syedzayyan/paper_mill_benchmark huggingface dataset:
Effect of biphenyl hydrolase-like (BPHL) gene disruption on the intestinal stability, permeability and absorption of valacyclovir in wildtype and Bphl knockout mice.

Biphenyl hydrolase-like protein (bphl) is a novel human serine hydrolase that was originally cloned from a breast carcinoma c dna library and shown to convert valacyclovir to acyclovir and valganciclovir to ganciclovir.However, the exclusivity of this process has not been determined and, indeed, it is possible that a number of esterases/proteases may mediate the hydrolysis of valacyclovir and similar prodrugs.The objectives of the present study were to evaluate the in situ intestinal permeability and stability of valacyclovir in wildtype (wt) and bphl knockout (ko) mice, as well as the in vivo oral absorption and intravenous disposition of valacyclovir and acyclovir in the two mouse genotypes.We found that bphl knockout mice had no obvious phenotype and that bphl ablation did not alter the jejunal permeability of valacyclovir during in situ perfusions (i.e., 0.54 × 10-4in wt vs.0.53 × 10-4cm/s in ko).Whereas no meaningful changes occurred between genotypes in the gene expression of proton-coupled oligopeptide transporters (i.e., pep t1, pep t2, ph t1, ph t2), enzymatic upregulation of cyp3a11, cyp3a16, abhd14a and abhd14b was observed in some tissues of bphl knockout mice.Most importantly, we found that valacyclovir was rapidly and efficiently hydrolyzed to acyclovir in the absence of bphl, and that hydrolysis was more extensive after the oral vs.Intravenous route of administration (for both genotypes).Taken as a whole, bphl is not obligatory for the conversion of valacyclovir to acyclovir either presystemically or systemically.

Journal: Biochemical pharmacology (2018)
Publication types: Journal Article;Research Support, N.I.H., Extramural
Influence of serum progesterone levels on the inflammatory response of female dogs with visceral leishmaniosis.

The aim of this study was to evaluate the histopathological changes to the mammary gland that occur in female dogs with visceral leishmaniosis and to correlate the findings with the parasite load, inflammatory cell profile in mammary tissue and serum progesterone levels.For this, 20 adult female dogs that were naturally infected with leishmania infantum, not spayed, not pregnant and free from mammary tumors were used.They were divided into two groups: g1 (n = 9) with high serum progesterone levels and g2 (n = 11) with low serum progesterone levels.The parasite load and the immunophenotype of leukocytes infiltrated into the mammary tissue (cd3, cd4, cd8 and mca874) were evaluated using the immunohistochemical technique.In the mammary gland, chronic inflammatory infiltrate was mainly found in g1, sometimes associated with granulomatous inflammation, higher parasite load and higher density of cells immunolabeled for cd3, cd4, cd8 and mca874.A significant positive correlation (p < 0.05) was observed between the parasite load and the immunolabeled leukocytes.The influence of the serum progesterone level in the mammary gland of infected female dogs can contribute to the maintenance of an immunosuppressive cell profile and favor the persistence of the parasite in this site.

Journal: Veterinary parasitology (2022)
Publication types: Journal Article
A Prospective Study of Clinical Characteristics and Interventions Required in Critically Ill Obstetric Patients.

