syedzayyan/paper_mill_benchmark huggingface dataset:
Simulation Models for Prediction of Bioavailability of Medicinal Drugs-the Interface Between Experiment and Computation.

The oral drug bioavailability (ba) problems have remained inevitable over the years, impairing drug efficacy and indirectly leading to eventual human morbidity and mortality.However, some conventional lab-based methods improve drug absorption leading to enhanced ba, and the recent experimental techniques are up-and-coming.Nevertheless, some have inherent drawbacks in improving the efficacy of poorly insoluble and low impermeable drugs.Drug ba and strategies to overcome these challenges were briefly highlighted.This review has significantly unravelled the different computational models for studying and predicting drug bioavailability.Several computational approaches provide mechanistic insights into the oral drug delivery system simulation of descriptors like solubility, permeability, transport protein-ligand interactions, and molecular structures.The in silico techniques have long been known still are just being applied to unravel drug bioavailability issues.Many publications have reported novel applications of the computational models towards achieving improved drug ba, including predicting gastrointestinal tract (git) drug absorption properties and passive intestinal membrane permeability, thus maximizing time and resources.Also, the classical molecular simulation models for free solvation energies of soluble-related processes such as solubilization, dissolutions, supersaturation, and precipitation have been used in virtual screening studies.A few of the tools are gastro plus tmthat supports biowaiver for drugs, mainly bcs class iii and predicts drug compounds' absorption and pharmacokinetic process; sim cyp® simulator for mechanistic modelling and simulation of drug formulation processes; pharmacodynamics analysis on non-linear mixed-effects modelling; and mathematical models, predicting absorption potential/maximum absorption dose.This review provides in silico-experiment annexation in the drug bioavailability enhancement, possible insights that lead to critical opinion on the applications and reliability of the various in silico models as a growing tool for drug development and discovery, thus accelerating drug development processes.

Journal: AAPS PharmSciTech (2022)
Publication types: Journal Article;Review
Molecular Surveillance and Prediction of Antimicrobial Resistance of Neisseria gonorrhoeae in Northern Alberta, Canada, 2015 to 2018.

The aims of this study was to describe molecular surveillance of neisseria gonorrhoeae in the north zone of alberta (nz) and to determine its value in predicting antimicrobial resistance.Methods sequence types (sts) and single-nucleotide polymorphism (snp) assays were performed on nucleic acid amplification testing (naat) samples.Sequence types of naats were matched to st of cultures from across alberta.Antimicrobial resistance prediction of naats for cephalosporins, azithromycin, and ciprofloxacin using snp was compared with matching st culture results using agar dilution and whole-genome sequencing.Results of 2755 eligible specimens (2492 cases), 61.9% (1646 specimens) were sent for sequence typing, identifying 196 unique st.Antimicrobial resistance data for 1307 additional cases were available using matching cultures.Decreased susceptibility (ds) to antimicrobials used for gonorrhea treatment was rare in the nz; according to the snp assay, none of the specimens had predicted ds to cephalosporins or azithromycin resistance.However, of the nz naat samples tested in this study, 10.7% (131 of 1220) were predicted to have intermediate cephalosporin minimum inhibitory concentrations and 9.6% (115 of 1204) were resistant to ciprofloxacin.Based on cultures, the proportions of resistance in all of alberta were as follows: ds to cephalosporins, 0.6% (20 of 3373); ds to intermediate cephalosporin, 16.9% (570 of 3373); azithromycin resistance, 1.2% (41 of 3373); and ciprofloxacin resistance, 32.2% (1087 of 3373).Conclusions our results highlight our ability to use culture-independent methods to predict antimicrobial resistance in n.Gonorrhoeae.

Journal: Sexually transmitted diseases (2022)
Publication types: Journal Article
Molecular epidemiology of SARS-CoV-2 isolated from COVID-19 family clusters.

