Miracle-dz/UniFAR-FTUs huggingface dataset:
Management of diabetic women with threatened preterm birth: a survey of Maternal-Fetal Medicine providers

Abstract Objective: To evaluate variation in management of diabetic women with threatened preterm birth (PTB). Study design: Thirty-two-question electronic maternal-fetal medicine (MFM) provider survey advertised on the Society for MFM website, newsletter, and Facebook page with questions about antenatal steroid use in diabetic women and glycemic management strategy after steroid administration. Descriptive statistics were used to summarize respondent characteristics, practice patterns, and satisfaction with current practice. Multivariable logistic regression was performed to determine if there were any factors independently associated with provider-reported satisfaction. Result: We obtained 159 completed surveys: 69% from board-certified MFM providers and 31% from MFM fellows. Almost half (48%) of respondents reported caring for diabetic women with threatened PTB at least weekly. Overall, 74% were concerned about the risk of maternal hyperglycemia after steroids, but 86% believed the neonatal benefit outweighed maternal risk. More than half (64%) agreed or strongly agreed that steroids for diabetic pregnant women were “evidence-based,” and as such, the majority answered that they administer steroids always or most of the time, ranging from 92% for women with uncontrolled type 1 diabetes to 100% for women with diet-controlled gestational diabetes. The frequency of hospitalization and management approach to obtain glycemic control varied by diabetes type and degree of antepartum glycemic control. Two-thirds of MFM providers reported being satisfied with their current practice in caring for these women. Use of a standard protocol for glycemic management was also associated with increased odds of satisfaction (aOR 4.5, 95% CI 1.3–16.1) whereas use of a continuous insulin infusion for all women with insulin-dependent diabetes was associated with decreased odds of satisfaction (aOR 0.3, 95% CI 0.1–0.8). There was no significant association observed between number of years in practice or frequency of care for diabetic women with threatened PTB and provider satisfaction. Overall, 49% of respondents desired a protocol to guide glycemic management, and 74% believed more research is needed to optimize care of diabetic women receiving steroids for threatened PTB. Conclusion: While there are no prospective studies examining the neonatal benefit of antenatal steroids in diabetic women, MFM respondents believe steroid use in this context is evidence-based and report they are administering steroids almost universally in this population. Variation exists in the glycemic management strategy used after steroid administration. While use of a standard protocol for glycemic control was associated with practice satisfaction, routine use of a continuous insulin infusion for all women with insulin-dependent diabetes was associated with lower odds of satisfaction. More research is needed to optimize care of diabetic women receiving steroids for threatened PTB as maternal and neonatal outcomes related to these practices remain unknown.
Secalonic Acid-F, a Novel Mycotoxin, Represses the Progression of Hepatocellular Carcinoma via MARCH1 Regulation of the PI3K/AKT/β-catenin Signaling Pathway

Liver cancer is a very common and significant health problem. Therefore, powerful molecular targeting agents are urgently needed. Previously, we demonstrated that secalonic acid-F (SAF) suppresses the growth of hepatocellular carcinoma (HCC) cells (HepG2), but the other anticancer biological functions and the underlying mechanism of SAF on HCC are unknown. In this study, we found that SAF, which was isolated from a fungal strain in our lab identified as Aspergillus aculeatus, could inhibit the progression of hepatocellular carcinoma by targeting MARCH1, which regulates the PI3K/AKT/β-catenin and antiapoptotic Mcl-1/Bcl-2 signaling cascades. First, we confirmed that SAF reduced the proliferation and colony formation of HCC cell lines (HepG2 and Hep3B), promoted cell apoptosis, and inhibited the cell cycle in HepG2 and Hep3B cells in a dose-dependent manner. In addition, the migration and invasion of HepG2 and Hep3B cells treated with SAF were significantly suppressed. Western blot analysis showed that the level of MARCH1 was downregulated by pretreatment with SAF through the regulation of the PI3K/AKT/β-catenin signaling pathways. Moreover, knockdown of MARCH1 by small interfering RNAs (siRNAs) targeting MARCH1 also suppressed the proliferation, colony formation, migration, and invasion as well as increased the apoptotic rate of HepG2 and Hep3B cells. These data confirmed that the downregulation of MARCH1 could inhibit the progression of hepatocellular carcinoma and that the mechanism may be via PI3K/AKT/β-catenin inactivation as well as the downregulation of the antiapoptotic Mcl-1/Bcl-2. In vivo, the downregulation of MARCH1 by treatment with SAF markedly inhibited tumor growth, suggesting that SAF partly blocks MARCH1 and further regulates the PI3K/AKT/β-catenin and antiapoptosis Mcl-1/Bcl-2 signaling cascade in the HCC nude mouse model. Additionally, the apparent diffusion coefficient (ADC) values, derived from magnetic resonance imaging (MRI), were increased in tumors after SAF treatment in a mouse model. Taken together, our findings suggest that MARCH1 is a potential molecular target for HCC treatment and that SAF is a promising agent targeting MARCH1 to treat liver cancer patients.
Acute cannabis toxicity

