The prognostic effect of mechanical, ultrastructural, and ECM signatures in glioblastoma core and rim.

Glioblastoma (GBM) is a highly invasive, aggressive brain cancer that carries a median survival of 15 months and is resistant to standard therapeutics. Recent studies have demonstrated that intratumoral heterogeneity plays a critical role in promoting resistance by mediating tumor adaptation through microenvironmental cues. GBM can be separated into two distinct regions-a core and a rim, which are thought to drive specific aspects of tumor evolution. These differences in tumor progression are regulated by the diverse biomolecular and biophysical signals in these regions, but the acellular biophysical characteristics remain poorly described. This study investigates the mechanical and ultrastructural characteristics of the tumor extracellular matrix (ECM) in patient-matched GBM core and rim tissues. Seven patient-matched tumor core and rim samples and one non-neoplastic control were analyzed using atomic force microscopy, scanning electron microscopy, and immunofluorescence imaging to quantify mechanical, ultrastructural, and ECM composition changes. The results reveal significant differences in biophysical parameters between GBM core, rim, and non-neoplastic tissues. The GBM core is stiffer, denser, and is rich in ECM proteins hyaluronic acid and tenascin-C when compared to tumor rim and non-neoplastic tissues. These alterations are intimately related and have prognostic effect with stiff, dense tissue correlating with longer progression-free survival. These findings reveal new insights into the spatial heterogeneity of biophysical parameters in the GBM tumor microenvironment and identify a set of characteristics that may correlate with patient prognosis. In the long term, these characteristics may aid in the development of strategies to combat therapeutic resistance.

The importance of secondary cancer screening programs in Hodgkin lymphoma survivors.

Not available.

Exploring access cavity through non-carious cervical lesions: Impacts on instrumentation, obturation, and fracture resistance in mandibular incisors.

AIM: To compare the effects of Cervical Access Cavity (CervAC) and Traditional Access Cavity (TradAC) on root canal preparation, root canal filling, and fracture resistance in mandibular incisors. METHODOLOGY: Twenty recently extracted and intact mandibular incisors were initially scanned using a micro-CT device. The specimens were anatomically matched to create two groups (n = 10). A wedge-shaped non-carious cervical lesion (NCCL) was created on the buccal aspect of all teeth using a double-faced segmented diamond disc. In group 1, a TradAC was prepared, whilst in group 2, access was created through the simulated NCCL using a round diamond bur 1012. After root canal preparation with Rotate instruments sizes 15/0.04, 20/0.04, and 25/0.04, the teeth were scanned again and evaluated for root canal volume and surface area, static voxels, volume of removed dental tissue, and dentine thickness. After that, the root canals were filled using the single-cone technique, teeth were restored with composite resin, and subsequently rescanned to calculate the volume of filling materials and voids. Then, the restored teeth were subjected to fracture resistance tests using a universal testing machine. Statistical comparisons between groups were performed with the Mann-Whitney test or the Student's t-test, with a statistical significance level of 5%. RESULTS: Statistical comparisons indicated no significant differences between groups in terms of root canal volume, surface area, static voxels, removed root dentine, root canal filling volume, percentage of voids, or fracture resistance load (p > .05). Conversely, teeth prepared with TradAC showed a significantly higher percentage of dental tissue removed from the crown (p = .001) and a greater volume of filling material remnants in the pulp chamber (p < .001) compared to the CervAC group. A significantly lower percentage reduction in dentine thickness was observed only on the mesial aspect of root at Level 1 in TradAC group (p = .008). CONCLUSIONS: CervAC can be considered a viable alternative approach in the presence of NCCL in mandibular incisors.

Making the case for a new typology of dental care systems.

