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We aimed to develop, train, and validate machine learning models for predicting preterm birth (<37 weeks' gestation) in singleton pregnancies at different gestational intervals. Models were developed based on complete data from 22,603 singleton pregnancies from a prospective population-based cohort study that was conducted in 51 midwifery clinics and hospitals in Wenzhou City of China between 2014 and 2016. We applied Catboost, Random Forest, Stacked Model, Deep Neural Networks (DNN), and Support Vector Machine (SVM) algorithms, as well as logistic regression, to conduct feature selection and predictive modeling. Feature selection was implemented based on permutation-based feature importance lists derived from the machine learning models including all features, using a balanced training data set. To develop prediction models, the top 10%, 25%, and 50% most important predictive features were selected. Prediction models were developed with the training data set with 5-fold cross-validation for internal validation. Model performance was assessed using area under the receiver operating curve (AUC) values. The CatBoost-based prediction model after 26 weeks' gestation performed best with an AUC value of 0.70 (0.67, 0.73), accuracy of 0.81, sensitivity of 0.47, and specificity of 0.83. Number of antenatal care visits before 24 weeks' gestation, aspartate aminotransferase level at registration, symphysis fundal height, maternal weight, abdominal circumference, and blood pressure emerged as strong predictors after 26 completed weeks. The application of machine learning on pregnancy surveillance data is a promising approach to predict preterm birth and we identified several modifiable antenatal predictors.
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Paraganglioma is derived from the paraganglia tissue in the neck, along the sympathetic trunk, and in the pelvis. Paraganglioma has malignant potential and can metastasize to remote organs such as the liver, lungs, and bones. Most metachronous metastases occur within several years after the initial diagnosis of paraganglioma. Here, we report the case of a 71-year-old male patient who developed bony metastasis 52 years after the resection of a large paraganglioma at the aortic bifurcation. The biopsy-proven paraganglioma metastasis to the lesser trochanter of left femur presented as an avulsion fracture. His normetanephrine level was elevated. DOTATATE PET (positron emission tomography) did not find any other metastatic lesions. The bony metastasis was treated with radiation therapy. We believe that the patient had one of the longest gaps ever reported, 52 years, between the initial diagnosis and metastasis of paraganglioma. This case highlights the importance of long-term surveillance of patients with paraganglioma for metastasis.
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Glioblastoma (GBM) is an extremely aggressive tumor associated with a poor prognosis that impacts the central nervous system. Increasing evidence suggests an inherent association between glucose metabolism dysregulation and the aggression of GBM. Polo-like kinase 4 (PLK4), a highly conserved serine/threonine protein kinase, was found to relate to glioma progression and unfavorable prognosis. As revealed by the integration of proteomics and phosphoproteomics, PLK4 was found to be involved in governing metabolic processes and the PI3K/AKT/mTOR pathway. For the first time, this study supports evidence demonstrating that PLK4 activated PI3K/AKT/mTOR signaling through direct binding to AKT1 and subsequent phosphorylating AKT1 at S124, T308, and S473 to promote tumorigenesis and glucose metabolism in glioma. In addition, PLK4-mediated phosphorylation of AKT1 S124 significantly augmented the phosphorylation of AKT1 S473. Therefore, PLK4 exerted an influence on glucose metabolism by stimulating PI3K/AKT/mTOR signaling. Additionally, the expression of PLK4 protein exhibited a positive correlation with AKT1 phosphorylation in glioma patient tissues. These findings highlight the pivotal role of PLK4-mediated phosphorylation of AKT1 in glioma tumorigenesis and dysregulation of glucose metabolism.
Subject(s)
Glioblastoma , Glioma , Naphthalenes , Piperazines , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , TOR Serine-Threonine Kinases/metabolism , Glioma/genetics , Glioma/pathology , Phosphorylation , Glioblastoma/pathology , Carcinogenesis , Cell Transformation, Neoplastic , Glucose , Protein Serine-Threonine Kinases/metabolismABSTRACT
Hand, foot, and mouth disease is a serious public health problem, and the main pathogen is enterovirus 71 (EV71). Its capsid assembly mechanism including capsid protein processing has been widely studied. Full and empty capsids have different immunological efficacy. Therefore, tracking full/empty capsid ratio throughout the EV71 production process is important to ensure consistent product quality and proper dosing response. The analysis of full/empty capsid ratio of intact virus has been widely reported as well. A variety of techniques have been employed to evaluate the full/empty capsid ratios. However, there has not been a rapid, reproducible, and robust assay to determine the full/empty capsid ratios of final and in-process products. In this study, a novel assay based on capillary zone electrophoresis was established. The separation of full and empty species could be achieved within 10 min and the ratio of peak areas was used to calculate the full/empty capsid ratio directly. The results showed good reproducibility and linearity for the determination of full/empty capsid ratios.
