Superenhancer drives a tumor-specific splicing variant of MARCO to promote triple-negative breast cancer progression.

The transcription variation, leading to various forms of transcripts and protein diversity, remains largely unexplored in triple-negative breast cancers (TNBCs). Here, we presented a comprehensive analysis of RNA splicing in breast cancer to illustrate the biological function and clinical implications of tumor-specific transcripts (TSTs) arising from these splicing junctions. Aberrant RNA splicing or TSTs were frequently harbored in TNBC and were correlated with a poor outcome. We discovered a tumor-specific splicing variant of macrophage receptor with collagenous structure-TST (MARCO-TST), which was distinguished from myeloid cell-specific wild-type MARCO. MARCO-TST expression was associated with poor outcomes in TNBC patients and could promote tumor progression in vitro and in vivo. Mechanically, MARCO-TST interacted with PLOD2 and enhanced the stability of HIF-1α, which resulted in the metabolic dysregulation of TNBC to form a hypoxic tumor microenvironment. MARCO-TST was initiated from a de novo alternative transcription initiation site that was activated by a superenhancer. Tumors with MARCO-TST expression conferred greater sensitivity to bromodomain and extraterminal protein inhibitors. This treatment strategy was further validated in patient-derived organoids. In conclusion, our results revealed the transcription variation landscape of TNBC, highlighting MARCO-TST as a crucial oncogenic transcript and therapeutic target.

Dynamic Nanocrystal Superlattices with Thermally Triggerable Lubricating Ligands.

The size-dependent and collective physical properties of nanocrystals (NCs) and their self-assembled superlattices (SLs) enable the study of mesoscale phenomena and the design of metamaterials for a broad range of applications. However, the limited mobility of NC building blocks in dried NCSLs often hampers the potential for employing postdeposition methods to produce high-quality NCSLs. In this study, we present tailored promesogenic ligands that exhibit a lubricating property akin to thermotropic liquid crystals. The lubricating ability of ligands is thermally triggerable, allowing the dry solid NC aggregates deposited on the substrates with poor ordering to be transformed into NCSLs with high crystallinity and preferred orientations. The interplay between the dynamic behavior of NCSLs and the molecular structure of the ligands is elucidated through a comprehensive analysis of their lubricating efficacy using both experimental and simulation approaches. Coarse-grained molecular dynamic modeling suggests that a shielding layer from mesogens prevents the interdigitation of ligand tails, facilitating the sliding between outer shells and consequently enhancing the mobility of NC building blocks. The dynamic organization of NCSLs can also be triggered with high spatial resolution by laser illumination. The principles, kinetics, and utility of lubricating ligands could be generalized to unlock stimuli-responsive metamaterials from NCSLs and contribute to the fabrication of NCSLs.

Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery.

Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly established itself in cancer research. To highlight its versatility, we delved into how melatonin interacts with key signaling pathways, such as the Wnt/ß-Catenin, PI3K, and NF-κB pathways, which play foundational roles in tumor development and progression. Notably, melatonin can intricately modulate these pathways, potentially affecting various cellular functions such as apoptosis, metastasis, and immunity. Additionally, a comprehensive review of current clinical studies provides a dual perspective. These studies confirm melatonin's potential in cancer management but also underscore its inherent limitations, particularly its limited bioavailability, which often relegates it to a supplementary role in treatments. Despite this limitation, there is an ongoing quest for innovative solutions and current advancements include the development of melatonin derivatives and cutting-edge delivery systems. By synthesizing the past, present, and future, this review provides a detailed overview of melatonin's evolving role in oncology, positioning it as a potential cornerstone in future cancer therapeutics.

Phospholipase D Mediates Glutamine-Induced mTORC1 Activation to Promote Porcine Intestinal Epithelial Cell Proliferation.

