High Response Research Articles

Prognostic Value of CSF IL-10 at Early Assessment of Induction Chemotherapy in Primary CNS Lymphomas: A LOC Network Study.

Despite a high response rate at the first evaluation during induction chemotherapy, the risk of early relapse remains high and unpredictable in primary CNS lymphomas (PCSNLs). We aimed to assess the prognostic value of early IL-10 levels in CSF (e-IL-10) after 2 months of induction chemotherapy. We retrospectively selected from the LOC (Lymphomes Oculo-Cérébraux) network database patients with PCSNLs who had complete or partial response at the 2-month evaluation of a high-dose methotrexate-based first-line chemotherapy for whom e-IL-10 was available. Thirty patients (median age: 62 years, brain involvement in 30/30, CSF involvement in 10/30, median baseline CSF IL-10: 27.5 pg/mL) met the selection criteria. e-IL-10 was undetectable in 22 patients and detectable in 8 patients. At the end of induction treatment, 7 of 8 and 4 of 22 of the patients with detectable and undetectable e-IL-10 had experienced progressive disease, respectively (p = 0.001, OR: 26.8, 95% CI 2-1,478). The median progression-free survival times were 5.8 months (95% CI 2.8-8.8) and 28.7 months (95% CI 13.4-43.9) in the groups with detectable and undetectable e-IL-10, respectively (p < 0.001). Our results suggest that despite an objective response, the persistence of detectable e-IL-10 is associated with a high risk of early relapse in PCNSL. A closer follow-up of such patients is warranted.

Long-Term Epidural Patching Outcomes and Predictors of Benefit in Patients With Suspected CSF Leak Nonconforming to ICHD-3 Criteria.

Spinal CSF leaks lead to spontaneous intracranial hypotension (SIH). While International Classification of Headache Disorders, Third Edition (ICHD-3) criteria necessitate imaging confirmation or low opening pressure (OP) for SIH diagnosis, their sensitivity may be limited. We offered epidural blood patches (EBPs) to patients with symptoms suggestive of SIH, with and without a documented low OP or confirmed leak on imaging. This study evaluates the efficacy of this strategy. We conducted a prospective cohort study with a nested case-control design including all patients who presented to a tertiary headache clinic with clinical symptoms of SIH who completed study measures both before and after receiving an EBP between August 2016 and November 2018. The mean duration of symptoms was 8.7 ± 8.1 years. Of 85 patients assessed, 69 did not meet ICHD-3 criteria for SIH. At an average of 521 days after the initial EBP, this ICHD-3-negative subgroup experienced significant improvements in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health score of +3.3 (95% CI 1.5-5.1), PROMIS Global Mental Health score of +1.8 (95% CI 0.0-3.5), Headache Impact Test (HIT)-6 head pain score of -3.8 (95% CI -5.7 to -1.8), Neck Disability Index of -4.8 (95% CI -9.0 to -0.6) and PROMIS Fatigue of -2.3 (95% CI -4.1 to -0.6). Fifty-four percent of ICHD-3-negative patients achieved clinically meaningful improvements in PROMIS Global Physical Health and 45% in HIT-6 scores. Pain relief following lying flat prior to treatment was strongly associated with sustained clinically meaningful improvement in global physical health at an average of 521 days (odds ratio 1.39, 95% CI 1.1-1.79; p < 0.003). ICHD-3-positive patients showed high rates of response and previously unreported, treatable levels of fatigue and cognitive deficits. Patients who did not conform to the ICHD-3 criteria for SIH showed moderate rates of sustained, clinically meaningful improvements in global physical health, global mental health, neck pain, fatigue, and head pain after EBP therapy. Pre-treatment improvement in head pain when flat was associated with later, sustained improvement after EBP therapy among patients who did not meet the ICHD-3 criteria. This study provides Class IV evidence that epidural blood patch is an effective treatment of suspected CSF leak not conforming to ICHD-3 criteria for SIH.