Introduction obstetric patients are a special group of patients whose management is challenged by concerns for fetal viability, altered maternal physiology, and diseases specific to pregnancy.Materials and methods a prospective analysis of all obstetric patients admitted to the critical care department was done to assess reasons for transfer to the critical care unit (ccu) and the interventions required for management of these patients.Results between june 2013 and september 2017, obstetric admission comprised 95 women (5.9%) of the total critical care admissions.There were 77 patients (81.1%) who were discharged from the hospital and 18 patients (18.9%) died.In most of the cases, the primary reasons for shifting the patient to the ccu were severe preeclampsia with pulmonary edema (22.1%), eclampsia (8.4%), acute respiratory distress syndrome (ards) (14.7%), and hypovolemic shock in antepartum hemorrhage (aph) and postpartum hemorrhage (pph) (10.5 and 13.7%, respectively).It was seen that 73 patients (76.8%) required ventilator support, 58 patients (57.4%) required vasopressor support, and intensive hemodynamic monitoring and blood/blood products were transfused in 55 patients (54.5%).The need for ventilator support was more in patients with a lower pa o2/fi o2and a higher apache ii score.Patients with a high severity of illness score and a lower pa o2/fi o2had higher odds of requiring vasopressors.Low hemoglobin at the time of transfer to the ccu and a prolonged hospital stay were found to predict the need for blood transfusion.Conclusion obstetric patients are susceptible to critical illnesses but timely management improves the outcome of these young women.How to cite this article suri j, kumar r, gupta a, mittal p, suri jc.A prospective study of clinical characteristics and interventions required in critically ill obstetric patients.Indian j crit care med 2020;24(8):677-682.

Journal: Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine (2020)
Publication types: Journal Article
A decay-based account of learning and adaptation in complex skills.

How do humans adapt to parametric changes in a task without having to learn a new skill from scratch?Many studies of memory and sensorimotor adaptation have proposed theories that incorporate a decay on prior events, which leads the agent to eventually forget old experiences.This study investigates if a similar decay mechanism can account for human adaptation in complex skills that require the simultaneous integration of cognitive, motor, and perceptual processes.In 2 experiments, subjects learned to play a novel racing video game while adapting to parametric changes in the physics of the game's controls.Human learning and performance were modeled using the act-r cognitive architecture, which has been used successfully to model learning and fluency across a wide range of skills in prior research.Anderson et al.(2019) introduced the controller module, a new component of the architecture that learns the setting of control parameters for actions and allows the agent to execute the rapid and precise actions that are necessary for good performance on complex tasks.Model simulations support including a moderate time-based decay on the weight of the experiences that the controller uses.This is implemented in the controller module by discounting the influence of older observations which helps the agent to focus on recent experiences that better reflect the current relationship between different settings of a control parameter and the rate of payoff from using that setting.(psyc info database record (c) 2022 apa, all rights reserved).

Journal: Journal of experimental psychology. Learning, memory, and cognition (2021)
Publication types: Journal Article
Assessment of heavy metals in surface water, sediment and macrozoobenthos in inland rivers: a case study of the Heihe River, Northwest China.

Long-term retention and accumulation of heavy metals in surface water and sediment pose a great threat to the sustainable development of aquatic ecosystems and human health.In this research, macrozoobenthos, and surface water and sediment heavy metal (mn, cr, cu, ni, pb, zn, cd, and as) samples were collected from 23 sites in the upper and middle reaches of the heihe river in the summers of 2019-2020.The interrelationships between heavy metals and macrozoobenthos were analyzed by pearson correlation analysis and redundancy analysis (rda), and the contamination level and potential ecological risk of the heavy metals in surface water and sediments were assessed by comprehensive pollution index (wqi), single potential ecological risk index ([formula: see text]), and sediment quality guideline-quotient (sqg-q), respectively.The results showed that the level of heavy metal pollution in the surface water of the heihe river was extremely low, but the contents of mn and pb exceeded the third class of surface water environmental quality standards (gb 3838-2002).The spatial distribution of heavy metals in surface sediments were significantly different, and the average concentration of 8 heavy metals exceeded the background values of gansu province.Meanwhile, the pollution level of heavy metals in surface sediments was high pollution, and the ecological risk level was moderate risk.Combining [formula: see text] and sqg-q evaluations showed that cd, ni, and cr were the main ecological risk factors.In addition, the distribution coefficients of cr and cd were low, indicating that cr and cd were easily released from the surface sediments, causing secondary pollution.In terms of the source of the heavy metals, cu, as, zn, cr, and ni mainly came from industrial and agricultural wastewaters, pb was from the mining industry and natural sources, and mn and cd mainly came from tailings and their landfill leachate.Basommatophora and araneae can be used as potential indicator organisms for heavy metal pollution in surface water, and basommatophora, coleoptera, hemiptera, and araneae can be used as indicator species for heavy metal pollution in surface sediments.The study showed that macroinvertebrate community characteristics had a sensitive response to heavy metals in the surface waters and sediments of the heihe river, which can be used to evaluate the pollution status of heavy metals in inland rivers.

