Apolipoprotein E in patients with undiagnosed pleural effusion: a prospective diagnostic test accuracy study.

INTRODUCTION: Pleural effusion is common in clinical practice, and its differential diagnosis remains challenging for clinicians. This study investigates the diagnostic value of apolipoprotein E (apoE) in patients with undetermined pleural effusion. METHODS: This prospective, double-blind study enrolled 152 patients with undiagnosed pleural effusion. Their pleural fluid apoE levels were measured, and a receiver operating characteristics (ROC) curve was used to evaluate the diagnostic accuracy of apoE. Decision curve analysis (DCA) was used to assess apoE's net benefit. Subgroup analyses were performed to investigate the effect of age on the diagnostic accuracy of apoE. RESULTS: Among the included participants, 23 had heart failure (HF). HF patients had the lowest apoE level among pleural effusion patients. The area under the curve (AUC) of apoE for HF was 0.79 (95% CI: 0.69-0.89). At the threshold of 40 mg/L, the sensitivity and specificity of apoE were 0.96 (95% CI: 0.87-1.00) and 0.33 (95% CI: 0.25-0.42), respectively. The decision curve for apoE was above reference lines. The AUC of apoE decreased in older patients. CONCLUSION: Pleural fluid apoE has moderate diagnostic value for HF and has net benefits in patients with undiagnosed pleural effusion. The diagnostic accuracy of apoE decreases with age.

Identification and validation of inflammatory subtypes in intrahepatic cholangiocellular carcinoma.

BACKGROUND: Inflammation plays a critical role in tumor development. Inflammatory cell infiltration and inflammatory mediator synthesis cause changes in the tumor microenvironment (TME) in several cancers, especially in intrahepatic cholangiocellular carcinoma (ICC). However, methods to ascertain the inflammatory state of patients using reliable biomarkers are still being explored. METHOD: We retrieved the RNA sequencing and somatic mutation analyses results and the clinical characteristics of 244 patients with ICC from published studies. We performed consensus clustering to identify the molecular subtypes associated with inflammation. We compared the prognostic patterns, clinical characteristics, somatic mutation profiles, and immune cell infiltration patterns across inflammatory subtypes. We performed quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to confirm gene expression. We performed logistic regression analyses to construct a nomogram predicting the inflammatory status of patients with ICC. RESULTS: Our results confirmed that ICC can be categorized into an inflammation-high subtype (IHS) and an inflammation-low subtype (ILS). Patients from each group had distinct prognosis, clinical characteristics, and TME composition. Patients with ICC in the IHS group showed poorer prognosis owing to the immunosuppressive microenvironment and high frequency of KRAS and TP53 mutations. Cancer-associated fibroblast (CAF)-derived COLEC11 reduced myeloid inflammatory cell infiltration and attenuated inflammatory responses. The results of qRT-PCR and IHC experiments confirmed that COLEC11 expression levels were significantly reduced in tumor tissues compared to those in paracancerous tissues. Patients with ICC in the IHS group were more likely to respond to treatment with immune checkpoint inhibitors (ICIs) owing to their higher tumor mutational burden (TMB) scores, tumor neoantigen burden (TNB) scores, neoantigen counts, and immune checkpoint expression levels. Finally, we developed a nomogram to effectively predict the inflammatory status of patients with ICC based on their clinical characteristics and inflammatory gene expression levels. We evaluated the calibration, discrimination potential, and clinical utility of the nomogram. CONCLUSION: The inflammatory response in IHS is primarily induced by myeloid cells. COLEC11 can reduce the infiltration level of this group of cells, and myeloid inflammatory cells may be a novel target for ICC treatment. We developed a novel nomogram that could effectively predict the inflammatory state of patients with ICC, which will be useful for guiding individualized treatment plans.

Vapor Growth of All-Inorganic 2D Ruddlesden-Popper Lead- and Tin-Based Perovskites.

