Kwas zoledronowy stosowany przez dwa lata u Chinek z osteoporozą pomenopauzalną zwiększa gęstość mineralną tkanki kostnej i poprawia jakość życia związaną ze stanem zdrowia

Introduction: Osteoporosis is characterised by decreased bone mass and weakened bones, with an increased risk of fractures. Osteoporotic fracture, the most serious complication of osteoporosis, is related not only to lower bone mineral density (BMD), but also falls. Osteoporosis and fractures are associated with a decreased health-related quality of life (HRQL). Zoledronic acid (ZOL) is an intravenous once-yearly bisphosphonate that has been shown to be effective and safe in improving BMD and reducing fracture risk in controlled clinical trials.Material and methods: In this self-controlled, prospective trial, 220 postmenopausal women with osteoporosis (mean age 67 years) received a single infusion of ZOL 5 mg at baseline and month 12. BMD, HRQL and Fall Index (FI) were measured at baseline, and months 12 and 24 (before each use of ZOL). The main outcome measures were the changes in lumbar spine and hip BMD and the changes in HRQL, the Short Form-36 questionnaire (SF-36). Additional comparisons were based on the FI. LSD multiple comparisons were used in the comparisons of BMD, SF-36 domain scores and FI.Results: The patients had significantly higher L1-4, total hip, femoral neck and trochanter BMD (P < 0.05) with improved HRQL (P < 0.05) over two years of treatment of once-yearly ZOL 5mg. FI was reduced (P < 0.05) with oral daily elemental calcium and vitamin D in the treatment course.Conclusions: ZOL improves BMD and HRQL, especially in the physical aspects, over two years of treatment in women with postmenopausal osteoporosis, and can help improve balance ability. (Endokrynol Pol 2014; 65 (2): 96–104)Wstęp: Osteoporoza to schorzenie cechujące się obniżeniem masy kostnej i wytrzymałości mechanicznej kości z towarzyszącym zwiększeniem ryzyka złamań. Złamania osteoporotyczne, będące najpoważniejszym powikłaniem osteoporozy, wiążą się nie tylko z obniżoną gęstością mineralną tkanki kostnej (BMD, bone mineral density) ale też z upadkami. Z osteoporozą i złamaniami wiąże się obniżenie jakości życia związanej ze stanem zdrowia (HRQoL, health-related quality of life). Kwas zoledronowy (ZOL) to bisfosfonian w postaci dożylnej przeznaczony do podawania raz w roku, w przypadku którego w badaniach klinicznych z grupą kontrolną wykazano skuteczność i bezpieczeństwo w zwiększaniu BMD i zmniejszaniu ryzyka złamań.Materiał i metody: Autorzy przeprowadzili samodzielnie kontrolowane, prospektywne badanie z udziałem 220 znajdujących się w wieku pomenopauzalnym kobiet z osteoporozą (średnia wieku 67 lat), które otrzymały jednorazowo roztwór ZOL w dawce 5 mg na początku badania i 12 miesięcy później. Na początku badania, w 12. miesiącu i w 24. miesiącu badania (za każdym razem przed podaniem ZOL) oznaczano BMD, HRQoL i wskaźnik upadków (FI, fall index). Główne punkty końcowe obejmowały zmiany BMD w odcinku lędźwiowym kręgosłupa i BMD w okolicy biodra, a także zmiany HRQoL w kwestionariuszu SF-36. Dodatkowe porównania będą oparte na FI. W porównaniach wartości BMD, liczby punktów w poszczególnych domenach kwestionariusza SF-36 i wartości FI zastosowano metodę wielokrotnych porównań najmniejszej istotnej różnicy.Wyniki: U pacjentek stwierdzono znamiennie większe wartości BMD na poziomie L1–4, BMD w całkowitym obszarze biodra, BMD w obrębie szyjki kości udowej oraz BMD w obrębie krętarza (p < 0,05) oraz znamienną poprawę HRQoL (p < 0,05) w okresie 2 lat leczenia podawanym raz w roku ZOL w dawce 5 mg. Stwierdzono też zmniejszenie FI (p < 0,05) dzięki codziennemu przyjmowaniu wapnia i witaminy D w okresie leczenia.Wnioski: Stosowanie ZOL prowadzi do poprawy BMD i HRQoL, zwłaszcza w aspekcie fizycznym, w okresie 2 lat stosowania u kobiet z osteoporozą pomenopauzalną, i może przyczyniać się do poprawy zdolności utrzymania równowagi. (Endokrynol Pol 2014; 65 (2): 96–104

Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V

Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is one of the most frequent oncogenes. However, there are limited treatment options due to its intracellular expression. To address this, we developed a novel bispecific T-cell engager (BiTE) antibody targeting HLA-A2/KRAS G12V complex and CD3 (HLA-G12V/CD3 BiTE). We examined its specific binding to tumor cells and T cells, as well as its anti-tumor effects in vivo. HLA-G12V/CD3 BiTE was expressed in Escherichia coli and its binding affinities to CD3 and HLA-A2/KRAS G12V were measured by flow cytometry, along with T-cell activation. In a xenograft pancreatic tumor model, the HLA-G12V/CD3 BiTE's anti-tumor effects were assessed through tumor growth, survival time, and safety. Our results demonstrated specific binding of HLA-G12V/CD3 BiTE to tumor cells with an HLA-A2/KRAS G12V mutation and T cells. The HLA-G12V/CD3 BiTE also activated T-cells in the presence of tumor cells in vitro. HLA-G12V/CD3 BiTE in vivo testing showed delayed tumor growth without severe toxicity to major organs and prolonged mouse survival. This study highlights the potential of constructing BiTEs recognizing an HLA-peptide complex and providing a novel therapy for cancer treatment targeting the intracellular tumor antigen

Rethinking Human-AI Collaboration in Complex Medical Decision Making: A Case Study in Sepsis Diagnosis

Today's AI systems for medical decision support often succeed on benchmark datasets in research papers but fail in real-world deployment. This work focuses on the decision making of sepsis, an acute life-threatening systematic infection that requires an early diagnosis with high uncertainty from the clinician. Our aim is to explore the design requirements for AI systems that can support clinical experts in making better decisions for the early diagnosis of sepsis. The study begins with a formative study investigating why clinical experts abandon an existing AI-powered Sepsis predictive module in their electrical health record (EHR) system. We argue that a human-centered AI system needs to support human experts in the intermediate stages of a medical decision-making process (e.g., generating hypotheses or gathering data), instead of focusing only on the final decision. Therefore, we build SepsisLab based on a state-of-the-art AI algorithm and extend it to predict the future projection of sepsis development, visualize the prediction uncertainty, and propose actionable suggestions (i.e., which additional laboratory tests can be collected) to reduce such uncertainty. Through heuristic evaluation with six clinicians using our prototype system, we demonstrate that SepsisLab enables a promising human-AI collaboration paradigm for the future of AI-assisted sepsis diagnosis and other high-stakes medical decision making.Comment: Under submission to CHI202

Highly Efficient Electrochemical Reforming of CH\u3csub\u3e4\u3c/sub\u3e/CO\u3csub\u3e2\u3c/sub\u3e in a Solid Oxide Electrolyser

Reforming CH4 into syngas using CO2 remains a fundamental challenge due to carbon deposition and nanocatalyst instability. We, for the first time, demonstrate highly efficient electrochemical reforming of CH4/CO2 to produce syngas in a solid oxide electrolyser with CO2 electrolysis in the cathode and CH4 oxidation in the anode. In situ exsolution of an anchored metal/oxide interface on perovskite electrode delivers remarkably enhanced coking resistance and catalyst stability. In situ Fourier transform infrared characterizations combined with first principle calculations disclose the interface activation of CO2 at a transition state between a CO2 molecule and a carbonate ion. Carbon removal at the interfaces is highly favorable with electrochemically provided oxygen species, even in the presence of H2 or H2O. This novel strategy provides optimal performance with no obvious degradation after 300 hours of high-temperature operation and 10 redox cycles, suggesting a reliable process for conversion of CH4 into syngas using CO2

Efficacy and safety of second-line therapy by S-1 combined with sintilimab and anlotinib in pancreatic cancer patients with liver metastasis: a single-arm, phase II clinical trial

