identity is preserved despite active gene exchange. The genomes of most eukaryotic species are highly heterogeneous with regard to gene density, abundance of repetitive DNA, chromatin compactisation etc, which can make certain genomic regions more prone or more resistant to introgression of genetic material from other species. Heterogeneity in local recombination rate underpins many of the observed patterns across the genome (e.g. actively recombining regions are typically gene rich and depleted for repetitive DNA) and it can strongly affect the permeability of genomic regions to interspecific introgression. The larger the region lacking recombination, the higher the chance for the presence of species incompatibility gene(s) in that region, making the entire non- or rarely recombining block impermeable to interspecific introgression. Large plant genomes tend to have highly heterogeneous recombination landscape, with recombination frequently occurring at the ends of the chromosomes and central regions lacking recombination. In this paper we review the relationship between recombination and introgression in plants and argue that large rarely recombining regions likely play a major role in preserving species identity in actively hybridising plant species.

Impact of allele-specific anti-human leukocyte antigen class I antibodies on organ allocation.

Technological advances in the field of histocompatibility have allowed us to define anti-human leukocyte antigen (HLA) antibody specificity at the allelic level. However, how allele-specific antibodies affect organ allocation is poorly studied. We examined allelic specificities of class I HLA antibodies in 6726 consecutive serum samples from 2953 transplant candidates and evaluated their impact on the corresponding crossmatch and organ allocation. Out of 17 class I HLA antigens represented by >1 allele in the LABScreen single antigen bead assay, 12 had potential allele-specific reactivity. Taking advantage of our unbiased cohort of deceased donor-candidate testing (123,135 complement-dependent cytotoxicity crossmatches between 2014 and 2017), we estimated that the presence of allele-specific antibody detected using a single antigen bead assay (median fluorescence intensity, >3000) against only the rare allele was a poor predictor of a positive complement-dependent cytotoxicity crossmatch, with a positive predictive value of 0% to 7%, compared with 52.5% in allele-concordant class I HLA antibodies against A or B locus antigens. Further, we confirmed allele-specific reactivity using flow crossmatch in 3 scenarios: A11:01/A11:02, A68:01/A68:02, and B44:02/B44:03. Our results suggest that allele-specific antibodies may unnecessarily exclude transplant candidates (up to 10%) from organ offers by overcalling unacceptable antigens; incorporation of selective reactivity pattern in allocation may promote precision matching and more equitable allocation.

Impact of oestrus synchronization devices on ewes vaginal microbiota and artificial insemination outcome.

Introduction: The low pregnancy rate by artificial insemination in sheep represents a fundamental challenge for breeding programs. In this species, oestrus synchronization is carried out by manipulating hormonal regimens through the insertion of progestogen intravaginal devices. This reproductive strategy may alter the vaginal microbiota affecting the artificial insemination outcome. Methods: In this study, we analyzed the vaginal microbiome of 94 vaginal swabs collected from 47 ewes with alternative treatments applied to the progesterone-releasing intravaginal devices (probiotic, maltodextrin, antibiotic and control), in two sample periods (before placing and after removing the devices). To our knowledge, this is the first study using nanopore-based metagenome sequencing for vaginal microbiome characterization in livestock. Results: Our results revealed a significant lower abundance of the genera Oenococcus (Firmicutes) and Neisseria (Proteobacteria) in pregnant compared to non-pregnant ewes. We also detected a significant lower abundance of Campylobacter in the group of samples treated with the probiotic. Discussion: Although the use of probiotics represents a promising practice to improve insemination results, the election of the suitable species and concentration requires further investigation. In addition, the use of progestogen in the synchronization devices seemed to increase the alpha-diversity and decrease the abundance of harmful microorganisms belonging to Gammaproteobacteria and Fusobacteriia classes, suggesting a beneficial effect of their use.

Impact of Novel Treatments in Patients with Melanoma Brain Metastasis: Real-World Data.

