syedzayyan/paper_mill_benchmark huggingface dataset:
Effects of 18-months metformin versus placebo in combination with three insulin regimens on RNA and DNA oxidation in individuals with type 2 diabetes: A post-hoc analysis of a randomized clinical trial.

Formation of reactive oxygen species has been linked to the development of diabetes complications.Treatment with metformin has been associated with a lower risk of developing diabetes complications, including when used in combination with insulin.Metformin inhibits complex 1 in isolated mitochondria and thereby decreases the formation of reactive oxygen species.Thus, we post-hoc investigated the effect of metformin in combination with different insulin regimens on rna and dna oxidation in individuals with type 2 diabetes.Four hundred and fifteen individuals with type 2 diabetes were randomized (1:1) to blinded treatment with metformin (1,000 mg twice daily) versus placebo and to (1:1:1) open-label biphasic insulin, basal-bolus insulin, or basal insulin therapy in a 2 × 3 factorial design.Rna and dna oxidation were determined at baseline and after 18 months measured as urinary excretions of 8-oxo-7,8-dihydroguanosine (8-oxo guo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxod g), respectively.Urinary excretion of 8-oxo guo changed by +7.1% (95% ci: 0.5% to 14.0%, p = 0.03) following metformin versus placebo, whereas changes in 8-oxod g were comparable between intervention groups.Biphasic insulin decreased urinary excretion of 8-oxo guo (within-group: -9.6% (95% ci: -14.4% to -4.4%)) more than basal-bolus insulin (within-group: 5.2% (95% ci: -0.5% to 11.2%)), p = 0.0002 between groups, and basal insulin (within-group: 3.7% (95% ci: -2.0% to 9.7%)), p = 0.0007 between groups.Urinary excretion of 8-oxod g decreased more in the biphasic insulin group (within-group: -9.9% (95% ci: -14.4% to -5.2%)) than basal-bolus insulin (within group effect: -1.2% (95% ci: -6.1% to 3.9%)), p = 0.01 between groups, whereas no difference was observed compared with basal insulin.In conclusion, eighteen months of metformin treatment in addition to different insulin regimens increased rna oxidation, but not dna oxidation.Biphasic insulin decreased both rna and dna oxidation compared with other insulin regimens.

Journal: Free radical biology & medicine (2022)
Publication types: Journal Article;Randomized Controlled Trial;Research Support, Non-U.S. Gov't
Outcomes With Intermediate Left Main Disease: Analysis From the ISCHEMIA Trial.

Patients with significant (≥50%) left main disease (lmd) have a high risk of cardiovascular events, and guidelines recommend revascularization to improve survival.However, the impact of intermediate lmd (stenosis, 25%-49%) on outcomes is unclear.Methods randomized ischemia (international study of comparative health effectiveness with medical and invasive approaches) participants who underwent coronary computed tomography angiography at baseline were categorized into those with (25%-49%) and without (<25%) intermediate lmd.The primary outcome was a composite of cardiovascular mortality, myocardial infarction (mi), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.The primary quality of life outcome was the seattle angina questionnaire summary score.Results among the 3699 participants who satisfied the inclusion criteria, 962 (26%) had intermediate lmd.Among invasive strategy participants with intermediate lmd on coronary computed tomography angiography, 49 (7.0%) had significant (≥50% stenosis) left main stenosis on invasive angiography.Patients with intermediate lmd had a higher risk of cardiovascular events in the unadjusted but not in the fully adjusted model compared with those without intermediate lmd.An invasive strategy increased procedural mi and decreased nonprocedural mi with no significant difference for other outcomes including the primary end point.There was no meaningful heterogeneity of treatment effect based on intermediate lmd status except for nonprocedural mi for which there was a greater absolute reduction with invasive management in the intermediate lmd group (-6.4% versus -2.0%;pinteraction=0.049).The invasive strategy improved angina-related quality of life and the benefit was durable throughout follow-up without significant heterogeneity based on intermediate lmd status.Conclusions in the ischemia trial, there was no meaningful heterogeneity of treatment benefit from an invasive strategy regardless of intermediate lmd status except for a greater absolute risk reduction in nonprocedural mi with invasive management in those with intermediate lmd.An invasive strategy increased procedural mi, reduced nonprocedural mi, and improved angina-related quality of life.Registration url: clinicaltrials gov; unique identifier: nct01471522.

