Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Kinins in Hypertension and Heart Failure

The kallikrein–kinin system (KKS) is proposed to act as a counter regulatory system against the vasopressor hormonal systems such as the renin-angiotensin system (RAS), aldosterone, and catecholamines. Evidence exists that supports the idea that the KKS is not only critical to blood pressure but may also oppose target organ damage. Kinins are generated from kininogens by tissue and plasma kallikreins. The putative role of kinins in the pathogenesis of hypertension is discussed based on human mutation cases on the KKS or rats with spontaneous mutation in the kininogen gene sequence and mouse models in which the gene expressing only one of the components of the KKS has been deleted or over-expressed. Some of the effects of kinins are mediated via activation of the B2 and/or B1 receptor and downstream signaling such as eicosanoids, nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and/or tissue plasminogen activator (T-PA). The role of kinins in blood pressure regulation at normal or under hypertension conditions remains debatable due to contradictory reports from various laboratories. Nevertheless, published reports are consistent on the protective and mediating roles of kinins against ischemia and cardiac preconditioning; reports also demonstrate the roles of kinins in the cardiovascular protective effects of the angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor blockers (ARBs).
Factors influencing the bias between blood gas analysis versus central laboratory hemoglobin testing. A secondary analysis of a randomized controlled trial

Background Anemia is the most important complication during major surgery and transfusion of red blood cells is the mainstay to compensate for life threating blood loss. Therefore, accurate measurement of hemoglobin (Hb) concentration should be provided in real-time. Blood Gas Analysis (BGA) provides rapid point-of-care assessment using smaller sampling tubes compared to central laboratory (CL) services. Objective This study aimed to investigate the accuracy of BGA hemoglobin testing as compared to CL services. Methods Data of the ongoing LIBERAL-Trial (Liberal transfusion strategy to prevent mortality and anemia-associated ischemic events in elderly non-cardiac surgical patients, LIBERAL) was used to assess the bias for Hb level measured by BGA devices (ABL800 Flex analyzer®, GEM series® and RapidPoint 500®) and CL as the reference method. For that, we analyzed pairs of Hb level measured by CL and BGA within two hours. Furthermore, the impact of various confounding factors including age, gender, BMI, smoker status, transfusion of RBC, intraoperative hemodilution, and co-medication was elucidated. In order to ensure adequate statistical analysis, only data of participating centers providing more than 200 Hb pairs were used. Results In total, three centers including 963 patients with 1,814 pairs of Hb measurements were analyzed. Mean bias was comparable between ABL800 Flex analyzer® and GEM series®: - 0.38 ± 0.15 g/dl whereas RapidPoint 500® showed a smaller bias (-0.09 g/dl) but greater median absolute deviation (± 0.45 g/dl). In order to avoid interference with different standard deviations caused by the different analytic devices, we focused on two centers using the same BGA technique (309 patients and 1,570 Hb pairs). A Bland-Altman analysis and LOWESS curve showed that bias decreased with smaller Hb values in absolute numbers but increased relatively. The smoker status showed the greatest reduction in bias (0.1 g/dl, p<0.001) whereas BMI (0.07 g/dl, p = 0.0178), RBC transfusion (0.06 g/dl, p<0.001), statins (0.04 g/dl, p<0.05) and beta blocker (0.03 g/dl, p = 0.02) showed a slight effect on bias. Intraoperative substitution of volume and other co-medications did not influence the bias significantly. Conclusion Many interventions like substitution of fluids, coagulating factors or RBC units rely on the accuracy of laboratory measurement devices. Although BGA Hb testing showed a consistently stable difference to CL, our data confirm that BGA devices are associated with different bias. Therefore, we suggest that hospitals assess their individual bias before implementing BGA as valid and stable supplement to CL. However, based on the finding that bias decreased with smaller Hb values, which in turn are used for transfusion decision, we expect no unnecessary or delayed RBC transfusion, and no major impact on the LIBERAL trial performance.
Tricky partners: native plants show stronger interaction preferences than their exotic counterparts.