The 2D Ruddlesden-Popper (RP) perovskites Cs2PbI2Cl2 (Pb-based, n = 1) and Cs2SnI2Cl2 (Sn-based, n = 1) stand out as unique and rare instances of entirely inorganic constituents within the more expansive category of organic/inorganic 2D perovskites. These materials have recently garnered significant attention for their strong UV-light responsiveness, exceptional thermal stability, and theoretically predicted ultrahigh carrier mobility. In this study, we synthesized Pb and Sn-based n = 1 2D RP perovskite films covering millimeter-scale areas for the first time, utilizing a one-step chemical vapor deposition (CVD) method under atmospheric conditions. These films feature perovskite layers oriented horizontally relative to the substrate. Multilayered Cs3Pb2I3Cl4 (Pb-based, n = 2) and Cs3Sn2I3Cl4 (Sn-based, n = 2) films were also obtained for the first time, and their crystallographic structures were refined by combining X-ray diffraction (XRD) and density functional theory (DFT) calculations. DFT calculations and experimental optical spectroscopy support band-gap energy shifts related to the perovskite layer thickness. We demonstrate bias-free photodetectors using the Sn-based, n = 1 perovskite with reproducible photocurrent and a fast 84 ms response time. The present work not only demonstrates the growth of high-quality all-inorganic multilayered 2D perovskites via the CVD method but also suggests their potential as promising candidates for future optoelectronic applications.

Pleural pro-gastrin releasing peptide is a potential diagnostic marker for malignant pleural effusion induced by small-cell lung cancer.

Background: Serum pro-gastrin releasing peptide (proGRP) is a well-recognized diagnostic marker for small cell lung cancer (SCLC). Pleural effusion is common in patients with advanced SCLC. The diagnostic accuracy of pleural proGRP for malignant pleural effusion (MPE) has not yet been established. This study aimed to evaluate the diagnostic accuracy of pleural proGRP for MPE. Methods: We prospectively recruited patients with undiagnosed pleural effusions from two centers (Hohhot and Changshu). An electrochemiluminescence immunoassay was used to detect pleural fluid proGRP. The diagnostic accuracy of proGRP for MPE was evaluated using a receiver operating characteristic (ROC) curve. Results: In both the Hohhot (n=153) and Changshu (n=58) cohorts, pleural proGRP in MPE patients did not significantly differ from that in patients with benign pleural effusions (BPEs) (Hohhot, P=0.91; Changshu, P=0.12). In the Hohhot and Changshu cohorts, the areas under the curves (AUCs) of proGRP were 0.51 [95% confidence interval (CI): 0.41-0.60] and 0.62 (95% CI: 0.47-0.77), respectively. However, patients with SCLC-induced MPE had significantly higher proGRP levels than those with BPE and other types of MPE (P=0.001 for both). In the pooled cohort, the AUC of proGRP for SCLC-induced MPE was 0.90 (95% CI: 0.78-1.00, P=0.001). At a threshold of 40 pg/mL, proGRP had a sensitivity of 1.00 (95% CI: 0.61-1.00) and specificity of 0.59 (95% CI: 0.52-0.66). The positive likelihood ratio was 2.61 (95% CI: 1.99-3.41), and the negative likelihood ratio was 0. Conclusions: Pleural proGRP has no diagnostic value for MPE, but has high diagnostic accuracy for SCLC-induced MPE. In patients with proGRP levels <40 pg/mL, MPE secondary to SCLC can be excluded.

Self-Growing Hydrogel Bioadhesives for Chronic Wound Management.

Hydrogel bioadhesives have emerged as a promising alternative to wound dressings for chronic wound management. However, many existing bioadhesives do not meet the functional requirements for efficient wound management through dynamically mechanical modulation, due to the reduced wound contractibility, frequent wound recurrence, incapability to actively adapt to external microenvironment variation, especially for those gradually-expanded chronic wounds. Here, a self-growing hydrogel bioadhesive (sGHB) patch that exhibits instant adhesion to biological tissues but also a gradual increase in mechanical strength and interfacial adhesive strength within a 120-h application is presented. The gradually increased mechanics of the sGHB patch could effectively mitigate the stress concentration at the wound edge, and also resist the wound expansion at various stages, thus mechanically contracting the chronic wounds in a programmable manner. The self-growing hydrogel patch demonstrated enhanced wound healing efficacy in a mouse diabetic wound model, by regulating the inflammatory response, promoting the faster re-epithelialization and angiogenesis through mechanical modulation. Such kind of self-growing hydrogel bioadhesives have potential clinical utility for a variety of wound management where dynamic mechanical modulation is indispensable.