Journal: Environmental science and pollution research international (2022)
Publication types: Journal Article
Targeting bacterial pathogenesis by inhibiting virulence-associated Type III and Type IV secretion systems.

Infections caused by gram-negative pathogens pose a major health burden.Both respiratory and gastrointestinal infections are commonly associated with these pathogens.With the increase in antimicrobial resistance (amr) over the last decades, bacterial infections may soon become the threat they have been before the discovery of antibiotics.Many gram-negative pathogens encode virulence-associated type iii and type iv secretion systems, which they use to inject bacterial effector proteins across bacterial and host cell membranes into the host cell cytosol, where they subvert host cell functions in favor of bacterial replication and survival.These secretion systems are essential for the pathogens to cause disease, and secretion system mutants are commonly avirulent in infection models.Hence, these structures present attractive targets for anti-virulence therapies.Here, we review previously and recently identified inhibitors of virulence-associated bacterial secretions systems and discuss their potential as therapeutics.

Journal: Frontiers in cellular and infection microbiology (2022)
Publication types: Journal Article;Review;Research Support, Non-U.S. Gov't
Saudi Healthcare Students' Perceptions and Beliefs About Immunizations: a Descriptive, Cross-Sectional Study.

Immunization has been one of the most successful public health measures ever undertaken.However, a degree of hesitancy about vaccine use still exists.Healthcare professionals are in a unique position to provide advice and education to the public and may influence the decision to undergo immunization.Objective the aim of this study was to explore perceptions and beliefs regarding immunizations and immunization-preventable diseases.Methods a descriptive cross-sectional study was undertaken at the imam abdulrahman bin faisal university, located in dammam, saudi arabia.In the kingdom of saudi arabia, a survey of 564 saudi undergraduate healthcare students was conducted.77.8% of participants replied (439).Information was collected regarding perceptions of; severity of immunization-preventable diseases, contracting these diseases, immunization safety, and immunization beliefs.The statistical analysis was performed using the statistical package for the social sciences (ibm spss v25).Non-parametric analyses were utilized.Descriptive data were generated as appropriate, including frequencies, median, and inter-quartile range.Statistical relationships of demographic variables were explored using kruskal wallis h-test and spearman's rank-order correlation.A p-value < 0.05 was considered statistically significant.Results meningitis was perceived as the most severe disease and covid-19 as having the highest likelihood of infection.Concern regarding vaccine side effects was most evident for the covid-19 vaccine.Student year level and profession resulted in statistically significant differences for all three assessed perceptions.Substantial differences were also identified regarding views on immunization belief statements.Conclusion this study identified considerable heterogeneity in saudi healthcare students' perceptions and beliefs regarding immunization-preventable diseases and vaccination.Further education is required to produce well-informed and confident healthcare professionals around these issues.

Journal: Medical archives (Sarajevo, Bosnia and Herzegovina) (2022)
Publication types: Journal Article
Estimation of the prevalence and direct medical costs of chronic myeloid leukemia in the I.R. of Iran in the era of tyrosine kinase inhibitors.

