Transvaginal Reduction of a Heterotopic Cornual Pregnancy with Conservation of Intrauterine Pregnancy.

Here we report a case of heterotopic cornual pregnancy after in vitro fertilization who was diagnosed at 6 weeks after frozen embryos transfer. The heterotopic pregnancy was successfully terminated by transvaginal ultrasound-guided selective fetal reduction. At 38+1 weeks, she underwent a cesarean section and delivered a healthy 3300 g male infant with Apgar score of 10-10' evaluated at 1 min and 5 min.

Pine bark extracts: nutraceutical, pharmacological, and toxicological evaluation.

Proanthocyanidins are among the most abundant constituents in pine bark extracts (PBEs). This review summarizes medical research on PBEs from Pinus pinaster, Pinus radiata, Pinus massoniana, and other less well characterized species. The precise mechanisms of the important physiologic functions of PBE components remain to be elucidated, but there is evidently great potential for the identification and development of novel antioxidant, anti-inflammatory, cardiovascular, neuroprotective, and anticancer medicines. Although toxicological data for PBEs are limited, no serious adverse effects have been reported. PBEs, therefore, may have potential as nutraceuticals and pharmaceuticals and should be safe for use as food ingredients.

From explainable to interpretable deep learning for natural language processing in healthcare: How far from reality?

Deep learning (DL) has substantially enhanced natural language processing (NLP) in healthcare research. However, the increasing complexity of DL-based NLP necessitates transparent model interpretability, or at least explainability, for reliable decision-making. This work presents a thorough scoping review of explainable and interpretable DL in healthcare NLP. The term "eXplainable and Interpretable Artificial Intelligence" (XIAI) is introduced to distinguish XAI from IAI. Different models are further categorized based on their functionality (model-, input-, output-based) and scope (local, global). Our analysis shows that attention mechanisms are the most prevalent emerging IAI technique. The use of IAI is growing, distinguishing it from XAI. The major challenges identified are that most XIAI does not explore "global" modelling processes, the lack of best practices, and the lack of systematic evaluation and benchmarks. One important opportunity is to use attention mechanisms to enhance multi-modal XIAI for personalized medicine. Additionally, combining DL with causal logic holds promise. Our discussion encourages the integration of XIAI in Large Language Models (LLMs) and domain-specific smaller models. In conclusion, XIAI adoption in healthcare requires dedicated in-house expertise. Collaboration with domain experts, end-users, and policymakers can lead to ready-to-use XIAI methods across NLP and medical tasks. While challenges exist, XIAI techniques offer a valuable foundation for interpretable NLP algorithms in healthcare.

Evaluating the ChatGPT family of models for biomedical reasoning and classification.

OBJECTIVE: Large language models (LLMs) have shown impressive ability in biomedical question-answering, but have not been adequately investigated for more specific biomedical applications. This study investigates ChatGPT family of models (GPT-3.5, GPT-4) in biomedical tasks beyond question-answering. MATERIALS AND METHODS: We evaluated model performance with 11 122 samples for two fundamental tasks in the biomedical domain-classification (n = 8676) and reasoning (n = 2446). The first task involves classifying health advice in scientific literature, while the second task is detecting causal relations in biomedical literature. We used 20% of the dataset for prompt development, including zero- and few-shot settings with and without chain-of-thought (CoT). We then evaluated the best prompts from each setting on the remaining dataset, comparing them to models using simple features (BoW with logistic regression) and fine-tuned BioBERT models. RESULTS: Fine-tuning BioBERT produced the best classification (F1: 0.800-0.902) and reasoning (F1: 0.851) results. Among LLM approaches, few-shot CoT achieved the best classification (F1: 0.671-0.770) and reasoning (F1: 0.682) results, comparable to the BoW model (F1: 0.602-0.753 and 0.675 for classification and reasoning, respectively). It took 78 h to obtain the best LLM results, compared to 0.078 and 0.008 h for the top-performing BioBERT and BoW models, respectively. DISCUSSION: The simple BoW model performed similarly to the most complex LLM prompting. Prompt engineering required significant investment. CONCLUSION: Despite the excitement around viral ChatGPT, fine-tuning for two fundamental biomedical natural language processing tasks remained the best strategy.