A parylene/graphene UV photodetector with ultrahigh responsivity and long term stability

Long term stability, high responsivity, and fast response speed are essential for the commercialization of graphene photodetectors (GPDs). In this work, a parylene/graphene UV photodetector with long term stability, ultrahigh responsivity and fast response speed, is demonstrated. Parylene as a stable physical and chemical insulating layer reduces the environmental sensitivity of graphene, and enhances the performances of GPDs. In addition, utilizing bilayer electrodes reduces the buckling and damage of graphene after transferring. The parylene/graphene UV photodetector exhibits an ultrahigh responsivity of 5.82 × 105 AW−1 under 325 nm light irradiation at 1 V bias. Additionally, it shows a fast response speed with a rise time of 80 μs and a fall time of 17 μs, and a long term stability at 405 nm wavelength which is absent in the device without parylene. The parylene/graphene UV photodetector possesses superior performances. This paves the way for the commercial application of the high-performance graphene hybrid photodetectors, and provides a practical method for maintaining the long term stability of two dimensional (2D) materials.

Organizational learning in surgery in Tanzania's health system: a descriptive cross-sectional study.

Organizational learning is critical for delivering safe, high-quality surgical care, especially in low- and middle-income countries (LMICs) where perioperative outcomes remain poor. While current investments in LMICs prioritize physical infrastructure, equipment, and staffing, investments in organizational learning are equally important to support innovation, creativity, and continuous improvement of surgical quality. This study aims to assess the extent to which health facilities in Tanzania's Lake Zone perform as learning organizations from the perspectives of surgical providers. The insights gained from this study can motivate future quality improvement initiatives and investments to improve surgical outcomes. We conducted a cross-sectional analysis using data from an adapted survey to explore the key components of organizational learning, including a supportive learning environment, effective learning processes, and encouraging leadership. Our sample included surgical team members and leaders at 20 facilities (health centers, district hospitals, and regional hospitals). We calculated the average of the responses at individual facilities. Responses that were 5+ on a 7-point scale or 4+ on a 5-point scale were considered positive. We examined the variation in responses by facility characteristics using a one-way ANOVA or Student's t-test. We used univariate and multiple regression to assess relationships between facility characteristics and perceptions of organizational learning. Ninety-eight surgical providers and leaders participated in the survey. The mean facility positive response rate was 95.1% (SD 6.1%). Time for reflection was the least favorable domain with a score of 62.5% (SD 35.8%). There was variation by facility characteristics including differences in time for reflection when comparing by level of care (P = .02) and location (P = .01), and differences in trying new approaches (P = .008), capacity building (P = .008), and information transfer (P = .01) when comparing public versus faith-based facilities. In multivariable analysis, suburban centers had less time for reflection than urban facilities (adjusted difference = -0.48; 95% CI: -0.95, -0.01; P = .046). Surgical team members reported more positive responses compared to surgical team leaders. We found a high overall positive response rate in characterizing organizational learning in surgery in 20 health facilities in Tanzania's Lake Zone. Our findings identify areas for improvement and provide a baseline for assessing the effectiveness of change initiatives. Future research should focus on validating the adapted survey and exploring the impact of strong learning environments on surgical outcomes in LMICs. Organizational learning is crucial in surgery and further research, funding, and policy work should be dedicated to improving learning cultures in health facilities.

A thiol-anchored solvatochromic and fluorogenic molecular rotor for covalent protein labeling in SDS-PAGE and mitochondria specific fluorescence imaging.

Fluorescent labeling is a widely used method for protein detection and fluorescence imaging. A solvatochromic and fluorogenic molecular rotor DASPBCl was developed for covalent protein labeling in solution and SDS-PAGE, and also for stable mitochondria labeling and fluorescence imaging. The dye DASPBCl consisted of a 4-(N,N-dimethylamino)phenyl moiety as the electron donor and a positively charged N-benzylpyridinium moiety as the electron acceptor. A benzyl chloride group was introduced into the pyridine moiety for covalent labeling of thiol in proteins. When the fluorescent dye DASPBCl is covalently labeled to the thiol of proteins, significantly enhanced fluorescence was obtained, which is attributed to the polarity sensitivity caused solvatochromic effect from the hydrophobic protein structure and the viscosity sensitivity caused fluorogenic effect from the restriction of single bond rotation. DASPBCl exhibits high sensitivity and good linear response for protein detection in SDS-PAGE analysis with both the pre-staining method and post-staining method. DASPBCl was also successfully used for covalently protein-anchored fluorescence imaging of mitochondria in living cells.

Adherence in Hepatitis C Virus Treatment: What We Know.