Subject(s)
Enterovirus A, Human , Enterovirus A, Human/metabolism , Reproducibility of Results , Capsid Proteins , Capsid/metabolism , Protein Processing, Post-TranslationalABSTRACT
We present a case series of 3 patients who developed iatrogenic hypothalamic-pituitary-adrenal axis disruption while taking Artri King, an over-the-counter supplement marketed for joint pain that is reported to contain dexamethasone not listed on the supplement's label. Patient 1, a 58-year-old woman, presented with persistent hyponatremia, weight gain, proximal muscle weakness, dorsocervical fat pad, and new, red striae on her breast and abdomen in the setting of Artri King use. Her dexamethasone level was elevated (Table 1), confirming the suspicion of dexamethasone content in this supplement. Patient 2, a 55-year old woman, had presented with cushingoid features and a low morning cortisol level (Table 1) in the setting of Artri King use. Patient 3, a 59-year-old man, presented with poorly controlled diabetes in the setting of Artri King use and an elevated serum dexamethasone level. Supplements containing hidden glucocorticoids can cause not only iatrogenic Cushing syndrome, but also adrenal suppression, providing a diagnostic challenge for providers.
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Background/Objective: Clinical diagnosis of rare aggressive sellar malignancies requires a high index of suspicion. The objective was to report 2 patients with primary sellar atypical teratoid (AT)/rhabdoid tumor (RT) who presented with acute-onset headache and visual symptoms. Case Report: Patient 1 was a 45-year-old woman who presented with 3 weeks of headache and 1 week of eye pain and diplopia. Magnetic resonance imaging (MRI) identified a 2.2-cm sellar mass. Pituitary hormone testing showed elevated prolactin and suppressed luteinizing hormone, follicle-stimulating hormone, and estradiol levels. Patient 2 was a 32-year-old woman who presented with 1 month of headache and 1 week of diplopia. MRI showed a 2.1-cm sellar mass. Hormonal test results were reportedly unremarkable. Both patients did not have a significant medical history. They each underwent transsphenoidal resection. Surgical histology and molecular studies were consistent with primary sellar AT/RT. After surgery, patient 1 developed bilateral blindness and was lost to follow-up. Patient 2 developed hypopituitarism; her visual symptoms improved temporarily but recurred 2 weeks later. Pituitary MRI showed sellar recurrence. She underwent further debulking, but the tumor recurred promptly again. Despite radiation therapy, she died 4 months after the original presentation. Discussion: AT/RT appears to be the most aggressive sellar malignancy. Conclusion: Based on the 2 cases presented and the literature, I conclude that rapidly progressive headache with subsequent visual impairment in women with large sellar masses is almost pathognomonic of sellar AT/RT.
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Background: Documented symptomatic progression of a paraganglioma (PGL) over many years is unusual. Our objective is to report a young man with such an occurrence. Case Report: A 27-year-old male presented with headache, sweating, and palpitation. He had a history of cyanotic congenital heart disease. Five years before presentation, he had 24-hour urine metanephrines 43 mcg/d (25-222), vanillylmandelic acid 3 mg/d (<6), and homovanillic acid 2.4 mg/d (1.6-7.5) levels and a 3.13 cm mass in the upper aortocaval space. Subsequent imaging showed slow growth of the mass. On admission, his blood pressure was 197/134 mm Hg, heart rate was 163 beats per minute, respiratory rate was 25 per minute, and oxygen saturation was 76% on room air. His 24-hour urine normetanephrine level was 2644 mcg/d (81-667) while metanephrine was 405 mcg/d (55-320). Plasma free metanephrine level was 0.92 nmol/L (0-0.49) and normetanephrine was 11.85 nmol/L (0-0.89). DOTATATE positron emission tomography-computed tomography revealed a 4.3 × 3.1 × 4.9 cm mass with activity in the right upper aortocaval space. He was treated with Prazosin. Two months later, he underwent resection of the mass. Pathology diagnosed a 4.9 cm PGL. He had improvement in metanephrine levels. Discussion: PGL is diagnosed by documenting excess catecholamines and identifying a lesion on imaging. False negative laboratory testing is rare but can occur. Patients with cyanotic congenital heart disease have a greater risk of developing PGL. Conclusion: It is crucial to evaluate a patient for PGL if clinical conditions suggest catecholamine excess, especially if a retroperitoneal tumor has grown or the patient has risk factors.