Abstract Objective: We describe the clinical effects of, and products associated with, acute exposures to cannabis during the early legalization period of recreational cannabis in Oregon and Alaska. Methods: This was an observational study of Oregon/Alaska Poison Center data between 4 December 2015 and 15 April 2017. A standardized data collection instrument was created for this study that captured information about cannabis product description, route of exposure, intentional vs unintentional exposure, product dose, product manufacture source, product ownership source, initial vital signs, clinical signs and symptoms, and subject disposition. Subjects were included if the Poison Center received a call about an acute exposure to cannabis from the subject, subject’s family member or friend, or healthcare worker participating in the subject’s care. Subjects were excluded if there was no evident exposure, the exposure was chronic, there were co-ingestants, or the subject was non-human (e.g. pet). Results: Two hundred fifty three individuals were acutely exposed to cannabis (median age 20 years; range 8 months – 96 years; 54.2% males): 71 (28.1%) children (<12 years), 42 (16.6%) adolescents (12–17 years), and 140 (55.3%) adults (≥18 years). Children were most likely to unintentionally (98.6%) ingest (97.2%) homemade (35.2%) edibles (64.8%) belonging to a family member (73.2%) and experience sedation (52.1%). Adults were most likely to intentionally (88.6%) ingest (66.4%) retail (40.0%) edibles (48.6%) and experience neuroexcitation (47.1%). Adolescents’ exposures had similarities to both adult and children; they were most likely to intentionally (81.0%) ingest (50.0%) homemade (23.8%) edibles (45.2%) belonging to a friend (47.3%) and to experience either neuroexcitation (42.9%) or sedation (40.5%). Among all ages, tachycardia and neuroexcitation were more likely following inhalation exposures compared to ingestions. Eight subjects were admitted to an intensive care unit, including three patients who were intubated; one subject died. Edibles were the most common products to cause symptoms in all age groups, while concentrated products were more likely to lead to intubation, especially when ingested. Children in particular had a higher likelihood of intensive care unit admission and intubation following exposure to concentrated products. Conclusions: Neurotoxicity is common after acute cannabis exposures. Children experienced unintentional exposures, particularly within the home and occasionally with major adverse outcomes. Concentrated products such as resins and liquid concentrates were associated with greater toxicity than other cannabis products. These findings may help guide other states during the early retail cannabis legalization period.
Prospects for the Use of Cannabinoids in Oncology and Palliative Care Practice: A Review of the Evidence

There is an increased interest in the use of cannabinoids in the treatment of symptoms in cancer and palliative care patients. Their multimodal action, in spite of limited efficacy, may make them an attractive alternative, particularly in patients with multiple concomitant symptoms of mild and moderate intensity. There is evidence to indicate cannabis in the treatment of pain, spasticity, seizures, sleep disorders, nausea and vomiting, and Tourette syndrome. Although the effectiveness of cannabinoids is limited, it was confirmed in neuropathic pain management and combination with opioids. A relatively favorable adverse effects profile, including no depressive effect on the respiratory system, may make cannabis complement a rather narrow armamentarium that is in the disposition of a palliative care professional.
Temperature and external K+ dependence of electrical excitation in ventricular myocytes of cod-like fishes

