Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I Targeted Combination Trial of Sorafenib and GW5074 in Patients with Advanced Refractory Solid Tumors

Background: Combination therapy with the administration of GW5074 and sorafenib significantly induced necrotic death in various cancer cells in vivo, as well as prolonging the survival of an animal disease model due to significant suppression of the primary and metastatic lesions. We sought to determine the safety, tolerability, pharmacokinetics, and anti-tumor activity of this co-administration therapy in patients with refractory advanced solid cancers. Methods: Twelve patients were enrolled. Eligible subjects received different dosages of GW5074 in one of the three dose cohorts (Cohort 1: 750 mg daily, Cohort 2: 1500 mg daily, Cohort 3: 750 mg twice daily) plus 200 mg of sorafenib daily to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) at phase 1. Furthermore, the expression level of phosphorylated DAPKS308 in primary tumor, metastatic tumor, and circulating tumor cells (CTC) were evaluated to investigate the relationship between biomarker and the efficacy profile. Results: Among the 12 enrolled patients in this phase 1 trial, most adverse effects (AE) were grade 1, with two being grade 3. The most frequent AE of all grades were weight loss and hypertension, occurring in 16.7% of participants. Eight patients (66.7%) had the disease controlled by receiving co-administration therapy of GW5074 and sorafenib. GW5074 was found to have poor absorption, as increasing the dosage did not result in a significant increase in the bioavailability of GW5074 in subjects. Furthermore, the expression level of phosphorylated DAPKS308 in tumor and CTCs were correlated with the disease control rate (DCR) and duration of response (DOR). Conclusions: Co-administration therapy of GW5074 and sorafenib demonstrated a favorable safety profile and showed anti-tumor activity in a variety of tumor types. However, the solubility of GW5074 is not satisfactory. A future phase 2a trial will be carried out using the new salted form that has been proven to be more effective.
Relationships among Calibrachoa, Fabiana and Petunia (Petunieae tribe, Solanaceae) and a new generic placement of Argentinean endemic Petuniapatagonica

﻿Abstract Calibrachoa Cerv. , Fabiana Ruiz & Pav. , and Petunia Juss. form a clade within tribe Petunieae (Solanaceae). Phylogenetic studies of Petunieae, either as part of a family-wide analysis or focusing on the genera Calibrachoa and Petunia, have either left Fabiana unsampled or included only a single species. These studies have found conflicting relationships among the three genera with all three possible topologies obtained. Petuniapatagonica (Speg.) Millán, originally described in the genus Nierembergia Ruiz & Pav. , is morphologically distinct within Petunia and geographically disjunct from other members of the genus. For the first time, in this study we include multiple species of Fabiana, Calibrachoa, and Petunia, including P.patagonica. Using three chloroplast DNA regions and the nuclear gene GBSSI, or “waxy,” our results provide strong support for a sister group relationship between Calibrachoa and Fabiana and for the placement of P.patagonica within Fabiana. Since there is already a species Fabianapatagonica Speg. , we provide the new name Fabianaaustralis Alaria nom. nov. to replace Petuniapatagonica.
Trade off between simplicity and precision of index models

In the basis of contemporary portfolio theory is Markowitz model of portfolio analysis which accurately defines a set of efficient portfolios for a relatively small number of securities in its composition. With the increase in the number of securities in the portfolio, the application of the Markowitz's model becomes complex, so financial theory found the solution of the problem in the single-index Sharpe's model. The later emergence of multi-index models, which better reflect reality, increased precision in determining a set of efficient portfolios, but at the cost of greater complexity of the model. The aim of the research is to analyze a kind of substitution between the simplicity and precision of the model, and to search answer to the question of what is the optimal number of explanatory factors of the model. Using qualitative economic analysis method, it was concluded that the number of factors (indexes) in the model should be increased until marginal benefits in the form of increased precision are equalized with marginal costs in the form of increased complexity, reduced applicability and associated costs of obtaining informations. In striving for greater precision of models, financial analysts must not overlook that the index models emerged from the practical necessity of simplifying the original Markowitz's model.
An Update on Sphingosine-1-Phosphate and Lysophosphatidic Acid Receptor Transcripts in Rodent Olfactory Mucosa

