Targeted linked-read sequencing for direct haplotype phasing of parental GJB2/SLC26A4 alleles: A universal and dependable noninvasive prenatal diagnosis method applied to autosomal recessive nonsyndromic hearing loss in at-risk families.

Noninvasive prenatal diagnosis (NIPD) for autosomal recessive nonsyndromic hearing loss (ARNSHL) has been rarely reported until recent years. However, the previous method could not be performed on challenging genome loci (e.g. CNVs, deletions, inversions, or gene recombinants) or on families without proband genotype. Here, this study assesses the performance of relative haplotype dosage analysis (RHDO)-based NIPD for identifying fetal genotyping in pregnancies at risk of ARNSHL. Fifty couples carrying pathogenic variants associated with ARNSHL in either GJB2 or SLC26A4 were recruited. The RHDO-based targeted linked-read sequencing combined with whole gene coverage probes was used to genotype the fetal cell-free DNA (cfDNA) of 49 families that met the quality control standard.. Fetal amniocyte samples were genotyped using invasive prenatal diagnosis (IPD) to assess the performance of NIPD. The NIPD results showed 100%(49/49) concordance with those obtained through IPD. Two families with copy number variation and recombination were also successfully identified. Sufficient specific informative SNPs for haplotyping, as well as the fetal cfDNA concentration and sequencing depth, are prerequisites for RHDO-based NIPD. This method has the merits of covering the entire genes of GJB2 and SLC26A4, qualifying for copy number variation and recombination analysis with remarkable sensitivity and specificity. Therefore, it has clinical potential as an alternative to traditional IPD for ARNSHL.

Meta-analysis of the clinical efficacy of the Gamma3 nail vs Gamma3U-blade system in the treatment of intertrochanteric fractures.

BACKGROUND: The traditional Gamma3 nail is a mainstream treatment for femoral intertrochanteric fractures. Literature reports that the Gamma3U-blade system can increase the stability of the Gamma3 nail and reduce complication incidence. However, comparative studies between the Gamma3U-blade and Gamma3 systems are limited; hence, this meta-analysis was performed to explore the clinical efficacy of these two surgical methods. AIM: To investigate the clinical efficacy of Gamma3 and Gamma3 U-blade for intertrochanteric fractures. METHODS: A computerized search for Chinese and English literature published from 2010 to 2022 was conducted in PubMed, Cochrane, CNKI, Wanfang, and VIP databases. The search keywords were gamma 3, gamma 3 U blade, and intertrochanteric fracture. Additionally, literature tracking was performed on the references of published literature. The data were analyzed using Revman 5.3 software. Two individuals checked the inputs for accuracy. Continuous variables were described using mean difference and standard deviation, and outcome effect sizes were expressed using ratio OR and 95% confidence interval (CI). High heterogeneity was considered at (P < 0.05, I2 > 50%), moderate heterogeneity at I2 from 25% to 50%, and low heterogeneity at (P ≥ 0.05, I2 < 50%). RESULTS: Following a comprehensive literature search, review, and analysis, six articles were selected for inclusion in this study. This selection comprised five articles in English and one in Chinese, with publication years spanning from 2016 to 2022. The study with the largest sample size, conducted by Seungbae in 2021, included a total of 304 cases. Statistical analysis: A total of 1063 patients were included in this meta-analysis. The main outcome indicators were: Surgical time: The Gamma3U blade system had a longer surgical time compared to Gamma3 nails (P = 0.006, I2 = 76%). Tip-apex distance: No statistical significance or heterogeneity was observed (P = 0.65, I2 = 0%). Harris Hip score: No statistical significance was found, and low heterogeneity was detected (P = 0.26, I2 = 22%). Union time: No statistical significance was found, and high heterogeneity was detected (P = 0.05, I2 = 75%). CONCLUSION: Our study indicated that the Gamma3 system reduces operative time compared to the Gamma3 U-blade system in treating intertrochanteric fractures. Both surgical methods proved to be safe and effective for this patient group. These findings may offer valuable insights and guidance for future surgical protocols in hip fracture patients.