ABSTRACT Electrical excitability (EE) is vital for cardiac function and strongly modulated by temperature and external K+ concentration ([K+]o), as formulated in the hypothesis of temperature-dependent deterioration of electrical excitability (TDEE). As little is known about EE of arctic stenothermic fishes, we tested the TDEE hypothesis on ventricular myocytes of polar cod (Boreogadus saida) and navaga (Eleginus nawaga) of the Arctic Ocean and those of temperate freshwater burbot (Lota lota). Ventricular action potentials (APs) were elicited in current-clamp experiments at 3, 9 and 15°C, and AP characteristics and the current needed to elicit APs were examined. At 3°C, ventricular APs of polar cod and navaga were similar but differed from those of burbot in having a lower rate of AP upstroke and a higher rate of repolarization. EE of ventricular myocytes – defined as the ease with which all-or-none APs are triggered – was little affected by acute temperature changes between 3 and 15°C in any species. However, AP duration (APD50) was drastically reduced at higher temperatures. Elevation of [K+]o from 3 to 5.4 mmol l−1 and further to 8 mmol l−1 at 3, 9 and 15°C strongly affected EE and AP characteristics in polar cod and navaga, but had a lesser effect in burbot. In all species, ventricular excitation was resistant to acute temperature elevations, while small increases in [K+]o severely compromised EE, in particular in the marine stenotherms. This suggests that EE of the heart in these Gadiformes species is resistant against acute warming, but less so against the simultaneous temperature and exercise stresses. Summary: Electrical excitability of the heart in three Gadiformes species (polar cod, navaga and burbot) is resistant against acute warming, but less so against simultaneous temperature and exercise stress.
Periarticular Mesenchymal Progenitors Initiate and Contribute to Secondary Ossification Center Formation During Mouse Long Bone Development

Long bone development involves the embryonic formation of a primary ossification center (POC) in the incipient diaphysis followed by postnatal development of a secondary ossification center (SOC) at each epiphysis. Studies have elucidated major basic mechanisms of POC development, but relatively little is known about SOC development. To gain insights into SOC formation, we used Col2‐Cre Rosa‐tdTomato (Col2/Tomato) reporter mice and found that their periarticular region contained numerous Tomato‐positive lineage cells expressing much higher Tomato fluorescence (termed TomatoH) than underlying epiphyseal chondrocytes (termed TomatoL). With time, the TomatoH cells became evident at the SOC invagination site and cartilage canal, increased in number in the expanding SOC, and were present as mesenchymal lineage cells in the subchondral bone. These data were verified in two mouse lineage tracing models, Col2‐CreER Rosa‐tdTomato and Gli1‐CreER Rosa‐tdTomato. In vitro tests showed that the periarticular TomatoH cells from Col2/Tomato mice contained mesenchymal progenitors with multidifferentiation abilities. During canal initiation, the cells expressed vascular endothelial growth factor (VEGF) and migrated into epiphyseal cartilage ahead of individual or clusters of endothelial cells, suggesting a unique role in promoting vasculogenesis. Later during SOC expansion, chondrocytes in epiphyseal cartilage expressed VEGF, and angiogenic blood vessels preceded TomatoH cells. Gene expression analyses of microdissected samples revealed upregulation of MMPs in periarticular cells at the invagination site and suggested potential roles for novel kinase and growth factor signaling pathways in regulating SOC canal initiation. In summary, our data indicate that the periarticular region surrounding epiphyseal cartilage contains mesenchymal progenitors that initiate SOC development and form subchondral bone. Stem Cells 2019;37:677–689
The Effect of Barley and Lysine Supplementation of Pasture-Based Diet on Growth, Carcass Composition and Physical Quality Attributes of Meat from Farmed Fallow Deer (Dama dama)