Olfactory neurons connect the external environment and the brain, allowing the translocation of materials from the nasal cavity into the brain. The olfactory system is involved in SARS-CoV-2 infections; early in the pandemic declared in 2020, a loss of the sense of smell was found in many infected patients. Attention has also been focused on the role that the olfactory epithelium appears to play in the entry of the SARS-CoV-2 virus into the brain. Specifically, SARS-CoV-2 enters cells via the angiotensin-converting enzyme 2 protein (ACE2), which is found on supporting cells in the olfactory epithelium. The intranasal administration of sphingosine has been proposed to prevent the binding of SARS-CoV-2 to ACE2. Further, sphingosine-1-phosphate (S1P) receptors appear to facilitate the entry of SARS-CoV-2 into the brain. The goal of these studies was to characterize S1P receptor expression status in rodent olfactory mucosa. The expression of receptors for a related sphingolipid, lysophosphatidic acid (LPA), was also assessed. The results confirm previous reports of S1P1 and S1P3 receptor expression, as well as LPA receptor 1, in mouse olfactory mucosa; moreover, they extend the previous findings to identify additional S1P and LPA receptor transcripts in rat and mouse olfactory mucosa, as well as in cultured olfactory neurons. These findings may enhance the utility of rodent models in identifying agonists and/or antagonists of S1P and LPA receptors that may block the entry of SARS-CoV-2 and other viruses into nasal epithelial cells, and prevent transmission from the nasal cavity into the brain.
Changes in Histological Structure, Interleukin 12, Smooth Muscle Actin and Nitric Oxide Synthase 1. and 3. Expression in the Liver of Running and Non-Running Wistar Rats Supplemented with Bee Pollen or Whey Protein

Abstract Introduction: Bee pollen is a natural substance obtained from flowers by bees. It is a rich source of protein, vitamins and minerals. It can be used as a dietary supplement. Bee pollen has been investigated for the treatment of some diseases with promising potential. It can be helpful in supportive therapy for dyslipidemia, metabolic syndrome, diabetes type 2, as well the prevention and control of coronary heart disease and myocardial infarction. Whey protein is a rich source of amino acids. It is a basic dietary supplement for many athletes, both professional and amateur. It stimulates muscle growth and provides nutrition for cachectic patients. Aim of the study: The objective of the study was to assess the impact of dietary supplementation of bee pollen or whey protein on the Wistar rat liver histological structure and expression of interleukin 12, smooth muscle actin and nitric oxide synthases among running and non-running rats. Material and methods: Thirty male Wistar rats were divided into six equal groups, three running and three non-running. Among both there was one control, one supplemented with bee pollen and one receiving whey proteins. After 8 weeks, all animals were decapitated and their livers were collected. Five micrometer thick slides were prepared and used for classical histological staining and immuno-histochemistry. ImageJ image analysis software was used to measure optical density and immunohistochemistry profile coverage. Results: Among all groups, morphology of liver was similar. In the running control group, expression of interleukin-12 (IL-12) was decreased as well as expression of endothelial nitric oxide synthase (eNOS) in a group of bee pollen supplemented rats. No significant changes in α- smooth muscle actin (α-SMA) expression was observed. Conclusions: Bee pollen is proving to be a questionable choice for athletes as an alternative to whey protein. Bee pollen supplementation affects hepatocyte cellular activity and has hepatoprotective effects. Whey protein performs worse in this regard. Lower antioxidant properties were found in groups supplemented with bee pollen than with whey protein.
Cardiac myxomas: A narrative review