BACKGROUND: Melanoma brain metastasis (MBM) is associated with poor outcome, but targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) have revolutionized treatment over the past decade. We assessed the impact of these treatments in a real-world setting. METHODS: A single-center cohort study was performed at a large, tertiary referral center for melanoma (Erasmus MC, Rotterdam, the Netherlands). Overall survival (OS) was assessed before and after 2015, after which TTs and ICIs were increasingly prescribed. RESULTS: There were 430 patients with MBM included; 152 pre-2015 and 278 post-2015. Median OS improved from 4.4 to 6.9 months (HR 0.67, p < 0.001) after 2015. TTs and ICIs prior to MBM diagnosis were associated with poorer median OS as compared to no prior systemic treatment (TTs: 2.0 vs. 10.9 and ICIs: 4.2 vs. 7.9 months, p < 0.001). ICIs directly after MBM diagnosis were associated with improved median OS as compared to no direct ICIs (21.5 vs. 4.2 months, p < 0.001). Stereotactic radiotherapy (SRT; HR 0.49, p = 0.013) and ICIs (HR 0.32, p < 0.001) were independently associated with improved OS. CONCLUSION: After 2015, OS significantly improved for patients with MBM, especially with SRT and ICIs. Demonstrating a large survival benefit, ICIs should be considered first after MBM diagnosis, if clinically feasible.

Complete Chloroplast Genome Sequence of the Western Poison Oak, Toxicodendron diversilobum (Anacardiaceae), from California.

Here, we present the complete chloroplast genome sequence of Toxicodendron diversilobum, western poison oak, from Pacific Grove, California. The genome is 159,543 bp in length, contains 133 genes, and has a high level of gene synteny to other species of Toxicodendron.

ABO Genotyping finds more A2 to B kidney transplant opportunities than lectin-based subtyping.

ABO compatibility is important for kidney transplantation, with longer waitlist times for blood group B kidney transplant candidates. However, kidneys from non-A1 (eg, A2) subtype donors, which express less A antigen, can be safely transplanted into group B recipients. ABO subtyping is routinely performed using anti-A1 lectin, but DNA-based genotyping is also possible. Here, we compare lectin and genotyping testing. Lectin and genotype subtyping was performed on 554 group A deceased donor samples at 2 transplant laboratories. The findings were supported by 2 additional data sets of 210 group A living kidney donors and 124 samples with unclear lectin testing sent to a reference laboratory. In deceased donors, genotyping found 65% more A2 donors than lectin testing, most with weak lectin reactivity, a finding supported in living donors and samples sent for reference testing. DNA sequencing and flow cytometry showed that the discordances were because of several factors, including transfusion, small variability in A antigen levels, and rare ABO∗A2.06 and ABO∗A2.16 sequences. Although lectin testing is the current standard for transplantation subtyping, genotyping is accurate and could increase A2 kidney transplant opportunities for group B candidates, a difference that should reduce group B wait times and improve transplant equity.

Prognostic Value of Left Atrial Strain in Aortic Stenosis: A Competing Risk Analysis.

BACKGROUND: The role of left atrial (LA) strain as an imaging biomarker in aortic stenosis is not well established. The aim of this study was to investigate the prognostic performance of phasic LA strain in relation to clinical and echocardiographic variables and N-terminal pro-B-type natriuretic peptide in asymptomatic and minimally symptomatic patients with moderate to severe aortic stenosis and left ventricular ejection fraction > 50%. METHODS: LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured using speckle-tracking echocardiography. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, progression to New York Heart Association functional class III or IV, acute coronary syndrome, or syncope. Secondary outcomes 1 and 2 comprised the same end points but excluded acute coronary syndrome and additionally syncope, respectively. The prognostic performance of phasic LA strain cutoffs was evaluated in competing risk analyses, aortic valve replacement being the competing risk. RESULTS: Among 173 patients (mean age, 69 ± 11 years; mean peak transaortic velocity, 4.0 ± 0.8 m/sec), median LASr, LAScd, and LASct were 27% (interquartile range [IQR], 22%-32%), 12% (IQR, 8%-15%), and 16% (IQR, 13%-18%), respectively. Over a median of 2.7 years (IQR, 1.4-4.6 years), the primary outcome and secondary outcomes 1 and 2 occurred in 66 (38%), 62 (36%), and 59 (34%) patients, respectively. LASr < 20%, LAScd < 6%, and LASct < 12% were identified as optimal cutoffs of the primary outcome. In competing risk analyses, progressing from echocardiographic to echocardiographic-clinical and combined models incorporating N-terminal pro-B-type natriuretic peptide, LA strain parameters outperformed other key echocardiographic variables and significantly predicted clinical outcomes. LASr < 20% was associated with the primary outcome and secondary outcome 1, LAScd < 6% with all clinical outcomes, and LASct < 12% with secondary outcome 2. LAScd < 6% had the highest specificity (95%) and positive predictive value (82%) for the primary outcome, and competing risk models incorporating LAScd < 6% had the best discriminative value. CONCLUSIONS: In well-compensated patients with moderate to severe aortic stenosis and preserved left ventricular ejection fractions, LA strain was superior to other echocardiographic indices and incremental to N-terminal pro-B-type natriuretic peptide for risk stratification. LAScd < 6%, LASr < 20%, and LASct < 12% identified patients at higher risk for adverse outcomes.

