Search Results (1,448)

Objectives: To perform the first national analysis of demographic and clinicopathological features associated with the HER2 positive, HER2-low, and HER2-zero invasive breast cancers in New Zealand. The study will reveal the proportion of women who may benefit from new HER2-targeted antibody drug conjugate (ADC) therapies. Methods: Utilising data from Te Rēhita Mate Ūtaetae (Breast Cancer Foundation NZ National Register), the study analysed data from women diagnosed with invasive breast cancer over a 21-year period. The HER2 status of tumours was classified into three categories—HER2-zero, HER2-low, HER2-positive. Results: From 2009–2021, 94% of women underwent HER2 testing, with 14% diagnosed with HER2-positive breast cancer. For advanced-stage disease, 38% of those formerly classified as HER2-negative were reclassified as HER2-low. Including HER2-positive breast cancers, this indicates that 60% of women with advanced breast cancer may potentially benefit from the new HER2-directed ADCs (approximately 120 women per year). Conclusions: The findings suggest a significant proportion of women with invasive breast cancer in New Zealand could benefit from new HER2-targeted treatments. There is a need to standardise HER2 testing to enhance personalised treatment and improve outcomes. Full article

Background: Epstein–Barr virus (EBV) is involved in the development of lymphomas, nasopharyngeal carcinomas (NPC), and a subgroup of gastric carcinomas (GC), and has also been detected in lung carcinomas, even though the role of the virus in this malignancy has not yet been established. BamH1-A Rightward Frame 1 (BARF1), a suggested exclusive epithelial EBV oncoprotein, is detected in both EBV-associated GCs (EBVaGC) and NPC. The expression and role of BARF1 in lung cancer is unknown. Methods: A total of 158 lung carcinomas including 80 adenocarcinomas (AdCs) and 78 squamous cell carcinomas (SQCs) from Chilean patients were analyzed for EBV presence via polymerase chain reaction (PCR), Immunohistochemistry (IHC), or chromogenic in situ hybridization (CISH). The expression of BARF1 was evaluated using Reverse Transcription Real-Time PCR (RT-qPCR). Additionally, A549 and BEAS-2B lung epithelial cells were transfected with a construct for ectopic BARF1 expression. Cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) were evaluated. Results: We found that EBV was present in 37 out of 158 (23%) lung carcinomas using PCR. Considering EBV-positive specimens using PCR, IHC for Epstein–Barr nuclear antigen 1 (EBNA1) detected EBV in 24 out of 30 (80%) cases, while EBERs were detected using CISH in 13 out of 16 (81%) cases. Overall, 13 out of 158 (8%) lung carcinomas were shown to be EBV-positive using PCR/IHC/CISH. BARF1 transcripts were detected in 6 out of 13 (46%) EBV-positive lung carcinomas using RT qPCR. Finally, lung cells ectopically expressing BARF1 showed increased migration, invasion, and EMT. Conclusions. EBV is frequently found in lung carcinomas from Chile with the expression of BARF1 in a significant subset of cases, suggesting that this viral protein may be involved in EBV-associated lung cancer progression. Full article

Carbon nanotube field-effect transistors (CNT-FETs) have shown great promise in infrared image detection due to their high mobility, low cost, and compatibility with silicon-based technologies. This paper presents the design and simulation of a column-level analog front-end (AFE) circuit tailored for carbon-based short-wave infrared (SWIR) photodetectors. The AFE integrates a Capacitor Trans-impedance Amplifier (CTIA) for current-to-voltage conversion, coupled with Correlated Double Sampling (CDS) for noise reduction and operational amplifier offset suppression. A 10-bit/125 kHz Successive Approximation analog-to-digital converter (SAR ADC) completes the signal processing chain, achieving rail-to-rail input/output with minimized component count. Fabricated using 0.18 μm CMOS technology, the AFE demonstrates a high signal-to-noise ratio (SNR) of 59.27 dB and an Effective Number of Bits (ENOB) of 9.35, with a detectable current range from 500 pA to 100.5 nA and a total power consumption of 7.5 mW. These results confirm the suitability of the proposed AFE for high-precision, low-power SWIR detection systems, with potential applications in medical imaging, night vision, and autonomous driving systems. Full article