In ecological networks, neutral predictions suggest that species' interaction frequencies are proportional to their relative abundances. Deviations from neutral predictions thus correspond to interaction preferences (when positive) or avoidances (when negative), driven by non-neutral (e.g. niche-based) processes. Exotic species interact with many partners with which they have not coevolved, and it remains unclear whether this systematically influences the strength of neutral processes on interactions, and how these interaction-level differences scale up to entire networks. To fill this gap, we compared interactions between plants and frugivorous birds at nine forest sites in New Zealand varying in the relative abundance and composition of native and exotic species, with independently sampled data on bird and plant abundances from the same sites. We tested if the strength and direction of interaction preferences differed between native and exotic species. We further evaluated whether the performance of neutral predictions at the site level was predicted by the proportion of exotic interactions in each network from both bird and plant perspectives, and the species composition in each site. We found that interactions involving native plants deviated more strongly from neutral predictions than did interactions involving exotics. This "pickiness" of native plants could be detrimental in a context of global biotic homogenization where they could be increasingly exposed to novel interactions with neutrally-interacting mutualists. However, the realization of only a subset of interactions in different sites compensated for the neutrality of interactions involving exotics, so that neutral predictions for whole networks did not change systematically with the proportion of exotic species nor species composition. Therefore, the neutral and niche processes that underpin individual interactions may not scale up to entire networks. This shows that seemingly simplistic neutral assumptions entail complex processes and can provide valuable understanding of community assembly or invasion dynamics.
Targeting CREB in Cancer Therapy: A Key Candidate or One of Many? An Update

Simple Summary Only 5% of all drug-related targets currently move from preclinical to clinical in cancer, and just some of them achieve patient’s bedside. Among others, intratumor heterogeneity and preclinical cancer model limitations actually represent the main reasons for this failure. Cyclic-AMP response element-binding protein (CREB) has been defined as a proto-oncogene in different tumor types, being involved in maintenance and progression. Due to its relevance in tumor pathophysiology, many CREB inhibitor compounds have been developed and tested over the years. Herein, we examine the current state-of-the-art of both CREB and CREB inhibitors in cancer, retracing some of the most significant findings of the last years. While the scientific statement confers on CREB a proactive role in cancer, its therapeutic potential is still stuck at laboratory bench. Therefore, pursuing every concrete result to achieve CREB inhibition in clinical might give chance and future to cancer patients worldwide. Abstract Intratumor heterogeneity (ITH) is considered the major disorienting factor in cancer treatment. As a result of stochastic genetic and epigenetic alterations, the appearance of a branched evolutionary shape confers tumor plasticity, causing relapse and unfavorable clinical prognosis. The growing evidence in cancer discovery presents to us “the great paradox” consisting of countless potential targets constantly discovered and a small number of candidates being effective in human patients. Among these, cyclic-AMP response element-binding protein (CREB) has been proposed as proto-oncogene supporting tumor initiation, progression and metastasis. Overexpression and hyperactivation of CREB are frequently observed in cancer, whereas genetic and pharmacological CREB downregulation affects proliferation and apoptosis. Notably, the present review is designed to investigate the feasibility of targeting CREB in cancer therapy. In particular, starting with the latest CREB evidence in cancer pathophysiology, we evaluate the advancement state of CREB inhibitor design, including the histone lysine demethylases JMJD3/UTX inhibitor GSKJ4 that we newly identified as a promising CREB modulator in leukemia cells. Moreover, an accurate analysis of strengths and weaknesses is also conducted to figure out whether CREB can actually represent a therapeutic candidate or just one of the innumerable preclinical cancer targets.
Beyond Mohs surgery and excisions: A focused review of treatment options for subtypes of basal cell carcinoma

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. It originates from undifferentiated cells in the basal cell layer of the epidermis or from the outer root sheath of the hair follicle. The most important factor in development of BCC is ultraviolet radiation. Surgery is considered the gold standard of treatment for BCC. However, nonsurgical options are available for individuals who are unsuitable for surgery. The purpose of this review is to summarize the efficacy and indications of alternative, nonsurgical treatments that can be used in the management of BCC. An extensive literature review was performed for the nonsurgical options for the treatment of BCC. Resources searched included PubMed and Google Scholars, limited to the years 1995 to 2020. Key words searched included BCC, destructive methods, photodynamic therapy (PDT), radiotherapy, topical medication, laser, hedgehog pathway inhibitors (HPIs). The most relevant results such as systematic reviews, randomized controlled trials, or comparative studies were selected to provide a summary for the most common nonsurgical methods used for treating BCC. Effective nonsurgical treatments for BCC include destructive methods (eg, curettage alone, cryosurgery, or electrodessication), PDT, topical medications, radiotherapy, laser, and HPIs. Nonsurgical therapeutic alternatives are safe and effective for the treatment of BCC. Factors such as tumor location, size, and histopathological subtype should be taken into consideration when selecting optimal treatment. In addition to clinical factors, cosmetic results and patient preference should be considered.
Characteristics of Thermosetting Polymer Nanocomposites: Siloxane-Imide-Containing Benzoxazine with Silsesquioxane Epoxy Resins

A series of innovative thermosetting polymer nanocomposites comprising of polysiloxane-imide-containing benzoxazine (PSiBZ) as the matrix and double-decker silsesquioxane (DDSQ) epoxy or polyhedral oligomeric silsesquioxane (POSS) epoxy were prepared for improving thermosetting performance. Thermomechanical and dynamic mechanical characterizations indicated that both DDSQ and POSS could effectively lower the coefficient of thermal expansion by up to approximately 34% and considerably increase the storage modulus (up to 183%). Therefore, DDSQ and POSS are promising materials for low-stress encapsulation for electronic packaging applications.
A survey of the young person’s experience of Graves’ disease and its management