BACKGROUND: The intestinal epithelium is one of the fastest self-renewal tissues in the body, and glutamine plays a crucial role in providing carbon and nitrogen for biosynthesis. In intestinal homeostasis, phosphorylation-mediated signaling networks that cause altered cell proliferation, differentiation, and metabolic regulation have been observed. However, our understanding of how glutamine affects protein phosphorylation in the intestinal epithelium is limited, and identifying the essential signaling pathways involved in regulating intestinal epithelial cell growth is particularly challenging. OBJECTIVES: This study aimed to identify the essential proteins and signaling pathways involved in glutamine's promotion of porcine intestinal epithelial cell proliferation. METHODS: Phosphoproteomics was applied to describe the protein phosphorylation landscape under glutamine treatment. Kinase-substrate enrichment analysis was subjected to predict kinase activity and validated by qRT-PCR and Western blotting. Cell Counting Kit-8, glutamine rescue experiment, chloroquine treatment, and 5-fluoro-2-indolyl deschlorohalopemide inhibition assay revealed the possible underlying mechanism of glutamine promoting porcine intestinal epithelial cell proliferation. RESULTS: In this study, glutamine starvation was found to significantly suppress the proliferation of intestinal epithelial cells and change phosphoproteomic profiles with 575 downregulated sites and 321 upregulated sites. Interestingly, phosphorylation of eukaryotic initiation factor 4E-binding protein 1 at position Threonine70 was decreased, which is a crucial downstream of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Further studies showed that glutamine supplementation rescued cell proliferation and mTORC1 activity, dependent on lysosomal function and phospholipase D activation. CONCLUSION: In conclusion, glutamine activates mTORC1 signaling dependent on phospholipase D and a functional lysosome to promote intestinal epithelial cell proliferation. This discovery provides new insight into regulating the homeostasis of the intestinal epithelium, particularly in pig production.

Population Balance Equations for Reactive Separation in Polymer Upcycling.

Many polymer upcycling efforts aim to convert plastic waste into high-value liquid hydrocarbons. However, the subsequent cleavage of middle distillates to light gases can be problematic. The reactor often contains a vapor phase (light gases and middle distillates) and a liquid phase (molten polymers and waxes with a suspended or dissolved catalyst). Because the catalyst resides in the liquid phase, middle distillates that partition into the vapor phase are protected against further cleavage into light gases. In this paper, we consider a simple reactive separation strategy, in which a gas outflow removes the volatile products as they form. We combine vapor-liquid equilibrium models and population balance equations (PBEs) to describe polymer upcycling in a two-phase semibatch reactor. The results suggest that the temperature, headspace volume, and flow rate of the reactor can be used to tune selectivity toward the middle distillates, in addition to the molecular mechanism of catalysis. We anticipate that two-phase reactor models will be important in many polymer upcycling processes and that reactive separation strategies will provide ways to boost the yield of the desired products in these cases.

A multiangle polarised imaging-based method for thin section segmentation.

The most crucial task of petroleum geology is to explore oil and gas reservoirs in the deep underground. As one of the analysis techniques in petroleum geological research, rock thin section identification method includes particle segmentation, which is one of the key steps. A conventional sandstone thin section image typically contains hundreds of mineral particles with blurred boundaries and complex microstructures inside the particles. Moreover, the complex lithology and low porosity of tight sandstone make traditional image segmentation methods unsuitable for solving the complex thin section segmentation problems. This paper combines petrology and image processing technologies. First, polarised sequence images are aligned, and then the images are transformed to the HSV colour space to extract pores. Second, particles are extracted according to their extinction characteristics. Last, a concavity and corner detection matching method is used to process the extracted particles, thereby completing the segmentation of sandstone thin section images. The experimental results show that our proposed method can more accurately fit the boundaries of mineral particles in sandstone images than existing image segmentation methods. Additionally, when applied in actual production scenarios, our method exhibits excellent performance, greatly improving thin section identification efficiency and significantly assisting experts in identification.

The efficacy of nutritional screening indexes in predicting the incidence of osteosarcopenia and major osteoporotic fracture in the elderly.