Although therapy with direct-acting antiviral (DAA) agents achieves high hepatitis C virus (HCV) cure rates and is forgiving of missed doses, certain patient populations, such as people who inject drugs (PWID), are often denied therapy because of a perceived high risk of nonadherence. However, a relationship between adherence to DAAs for various patient populations and efficacy has not been well defined. The lack of a standardized method for evaluating adherence complicates making comparisons between studies, making it difficult to develop and implement novel measures that may improve adherent behavior. Traditional methods for assessing adherence may overestimate medication adherence, while newer, technology-based methods may assist with accurately assessing and maintaining patient adherence to therapy. Data demonstrate that special populations of patients with HCV, such as PWID, can be successfully treated, with relatively high rates of sustained virologic response (SVR) despite less-than-optimal adherence. While rates of adherence, and subsequently SVR, can be improved, antiviral therapy should not be withheld because of fear of nonadherence. This article addresses medication adherence and forgiveness of DAA regimens, such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, in different patient populations with HCV. Considerations in evaluating adherence in HCV therapy and available methods for assessing adherence are detailed.

Switching from eltrombopag to hetrombopag in patients with primary immune thrombocytopenia: a post-hoc analysis of a multicenter, randomized phase III trial.

While studies have explored the feasibility of switching between various thrombopoietin receptor agonists in treating immune thrombocytopenia (ITP), data on the switching from eltrombopag to hetrombopag remains scarce. This post-hoc analysis of a phase III hetrombopag trial aimed to assess the outcomes of ITP patients who switched from eltrombopag to hetrombopag. In the original phase III trial, patients initially randomized to the placebo group were switched to eltrombopag. Those who completed this 14-week eltrombopag were eligible to switch to a 24-week hetrombopag. Treatment response, defined as a platelet count of ≥ 50 × 109/L, and safety were evaluated before and after the switch. Sixty-three patients who completed the 14-week eltrombopag and switched to hetrombopag were included in this post-hoc analysis. Response rates before and after the switch were 66.7% and 88.9%, respectively. Among those with pre-switching platelet counts below 30 × 109/L, eight out of 12 patients (66.7%) responded, while eight out of nine patients (88.9%) with pre-switching platelet counts between 30 × 109/L and 50 × 109/L responded post-switching. Treatment-related adverse events were observed in 50.8% of patients during eltrombopag treatment and 38.1% during hetrombopag treatment. No severe adverse events were noted during hetrombopag treatment. Switching from eltrombopag to hetrombopag in ITP management appears to be effective and well-tolerated. Notably, hetrombopag yielded high response rates, even among patients who had previously shown limited response to eltrombopag. However, these observations need to be confirmed in future trials.

Using the Novel Musculoskeletal Emergency Medicine Assessment Tool: A Feasibility Study.

Background and objective While musculoskeletal (MSK) disorders account for a significant number of primary care and emergency department (ED) visits, there are widely recognized shortcomings and gaps in MSK education throughout medical training. Undergraduate medical education (UME) frequently fails to impart clinically relevant MSK knowledge, while many emergency medicine (EM) residency graduates report feeling unprepared to manage MSK complaints. Existing MSK assessments are not tailored to EM and may inaccurately assess specialty-specific MSK knowledge. The novel validated Musculoskeletal Emergency Medicine Assessment Tool (MEAT) holds great promise in standardizing EM MSK knowledge assessment. This trial of feasibility was conducted to assess the viability and practicality of using MEAT to evaluate MSK knowledge among incoming resident physicians in EM programs. Methods This feasibility study involved 21 incoming EM resident physicians from two programs at a single institution. MEAT was administered online during orientation, and demographic data and survey metadata were collected. UME MSK education details were obtained, and MEAT scores were analyzed. Results Participants reported no difficulties in accessing or understanding the 50-question online MEAT, resulting in a 100% response rate. The average pretest score for all interns was 29.9, with a median of 30. Most participants had documented UME MSK education, but curricular content varied widely. The participants took an average of 32 minutes to complete the assessment. Conclusions MEAT demonstrated successful implementation and high response rates, suggesting a high level of feasibility. Thetool can be used to assess baseline MSK knowledge and ultimately track progression during residency with the potential for evaluating educational interventions once further validation studies have been performed.Further adoption of MEAT across multiple EM residency programs will help to enhance the tool's generalizability.

