Miracle-dz/UniFAR-FTUs huggingface dataset:
Blood Salvage and Autotransfusion With Single Leukoreduction Does Not Increase the Risk of Tumor Recurrence After Liver Transplantation for Advanced Hepatocellular Carcinoma

Objective: The aim of this study was to determine whether autotransfusion of salvaged blood with single leukoreduction is associated with post-transplant tumor recurrence in patients with advanced hepatocellular carcinoma (HCC). Background: Previous studies have consistently demonstrated the safety of autotransfusion of salvaged and leukoreduced blood during liver transplantation for HCC. However, the effects of this technique remained unknown for advanced HCC. Methods: Of 349 patients who underwent living donor liver transplantation for advanced HCC: 74 of 129 without autotransfusion were matched with 74 of 220 with autotransfusion using propensity score based on tumor biology, allogeneic transfusion, and others. Survival analysis was performed with death as a competing risk event. The primary outcome was HCC recurrence. Results: Recipients in autotransfusion group received 811 (497–1247) mL of salvaged blood with single leukoreduction. In the matched cohort, cumulative overall recurrence probability at 1/2/5 years after transplantation was 24.6%/ 38.3%/39.7% for nonautotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the 2 groups in overall recurrence [hazard ratio (HR) = 0.72 (0.43–1.21)], intrahepatic recurrence [HR = 0.70 (0.35–1.40)], and extrahepatic recurrence [HR = 0.82 (0.46–1.47)]. Also, there were no significant differences in overall death [HR = 0.57 (0.29–1.12)], HCC-related death [HR = 0.59 (0.29–1.20)], and HCC-unrelated death [HR = 0.48 (0.09–2.65)]. Conclusions: When allogeneic transfusion was matched, autotransfusion was not significantly related to HCC recurrence, with more favorable probabilities for autotransfusion, in patients with advanced HCC. Thus, blood salvage and autotransfusion could be safely used with single leukoreduction, without double-filtered leukoreduction, during liver transplantation for HCC with potential benefits from avoiding allogeneic red blood cell transfusion.
Tumor Biological Feature and Its Association with Positive Surgical Margins and Apical Margins after Radical Prostatectomy in Non-Metastasis Prostate Cancer

Purpose: We assessed clinical and tumor biological features and evaluated their association with positive surgical margins (PSMs) and positive apical margins (PAMs) variability after radical prostatectomy (RP) in men with non-metastasis prostate cancer (nmPCa) in our institute. Patients and methods: During the period from January 2013 to December 2017, clinical and pathological data were collected in 200 patients with nmPCa undergoing RP in the Urological department of Peking University Cancer Hospital & Institute. Surgical and apical margins were stated negative and positive, separately. A dichotomous logistic regression model was used to assess clinical and tumor biological features including age, total prostate volume (TPV), biopsy positive cores (BPC), D’Amico risk grade, tumor clinical stage, International Society of Urologic Pathology (ISUP) grade, tPSA, f/t and pelvic lymph nodes (PLN) invasion, and their association with PSMs and PAMs was evaluated. Results: Overall, men with nmPCa in this study had a high ISUP grade (58.5% grade 3–5), high risk grade (89.4%) and high clinical T stage (56% cT3-4). PSMs were detected in 106 patients; the rate of PSMs was 53%. Among patients with PSMs, 83% were PAMs; the overall rate of PAMs was 44%. Among patients with PSMs, high risk (OR, 1.439; p = 0.023), cT3a (OR, 1.737; p = 0.045), cT3b (OR, 5.286; p < 0.001), cT4 (OR, 6.12; p < 0.001), ISUP Grade 4 (OR, 2; p = 0.034) and Grade 5 (OR, 6.167; p < 0.001) and PLN invasion (OR, 6; p = 0.019) were strongly associated with PSMs using a dichotomous logistic regression univariable model, and high risk (OR, 6; p = 0.019), cT3a (OR, 5.116; p = 0.048), cT3b (OR, 9.194; p = 0.008), cT4 (OR, 4.58; p = 0.01), ISUP Grade 4 (OR, 7.04; p = 0.035), Grade 5 (OR, 16.514; p = 0.002) and PLN invasion (OR, 5.516; p = 0.03) were independently associated with PSMs by using multivariable analysis. Among patients with PAMs, cT3b (OR, 2.667; p = 0.004), cT4 (OR, 3; p = 0.034) and proportion of BPC (OR, 4.594; p = 0.027) were strongly associated with PAMs by using a dichotomous logistic regression univariable model, and cT3b (OR, 3.899; p = 0.02), cT4 (OR, 2.8; p = 0.041) and proportion of BPC (OR, 5.247; p = 0.04) were independently associated with PSMs by using multivariable analysis. Conclusions: Patients with nmPCa in our institute had high risk, high ISUP grade and high clinical stage. Tumor biological factors were strongly associated with PSMs and PAMs, and PLN invasion was independently associated with PSMs. The risk factors influenced the status of surgical margins, and apical margins were different.
Accounting for Cooperativity in the Thermotropic Volume Phase Transition of Smart Microgels