Molecular Mechanisms of Same TCM Syndrome for Different Diseases and Different TCM Syndrome for Same Disease in Chronic Hepatitis B and Liver Cirrhosis.

Traditional Chinese medicine (TCM) treatment is based on the traditional diagnose method to distinguish the TCM syndrome, not the disease. So there is a phenomenon in the relationship between TCM syndrome and disease, called Same TCM Syndrome for Different Diseases and Different TCM Syndrome for Same Disease. In this study, we demonstrated the molecular mechanisms of this phenomenon using the microarray samples of liver-gallbladder dampness-heat syndrome (LGDHS) and liver depression and spleen deficiency syndrome (LDSDS) in the chronic hepatitis B (CHB) and liver cirrhosis (LC). The results showed that the difference between CHB and LC was gene expression level and the difference between LGDHS and LDSDS was gene coexpression in the G-protein-coupled receptor protein-signaling pathway. Therein genes GPER, PTHR1, GPR173, and SSTR1 were coexpressed in LDSDS, but not in LGDHS. Either CHB or LC was divided into the alternative LGDHS and LDSDS by the gene correlation, which reveals the molecular feature of Different TCM Syndrome for Same Disease. The alternatives LGDHS and LDSDS were divided into either CHB or LC by the gene expression level, which reveals the molecular feature of Same TCM Syndrome for Different Diseases.

DNA methylation status of imprinted H19 and KvDMR1 genes in human placentas after conception using assisted reproductive technology.

BACKGROUND: Assisted reproductive technologies (ARTs), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are thought to destabilize genomic imprints. Previous studies examining the association between ART and aberrant DNA methylation have been inconclusive. METHOD: The DNA methylation status of H19 and KvDMR1was compared between newborns conceived through ART and those conceived naturally to evaluate the safety of ART. Placental tissues from 6 full-term, naturally conceived pregnancies (no gestational comorbidities) and six full-term ART pregnancies (no gestational complication) were collected. Genomic DNA (gDNA) and RNA were extracted from both groups. Real-time PCR was used to analyze the mRNA expression levels of H19 and KvDMR1 in the placenta for both groups. A whole-genome DNA methylation microarray was used to examine three placentas from full-term, naturally conceived pregnancies and three placentas from full-term IVF pregnancies. RESULT: The expression level of H19 in the IVF group was significantly higher than that in the natural pregnancy group, whereas the expression level of KvDMR1 was significantly lower in the ART group than in the natural pregnancy group. Also, human ART manipulation resulted in placental gDNA methylation modifications. Conclusion: Abnormal methylation patterns were detected in phenotypically normal phenotype conceived by ART, which may occur due to imprinting errors in sperm/oocyte cells or side effects of in vitro embryo culture procedures. Further investigation is necessary to determine whether imprinted gene expression and DNA methylation can be regulated through other mechanisms. KEYWORDS: Assisted reproductive technology (ART); placenta; methylation; H19; KvDMR1.

Participation of the inositol 1,4,5-trisphosphate-gated calcium channel in the zona pellucida- and progesterone-induced acrosome reaction and calcium influx in human spermatozoa.