Journal: Circulation. Cardiovascular interventions (2022)
Publication types: Journal Article;Randomized Controlled Trial;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
The Value of Medical Registries and Observational Studies Early in Pandemics: The Coronavirus Disease 2019 (COVID-19) Experience.

Whereas randomized clinical trials remain the gold standard for evaluating new therapies for infections, we argue that registries and observational studies early in the coronavirus disease 2019 (covid-19) pandemic provided invaluable understanding of the natural history and preliminary data on risk factors and possible treatments.We review the data from the current pandemic, the history of registries in general, and their value in public health emergencies.Lessons from these experiences should be incorporated into rigorous planning for the next pandemic.

Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2022)
Publication types: Journal Article;Review
Electronic Noses and Their Applications for Sensory and Analytical Measurements in the Waste Management Plants-A Review.

Waste management plants are one of the most important sources of odorants that may cause odor nuisance.The monitoring of processes involved in the waste treatment and disposal as well as the assessment of odor impact in the vicinity of this type of facilities require two different but complementary approaches: analytical and sensory.The purpose of this work is to present these two approaches.Among sensory techniques dynamic and field olfactometry are considered, whereas analytical methodologies are represented by gas chromatography-mass spectrometry (gc-ms), single gas sensors and electronic noses (en).The latter are the core of this paper and are discussed in details.Since the design of multi-sensor arrays and the development of machine learning algorithms are the most challenging parts of the en construction a special attention is given to the recent advancements in the sensitive layers development and current challenges in data processing.The review takes also into account relatively new en systems based on mass spectrometry and flash gas chromatography technologies.Numerous examples of applications of the en devices to the sensory and analytical measurements in the waste management plants are given in order to summarize efforts of scientists on development of these instruments for constant monitoring of chosen waste treatment processes (composting, anaerobic digestion, biofiltration) and assessment of odor nuisance associated with these facilities.

Journal: Sensors (Basel, Switzerland) (2022)
Publication types: Journal Article;Review
Effect of ultrasonic treatment on yield stress of highly concentrated cellulose nano-crystalline (CNC) aqueous suspensions.

The yield stress of highly concentrated cellulose nano-crystalline (cnc) suspensions is an important rheological property for different applications.The ultrasonic treatment is a common technique for dispersing cncs in aqueous media.Although the effect of ultrasonic processing on rheology of cnc suspensions has been previously investigated, a systematic approach studying the sonication effect on yield stress is missing in the literature.In this study, we investigated the effect of sonication energy within the energy level of 0-5000 j/g cncon static, dynamic and true yield points of a highly concentrated (8 wt%) aqueous cnc suspension, through a rheo-optics analysis.To better understand the yielding behaviour, the sonication effect on physicochemical properties of the cncs was also investigated.The results revealed that yield stress decreases with sonication energy through a four-step mechanism governed by the microstructural transformations of the cnc agglomerates.

Journal: Carbohydrate polymers (2022)
Publication types: Journal Article
Neurological manifestations in Onchocerca volvulus infection: A review.

Human onchocerciasis, caused by infection by the filarial nematode onchocerca volvulus, is a major neglected public health problem that affects millions of people in the endemic regions of sub-saharan africa and latin america.Onchocerciasis is known to be associated with skin and eye disease and more recently, neurological features have been recognized as a major manifestation.Especially the latter poses a severe burden on affected individuals and their families.Although definite studies are awaited, preliminary evidence suggests that neurological disease may include the nodding syndrome, nakalanga syndrome and epilepsy but to date, the exact pathophysiological mechanisms remain unclear.Currently, the only way to prevent onchocera volvulus associated disease is through interventions that target the elimination of onchocerciasis through community distribution of ivermectin and larviciding the breeding sites of the similium or blackfly vector in rivers.In this review, we discuss the epidemiology, potential pathological mechanisms as well as prevention and treatment strategies of onchocerciasis, focusing on the neurological disease.

Journal: Brain research bulletin (2019)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Review
The grass root endophytic fungus Flavomyces fulophazii: An abundant source of tetramic acid and chlorinated azaphilone derivatives.

