Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and ...interpretation of pathway alteration patterns of individual patients.
We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets.
Postulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target.
Genetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.
Osteoporosis is a major skeletal disease associated with estrogen deficiency in postmenopausal women. Kefir-fermented peptides (KPs) are bioactive peptides with health-promoting benefits that are ...produced from the degradation of dairy milk proteins by the probiotic microflora in kefir grains. This study aimed to evaluate the effects of KPs on osteoporosis prevention and the modulation of the composition of the gut microbiota in ovariectomized (OVX) mice. OVX mice receiving an 8-week oral gavage of 100 mg of KPs and 100 mg of KPs + 10 mg Ca exhibited lower trabecular separation (Tb. Sp), and higher bone mineral density (BMD), trabecular number (Tb. N) and bone volume (BV/TV), than OVX groups receiving Ca alone and untreated mice, and these effects were also reflected in bones with better mechanical properties of strength and fracture toughness. The gut microbiota of the cecal contents was examined by 16S rDNA amplicon sequencing. α-Diversity analysis indicated that the gut microbiota of OVX mice was enriched more than that of sham mice, but the diversity was not changed significantly. Treatment with KPs caused increased microbiota richness and diversity in OVX mice compared with those in sham mice. The microbiota composition changed markedly in OVX mice compared with that in sham mice. Following the oral administration of KPs for 8 weeks, the abundances of
,
,
,
,
and
genera were restored to levels close to those in the sham group. However, the correlation of these bacterial populations with bone metabolism needs further investigation. Taken together, KPs prevent menopausal osteoporosis and mildly modulate the structure of the gut microbiota in OVX mice.
Food adulteration, mislabeling, and fraud, are rising global issues. Therefore, a number of precise and reliable analytical instruments and approaches have been proposed to ensure the authenticity ...and accurate labeling of food and food products by confirming that the constituents of foodstuffs are of the kind and quality claimed by the seller and manufacturer. Traditional techniques (e.g., genomics-based methods) are still in use; however, emerging approaches like mass spectrometry (MS)-based technologies are being actively developed to supplement or supersede current methods for authentication of a variety of food commodities and products. This review provides a critical assessment of recent advances in food authentication, including MS-based metabolomics, proteomics and other approaches.
Electronic skin sensing devices are an emerging technology and have substantial demand in vast practical fields including wearable sensing, robotics, and user‐interactive interfaces. In order to ...imitate or even outperform the capabilities of natural skin, the keen exploration of materials, device structures, and new functions is desired. However, the very high resistance and the inadequate current switching and sensitivity of reported electronic skins hinder to further develop and explore the promising uses of the emerging sensing devices. Here, a novel resistive cloth‐based skin‐like sensor device is reported that possesses unprecedented features including ultrahigh current‐switching behavior of ≈107 and giant high sensitivity of 1.04 × 104–6.57 × 106 kPa−1 in a low‐pressure region of <3 kPa. Notably, both superior features can be achieved by a very low working voltage of 0.1 V. Taking these remarkable traits, the device not only exhibits excellent sensing abilities to various mechanical forces, meeting various applications required for skin‐like sensors, but also demonstrates a unique competence to facile integration with other functional devices for various purposes with ultrasensitive capabilities. Therefore, the new methodologies presented here enable to greatly enlarge and advance the development of versatile electronic skin applications.
A newly designed cloth‐based resistive electronic skin features ultrahigh current switching of ≈107 and extremely high sensitivity of 1.04 × 104–6.57 × 106 kPa–1 at pressures <3 kPa. And, notably, both features are achieved by a very low working voltage of 0.1 V. Taking these traits, our devices not only function as ultrasensitive sensors but can also be integrated with various functional components for multipurpose uses.
Cytomegalovirus (CMV) gastrointestinal (GI) diseases impact both immunocompromised and immunocompetent individuals, yet comprehensive studies highlighting the differences between these groups are ...lacking.
In this retrospective study (January 2000 to July 2022) of 401 patients with confirmed CMV GI diseases, we categorized them based on immunological status and compared manifestations, treatments, outcomes, and prognostic factors.
The immunocompromised patients (n = 193) showed older age, severe illnesses, and higher comorbidity rates. GI bleeding, the predominant manifestation, occurred more in the immunocompetent group (92.6% vs. 63.6%,
= 0.009). Despite longer antiviral therapy, the immunocompromised patients had higher in-hospital (32.2% vs. 18.9%,
= 0.034) and overall mortality rates (91.1% vs. 43.4%,
< 0.001). The independent factors influencing in-hospital mortality in the immunocompromised patients included GI bleeding (OR 5.782, 95% CI 1.257-26.599,
= 0.024) and antiviral therapy ≥ 14 days (OR 0.232, 95% CI 0.059-0.911,
= 0.036). In the immunocompetent patients, age (OR 1.08, 95% CI 1.006-1.159,
= 0.032), GI bleeding (OR 10.036, 95% CI 1.183-85.133,
= 0.035), and time to diagnosis (OR 1.029, 95% CI 1.004-1.055,
= 0.021) were significant prognostic factors, with the age and diagnosis time cut-offs for survival being 70 years and 31.5 days, respectively.
GI bleeding is the most common manifestation and prognostic factor in both groups. Early diagnosis and effective antiviral therapy can significantly reduce in-hospital mortality.
Go for gold: As‐prepared insulin–Au nanoclusters (NCs) show intense red fluorescence, excellent biocompatibility, and preservation of natural insulin bioactivity in lowering the blood‐glucose level. ...Their versatility in applications is demonstrated by fluorescence imaging, X‐ray computed tomography, and insulin–inhibitor interactions (see picture; IDE=insulin‐degrading enzyme).
This paper presents a high-reliability single-phase transformerless grid-connected inverter that utilizes superjunction MOSFETs to achieve high efficiency for photovoltaic applications. The proposed ...converter utilizes two split ac-coupled inductors that operate separately for positive and negative half grid cycles. This eliminates the shoot-through issue that is encountered by traditional voltage source inverters, leading to enhanced system reliability. Dead time is not required at both the high-frequency pulsewidth modulation switching commutation and the grid zero-crossing instants, improving the quality of the output ac-current and increasing the converter efficiency. The split structure of the proposed inverter does not lead itself to the reverse-recovery issues for the main power switches and as such superjunction MOSFETs can be utilized without any reliability or efficiency penalties. Since MOSFETs are utilized in the proposed converter high efficiency can be achieved even at light load operations achieving a high California energy commission (CEC) or European union efficiency of the converter system. It also has the ability to operate at higher switching frequencies while maintaining high efficiency. The higher operating frequencies with high efficiency enables reduced cooling requirements and results in system cost savings by shrinking passive components. With two additional ac-side switches conducting the currents during the freewheeling phases, the photovoltaic array is decoupled from the grid. This reduces the high-frequency common-mode voltage leading to minimized ground loop leakage current. The operation principle, common-mode characteristic and design considerations of the proposed transformerless inverter are illustrated. The total losses of the power semiconductor devices of several existing transformerless inverters which utilize MOSFETs as main switches are evaluated and compared. The experimental results with a 5 kW prototype circuit show 99.0% CEC efficiency and 99.3% peak efficiency with a 20 kHz switching frequency. The high reliability and efficiency of the proposed converter makes it very attractive for single-phase transformerless photovoltaic inverter applications.
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