Cardiac myxomas are common primary neoplasms of the heart. They are biologically benign but “functionally malignant” because of the potential for embolization. They arise most commonly from the left atrium, but no chambers of the heart are immune. They may be sporadic in the majority but also familial as a part of the Carney complex. Two morphological forms exist: polypoid and papillary. Polypoid myxomas often present with obstructive features, while the papillary forms are more prone to embolization. Histogenesis is still controversial; the current view centres around origin from the primitive pluripotent mesenchymal cells. They may be of giant proportion, be calcified or get infected. Clinical presentation typically involves the triad of intracardiac obstruction, embolic events and constitutional symptoms. Precordial examination findings may simulate those of mitral or tricuspid stenosis. The presence of tumour plop and change of the physical findings with changing position may help differentiation between the two. Echocardiography is the investigation of choice. Echogenic polypoid or papillary mobile mass within the atrial cavity remaining attached to the interatrial septum through a stalk are the tell-tale echocardiographic features. Cardiac magnetic resonance and computed tomographic scanning may have incremental diagnostic value. Histopathological examination reveals abundant loose myxoid stroma with scattered round, polygonal or stellate cells with dense irregular nuclei. Genetic testing may detect mutations in the PRKAR1A gene in the familial form of cardiac myxoma, i.e. the Carney complex. Surgical excision is the mainstay of treatment with low operative mortality, excellent postoperative survival and low recurrence rate. The current trend favours minimal-access surgery with or without robotic assistance. Physicians should have appropriate preparedness to make a timely diagnosis and enthusiastic treatment to avoid potentially fatal complications.
Gestational weight gain in persons with HIV in the United States

Objective: We evaluated gestational weight gain (GWG) in pregnant persons with HIV (PWH) enrolled in the Surveillance Monitoring for ART Toxicities study. Design: This was a cohort study. Methods: GWG was classified as excessive, adequate, or inadequate; weekly GWG in second and third trimesters was calculated using National Academy of Medicine standards. Adjusted modified Poisson and linear regression models were fit with generalized estimating equations to assess the association of antiretroviral treatment (ART) with GWG outcomes stratified by timing of ART initiation [at conception (ART-C) and initiating during pregnancy (ART-I)]. Results: We included 1477 pregnancies (847 ART-C, 630 ART-I) from 1282 PWH. The proportion of excessive, adequate, and inadequate GWG was 44, 24, and 32%, respectively. No associations of ART class with excessive GWG were observed overall. However, among ART-I pregnancies with overweight prepregnancy BMI-based, protease inhibitor-based, nonnucleoside reverse transcriptase inhibitor-based, and nucleoside reverse transcriptase inhibitor-based ART were associated with significantly lower GWG per week than integrase inhibitor (INSTI)-based ART [mean differences: −0.14, −0.27, and −0.29 kg/week, respectively]. Among ART-I pregnancies with obese prepregnancy BMI, lower weekly GWG was also observed for protease inhibitor-based vs. INSTI-based ART (mean difference: −0.14 kg/week). Conclusion: ART class type was not associated with excessive GWG. However, PWH entering pregnancy already overweight/obese and initiating INSTI-based ART had higher weekly GWG in second and third trimesters vs. other ART classes. Further studies to understand how increases in weekly GWG for overweight/obese PWH impinges on long-term maternal/child health are warranted.
A two step workflow for pulmonary embolism detection using deep learning and feature extraction

ABSTRACT Pulmonary embolism is among the leading causes of death all over the world. In order to achieve a fast diagnosis and response from the medical team, a CT exam is used as a means to detect embolisms. Over the years, different methods of computer-aided diagnosis systems (CADs) were implemented to facilitate the analysis of a CT exam for pulmonary embolism detection, and due to the high amount of data produced in these exams, methods that use deep learning are also growing as of late. This paper proposes a pipeline to detect pulmonary embolisms from a CT exam. It uses a U-net network to detect embolisms candidates and classifies them between false positives and true positives using machine learning algorithms. The method achieved a dice score of 0.81 and an IoU of 0.79.
Environmental and Regional Effects on Fiber Quality of Cotton Cultivated in Greece