Fungal endophytes are remarkable sources of biologically active metabolites of ecological and pharmacological significance.In this study, fungal isolates producing yellow pigments and originating from grass roots, were identified as the recently described grass root colonizing dark septate endophyte (dse), flavomyces fulophazii (periconiaceae, pleosporales).While analyzing the metabolite composition of 17 isolates of this fungus, 11 previously undescribed compounds, including four tetramic acids (dihydroxyvermelhotin, hydroxyvermelhotin, methoxyvermelhotin, oxovermelhotin), and seven chlorinated azaphilones (flavochlorines a-g), together with the known tetramic acid vermelhotin, were tentatively identified by high performance liquid chromatography (hplc)-tandem mass spectrometry (ms/ms).Among them, flavochlorine a, flavochlorine g, hydroxyvermelhotin and vermelhotin could be isolated by preparative hplc, thus their structures were also confirmed by nuclear magnetic resonance (nmr) spectroscopy.Vermelhotin was found to be the main compound, reaching its maximum level of 5.5 mg/g in the in vitro cultures of a selected f.Fulophazii isolate.A significant amount of vermelhotin was isolated by preparative hplc from these cultures (4.8 mg from 1.0 g lyophilized culture), confirming the practical utility of f.Fulophazii in high-yield vermelhotin production.The main compounds of this endophyte expressed no activity in standardized plant bioassays (i.e., in the lactuca sativa seed germination and lemna minor growth tests).An antiproliferative study of the isolated compounds confirmed moderate activity of vermelhotin against a panel of twelve cancer cell lines, with ic50ranges of 10.1-37.0 μm, without inhibiting the non-cancer vero cells, suggesting its selectivity towards cancers.

Journal: Phytochemistry (2021)
Publication types: Journal Article
Circadian rhythm disorder and anxiety as mental health complications in post-COVID-19.

In 2020, the world gained dramatic experience of the development of the 2019 coronavirus disease pandemic (covid-19) caused by severe acute respiratory syndrome 2 (sars-co v-2).Recent researches notice an increasing prevalence of anxiety and circadian rhythm disorders during covid-19 pandemic.The aim of the study was describing clinical features of circadian rhythm disorders and the level of anxiety in persons who have had covid-19.We have conducted a cohort retrospective study that included 278 patients who were divided into 2 study groups according to medical history: group 1 includes patients with a history of covid-19; group 2 consists of patients who did not have clinically confirmed covid-19 and are therefore considered not to have had this disease.To objectify circadian rhythm disorders, they were verified in accordance with the criteria of the international classification of sleep disorders-3.The level of anxiety was assessed by the state-trait anxiety inventory.The most common circadian rhythm disorders were sleep phase shifts.We found that covid-19 in the anamnesis caused a greater predisposition of patients to the development of circadian rhythm disorders, in particular delayed sleep phase disorder.In addition, it was found that after covid-19 patients have increased levels of both trait and state anxiety.In our study, it was the first time that relationships between post-covid-19 anxiety and circadian rhythm disorders had been indicated.Circadian rhythm disorders are associated with increased trait and state anxiety, which may indicate additional ways to correct post-covid mental disorders and their comorbidity with sleep disorders.

Journal: Environmental science and pollution research international (2022)
Publication types: Journal Article
Changes in emerging adults' alcohol and cannabis use from before to during the COVID-19 pandemic: Evidence from a prospective birth cohort.

Prospective research is needed to better-understand changes in substance use from before to during the coronavirus disease (covid-19) pandemic, among emerging adults (18-25 years), a high-risk group for substance use.Method n= 1,096 (weighted sample n= 1,080; 54% female) participants enrolled in the québec longitudinal study of child development, who completed prepandemic (2019; 21 years) and covid-19 (mid-march to mid-june 2020) surveys.Covid-19-related and preexisting factors were examined as moderators of change in substance use.Results full sample analyses revealed decreased binge drinking (p 150,f2 = 0.05) and binge drinking (p monthly use prepandemic decreased their binge drinking (p 150,f2 = .12) and cannabis use (p 150,f2 = .06), but did not change their alcohol use frequency.Several factors moderated change in substance use, including employment loss (p= .005, bf > 39,f2 = .03) and loneliness (p= .018, bf > 150,f2 = .10) during covid-19.Conclusions changes in alcohol and cannabis use frequency among emerging adults in the first 3 months of covid-19 largely differed according to prepandemic substance use, covid-19-related factors, and preexisting factors.While some youth with preexisting vulnerabilities (e.g., more frequent substance use prepandemic) remained stable or decreased their substance use during covid-19, emerging adults who experienced employment loss, loneliness, and financial concerns during covid-19 increased their substance use, highlighting the need for increased supports for vulnerable populations.(psyc info database record (c) 2022 apa, all rights reserved).

