syedzayyan/paper_mill_benchmark huggingface dataset:
Immunological Predictors of Dimethyl Fumarate-Induced Lymphopenia.

Treatment with dimethyl fumarate (dmf) leads to lymphopenia and infectious complications in a subset of patients with multiple sclerosis (ms).Here, we aimed to reveal immune markers of dmf-associated lymphopenia.This prospective observational study longitudinally assessed 31 individuals with ms by single-cell mass cytometry before and after 12 and 48 weeks of dmf therapy.Employing a neural network-based representation learning approach, we identified a ccr4-expressing t helper cell population negatively associated with relevant lymphopenia.Ccr4-expressing t helper cells represent a candidate prognostic biomarker for the development of relevant lymphopenia in patients undergoing dmf treatment.Ann neurol 2022;91:676-681.

Journal: Annals of neurology (2022)
Publication types: Journal Article;Observational Study;Research Support, Non-U.S. Gov't
OVO homologue-like 1 promotes osteoblast differentiation through BMP2 expression.

Ovo homologue-like 1 (ovol1) encodes a c2h2 zinc finger protein and is an evolutionarily conserved gene in mammals.The ovol1 expression is required for development.However, the function of ovol1 in bone metabolism remains unreported.Here, we show for the first time the role of ovol1 in osteoblast differentiation.To determine the role of ovol1 in osteogenic differentiation, we analyzed ovol1 expression in the preosteoblastic cell line.Ovol1 messenger rna expression was induced during osteoblast differentiation.In addition, ovol1 overexpression enhanced the expression of osteogenic genes including bone morphogenetic protein 2 (bmp2), the inhibitor of dna binding 1 (id1), distal-less homeobox 5 (dlx5), runt-related transcription factor 2 (runx2), osteocalcin (oc), and alkaline phosphatase (alp).Moreover, mineralization of the extracellular matrix was increased by ovol1 overexpression in mc3t3-e1 cells.Furthermore, knockdown of the ovol1 experiment demonstrated that ovol1 is required for osteoblast differentiation.Collectively, these results suggest that ovol1 function as an important regulator of osteoblast differentiation by inducing bmp2 expression in mc3t3-e1 cells.

Journal: Journal of cellular physiology (2019)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Hyoid Bone Syndrome and Dysphonia: Can Throat Pain Affect the Voice?

S/hypothesis to investigate the relationship of throat pain and dysphonia.Study design prospective cohort study.Methods forty-five subjects presenting with hyoid bone syndrome (hbs) and dysphonia were asked to rate their pain on a numerical rating scale and complete the 10-item voice-related quality of life (v-rqol) questionnaire prior to and at 1-week follow-up after treatment with triamcinolone injection into the attachments to the affected greater cornu(s).Wilcoxon signed-rank tests were applied to evaluate if the overall v-rqol scores, the physical functioning (pf) and social-emotional (se) domain scores, and pain scores changed significantly after treatment.To evaluate how change in perceived pain affected v-rqol, the differences in the v-rqol, pf, and se domain scores, and in pain scores were calculated for each subject.Three linear models were fit to the response variables, δv-rqol, δpf, and δse, using δpain as a predicting variable.Results v-rqol, pf, and se domain scores, and pain scores all improved significantly with treatment.A bigger decrease in the pain score led to a bigger increase in v-rqol and domain scores, with slopes varying between -1.1 and -1.4.The pf domain scores showed the greatest improvement with decrease in pain scores.Conclusions effective treatment of hbs led to improvement in patients' voice complaints, suggesting that throat pain may have a direct effect on voice.This may be related to compensatory perilaryngeal adjustments patients make when speaking with a "guarding" effect when they have throat pain.Level of evidence iv (cohort study) laryngoscope, 131:e2303-e2308, 2021.

Journal: The Laryngoscope (2021)
Publication types: Journal Article
The effect of granulocyte colony-stimulating factors on survival parameters in pediatric patients with acute lymphoblastic leukemia: A retrospective study.