Simple Summary Interest in deer farming has become more popular in European countries and, thus, production of venison under farm conditions is of utmost importance. Despite an increasing demand and interest in venison, only a few studies summarizing the effects of different diets on the growth, carcass parameters and the quality of meat from fallow deer have been published. Our study was the first to evaluate the effects of dietary barley and lysine supplementation on carcass parameters and physical quality of venison from farm-raised fallow deer. Supplementation with barley increased live weight gain, slaughter and carcass weights and fatness characteristics, whereas the addition of lysine to the barley-supplemented diet reduced the amounts of internal and carcass fat. Abstract Fallow deer (Dama dama) are important meat producing species providing venison and other products to an international market. The present study investigated the effects of different feed rations on the growth, carcass characteristics and physical attributes of the longissimus lumborum (LL) and semitendinosus (SET) muscles of 45 farm-raised male fallow deer. The animals were divided into three separate groups: 15 pasture-fed (P), 15 pasture-fed and supplemented with barley (B), and 15 pasture-fed and supplemented with barley and lysine (BL). The animals were slaughtered at an average age of 17 months at three time points: after 155, 169 and 183 days on feed. The addition of barley to the feed ration significantly increased weight gain and had positive effects on slaughter and carcass weights, dressing-out proportion, carcass composition, the weight of LL muscle, and increased the redness, yellowness and chroma values of LL muscle. The supplementation with lysine reduced the amounts of carcass and internal fats without compromising other economically important traits.
Patterns in Outpatient Benzodiazepine Prescribing in the United States

Key Points Question How are benzodiazepines being prescribed, and how have prescribing patterns changed over time? Findings In this serial cross-sectional study of 386 457 ambulatory care visits from 2003 through 2015, the use of benzodiazepines in ambulatory care increased substantially from 3.8% to 7.4% of visits, including coprescribing with other sedating medications. Use among psychiatrists was stable (29.6% vs 30.2%) but increased among all other types of physicians, including primary care physicians (3.6% vs 7.5%), who as a group accounted for about half of all benzodiazepine visits. Meaning In light of increasing death rates associated with benzodiazepine overdose, addressing prescribing patterns may help curb the growing use of benzodiazepines.
GHSR DNA hypermethylation is a new epigenetic biomarker for gastric adenocarcinoma and beyond

Aberrations of DNA methylation are early events in the development of tumors. In this study, we investigated the DNA methylation status of growth hormone secretagogue receptor (GHSR), a promising pan‐cancer biomarker, in gastric cancer (GC). Initially, data sets from DNA methylation and gene expression studies available at Gene Expression Omnibus (GEO) were analyzed. Confirmation was done on primary tumor specimens and adjacent normal stomach tissue samples. Both analyses showed significant hypermethylation of GHSR. For further validation, The Cancer Genome Atlas data on stomach cancer was used. A receiver operating characteristic curve analysis yielded an area under the curve value of 0.85, corroborating its usefulness as a diagnostic marker. A genome‐wide comethylation analysis revealed several correlated genes. CREB1 was found to act as an upstream regulator of this gene network. Furthermore, GHSR methylation was found to be a biomarker in several other tumor entities, namely cancers of the bladder, endometrium, esophagus, head and neck, liver, thyroid, kidney, and ovary. Our findings along with previous reports on other types of cancer suggest a high potential of GHSR gene methylation as a pan‐cancer biomarker, which could be considered for liquid biopsy applications.
Patterns of Referral for Fertility Preservation Among Female Adolescents and Young Adults with Breast Cancer: A Population-Based Study

Purpose: To assess the fertility preservation (FP) referral rates and patterns of newly diagnosed breast cancer in female adolescent and young adult (AYA) patients. Methods: Women aged 15–39 years with newly diagnosed breast cancer in Ontario from 2000 to 2017 were identified using the Ontario Cancer Registry. Exclusion criteria included prior sterilizing procedure, health insurance ineligibility, and prior infertility or cancer diagnosis. Women with a gynecology consult between cancer diagnosis and chemotherapy commencement with the billed infertility diagnostic code (ICD-9 628) were used as a surrogate for FP referral. The effect of age, parity, year of cancer diagnosis, staging, income, region, neighborhood marginalization, and rurality on referral status was investigated. Results: A total of 4452 patients aged 15–39 with newly diagnosed breast cancer met the inclusion criteria. Of these women, 178 (4.0%) were referred to a gynecologist with a billing code of infertility between cancer diagnosis and initiation of chemotherapy. Older patients, prior parity, and advanced disease were inversely correlated with referrals. Referral rates also varied regionally: patients treated in the south-east and south-west Local Health Integration Networks (LHINs) had the highest probability of referral, and patients covered by north LHINs had the lowest (central LHIN as reference). General surgeons accounted for 36.5% of all referrals, the highest percentage of all specialists. Referral rates significantly increased over time from 0.4% in 2000 to 10.7% in 2016. Conclusion: FP referral rates remain low and continue to be influenced by patient demographics and prognosis. These findings highlight the need for further interdisciplinary coordination in addressing the fertility concerns of AYA with newly diagnosed breast cancers.
Rapid Water Softening with TEMPO-Oxidized/Phosphorylated Nanopapers