Journal: Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors (2022)
Publication types: Journal Article
PI3K/AKT/mTOR and TLR4/MyD88/NF-κB Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma.

Asthma is an inflammatory airway disease wherein bronchoconstriction, airway inflammation, and airway obstruction during asthma attacks are the main problems.It is recognized that imbalance of th1/th2 and th17/treg is a critical factor in asthma pathogenesis.Manipulation of these with signaling molecules such as m tor, pi3k, akt, and my d88 can control asthma.Mouse model of allergic asthma was produced and treated with ketamine, metformin, metformin and ketamine, triciribine, ly294002, and torin2.Mch challenge test, balf's eos count, the il-4, 5, inf-γ, eicosanoid, total ig e levels were determined.The muc5a, foxp3, rorγt, pi3k, m tor, akt, pu.1, and my d88 gene expressions and histopathology study were done.Asthma groups that were treated with all six components had reduced penh value, total ig e, il-4 and il-5 levels, muc5a, rorγt, my d88 and m tor expression, goblet cell hyperplasia, and mucus hyper-secretion.The eosinophil percentage and cys-lt level were decreased by metformin and ketamine, triciribine, ly294002, and torin2.The level of ifn-γ was increased in triciribine, ly294002, and torin2.Metformin, metformin and ketamine, triciribine, ly294002, and torin2 reduced akt and pi3k expression, peribronchial and perivascular inflammation, and increased expression of foxp3.Torin2 had an effect on pu.1 expression.Inhibition of pi3k/akt/m tor and tlr4/my d88/nf-κb signaling with targeted molecules can attenuate asthma pathology and play an important role in airways protection.

Journal: Inflammation (2021)
Publication types: Journal Article
Plasminogen activator receptor assemblies in cell signaling, innate immunity, and inflammation.

Tissue-type plasminogen activator (t pa) and urokinase-type plasminogen activator (u pa) are serine proteases and major activators of fibrinolysis in mammalian systems.Because fibrinolysis is an essential component of the response to tissue injury, diverse cells, including cells that participate in the response to injury, have evolved receptor systems to detect t pa and u pa and initiate appropriate cell-signaling responses.Formation of functional receptor systems for the plasminogen activators requires assembly of diverse plasma membrane proteins, including but not limited to: the urokinase receptor (u par); integrins;n-formyl peptide receptor-2 (fpr2), receptor tyrosine kinases (rtks), the n-methyl-d-aspartate receptor (nmda-r), and low-density lipoprotein receptor-related protein-1 (lrp1).The cell-signaling responses elicited by t pa and u pa impact diverse aspects of cell physiology.This review describes rapidly evolving knowledge regarding the structure and function of plasminogen activator receptor assemblies.How these receptor assemblies regulate innate immunity and inflammation is then considered.

Journal: American journal of physiology. Cell physiology (2021)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Review
SARS-CoV-2 and Emerging Foodborne Pathogens: Intriguing Commonalities and Obvious Differences.