A suboptimal quality of life (QoL) has been reported in patients with Graves’ disease treated in adult life, but long‐term QoL in those treated in childhood and adolescence is unclear. We wanted to understand how Graves’ disease and its management impact on the physical, psychological and social well‐being of young people and their longer‐term QoL.
Single versus bilateral internal thoracic artery grafting in patients with low ejection fraction

Abstract Coronary artery bypass grafting (CABG) is the standard of care for the treatment of complex coronary artery disease. However, the optimal surgical treatment for patients with reduced left ventricular function with low ejection fraction (EF) is inconclusive. In our center, left-sided coronary grafting with bilateral internal thoracic artery (BITA) is generally the preferred method for surgical revascularization, also for patients with low EF. We compared early and long-term outcomes between BITA grafting and single internal thoracic artery (SITA) grafting in patients with low EF. We evaluated short- and long-term outcomes of all patients who underwent surgical revascularization in our center during 1996 to 2011, according to EF ≥30% and <30%. Univariate and multivariate analyses were performed. In addition, patients who underwent BITA and SITA grafting were matched using propensity score matching. In total, 5337 patients with multivessel disease underwent surgical revascularization during the study period. Of them, 394 had low EF. Among these, 188 underwent SITA revascularization and 206 BITA grafting. Those who underwent SITA were more likely to have comorbidities such as chronic obstructive pulmonary disease, diabetes, congestive heart failure, chronic renal failure, and a critical preoperative condition including preoperative intra-aortic balloon pump insertion. Statistically significant differences were not observed between the SITA and BITA groups in 30-day mortality (8.5% vs 6.8%, P = .55), sternal wound infection (2.7% vs 1.0%, P = .27), stroke (3.7% vs 6.3%, P = .24), and perioperative myocardial infarction (5.9% vs 2.9%, P = .15). Long-term survival (median follow up of 14 years, interquartile range, 11.2–18.9) was also similar between the groups. Propensity score matching (129 matched pairs) yielded similar early and long-term outcomes for the groups. This study did not demonstrate any clinical benefit for BITA compared with SITA revascularization in individuals with low EF.
let-7 controls the transition to adulthood by releasing select transcriptional regulators from repression by LIN41

Development of multicellular organisms relies on faithful temporal control of cell fates. In Caenorhabditis elegans, the heterochronic pathway governs temporal patterning of somatic cells. This function may be phylogenetically conserved as several heterochronic genes have mammalian orthologues, and as the heterochronic let-7 miRNA and its regulator LIN28 appear to time the onset of puberty in mice and humans. Here, we have investigated how let-7 promotes the transition to adulthood in C. elegans. We find that let-7 controls each of three relevant processes, namely male and female sexual organ morphogenesis as well as changes in skin progenitor cell fates, through the same single target, lin-41. LIN41 in turn silences two pairs of targets post-transcriptionally, by binding and silencing their mRNAs. The EGR-type transcription factor LIN-29a and its co-factor, the NAB1/2 orthologous MAB-10, mediate control of progenitor cell fates and vulval integrity. By contrast, male tail development depends on regulation of the DM domain-containing transcription factors DMD-3 and MAB-3. Our results provide mechanistic insight into an exemplary temporal patterning pathway, demonstrate that let-7 – LIN41 function as a versatile regulatory module that can be connected to different outputs, and reveal how several levels of post-transcriptional regulation ultimately achieve effects through controlling transcriptional outputs.
Maternal Dietary Patterns during Pregnancy and Their Association with Gestational Weight Gain and Nutrient Adequacy

Several epidemiologic studies have shown an association between Gestational Weight Gain (GWG) and offspring complications. The GWG is directly linked to maternal dietary intake and women’s nutritional status during pregnancy. The aim of this study was (1) to assess, in a sample of Spanish pregnant women, the association between maternal dietary patterns and GWG and (2) to assess maternal dietary patterns and nutrient adequate intake according to GWG. A retrospective study was conducted in a sample of 503 adult pregnant women in five hospitals in Eastern Andalusia (Spain). Data on demographic characteristics, anthropometric values, and dietary intake were collected from clinical records by trained midwives. Usual food intake was gathered through a validated Food Frequency Questionnaire (FFQ), and dietary patterns were obtained by principal component analysis. Nutrient adequacy was defined according to European dietary intake recommendations for pregnant women. Regression models adjusted by confounding factors were constructed to study the association between maternal dietary pattern and GWG, and maternal dietary patterns and nutritional adequacy. A negative association was found between GWG and the Mediterranean dietary pattern (crude β = −0.06, 95% CI: −0.11, −0.04). Independent of maternal dietary pattern, nutrient adequacy of dietary fiber, vitamin B9, D, E, and iodine was related to a Mediterranean dietary pattern (p < 0.05). A Mediterranean dietary pattern is related to lower GWG and better nutrient adequacy. The promotion of healthy dietary behavior consistent with the general advice promoted by the Mediterranean Diet (based on legumes, vegetables, nuts, olive oil, and whole cereals) will offer healthful, sustainable, and practical strategies to control GWG and ensure adequate nutrient intake during pregnancy.
Management of a “suspected ward” in a COVID-19 designated hospital in Wuhan