INTRODUCTION: The effect of nutritional status on osteosarcopenia (OS) and major osteoporotic fracture (MOF) among the elderly is still unclear. So we aimed to compare the efficacy of the Mini-Nutrition Assessment-Short Form (MNA-sf), the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT) for predicting OS and MOF among the elderly. MATERIALS AND METHODS: A total of 409 participants were enrolled in this prospective study. Blood biochemical indexes, nutritional status, and bone- and muscle-related examinations were assessed at initial visit to the outpatient. Participants were divided into 4 groups: (1) control; (2) osteopenia/osteoporosis; (3) sarcopenia; (4) osteosarcopenia, and then followed for 5 years, recording the occurrence time of MOF. RESULTS: The frequency values of osteopenia/osteoporosis, sarcopenia, and OS, at baseline, were respectively 13.4, 16.1, and 12% among the study samples. Correlation analysis showed that nutritional status scores were associated with body mass index, handgrip strength, albumin, bone mineral density, and physical functions. According to multivariate models, poor nutritional status was significantly associated with a higher risk of OS and MOF (P < 0.05). Survival analysis showed that the MOF rate in malnutrition group was significantly higher than normal nutrition group (P < 0.05). The receiver operator characteristic curve shows that the value of MNA-sf to diagnose OS and MOF is greater (P < 0.05). CONCLUSION: The poor nutritional status was associated with a higher risk of both OS and MOF. MNA-sf showed a superior diagnostic power for OS and MOF among the elderly. Early nutrition assessments and interventions may be key strategies to prevent OS and fractures.

Changes of intestinal barrier in the process of intestinal inflammation induced by Aeromonas hydrophila in snakehead (Channa argus).

Bacterial intestinal inflammation frequently occurs in cultured fish. Nevertheless, research on intestinal barrier dysfunction in the process of intestinal inflammation is deficient. In this study, we explored the changes of intestinal inflammation induced by Aeromonas hydrophila (A. hydrophila) in snakehead and the relationship between intestinal barrier and inflammation. Snakehead [(13.05 ± 2.39) g] were infected via anus with A. hydrophila. Specimens were collected for analysis at 0, 1, 3, 7 and 21 d post-injection. The results showed that with the increase of exposure time, the hindgut underwent stages of normal function, damage, damage deterioration, repair and recovery. Relative to 0 d, the levels of IL-1ß and TNF-α in serum, and the expression of nod1, tlr1, tlr5, nf-κb, tnf-α and il-1ß in intestine were significantly increased, and showed an upward then downward pattern over time. However, the expression of tlr2 and il-10 were markedly decreased, and showed the opposite trend. In addition, with the development of intestinal inflammation, the diversity and richness of species, and the levels of phylum and genus in intestine were obviously altered. The levels of trypsin, LPS, AMS, T-SOD, CAT, GPx, AKP, LZM and C3 in intestine were markedly reduced, and displayed a trend of first decreasing and then rebounding. The ultrastructure observation showed that the microvilli and tight junction structure of intestinal epithelial cells experienced normal function initially, then damage, and finally recovery over time. The expression of claudin-3 and zo-1 in intestine were significantly decreased, and showed a trend of first decreasing and then rebounding. Conversely, the expression of mhc-i, igm, igt and pigr in intestine were markedly increased, and displayed a trend of increasing first and then decreasing. The above results revealed the changes in intestinal barrier during the occurrence and development of intestinal inflammation, which provided a theoretical basis for explaining the relationship between the two.

Inducing abundant magnetic phases and enhancing magnetic stability by edge modifications and physical regulations for NiI2 nanoribbons.