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Direct arylation of the benzylic C(sp3)-H bond is one of the most straightforward strategies for the construction of multi-aryl methanes, owing to the extraordinary step and atom economy. In this paper, we developed the first metal-free arylation of the C(sp3)-H bond in 3-methylindoles, thereby providing rapid access to a range of diaryl- and triarylmethanes with two indole rings. Mechanistically, 3-indole imine methide serves as the key intermediate. Water plays a crucial role in this process, likely serving as a proton shuttle to facilitate the key 1,3-proton transfer step in this reaction and, thus, enhance the reaction efficiency.
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Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.
Subject(s)
Genetic Diseases, Inborn , Glucagon , Hypertension, Portal , Liver Transplantation , Female , Humans , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/surgery , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Glucagon/blood , Glucagon/genetics , Hypertension, Portal/blood , Hypertension, Portal/etiology , Hypertension, Portal/genetics , Hypertension, Portal/surgery , Hypertrophy/genetics , Liver Cirrhosis , Genetic Diseases, Inborn/blood , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/surgery , Pancreatic Diseases/genetics , Pancreatic Diseases/pathology , Pancreatic Diseases/surgery , Glucagon-Secreting Cells/pathologyABSTRACT
Skeletal muscle comprises a large, heterogeneous assortment of cell populations that interact to maintain muscle homeostasis, but little is known about the mechanism that controls myogenic development in response to artificial selection. Different pig (Sus scrofa) breeds exhibit distinct muscle phenotypes resulting from domestication and selective breeding. Using unbiased single-cell transcriptomic sequencing analysis (scRNA-seq), the impact of artificial selection on cell profiles is investigated in neonatal skeletal muscle of pigs. This work provides panoramic muscle-resident cell profiles and identifies novel and breed-specific cells, mapping them on pseudotime trajectories. Artificial selection has elicited significant changes in muscle-resident cell profiles, while conserving signs of generational environmental challenges. These results suggest that fibro-adipogenic progenitors serve as a cellular interaction hub and that specific transcription factors identified here may serve as candidate target regulons for the pursuit of a specific muscle phenotype. Furthermore, a cross-species comparison of humans, mice, and pigs illustrates the conservation and divergence of mammalian muscle ontology. The findings of this study reveal shifts in cellular heterogeneity, novel cell subpopulations, and their interactions that may greatly facilitate the understanding of the mechanism underlying divergent muscle phenotypes arising from artificial selection.
Subject(s)
Adipogenesis , Muscle, Skeletal , Humans , Animals , Mice , Phenotype , Muscle Development/genetics , RNA , MammalsABSTRACT
Background: Solid pseudopapillary neoplasms (SPNs) are uncommon tumors of low malignancy with a generally favorable prognosis, mostly originating from the pancreas. To date, 12 cases of SPNs with a primary ovarian origin (SPN-Os) have been reported globally, and their detailed characteristics have not been fully elucidated. Case description: We reported the 13th SPN-O case, which occurred in a 52-year-old woman with an 18.5 cm left ovarian mass. Four imaging methods, including ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography, were utilized before surgery. An elevated level of serum cancer antigen 125 was detected and a total hysterectomy plus bilateral salpingo-oophorectomy was performed. Microscopic examination revealed a typical solid pseudopapillary structure. The tumor cells were stained focally for pan-cytokeratin, synaptophysin, CD99 and CD10, while ß-catenin, vimentin and CD56 were diffusely expressed. The Ki-67 proliferation index was 3%, and immunohistochemical (IHC) staining for chromogranin-A, inhibin-a, and E-cadherin was negative. No evidence of recurrence or metastasis was observed by clinical and imaging data during a 5-month postoperative follow-up. Conclusion: This is a report of an unusual case of a primary ovarian SPN with an up-to-date review of SPN-Os. A minimum combination of imaging methods and IHC stains was proposed for SPN-Os, which may prove beneficial in clinical practice.
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This paper presents an innovative approach for predicting timing errors tailored to near-/sub-threshold operations, addressing the energy-efficient requirements of digital circuits in applications, such as IoT devices and wearables. The method involves assessing deep path activity within an adjustable window prior to the root clock's rising edge. By dynamically adapting the prediction window and supply voltage based on error detection outcomes, the approach effectively mitigates false predictions-an essential concern in low-voltage prediction techniques. The efficacy of this strategy is demonstrated through its implementation in a near-/sub-threshold 32-bit microprocessor system. The approach incurs only a modest 6.84% area overhead attributed to well-engineered lightweight design methodologies. Furthermore, with the integration of clock gating, the system functions seamlessly across a voltage range of 0.4 V-1.2 V (5-100 MHz), effectively catering to adaptive energy efficiency. Empirical results highlight the potential of the proposed strategy, achieving a significant 46.95% energy reduction at the Minimum Energy Point (MEP, 15 MHz) compared to signoff margins. Additionally, a 19.75% energy decrease is observed compared to the zero-margin operation, demonstrating successful realization of negative margins.