Abstract During December 2019, an outbreak of unexplained pneumonia occurred in Wuhan, Hubei Province. The disease was subsequently named coronavirus disease 2019 (COVID-19) and the causative virus as severe acute respiratory syndrome conronavirus-2 (SARS-CoV-2). Based on experience, it is vital to exclude or diagnose suspected patients as soon as possible to prevent disease spread. Our hospital is a COVID-19 designated hospital in Wuhan. During the epidemic period, there was a reconstruction of the medical facilities to accommodate patients with different disease status. We document the development of “suspected ward,” a ward that cared for patients with suspected COVID-19, in a large designated hospital during the COVID-19 outbreak in Wuhan City, China, and explain the suspected ward spatial layout, organization structure, diagnosis, and treatment flow chart of suspected cases. The key characteristics of our “suspected ward” is isolation, triage, fast diagnosis, and rapid referral. Our description of this suspected ward provides a reference for further improvements in the care of patients with suspected disease in emergency medical institutions.
Inferior epigastric artery lymph nodes: A pathway for systemic dissemination from peritoneal carcinomatosis?

We report, for the first time in the literature, a metastatic lymphatic pathway along the inferior epigastric vessels, through the inferior epigastric lymph nodes (IELNs), in patients with peritoneal carcinomatosis (PC). Interestingly, these lymph nodes (LNs) in the anterior retroperitoneum were not detectable on preoperative imaging. They may, however, represent a pertinent systemic dissemination pathway for PC.
The Effect of Smoking during Pregnancy on Severity and Directionality of Externalizing and Internalizing Symptoms: A Genetically Informed Approach

The objective was to examine the association between maternal smoking during pregnancy (SDP) and (I) severity and (II) directionality of externalizing and internalizing symptoms in a sample of sibling pairs while rigorously controlling for familial confounds. The Missouri Mothers and Their Children Study is a family study (N = 173 families) with sibling pairs (aged 7 to 16 years) who are discordant for exposure to SDP. This sibling comparison study is designed to disentangle the effects of SDP from familial confounds. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount). Principal component analysis of externalizing and internalizing behavior, assessed with the Child Behavior Checklist and Teacher Report Form, was used to create symptom severity and directionality scores. The variance in severity and directionality scores was primarily a function of differences between siblings (71% and 85%, respectively) rather than differences across families (29% and 15%, respectively). The severity score that combines externalizing and internalizing symptom severity was not associated with SDP. However, a significant within-family effect of SDP on symptom directionality (b = 0.07, p = 0.04) was observed in the sibling comparison model. The positive directionality score indicates that SDP is associated with differentiation of symptoms towards externalizing rather than internalizing symptoms after controlling for familial confounds with a sibling comparison model. This supports a potentially causal relationship between SDP and externalizing behavior.
Loop-Mediated Isothermal Amplification as Point-of-Care Diagnosis for Neglected Parasitic Infections

The World Health Organisation (WHO) has placed twenty diseases into a group known as neglected tropical diseases (NTDs), twelve of them being parasitic diseases: Chagas’ disease, cysticercosis/taeniasis, echinococcosis, food-borne trematodiasis, human African trypanosomiasis (sleeping sickness), leishmaniasis, lymphatic filariasis, onchocerciasis (river blindness), schistosomiasis, soil-transmitted helminthiasis (ascariasis, hookworm, trichuriasis), guinea-worm and scabies. Such diseases affect millions of people in developing countries where one of the main problems concerning the control of these diseases is diagnosis-based due to the most affected areas usually being far from laboratories having suitable infrastructure and/or being equipped with sophisticated equipment. Advances have been made during the last two decades regarding standardising and introducing techniques enabling diagnoses to be made in remote places, i.e., the loop-mediated isothermal amplification (LAMP) technique. This technique’s advantages include being able to perform it using simple equipment, diagnosis made directly in the field, low cost of each test and the technique’s high specificity. Using this technique could thus contribute toward neglected parasite infection (NPI) control and eradication programmes. This review describes the advances made to date regarding LAMP tests, as it has been found that even though several studies have been conducted concerning most NPI, information is scarce for others.