Recently, a magnetic semiconducting NiI2 monolayer was successfully fabricated. To obtain richer magneto-electronic properties and find new physics for NiI2, we studied the zigzag-type NiI2 nanoribbon (ZNiI2NR) with edges modified by different concentrations of H and/or O atoms. Results show that these ribbons hold a higher energy stability, thermal stability, and magnetic stability, and the Curie temperature can be increased to 143 from 15 K for the bare-edged ribbons. They feature a half-semiconductor, bipolar magnetic semiconductor, or half-metal, depending on the edge-terminated atomic species and concentrations, and are closely related to the ribbon edge states, impurity bands or hybridized bands. By applying strain or an electric field, ribbons can achieve a reversible multi-magnetic phase transition among a bipolar magnetic semiconductor, half-semiconductor, half-metal, and magnetic metal. This is because strain changes the Ni-I bond length, resulting in a variation of bond configurations (weight of ionic and covalent bonds) and the number of unpaired electrons. The compressive strain can increase the Curie temperature because it makes the edged Ni-I-Ni bond angle closer to 90°, leading to the FM d-p-d superexchange interaction being increased. The electric field varies the magnetic phase because it alters the electrostatic potential of the ribbon edges, and the Curie temperature is enhanced under the electric field because the ribbon is changed to a metallic state (half-metal or magnetic metal), in which the magnetic Ni atoms satisfy the Stoner criterion and hold a large magnetic exchange coefficient and electron state density at the Fermi surface.

Screening and isolation of quorum sensing inhibitors of Pseudomonas aeruginosa from Phellodendron amurense extracts using bio-affinity chromatography.

Drug-resistant bacterial infections pose a significant challenge in the field of bacterial disease treatment. Finding new antibacterial pathways and targets to combat drug-resistant bacteria is crucial. The bacterial quorum sensing (QS) system regulates the expression of bacterial virulence factors. Inhibiting bacterial QS and reducing bacterial virulence can achieve antibacterial therapeutic effects, making QS inhibition an effective strategy to control bacterial pathogenicity. This article mainly focused on the PqsA protein in the QS system of Pseudomonas aeruginosa. An affinity chromatography medium was developed using the SpyTag/SpyCatcher heteropeptide bond system. Berberine, which can interact with the PqsA target, was screened from Phellodendron amurense by affinity chromatography. We characterized its structure, verified its inhibitory activity on P. aeruginosa, and preliminarily analyzed its mechanism using molecular docking technology. This method can also be widely applied to the immobilization of various protein targets and the effective screening of active substances.

Free-space coupled, large-active-area superconducting microstrip single-photon detector for photon-counting time-of-flight imaging.

Numerous applications at the photon-starved regime require a free-space coupling single-photon detector with a large active area, low dark count rate (DCR), and superior time resolutions. Here, we developed a superconducting microstrip single-photon detector (SMSPD), with a large active area of 260 µm in diameter, a DCR of ∼5k c p s, and a low time jitter of ∼171p s, operated at a near-infrared of 1550 nm and a temperature of ∼2.0K. As a demonstration, we applied the detector to a single-pixel galvanometer scanning system and successfully reconstructed the object information in depth and intensity using a time-correlated photon counting technology.

Bridging the gap in managing dry eye disease: a consensus report by the Taiwan society of cataract and refractive surgeons.

BACKGROUND: An impaired ocular surface presents substantial challenges in terms of planning for cataract surgery. As a multifactorial ocular disorder, dry eye disease (DED) is common in the general population and prevalent in patients scheduled for lens replacement surgery. Cataract surgery can exacerbate DED and worsen several ocular parameters. Timely diagnosis and appropriate treatment of DED are vital to ensuring positive ophthalmic surgical outcomes. This consensus report of the Taiwan Society of Cataract and Refractive Surgeons (TSCRS) regarding the management of DED before, during, and after cataract surgery highlights the gaps between clinical guidelines and several aspects of DED, including diagnostic testing, diagnostic criteria, and clinical practice treatment. METHODS: An expert panel of five specialists in the field of ophthalmology was recruited to develop consensus statements regarding the management of DED in both the general population and in patients undergoing cataract surgery in Taiwan. Two separate meetings of the five specialists, who were endorsed by the TSCRS, were convened for this purpose. A survey questionnaire consisting of binary or multiple-choice questions was developed through a consensus-driven formulation process. A percentage value was calculated for each statement, and a minimum of 60% agreement (equivalent to three out of five members) was required to achieve consensus. The second discussion meeting involved the presentation of the finalized consensus statements and concluded the consensus development process. Lastly, the finalized consensus statements were approved by all the experts, and the formulated recommendations for DED in the general population and prospective cataract surgery patients were accordingly presented. RESULTS: The optimal algorithm for managing DED in the general population and in patients scheduled for cataract surgery was developed to address the unmet needs of this cohort in Taiwan. CONCLUSION: This report provides recommendations for managing dry eye disease. It is essential to screen and confirm DED through endorsed questionnaires and tests and then diagnose it. Treatment and management of DED should follow a stepwise approach. Screening and diagnosing DED is also recommended before cataract surgery. After cataract surgery, relatively aggressive treatment strategies are recommended to manage DED effectively.