Prevalence and Distribution of Phony Peach Disease (Caused by Xylella fastidiosa) in the United States.

Peach is an important specialty fruit crop in the United States, and phony peach disease (PPD), caused by Xylella fastidiosa subsp. multiplex, has been a major cause of yield loss since it was first observed in 1885. Under a federal eradication program, surveys of PPD were conducted from 1929 to 1972, when the program was terminated. No surveys have been conducted in approximately 50 years; therefore, the current prevalence of PPD in the United States is unknown, especially in the Southeast, where damage was previously most severe. To ascertain the status of PPD, we surveyed orchards in Alabama, Florida, Georgia, and South Carolina from June to August 2020 and, except for South Carolina and northern Georgia, PPD was prevalent. Trees in 17 orchards were subjected to confirmation of X. fastidiosa using the AmplifyRP XRT+ for X. fastidiosa to corroborate our visual assessments; based on these tests, PPD incidence in the orchards ranged from 0 to 30.5%. Ancillary written surveys of relative PPD presence and prevalence were sent to fruit pathologists from universities in 20 states where PPD was historically reported. Only 35.0% of respondents reported that PPD either currently or recently occurred in their state and, of these, three reported PPD to be of significant concern. The results of the physical and written surveys indicate that PPD remains prevalent mainly in the southeastern region of the United States but, in other states where previously reported, it is either not present or has very low prevalence when compared with historical accounts of the disease.

Rapid evolution of hybrid breakdown following recent divergence with gene flow in Senecio species on Mount Etna, Sicily.

How do nascent species evolve reproductive isolation during speciation with on-going gene flow? How do hybrid lineages become stabilised hybrid species? While commonly used genomic approaches provide an indirect way to identify species incompatibility factors, synthetic hybrids generated from interspecific crosses allow direct pinpointing of phenotypic traits involved in incompatibilities and the traits that are potentially adaptive in hybrid species. Here we report the analysis of phenotypic variation and hybrid breakdown in crosses between closely-related Senecio aethnensis and S. chrysanthemifolius, and their homoploid hybrid species, S. squalidus. The two former species represent a likely case of recent (<200 ky) speciation with gene flow driven by adaptation to contrasting conditions of high- and low-elevations on Mount Etna, Sicily. As these species form viable and fertile hybrids, it remains unclear whether they have started to evolve reproductive incompatibility. Our analysis represents the first study of phenotypic variation and hybrid breakdown involving multiple Senecio hybrid families. It revealed wide range of variation in multiple traits, including the traits previously unrecorded in synthetic hybrids. Leaf shape, highly distinct between S. aethnensis and S. chrysanthemifolius, was extremely variable in F2 hybrids, but more consistent in S. squalidus. Our study demonstrates that interspecific incompatibilities can evolve rapidly despite on-going gene flow between the species. Further work is necessary to understand the genetic bases of these incompatibilities and their role in speciation with gene flow.

Effect of the Addition of Corn Husk Cellulose Nanocrystals in the Development of a Novel Edible Film.