BACKGROUND AND RATIONALE: Dental care systems have the potential to influence population oral health and patterns of socioeconomic inequalities. Therefore, understanding the impact of the ways in which countries fund, provide, and organize their dental care services is key in the analysis of determinants of oral health. In this commentary we offer a synopsis of recent typologies of healthcare systems, based on a rapid review, and highlight that none of them fit dental care services given the separation of dental care from general healthcare provision in many countries. The paper also summarizes evidence on dental care systems as determinants of population oral health and argues why a new typology of dental care systems is needed. CHALLENGES AND WAYS FORWARD: We argue that a typology must consider institutional arrangements, structures, and processes behind the provision of dental care, and that specific dimensions/variables that inform the typology should result from a process of discussion and consensus. Some methodological considerations for developing typologies are also discussed, including the challenges in the collection and analysis of data followed by an advanced cluster analysis. Despite their limitations, typologies have evolved into an essential tool for comparing the similarities and differences of healthcare systems across countries. Therefore, a dental specific typology for health systems will be useful for researchers, policymakers, and dental professionals to characterize the provision of dentalcare services in different countries. This will also enable examining their potential role as determinants of population oral health and inequalities.

Surgical Management of a Giant Inflammatory Hepatocellular Adenoma in a Young Female.

Hepatocellular adenomas are rare and benign primary neoplasms of phenotypically mature hepatocytes. Our understanding of this pathology has greatly improved due to advances in molecular and anatomic knowledge. This article provides an in-depth review of hepatic adenomas (HCA) while presenting the case of a 20-year-old patient with a giant inflammatory hepatocellular adenoma with an atypical presentation, in whom surgical intervention was performed via right hepatectomy. In the post-surgical course, the patient had an in-hospital stay of three days with no complications. During outpatient monitoring via laboratory tests and imaging at eight months, the patient did not present any trace of recurrence.

Performance of V-Fe based catalysts on the oxidation of dibenzothiophenes.

To obtain fossil fuels with ultra-low S levels at friendly conditions, different V oxides formulations on alumina modified with Fe were characterized and selected to oxidize dibenzothiophene (DBT), 4-methyl DBT and 4,6-dimethyl DBT prevailing in diesel fuel. V-Fe based catalysts (5 or 10 wt% of V) were obtained by impregnation of ammonium metavanadate solutions on Fe-modified alumina, obtained by impregnation of Mohr salt on pseudoboehmite (2 wt% of Fe). The catalysts were calcined in air atmosphere, and after were partially reduced with H2 flux to obtain a mix of several oxidation states of V and Fe species, to evaluate the interaction of Fe in VOx/Al2O3 catalysts and determine its effect on the oxidation processes. The structural and optical properties, as well as surface species, were determined by SEM-EDS, TPR, XRD, Raman, ATR-FTIR, photoluminescence, UV-Vis diffuse reflectance, and XPS spectroscopy. The catalytic performance was evaluated in oxidative desulfurization (ODS) and photocatalytic ODS (PODS) processes. The experimental results showed the addition of Fe promoted the catalytic activity of both ODS and PODS reactions. ODS activities of V-Fe catalysts increase up to 7.5 times with respect to V catalysts without Fe, and the most active catalyst (V5Fer) presents a characteristic oxidation time of 50 min for 4,6-DMDBT. The PODS activity of V10Fec was like ODS activity, showing it is possible to oxidize the dibenzothiophenes under friendly conditions to obtain lower S levels. The promoting effect of Fe was due to the interaction of Fe2+ and Fe3+ with the catalytic support, favoring the distribution of surface V3+ and V4+ species. Additionally, Fe improved the optical properties of the catalysts since the bandgap energy decrease and low recombination rate of the electron-hole pair were observed. Therefore, V-Fe based catalysts are photocatalytically actives to be used in PODS processes.

Intraspecific variation in crayfish behavioral traits affects leaf litter breakdown in streams.