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In the photovoltaic community, short circuit current (Isc) of a current mismatched multijunction photovoltaic (MJPV) cell was usually thought to be limited by the lowest subcell photocurrent (Imin). However, under certain conditions for multijunction solar cells, Isc≠Imin was observed by researchers, while this effect has not been studied in multijunction laser power converters (MJLPCs). In this work, we provide an in-depth analysis of the formation mechanisms for the Isc of the MJPV cell by measuring I-V curves of the GaAs and InGaAs LPCs with different number of subcells and simulating the I-V curves with the reverse breakdown of each subcell considered. It is found that Isc of an N-junction PV cell can be theoretically equal to any current value within a range from a current lower than Imin to the maximum subcell photocurrent, which is up to the number of subcell current steps in the forward biased I-V curve. An MJPV cell with a constant Imin will demonstrate a higher Isc if it has more subcells, smaller subcell reverse breakdown voltage and smaller series resistance. As a result, Isc tends to be limited by the photocurrent of a subcell closer to the middle cell and is less sensitive to the optical wavelength than Imin. This should be another possible reason why the measured EQE of a multijunction LPC exhibits a wider spectrum width than the calculated Imin-based EQE, whereas this was usually attributed to the luminescent coupling effect merely.
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Background: Acetabular metastasis is a type of metastatic bone cancer, and it mainly metastasizes from cancers such as lung cancer, breast cancer, and renal carcinoma. Acetabular metastasis often causes severe pain, pathological fractures, and hypercalcemia which may seriously affect the quality of life of acetabular metastasis patients. Due to the characteristics of acetabular metastasis, there is no most suitable treatment to address it. Therefore, our study aimed to investigate a novel treatment technique to relieve these symptoms. Methods: Our study explored a novel technique to reconstruct the stability of the acetabular structure. A surgical robot was used for accurate positioning and larger-bore cannulated screws were accurately inserted under the robot's guidance. Then, the lesion was curetted and bone cement was injected through a screw channel to further strengthen the structure and kill tumor cells. Results: A total of five acetabular metastasis patients received this novel treatment technique. The data relating to surgery were collected and analyzed. The results found that this novel technique can significantly reduce operation time, intraoperative bleeding, visual analogue score scores, Eastern Cooperative Oncology Group scores, and postoperative complications (e.g., infection, implant loosening, hip dislocation) after treatment. Follow-up time ranged from 3 months to 6 months, and the most recent follow-up results showed that all patients survived and no acetabular metastasis progressed in any of the patients after surgery. Conclusion: Surgical robot-assisted tripod percutaneous reconstruction combined with the bone cement filling technique may be a novel and suitable treatment in acetabular metastasis patients. Our study may provide new insights into the treatment of acetabular metastasis.
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Background/Objective: Large amount of protein wasting such as in nephrotic syndrome is a rare cause of high levothyroxine (LT4) replacement dose requirement. A case has been reported here that demonstrates that protein-losing enteropathy is a novel and yet unrecognized cause of high LT4 replacement dose requirement. Case Report: A 21-year-old man with congenital heart disease was found to have primary hypothyroidism and started LT4 replacement. His weight was approximately 60 kg. Nine months later, while he was taking LT4 100 µg daily, thyroid-stimulating hormone (TSH) level was >200 µIU/mL (normal range, 0.3-4.7 µIU/mL) and free thyroxine level was 0.3 ng/dL (normal range, 0.8-1.7 ng/dL). The patient had excellent medication compliance. LT4 dose was increased to 200 µg daily and then 200 and 300 µg every other day. Two months later, TSH level was 3.1 µIU/mL and free thyroxine level was 1.1 ng/dL. He did not exhibit malabsorption or proteinuria. His albumin levels had been low since the age of 18 years (mostly <2.5 g/dL). Stool α-1-antitrypsin levels and calprotectin levels were elevated on multiple occasions. Protein-losing enteropathy was diagnosed. Discussion: As most circulating LT4 is protein-bound, loss of protein-bound LT4 due to protein-losing enteropathy is the most plausible cause of the large LT4 dose requirement in this case. Conclusion: This case demonstrates that protein-losing enteropathy, through loss of protein-bound thyroxine, is a novel and yet unrecognized cause of high LT4 replacement dose requirement. In patients who require high LT4 dose for unclear reasons, albumin levels should be examined and protein wasting be suspected in those with low albumin levels.