The cellulose from agroindustrial waste can be treated and converted into nanocrystals or nanofibers. It could be used to produce biodegradable and edible films, contributing to the circular economy and being environmentally friendly. This research aimed to develop an edible film elaborated with activated cellulose nanocrystals, native potato starch, and glycerin. The activated cellulose nanocrystals were obtained by basic/acid digestion and esterification with citric acid from corn husks. The starch was extracted from the native potato cultivated at 3500 m of altitude. Four film formulations were elaborated with potato starch (2.6 to 4.4%), cellulose nanocrystals (0.0 to 0.12%), and glycerin (3.0 to 4.2%), by thermoforming at 60 °C. It was observed that the cellulose nanocrystals reported an average size of 676.0 nm. The films mainly present hydroxyl, carbonyl, and carboxyl groups that stabilize the polymeric matrix. It was observed that the addition of cellulose nanocrystals in the films significantly increased (p-value < 0.05) water activity (0.409 to 0.447), whiteness index (96.92 to 97.27), and organic carbon content. In opposition to gelatinization temperature (156.7 to 150.1 °C), transparency (6.69 to 6.17), resistance to traction (22.29 to 14.33 N/mm), and solubility in acidic, basic, ethanol, and water media decreased. However, no significant differences were observed in the thermal decomposition of the films evaluated through TGA analysis. The addition of cellulose nanocrystals in the films gives it good mechanical and thermal resistance qualities, with low solubility, making it a potential food-coating material.

Effect of the Application of a Coating Native Potato Starch/Nopal Mucilage/Pectin on Physicochemical and Physiological Properties during Storage of Fuerte and Hass Avocado (Persea americana).

The avocado fruit is an agro-industrial product with high export demand in Peru due to its sensory and nutritional qualities, which can be affected during storage. The study aimed to evaluate the effect of the application of a coating formulated with potato starch (Solanum tuberosum ssp andigena), nopal mucilage (Opuntia ficus indica), and pectin on the physicochemical and physiological properties during the storage of Fuerte and Hass avocados. Samples were taken in their harvest state from the plantation in "Occobamba", which is cultivated by the Avocado Producers Association in Chincheros, Apurímac, Peru. Physicochemical properties (titratable acidity, pH, total soluble solids) and physiological properties (weight loss, firmness, and color L* a* b*) were determined during 20 days of storage at 20 °C. The elaborated films present high transparency and low aw values. In the coated avocado of the Hass and Fuerte varieties, acidity and total soluble solids decreased significantly (p-value < 0.05) during the storage time. Weight loss and firmness of coated fruits decrease to a lesser extent. Luminosity L*, color index, and color variation showed better attributes for the coated samples. The use of coatings made with potato starch, nopal mucilage, and pectin allows the physicochemical and physiological properties of avocado fruits to be maintained for a longer time during storage.

Presence of Human Papillomavirus DNA in Malignant Neoplasia and Non-Malignant Breast Disease.

Breast cancer is the leading cause of cancer death among women worldwide. Multiple extrinsic and intrinsic factors are associated with this disease's development. Various research groups worldwide have reported the presence of human papillomavirus (HPV) DNA in samples of malignant breast tumors. Although its role in mammary carcinogenesis is not fully understood, it is known that the HPV genome, once inserted into host cells, has oncogenic capabilities. The present study aimed to detect the presence of HPV DNA in 116 breast tissue biopsies and classify them according to their histology. It was found that 50.9% of the breast biopsies analyzed were malignant neoplasms, of which 74.6% were histologically classified as infiltrating ductal carcinoma. In biopsies with non-malignant breast disease, fibroadenoma was the most common benign neoplasm (39.1%). Detection of HPV DNA was performed through nested PCR using the external primer MY09/11 and the internal primer GP5+/6+. A hybridization assay genotyped HPV. HPV DNA was identified in 20.3% (12/59) of malignant neoplasms and 35% non-malignant breast disease (16/46). It was also detected in 27.3% (3/11) of breast tissue biopsies without alteration. However, there are no statistically significant differences between these groups and the existence of HPV DNA (p = 0.2521). Its presence was more frequent in non-malignant alterations than in malignant neoplasias. The most frequent genotypes in the HPV-positive samples were low-risk (LR) HPV-42 followed by high-risk (HR) HPV-31.