Although intraspecific trait variation is increasingly recognized as affecting ecosystem processes, few studies have examined the ecological significance of among-population variation in behavioral traits in natural ecosystems. In freshwater habitats, crayfish are consumers that can influence ecosystem structure (e.g., macroinvertebrate communities) and function (e.g., leaf litter breakdown). To test whether crayfish behavioral traits (activity, boldness, and foraging voracity) are major contributors of leaf litter breakdown rates in the field, we collected rusty crayfish (Faxonius rusticus) from eight streams across the midwestern USA and measured behaviors using laboratory assays. At the same streams, we measured breakdown rates of leaf packs that were accessible or inaccessible to crayfish. Our results provide evidence that among-population variation in crayfish boldness and foraging voracity was a strong predictor of leaf litter breakdown rates, even after accounting for commonly appreciated environmental drivers (water temperature and human land use). Our results suggest that less bold rusty populations (i.e., emerged from shelter more slowly) had greater direct impacts on leaf litter breakdown than bold populations (P = 0.001, r2 = 0.85), potentially because leaf packs can be both a shelter and food resource to crayfish. Additionally, we found that foraging voracity was negatively related to breakdown rates in leaf packs that were inaccessible to crayfish (P = 0.025, r2 = 0.60), potentially due to a trophic cascade from crayfish preying on other invertebrates that consume leaf litter. Overall, our results add to the growing evidence that trait variation in animals may be important for understanding freshwater ecosystem functioning.

A Giant Malignant Solitary Fibrous Tumor of the Pancreas: A Case Report and Review of the Literature.

We present a case report of a giant solitary fibrous tumor (SFT) with a review of the literature and discuss its biological features and diagnosis. A 43-year-old man presented to our emergency department with abdominal pain and distension with an evolution of two days. Contrast-enhanced computed tomography (CT) showed a large, well-circumscribed semisolid mass (12 cm x 10 cm x 12 cm) localized in the pancreatic head. The histological diagnosis obtained by endoscopic ultrasound-guided trans-duodenal tumor biopsy with fine-needle aspiration showed proliferating short spindle-shaped cells, suggesting a mesenchymal neoplasia of low grade. We proceeded to a Whipple surgical technique. The histopathological study of the resected tumor confirmed proliferating spindle-shaped cells in the tissue, and one mitotic figure was observed in 10 high-power fields (HPFs). Immunostaining was positive for CD34 and STAT-6. The histological diagnosis was a malignant pancreatic SFT. In the six months posterior to the surgical procedure, the patient has been free of recurrent disease. Preoperative diagnosis is difficult and requires comprehensive evidence including clinical, immunohistochemistry, and histological features. Since there are currently no recognized best practices, we advise total surgical excision and careful clinical monitoring.

Entanglement Kinetics in Polymer Melts Are Chemically Specific.

We investigate the universality of entanglement kinetics in polymer melts. We compare predictions of a recently developed constitutive equation for disentanglement to molecular dynamics simulations of both united-atom polyethylene and Kremer-Grest models for polymers in shear and extensional flow. We confirm that entanglements recover on the retraction time scale, rather than the reptation time scale. We find that the convective constraint release parameter ß is independent of molecular weight, but that it increases with the ratio of Kuhn length bK to packing length p as ß âˆ¼ (bK/p)α, with an exponent α = 1.9, which may suggest that disentanglement rate correlates with an increase in the tube diameter. These results may help shed light on which polymers are more likely to undergo shear banding.

Epidemiological factors conditioning sarcoptic mange spreading in wild boar (Sus scrofa).

Sarcoptic mange is a widely distributed disease, with numerous potential hosts among domestic and wild animals. Nowadays it is considered a neglected re-emergent infection in humans. As a difference with domestic pigs, and even with several clinical cases reported in some European countries, it seems that Eurasian wild boars (Sus scrofa) have a low susceptibility to clinical mange. However, because of a case of confirmed transmission from Spanish ibex (Capra pyrenaica) to wild boar in the province of Tarragona, we planned a large-scale ELISA survey in the neighboring Valencian Community (SE Spain). We compared 419 wild boar sera from different management systems (fenced vs. open game estates), different ages (piglets, juveniles, and adults), with different behaviour (gregarious females of all ages and male piglets vs. solitary juveniles and adult males), from areas with different wild boar densities, different wild ruminant densities and different sarcoptic mange epidemiologic situations. The whole prevalence of antibodies against sarcoptic mange in the tested wild boars was 10.5%. No significant differences were found when comparing fenced and free ranging wild boars, males and females, gregarious vs. solitary individuals or among different ages. However, wild boar density was a relevant factor. In areas with a hunting bag of <1 wild boar/km2, considered as a low density of suids, the seroprevalence was 2.94%, but rose to 11.52% in high density districts, constituting a significant difference (p = 0.037). Low wild boar populations would act as a protective factor (OR 0.233; p = 0.049) against coming into contact with the mite. The wild ruminant densities or their sarcoptic mange status did not show any effect on wild boars seroprevalence against this disease. These results reinforce the suggested host-taxon Sarcoptes scabiei specificity and the independence of host-species foci.