Adding carbon sources to the substrates enhances Cr and Ni removal and mitigates greenhouse gas emissions in constructed wetlands.

Constructed wetlands for wastewater treatment pose challenges related to long-term operational efficiency and greenhouse gas emissions on a global scale. This study investigated the impact of adding peat, humic acid, and biochar into the substrates of constructed wetlands and focused on Cr, and Ni removal, greenhouse gas emissions, and microbial communities in constructed wetlands. Biochar addition treatment achieved the highest removal efficiencies for total Cr (99.96%), Cr (VI) (100%), and total Ni (91.04%). Humic acid and biochar addition both significantly increased the heavy metal content in wetland plant Leersia hexandra and substrates of constructed wetlands. Further analysis of microbial community proportions by high-throughput sequencing revealed that biochar and humic acid treatments enhanced Cr and Ni removal efficiency by increasing the abundance of Bacteroidetes, Geobacter and Ascomycota. Humic acid addition treatment reduced CO2 emissions by decreasing the abundance of Bacteroidetes and increasing that of Basidiomycota. Peat treatment decreased CH4 emissions by reducing the abundance of the Bacteroidetes. Biochar treatment increased the abundance of the Firmicutes, Bacteroidetes, Proteobacteria as well as Basidiomycota, resulting in reduced N2O emissions. Biochar and humic acid treatments efficiently removed heavy metals from wastewater and mitigated greenhouse gas emissions in constructed wetlands by modifying the microbial communities.

Biobased Inks Based on Cuttlefish Ink and Cellulose Nanofibers for Biodegradable Patterned Soft Actuators.

Soft actuators with stimuli-responsive and reversible deformations have shown great promise in soft robotics. However, some challenges remain in existing actuators, such as the materials involved derived from nonrenewable resources, complex and nonscalable preparation methods, and incapability of complex and programmable deformation. Here, a biobased ink based on cuttlefish ink nanoparticles (CINPs) and cellulose nanofibers (CNFs) was developed, allowing for the preparation of biodegradable patterned actuators by direct ink writing technology. The hybrid CNF/CINP ink displays good rheological properties, allowing it to be accurately printed on a variety of flexible substrates. A bilayer actuator was developed by printing an ink layer on a biodegradable poly(lactic acid) film using extrusion-based 3D printing technology, which exhibits reversible and large bending behavior under the stimuli of humidity and light. Furthermore, programmable and reversible folding and coiling deformations in response to stimuli have been achieved by adjusting the ink patterns. This work offers a fast, scalable, and cost-effective strategy for the development of biodegradable patterned actuators with programmable shape-morphing.

Using an ER-specific optogenetic mechanostimulator to understand the mechanosensitivity of the endoplasmic reticulum.

The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.

[Identification and expression pattern analysis of a secretory phospholipase A2 gene in Bombyx mori].

Phospholipase A2 (PLA2) is widely distributed in animals, plants, and microorganisms, and it plays an important role in many physiological activities. In a previous study, we have identified a secretory PLA2 in Bombyx mori (BmsPLA2-1-1). In this study, we further identified four new sPLA2 genes (BmsPLA2-1-2, BmsPLA2-2, BmsPLA2-3, and BmsPLA2-4) in B. mori genome. All four genes exhibits the characteristic features of sPLA2, including the sPLA2 domain, metal binding sites, and highly conserved catalytic domain. This study completed the cloning, in vitro expression, and expression pattern analysis of the BmsPLA2-4 gene in B. mori. The full length of BmsPLA2-4 is 585 bp, and the recombinant protein obtained through prokaryotic expression has an estimated size of 25 kDa. qRT-PCR analysis revealed that the expression level of BmsPLA2-4 reached its peak on the first day of the fifth instar larval stage. Tissue expression profiling analysis showed that BmsPLA2-4 had the highest expression level in the midgut, followed by the epidermis and fat body. Western blotting analysis results were consistent with those of qRT-PCR. Furthermore, after infecting fifth instar 1-day-old larvae with Escherichia coli and Staphylococcus aureus, the expression level of the BmsPLA2-4 gene significantly increased in 24 h. The findings of this study provides a theoretical basis and valuable experimental data for future related research.

