Land use change frequency influences the achievement of land degradation neutrality: Evidence from the Yunnan-Guangxi-Guizhou key rocky desertification areas in China.

Gastric cancer is one of the most common malignant tumors in China. Gastric signet ring cell carcinoma (SRCC) belongs to highly malignant undifferentiated gastric cancer, originating from the epithelial cells of the gastric mucosa. Research has shown that the incidence of gastric cancer is gradually decreasing, but the incidence of gastric SRCC is gradually increasing. We report an extremely rare case of dual primary SRCC involving the gastric cardia and antrum. This case highlights the diagnostic challenges of synchronous SRCC, where a high level of suspicion, comprehensive endoscopic evaluation, and multidisciplinary management are crucial for achieving optimal treatment outcomes. The 69-year-old female patient presented with poor appetite and significant weight loss, prompting her hospitalization. Following diagnostic evaluations, she was diagnosed with dual primary SRCC involving both the gastric cardia and antrum. Postsurgery, she experienced severe complications, including malnutrition, postoperative infections, and intestinal obstruction, significantly impairing her quality of life. Currently, she remains under regular chemotherapy (Tegio) and trastuzumab-targeted therapy. The patient was finally diagnosed with double primary SRCC of the cardia and antrum of the stomach through gastroscopy and pathological tissue biopsy. Laparoscopic radical total gastrectomy (October 28, 2024)Adjuvant therapy: Tegio chemotherapy + trastuzumab (human epidermal growth factor receptor 2 [HER2] targeted). Complications such as malnutrition, postoperative infection, intestinal obstruction, as well as complications related to chemotherapy and targeted therapy, which had a serious impact on the quality of life. Importance of clinical vigilance: Although this patient had no family history of gastric cancer, her nonspecific gastrointestinal symptoms ultimately led to the diagnosis of dual primary SRCC. This highlights the need for high suspicion of malignancy in elderly patients presenting with nonspecific symptoms.Diagnostic value of multidisciplinary collaboration: The integration of endoscopic, pathological, imaging (computed tomography/magnetic resonance imaging), and immunohistochemical findings enabled accurate diagnosis of this rare case of dual primary gastric malignancy and identification of HER2 expression heterogeneity. The heterogeneity in HER2 expression (1+ vs 3+) demonstrates potential molecular differences between lesions in the same patient, emphasizing the necessity for comprehensive biopsy sampling.

Human epidermal growth factor receptor 2 (HER2) is a critical therapeutic target in various cancers, but its accurate noninvasive quantification remains challenging. Existing positron emission tomography (PET) tracers, such as antibodies and peptides, are limited by suboptimal clearance, insufficient tumor uptake and retention, and poor proteolytic stability. Here, we introduce a new class of disulfide-directed multicyclic peptides (DDMPs) that combine a conformationally rigid and stable scaffold with excellent HER2-binding properties. Using yeast display and directed evolution, we identified optimized DDMPs with single-digit nanomolar affinity for HER2. Alanine scanning mutagenesis revealed conserved residues that were amenable to functional modification. After gallium-68 (68Ga) radiolabeling, these DDMPs demonstrated significantly enhanced tumor accumulation, prolonged retention, and superior sensitivity in detecting HER2-expressing tumors compared to those of existing peptide tracers. Our work establishes DDMPs as a structurally distinct class of peptide tracers with superior performance, representing a significant advancement toward the clinical translation of precision PET imaging for HER2-positive cancers.