Superior Outcomes of Dual-Arterial Coronary Artery Bypass Grafting Are Maintained in the Veterans Health Administration.

INTRODUCTION: Controversy surrounds the long-term clinical benefit of coronary artery bypass grafting (CABG) using dual arterial grafts (DAGs) compared to single arterial grafts (SAGs). We investigated outcomes of DAG, using single internal thoracic artery and radial artery (DAG-RA) or bilateral internal thoracic artery grafts (DAG-BITA), compared to SAG, using the left internal thoracic artery and saphenous vein grafts, in the U.S. Veterans Health Administration (VA). METHODS: We conducted a cross-sectional study of U.S. Veterans undergoing isolated on-pump CABG between 2005 and 2015 at 44 VA medical centers. The primary composite outcome was first occurrence of a major adverse cardiac and cerebrovascular event (MACCE), comprised of death from any cause, myocardial infarction, stroke, or repeat revascularization. RESULTS: Among 25,969 Veterans undergoing isolated CABG, 1261 (4.9%) underwent DAG (66.8% DAG-RA and 33.2% DAG-BITA). Over a 5-y follow-up, DAG was associated with lower rates of all-cause death (adjusted hazard ratio [AHR] 0.70, 95% confidence interval [CI] 0.58-0.85), MACCE (AHR 0.80, 95% CI 0.71-0.91), and stroke (AHR 0.74, 95% CI 0.57-0.96) versus SAG. DAG-BITA was associated with lower rates of all-cause death (AHR 0.52, 95% CI 0.35-0.77) and MACCE (AHR 0.66, 95% CI 0.51-0.84) than SAG, while DAG-RA was associated with lower rates of all-cause death (AHR 0.79, 95% CI 0.64-0.99). CONCLUSIONS: In the VA, DAG was associated with improved long-term MACCE outcomes compared to SAG. These results suggest that the practice of DAG in the VA benefits Veterans and should be promoted further.

Quantitative Visualization of Lipid Nanoparticle Fusion as a Function of Formulation and Process Parameters.

Lipid nanoparticles (LNPs) have proven to be promising delivery vehicles for RNA-based vaccines and therapeutics, particularly in LNP formulations containing ionizable cationic lipids that undergo protonation/deprotonation in response to buffer pH changes. These nanoparticles are typically formulated using a rapid mixing technique at low pH, followed by a return to physiological pH that triggers LNP-LNP fusion. A detailed understanding of these dynamic processes is crucial to optimize the overall performance and efficiency of LNPs. However, knowledge gaps persist regarding how particle formation mechanisms impact drug loading and delivery functions. In this work, we employ single-molecule Convex Lens-induced Confinement (CLiC) microscopy in combination with Förster resonance energy transfer (FRET) measurements to study LNP fusion dynamics in relation to various formulation parameters, including lipid concentration, buffer conditions, drug loading ratio, PEG-lipid concentrations, and ionizable lipid selection. Our results reveal a strong correlation between the measured fusion dynamics and the formulation parameters used; these findings are consistent with DLS and Cryo-TEM-based assays. These measurements offer a cost-effective method for characterizing and screening potential drug candidates and can provide additional insights into their design, with opportunities for optimization.

Early life adversities, psychopathologies and novel pharmacological strategies.