Safety and efficacy of CT-guided percutaneous radiofrequency ablation for non-small cell lung cancer: a single-center, single-arm analysis.

Non-small cell lung cancer (NSCLC) is a prevalent malignant tumor, and the commonly treatment modalities include surgery, radiotherapy, chemotherapy, etc. Currently, CT-guided percutaneous radiofrequency ablation (RFA) for the treatment of cancers has been widely performed. This study aimed to evaluate the safety and efficacy of this therapy in NSCLC patients. Thirty-five NSCLC patients were enrolled in this study and all received CT-guided percutaneous RFA therapy. The outcome measures included the changes in forced respiratory volume in the first second (FEV1), total lung volume (TLC), lesion size and computed tomography (CT) values of the region of interest (ROI) before and after treatment. The main efficacy measures comprised complete tumor ablation and local recurrence after initial treatment, as well as the objective response rate (ORR) and disease control rate (DCR) after 6 months of treatment. After receiving CT-guided percutaneous RFA therapy, the target lesion was effectively controlled and CT values gradually decreased. Besides, no significant changes were observed in the patient's lung function, postoperative complications were experienced by a total of 10 patients, primarily including pneumothorax, infection, lung hollowing. Fortunately, all these complications were successfully managed with appropriate treatment. Following the initial RFA treatment, 31 patients (88.57%) achieved complete ablation, while 6 patients experienced local recurrence. After 6 months of treatment, the ORR and DCR were found to be 68.57% and 82.86% respectively. CT-guided percutaneous RFA has demonstrated favorable safety and efficacy in the treatment of patients with NSCLC at different stages, which represented a promising therapeutic modality.

Adverse events following immunization of co- and separate administration of DTaP-IPV/Hib vaccines: A real-world comparative study.

To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.

New Perspective to Evaluate the Carbon Offsetting by Urban Blue-Green Infrastructure: Direct Carbon Sequestration and Indirect Carbon Reduction.

Urban blue-green infrastructure (BGI) offers a multitude of ecological advantages to residents, thereby playing a pivotal role in fortifying urban resilience and fostering the development of climate-resilient cities. Nonetheless, current research falls short of a comprehensive analysis of BGI's overall potential for carbon reduction and its indirect carbon reduction impact. To fill this research gap, we utilized the integrated valuation of ecosystem services and trade-offs model and remote sensing estimation algorithm to quantify the direct carbon sequestration and resultant indirect carbon reduction facilitated by the BGI within the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) (China). To identify the regions that made noteworthy contributions to carbon offsets and outliers, spatial autocorrelation analysis was also employed. The findings of this study reveal that in 2019, the BGI within the study area contributed an overall carbon offset of 1.5 × 108 t·C/yr, of which 3.5 × 107 and 11.0 × 107 t·C/yr were the result of direct carbon sequestration and indirect carbon reduction, respectively. The GBA's total CO2 emissions were 1.1 × 108 t in 2019. While the direct carbon sequestration offset 32.0% of carbon emissions, the indirect carbon reduction mitigated 49.9% of potential carbon emissions. These results highlight the critical importance of evaluating BGI's indirect contribution to carbon reduction. The findings of this study provide a valuable reference for shaping management policies that prioritize the protection and restoration of specific areas, thereby facilitating the harmonized development of carbon offset capabilities within urban agglomerations.

Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma.