To compare camrelizumab plus capecitabine and oxaliplatin followed by camrelizumab plus apatinib (camre+CAPOX followed by camre+apa), CAPOX alone, and camrelizumab plus CAPOX followed by camrelizumab (camre+CAPOX followed by camre) as initial treatment for gastric or gastro-oesophageal junction adenocarcinoma. Randomised, open label, phase 3 study. 75 hospitals in China, 13 March 2019 to 16 August 2021. 885 adults (≥18 years) with previously untreated, human epidermal growth factor receptor 2 (HER2) negative, unresectable, locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Patients were randomised (2:2:1) to receive camre+CAPOX followed by camre+apa, CAPOX only, or camre+CAPOX followed by camre, stratified by Eastern Cooperative Oncology Group performance status, peritoneal metastasis, and programmed death ligand 1 (PD-L1) combined positive score. Assignment to camre+CAPOX followed by camre was introduced midway through enrolment. The primary endpoint was overall survival for camre+CAPOX followed by camre+apa versus CAPOX alone in the PD-L1 positive population (combined positive score >1) and the overall population who received at least one dose of study drug. Comparisons of camre+CAPOX followed by camre versus CAPOX alone and of camre+CAPOX followed by camre+apa versus camre+CAPOX-camre were descriptive. Safety was assessed in all patients who received at least one dose of study drug. 352 patients received camre+CAPOX followed by camre+apa, 349 received CAPOX alone, and 177 received camre+CAPOX followed by camre. At the time of data cut off, 454 of 592 (76.7%) deaths had occurred in the PD-L1 positive population and 709 of 878 (80.8%) in the overall population. Overall survival was longer with camre+CAPOX followed by camre+apa than with CAPOX alone in the PD-L1 positive population (median 15.0 v 12.5 months; hazard ratio 0.80 (95% CI 0.65 to 0.98); one sided P=0.02) and in the overall population (median 13.5 v 12.1 months; hazard ratio 0.80 (0.68 to 0.94); one sided P=0.004). Use of camre+CAPOX followed by camre also showed longer overall survival versus CAPOX in the PD-L1 positive population (median 15.3 v 12.5 months; hazard ratio 0.76 (0.58 to 0.97); one sided nominal P=0.01) and overall population (median 14.2 v 12.1 months; hazard ratio 0.80 (0.65 to 0.98); one sided nominal P=0.02). No overall survival benefit was observed with camre+CAPOX followed by camre+apa versus camre+CAPOX followed by camre. Treatment related adverse events of grade ≥3 occurred in 239 of 352 (67.9%) patients in the camre+CAPOX followed by camre+apa group, 158 of 349 (45.3%) in the CAPOX alone group, and 83 of 177 (46.9%) in the camre+CAPOX followed by camre group. Initial treatment with camrelizumab plus CAPOX followed by camrelizumab based maintenance was associated with longer overall survival than CAPOX alone in human epidermal growth factor receptor 2 (HER2) negative, unresectable, locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Exploratory comparisons between the two camrelizumab based regimens showed no additional survival benefit, with higher rates of treatment related adverse events of grade ≥3 and treatment discontinuations when apatinib was added during maintenance. ClinicalTrials.gov NCT03813784.

Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have been widely used for human epidermal growth factor receptor 2 (HER2) status determination in breast cancers for about 25 years. Most laboratories use IHC as the first line of testing in both primary and metastatic breast cancers. Implementation of and updates to the ASCO/CAP guidelines have improved the reported discrepancy between IHC and FISH results. To investigate the incidence of discordance between IHC and FISH after the most recent guideline update and to determine possible underlying causes. Breast cancer cases simultaneously tested for HER2 by IHC and FISH from January 2023 through July 2024 were identified. Information on clinicopathologic features and follow-up on cases with discordant results were obtained from electronic records. IHC-negative/FISH-positive discordance was identified in 10 of 956 cases (1.1%). Discordance was significantly more commonly seen in tissues from metastatic sites where ischemic and fixation times were not documented owing to unknown primary site at the time of biopsy. IHC-negative/FISH-positive cases had significantly lower HER2 copy number per cell in discordant cases. Dual IHC and FISH testing, especially from metastatic sites, may need to be considered to ensure all patients eligible for targeted therapies are identified. Significant differences in HER2 copy numbers between discordant and concordant cases raise the possibility of underlying biologic differences and require further investigation.

To evaluate the impact of a patient support program (PSP) on the management of abemaciclib-related diarrhea in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) and its influence on adherence and patient-reported outcomes in routine clinical practice. This is a multicenter, prospective, observational Spanish study in patients with locally advanced or MBC receiving abemaciclib and enrolled in the PSP, assessed over 6months. The primary endpoint was the proportion of patients reducing or discontinuing abemaciclib due to diarrhea. The secondary endpoints included diarrhea-related temporary interruptions, diarrhea management, adherence, HRQoL, and satisfaction with the PSP. Descriptive statistics were applied and treatmentmodification endpoints were analyzed using Kaplan-Meier. The study included 39 patients (median age: 58years), with a median time since diagnosis of MBC of 2months. Diarrhea occurred in 89.7% of patients, with grade 3 events in 7.7% and no grade ≥ 4 events. Nine patients (23.1%) experienced treatment modifications due to diarrhea; however, no permanent treatment discontinuations were reported. Loperamide (over 75% of patients) and dietary modifications were the most used self-care strategies. At week 24, results from the adhoc questionnaires showed that over 70% of the patients reported high satisfaction with all PSP aspects, and 80% were classified as treatment adherent. Episodes of diarrhea were mostly graded 1-2 and no patients discontinued abemaciclib due to diarrhea. Patients reported high satisfaction with abemaciclib PSP, good adherence, and favorable quality of life, supporting the use of PSP in clinical practice.