Biological barriers remain a major obstacle for the development of innovative therapeutics. Depending on a disease’s pathophysiology, the involved tissues, cell populations, and cellular components, drugs often have to overcome several biological barriers to reach their target cells and become effective in a specific cellular compartment. Human biological barriers are incredibly diverse and include multiple layers of protection and obstruction. Importantly, biological barriers are not only found at the organ/tissue level, but also include cellular structures such as the outer plasma membrane, the endolysosomal machinery, and the nuclear envelope. Nowadays, clinicians have access to a broad arsenal of therapeutics ranging from chemically synthesized small molecules, biologicals including recombinant proteins (such as monoclonal antibodies and hormones), nucleic-acid-based therapeutics, and antibody-drug conjugates (ADCs), to modern viral-vector-mediated gene therapy. In the past decade, the therapeutic landscape has been changing rapidly, giving rise to a multitude of innovative therapy approaches. In 2018, the FDA approval of patisiran paved the way for small interfering RNAs (siRNAs) to become a novel class of nucleic-acid-based therapeutics, which—upon effective drug delivery to their target cells—allow to elegantly regulate the post-transcriptional gene expression. The recent approvals of valoctocogene roxaparvovec and etranacogene dezaparvovec for the treatment of hemophilia A and B, respectively, mark the breakthrough of viral-vector-based gene therapy as a new tool to cure disease. A multitude of highly innovative medicines and drug delivery methods including mRNA-based cancer vaccines and exosome-targeted therapy is on the verge of entering the market and changing the treatment landscape for a broad range of conditions. In this review, we provide insights into three different disease entities, which are clinically, scientifically, and socioeconomically impactful and have given rise to many technological advancements: acquired immunodeficiency syndrome (AIDS) as a predominant infectious disease, pancreatic carcinoma as one of the most lethal solid cancers, and hemophilia A/B as a hereditary genetic disorder. Our primary objective is to highlight the overarching principles of biological barriers that can be identified across different disease areas. Our second goal is to showcase which therapeutic approaches designed to cross disease-specific biological barriers have been promising in effectively treating disease. In this context, we will exemplify how the right selection of the drug category and delivery vehicle, mode of administration, and therapeutic target(s) can help overcome various biological barriers to prevent, treat, and cure disease. Full article

Objective: The diagnostic efficacy of the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging (DW-MRI) for lymph node metastasis in biliary tract cancer was investigated in the present study. Methods: In total, 112 surgically resected lymph nodes from 35 biliary tract cancer patients were examined in this study. The mean and minimum ADC values of the lymph nodes as well as the long-axis and short-axis diameters of the lymph nodes were assessed by computed tomography (CT). The relationship between these parameters and the presence of histological lymph node metastasis was evaluated. Results: Histological lymph node metastasis was detected in 31 (27.7%) out of 112 lymph nodes. Metastatic lymph nodes had a significantly larger short-axis diameter compared with non-metastatic lymph nodes (p = 0.002), but the long-axis diameter was not significantly different between metastatic and non-metastatic lymph nodes. The mean and minimum ADC values for metastatic lymph nodes were significantly reduced compared with those for non-metastatic lymph nodes (p < 0.001 for both). However, the minimum ADC value showed the highest accuracy for the diagnosis of histological lymph node metastasis, with an area under the curve of 0.877, sensitivity of 87.1%, specificity of 82.7%, and accuracy of 83.9%. Conclusions: The minimum ADC value in DW-MRI is highly effective for the diagnosis of lymph node metastasis in biliary tract cancer. Accurate preoperative diagnosis of lymph node metastasis in biliary tract cancer should enable the establishment of more appropriate treatment strategies. Full article

HER2-low tumors have shown promise in response to antibody–drug conjugates (ADCs) in recent clinical trials, underscoring the need to characterize this group’s clinical phenotype. In this study, we aimed to explore the clinicopathological features, survival rates, and HER2 amplicon mRNA expression of women affected with HER2-low breast cancer, compared with HER2-negative and HER2-positive groups. We included 516 breast cancer patients from Colombia, for whom we compared clinicopathological features, mRNA expression of three HER2 amplicon genes (ERBB2, GRB7 and MIEN1), survival and risk of mortality between HER2-low cases (1+ or 2+ with negative in situ hybridization (ISH) result) with HER2-positive (3+ or 2+ with positive ISH test) and HER2-negative (0+) cases. A higher proportion of patients with better-differentiated tumors and a lower proliferation index were observed for HER2-low tumors compared to the HER2-positive group. Additionally, HER2-low tumors showed higher mRNA expression of the ERBB2 gene and longer overall survival rates compared to HER2-negative cases. Nonetheless, a Cox-adjusted model by ER status and clinical stage showed no statistically significant differences between these groups. Our results show differences in important clinicopathological features between HER2-low and both HER2-positive and negative tumors. Given this unique phenotype, it is crucial to evaluate the potential advantages of ADC therapies for this emerging subtype of breast cancer. Full article

A carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak in an intensive care unit (ICU) was contained by an improved infection-control measure that included a disinfectant policy. In our retrospective cohort study, we describe the epidemiological investigations and infection-control measures during this outbreak. Descriptive analysis was used to summarize patient demographics, neurological diseases, surgical treatment, underlying diseases, infection, and outcomes. In December 2023, two CARB-positive patients were observed in the ICU, and four more patients became CRAB-positive in January. During this outbreak, there was an overlap of hospitalization periods among the CRAB-positive patients, and CRAB was isolated from the environment; the isolated CRAB strain was identical. Infection-control measures, including hand hygiene, contact precautions and isolation, surveillance, decolonization, environmental cleaning, and disinfection, were reviewed and modified. The aim of this study was to examine the molecular background of the effectiveness of the disinfectant shift used during successful outbreak control. Experiments were carried out to study the phenotypic sensitivity and genetic background of different disinfectant agents. A thorough analysis of the detected CRAB strain included whole-genome sequencing (WGS), investigation of the qacE and qacEΔ1 genes’ relative expression by qPCR after exposure to different disinfectant solutions, as well as an analysis of biofilm formation. WGS analysis of the CRAB strain identified that an ST2 high-risk clone was responsible for the outbreak, which produced OXA-83 and ADC-30 beta-lactamases; in addition, qacE and qacEΔ1 genes were also detected, which confer resistance to disinfectants containing quaternary ammonium compounds (QACs). A qPCR analysis demonstrated that after exposure to different disinfectants, the gene expression levels of qacE and qacEΔ1 increased and correlated with concentrations of QACs of disinfectants. During the outbreak, the standard-of-care QAC-based disinfectant was changed to a mainly alcohol-based agent in the ICU, which contributed to the successful control of this outbreak, and no additional patients were identified with CRAB. We conclude that continuous surveillance and hand hygiene training combined with fast identification and reaction to new cases, as well as an in-depth analysis of multidrug-resistant outbreak strains and investigation of their disinfectant tolerance/resistance during an outbreak, are essential to effectively control the spread of nosocomial pathogens. The smart policy of disinfectant agent selection played a crucial role in controlling the outbreak and ensuring patient safety in the ICU. Full article

Studying air Urban Heat Islands (AUHI) in African cities is limited by building height data scarcity and sparse air temperature (T_air) networks, leading to classification confusion and gaps in T_air data. Satellite imagery used in surface UHI (SUHI) applications overcomes the gaps which befall AUHI, thus making it the primary focus of UHI studies in areas with limited T_air stations. Consequently, we used Landsat 30 m imagery to analyse SUHI patterns using Land Surface Temperature (LST) data. Local climate zones (LCZ) as a UHI study tool have been documented to not result in distinct thermal environments at the surface level per LCZ class. The goal in this study was thus to explore relationships between LCZs and LST patterns, aiming to create a building height (BH)-independent LCZ framework capable of creating distinct thermal environments to study SUHI in African cities where LiDAR data are scarce. Random forests (RF) classified LCZ in R, and the Single Channel Algorithm (SCA) extracted LST via the Google Earth Engine. Statistical analyses, including ANOVA and Tukey’s HSD, assessed thermal distinctiveness, using a 95% confidence interval and 1 °C threshold for practical significance. Semi-Automated Agglomerative Clustering (SAAC) and Automated Divisive Clustering (ADC) grouped LCZs into thermally distinct clusters based on physical characteristics and LST data internal patterns. Built LCZs (1–9) had higher mean LSTs; LCZ 8 reached 37.6 °C in Spring, with a smaller interquartile range (IQR) (34–36 °C) and standard deviation (SD) (1.85 °C), compared to natural classes (A–G) with LCZ 11 (A–B) at 14.9 °C/LST, 17–25 °C/IQR, and 4.2 °C SD. Compact LCZs (2, 3) and open LCZs (5, 6), as well as similar LCZs in composition and density, did not show distinct thermal environments even with building height included. The SAAC and ADC clustered the 14 LCZs into six thermally distinct clusters, with the smallest LST difference being 1.19 °C, above the 1 °C threshold. This clustering approach provides an optimal LCZ framework for SUHI studies, transferable to different urban areas without relying on BH, making it more suitable than the full LCZ typology, particularly for the African context. This clustered framework ensures a thermal distinction between clusters large enough to have practical significance, which is more useful in urban planning than statistical significance. Full article