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Introduction: The similarity between ankylosing spondylitis (AS) and ulcerative colitis (UC) in incidence rate and pathogenesis has been revealed. But the common pathogenesis that explains the relationship between AS and UC is still lacked, and the related genetic research is limited. We purposed to explore shared biomarkers and pathways of AS and UC through integrated bioinformatics. Methods: Gene expression data of AS and UC were obtained in the GEO database. We applied weighted gene co-expression network analysis (WGCNA) to identify AS-related and UC-related co-expression gene modules. Subsequently, machine learning algorithm was used to further screen hub genes. We validated the expression level and diagnostic efficiency of the shared diagnostic gene of AS and UC in external datasets. Gene set enrichment analysis (GSEA) was applied to analyze pathway-level changes between disease group and normal group. Finally, we analyzed the relationship between hub biomarker and immune microenvironment by using the CIBERSORT deconvolution algorithm. Results: 203 genes were obtained by overlapping AS-related gene module and UC-related gene module. Through SVM-RFE algorithm, 19 hub diagnostic genes were selected for AS in GSE25101 and 6 hub diagnostic genes were selected for UC in GSE94648. KCNJ15 was obtained as a common diagnostic gene of AS and UC. The expression of KCNJ15 was validated in independent datasets, and the results showed that KCNJ15 were similarly upregulated in AS samples and UC samples. Besides, ROC analysis also revealed that KCNJ15 had good diagnostic efficacy. The GSEA analysis revealed that oxidative phosphorylation pathway was the shared pathway of AS and UC. In addition, CIBERSORT results revealed the correlation between KCNJ15 gene and immune microenvironment in AS and UC. Conclusion: We have explored a common diagnostic gene KCNJ15 and a shared oxidative phosphorylation pathway of AS and UC through integrated bioinformatics, which may provide a potential diagnostic biomarker and novel insight for studying the mechanism of AS-related UC.
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Osteosarcoma is a malignant tumor that predominantly occurs in children or adolescents under the age of 20 years old. Metastasis and chemotherapy resistance are two problems in the treatment of osteosarcoma, and the lack of definite biomarkers impairs the course of treatment. In recent years, non-coding RNA, as a biomarker of osteosarcoma, has become an area of research focus. The role of long non-coding RNAs (lncRNAs), such as lncRNA OIP5-AS1, and circular RNAs, such as hsa_circ_0004674, in osteosarcoma have previously been revealed, and the present study investigated their clinical significance. A total of 20 samples were collected from patients with osteosarcoma. The expression levels of lncRNA OIP5-AS1 and hsa_circ_0004674 were analyzed in tumor tissues and patient serum, and their associations with chemotherapy sensitivity, lung metastasis and prognosis were assessed. The results revealed that these two non-coding RNAs were significantly upregulated in the osteosarcoma tissues of patients compared with those in the adjacent tumor tissues. In addition, the expression levels of the two non-coding RNAs were increased in the serum of patients with osteosarcoma compared with those in patients with bone fractures (P<0.01). In patients with lung metastasis or chemotherapy resistance (tumor necrosis rate <90%), the expression levels of the two non-coding RNAs were similarly increased. By plotting the receiver operating characteristic curve, it was revealed that the combination of hsa_circ_0004674 and lncRNA OIP5-AS1 was better than ALP or either non-coding RNA alone in predicting chemotherapy sensitivity and metastasis. Kaplan-Meier survival analysis showed that, in patients with osteosarcoma, higher expression of both non-coding RNAs was associated with worse survival time (log-rank test P=0.006). In conclusion, the combination of hsa_circ_0004674 and lncRNA OIP5-AS1 may be used as a better biomarker than traditional biomarkers, such as ALP, in a clinical setting.
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Gardenia jasminoides is an important ornamental greening plant with medicinal and edible values. This study investigated volatile constituents, alcoholic components and physiological activities on flowers of G. jasminoides Ellis and its variety. It was found that a total of 56 volatile components were identified, and terpenoids and esters were the main compounds to distinguish these species. Furthermore, the alcohol-soluble extracts of G. jasminoides flowers have the high contents of total phenols and total flavonoids, with potential antioxidant and hypoglycemic activities. In addition, nine compounds were identified, whose distribution in petals and stamens of G. jasminoides were significantly dissimilar. The contents of flavonoids and phenolics were stable after blanching confirmed by our findings, while iridoids were remarkably higher after freeze-drying (FD) and hot-air drying (HD). This research provides evidences that the fragrance, active components and activity of flowers of these species were affected by species, flower parts and processing methods.