Multi-Parametric Super-Resolution Ultrasound for Evaluating Breast Cancer Characteristics: Improved Diagnostic Performance Over Contrast-Enhanced Ultrasound.

This paper introduces Monotone Delta (δ), an order-theoretic measure for assessing the internal consistency of survey-based instruments. Classical coefficients such as Cronbach's Alpha and McDonald's Omega can yield misleading estimates under practical violations, including redundancy, multidimensional constructs, and correlated errors. Monotone Delta avoids parametric and factor-model assumptions by quantifying internal consistency through contradiction minimization with a weighted tournament formulation, aligning responses to an optimal unidimensional latent order. In controlled synthetic studies across four scenarios (tau-equivalence, redundancy, multidimensionality, and non-normal/correlated errors), Monotone Delta stays closest to the theoretical reliability, with absolute error ≤ 0.02 in the challenging scenarios where Alpha and Omega deviate by as much as 0.22 and 0.14, respectively. On a 350-participant human study for AI-generated image assessment, Monotone Delta agrees with Alpha/Omega under near-ideal conditions (overall δ = 0.91 vs. α = 0.92, ω = 0.94) while remaining stable under redundancy and non-normal perturbations (overall δ = 0.84 and δ = 0.81, respectively, where Alpha drops to 0.95 and 0.35). These results position Monotone Delta as a practical alternative for reliability assessment in socio-technical systems, human factors, healthcare, and interactive system design.

This study develops and applies an integrated methodology that combines deep learning-based computer vision and spatial statistics to automate the large-scale identification and analysis of morphological features in vernacular courtyard dwellings. Focusing on Liangshuaixiu dwellings in Wu’an, southern Hebei, we trained an HRNetV2 semantic segmentation model on high-resolution satellite imagery to identify and extract contours for 134,280 courtyard spaces. Core morphological parameters (area, orientation) were calculated and analyzed using GIS spatial statistics and the geographic detector model. The results show that (1) the computer vision pipeline achieved efficient recognition with satisfactory accuracy (~10% mean error); (2) spatial autocorrelation and hotspot analysis revealed distinct regional patterns, including a west–east increase in average courtyard area; and (3) geographic detector analysis demonstrated that courtyard morphology is shaped by complex interactions between natural and socio-economic factors. While average area and orientation were primarily governed by climate (air pressure, wind, temperature) and topography (elevation), diversity and internal variation were strongly influenced by nonlinear interactions, particularly between natural factors (e.g., wind–aspect) and between natural and human factors (e.g., population–climate). This work provides a scalable, data-driven framework for the quantitative spatial analysis of vernacular architectural heritage, advancing the understanding of building morphology as an outcome of coupled human–environment systems.

Since its description by Hull and colleagues in 1981, several case series have described the clinicopathological features of glycogen-rich breast carcinoma (GRC); however, no detailed genetic study has been performed. We identified 10 patients with GRC; all were female (ages: 32 to 74y; median: 51). Tumor size ranged from 0.7 to 3.8cm (median: 1.45). All except one GRC showed relatively well-defined borders, and all were composed predominantly of nests containing clear cells with glycogen accumulation in cytoplasm confirmed by Periodic Acid-Schiff/Periodic Acid-Schiff- Diastase (PAS/PAS-D)staining. Using Nottingham grading, four were grade 2 and six were grade 3. Seven showed associated ductal carcinoma in situ (DCIS) with glycogen-rich features. Lymph node macrometastasis was seen in 2=two. Six were hormone receptor (HR) +/ human epidermal growth factor receptor 2 (HER2)-, 2 HR low +/ HER2- and 2 triple-negative. Follow-up (available for 9/10) ranged from 9 to 186 months (median: 38). All patients were alive; two patients had distant metastasis, one patient had local recurrence and six had no evidence of disease. DNA sequencing suggested two molecular subgroups: GATA3-mutant GRCs (5/10) with frequent RPKSB1 copy number gain (4/5) and TP53-mutant GRCs (4/10). GATA3-mutant GRCs were mixed grade 2/3, all were HR+ without distant metastasis while TP53-mutant GRCs were all grade 3, showed low +/- HR, and 3/4 patients showed distant metastasis/local recurrence. p53 immunohistochemistry showed mutant-pattern staining in three TP53-mutant GRCs tested as opposed to wild-type pattern in five GATA3-mutant GRCs. Molecular studies or p53 immunohistochemistry as a surrogate could be helpful to identify the TP53-mutant subgroup for closer follow-up and/or more aggressive treatment.