Calcified apoptotic vesicles from PROCR+ fibroblasts initiate heterotopic ossification.

Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single-cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV-releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification.

Identifying the Active Sites in MoSi2@MoO3 Heterojunctions for Enhanced Hydrogen Evolution.

Developing Two-dimensional (2D) Mo-based heterogeneous nanomaterials is of great significance for energy conversion, especially in alkaline hydrogen evolution reaction (HER), however, it remains a challenge to identify the active sites at the interface due to the structure complexity. Herein, the real active sites are systematically explored during the HER process in varied Mo-based 2D materials by theoretical computational and magnetron sputtering approaches first to filtrate the candidates, then successfully combined the MoSi2 and MoO3 together through Oxygen doping to construct heterojunctions. Benefiting from the synergistic effects between the MoSi2 and MoO3, the obtained MoSi2@MoO3 exhibits an unprecedented overpotential of 72 mV at a current density of 10 mA cm-2. Density functional theory calculations uncover the different Gibbs free energy of hydrogen adsorption (ΔGH*) values achieved at the interfaces with different sites as adsorption sites. The results can facilitate the optimization of heterojunction electrocatalyst design principles for the Mo-based 2D materials.

Exosomes for neurodegenerative diseases: diagnosis and targeted therapy.

PURPOSE OF REVIEW: Neurodegenerative diseases are still challenging clinical issues, with no curative interventions available and early, accurate diagnosis remaining difficult. Finding solutions to them is of great importance. In this review, we discuss possible exosomal diagnostic biomarkers and explore current explorations in exosome-targeted therapy for some common neurodegenerative diseases, offering insights into the clinical transformation of exosomes in this field. RECENT FINDINGS: The burgeoning research on exosomes has shed light on their potential applications in disease diagnosis and treatment. As a type of extracellular vesicles, exosomes are capable of crossing the blood - brain barrier and exist in various body fluids, whose components can reflect pathophysiological changes in the brain. In addition, they can deliver specific drugs to brain tissue, and even possess certain therapeutic effects themselves. And the recent advancements in engineering modification technology have further enabled exosomes to selectively target specific sites, facilitating the possibility of targeted therapy for neurodegenerative diseases. The unique properties of exosomes give them great potential in the diagnosis and treatment of neurodegenerative diseases, and provide novel ideas for dealing with such diseases.

Interplay Between Intracellular Transport Dynamics and Liquid-Liquid Phase Separation.

Liquid-liquid phase separation (LLPS) is a ubiquitous process in which proteins, RNA, and biomolecules assemble into membrane-less compartments, playing important roles in many biological functions and diseases. The current knowledge on the biophysical and biochemical principles of LLPS is largely from in vitro studies; however, the physiological environment in living cells is complex and not at equilibrium. The characteristics of intracellular dynamics and their roles in physiological LLPS remain to be resolved. Here, by using single-particle tracking of quantum dots and dynamic monitoring of the formation of stress granules (SGs) in single cells, the spatiotemporal dynamics of intracellular transport in cells undergoing LLPS are quantified. It is shown that intracellular diffusion and active transport are both reduced. Furthermore, the formation of SG droplets contributes to increased spatial heterogeneity within the cell. More importantly, the study demonstrated that the LLPS of SGs can be regulated by intracellular dynamics in two stages: the reduced intracellular diffusion promotes SG assembly and the microtubule-associated transport facilitates SG coalescences. The work on intracellular dynamics not only improves the understanding of the mechanism of physiology phase separations occurring in nonequilibrium environments but also reveals an interplay between intracellular dynamics and LLPS.