While traditional combination anticancer treatments have shown promising results, there remains significant interest in developing innovative methods to enhance and integrate chemotherapy and immunotherapy. This study introduces a recombinant fusion protein-based cell surface modification system that synergistically combines chemotherapy and immunotherapy into a single-targeted chemo-immunotherapy approach. A cell surface-modified protein composed of an antibody-specific binding domain and a cell-penetrating domain rapidly converts immune cells into chemo-immuno therapeutics by binding to antibodies on the surface of immune cells. Utilizing a non-invasive, non-toxic approach free of chemical modifications and binding, our system homogeneously transforms immune cells by transiently introducing targeted cytotoxic drugs into them. The surface-engineered immune cells loaded with antibody–drug conjugates (ADCs) significantly inhibit the growth of target tumors and enhance the targeted elimination of cancer cells. Therefore, NK cells modified by the cell surface-modified protein to incorporate ADCs could be expected to achieve the combined effects of targeted cancer cell recognition, chemotherapy, and immunotherapy, thereby enhancing their therapeutic efficacy against cancer. This strategy allows for the efficient and rapid preparation of advanced chemo-immuno therapeutics to treat various types of cancer and provides significant potential to improve the efficacy of cancer treatment. Full article

Cervical cancer related to high-risk human papillomavirus (HR-HPV) is the second female cancer in Mauritania (Northwest Sahelian Africa). We assessed the distribution of HPV genotypes in Mauritanian women with high-grade cervical intraepithelial neoplasia (CIN2/3) or invasive cervical cancer (ICC). A prospective study was conducted in the Centre Hospitalier National, Nouakchott, Mauritania, to collect cervical biopsies among women suspected of CIN2/3 or cancer. HPV DNA detection and genotyping were carried out from formalin-fixed, paraffin-embedded biopsies using multiplex PCR (Human Papillomavirus Genotyping Real-Time PCR Kit, Bioperfectus Technologies Co., Taizhou, China). Fifty biopsies were included from women (mean age: 56.7 years) suffering from CIN2/3 (28.0%) and ICC (72.0%) which corresponded to 32 (64.0%) squamous cell carcinomas (SCC) and 4 (8.0%) adenocarcinomas (ADC). HPV DNA detection was successful in 47 (94.0%) samples. The most prevalent HR-HPV genotypes were HPV-45 (40.4%), HPV-16 (38.3%), HPV-39 and HPV-52 (23.4%), HPV-33 (17.0%), HPV-18 (14.9%), HPV-35 (4.2%), and HPV-56 (2.1%). The majority (93.6%) of HPV-positive biopsies contained at least one HPV type covered by the 9-valent Gardasil-9^® vaccine, and 40.9% were infected by multiple vaccine HPV genotypes. To eradicate cervical cancer in Mauritania, prophylactic HPV vaccination must be combined with primary molecular screening of cervical HR-HPV infection. Full article

Accurate prediction of renal mass subtypes, along with the WHO/ISUP grade and pathological T (pT) stage of clear cell renal cell carcinoma (ccRCC), is crucial for optimal decision making. Our study aimed to investigate the feasibility and reproducibility of motion-robust radial T2 mapping in differentiating lipid-poor angiomyolipoma (MFAML) from RCC and characterizing the WHO/ISUP grade and pT stage of ccRCC. Finally, 92 patients undergoing renal radial T2 mapping and ZOOMit DWI were recruited. The T2 values and apparent diffusion coefficient (ADC) were analyzed. Correlation coefficients were calculated between ADC and T2 values. Notably, ccRCC exhibited higher T2 and ADC values than MFAML (p < 0.05). T2 values were lower in the higher WHO/ISUP grade and pT stage of ccRCC (all p < 0.05). ADC showed no significant difference for pT stage (p = 0.056). T2 values revealed a higher area under the curve (AUC) in evaluating the WHO/ISUP grade compared to ADC (0.936 vs. 0.817, p = 0.027). T2 values moderately positively correlated with ADC (r = 0.675, p < 0.001). In conclusion, quantitative motion-robust radial T2 mapping is feasible for characterizing solid renal masses and could provide additional value for multiparametric imaging in predicting WHO/ISUP grade and pT stage of ccRCC. Full article