Transmission within families and multiple spike protein mutations have been associated with the rapid transmission of sars-co v-2.We aimed to: (1) describe full genome characterization of sars-co v-2 and correlate the sequences with epidemiological data within family clusters, and (2) conduct phylogenetic analysis of all samples from yogyakarta and central java, indonesia and other countries.Methods the study involved 17 patients with covid-19, including two family clusters.We determined the full-genome sequences of sars-co v-2 using the illumina mi seq next-generation sequencer.Phylogenetic analysis was performed using a dataset of 142 full-genomes of sars-co v-2 from different regions.Results ninety-four snps were detected throughout the open reading frame (orf) of sars-co v-2 samples with 58% (54/94) of the nucleic acid changes resulting in amino acid mutations.About 94% (16/17) of the virus samples showed d614g on spike protein and 56% of these (9/16) showed other various amino acid mutations on this protein, including l5f, v83l, v213a, w258r, q677h, and n811i.The virus samples from family cluster-1 (n = 3) belong to the same clade gh, in which two were collected from deceased patients, and the other from the survived patient.All samples from this family cluster revealed a combination of spike protein mutations of d614g and v213a.Virus samples from family cluster-2 (n = 3) also belonged to the clade gh and showed other spike protein mutations of l5f alongside the d614g mutation.Conclusions our study is the first comprehensive report associating the full-genome sequences of sars-co v-2 with the epidemiological data within family clusters.Phylogenetic analysis revealed that the three viruses from family cluster-1 formed a monophyletic group, whereas viruses from family cluster-2 formed a polyphyletic group indicating there is the possibility of different sources of infection.This study highlights how the same spike protein mutations among members of the same family might show different disease outcomes.

Journal: BMC medical genomics (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Ten-Step Minimally Invasive Treatment of Lumbar Giant Disc Herniation via Unilateral Tubular Laminotomy for Bilateral Decompression: 2-Dimensional Operative Video.

Giant disc herniation (gdh) is generally defined as a lumbar disc herniation that obstructs 50% or more of the space in the spinal canal.1-3 common treatment options for gdh include unilateral interlaminar approach, bilateral approach, or open full laminectomy.4,5 surgical treatment of gdh may be challenging because severe bilateral compression of neural elements in the spinal canal increases the risk of iatrogenic injury to nerve roots and dura.The surgical approach can be further complicated by calcification, hardening, and dehydration of the gdh tissue.The prevailing opinion in the literature is that giant disc herniations cannot safely be treated via tubular minimally invasive approaches.5-7 in this video, we present a case of a 52-yr-old male patient with a history of progressive low back pain that radiates bilaterally from the buttocks toward the posterior legs and knees for 2 yr because of a gdh at the l4-5 level.The patient was treated via a tubular "over-the-top" minimally invasive decompression in order to first provide generous bilateral decompression of neural elements and dura.8,9 after sufficient decompression at the surgical level, the discectomy was performed via an ipsilateral piecemeal resection of the gdh.The "over-the-top" contralateral mobilization of disc herniation was also achieved with this approach, which facilitated the removal of the entire disc fragment.Patient consent was obtained prior to performing the procedure.Therefore, gdh should not be considered as a contraindication for tubular decompression when this modified technique is performed.

Journal: Operative neurosurgery (Hagerstown, Md.) (2021)
Publication types: Journal Article
Interaction and mediation effects of economic growth and innovation performance on carbon emissions: Insights from 282 Chinese cities.