OBJECTIVE: TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first-in-human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). METHODS: This is a multicenter phase I clinical trial consisting of the 3+3 dose-escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28-day cycle. RESULTS: Twenty-five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose-limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any-grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time-to-plasma peak concentration of 0.8-1.5 h. The mean half-life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response-evaluable patients, 63.7% achieved stable disease or better. CONCLUSIONS: TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose-expansion phase.

Numerical study on the stimulation effect of boundary sealing and hot water injection in marine challenging gas hydrate extraction.

This study proposed a novel development mode combining boundary sealing and hot water injection to address the challenges of gas leakage, limited reservoir sensible heat, boundary water intrusion, and low productivity faced by challenging hydrate extraction, and the stimulation effect was numerically investigated with Shenhu hydrates as the geological background. The results showed that lower boundary permeability facilitated pressure propagation and achieved volumetric dissociation of hydrates, whereas insufficient formation energy resulted in substantial gas retention. Hot water injection was effective for stimulation, but open boundaries could not maintain the high injection pressure, leading to massive hot water losses and gas escapes. However, their combination achieved a synergistic stimulation like "1 + 1 > 2" because a piston water drive similar to secondary recovery in oil and gas development was formed. Relative to three-spot well patterns, the five-spot shortened the extraction cycle by 680 days and enhanced the gas-to-water ratio by 17%. Increasing injection pressure enhanced water yield more significantly while the improvement of gas yield was more significant by increasing hot water temperature. Overall, high-pressure and high-temperature injection was suggested for gas enhancement and water control. These findings provide important guidance for advancing the commercial development of challenging hydrates.

Pleural carbohydrate antigen 50 and malignant pleural effusion: a prospective, double-blind diagnostic accuracy test.

Background: Serum carbohydrate antigen 50 (CA50) is an auxiliary diagnostic marker for various solid tumors, but it remains unclear whether CA50 in pleural fluid can assist in the diagnosis of malignant pleural effusion (MPE). This study aimed to evaluate the diagnostic accuracy of pleural fluid CA50 for MPE in pleural effusion patients with undetermined causes. Methods: This study prospectively recruited pleural effusion patients with undetermined causes who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. We measured pleural fluid CA50 level with an electrochemiluminescence assay. We analyzed the diagnostic accuracy of CA50 and carcinoembryonic antigen (CEA) for MPE with the receiver operating characteristic (ROC) curve. The net benefits of CA50 and CEA were analyzed using the decision curve analysis (DCA). Results: We enrolled 66 MPEs and 87 benign pleural effusions (BPEs). MPE patients had significantly higher CA50 and CEA than BPE patients. The area under the ROC curve (AUC) of CA50 was 0.72 (95% CI: 0.63-0.80). CA50 had a sensitivity of 0.30 (95% CI: 0.19-0.41) and a specificity of 1.00 (95% CI: 1.00-1.00) at the threshold of 15 IU/mL. The decision curve of CA50 was above the reference line at the calculated risk probability of between 0.30 and 1.00. Venn diagram indicated that some patients with low CEA (<50 or <150 ng/mL) and/or negative cytology can be identified by positive CA50 (>15 IU/mL). Conclusions: Pleural fluid CA50 has moderate accuracy and net benefit for detecting MPE. CA50 >15 IU/mL can be used to diagnose MPE. The combination of CA50 and CEA improves the diagnostic sensitivity for MPE.

Single-frequency DBR lasing by integrating FBGs into germanium-free photosensitive highly Yb3+-doped silica fibers.

Monolithic distributed Bragg reflector (DBR) cavity which directly integrates fiber Bragg gratings (FBGs) into the photosensitive RE-doped fibers is a promising configuration in constructing compact and efficient single frequency fiber lasers (SFFLs). Yet, the doping level of rare-earth (RE) ions has generally to be sacrificed in the classical Ge-photosensitized RE-doped silica fibers because of the dramatic refractive index increase caused by the introduction of Ge. Here, we demonstrate an approach to realize the trade-off between photosensitivity and RE doping concentration. We validate that the addition of a small amount of cerium (0.37wt.%) instead of Ge could photosensitize Yb3+-doped silica fiber (YDF), while maintaining fiber numerical aperture (NA) at 0.12 under a high 2.5-wt.% Yb doping level. Based on the short monolithic DBR cavity constructed by this germanium-free photosensitive highly YDF, a 1064 nm fiber laser with a 48.6% slope efficiency and an over 200 mW power on two orthogonally polarized modes could be realized. Further stable and linear-polarized 1064 nm SFFL is also demonstrated in a designed monolithic polarization maintaining cavity with an output power of 119 mW and an efficiency of 26.4%. Our results provide an alternative way to develop photosensitive highly RE-doped fibers towards monolithic laser cavity application.