Effects of Surface Textures Created Using Additive Manufacturing on Shear Bond Strength Between Resin and Zirconia.

PURPOSE: This investigation aimed to assess the impact of additive manufacturing-generated surface textures on zirconia bond strength. MATERIALS AND METHODS: Zirconia samples (n = 144) fabricated using digital light-processing (DLP) technology were categorized into 6 groups according to the type of surface conditioning (group NN: no designs, no air abrasion; group NY: no designs, with air abrasion; group GN: groove designs, no air abrasion; group GY: groove designs with air abrasion; group HN: hexagon grid, no air abrasion; group HY: hexagon grid, with air abrasion). Composite resin cylinders were cemented to the treated zirconia surfaces with dual-curing, self-adhesive resin cement (Clearfil SA Luting). The shear bond strength (SBS) was tested after water storage for 3 days or 3 days with an additional 10,000 thermocycles. RESULTS: The zirconia samples fabricated using DLP technology have high accuracy. The SBS of the NY, GY, and HY groups did not significantly differ after 3 days, and neither did the SBS of the NN, GN, and HN groups. The NN, NY, and HY groups exhibited reduced SBS compared to their initial values following artificial aging, while the SBS of the remaining three groups were not diminished. The GY group obtained the highest SBS value after aging. CONCLUSION: Printing grooves with air abrasion can improve the bond strength.

Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer.

BACKGROUND: The controlling nutritional status (CONUT) score effectively reflects a patient's nutritional status, which is closely related to cancer prognosis. This study investigated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer, and compared the predictive ability of the CONUT score with other indexes. AIM: To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection. METHODS: This retrospective analysis included 217 patients with newly diagnosed colorectal. The CONUT score was calculated based on the serum albumin level, total lymphocyte count, and total cholesterol level. The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve. The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: Using the cutoff value of the CONUT score, patients were stratified into CONUT low (n = 189) and CONUT high groups (n = 28). The CONUT high group had worse overall survival (OS) (P = 0.013) and relapse-free survival (RFS) (P = 0.015). The predictive performance of CONUT was superior to the modified Glasgow prognostic score, the prognostic nutritional index, and the neutrophil-to-lymphocyte ratio. Meanwhile, the predictive performances of CONUT + tumor node metastasis (TNM) stage for 3-year OS [area under the receiver operating characteristics curve (AUC) = 0.803] and 3-year RFS (AUC = 0.752) were no less than skeletal muscle mass index (SMI) + TNM stage. The CONUT score was negatively correlated with SMI (P < 0.01). CONCLUSION: As a nutritional indicator, the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer, and its predictive ability was superior to other indexes. The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

A novel digital intermediate frequency module for hyperspectral microwave radiometers based on the parallel fast Fourier transform algorithm.

Microwave radiometers, possessing all-day and all-weather operational capabilities, are extensively utilized in the exploration of planetary atmospheres and surfaces. The potential of the hyperspectral detection technology to enhance the precision and resolution of microwave radiometer detection has made it a crucial research focus. This paper introduces an intermediate frequency (IF) module for hyperspectral microwave radiometers. The IF module is constructed with two 6.4 gigabit samples per second sampling-rate analog-to-digital converter (ADC) chips and a Xilinx Virtex-7 field programmable gate array. By implementing a parallel fast Fourier transform algorithm and a pipeline architecture, the IF module can efficiently process all ADC sampling data in real-time, generating 512 channels of output for each ADC. The test results, including linearity, sensitivity, and flatness, are presented and thoroughly analyzed for the IF module. Furthermore, the module is interfaced with the radio frequency front-end of the microwave radiometer to measure hot and cold calibration sources and assess its sensitivity. When combined with a suitable front-end receiver, the IF module can form a radiometer system suitable for various applications of microwave remote sensing.

Design of Mantis-Shrimp-Inspired Multifunctional Imaging Sensors with Simultaneous Spectrum and Polarization Detection Capability at a Wide Waveband.