After the introduction of tyrosine kinase inhibitors for chronic myeloid leukemia (cml), the survival of these patients has increased significantly.However, these new drugs are expensive and impose considerable expense to patients and governments.Epidemiologic and economic evaluation studies provide good information for resource allocation and decision making.We estimated the incidence, prevalence and direct medical cost of cml in iran.Methods we used the national cancer registry (ncr) data from 2006 to 2009 to estimate the incidence rate of cml (icd-10 code c92.1).After adjustment for the underestimation of incidence rates, we used survival rates of cml and estimated the 5-year prevalence for these patients.In addition, we used clinical practice guideline, expert opinions and medical tariffs to estimate the direct medical costs through the prevalence approach.Results after an adjustment for the underestimation, the incidence rate of cml was 0.5 per 100 000 in the i.r.Of iran.The 5-year prevalence was about 2263 cases (2.98 per 100 000).The total direct medical cost of cml was $23 089 323 and the majority of the cost (97%) was related to drug costs.The total cost will increase considerably to $40 728 869 if all patients use the new drug nilotinib (800 mg/day) as a second-line treatment.Conclusions the increased survival of cml patients and a possible increase in incidence of cml in iran will most likely lead to a considerable rise in its prevalence and economic burden.

Journal: Asia-Pacific journal of clinical oncology (2017)
Publication types: Journal Article
Analysis of CX3CR1 haplodeficiency in male and female APPswe/PSEN1dE9mice along Alzheimer disease progression.

Microglia, the resident immune cells of the brain, have recently emerged as key players in alzheimer disease (ad) pathogenesis, but their roles in ad remain largely elusive and require further investigation.Microglia functions are readily altered when isolated from their brain environment, and microglia reporter mice thus represent valuable tools to study the contribution of these cells to neurodegenerative diseases such as ad.The cx3cr1+/e gfpmice is one of the most popular microglia reporter mice, and has been used in numerous studies to investigate in vivo microglial functions, including in the context of ad research.However, until now, the impact of cx3cr1 haplodeficiency on the typical features of alzheimer disease has not been studied in depth.To fill this gap, we generated appswe/psen1d e9:cx3cr1+/e gfpmice and analyzed these mice for alzheimer's like pathology and neuroinflammation hallmarks.More specifically, using robust multifactorial statistical and multivariate analyses, we investigated the impact of cx3cr1 deficiency in both males and females, at three typical stages of the pathology progression: at early stage when amyloid-β (aβ) deposition just starts, at intermediate stage during aβ accumulation phase and at more advanced stages when aβ plaque number stabilizes.We found that cx3cr1 haplodeficiency had little impact on the progression of the pathology in the appswe/psen1d e9model and demonstrated that the appswe/psen1d e9:cx3cr1+/e gfpline is a relevant and useful model to study the role of microglia in alzheimer disease.In addition, although aβ plaques density is higher in females compared to age-matched males, we show that their glial reaction, inflammation status and memory deficits are not different.

Journal: Brain, behavior, and immunity (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Fabrication and Characterization of Chicken- and Bovine-Derived Chondroitin Sulfate/Sodium Alginate Hybrid Hydrogels.

The physicochemical properties and microstructure of hybrid hydrogels prepared using sodium alginate (sa) and chondroitin sulfate (cs) extracted from two animal sources were investigated.Sa-based hybrid hydrogels were prepared by mixing chicken- and bovine-derived cs (ccs and bcs, respectively) with sa at 1/3 and 2/3 (w/w) ratios.The results indicated that the evaporation water loss rate of the hybrid hydrogels increased significantly upon the addition of cs, whereas ccs/sa (2/3) easily absorbed moisture from the environment.The thermal stability of the bcs/sa (1/3) hybrid hydrogel was higher than that of ccs/sa (1/3) hybrid hydrogel, whereas the hardness and adhesiveness of the ccs/sa (1/3) hybrid hydrogel were lower and higher, respectively, than those of the bcs/sa (1/3) hybrid hydrogel.Low-field nuclear magnetic resonance experiments demonstrated that the immobilized water content of the ccs/sa (1/3) hybrid hydrogel was higher than that of the bcs/sa (1/3) hybrid hydrogel.Ftir showed that s=o characteristic absorption peak intensity of bcs/sa (2/3) was obviously higher, suggesting that bcs possessed more sulfuric acid groups than ccs.Sem showed that the hybrid hydrogels containing ccs have more compact porous microstructure and better interfacial compatibility compared to bcs.