The rapid advancement of robotics presents significant opportunities and challenges for human–robot interaction (HRI) in intralogistics. While prior research has largely relied on frameworks driven by adoption intention, empirical evidence on how HRI unfolds in real-world intralogistics remains limited. To address this gap, this study adopts a methodological triangulation approach that integrates a systematic literature review of 93 academic papers with 23 semi-structured expert interviews involving 3 stakeholder groups: current HRI users, potential users or failed adopters, and external stakeholders including robot manufacturers and consultants. Capturing these diverse perspectives is essential for reflecting the different experiences, expectations, and constraints that shape HRI in practice. The analysis identifies four key opportunities associated with HRI: enhanced operational performance, improved working conditions, increased system resilience, and sustainability. Furthermore, nine interdependent challenges are revealed, namely process complexity, human behavioural factors, occupational safety, training and skill requirements, trust and acceptance, costs, technology and infrastructure design, deteriorating working conditions, and legal issues. Using socio-technical systems theory as an analytical lens, the study demonstrates that effective HRI depends on the alignment of people, organisational structures, technologies, and tasks, and proposes a conceptual framework to support the balanced integration of HRI challenges and opportunities.

This qualitative study investigates the practices of oral health therapy and dental students who took part in an elective narrative dentistry course. The use of narratives as a teaching method is underpinned in this work by the writing of Arthur Frank, where he promotes storytelling to counteract the diminishing effects of disease and ill-health. Students enrolled in professional dental courses were invited to take part in a voluntary short learning programme based on the concept of narrative dentistry involving didactic instruction, class discussion and a writing task. In total, 25 students enrolled in the course. Data analysis involved triangulation of field data from the online module and on-line zoom classes, focus group discussion and students' narratives. The analysis was guided by principles outlined by Arthur Frank on diminished lives. The themes arising from analysis were (1) narrative dentistry making overlooked human factors in students' routine practice visible; (2) narrative dentistry as a teaching tool for students to see loss and grief connected with dental disease; and (3) narrative dentistry as a teaching tool which enables students to express a hope for care. The narratives created by the participants and engagement with the learning activities suggest that narrative dentistry courses can provide students with a way to make sense of patient experiences in dental care, help to facilitate reflection on empathy and connect students with understanding of what it might mean to provide person-centred dentistry.

The integration of Artificial Intelligence (AI) into academic mentoring has the potential to transform conventional approaches by increasing efficiency, availability, and accuracy. However, the challenge lies in ensuring that such advances do not supplant the essential human factors of empathy, intuition, and contextual understanding. This chapter aims to design a sustainable framework that combines AI-driven effectiveness with human-centred mentorship practices, thereby achieving an optimal equilibrium between technological advancement and personalised guidance. To this end, a qualitative methodological approach was employed, with data collected through semi-structured interviews with ten academic mentors and fifteen postgraduate mentees from a range of multidisciplinary fields of study. Thematic data analysis was utilised to examine the data. The findings reveal that while AI significantly enhances routine tasks such as feedback, scheduling, and resource allocation, mentees consistently value human interaction for emotional support, nuanced advice, and contextual adaptability. The proposed framework underscores the integration of AI tools and human guidance, highlighting areas where AI excels and domains where human insight remains irreplaceable. This chapter emphasises the importance of promoting synergy between AI and human mentors, which ultimately aims to improve the quality, accessibility, and inclusiveness of mentorship in academia. Furthermore, the chapter serves as a foundation for further research on sustainable, AI-enhanced mentorship paradigms.

With the ongoing industrial revolution, the innovative approaches to marketing strategies are being introduced, including the drones’ usage of online food delivery services. However, drone adoption involve into the food delivery sector remains limited and has yet to take hold in Malaysia. While drones are already utilized in various Malaysian industries—such as border security surveillance, aerial photography, and disaster relief operations, including the delivery of critical supplies during floods—the food delivery industry has not yet embraced this technology. This study seeks to prolong Technology Readiness and Acceptance Model (TRAM) by integrating delivery risk as main independent variable to better understand individual behavior toward adopting emerging technologies. Gaining deeper insights into these human factors can assist decision-makers and marketers in crafting strategies that better align with customer expectations. Specifically, two new constructs—delivery risk and generation gap—were incorporated into the model. The extended framework was empirically tested using a quantitative approach within the Malaysian context. Out of 400 questionnaires distributed, 384 valid responses were obtained. The results indicated that respondents’ views did not fully align with the hypothesized relationships concerning the two additional constructs and their influence on adoption intention, particularly regarding drone use in food delivery services.

Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant. This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-), PIK3CA wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment. Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective. A total of 392 patients were randomly assigned 1:1:1. The median study follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%). Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients. The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor-positive/HER2-, PIK3CA WT advanced breast cancer.

This study aims to evaluate the clinical utility of a radiomics model derived from post-neoadjuvant chemotherapy (post-NAC) preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for predicting pathologic complete response (pCR) to NAC in patients with breast cancer exhibiting non-mass lesions (NMLs). A total of 121 patients were included (training: n = 85; validation: n = 36), of whom 56 achieved pCR. The radiomics-only model demonstrated good discriminative performance (training AUC: 0.927; validation AUC: 0.867), outperforming both the clinical data model (AUCs: 0.577, 0.608) and radiologist assessment (AUCs: 0.708, 0.571). Incorporating clinical variables further improved predictive accuracy (training AUC: 0.933; validation AUC: 0.870). The triple-integration model attained AUCs of 0.936 and 0.810, with no statistically significant difference compared with the radiomics-only model P = 0.450 and P = 0.235 for training and validation, respectively. In addition, SHAP analysis showed radiomic features contributed most to prediction, followed by human epidermal growth factor receptor 2 and hormone receptor status. Post-NAC preoperative DCE-MRI-based radiomics provides a non-invasive method for predicting pCR in non-mass enhancement breast cancer. The combined radiomics-clinical model achieves superior performance and offers potential value for individualized NAC response assessment. Radiomic features effectively characterize the chemotherapy-altered tissue phenotype, offering an objective and quantitative approach for preoperative treatment response assessment in complex NML-type breast cancer, supporting individualized treatment planning. Accurate early prediction of pCR could help identify patients most likely to benefit from NAC and avoid ineffective treatment in non-responders. The developed radiomics model offers an interpretable and reproducible tool; upon successful external validation, it has the potential to support personalized treatment planning in patients with NML-type breast cancer.

Cell-free protein synthesis has become a powerful tool for producing functional proteins, circumventing many limitations of live-cell systems. Platforms based on wheat germ extract are favored for their high efficiency in translating and folding complex eukaryotic proteins. To overcome the energy limitation common in such systems, we engineered an Escherichia coli strain to function as a self-renewing ATP source. This strain co-expresses a three-enzyme cascade—adenosine kinase, adenylate kinase, and acetate kinase—that efficiently converts adenosine and acetyl phosphate into ATP. Using the lysate from this biocatalyst to energize an optimized wheat germ extract, we established a high-performance cell-free synthesis platform. This integrated system supported the robust production of multiple recombinant proteins. As a key demonstration, we synthesized human vascular endothelial growth factor 165, which exhibited full biological activity. The cell-free-produced VEGF165 significantly stimulated the proliferation of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs). It also potently induced angiogenic responses, including the formation of extensive, interconnected capillary-like networks by HUVECs in vitro and accelerated cell migration in scratch-wound assays. Our work establishes a scalable and efficient platform for on-demand production of bioactive eukaryotic proteins, highlighting its considerable potential for advancing regenerative medicine and related therapeutic applications.

Comparison of CT-based radiomics models for the prediction of human epidermal growth factor receptor 2 status in gastric cancer.

Polyphenols represent the largest and most diverse class of dietary antioxidants. Epidemiological evidence linking specific (poly)phenol classes, such as flavonoids and lignans, to breast cancer (BC) risk remains limited and largely inconclusive in prospective studies. The aim of this study is to examine the association between the intake of total (poly)phenols—and its classes and subclasses—and BC risk—overall and by subtypes (estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2))—in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The EPIC cohort includes 257,960 adult women from seven European countries. During a mean follow-up of 14 years, there were 10,722 incident overall BC cases. Associations were computed using Cox regression models adjusted for potential confounders. No significant associations were found between total (poly)phenol intake and overall BC risk (HRQ5 vs. Q1 = 1.02; 95% CI: 0.95–1.11). In addition, null associations were mostly found between classes and subclasses of (poly)phenols and BC subtypes. After stratifying by menopausal status, no significant associations were observed. In conclusion, this study found no evidence of associations between the intake of any class or subclass of (poly)phenols and BC risk in the European population.

Longitudinal wastewater metagenomics reveals distinct environmental and anthropogenic associations with resistance, virulence, and viral communities.