Exposure to adversities during early life stages (early life adversities - ELA), ranging from pregnancy to adolescence, represents a major risk factor for the vulnerability to mental disorders. Hence, it is important to understand the molecular and functional underpinning of such relationship, in order to develop strategies aimed at reducing the psychopathologic burden associated with ELA, which may eventually lead to a significant improvement in clinical practice. In this review, we will initially recapitulate clinical and preclinical evidence supporting the link between ELA and psychopathology and we will primarily discuss the main biological mechanisms that have been described as potential mediators of the effects of ELA on the psychopathologic risk, including the role for genetic factors as well as sex differences. The knowledge emerging from these studies may be instrumental for the development of novel therapeutic strategies aimed not only at correcting the deficits that emerge from ELA exposure, but also in preventing the manifestation of a full-blown psychopathologic condition. With this respect, we will specifically focus on adolescence as a key time frame for disease onset as well as for early therapeutic intervention. We believe that incorporating clinical and preclinical research data in the context of early life adversities can be instrumental to elucidate the mechanisms contributing to the risk for psychopathology or that may promote resilience. This will ultimately allow the identification of 'at risk' individuals who may benefit from specific forms of interventions that, by interfering with disease trajectories, could result in more benign clinical outcomes.

Cutoffs for white-coat and masked blood pressure effects: an ambulatory blood pressure monitoring study.

The values used to define white-coat and masked blood pressure (BP) effects are usually arbitrary. This study aimed at investigating the accuracy of various cutoffs based on the differences (ΔBP) between office BP (OBP) and 24h-ambulatory BP monitoring (ABPM) to identify white-coat (WCH) and masked (MH) hypertension, which are phenotypes coupled with adverse prognosis. This cross-sectional study included 11,350 [Derivation cohort; 45% men, mean age = 55.1 ± 14.1 years, OBP = 132.1 ± 17.6/83.9 ± 12.5 mmHg, 24 h-ABPM = 121.6 ± 11.4/76.1 ± 9.6 mmHg, 25% using antihypertensive medications (AH)] and 7220 (Validation cohort; 46% men, mean age = 58.6 ± 15.1 years, OBP = 136.8 ± 18.7/87.6 ± 13.0 mmHg, 24 h-ABPM = 125.5 ± 12.6/77.7 ± 10.3 mmHg; 32% using AH) unique individuals who underwent 24 h-ABPM. We compared the sensitivity, specificity, positive and negative predictive values and area under the curve (AUC) of diverse ΔBP cutoffs to detect WCH (ΔsystolicBP/ΔdiastolicBP = 28/17, 20/15, 20/10, 16/11, 15/9, 14/9 mmHg and ΔsystolicBP = 13 and 10 mmHg) and MH (ΔsystolicBP/ΔdiastolicBP = -14/-9, -5/-2, -3/-1, -1/-1, 0/0, 2/2 mmHg and ΔsystolicBP = -5 and -3mmHg). The 20/15 mmHg cutoff showed the best AUC (0.804, 95%CI = 0.794-0.814) to detect WCH, while the 2/2 mmHg cutoff showed the highest AUC (0.741, 95%CI = 0.728-0.754) to detect MH in the Derivation cohort. Both cutoffs also had the best accuracy to detect WCH (0.767, 95%CI = 0.754-0.780) and MH (0.767, 95%CI = 0.750-0.784) in the Validation cohort. In secondary analyses, these cutoffs had the best accuracy to detect individuals with higher and lower office-than-ABPM grades in both cohorts. In conclusion, the 20/15 and 2/2 mmHg ΔBP cutoffs had the best accuracy to detect hypertensive patients with WCH and MH, respectively, and can serve as indicators of marked white-coat and masked BP effects derived from 24 h-ABPM.

Genomes of the Orestias pupfish from the Andean Altiplano shed light on their evolutionary history and phylogenetic relationships within Cyprinodontiformes.