BF3·OEt2 Catalyzed Cascade [4 + 2] Benzannulation of Vinyloxiranes with Coumarins to Construct Benzocoumarin Derivatives.

A BF3·OEt2-catalyzed cascade cyclization reaction of vinyloxirane with coumarin is described, affording the benzocoumarin derivatives with moderate to excellent yields (72-92%). The reaction demonstrates exceptional substrate tolerance and has been extensively explored for its potential in drug development, including scale-up experiments, functional group transformations, and screening of the products for anticancer activity. Moreover, the reaction mechanism has been rigorously validated through intermediate trapping and control experiments. Additionally, this reaction represents the uncommon nonmetal catalyzed intermolecular cyclization of vinyloxiranes.

Defective ferritinophagy and imbalanced iron metabolism in PBDE-47-triggered neuronal ferroptosis and salvage by Canolol.

The brominated flame retardant 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) is a ubiquitous environmental pollutant that causes neurotoxicity. However, incomplete understanding of the underlying mechanisms has hampered the development of effective intervention strategies. Oxidative stress and related cell death are the modes of action for PBDE-47 neurotoxicity, which are also the characteristics of ferroptosis. Nonetheless, the role of ferroptosis in PBDE-47-induced neurotoxicity remains unclear. In the present study, we found that PBDE-47 triggered ferroptosis in neuron-like PC12 cells, as evidenced by intracellular iron overload, lipid peroxidation, and mitochondrial damage. This was confirmed by ferroptosis inhibitors including the lipid reactive oxygen species scavenger ferrostatin-1 and iron chelator deferoxamine mesylate. Mechanistically, PBDE-47 impaired ferritinophagy by disrupting nuclear receptor coactivator 4-mediated lysosomal degradation of the iron storage protein ferritin. Moreover, PBDE-47 disturbed iron metabolism by increasing cellular iron import via upregulation of transferrin receptor 1 and decreasing cellular iron export via downregulation of ferroportin 1 (FPN1). Intriguingly, rescuing lysosomal function by overexpressing cathepsin B (CatB) mitigated PBDE-47-induced ferroptosis by partially restoring dysfunctional ferritinophagy and enhancing iron excretion via the upregulation of FPN1. However, FPN1 knockdown reversed the beneficial effects of CatB overexpression on the PBDE-47-induced iron overload. Finally, network pharmacology integrated with experimental validation revealed that Canolol, the main phenolic compound in canola oil, protected against PBDE-47-evoked iron overload, resulting in ferroptosis by restoring defective ferritinophagy and improving abnormal iron metabolism via lowering iron uptake and facilitating iron excretion. Overall, these data suggest that ferroptosis is a novel mechanism of PBDE-47-induced neuronal death and that manipulation of ferritinophagy and iron metabolism via Canolol represents a promising therapeutic strategy.

Integration of MoS2 Memtransistor Devices and Analogue Circuits for Sensor Fusion in Autonomous Vehicle Target Localization.