Evaluating the risk of new-onset glaucoma in chronic kidney disease patients: a nationwide cohort study.

BACKGROUND: A better understanding of the association between chronic kidney disease (CKD) and glaucoma is required to optimize clinical outcomes. Therefore, this study aimed to investigate the association of chronic kidney disease (CKD) with new diagnoses of glaucoma over time from January 2009 to December 2019. METHOD: This retrospective propensity-matched cohort study utilizing Taiwanese electronic health records examined the incidence of newly diagnosed glaucoma in patients with and without chronic kidney disease (CKD). The exposure variable was the diagnosis of CKD, identified through diagnostic codes. The primary outcome was the incidence of new-onset glaucoma. Subgroup analyses on glaucoma risk included age, gender, comorbidities, glaucoma subtypes, and dialysis status. Statistical analyses included Kaplan-Meier analysis, Cox proportional hazards models, and Poisson regression models, with the associated hazard ratios and confidence intervals reported. RESULTS: Seven hundred twenty-three thousand two hundred sixteen patients with CKD (42.3% female; mean [SD] age at index, 66.3 [15.6] years) and 723,216 patients without CKD (42.3% female; mean [SD] age at index, 66.3 [15.7]) were recruited. We showed a significantly increased risk of glaucoma irrespective of subtypes in CKD patients compared to those without CKD (HR: 1.29 [CI: 1.26-1.32], p < 0.001). Kaplan-Meier curves revealed a significantly increased glaucoma risk in both the dialytic subtype and non-dialytic CKD patients when compared to their non-CKD counterparts (p < 0.001). We also showed that all genders (aHR 1.17 [CI: 1.13-1.21] for females vs. aHR 1.39 [CI:1.35-1.43] for males), all ages (< = 49: aHR 1.49 [CI: 1.37-1.62]; 50-59: aHR 1.48 [CI: 1.40-1.56]; 60-69: aHR 1.30 [CI: 1.25-1.6]; 70-79: aHR 1.21 [CI: 1.17-1.26]; > 80: aHR 1.29 [CI: 1.21-1.37]); all income brackets and all urbanization status were associated with significantly increased risk of glaucoma from among the CKD cohort when compared to their respective non-CKD cohort (p < 0.001). CONCLUSIONS: Our cohort study spanning 12 years showed an elevated glaucoma risk following a CKD diagnosis compared to a frequency-matched non-CKD cohort. Our findings have relevance for the clinical practice of at-risk CKD patients. TRIAL REGISTRATION: Due to the retrospective nature of the study, no registration was necessary.

A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment.

The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded clinical application. Herein, BPRCX807, known as a safe, selective, and potent CXCR4 antagonist, has been designed and experimentally realized. In in vitro and in vivo hepatocellular carcinoma mouse models it can significantly suppress primary tumor growth, prevent distant metastasis/cell migration, reduce angiogenesis, and normalize the immunosuppressive tumor microenvironment by reducing tumor-associated macrophages (TAMs) infiltration, reprogramming TAMs toward an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. Although BPRCX807 treatment alone prolongs overall survival as effectively as both marketed sorafenib and anti-PD-1, it could synergize with either of them in combination therapy to further extend life expectancy and suppress distant metastasis more significantly.