The cultivation of cotton and in particular the quality characteristics of the fiber are mainly influenced by the growing conditions, the cultivation techniques as well as the climatic changes of the environment. The current study aimed to quantify the impact of environment, season, and their interactions on cotton fiber quality of different areas where cotton is grown in Greece. A large-scale database was created, consisting of more than 20,000 fiber samples from cotton fields of the four major cotton-producing regions of Greece (Thrace, Macedonia, Central Greece, and Thessaly) during 2016–2020, in order to evaluate thirteen fiber quality traits that were divided into four groups (fiber maturity, fiber length, color, and trash traits). The results of this work demonstrated that the effect of the environment and the interaction of the environment with year (season), were the important source of variance for almost all the qualitative characteristics studied. Regional climatic characteristics such as temperature, humidity and rainfall also significantly affected to a greater or lesser extent all quality characteristics. In conclusion, the different cultivation regions, in the broader sense of an environment that incorporates both climatic and management parameters, show stability in terms of the studied groups of quality parameters. This stability is independent of the high or low performance of the group features.
Revalidating the Positive Achievement Change Tool (PACT) in a Major City: A Survival Analysis

The Positive Achievement Change Tool (PACT) is a popular risk-assessment tool used in juvenile justice systems across the country. This study is an effort at revalidating the PACT in the context of a large Southern city by utilizing days to recidivism in the context of survival analysis. The current research is concerned with whether the PACT’s risk classifications are effective in predicting recidivism. Findings indicate that the PACT effectively predicts recidivism better than chance and that recidivism is especially common early on in probation, with most incidents taking place within the first 200 days. However, the predictive validity of the PACT is not strong for the study population, and its implementation may benefit from context-specific reforms.
The Development of Prison Officers’ Job Satisfaction and its Impact on Depersonalization of Incarcerated Persons: The Role of Organizational Dehumanization

This article contributes to the literature on the antecedents and consequences of prison officers’ job satisfaction. First, we argue that organizational dehumanization (i.e., employees’ perceptions of being treated as tools by their organization) explains how work environment factors determine job satisfaction. Second, we propose that the role played by organizational dehumanization in the development of job satisfaction carries over depersonalization of incarcerated persons. The study (N = 357 Belgian prison officers) supports the mediating role of organizational dehumanization in the relationships between four work environment factors (organizational justice, appropriateness of material resources, quality of the physical environment, and perceived organizational support compared with that of the persons who are incarcerated) and job satisfaction. In addition, the findings indicate that prison officers’ perception of being dehumanized by their prison trickles down in the development of depersonalized relationships with incarcerated persons, and this effect is mediated by prison officers’ job satisfaction.
Chronic Pain: Among Tertiary Care Psychiatric Out-Patients in Singapore—Prevalence and Associations with Psychiatric Disorders

Objective The study aimed to determine the prevalence and severity of chronic pain and its associations amongst psychiatric out-patients in a tertiary care hospital in Singapore. Methodology. The cross-sectional study was conducted among 290 psychiatric out-patients aged 21–65 years. Sociodemographic and clinical information, as well as data from Brief Pain Inventory-Short Form (BPI-sf), Beck's Depression Inventory II (BDI-II), and Beck's Anxiety Inventory (BAI) were collected. Cut points (C.P.s) dividing the sample into mild, moderate, and severe groups were created for the ratings of average pain. Eight possible cut-off values for the C.P.s between 3 and 7, representing 8 different categorical variables, were created and their relationships were examined with BPI's set of seven interference items using multivariate analysis of variance. Sociodemographic and clinical correlates of chronic pain were determined using multinomial logistic regression analysis. Analysis of covariance was used to determine the association of BPI with continuous scores of BAI and BDI. Results Based on the C.P. pain severity classification, 38.5% of the sample had mild pain, 22.9% had moderate pain, and 11.8% had severe pain. Patients with severe pain were more likely to be associated with older age (p ≤ 0.006) (versus young age), less likely to be married (p ≤ 0.025) (versus single), and more likely to have high risk for obesity (p ≤ 0.030) (versus low risk for obesity). Participants with mild pain were seen to be significantly associated with older age (p ≤ 0.021), whereas moderate pain (p ≤ 0.002) and severe pain (p ≤ 0.001) (versus no pain) were seen to be significantly associated with higher BAI scores. Conclusion The current study observed high prevalence of pain among patients with psychiatric illness that was determined by optimal C.P.s for mild, moderate, and severe pain. Patients diagnosed with anxiety disorders and those with higher BMI were seen to be associated with pain of moderate to severe intensity. Improving the knowledge of correlates and co-morbidities of physical pain would aid in early identification, use of prophylactic strategies, and the intervention techniques to formulate basic guidelines for pain management among psychiatric population.
Lactobacillus Ameliorates SD-Induced Stress Responses and Gut Dysbiosis by Increasing the Absorption of Gut-Derived GABA in Rhesus Monkeys