There is a paucity of data concerning the use of granulocyte colony-stimulating factors (g-csfs) in pediatric patients with acute lymphoblastic leukemia (all).The aim of the present study was to evaluate the effect of g-csf use on relapse-free and overall survival in 358 consecutive, newly diagnosed pediatric all patients uniformly treated at the same institution between april 2012 and april 2020.Materials and methods patients were evaluated in two separate periods, based on the g-csf treatment approach.All patients who underwent all treatment between april 2012 and december 2016 received g-csf (g-csf+arm; n: 245) in the course of the protocol for reducing the risk of febrile neutropenia and/or inducing neutrophil recovery to prevent any treatment delay.No patients after december 2016 received g-csf, even if they belonged to the high-risk group, and these were included in the g-csf-arm (n: 113).Results estimated mean relapse-free (106.5 months; 95 % ci 102-110.8 vs 82 months 95 % ci 75.2-88.9; p: 0.794) and overall survival (111.4 months; 95 % ci 108-114.8 vs 85 months 95 % ci 80.4-89.8; p: 0.431) rates were similar between the g-csf+and g-csf-groups.Conclusions our findings indicate that g-csf use during all treatment had no effect on relapse rates or overall survival.

Journal: Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis (2022)
Publication types: Journal Article;Review
A health promotion perspective for the control and prevention of Brucellosis (Brucella melitensis); Israel as a case study.

Brucellosis (brucella melitensis) is endemic in many countries around the world, therefore, identifying what is required to control and prevent the disease is essential.The health promotion concept and five areas of action, presented in the ottawa charter (1986) may help understand how to go forward in the prevention of the disease.Israel serves as a case study.Aim to identify barriers to the control and prevention of brucellosis (brucella melitensis) in israel by analyzing trends in incidence in conjunction with interventions implemented over the last seven decades, applying the health promotion areas of action.Methods 1.A document review approach was adopted to develop a list of interventions implemented in israel to prevent and control brucellosis and identify barriers to implementation.These were analysed using the health promotion areas of action.2.Data from the mandatory reporting of infectious diseases in israel regarding brucellosis in humans between 1951 and 2021 are presented and analyzed in conjunction with the interventions implemented.Results a large range of interventions were implemented following outbreaks of the disease.These interventions followed the health promotion areas of action, including mainly: policy, education and environment and brought about a decrease in the disease among both animals and humans.However, major interventions were discontinued after a few years.In addition, we identified some areas of action that could be much improved on.The interventions, in many cases were not simultaneously implemented or coordinated, decreasing the chances of them having the expected long term impact.Conclusions control and prevention of the disease in israel is partial.Areas of action that could be improved include enforcement of regulations, strengthening community action and improving personal skills.Simultaneous and continuous implementation of the interventions may achieve the goals of sustained prevention and control.There seems to be a lack of a long-term strategy and an integrated holistic intervention approach that may contribute to the control and prevention of the disease.

Journal: PLoS neglected tropical diseases (2022)
Publication types: Journal Article
Radium-223 for metastatic, castration-resistant prostate cancer: A retrospective chart review study of real-world use in a tertiary hospital in Taiwan.

Radium-223 is an alpha-emitting, bone-targeting radiopharmaceutical that confers a survival benefit in patients with confirmed bone-metastatic, castration-resistant prostate cancer with no visceral metastases.We studied real-world use of radium-223 in eligible patients from a tertiary hospital.Methods we retrospectively collected clinical data of patients treated with radium-223 in tungs' taichung metro harbor hospital by chart review.Data included biochemical parameters, pain scores, other prostate cancer treatments received and adverse events (aes).Results of 36 patients included in the study, 12 patients received radium-223 as first-line therapy, 11 as second-line treatment and 13 as third-line treatment.Prostate-specific antigen significantly increased from baseline in patients who received radium-223 as third-line treatment and in patients who received radium-223 post-chemotherapy.Pain scores significantly decreased when radium-223 was given as second-line and as third-line treatment.In the patients who were naive to novel anti-hormone (nah) therapy and chemotherapy, mean alkaline phosphatase level significantly decreased from baseline.The most common ae was anemia, found in 16.7% of patients.Conclusion radium-223 had early biochemical benefits, while in the later stages of the disease, it reduced bone pain in this real-world cohort of chemotherapy-naive, nah-naive patients, and patients with prior therapy, from a tertiary institution in taiwan.