The acrosome reaction is a prerequisite for fertilization, and its signaling pathway has been investigated for decades. Regardless of the type of inducers present, the acrosome reaction is ultimately mediated by the elevation of cytosolic calcium. Inositol 1,4,5-trisphosphate-gated calcium channels are important components of the acrosome reaction signaling pathway and have been confirmed by several researchers. In this study, we used a novel permeabilization tool BioPORTER® and first demonstrated its effectiveness in spermatozoa. The inositol 1,4,5-trisphosphate type-1 receptor antibody was introduced into spermatozoa by BioPORTER® and significantly reduced the calcium influx and acrosome reaction induced by progesterone, solubilized zona pellucida, and the calcium ionophore A23187. This finding indicates that the inositol 1,4,5-trisphosphate type-1 receptor antibody is a valid inositol 1,4,5-trisphosphate receptor inhibitor and provides evidence of inositol 1,4,5-trisphosphate-gated calcium channel involvement in the acrosome reaction in human spermatozoa. Moreover, we demonstrated that the transfer of 1,4,5-trisphosphate into spermatozoa induced acrosome reactions, which provides more reliable evidence for this process. In addition, by treating the spermatozoa with inositol 1,4,5-trisphosphate/BioPORTER® in the presence or absence of calcium in the culture medium, we showed that the opening of inositol 1,4,5-trisphosphate-gated calcium channels led to extracellular calcium influx. This particular extracellular calcium influx may be the major process of the final step of the acrosome reaction signaling pathway.

Delta-6-desaturase inhibitor enhances radiation therapy in glioblastoma in vitro and in vivo.

BACKGROUND: It has been reported that cell inflammation pathways contribute to the development of prostaglandin E2 (PGE2)-inhibitor of DNA-binding protein-1 (ID1)-dependent radio-resistance in glioblastoma. Here, we proposed that inhibiting delta-6-desaturase (D6D) could block arachidonic acid synthesis and PGE2 production, thereby reversing PGE2-ID1-dependent radioresistance in glioblastoma cells and xenograft tumor models. MATERIALS AND METHODS: Two glioblastoma cell lines, namely, U-87 MG and LN-229, were used for the in vitro study. The combination effects of SC-26196 (a D6D inhibitor) and radiation were assessed by the MTS assay, colony formation assay, and cell apoptosis analysis. HPLC/MS analysis was performed to quantify the production of arachidonic acid and PGE2. For the in vivo study, 6-week-old nude mice, each bearing a U-87 MG xenograft tumor, were subjected to 4-week treatments of vehicle, SC-26196, radiation, or the combination of both. Tumor growth was monitored during the treatment, and the tumor tissues were collected at the end for further analysis. RESULTS: Treatment with SC-26196 significantly improved radiosensitivity in both glioblastoma cell lines in vitro, and radiosensitivity was associated with inhibited synthesis of arachidonic acid and PGE2. The combination of SC-26196 and radiation synergistically inhibited U-87 MG xenograft tumor growth, in association with the induction of tumor apoptosis and suppressed tumor proliferation. SC-26196 also inhibited arachidonic acid and PGE2 production in vivo and limited expression of ID1. CONCLUSION: These data suggested that the D6D inhibitor could reverse PGE2-ID1-dependent radioresistance in glioblastoma cells and xenograft tumor models by blocking the synthesis of arachidonic acid and PGE2. Although further investigation is required, the outcomes from this study may guide us in developing a potentially novel combination strategy for current glioblastoma therapy.

Pinus massoniana Bark Extract: Structure-Activity Relationship and Biomedical Potentials.

Proanthocyanidins (PAs) belong to the condensed tannin subfamily of natural flavonoids. Recent studies have shown that the main bioactive compounds of Pinus massoniana bark extract (PMBE) are PAs, especially the proanthocyanidins B series, which play important roles in cell cycle arrest, apoptosis induction and migration inhibition of cancer cells in vivo and in vitro. PA-Bs are mixtures of oligomers and polymers composed of flavan-3-ol, and the relationship between their structure and corresponding biomedical potentials is summarized in this paper. The hydroxyl at certain positions or the linkage between different carbon atoms of different rings determines or affects their anti-oxidant and free radical scavenging bioactivities. The degree of polymerization and the water solubility of the reaction system also influence their biomedical potential. Taken together, PMBE has a promising future in clinical drug development as a candidate anticancer drug and as a food additive to prevent tumorigenesis. We hope this review will encourage interested researchers to conduct further preclinical and clinical studies to evaluate the anticancer activities of PMBE, its active constituents and their derivatives.