China is under rapid urbanization and consequently facing increasing carbon emissions (ce).Economic growth (eg) and innovation performance (ip), as two critical indicators of urbanization, are considered the driving forces of ce.Although economy and innovation are entangled and can jointly affect ce in reality, the measured effects of economy and innovation on ce are often treated separately in traditional studies.We adopted a three-part research framework including the total, interaction and mediation effect tests to elucidate how eg and ip affected ce in china from 2005 to 2015 based on insights from 282 chinese cities.The empirical results showed that both economy and innovation contributed to ce, although the contribution has reduced over the 11 years.In particular, the interaction effect between economy and innovation for north china, northeast china, and southwest china was -4.201, -8.442, and - 3.897, respectively, in 2015, meaning that these regions adversely affect ce.In addition, we found that the economy helps reduce ce via innovation.When considering the changes of economy and innovation, their mediation effect on ce changes varied in different regions, attributable to the level of economy and innovation as well as the stocks of energy resources.Therefore, future planning for low-carbon transition should regard the economy and innovation together.Based on this principle, we propose five detailed policies.Overall, this study is valuable not only for further understanding the triangle relationship among economy, innovation, and ce, but also for reaching low-carbon goals.

Journal: The Science of the total environment (2022)
Publication types: Journal Article
Diluted aqueous extract of heat-not-burn tobacco product smoke causes less oxidative damage in fibroblasts than conventional cigarette.

Smoke from conventional cigarettes (c-cigarettes) contains various reactive oxygen species and toxic chemicals, which potentially cause oxidative damage not only to airways but also to the whole body, leading eventually to diseases, including emphysema, advanced atherosclerosis, and cancer.Many heat-not-burn tobacco products (htps) have been commercialized recently in japan to maintain the smoking population by advertising that htps are less toxic.However, there were few studies reported from neutral organizations whether htps are indeed less damaging.To evaluate the potential capacity of htps to induce oxidative stress, we here compared two different htps with two types of c-cigarettes, using human fibroblast imr90sv cells and 5% aqueous extracts in 10-ml phosphate-buffered saline (50-ml smoke/10 s).Htps exhibited significantly lower oxidative toxicity in comparison to c-cigarettes.Whereas c-cigarettes induced ferroptosis in fibroblasts, the effects of htps were significantly reduced by measuring the levels of peroxides, pro-inflammatory cytokine expression, autophagy, catalytic fe(ii) and 8-hydroxy-2'-deoxyguanosine.Notably, major portions of c-cigarettes-induced pathogenic responses were inhibited by catalase.However, htps still induced p62 autophagy-adaptor at 5%-dilution and caused lethal effects to fibroblasts with undiluted solution.In conclusion, htps smokeper secan be toxic despite less toxicity in comparison to c-cigarettes, which warrants further investigation.

Journal: Journal of clinical biochemistry and nutrition (2022)
Publication types: Journal Article
Treating the N0 neck in early stage oral cancer: a pause for re-assessment?

The incidence of metastases following neck dissection in the apparent lymph node negative neck in oral cancer is between 7% and 33%; early resection of cervical metastases may well increase survival.Modern imaging techniques can reduce the yield of previously undiagnosed metastatic nodes in elective neck dissection (end).An audit of 112 consecutive cases was conducted to determine the proportion of undiagnosed nodal metastases, after end.There were neck metastases in 10 cases (9%), which were mainly (but not all) micrometastic.The 20% likelihood of nodal metastases was only apparent in primary tumours greater than 6 mm thick.The length of inpatient stay was increased from 3.7 to 16.5 days with free vascularised transfer.There were complications including cranial nerve damage.There were two peri-operative deaths.No ipsilateral neck failures occurred, median follow up was 937 days.To reduce unnecessary end, resection can be undertaken as a prior procedure, subsequently only carrying out end on tumours greater than 6 mm, or with unfavourable tumour characteristics.

Journal: The British journal of oral & maxillofacial surgery (2021)
Publication types: Journal Article
Risk assessment and prediction for lung cancer among Hong Kong Chinese men.