Journal: Journal of the Formosan Medical Association = Taiwan yi zhi (2022)
Publication types: Journal Article
How evolution builds up complexity?: In vitro evolution approaches to witness complexification in artificial molecular replication systems.

How can evolution assemble lifeless molecules into a complex living organism?The emergent process of biological complexity in the origin of life is a big mystery in biology.In vitro evolution of artificial molecular replication systems offers unique experimental opportunities to probe possible pathways of a simple molecular system approaching a complex life-like system.This review focuses on experimental efforts to examine evolvability of molecules in vitro from the pioneering spiegelman's experiment to our latest research on an artificial rna self-replication system.Genetic translation and compartmentalization are shown to enable sustainable replication and evolution.Latest studies are revealing that coevolution of self-replicating "host replicators" and freeloading "parasitic replicators" is crucial to extend evolvability of a molecular replication system for continuous evolution and emergence of diversity.Intense competition between hosts and parasites would have existed even before the origin of life and contributed to generating complex molecular ecosystems.This review article is an extended version of the japanese article "anin vitroevolutionary journey of an artificial rna replication system towards biological complexity" published in seibutsu-butsuri vol.61, p.240-244 (2021)."

Journal: Biophysics and physicobiology (2022)
Publication types: Journal Article
Stochastic matched-field localization of an acoustic source based on principles of Riemannian geometry.

Passive localization of acoustic sources is treated within a geometric framework where non-euclidean distance measures are computed between a cross-spectral density estimate of received data on a vertical array and a set of stochastic replica steering matrices, rather than traditional replica steering vectors.A processing scheme involving matrix-matrix comparisons where steering matrices, as functions of the replica source coordinates, naturally incorporate environmental variability or uncertainty provides a general framework for considering the acoustic inverse source problem in an ocean waveguide.Within this context a subset of matched-field processors is examined, based on recent advances in the application of non-euclidean geometry to statistical classification of data feature clusters.The matrices are interpreted abstractly as points in a riemannian manifold, and an appropriately defined distance measure between pairs of matrices on this manifold defines a matched-field processor for estimating source location.Acoustic simulations are performed for a waveguide comprising both a depth-dependent sound-speed profile perturbed by linear internal gravity waves and a depth-correlated surface noise field, providing an example of the viability of this approach to passive source localization in the presence of sound-speed variability.

Journal: The Journal of the Acoustical Society of America (2018)
Publication types: Journal Article
An extremely rare case of anterior mediastinal leiomyosarcoma: a case report.

We herein report an extremely rare case of leiomyosarcoma found in the anterior mediastinum.A 79-year-old man presented to our hospital with an anterior mediastinal mass incidentally found by chest computed tomography (ct) scan.Percutaneous needle biopsy revealed the presence of an undifferentiated sarcoma.Transsternal resection of the tumor with adjacent left mediastinal pleura was performed, and pathological analysis revealed a leiomyosarcoma, which was 11 cm in diameter, with bare margins.He was followed up on an outpatient basis with no adjuvant therapy.Although mediastinal lymph node recurrence was suspected on chest ct scan 18 months after surgery, the patient remained asymptomatic and rejected any additional antitumor treatments.He died of respiratory failure after incidental traumatic spinal injury about 30 months after tumor resection.

Journal: Journal of surgical case reports (2022)
Publication types: Case Reports;Journal Article
Molecular chaperones and Parkinson's disease.