Screening of inhibitors on successful covalent tyrosinase coupling with help from SpyBank.

Microbial metabolites are an important source of tyrosinase (TYR) inhibitors because of their rich chemical diversity. However, because of the complex metabolic environment of microbial products, it is difficult to rapidly locate and identify natural TYR inhibitors. Affinity-based ligand screening is an important method for capturing active ingredients in complex samples, but ligand immobilization is an important factor affecting the screening process. In this paper, TYR was used as ligand, and the SpyTag/SpyCatcher coupling system was used to rapidly construct affinity chromatography vectors for screening TYR inhibitors and separating active components from complex samples. We successfully expressed SpyTag-TYR fusion protein and SpyCatcher protein, and incubated SpyCatcher protein with epoxy-activated agarose. The SpyTag-TYR protein was spontaneously coupled with SpyCatcher to obtain an affinity chromatography filler for immobilization of TYR, and the performance of the packaging material was characterized. Finally, compound 1 with enzyme inhibitory activity was successfully obtained from the fermentation product of marine microorganism C. Through HPLC, MS, 1H NMR and 13C NMR analyses, its structure was deduced as azelaic acid, and its activity was analyzed. The results showed that this is a feasible method for screening TYR inhibitors in complex systems.

A direct healthcare cost analysis of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

PURPOSE: We have previously published a retrospective matched-case control study comparing the effect of recombinant LH (r-hLH) versus highly purified human menopausal gonadotropin (hMG) supplementation on the follicle-stimulating hormone (FSH) during controlled ovarian hyperstimulation (COH) in the GnRH-antagonist protocol. The result from that study showed that the cumulative live birth rate (CLBR) was significantly higher in the r-hLH group (53% vs. 64%, p = 0.02). In this study, we aim to do a cost analysis between these two groups based on our previous study. METHODS: The analysis consisted of 425 IVF and ICSI cycles in our previous study. There were 259 cycles in the r-hFSH + hMG group and 166 cycles in the r-hFSH + r-hLH group. The total cost related to the treatment of each patient was recorded. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed and created. RESULTS: The total treatment cost per patient was significantly higher in the r-hFSH + r-hLH group than in the r-hFSH + hMG group ($4550 ± 798.86 vs. $4290 ± 734.6, p = 0.003). However, the mean cost per live birth in the r-hFSH + hMG group was higher at $8052, vs. $7059 in the r-hFSH + r-hLH group. The CEAC showed that treatment with hFSH + r-hLH proved to be more cost-effective than treatment with r-hFSH + hMG. Willingness-to-pay was evident when considering a hypothetical threshold of $18,513, with the r-hFSH + r-hLH group exhibiting a 99% probability of being considered cost-effective. CONCLUSION: The cost analysis showed that recombinant LH is more cost-effective than hMG supplementation on r-hFSH during COH in the GnRH-antagonist protocol.

Ototoxicity among cisplatin, carboplatin, and oxaliplatin in zebrafish model.

Platinum-based antineoplastic drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various cancers. Ototoxicity is a common adverse effect of platinum-based drugs. Ototoxicity leads to irreversible hearing impairment. We hypothesize that different platinum-based drugs exhibit varying ototoxic concentrations, time effects, and ototoxic mechanisms. We tested this hypothesis by using a zebrafish model (pvalb3b: TagGFP) to assess the viability of hair cells collected from zebrafish larvae. Cisplatin, carboplatin, and oxaliplatin were administered at dosages of 100, 200, or 400 µM, and the ototoxic effects of these drugs were assessed 1, 2, or 3 h after administration. Fm4-64 and a TUNEL assay were used to label the membranes of living hair cells and to detect cell apoptosis, respectively. We observed that >50% of hair cells were damaged at 1 h after cisplatin (100 µM) exposure, and this ototoxic effect increased at higher dosages and over time. Owing to the smaller ototoxic effects of carboplatin and oxaliplatin, we conducted higher-strength and longer-duration experiments with these drugs. Neither carboplatin nor oxaliplatin was obviously ototoxic, even at 1600 µM and after 6 h. Moreover, only cisplatin damaged the membranes of the hair cells. Cell apoptosis and significantly increased antioxidant gene expression were observed in only the cisplatin group. In conclusion, cisplatin significantly damages sensory hair cells and has notable dosage and time effects. Carboplatin and oxaliplatin are less ototoxic than cisplatin, likely due to having different ototoxic mechanisms than cisplatin.