Developmental outcomes of children born through ICSI versus conventional IVF (cIVF) in couples with non-male factor infertility.

In non-male factor infertile couples, are there any differences in the developmental outcomes between children born through ICSI and conventional IVF (cIVF)? In this preliminary study, ICSI and cIVF seem to have a comparable effect on developmental outcomes after 12 months in children born to non-male factor infertile couples. ICSI, an invasive technique, has raised concerns about potential developmental abnormalities in children. Limited data are available regarding the developmental outcomes of ICSI-conceived infants born to non-male factor infertile couples. This prospective cohort study involved a follow-up of all children aged 12 months or older who were born from pregnancies resulting from either ICSI or cIVF as part of a previous randomized controlled trial (RCT) (NCT03428919). In the original RCT, 1064 women were randomly assigned to the ICSI or cIVF groups (532 women for each group). Follow-up was conducted with 155 couples (195 children) in the ICSI group and 141 couples (185 children) in the cIVF group. The Vietnamese version of the Ages & Stages Third Edition Questionnaires (ASQ-3) and the Development Red Flags questionnaires were completed by the participants. A total of 141 (90.1%) women (177 children) in the ICSI group and 113 (80.1%) women (145 children) in the cIVF group returned fully completed questionnaires. The primary outcomes were the developmental outcomes based on responses to the ASQ-3 and the Red Flags questionnaire. The mean age of children at follow-up was 19.5 ± 5.0 months in the ICSI group and 19.3 ± 5.5 months in the cIVF group. The mean height and weight of children in both groups were similar. The overall proportion of children with any abnormal ASQ-3 score did not differ significantly between the ICSI and cIVF groups (16.9% vs 13.1%, P = 0.34). The proportion of children with Red Flag signs was also comparable between the two groups (6.2% vs 9.2%, P = 0.36, ICSI vs cIVF, respectively). Despite a reasonably high follow-up response rate, there is a potential risk of sampling bias, and overall, the number of children with developmental abnormalities was very small. The study relied solely on questionnaires as screening tools, rather than incorporating additional behavioral observations or physical developmental tests; this may have affected the statistical power and the significance of between-group comparisons. The current findings contribute to the existing evidence and support the comparative safety of ICSI and cIVF regarding early childhood development. However, more extensive and prolonged follow-up data for these children are needed to draw definitive conclusions. No external funding was received for this study, and no authors reported conflicting interests. NCT04866524 (clinicaltrials.gov).

Immune responses and reinfection of SARS-CoV-2 Omicron variant in patients with lung cancer.

A significant Omicron wave emerged in China in December 2022. To explore the duration of humoral and cellular response postinfection and the efficacy of hybrid immunity in preventing Omicron reinfection in patients with lung cancer, a total of 447 patients were included in the longitudinal study after the Omicron wave from March 2023 to August 2023. Humoral responses were measured at pre-Omicron wave, 3 months and 7 months postinfection. The detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies including total antibodies, anti-receptor binding domain (RBD) specific IgG, and neutralizing antibodies against SARS-CoV-2 wild type (WT) and BA.4/5 variant. T cell responses against SARS-CoV-2 WT and Omicron variant were evaluated in 101 patients by ELISpot at 3 months postinfection. The results showed that Omicron-infected symptoms were mild, while fatigue (30.2%), shortness of breath (34.0%) and persistent cough (23.6%) were long-lasting, and vaccines showed efficacy against fever in lung cancer patients. Humoral responses were higher in full or booster vaccinated patients than those unvaccinated (p < .05 for all four antibodies), and the enhanced response persisted for at least 7 months. T cell response to Omicron was higher than WT peptides (21.3 vs. 16.0 SFUs/106 PBMCs, p = .0093). Moreover, 38 (9.74%) patients were reinfected, which had lower antibody responses than non-reinfected patients (all p < .05), and those patients of unvaccinated at late stage receiving anti-cancer immunotherapy alone were at high risk of reinfection. Collectively, these data demonstrate the Omicron infection induces a high and durable immune response in vaccinated patients with lung cancer, which protects vaccinated patients from reinfection.

Room temperature NH3 gas sensor based on In(OH)3/Ti3C2Tx nanocomposites.