A full quantitative description of the swelling of smart microgels is still problematic in many cases. The original approach of Flory and Huggins for the monomer–solvent interaction parameter χ cannot be applied to some microgels. The reason for this obviously is that the cross-linking enhances the cooperativity of the volume phase transitions, since all meshes of the network are mechanically coupled. This was ignored in previous approaches, arguing with distinct transition temperatures for different meshes to describe the continuous character of the transition of microgels. Here, we adjust the swelling curves of a series of smart microgels using the Flory–Rehner description, where the polymer–solvent interaction parameter χ is modeled by a Hill-like equation for a cooperative thermotropic transition. This leads to a very good description of all measured microgel swelling curves and yields the physically meaningful Hill parameter ν. A linear decrease of ν is found with increasing concentration of the cross-linker N,N′-methylenebisacrylamide in the microgel particles p(NIPAM), p(NNPAM), and p(NIPMAM). The linearity suggests that the Hill parameter ν corresponds to the number of water molecules per network chain that cooperatively leave the chain at the volume phase transition. Driven by entropy, ν water molecules of the solvate become cooperatively “free” and leave the polymer network.
Prenatal medication exposure and epigenetic outcomes: a systematic literature review and recommendations for prenatal pharmacoepigenetic studies

ABSTRACT When used during pregnancy, analgesics and psychotropics pass the placenta to enter the foetal circulation and may induce epigenetic modifications. Where such modifications occur and whether they disrupt normal foetal developme nt, are currently unanswered questions. This field of prenatal pharmacoepigenetics has received increasing attention, with several studies reporting associations between in utero medication exposure and offspring epigenetic outcomes. Nevertheless, no recent systematic review of the literature is available. Therefore, the objectives of this review were to (i) provide an overview of the literature on the association of prenatal exposure to psychotropics a nd analgesics with epigenetic outcomes, and (ii) suggest recommendations for future studies within prenatal pharmacoepigenetics. We performed systematic literature searches in five databases. The eligible studies assessed human prenatal exposure to psychotropics or analgesics, with epigenetic analyses of offspring tissue as an outcome. We identified 18 eligible studies including 4,419 neonates exposed to either antidepressants, antiepileptic drugs, paracetamol, acetylsalicylic acid, or methadone. The epigenetic outcome in all studies was DNA methylation in cord blood, placental tissue or buccal cells. Although most studies found significant differences in DNA methylation upon medication exposure, almost no differences were persistent across studies for similar medications and sequencing methods. The reviewed studies were challenging to compare due to poor transparency in reporting, and heterogeneous methodology, design, genome coverage, and statistical modelling. We propose 10 recommendations for future prenatal pharmacoepigenetic studies considering both epidemiological and epigenetic perspectives. These recommendations may improve the quality, comparability, and clinical relevance of such studies. PROSPERO registration ID: CRD42020166675.
The Holistic Coronary Physiology Display: Calculation of the Flow Separation Index in Vessel-Specific Individual Flow Range during Fractional Flow Reserve Measurement Using 3D Coronary Reconstruction