BackgroundPancreatic adenocarcinoma carries a grim prognosis, and there are few recognized effective second-line treatment strategies. We attempted to evaluate the efficacy and safety of a combination of S-1, sintilimab, and anlotinib as a second-line treatment in pancreatic cancer patients with liver metastasis.MethodsPancreatic cancer patients with liver metastases were recruited. S-1 was administered orally at 25 mg/m2 bid, anlotinib was administered orally at 12 mg qd from day 1 to day 14, and sintilimab was administered intravenously at 200 mg on day 1. This method was repeated every 21 days, and the therapeutic effect was evaluated every 3 cycles. The primary outcome was the objective response rate (ORR).ResultsOverall, 23 patients were enrolled in this study of whom 19 patients had objective efficacy evaluation. The ORR was 10.5% (95% CI 0.4%–25.7%) in the evaluable population. The progression-free survival (PFS) was 3.53 (95% CI 2.50–7.50) months, and the overall survival (mOS) was 8.53 (95% CI 4.97–14.20) months. Grade 3 adverse events were 26.1%, and no grade 4 or above adverse events occurred. High-throughput sequencing was performed on the tumor tissues of 16 patients; patients with HRD-H (n = 10) had shorter PFS than those with HRD-L (n = 6) (2.43 vs. 5.45 months; P = 0.043), but there was no significant difference in OS between the two groups (4.43 vs. 9.35 months; P = 0.11).ConclusionsThis study suggests the advantage of S-1 combined with sintilimab and anlotinib in extending OS as a second-line therapy in pancreatic cancer patients with liver metastasis.Clinical Trial Registration: ChiCTR200003065

Charge Transfer Tuned by the Surrounding Dielectrics in TiO₂-Ag Composite Arrays

TiO2/Ag bilayer films sputtered onto a 2D polystyrene (PS) bead array in a magnetron sputtering system were found to form a nanocap-shaped nanostructure composed of a TiO2-Ag composite on each PS bead, in which the Ag nanoparticles were trapped partially or fully in the TiO2 matrix, depending on the TiO2 thickness. X-ray Photoelectron Spectroscopy (XPS) results showed the opposite shifts of binding energy for Ti 2p and Ag 3d, indicating the transfer of electrons from metallic Ag to TiO2 owing to the Ag-O-TiO2 composite formation. UV-Vis absorption spectra showed the blue shifts of the surface plasma resonance peaks, and the maximum absorption peak intensity was obtained for TiO2 at 30 nm. The surface-enhanced Raman scattering (SERS) peak intensity first increased and then decreased when the TiO2 thickness changed. The observations of SERS, XPS, and UV-Vis absorption spectra were explained by the dependency of the charge-transfer process on TiO2 thickness, which was ascribed to the changing dielectric properties in the metal/semiconductor system

PROZ Associated with Sorafenib Sensitivity May Serve as a Potential Target to Enhance the Efficacy of Combined Immunotherapy for Hepatocellular Carcinoma

Targeted combined immunotherapy has significantly improved the prognosis of patients with advanced hepatocellular carcinoma and has now become the primary treatment for advanced hepatocellular carcinoma. However, some patients still have poor efficacy or are resistant to treatment. The further exploration of molecular markers related to efficacy or finding molecular targets to increase efficacy is an urgent problem that needs to be resolved. In this research, we found that PROZ was a gene related to KDR expression that had significantly low expression in cancer tissue by analyzing the differential genes of cancer tissue and adjacent tissue and the intersection of KDR-related genes in hepatocellular carcinoma. The correlation analysis of clinical data showed that the low expression of PROZ was significantly correlated with the poor prognosis of hepatocellular carcinoma, and further studies found that PROZ was closely related to the expression of p-ERK and VEGFR2 in hepatocellular carcinoma. In addition, intracellular detection also showed that the expression of p-ERK increased and VEGFR2 expression decreased after PROZ interference, and PROZ downregulation with increased p-ERK and decreased VEGFR2 was also detected in sorafenib-resistant strains. At the same time, our analysis found that PROZ was negatively correlated with genes related to immunotherapy efficacy such as CD8A, CD274 and GZMA, and was also negatively correlated with T-cell infiltration in tumor tissue. Conclusion: PROZ is a gene related to the prognosis of hepatocellular carcinoma and it is closely related to the efficacy of sorafenib and immunotherapy. It may serve as a potential molecular target to improve the efficacy of targeted combined immunotherapy