Industrialization and agricultural demand have both improved human life and led to environmental contamination. Especially thedischarge of a lot of poisonous and harmful gases, including ammonia, ammonia pollution has become a pressing problem. High concentrations of ammonia can pose significant threats to both the environment and human health. Therefore, accurate monitoring and detection of ammonia gas are crucial. To address this challenge, we have developed an ammonia gas sensor using In(OH)3/Ti3C2Tx nanocomposites through an in-situ electrostatic self-assembly process. This sensor was thoroughly characterized using advanced techniques like XRD, XPS, BET, and TEM. In our tests, the I/M-2 sensor exhibited remarkable performance, achieving a 16.8% response to 100ppm NH3 at room temperature, which is a 3.5-fold improvement over the pure Ti3C2Tx MXene sensor. Moreover, it providesswift response time (20s), high response to low NH3concentrations (≤ 10ppm), and excellent long-term stability (30days). These exceptional characteristics indicate the immense potential of our In(OH)3/Ti3C2Tx gas sensor in ammonia detection.

2D Growth of BiSCl as Anisotropic Photodetector with Ultrahigh Responsivity and Detectivity

AbstractBiSCl, which shares the anisotropic chain‐like lattice configuration with the BiVXVIYVII (XS, Se; YCl, Br, I) family displays high photoelectric conversion efficiency in the UV–vis wavelength region. The current difficulty in 2D growth restricts the investigation of device performance and further integration. Herein, an epitaxial growth strategy for 2D BiSCl is proposed based on the principle of sharing a chloridion layer at the BiSCl/BiOCl interface. The interfacial atomic arrangement is carefully revealed using atomic resolved AC‐TEM(Spherical Aberration High Transmission Electron Microscope) and demonstrated by calculations based on density functional theory. Benefiting from its compatibility with PS‐assisted large‐scale transfer technology, the photoelectric performance is evaluated by constructing a standard symmetrical photoconductor and Graphene‐BiSCl Schottky junction device. High responsivity (1.71 × 104 A W−1) and detectivity (5.9 × 1016. Jones) are achieved at 405 nm, and robustness is shown in a broadband spectrum, which manifested prominent anisotropic photoelectric behavior and great potential in weak‐light detection. These results elucidate the photoelectric applications of BiSCl semiconductors and the structural design of the BiVXVIYVII family.

High-Precision and Real-Time Measurement of Water Isotope Ratios Based on a Mid-Infrared Optical Sensor.

A compact spectrometer based on a mid-infrared optical sensor has been developed for high-precision and real-time measurement of water isotope ratios. The instrument uses laser absorption spectroscopy and applies the weighted Kalman filtering method to determine water isotope ratios with high precision and fast time response. The precision of the measurements is 0.41‰ for δ18O and 0.29‰ for δ17O with a 1 s time. This is much faster than the standard running average technique, which takes over 90 s to achieve the same level of precision. The successful development of this compact mid-infrared optical sensor opens up new possibilities for its future applications in atmospheric and breath gas research.

Predictive value of lymphocyte subsets and lymphocyte-to-monocyte ratio in assessing the efficacy of neoadjuvant therapy in breast cancer

Lymphocyte subsets are the most intuitive expression of the body’s immune ability, and the lymphocyte-to-monocyte ratio (LMR) also clearly reflect the degree of chronic inflammation activity. The purpose of this study is to investigate their predictive value of lymphocyte subsets and LMR to neoadjuvant therapy (NAT) efficacy in breast cancer patients. In this study, lymphocyte subsets and LMR were compared between breast cancer patients (n = 70) and benign breast tumor female populations (n = 48). Breast cancer patients were treated with NAT, and the chemotherapy response of the breast was evaluated using established criteria. The differences in lymphocyte subsets and LMR were also compared between pathological complete response (pCR) and non-pCR patients before and after NAT. Finally, data were analyzed using SPSS. The analytical results demonstrated that breast cancer patients showed significantly lower levels of CD3 + T cells, CD4 + T cells, CD4 + /CD8 + ratio, NK cells, and LMR compared to benign breast tumor women (P < 0.05). Among breast cancer patients, those who achieved pCR had higher levels of CD4 + T cells, NK cells, and LMR before NAT (P < 0.05). NAT increased CD4 + /CD8 + ratio and decreased CD8 + T cells in pCR patients (P < 0.05). Additionally, both pCR and non-pCR patients exhibited an increase in CD3 + T cells and CD4 + T cells after treatment, but the increase was significantly higher in pCR patients (P < 0.05). Conversely, both pCR and non-pCR patients experienced a decrease in LMR after treatment. However, this decrease was significantly lower in pCR patients (P < 0.05). These indicators demonstrated their predictive value for therapeutic efficacy. In conclusion, breast cancer patients experience tumor-related immunosuppression and high chronic inflammation response. But this phenomenon can be reversed to varying degrees by NAT. It has been found that lymphocyte subsets and LMR have good predictive value for pCR. Therefore, these markers can be utilized to identify individuals who are insensitive to NAT early on, enabling the adjustment of treatment plans and achieving precise breast cancer treatment.