The coronavirus disease 2019 (covid-19) has resulted in tremendous human and economic losses around the globe.The pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (sars-co v-2), a virus that is closely related to sars-co v and other human and animal coronaviruses.Although foodborne diseases are rarely of pandemic proportions, some of the causative agents emerge in a manner remarkably similar to what was observed recently with sars-co v-2.For example, shiga toxin-producing escherichia coli(stec), the most common cause of hemolytic uremic syndrome, shares evolution, pathogenesis, and immune evasion similarities with sars-co v-2.Both agents evolved over time in animal hosts, and during infection, they bind to specific receptors on the host cell's membrane and develop host adaptation mechanisms.Mechanisms such as point mutations and gene loss/genetic acquisition are the main driving forces for the evolution of sars-co v-2 and stec.Both pathogens affect multiple body organs, and the resulting diseases are not completely cured with non-vaccine therapeutics.However, sars-co v-2 and stec obviously differ in the nature of the infectious agent (i.e., virus vs.Bacterium), disease epidemiological details (e.g., transmission vehicle and symptoms onset time), and disease severity.Sars-co v-2 triggered a global pandemic while stec led to limited, but sometimes serious, disease outbreaks.The current review compares several key aspects of these two pathogenic agents, including the underlying mechanisms of emergence, the driving forces for evolution, pathogenic mechanisms, and the host immune responses.We ask what can be learned from the emergence of both infectious agents in order to alleviate future outbreaks or pandemics.

Journal: Pathogens (Basel, Switzerland) (2022)
Publication types: Journal Article;Review
Efficacy of Transarterial Chemoembolization Combined with Molecular Targeted Agents for Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis.

Transarterial chemoembolization (tace) combined with tyrosine kinase inhibitors (tkis) is the mainstay treatment for unresectable hepatocellular carcinoma (u hcc).However, studies investigating different combinations of agents have shown inconsistent results.Here, we used network meta-analysis (nma) to compare different agents across 41 studies (36 cohort studies and five rcts) in 11,540 patients.Multiple rcts and cohort studies were searched to evaluate tace combined with different tkis.Outcomes of interest included overall survival (os), progression-free survival (pfs), and tumor response.Nma used a random-effects consistency model to pool evidence from direct and indirect comparisons.Hazard ratio (hr) and relative risks (rr) with 95% confidence intervals (ci) were analyzed.Further, heterogeneity and publication bias analyses were performed and agents were ranked.Tace plus lenvatinib provided the maximal os (rank probability: 0.7559), pfs (rank probability: 0.8595), cr (rank probability: 0.4179), and dcr (rank probability: 0.3857).Tace plus anlotinib demonstrated the highest pr (p= 0.62649) and orr (p= 0.51158).Sd was more often associated with tace plus sorafenib (rank probability: 0.601685).Tace plus lenvatinib provides optimal treatment for u hcc based on the highest ranking of os, pfs, and dcr rates.However, given the lack of statistically significant os benefit, shared decision making should include other tkis as acceptable alternatives.

Journal: Cancers (2022)
Publication types: Journal Article;Review
Downregulation of hsa_circ_0001681 suppresses epithelial-mesenchymal transition in thyroid carcinoma via targeting to miR-942-5p/TWIST1 signaling pathway.

Thyroid carcinoma (tc) seriously threatens the health and safety of patients, and the treatment target of it still is poor.Rt-q pcr and western blot were carried out to detect the expression of genes and proteins, respectively.Cell proliferation was confirmed using colony formation assay.Transwell assay were performed to measure the cell migration and invasion.Besides, luciferase reporter assay was accomplished to ensure the target relationship between mi r-942-5p and twist1 m rna as well as hsa_circ_0001681.Here, we proved that hsa_circ_0001681 was increased in tc, and located majorly in the cytoplasm of tc cells.However, mi r-942-5p was decreased in tc, and was negatively correlated with hsa_circ_0001681 expression.Knockdown of hsa_circ_0001681 significantly repressed the proliferation, migration, invasion and emt of tc cells.We also found that the process of hsa_circ_0001681 silencing limited emt, which was obstructed by twist1 increasing.Moreover, hsa_circ_0001681 acted as a mi rna sponge and completed with twist1 m rna for binding to mi r-942-5p, thus downregulation of hsa_circ_0001681 repressed emt and subsequent malignant phenotype of tc cells through targeting mi r-942-5p/twist1 signaling pathway.Finally, the studies in vivo showed that decreasing of hsa_circ_0001681 effectively inhibited the growth of tumor via repressing emt by regulating mi r-942-5p/twist1 signaling pathway.Overall, silencing of hsa_circ_0001681 significantly suppressed tc progression through inhibiting emt via acting as a mi r-942-5p sponge to facilitate the expression of twist1.Our data provided a reliable evidence for hsa_circ_0001681 is a potential treatment target in tc.

Journal: Journal of bioenergetics and biomembranes (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't