Most of the previous risk prediction models for lung cancer were developed from smokers, with discriminatory power ranging from 0.57 to 0.72.We constructed an individual risk prediction model for lung cancer among the male general population of hong kong.Methods epidemiological data of 1,069 histology confirmed male lung cancer cases and 1,208 community controls were included in this analysis.Residential radon exposure was retrospectively reconstructed based on individual lifetime residential information.Multivariable logistic regression with repeated cross-validation method was used to select optimal risk predictors for each prediction model for different smoking strata.Individual absolute risk for lung cancer was estimated by gail model.Receiver-operator characteristic curves, area under the curve (auc) and confusion matrix were evaluated to demonstrate the model performance and ability to differentiate cases from non-cases.Results smoking and smoking cessation, education, lung disease history, family history of cancer, residential radon exposure, dietary habits, carcinogens exposure, mask use and dust control in workplace were selected as the risk predictors for lung cancer.The auc of estimated absolute risk for all lung cancers was 0.735 (95% ci: 0.714-0.756).Using 2.83% as the cutoff point of absolute risk, the predictive accuracy, positive predictive value and negative predictive value were 0.715, 0.818 and 0.674, respectively.Conclusion we developed a risk prediction model with moderate discrimination for lung cancer among hong kong males.External validation in other populations is warranted for this model in future studies.

Journal: BMC cancer (2022)
Publication types: Journal Article
Bovine oocyte developmental competence and gene expression following co-culturing with ampullary cells: An experimental study.

There is no sufficient information on the impact of bovine ampullary oviductal epithelial cells (baoecs) on in vitro oocyte maturation competence and gene expression.Objective this study aimed to examine the oocyte developmental competence following co-culturing with a monolayer of fresh and frozen-thawed ampullary cells.Materials and methods bovine cumulus-oocyte complexes (cocs) were distributed into three groups: control group; where in cocs were cultured in cell-free media for 24 hr and fml and ftml groups in which the cocs were cultured in maturation media for 18 hr and then transferred into a media containing fresh and frozen-thawed baoecs monolayer, respectively (baoecs were extracted from the oviducts of slaughtered cattle and were then cultured freshly or frozen-thawed) for a further 6 hr.After 24 hr, the expanded cocs were evaluated for nuclear maturation, fertilization rate, and gene expression (gdf9, st ar, casp3, and fshr).Results nuclear maturation rate in the ftml group was significantly higher than the control group (p = 0.02).The fertilization rate of ftml group was significantly higher than the control and fml groups (p = 0.05 and p = 0.03, respectively).In terms of gene expression,gdf9were upregulated in the presence of the baoecs during the last 6 hr of the in vitro maturation (p<0.001).Furthermore, the expression of the st argene in the ftml group was higher than the other groups (p = 0.02).Conclusion ampullary cells co-culturing (especially frozen-thawed cells) for in vitro maturation of bovine oocytes yields encourages the results and demonstrates the beneficial effect of co-culture on gene expression and developmental competence.

Journal: International journal of reproductive biomedicine (2021)
Publication types: Journal Article
Intracranial aneurysm wall enhancement as an indicator of instability: a systematic review and meta-analysis.

And purpose aneurysm wall enhancement (awe) of intracranial aneurysms on magnetic resonance imaging has been described in previous studies as a surrogate marker of instability.With this study, an updated literature overview and summary risk estimates of the association between awe and different specific outcomes (i.e., rupture, growth or symptomatic presentation) for both cross-sectional and longitudinal studies are provided.Methods the prisma guideline was followed and a search was performed of pub med and embase to 1 january 2021 for studies that reported on awe and aneurysm instability.In cross-sectional studies, awe was compared between patients with stable and unstable aneurysms.In longitudinal studies, awe of stable aneurysms was assessed at baseline after which patients were followed longitudinally.Risk ratios were calculated for longitudinal studies, prevalence ratios for cross-sectional studies and then the ratios were pooled in a random-effects meta-analysis.Also, the performance of awe to differentiate between stable and unstable aneurysms was evaluated.Results twelve studies were included with a total of 1761 aneurysms.In cross-sectional studies, awe was positively associated with rupture (prevalence ratio 11.47, 95% confidence interval [ci] 4.05-32.46) and growth or symptomatic presentation (prevalence ratio 4.62, 95% ci 2.85-7.49).Longitudinal studies demonstrated a positive association between awe and growth or rupture (risk ratio 8.00, 95% ci 2.14-29.88).Assessment of the performance of awe showed high sensitivities, mixed specificities, low positive predictive values and high negative predictive values.Conclusions although awe is positively associated with aneurysm instability, current evidence mostly supports the use of its absence as a surrogate marker of aneurysm stability.