Journal: Gels (Basel, Switzerland) (2022)
Publication types: Journal Article
Conformity of the Virtual Surgical Plan to the Actual Result Comparing Five Craniofacial Procedure Types.

The "accuracy" of virtual surgical planning across multiple procedure types is not known.The authors aimed to compare the planned outcome from virtual surgical planning to the actual postoperative outcome for five craniofacial procedure types performed by a single surgeon: implant cranioplasty, cranial vault remodeling, orthognathic surgery, mandible reconstruction, and mandibular distraction.Methods stereolithography formats were obtained from virtual surgical planning and compared to postoperative computed tomographic scans for consecutive patients who underwent one of the five procedure types.Volumetric renderings of the operated bony region of interest were overlaid and compared using a boolean operation to compute conformity (as a percentage of the region of interest).Conformity across procedure type was analyzed using analysis of variance and post hoc bonferroni analysis, where appropriate.Results one hundred thirty patients were included (51.5 percent male and 49.5 percent female; mean age, 27 years; 59 orthognathic surgery, 32 cranial vault remodeling, 16 mandible reconstruction, 12 mandibular distraction, and 11 implant cranioplasty patients).The highest tier of conformity was obtained for implant cranioplasty (median, 76.8 ± 10.3 percent) and mandible reconstruction (mean, 69.4 ± 11.2 percent), followed by orthognathic surgery (mean, 55.0 ± 7.3 percent) and mandibular distraction (median, 41.9 ± 20.3 percent), followed by cranial vault remodeling (mean, 22.2 ± 12.1 percent) (p 0.05 among tiers).Conclusions virtual surgical planning resulting in custom permanent implants and intraoperative guides provides more predictable results compared to virtual surgical planning used for procedures involving higher degrees of skeletal repositioning and postoperative movement (i.e., mandibular distraction and nonrigid cranial vault remodeling).In cases with expectedly lower conformity, excellent outcomes can be achieved with sound intraoperative judgment.

Journal: Plastic and reconstructive surgery (2021)
Publication types: Comparative Study;Journal Article
The creation of "Ecosystem Core" hypothesis to explain ecosystem evolution.

Humans have dramatically changed natural ecosystems around the world as their capacity to manage their environment for multiple uses has evolved in step with agricultural, industrial and green revolutions.Numerous natural ecosystems have been replaced by various artificial or semi-artificial ecosystems, the ecosystem has changed.To a certain extent, this is ecosystem evolution.So far, there is no definite ecological theory about the mechanism for evolution of an ecosystem.Even though the discipline of community ecology has a relatively comprehensive and well-described theory of succession, at the different ecological research levels, is it the same mechanism for the community succession and ecosystem evolution?What is the factor that drives ecosystem evolution?Results this paper puts forward the "ecosystem core" hypothesis to scientifically address the above problems.We define abiotic component of ecosystem as "ecosystem core" or "resource core", which provides the foundation (matter and energy) for the existence and progress of organisms and should be the nucleus of an ecosystem.In this paper, we explain the basic meaning of this hypothesis, review its theoretical foundation, and provide a demonstration (based on emergy theory, which is an accounting tool that considers both the environmental and economic inputs that are directly or indirectly required by a process to generate a product and it measures real wealth, independent of financial considerations) of the hypothesis, and discuss the mechanism of ecosystem evolution.The "ecosystem core" hypothesis reveals the quantitative relationship between the energy input and ecosystem evolution.Conclusions the input of artificial auxiliary energy is the direct cause of ecosystem evolution.Different combinations of natural and purchased emergy are coupled to maintain the same ecosystem under the different environmental conditions.When artificial energy enters the ecosystem, its role is similar to that of the microscopic particles that collide with the nucleus in the nuclear reaction, and after mutual reaction, the atom will form a new atomic structure, and for the ecosystem, a new form of resource composition and energy action will appear, and the corresponding species of life will change, then ecosystem complete its evolution.

Journal: BMC ecology (2019)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Review