Sleep deprivation (SD) has become a health problem in the modern society. Although probiotics supplementation has been proven to improve SD-induced gut dysbiosis, the potential neuroendocrine mechanisms remain elusive. In this study, thirty rhesus monkeys (RMs) were recruited. Paradoxical sleep, bright light, and noise were used to build an RM SD model. We examined the plasma γ-aminobutyric acid (GABA), stress hormones, and inflammatory cytokines using ELISAs. 16S ribosomal DNA sequencing and untargeted metabolomics sequencing were employed to detect gut microbial community and metabolites, respectively. The results of our study showed that RMs subjected to SD had elevated plasma stress hormones (such as cortisol and norepinephrine) and proinflammatory cytokines (such as TNF-α, IL-6, and IL-8), and a decreased anti‐inflammatory cytokine IL-10 level. Additionally, SD could give rise to a significant change in gut microbiota and metabolites. The differential gut microbiota and metabolites caused by SD were enriched in the signaling pathways related to GABA metabolism. Pearson correlation analysis revealed that there is a significant correlation between plasma GABA and SD-induced stress responses and gut dysbiosis. The supplementation of GABA-producing probiotics could significantly increase the relative abundance of Lactobacillus and plasma GABA levels, and reverse SD‐induced stress responses and gut dysbiosis. Therefore, we speculated that SD-induced stress response and gut dysbiosis might be an outcome of reduced gut-derived GABA absorption. The supplementation of GABA-producing Lactobacillus might be beneficial for the treatment of SD-induced intestinal dysfunction.
An Analog EIC-PIC Receiver With Carrier Phase Recovery for Self-Homodyne Coherent DCIs

Coherent techniques, used for high-capacity optical links, conventionally use high-speed ADCs and digital signal processing, which make them power hungry. For short-reach coherent links such as data center interconnects, power consumption, form factor, cost, and latency have to be greatly reduced. Co-designed photonic and electronic integrated circuits, in the optical and electrical analog domains, respectively, can achieve these goals. In this brief, for the first time, we present integration of a silicon photonic integrated coherent receiver (ICR) front-end with an electronic carrier phase recovery chip, as a part of a complete coherent receiver solution. A phase shifter in the ICR (fabricated in a 220 nm silicon-on-insulator technology) receives feedback from the CPR chip, and the combination compensates for the time varying phase offset between the modulated signal and the unmodulated carrier in the closed loop configuration. In this proof-of-concept demonstration, we present experimental results obtained from the stand-alone ICR, and its system level integration with CPR chip, for QPSK signals. The technique can be extended to a higher-order modulation formats, such as 16-QAM, for capacity scaling. The proposed scheme is suitable for carrier-forwarded coherent links, such as polarization multiplexed carrier based self-homodyne links.
The Role of Perceived Entrepreneurial Passion on Creativity: A Study of Vietnamese Social Ventures

This research aims to examine whether social venture founder’s entrepreneurial passion can increase employee creativity via creative process engagement and the moderating role of employee mindfulness. A survey was conducted by asking employees of 109 social ventures in Vietnam to evaluate the founders’ entrepreneurial passion and the supervisors to evaluate employees’ creativity as well as employee creative process engagement. Drawing on the broaden-and-build theory, this study found that employee creativity increases when the employees perceive that the social venture founders have strong entrepreneurial passion as explain by higher creative process engagement. In addition, we revealed that the indirect influence of entrepreneurial passion on employee creativity remains significant regardless the employees’ mindfulness. Theoretical and practical contributions are further discussed.