Water hardness not only constitutes a significant hazard for the functionality of water infrastructure but is also associated with health concerns. Commonly, water hardness is tackled with synthetic ion-exchange resins or membranes that have the drawbacks of requiring the awkward disposal of saturated materials and being based on fossil resources. In this work, we present a renewable nanopaper for the purpose of water softening prepared from phosphorylated TEMPO-oxidized cellulose nanofibrils (PT-CNF). Nanopapers were prepared from CNF suspensions in water (PT-CNF nanopapers) or low surface tension organic liquids (ethanol), named EPT-CNF nanopapers, respectively. Nanopaper preparation from ethanol resulted in a significantly increased porosity of the nanopapers enabling much higher permeances: more than 10,000× higher as compared to nanopapers from aqueous suspensions. The adsorption capacity for Ca2+ of nanopapers from aqueous suspensions was 17 mg g−1 and 5 mg g−1 for Mg2+; however, EPT-CNF nanopapers adsorbed more than 90 mg g−1 Ca2+ and almost 70 mg g−1 Mg2+. The higher adsorption capacity was a result of the increased accessibility of functional groups in the bulk of the nanopapers caused by the higher porosity of nanopapers prepared from ethanol. The combination of very high permeance and adsorption capacity constitutes a high overall performance of these nanopapers in water softening applications.
Expression of Vascular Endothelial Growth Factor and Its Receptors in Thyroid Nodular Hyperplasia and Papillary Thyroid Carcinoma: A Tertiary Health Care Centre Based Study

Introduction: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in thyroid cancer. VEGF is known to have high affinity to VEGF receptors such as VEGFR-1 (Flt-1) and VEGFR-2 (KDR). Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and studies showed the increasing incidence of PTC arising in nodular hyperplasia. Targeted therapy on these growth factors and receptors are used in management of both differentiated and undifferentiated thyroid carcinoma. This study aims to determine the expression of VEGF and VEGF receptors (VEGFR) in thyroid nodular hyperplasia and PTC. Methods: A cross-sectional study based on paraffinized archival tissue blocks of 113 nodular hyperplasias and 67 PTC from the thyroidectomy specimens in the year of 2003 to 2014. The tissue sections were then stained by immunohistochemistry for VEGF, VEGFR-1 and VEGFR-2. The lymph node involvement and extrathyroid extension also were determined. Results: The mean age of PTC patients was 44.7±15.8 years and nodular hyperplasia were 42.2±13.6 years. There was a statistical difference of VEGFR-1 (p=0.028) and VEGFR-2 (p=0.003) expression between nodular hyperplasia and PTC. However, no significant difference of VEGF expression (p=0.576) between both diseases. Co-expression of VEGF and VEGFR-1 was significant in both nodular hyperplasia (p=0.016) and PTC (p=0.03), meanwhile no relevant relationship for VEGF and VEGFR-2 expression (p>0.05). No significant association (p>0.05) between lymph node status and extrathyroid extension with age groups, gender, VEGF and VEGFR expression. Conclusions: VEGF, VEGFR-1 and VEGFR-2 showed overexpression in both nodular hyperplasia and PTC. The expression of VEGFR-1 and VEGFR-2 are more significant in PTC with relevant co-expression of VEGF and VEGFR-1. Therefore, the inhibition of VEGFR offers a promising prospect for tumour management in thyroid carcinoma.