In contemporary autonomous driving systems relying on sensor fusion, traditional digital processors encounter challenges associated with analogue-to-digital conversion and iterative vector-matrix operations, which are encumbered by limitations in terms of response time and energy consumption. In this study, we present an analogue Kalman filter circuit based on molybdenum disulfide (MoS2) memtransistor, designed to accelerate sensor fusion for precise localization in autonomous vehicle applications. The nonvolatile memory characteristics of the memtransistor allow for the storage of a fixed Kalman gain, which eliminates the data convergence and thus accelerates the processing speeds. Additionally, the modulation of multiple conductance states by the gate terminal enables fast adaptability to diverse autonomous driving scenarios by tuning multiple Kalman filter gains. Our proposed analogue Kalman filter circuit accurately estimates the position coordinates of target vehicles by fusing sensor data from light detection and ranging (LiDAR), millimeter-wave radar (Radar), and camera, and it successfully solves real-word problems in a signal-free crossroad intersection. Notably, our system achieves a 1000-fold improvement in energy efficiency compared to that of digital circuits. This work underscores the viability of a memtransistor for achieving fast, energy-efficient real-time sensing, and continuous signal processing in advanced sensor fusion technology.

CeO2/Co heterostructure encapsulated in hollow necklace-like carbon fiber as an advanced host material for high-performance lithium-sulfur batteries.

The shuttle effect of lithium polysulfides (LiPSs) and the sluggish reaction kinetics of LiPSs conversion pose serious challenges to the commercial feasibility of lithium-sulfur (Li-S) batteries. To address these obstacles, herein, we construct CeO2/Co heterostructures in hollow necklace-like carbon fibers (CeO2/Co-CNFs) as the cathode host material for Li-S batteries. The specific surface area of fibers is significantly enhanced by using a template, thereby promoting the utilization efficiency of sulfur. Meanwhile, CeO2/Co-CNFs show strong conductivity, effective adsorption to LiPSs, and robust catalytic activity for LiPSs conversion. As a result, the Li-S battery with CeO2/Co-CNFs displays 961 mAh g-1 at 0.2 C, with an 86 % capacity retention rate after 100 cycles. At 2.0 C current density, the composite cathode maintains an initial discharge capacity of 782 mAh g-1, with a mere 0.044 % capacity loss per cycle. Furthermore, in situations with limited electrolytes, high sulfur loading, and high areal mass loading, the composite cathode can provide a high areal capacity of 6.2 mg cm-2 over 100 cycles. This work provides a useful approach for investigating high-performance Li-S battery cathodes.

A splice site variant in MADD affects hormone expression in pancreatic ß cells and pituitary gonadotropes.

MAPK activating death domain (MADD) is a multifunctional protein regulating small GTPases RAB3 and RAB27, MAPK signaling, and cell survival. Polymorphisms in the MADD locus are associated with glycemic traits, but patients with biallelic variants in MADD manifest a complex syndrome affecting nervous, endocrine, exocrine, and hematological systems. We identified a homozygous splice site variant in MADD in 2 siblings with developmental delay, diabetes, congenital hypogonadotropic hypogonadism, and growth hormone deficiency. This variant led to skipping of exon 30 and in-frame deletion of 36 amino acids. To elucidate how this mutation causes pleiotropic endocrine phenotypes, we generated relevant cellular models with deletion of MADD exon 30 (dex30). We observed reduced numbers of ß cells, decreased insulin content, and increased proinsulin-to-insulin ratio in dex30 human embryonic stem cell-derived pancreatic islets. Concordantly, dex30 led to decreased insulin expression in human ß cell line EndoC-ßH1. Furthermore, dex30 resulted in decreased luteinizing hormone expression in mouse pituitary gonadotrope cell line LßT2 but did not affect ontogeny of stem cell-derived GnRH neurons. Protein-protein interactions of wild-type and dex30 MADD revealed changes affecting multiple signaling pathways, while the GDP/GTP exchange activity of dex30 MADD remained intact. Our results suggest MADD-specific processes regulate hormone expression in pancreatic ß cells and pituitary gonadotropes.

Low repetition rate 915†nm figure-9 ultrafast laser with all-fiber structure.