The remarkable light perception abilities of the mantis shrimp, which span a broad spectrum ranging from 300 nm to 720 nm and include the detection of polarized light, serve as the inspiration for our exploration. Drawing insights from the mantis shrimp's unique visual system, we propose the design of a multifunctional imaging sensor capable of concurrently detecting spectrum and polarization across a wide waveband. This sensor is able to show spectral imaging capability through the utilization of a 16-channel multi-waveband Fabry-Pérot (FP) resonator filter array. The design incorporates a composite thin film structure comprising metal and dielectric layers as the reflector of the resonant cavity. The resulting metal-dielectric composite film FP resonator extends the operating bandwidth to cover both visible and infrared regions, specifically spanning a broader range from 450 nm to 900 nm. Furthermore, within this operational bandwidth, the metal-dielectric composite film FP resonator demonstrates an average peak transmittance exceeding 60%, representing a notable improvement over the metallic resonator. Additionally, aluminum-based metallic grating arrays are incorporated beneath the FP filter array to capture polarization information. This innovative approach enables the simultaneous acquisition of spectrum and polarization information using a single sensor device. The outcomes of this research hold promise for advancing the development of high-performance, multifunctional optical sensors, thereby unlocking new possibilities in the field of optical information acquisition.

Synthetic MRI and amide proton transfer-weighted MRI for differentiating between benign and malignant sinonasal lesions.

OBJECTIVES: To explore the value of the synthetic MRI (SyMRI), combined with amide proton transfer-weighted (APTw) MRI for quantitative and morphologic assessment of sinonasal lesions, which could provide relative scale for the quantitative assessment of tissue properties. METHODS: A total of 80 patients (31 malignant and 49 benign) with sinonasal lesions, who underwent the SyMRI and APTw examination, were retrospectively analyzed. Quantitative parameters (T1, T2, proton density (PD)) and APT % were obtained through outlining the region of interest (ROI) and comparing the two groups utilizing independent Student t test or a Wilcoxon test. Receiver operating characteristic curve (ROC), Delong test, and logistic regression analysis were performed to assess the diagnostic efficiency of one-parameter and multiparametric models. RESULTS: SyMRI-derived mean T1, T2, and PD were significantly higher and APT % was relatively lower in benign compared to malignant sinonasal lesions (p < 0.05). The ROC analysis showed that the AUCs of the SyMRI-derived quantitative (T1, T2, PD) values and APT % ranged from 0.677 to 0.781 for differential diagnosis between benign and malignant sinonasal lesions. The T2 values showed the best diagnostic performance among all single parameters for differentiating these two masses. The AUCs of combined SyMRI-derived multiple parameters with APT % (AUC = 0.866) were the highest than that of any single parameter, which was significantly improved (p < 0.05). CONCLUSION: The combination of SyMRI and APTw imaging has the potential to reflect intrinsic tissue characteristics useful for differentiating benign from malignant sinonasal lesions. CLINICAL RELEVANCE STATEMENT: Combining synthetic MRI with amide proton transfer-weighted imaging could function as a quantitative and contrast-free approach, significantly enhancing the differentiation of benign and malignant sinonasal lesions and overcoming the limitations associated with the superficial nature of endoscopic nasal sampling. KEY POINTS: • Synthetic MRI and amide proton transfer-weighted MRI could differentiate benign from malignant sinonasal lesions based on quantitative parameters. • The diagnostic efficiency could be significantly improved through synthetic MRI + amide proton transfer-weighted imaging. • The combination of synthetic MRI and amide proton transfer-weighted MRI is a noninvasive method to evaluate sinonasal lesions.

Optical Limiting Response of Porous Carbon Dispersions.