BACKGROUND: To unravel the evolutionary history of a complex group, a comprehensive reconstruction of its phylogenetic relationships is crucial. This requires meticulous taxon sampling and careful consideration of multiple characters to ensure a complete and accurate reconstruction. The phylogenetic position of the Orestias genus has been estimated partly on unavailable or incomplete information. As a consequence, it was assigned to the family Cyprindontidae, relating this Andean fish to other geographically distant genera distributed in the Mediterranean, Middle East and North and Central America. In this study, using complete genome sequencing, we aim to clarify the phylogenetic position of Orestias within the Cyprinodontiformes order. RESULTS: We sequenced the genome of three Orestias species from the Andean Altiplano. Our analysis revealed that the small genome size in this genus (~ 0.7 Gb) was caused by a contraction in transposable element (TE) content, particularly in DNA elements and short interspersed nuclear elements (SINEs). Using predicted gene sequences, we generated a phylogenetic tree of Cyprinodontiformes using 902 orthologs extracted from all 32 available genomes as well as three outgroup species. We complemented this analysis with a phylogenetic reconstruction and time calibration considering 12 molecular markers (eight nuclear and four mitochondrial genes) and a stratified taxon sampling to consider 198 species of nearly all families and genera of this order. Overall, our results show that phylogenetic closeness is directly related to geographical distance. Importantly, we found that Orestias is not part of the Cyprinodontidae family, and that it is more closely related to the South American fish fauna, being the Fluviphylacidae the closest sister group. CONCLUSIONS: The evolutionary history of the Orestias genus is linked to the South American ichthyofauna and it should no longer be considered a member of the Cyprinodontidae family. Instead, we submit that Orestias belongs to the Orestiidae family, as suggested by Freyhof et al. (2017), and that it is the sister group of the Fluviphylacidae family, distributed in the Amazonian and Orinoco basins. These two groups likely diverged during the Late Eocene concomitant with hydrogeological changes in the South American landscape.

Helical interfacial modulation for perovskite photovoltaics.

Hybrid metal halide perovskites have demonstrated remarkable performances in modern photovoltaics, although their stabilities remain limited. We assess the capacity to advance their properties by relying on interfacial modulators featuring helical chirality based on P,M-(1-methylene-3-methyl-imidazolium)[6]helicene iodides. We investigate their characteristics, demonstrating comparable charge injection for enantiomers and the racemic mixture. Overall, they maintain the resulting photovoltaic performance while improving operational stability, challenging the role of helical chirality in the interfacial modulation of perovskite solar cells.

Evaluation of Maternal-Fetal Medicine Fellowship Program Websites.

Introduction Due to the COVID-19 pandemic, the American Association of Medical Colleges (AAMC) recommended that all interviews for residencies and fellowships be conducted in a virtual format. As of March 2024, the Society of Maternal-Fetal Medicine (SMFM) continues to request that all fellowship interviews occur virtually. Without in-person interviews, prospective Maternal-Fetal Medicine (MFM) fellowship applicants must largely rely on program websites to gain insight into each program's offerings, culture, and application requirements. The purpose of this study was to evaluate the content of American College of Graduate Medical Education (ACGME)-accredited Maternal-Fetal Medicine (MFM) fellowship program websites and assess if regional differences exist among website content. Methods All ACGME-accredited MFM fellowship program websites were assessed for 21 defined criteria as of March 2024 and further compared by geographic regions (Midwest, Northeast, South, and West). Analyses were completed using chi-squared univariate tests, with a p < 0.05. Results Of the 108 accredited MFM fellowship programs, 106 programs had a dedicated website (98.15%). Most MFM programs (over 80%) included contact information (102/106), program director name (98/106), faculty names (95/106), application requirements (92/106), current fellow names (91/106), and the program coordinator name (89/106) on their website. Less programs (less than 30%) included diversity, equity, inclusion (DEI) content (28/106), interview dates (28/106), and current fellow research projects or publications (27/106). Western programs were less likely to include the program coordinator's name (12/18 (67%), p = 0.046), but more likely to include DEI content (10/18 (56%), p = 0.005). Northeastern programs were less likely to include their application requirements (24/32 (75%), p = 0.049) and less likely to include pictures of their current fellows (20/32 (63%), p = 0.045). Southern programs were more likely to include the yearly rotation schedule (19/32 (59%), p = 0.040). Midwestern programs were more likely to include information on fellowship benefits or salary (15/24 (63%), p = 0.046). Conclusion This study demonstrated that the content available on MFM fellowship websites varies greatly between programs and geographic regions. Efforts should be made by MFM training institutions to enhance website DEI content, curriculum information, recent fellow publications, and information on program alumni. A detailed and well-structured website may help applicants compare individual programs more equitably in the age of virtual interviewing.