Journal: European journal of neurology (2021)
Publication types: Journal Article;Meta-Analysis;Review;Systematic Review
Age-dependent aneuploidy in mammalian oocytes instigated at the second meiotic division.

Ageing severely affects the chromosome segregation process in human oocytes resulting in aneuploidy, infertility and developmental disorders.A considerable amount of segregation errors in humans are introduced at the second meiotic division.We have here compared the chromosome segregation process in young adult and aged female mice during the second meiotic division.More than half of the oocytes in aged mice displayed chromosome segregation irregularities at anaphase ii, resulting in dramatically increased level of aneuploidy in haploid gametes, from 4% in young adult mice to 30% in aged mice.We find that the post-metaphase ii process that efficiently corrects aberrant kinetochore-microtubule attachments in oocytes in young adult mice is approximately 10-fold less efficient in aged mice, in particular affecting chromosomes that show small inter-centromere distances at the metaphase ii stage in aged mice.Our results reveal that post-metaphase ii processes have critical impact on age-dependent aneuploidy in mammalian eggs.

Journal: Aging cell (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Accuracy of High-Frequency Ultrasound Scanner in Detecting Peri-implant Bone Defects.

The purpose of this study was to assess the accuracy of high-frequency ultrasound (us) in the measurement of peri-implant bone defects in comparison with cone-beam computed tomography (cbct) and micro-computed tomography (μct).Bone defects were mechanically created around dental implants inserted into porcine ribs (n = 10).The bone samples were scanned by cbct, μct and us.Linear dimensions of the peri-implant defects were determined for supra-alveolar component, intra-bony component and width.The accuracy of measurements was evaluated with repeated-measures analysis of variance and the intra-class correlation coefficient at p ≤ 0.05.Us underestimated the measurements for the supra-alveolar and intra-bony components in comparison to cbct and μct, and there were no statistically significant differences in the measurements of width.The intra-class correlation coefficient of us ranged from 0.96 to 0.98, whereas that for cbct ranged from 0.77 to 0.97.Us was accurate in measuring the width of peri-implant defects, although vertical measurements were underestimated by approximately 1 mm in comparison to those of cbct and μct.

Journal: Ultrasound in medicine & biology (2019)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Breeding More Crops in Less Time: A Perspective on Speed Breeding.

Breeding crops in a conventional way demands considerable time, space, inputs for selection, and the subsequent crossing of desirable plants.The duration of the seed-to-seed cycle is one of the crucial bottlenecks in the progress of plant research and breeding.In this context, speed breeding (sb), relying mainly on photoperiod extension, temperature control, and early seed harvest, has the potential to accelerate the rate of plant improvement.Well demonstrated in the case of long-day plants, the sb protocols are being extended to short-day plants to reduce the generation interval time.Flexibility in sb protocols allows them to align and integrate with diverse research purposes including population development, genomic selection, phenotyping, and genomic editing.In this review, we discuss the different sb methodologies and their application to hasten future plant improvement.Though sb has been extensively used in plant phenotyping and the pyramiding of multiple traits for the development of new crop varieties, certain challenges and limitations hamper its widespread application across diverse crops.However, the existing constraints can be resolved by further optimization of the sb protocols for critical food crops and their efficient integration in plant breeding pipelines.

Journal: Biology (2022)
Publication types: Journal Article;Review