With the wide application of intense lasers, the protection of human eyes and detectors from laser damage is becoming more and more strict. In this paper, we study the nonlinear optical limiting (OL) properties of porous carbon with a super large specific surface area (2.9 × 103 m2/g) using the nanosecond Z-scan technique. Compared to the traditional OL material C60, the porous carbon material shows an excellent broadband limiting effect, and the limiting thresholds correspond to 0.11 J/cm2 for 532 nm and 0.25 J/cm2 for 1064 nm pulses, respectively. The nonlinear scattering experiments showed that the OL behavior was mainly attributed to the nonlinear scattering effect, which is caused by the rapid growth and expansion of bubbles in the dispersion induced by laser irradiation, and the scattered light distribution is consistent with the results of Mie's scattering. These results suggest that porous carbon materials are expected to be applied to the field of laser protection in the future to further protect the human eye and precision optical instruments.

Glutamine Mitigates Oxidative Stress-Induced Matrix Degradation, Ferroptosis, and Pyroptosis in Nucleus Pulposus Cells via Deubiquitinating and Stabilizing Nrf2.

Aims: Intervertebral disc degeneration (IDD) is closely related to low back pain, which is a prevalent age-related problem worldwide; however, the mechanism underlying IDD is unknown. Glutamine, a free amino acid prevalent in plasma, is recognized for its anti-inflammatory and antioxidant properties in various diseases, and the current study aims to clarify the effect and mechanism of glutamine in IDD. Results: A synergistic interplay was observed between pyroptosis and ferroptosis within degenerated human disc specimens. Glutamine significantly mitigated IDD in both ex vivo and in vivo experimental models. Moreover, glutamine protected nucleus pulposus (NP) cells after tert-butyl hydroperoxide (TBHP)-induced pyroptosis, ferroptosis, and extracellular matrix (ECM) degradation in vitro. Glutamine protected NP cells from TBHP-induced ferroptosis by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitin-proteasome degradation and inhibiting lipid oxidation. Innovation and Conclusions: A direct correlation is evident in the progression of IDD between the processes of pyroptosis and ferroptosis. Glutamine suppressed oxidative stress-induced cellular processes, including pyroptosis, ferroptosis, and ECM degradation through deubiquitinating Nrf2 and inhibiting lipid oxidation in NP cells. Glutamine is a promising novel therapeutic target for the management of IDD.

Associations of Preoperative Nutritional Status and Sarcopenia With Mortality in Patients With Abdominal Aortic Aneurysm After Open and Endovascular Abdominal Aortic Aneurysm Repair: A Retrospective Study.

OBJECTIVE: The effect of preoperative malnutrition and sarcopenia on outcomes in patients with abdominal aortic aneurysm (AAA) after open surgical repair (OSR) and endovascular abdominal aortic aneurysm repair is undefined. The authors conducted the study to address this issue in this population. DESIGN: A retrospective observational study. SETTING: A large tertiary hospital. PARTICIPANTS: Patients with AAA who underwent OSR and endovascular aneurysm repair (EVAR). INTERVENTIONS: Evaluation of nutritional status (Nutritional Risk Screening 2002 [NRS 2002] and the Controlling Nutritional Status [CONUT] scores), muscle size (skeletal muscle index), and postoperative parameters. MEASUREMENTS AND MAIN RESULTS: A total of 199 patients were reviewed from January 2020 to December 2022. Patients weew categorized into group A (CONUT <4) and group B (CONUT ≥4) based on whether their CONUT scores were less than 4. The mortality (p = 0.004) and the incidence of Clavien-Dindo class III complications (p = 0.007) in group B were higher than those in group A. CONUT score was an independent risk factor for midterm mortality (hazard ratio 1.329; 95% CI, 1.104-1.697; p = 0.002) and Clavien-Dindo class III complications (odds ratio 1.225; 95% CI, 1.012-1.482; p = 0.037) according to univariate and multivariate analyses, whereas NRS 2002 score and sarcopenia were not. Kaplan-Meier curves showed a lower midterm survival rate in group B (log-rank p < 0.001). CONCLUSION: In patients with AAA undergoing OSR or EVAR, a CONUT score ≥4 was associated with increased Clavien-Dindo class III complications and mortality. Preoperative nutritional status should be evaluated and optimized in this high-risk population.