The advent of optical metrology applications has necessitated the development of compact, reliable, and cost-effective picosecond lasers operating around 900 nm, specifically catering to the requirements of precise ranging. In response to this demand, our work introduces an innovative solution-an all-fiber, all-polarization-maintaining (PM) figure-9 mode-locked laser operating at 915 nm. The proposed figure-9 Nd-doped fiber laser has a 69.2 m long cavity length, strategically designed and optimized to yield pulses with a combination of high pulse energy and low repetition rate. The laser can generate 915 nm laser pulses with a pulse energy of 4.65 nJ, a pulse duration of 15.2 ps under the repetition rate of 3.05 MHz. The 1064 nm amplified spontaneous emission (ASE) is deliberately filtered out, in order to prevent parasitic lasing and increase the spectral proportion of the 915 nm laser. The all-PM fiber configuration of this laser imparts exceptional mode-locking performance and environmental robustness, which is confirmed by long-term output power and spectral stability test. This compact and long-term reliable fiber laser could be a promising light source for applications like inter-satellite ranging.

Accuracy of cone-beam breast computed tomography for assessing breast cancer tumor size-comparison with breast magnetic resonance imaging.

Background: Accurate preoperative assessment of tumor size is important in developing a surgical plan for breast cancer. The purpose of this study was to evaluate the accuracy of cone-beam breast computed tomography (CBBCT) and magnetic resonance imaging (MRI) in the assessment of tumor size and to analyze the factors influencing the discordance. Methods: In this retrospective study, patients with breast cancer who underwent preoperative contrast-enhanced CBBCT (CE-CBBCT) and dynamic contrast-enhanced MRI (DCE-MRI) and received a complete pathologic diagnosis from August 2020 to December 2021 were included, using the pathological result as the gold standard. Two radiologists assessed the CBBCT and MRI features and measured the tumor size with a 2-week washout period. Intraclass correlation coefficient (ICC) and Bland-Altman analyses were used to assess inter-observer reproducibility and agreement based on CBBCT, MRI and pathology. Univariate analyses of differences in clinical, pathological and CBBCT/MRI features between the concordant and discordant groups was performed using the t-test, Mann-Whitney U-test, Chi-squared test and Fisher's exact test. Multivariate analyses were used to identify factors associated with discordance of CBBCT/MRI with pathology. Results: A total of 115 female breast cancer patients (115 lesions) were included. All patients had a single malignant tumor of the unilateral breast. The reproducibility and the agreement ranged from moderate to excellent (ICC =0.607-0.983). Receiver operating characteristic (ROC) analyses showed that the cut-off values of CBBCT-pathology and MRI-pathology discordance were 2.25 and 2.65 cm, respectively. CBBCT/MRI-pathology concordance was significantly associated with the extent of pathology, lesion type, presence of calcification, human epidermal growth factor receptor 2 (HER2) status and fatty infiltration (P<0.05). In lesions containing calcification, the difference of CBBCT-pathology was significantly smaller than MRI-pathology (P=0.021). Non-mass enhancement (NME) was the main predictor of CBBCT- or MRI-pathology discordance [odds ratio (OR) =3.293-6.469, P<0.05], and HER2 positivity was a predictor of CBBCT-pathology discordance (OR =3.514, P=0.019). Conclusions: CBBCT and MRI have comparable accuracy in measurement of tumor size, and CBBCT is advantageous in assessing the size of calcified lesions. NME and HER2 positivity are significant predictors of CBBCT-pathology discordance. This suggests that CBBCT might serve as an alternative imaging technique to assess tumor size when patients do not tolerate MRI.

Myeloid neoplasms post cytotoxic therapy: epidemiology, pathogenesis outcomes, prognostic factors, and treatment options.

Myeloid neoplasms post cytotoxic therapy (MN-pCT) are a category includes AML, MDS, and MDS/MPN arising in patients exposed to cytotoxic (DNA-damaging) therapy for an unrelated condition in 2022 version World Health Organization (WHO) classification. With improved survival of patients with tumors, the incidence of MN-pCT after chemotherapy and/or radiation therapy among patients with tumors has gradually risen. However, the outcome of MN-pCT is poorer than that of primary myeloid neoplasms. This review summarizes the current understanding based on existing research, as a foundation for further research on MN-pCT.