Relationship between human activities and environmental changes in the southern Tibetan Plateau since the Little Ice Age.

The Tibetan Plateau (TP) is one of the most challenging areas for human long-term settlement due to its extreme living environment. Understanding the relationship between human activities and environmental changes in this extreme environment is important and can provide a historical reference for adapting to future climate change. In this study, we took the Angren Basin in the southern TP as a case study to elucidate the relationship since Little Ice Age (LIA). Using fecal stanol in feces, lake and river surface sediments, surface soils, and sediment core, we found that specific indices S1 and S2 from the composition of coprostanol, epicoprostanol, 5ß-ethylcoprostanol and 5ß-ethylepicoprostanol can reflect changes in human population and herbivores, respectively. Through the comparison between environmental changes determined by grain size, elements, sedimentation rate, and other climate records, the relationship between human activities and environmental changes was interpreted. Our results indicate that: (i) during 1480-1820 CE, the fecal stanols in lake sediments mainly originated from livestock, and the human population was low. In contrast, during 1820-2021 CE, the proportion and flux of S1 have been continuously increasing, indicating significant population growth. (ii) During the middle LIA, the cold-dry climate inhibited the development of agriculture and farming. However, the increased precipitation during the late LIA promoted that development, resulting in an increase in human population and livestock in a short term. (iii) Since 1951, people have reclaimed wasteland and developed husbandry, leading to increased soil erosion. (iv) Over the past 40 years, with a warm-humid climate and good policy support, human activities, such as agriculture and husbandry, have rapidly increased, but soil erosion has declined in the recent 20 years due to good soil-water conservation efforts. This study sheds light on the relationship between human activities and environmental changes and provides insights into future climate change responses.

Comparative genomics of the closely related fungal genera Cryptococcus and Kwoniella reveals karyotype dynamics and suggests evolutionary mechanisms of pathogenesis.

In exploring the evolutionary trajectories of both pathogenesis and karyotype dynamics in fungi, we conducted a large-scale comparative genomic analysis spanning the Cryptococcus genus, encompassing both global human fungal pathogens and nonpathogenic species, and related species from the sister genus Kwoniella. Chromosome-level genome assemblies were generated for multiple species, covering virtually all known diversity within these genera. Although Cryptococcus and Kwoniella have comparable genome sizes (about 19.2 and 22.9 Mb) and similar gene content, hinting at preadaptive pathogenic potential, our analysis found evidence of gene gain (via horizontal gene transfer) and gene loss in pathogenic Cryptococcus species, which might represent evolutionary signatures of pathogenic development. Genome analysis also revealed a significant variation in chromosome number and structure between the 2 genera. By combining synteny analysis and experimental centromere validation, we found that most Cryptococcus species have 14 chromosomes, whereas most Kwoniella species have fewer (11, 8, 5, or even as few as 3). Reduced chromosome number in Kwoniella is associated with formation of giant chromosomes (up to 18 Mb) through repeated chromosome fusion events, each marked by a pericentric inversion and centromere loss. While similar chromosome inversion-fusion patterns were observed in all Kwoniella species with fewer than 14 chromosomes, no such pattern was detected in Cryptococcus. Instead, Cryptococcus species with less than 14 chromosomes showed reductions primarily through rearrangements associated with the loss of repeat-rich centromeres. Additionally, Cryptococcus genomes exhibited frequent interchromosomal translocations, including intercentromeric recombination facilitated by transposons shared between centromeres. Overall, our findings advance our understanding of genetic changes possibly associated with pathogenicity in Cryptococcus and provide a foundation to elucidate mechanisms of centromere loss and chromosome fusion driving distinct karyotypes in closely related fungal species, including prominent global human pathogens.

A Descriptive Study of Quality of Life Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment. METHODS: A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired t tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively. RESULTS: Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing (P = .7), social eating (P = .8), xerostomia (P = .9)]. CONCLUSION: In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function.