Parkinson's disease (pd) is a neurodegenerative disease characterized by progressive death of dopaminergic neurons in the substantia nigra and the formation of lewy bodies (lbs).Mutations in pd-related genes lead to neuronal pathogenesis through various mechanisms, with known examples including snca/α-synuclein (pakr1), parkin (park2), pink1 (park6), dj-1 (park7), and lrrk2 (park8).Molecular chaperones/co-chaperones are proteins that aid the folding of other proteins into a functionally active conformation.It has been demonstrated that chaperones/co-chaperones interact with pd-related proteins and regulate their function in pd.Hsp70, hsp90 and small heat shock proteins can prevent neurodegeneration by regulating α-syn misfolding, oligomerization and aggregation.The function of chaperones is regulated by co-chaperones such as hsp110, hsp40, hop, chip, and bag family proteins.Parkin, pink1 and dj-1 are pd-related proteins which are associated with mitochondrial function.Molecular chaperones regulate mitochondrial function and protein homeostasis by interacting with these pd-related proteins.This review discusses critical molecular chaperones/co-chaperones and pd-related proteins which contribute to the pathogenesis of pd, hoping to provide new molecular targets for therapeutic interventions to thwart the disease progression instead of only bringing symptomatic relief.Moreover, appreciating the critical role of chaperones in pd can also help us screen efficient biomarkers to identify pd at an early stage.

Journal: Neurobiology of disease (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Review
Validation of the Fracture Mobility Score against the Parker Mobility Score in hip fracture patients.

Introduction the parker mobility score has proven to be a valid and reliable measurement of hip fracture patient mobility.For hip fracture registries the fracture mobility score is advised and used, although this score has never been validated.This study aims to validate the fracture mobility score against the parker mobility score.Patients and methods the dutch hip fracture audit uses the fracture mobility score (categorical scale).For the purpose of this study, five hospitals registered both the fracture mobility score and the parker mobility score (0-9 scale) for every admitted hip fracture patient in 2018.The spearman correlation between the two scores was calculated.To test whether the correlation coefficient remained stable among different patient subgroups, analyses were stratified according to baseline patient characteristics.Results in total 1,201 hip fracture patients were included.The spearman correlation between the fracture mobility score and parker mobility score was strong: 0.73 (p = < 0.001).Stratified for gender, age, asa score, dementia, index of activities of daily living (katz-6 adl score), living situation and nutritional status, the correlation coefficient varied between 0.40-0.84.For patients aged 90 and over and having an asa score of iii-iv who suffered from dementia, had a katz-6 adl score of 1-6, lived in an institution and/or were malnourished, the correlation was moderate.Conclusion the fracture mobility score is overall strongly correlated with the parker mobility score and can be considered as a valid score to measure hip fracture patient mobility.This may encourage other hip fracture audits to also use the fracture mobility score, which would increase the uniformity of mobility score results among national hip fracture audits and decrease the overall registration load.

Journal: Injury (2020)
Publication types: Comparative Study;Journal Article
Design, synthesis, and biological evaluation of hederagenin derivatives with improved aqueous solubility and tumor resistance reversal activity.

Multidrug resistance (mdr) has become a major obstacle to malignancies treatment by chemotherapeutic drugs, therefore, it is important to develop mdr reversal agents with high activity.We have previously found that the hederagenin (hd) derivative hbq showed good tumor mdr reversal activity in vitro and in vivo but had poor solubility.In this study, to enhance the aqueous solubility and tumor mdr reversal activity of hbq, three series of hd derivatives were designed and synthesized.Nitrogen-containing heterocyclic-substituted, pegylated, and ring-a substituted derivatives significantly reversed the mdr phenotype of kbv (multidrug-resistant oral epidermoid carcinoma) cells toward paclitaxel at a concentration of 10 μm in mtt assays.The pegylated derivatives 10c-10e had increased aqueous solubility compared with hbq by 18-657 fold, while maintaining tumor mdr reversal activity.The most in vitro active compound 10c possessed good chemical stability to an esterase over 24 h and enhanced the sensitivity of kbv cells to paclitaxel and vincristine with ic50values of 4.58 and 0.79 n m, respectively.Mechanism studies indicated that compound 10c increased the accumulation of p-glycoprotein (p-gp) substrates rhodamine 123 and flutax1 in kbv cells and mcf-7t (paclitaxel-resistant breast carcinoma) cells, that is to say, compound 10c exerted the reversal effect of tumor mdr by inhibiting the efflux function of p-gp.Finally, the structure-activity relationships were further investigated by analyzing the relationship between structure and tumor mdr reversal activity of hd derivatives.This study highlights the potential of pegylated hd derivatives such as compound 10c for the development of tumor mdr reversal agents and provides information for the further improvement of the aqueous solubility and tumor mdr reversal activity of hd derivatives in the future.