Gas Sensor Based on Highly Effective Slot-Die Printed PEDOT:PSS@ZnO Hybrid Nanocomposite for Methanol Detection.

This study presents the development of gas sensors based on the PEDOT:PSS@ZnO hybrid active layer slot-die printing aqueous ink. Two different zinc oxide (ZnO) nanoparticles were studied to form the nanocomposites, as well as the use of glass and PET substrates to manufacture the devices. Despite the influence of the morphology of the active layer, all device variations studied here exhibited high response values for methanol gas at room temperature, in addition to presenting good repeatability, reversibility, and the possibility of technology transfer to flexible substrates. Furthermore, PEDOT:PSS@ZnO showed good selectivity to methanol compared to ethanol, ammonia, and CO2. The best devices showed responses greater than 700% in detecting methanol.

Multi-Gb/s free-space laser communication at 4.6-μm wavelength using a high-speed, room-temperature, resonant-cavity infrared detector (RCID) and a quantum-cascade laser

Research has shown that free-space laser communication systems may experience fewer outages due to atmospheric impairments such as haze, fog, clouds, and turbulence by operating at a longer wavelength in the mid-wave or long-wave infrared, if disadvantages such as lower-performance transceiver components may be overcome. Here we report a resonant cavity infrared detector (RCID) with 4.6-µm resonance wavelength that enables 20-dB larger link budget than has been reported previously for ∼ 5 Gb/s operation. The device combines high responsivity, 1.97 A/W, with a low noise equivalent power (NEP) of 0.7 pW/Hz at room temperature, and a high bandwidth of 6.7 GHz at 3-dB. The relatively large surface-normal-incidence device with 30-µm diameter simplifies the coupling relative to intra-subband quantum cascade detectors. Although the RCID NEP is expected to increase with frequency to ∼ 1.5 pW/Hz, we estimate that the total equivalent noise power in a 2.5-GHz bandwidth is less than 200 nW. When combined with a relatively high power (∼100-mW) distributed-feedback quantum cascade laser, the difference of &gt; 50 dB between modulated laser power and RCID noise significantly outpaces that of existing devices.

Notch-Targeted Therapeutic in Colorectal Cancer by Notch1 Attenuation Via Tumor Microenvironment-Responsive Cascade DNA Delivery.

The Notch signaling is a key molecular pathway that regulates cell fate and development. Aberrant Notch signaling can lead to carcinogenesis and progression of malignant tumors. However, current therapies targeting Notch pathway lack specificity and induce high toxicity. In this report, a tumor microenvironment-responsive and injectable hydrogel is designed to load plasmid DNA complexes as a cascade gene delivery system to achieve precise Notch-targeted gene therapy of colorectal cancer (CRC). The hydrogels are prepared through cross-linking between phenylboric acid groups containing poly(oligo(ethylene glycol)methacrylate) (POEGMA) and epigallocatechin gallate (EGCG), used to load the complexes between plasmid DNA encoding short hairpin RNAs of Notch1 (shNotch1) and fluorinated polyamidoamine (PAMAM-F) (PAMAM-F/shNotch1). In response to low pH and H2O2 in tumor microenvironment, the hydrogel can be dissociated and release the complexes for precise delivery of shNotch1 into tumor cells and inhibit Notch1 activity to suppress malignant biological behaviors of CRC. In the subcutaneous tumor model of CRC, PAMAM-F/shNotch1-loaded hydrogels can accurately attenuate Notch1 activity and significantly inhibit tumor growth without affecting Notch signal in adjacent normal tissues. Therefore, this therapeutic system can precisely inhibit Notch1 signal in CRC with high responsiveness and low toxicity, providing a promising Notch-targeted gene therapeutic for human malignancy.