Retrospective analysis of clinical characteristics and outcomes of patients with carcinoma of unknown primary from three tertiary centers in Australia.

BACKGROUND: Carcinoma of unknown primary (CUP) remains an important tumor entity and a disproportionate cause of cancer mortality. Little is known about the contemporary clinical characteristics, treatment patterns, and outcomes of CUP patients based on updated international classification guidelines. We evaluated a contemporary CUP cohort to provide insight into current clinical practice and the impact of tissue of origin assignment, site-specific and empirical therapy in a real-world setting. METHODS: We conducted a retrospective cohort study of CUP patients, as defined by the updated European Society of Medical Oncology (ESMO) 2023 guidelines, across three tertiary referral centers in Australia between 2015 and 2022. We analyzed clinical characteristics, treatment patterns, and survival outcomes using the Kaplan-Meier method and Cox regression proportional hazard model between favorable and unfavorable risk groups. RESULTS: We identified a total of 123 CUP patients (n = 86 unfavorable, n = 37 favorable risk as per the 2023 ESMO guidelines). Sixty-four patients (52%) were assigned a tissue of origin by the treating clinician. Median progression free survival (PFS) was 6.8 (95% confidence interval (CI) 5.1-12.1) months and overall survival (OS) 10.2 (95% CI 6.0-18.5) months. Unfavorable risk (hazard ratio [HR] 2.9, p = 0.006), poor performance status (HR 2.8, p < 0.001), and non-squamous histology (HR 2.5, p < 0.05) were associated with poor survival outcome. A total of 70 patients (57%) proceeded to systemic therapy. In patients with non-squamous histology and unfavorable risk, site-specific therapy compared to empirical chemotherapy did not improve outcome (median OS 8.2 vs. 11.8 months, p = 0.7). CONCLUSIONS: In this real-world cohort, CUP presentations were heterogenous. Overall survival and rates of systemic treatment were poor. Poor performance status and unfavorable risk were associated with worse survival. For most patients, site-specific therapy did not improve survival outcome. Improved and timely access to diagnostic tests and therapeutics for this group of patients is urgently required.

Novel Risk Factors for Cervical Facet Joint Degeneration in the Subaxial Cervical Spine: Correlation with Cervical Sagittal Alignment and Bone Mineral Density.

OBJECTIVE: The impact of cervical sagittal alignment on cervical facet joint degeneration (CFD) and the risk factors for CFD in patients with degenerative cervical myelopathy (DCM) were investigated in the current study. METHODS: A total of 250 surgical patients with DCM were recruited. The clinical data and radiographical characteristics, including CFD, cervical sagittal balance parameters, Hounsfield unit (HU) values, disc degeneration (DD), and modic change, were collected. The detailed correlation between these characteristics and CFD was analyzed. Characteristics, including CFD, were compared among the various cervical alignment types and different CFD groups. Finally, the risk factors for CFD were revealed via logistic regression. RESULTS: CFD was prevalent in DCM patients. Age, cervical sagittal vertical axis (cSVA), range of motion, T1 slope, thoracic inlet angle, DD, HU value, and modic change correlated with CFD segmentally and globally (P < 0.05). The lordosis and sigmoid types had a significantly higher CFD prevalence (P < 0.05). Furthermore, the average CFD threshold for the severe CFD group was 1.625 (area under the curve, 0.958). Additionally, 167 patients with average CFD <1.625 and 83 patients with CFD of ≥1.625 were classified into the mild CFD group and severe CFD group, respectively. Finally, multivariate analysis was performed, and age, cSVA, HU value, modic change, and DD were determined to be independent risk factors for CFD. CONCLUSIONS: The load distribution tends to shift to a more shear-like pattern in the sigmoid and kyphosis types and in those with a higher cSVA, thereby promoting CFD. Aging, cervical malalignment, low bone mineral density, DD, and modic change were revealed to result in high risks of CFD.