In order to make optimal decisions on the treatment of atherosclerotic coronary heart disease (CHD), appropriate evaluation is necessary, including both the anatomical and physiological assessment of the coronary arteries. According to current guidelines, a fractional flow reserve (FFR)–based clinical decision is recommended, but coronary flow reserve (CFR) measurements and microvascular evaluation should also be considered in special cases for a detailed exploration of the coronary disease state. We aimed to generate an extended physiological evaluation during routine FFR measurement and define a new pathological flow–related prognostic factor. Fluid dynamic equations were applied to calculate CFR on the basis of the three-dimensional (3D) reconstruction of the invasively acquired coronary angiogram and the measured intracoronary pressure data. A new, potentially robust prognostic parameter of a coronary lesion called the “flow separation index” (FSi), which is thought to detect the pathological flow amount through a stenosis was introduced in a vessel-specific flow range. Correlations between FSi and the clinically established physiological indices (CFR and FFR) were determined. The FSi was calculated in 19 vessels of 16 patients, including data from the pre- and post-stent revascularization treatment of 3 patients. There was no significant correlation between the FSi and the CFR (r = −0.23, p = 0.34); however, there was significant negative correlation between the FSi and the FFR (r = −0.66, p = 0.002). An even stronger correlation was found between the FSi and the ratio of the resting pressure ratio and the FFR (r = 0.92, p < 0.0001). The diagnostic power of the FSi for predicting the FFR value of <0.80, as a gold standard prognostic factor, was tested by receiver operating characteristic analysis. FSi > 0.022 proved to be the cutoff value of the prediction of a pathologically low FFR with a 0.856 area under the curve (95% confidence interval: 0.620 to 0.972). The present flow–pressure–velocity display provides a comprehensive summary of patient-specific pathophysiology in CHD. The consequences of epicardial stenoses can be evaluated together with their complex relations to microvascular conditions. Based on these values, clinical decision-making concerning both pharmacological therapy and percutaneous or surgical revascularization may be more precisely guided.
Quality of Life for Older Cancer Patients: Relation of Psychospiritual Distress to Meaning-Making During Dignity Therapy

Background: Nearly 500,000 older Americans die a cancer-related death annually. Best practices for seriously ill patients include palliative care that aids in promoting personal dignity. Dignity Therapy is an internationally recognized therapeutic intervention designed to enhance dignity for the seriously ill. Theoretically, Dignity Therapy provides opportunity for patients to make meaning by contextualizing their illness within their larger life story. The extent to which Dignity Therapy actually elicits meaning-making from patients, however, has not been tested. Aim: The current study examines (i) extent of patient meaning-making during Dignity Therapy, and (ii) whether baseline psychospiritual distress relates to subsequent meaning-making during Dignity Therapy. Design: Participants completed baseline self-report measures of psychospiritual distress (i.e., dignity-related distress, spiritual distress, quality of life), before participating in Dignity Therapy. Narrative analysis identified the extent of meaning-making during Dignity Therapy sessions. Participants: Twenty-five outpatients (M age = 63, SD = 5.72) with late-stage cancer and moderate cancer-related symptoms were recruited. Results: Narrative analysis revealed all patients made meaning during Dignity Therapy but there was wide variation (i.e., 1—12 occurrences). Patients who made greater meaning were those who, at baseline, reported significantly higher psychospiritual distress, including greater dignity-related distress (r = .46), greater spiritual distress (r = .44), and lower quality of life (r = -.56). Conclusion: Meaning-making was found to be a central component of Dignity Therapy. Particularly, patients experiencing greater distress in facing their illness use the Dignity Therapy session to express how they have made meaning in their lives.
Machine Learning-Inspired Hybrid Precoding for mmWave MU-MIMO Systems with Domestic Switch Network