Pathways to motherhood: A single-center retrospective study on fertility preservation and reproductive outcomes in patients with breast cancer.

BACKGROUND: Breast cancer treatments often have negative effects on fertility, which pose challenges among patients who want to be parents in the future. This study aimed to examine the efficacy of oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation in patients with breast cancer. METHODS: This retrospective review evaluated 42 patients with breast cancer who underwent fertility preservation at our center from January 2012 to December 2022. This review encompassed the demographic characteristics of the patients, cancer stages, treatment details, and types of fertility preservation procedures and their outcomes. RESULTS: The average age at disease diagnosis was 33.4 years. Approximately 90.4% of patients presented with early-stage cancer (≤2). Of 42 patients, 26 underwent oocyte cryopreservation; 17, embryo cryopreservation; and 2, ovarian tissue cryopreservation. Further, three patients received mixed treatment. The overall live birth rate was 63.2%. There are more live births in embryo cryopreservation group. The successful pregnancy group was significantly younger and had a remarkably higher quantity of preserved oocytes/embryos than the nonsuccessful pregnancy group. The oocyte and embryo utilization rates in cryopreservation were 7.69% and 52.94%, respectively. These findings underscored the importance of prompt, informed discussions about fertility preservation options. CONCLUSION: Fertility preservation in patients with breast cancer have promising reproductive outcomes, with embryo cryopreservation being particularly effective. Prompt counseling and individualized fertility preservation strategies are important for improving the likelihood of posttreatment pregnancy. Nevertheless, future research on the long-term psychological and emotional effects of different fertility preservation methods must be performed.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group. Design, Setting, and Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. Exposure: AHIs. Main Outcomes and Measures: Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Results: Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. Conclusions and Relevance: In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Serum NfL and GFAP as biomarkers of progressive neurodegeneration in TBI.

BACKGROUND: We examined spatial patterns of brain atrophy after mild, moderate, and severe traumatic brain injury (TBI), the relationship between progression of brain atrophy with initial traumatic axonal injury (TAI), cognitive outcome, and with serum biomarkers of brain injury. METHODS: A total of 143 patients with TBI and 43 controls were studied cross-sectionally and longitudinally up to 5 years with multiple assessments, which included brain magnetic resonance imaging, cognitive testing, and serum biomarkers. RESULTS: TBI patients showed progressive volume loss regardless of injury severity over several years, and TAI was independently associated with accelerated brain atrophy. Cognitive performance improved over time. Higher baseline serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were associated with greater rate of brain atrophy over 5 years. DISCUSSSION: Spatial patterns of atrophy differ by injury severity and TAI is associated with the progression of brain atrophy. Serum NfL and GFAP show promise as non-invasive prognostic biomarkers of progressive neurodegeneration in TBI. HIGHLIGHTS: In this longitudinal study of patient with mild, moderate, and severe traumatic brain injury (TBI) who were assessed with paired magnetic resonance imaging (MRI), blood biomarkers, and cognitive assessments, we found that brain atrophy after TBI is progressive and continues for many years even after a mild head trauma without signs of brain injury on conventional MRI. We found that spatial pattern of brain atrophy differs between mild, moderate, and severe TBI, where in patients with mild TBI , atrophy is mainly seen in the gray matter, while in those with moderate to severe brain injury atrophy is predominantly seen in the subcortical gray matter and whiter matter. Cognitive performance improves over time after a TBI. Serum measures of neurofilament light or glial fibrillary acidic protein are associated with progression of brain atrophy after TBI.