A capacitive humidity sensor based on nanodiamond/silver nanoparticles (ND/Ag) nanocomposite with high stability and rapid response for respiratory monitoring

In this work, a high-performance capacitive humidity sensor based on nanodiamond/silver nanoparticles (ND/Ag) nanocomposite is proposed. The influence of silver nanoparticles with different content in nanodiamond is investigated, and the optimum ratio of 5 wt% Ag in the composite shows the maximum humidity sensing performance, which is three times than that of the pure nanodiamond based humidity sensor. Moreover, the proposed sensor exhibits a superior repeatability, ultrafast response time (<2 s) and recovery time (<1 s). More importantly, the sensor can maintain a good repeatability and rapid response speed when exposure to high humidity for a long time, demonstrating the excellent stability of the proposed sensor. Furthermore, complex impedance spectroscopy was applied to account for the underlying sensing mechanisms of the ND/Ag composite film humidity sensor. Finally, we design a circuit to realize non-contact breathing control by using the fabricated humidity sensor, which demonstrate that the fabricated humidity sensor could be applied to some auto-control systems by human-breath. This work demonstrated that ND/Ag composite film is an ideal candidate material for constructing high-performance humidity sensors for respiratory applications.

Chinese exclusion? Agent response in the market for owner‐occupied housing

AbstractWe design and implement a correspondence experiment to test for differences in real estate agent response to Chinese clients. In the full sample, real estate agents are no more likely to respond to white clients than Chinese clients. Subsample results show statistically significant differential treatment of Chinese clients in rural areas and in some states. White real estate agents favor white clients (7.90% higher response rate), and Chinese real estate agents favor Chinese clients by a wide margin (151.11% higher response rate).

Prediction of therapeutic response and cancer outcomes in solid tumours via in silico clinical trials.

e13603 Background: Oncology therapeutic development has high failure rates with substantial costs. Advances in technology, including molecular characterisations of cancer and computational power, provide the opportunity to better model therapeutic response for existing and emerging therapies. Methods: Concr adapted Bayesian statistical principles used by astrophysicists to effectively integrate multi-dimensional data (genomic &amp; transcriptomic) for accurate modelling of cancer biology. Our proprietary computational framework was applied to predict clinical response and survival through construction of digital twins and in silico simulations of clinical trials. Predicted log odds ratios (LOR) were generated for drug response and compared to published data from 8 suitable historical clinical trials. Three distinct models underpin this framework: Drug Efficacy, Treatment Response &amp; Overall Survival (OS). Three publicly available datasets were used for training: Cancer Therapeutic Response Portal ( in vitro dose-response data), Cancer Cell Line Encyclopaedia and TCGA. Results: For all 8 clinical studies, the digital twin model accurately simulated both trial arms, compared drug efficacy across arms and predicted which treatment was most active. Unblinded evaluation: Our model accurately predicted gemcitabine would have greater clinical benefit than 5-FU (LOR -0.10, P &lt;0.0001) in metastatic pancreatic cancer. In advanced breast cancer, the model predicted docetaxel had a higher response rate than doxorubicin, and carboplatin response rates were similar to docetaxel in BRCA wild-type patients. In platinum-sensitive recurrent ovarian cancer, the model predicted cisplatin-based combination had a higher response rate than paclitaxel. Blinded evaluation: Using data for paclitaxel, the model correctly predicted that nab-paclitaxel+gemcitabine response rates were higher than gemcitabine in metastatic pancreatic cancer (predicted LOR -0.090, p = &lt;0.001). In all 3 early breast cancer studies, predictions mirrored clinical trial results, adjuvant ECF &gt; CMF, adjuvant TC &gt; AC and adjuvant tamoxifen was superior to capecitabine. The underlying pan-tumour Overall Survival model used a Random Survival Forest approach, trained on 23 cancers with predictive accuracy of 0.78 AUC ROC and C-index 0.71. To enable cohort enrichment for drug response, the model segmented patient cohorts into treatment responder and non-responder. Using this approach, the log odds increased for drug response rate for 16 of the 19 different cancers and 14 of the different 17 drugs. Conclusions: Our digital twin model represents transformative technology for clinical trial simulation with strong potential for accelerating and de-risking clinical drug development, and utility for synthetic control arms.