The standard of care for advanced or metastatic urothelial carcinoma (mUC) was historically identified with platinum-based chemotherapy. Thanks to the advances in biological and genetic knowledge and technologies, new therapeutic agents have emerged in this setting recently: the immune checkpoint inhibitors and the fibroblast growth factor receptor inhibitors as the target therapy for patients harboring alterations in the fibroblast growth factor receptor (FGFR) pathway. However, chasing a tumor’s tendency to recur and progress, a new class of agents has more recently entered the scene, with promising results. Antibody–drug conjugates (ADCs) are in fact the latest addition, with enfortumab vedotin being the first to receive accelerated approval by the U.S. Food and Drug Administration in December 2019, followed by sacituzumab govitecan. Many other ADCs are still under investigation. ADCs undoubtedly represent the new frontier, with the potential of transforming the management of mUC treatment in the future. Therefore, we reviewed the landscape of mUC treatment options, giving an insight into the molecular basis and mechanisms, and evaluating new therapeutic strategies in the perspective of more and more personalized treatments. Full article

This paper introduces a fully differential asynchronous successive approximation register analog-to-digital converter (SAR ADC) designed for biomedical signal processing. By extending the tracking time and utilizing fully differential inputs in the analog front-end circuit, the signal-to-noise ratio is enhanced in the system. Using an asynchronous clock can reduce power consumption across a wider range of sampling frequencies. In comparison to conventional architecture in high-speed SAR ADC, using an internal clock generator can operate at lower frequencies. A fully differential input can eliminate the DC offset of the analog front-end circuit and reduce the adverse effects of process variation, voltage variation, and temperature variation. The chip is implemented by TSMC 0.18 μm complementary metal-oxide-semiconductor (CMOS) technology, and the chip area is 0.680 mm² (including ESD I/O PAD). At a 1.2 V supply, the maximum sampling rate is 10 Kilo Samples per second (KSps). The implemented ADC has an 11-bit resolution, while the input voltage range is 300∼900 mV. The total power consumption is 1.7 μW, with the core power consumption at 932 nW. Full article

This work presents a novel ΣΔ analog-to-digital converter (ADC) architecture for a high-resolution sensor interface. The concept is to reduce the effect of kT/C noise generated by the loop filter by placing the gain stage in front of the loop filter. The proposed architecture effectively reduces the kT/C noise power from the loop filter by as much as the squared gain of the added gain stage. The gain stage greatly relaxes the loop filter’s sampling capacitor requirements. The target resolution is 20 bit. The sampling frequency is 512 kHz, and the oversampling ratio (OSR) is only 256 for a target resolution. Therefore, the proposed ΔΣ ADC structure allows for high-resolution ADC design in an environment with a limited OSR. The proposed ADC designed in 65 nm CMOS technology operates at supply voltages of 1.2 V and achieves a peak signal-to-noise ratio (SNR) and Schreier Figure of Merit (FoMs) of 117.7 dB and 180.4 dB, respectively. Full article

Antibody–drug conjugates (ADCs) consist of an antibody backbone that recognizes and binds to a target antigen expressed on tumor cells and a small molecule chemotherapy payload that is conjugated to the antibody via a linker. ADCs are one of the most promising therapeutic modalities for the treatment of various cancers. However, many patients have developed resistance to this form of therapy. Extensive efforts have been dedicated to identifying an effective combination of ADCs with other types of anticancer therapies to potentially overcome this resistance. A recent clinical study demonstrated that a combination of the ADC enfortumab vedotin (EV) with the immune checkpoint inhibitor (ICI) pembrolizumab can achieve remarkable clinical efficacy as the first-line therapy for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC)—leading to the first approval of a combination therapy of an ADC with an ICI for the treatment of cancer patients. In this review, we highlight knowledge and understanding gained from the successful development of EV and the combination therapy of EV with ICI for the treatment of la/mUC. Using urothelial carcinoma as an example, we will focus on dissecting the underlying mechanisms necessary for the development of this type of combination therapy for a variety of cancers. Full article