Hybrid precoding is an attractive technique in MU-MIMO systems with significantly reduced hardware costs. However, it still requires a complex analog network to connect the RF chains and antennas. In this paper, we develop a novel hybrid precoding structure for the downlink transmission with a compact RF structure. Specifically, the proposed structure relies on domestic connections instead of global connections to link RF chains and antennas. Fixed-degree phase shifters provide candidate signals, and simple on-off switches are used to route the signal to antennas, thus RF adders are no longer required. Baseband zero forcing and block diagonalization are used to cancel interference for single-antenna and multiple-antenna users, respectively. We formulate how to design the RF precoder by optimizing the probability distribution through cross-entropy minimization which originated in machine learning. To optimize the energy efficiency, we use the fractional programming technique and exploit the Dinkelbach method-based framework to optimize the number of active antennas. Simulation results show that proposed algorithms can yield significant advantages under different configurations.
Modeling Neurotransmission: Computational Tools to Investigate Neurological Disorders

The investigation of synaptic functions remains one of the most fascinating challenges in the field of neuroscience and a large number of experimental methods have been tuned to dissect the mechanisms taking part in the neurotransmission process. Furthermore, the understanding of the insights of neurological disorders originating from alterations in neurotransmission often requires the development of (i) animal models of pathologies, (ii) invasive tools and (iii) targeted pharmacological approaches. In the last decades, additional tools to explore neurological diseases have been provided to the scientific community. A wide range of computational models in fact have been developed to explore the alterations of the mechanisms involved in neurotransmission following the emergence of neurological pathologies. Here, we review some of the advancements in the development of computational methods employed to investigate neuronal circuits with a particular focus on the application to the most diffuse neurological disorders.
Quality of Life and Sleep in Patients with Pituitary Adenoma in Relation to Tumor Type and Compression of the Optic Chiasm

Objective: To determine the effect of transsphenoidal surgery on quality of life and sleep in patients with pituitary adenomas depending on tumor type and compression of the optic chiasm. Methods: In this prospective study, patients with pituitary adenomas who were scheduled for transsphenoidal surgery completed the Short Form 36 Questionnaire, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale preoperatively and 7.5 (±1.5) months after surgery. Patients were analyzed based on tumor type and compression of the optic chiasm. Results: Significant improvements with large effect sizes were seen for patients with Cushing’s disease in general health (Z = −2.37; p = 0.018), vitality (Z = −2.05; p = 0.041), and mental health (Z = −2.06; p = 0.040). A significant deterioration with large effect size occurred in physical functioning (Z = −2.02; p = 0.043) in patients with acromegaly. A significant improvement with medium effect size was seen in subjective sleep quality, (Z = −2.24; p = 0.025), sleep duration (Z = −2.11; p = 0.035), and habitual sleep efficiency (Z = −2.26; p = 0.024) after decompression of the optic chiasm. Multiple significant correlations were observed between sleep parameters and Short Form 36 subscales before and after treatment. Conclusions: Changes in quality of life during the follow-up period depend on tumor type. Circadian rhythm disturbances may resolve promptly after decompression of the optic chiasm. Quality of life in pituitary adenoma patients is associated with quality of sleep in many dimensions, thus implying that developing strategies to improve sleep quality could increase overall well-being and everyday functioning in pituitary adenoma patients.
Interplay between diet and gut microbiome, and circulating concentrations of trimethylamine N-oxide: findings from a longitudinal cohort of US men

Objectives Gut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red meat intake and poor cardiometabolic health. We investigated whether gut microbiome could modify associations of dietary precursors with TMAO concentrations and cardiometabolic risk markers among free-living individuals. Design We collected up to two pairs of faecal samples (n=925) and two blood samples (n=473), 6 months apart, from 307 healthy men in the Men’s Lifestyle Validation Study. Diet was assessed repeatedly using food-frequency questionnaires and diet records. We profiled faecal metagenome and metatranscriptome using shotgun sequencing and identified microbial taxonomic and functional features. Results TMAO concentrations were associated with the overall microbial compositions (permutational analysis of variance (PERMANOVA) test p=0.001). Multivariable taxa-wide association analysis identified 10 bacterial species whose abundance was significantly associated with plasma TMAO concentrations (false discovery rate <0.05). Higher habitual intake of red meat and choline was significantly associated with higher TMAO concentrations among participants who were microbial TMAO-producers (p<0.05), as characterised based on four abundant TMAO-predicting species, but not among other participants (for red meat, P-interaction=0.003; for choline, P-interaction=0.03). Among abundant TMAO-predicting species, Alistipes shahii significantly strengthened the positive association between red meat intake and HbA1c levels (P-interaction=0.01). Secondary analyses revealed that some functional features, including choline trimethylamine-lyase activating enzymes, were associated with TMAO concentrations. Conclusion We identified microbial taxa that were associated with TMAO concentrations and modified the associations of red meat intake with TMAO concentrations and cardiometabolic risk markers. Our data underscore the interplay between diet and gut microbiome in producing potentially bioactive metabolites that may modulate cardiometabolic health.
An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials

Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye’s accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.
Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans

Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual’s background affects the CSF lipid profile remains unclear, and the association between CSF and plasma lipid profiles in heathy individuals has not yet been defined. Herein, lipidomics approaches were employed to analyze CSF and plasma samples obtained from 114 healthy Japanese subjects. Results showed that the global lipid profiles differed significantly between CSF and plasma, with only 13 of 114 lipids found to be significantly correlated between the two matrices. Additionally, the CSF total protein content was the primary factor associated with CSF lipids. In the CSF, the levels of major lipids, namely, phosphatidylcholines, sphingomyelins, and cholesterolesters, correlated with CSF total protein levels. These findings indicate that CSF lipidomics can be applied to explore changes in lipid homeostasis in patients with brain diseases.
Prognostic and Predictive Biomarkers in Stage III Melanoma: Current Insights and Clinical Implications

Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melanoma patients ranges from 93% (IIIA) to 32% (IIID) with a high risk of recurrence after complete surgery. The introduction of target and immune therapies has dramatically improved the overall survival, but the identification of patients with a high risk of relapse who will benefit from adjuvant therapy and the determination of the best treatment choice remain crucial. Currently, patient prognosis is based on clinico-pathological features, highlighting the urgent need of predictive and prognostic markers to improve patient management. In recent years, many groups have focused their attention on identifying molecular biomarkers with prognostic and predictive potential. In this review, we examined the main candidate biomarkers reported in the literature.
In Vitro Cytotoxicity of Trastuzumab (Tz) and Se-Trastuzumab (Se-Tz) against the Her/2 Breast Cancer Cell Lines JIMT-1 and BT-474

Her/2+ breast cancer accounts for ~25% mortality in women and overexpression of Her/2 leads to cell growth and tumor progression. Trastuzumab (Tz) with Taxane is the preferred treatment for Her/2+ patients. However, Tz responsive patients often develop resistance to Tz treatment. Herein, redox selenides (RSe-) were covalently linked to Tz using a selenium (Se)-modified Bolton–Hunter Reagent forming Seleno-Trastuzumab (Se-Tz; ~25 µgSe/mg). Se-Tz was compared to Tz and sodium selenite to assess the viability of JIMT-1 and BT-474 cells. Comparative cell viability was examined by microscopy and assessed by fluorometric/enzymatic assays. Se-Tz and selenite redox cycle producing superoxide (O2•−) are more cytotoxic to Tz resistant JIMT-1 and Tz sensitive BT-474 cells than Tz. The results of conjugating redox selenides to Tz suggest a wider application of this technology to other antibodies and targeting molecules.