Journal: European journal of medicinal chemistry (2021)
Publication types: Journal Article
Pinolenic acid exhibits anti-inflammatory and anti-atherogenic effects in peripheral blood-derived monocytes from patients with rheumatoid arthritis.

Pinolenic acid (pnla), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects.We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of pnla on activated purified cd14 monocytes from peripheral blood of patients with rheumatoid arthritis (ra) in vitro.Flow cytometry was used to assess the proportions of cd14 monocytes expressing tnf-α, il-6, il-1β, and il-8 in purified monocytes from patients with ra after lipopolysaccharide (lps) stimulation with/without pnla pre-treatment.The whole genomic transcriptome (wgt) profile of pnla-treated, and lps-activated monocytes from patients with active ra was investigated by rna-sequencing.Pnla reduced percentage of monocytes expressing cytokines: tnf-α by 23% (p = 0.048), il-6 by 25% (p = 0.011), il-1β by 23% (p = 0.050), il-8 by 20% (p = 0.066).Pathway analysis identified upstream activation of peroxisome proliferator-activated receptors (ppars), sirtuin3, and let7 mi rna, and klf15, which are anti-inflammatory and antioxidative.In contrast, dap3, lif and stat3, which are involved in tnf-α, and il-6 signal transduction, were inhibited.Canonical pathway analysis showed that pnla inhibited oxidative phosphorylation (p = 9.14e-09) and mitochondrial dysfunction (p = 4.18e-08), while the sirtuin (sirts) signalling pathway was activated (p = 8.89e-06) which interfere with the pathophysiological process of atherosclerosis.Many mi rnas were modulated by pnla suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously.Multiple mi rnas target pyruvate dehydrogenase kinase-4 (pdk4), single-immunoglobulin interleukin-1 receptor molecule (sigirr), mitochondrially encoded atp synthase membrane subunit 6 (mt-atp6) and acetyl-co a acyltranferase2 (acaa2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction.Pnla has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in ra and atherosclerosis.Dietary pnla supplementation regulates key mi rnas that are involved in metabolic, mitochondrial, and inflammatory pathways.

Journal: Scientific reports (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
A case and literature review of intraocular echinococcus causing bilateral visual loss in a HIV-infected patient.

Although echinococcosis is a common parasitic disease endemic to africa, ocular echinococcosis is rare.We present a case of intraocular echinococcosis in a hiv-infected patient.A 38-year-old south african hiv-infected woman presented to a district-level hospital in kwa-zulu natal on 10 march 2020.Her main presenting complaint was that of progressive, painless, bilateral visual loss.A b-ultrasonography scan revealed tractional retinal detachment on the right eye, while the left eye had tractional bands with a 'double-walled' cystic cavity causing retinal traction.A systemic work-up revealed a positive echinococcus elisa ig g with a value of 1.3, eosinophilia of 5.70% (0.41 × 109), and elevated c-reactive protein and erythrocyte sedimentation rate of 47 mg/l and 93 mm/hr, respectively.Based on the above clinical, biochemical and ultrasonographical evidence, a diagnosis of ocular echinococcosis was made.Our differential diagnosis includes toxic optic neuropathy, jarisch-herxheimer-like reaction secondary to immune reconstitution and necrotizing herpetic retinitis.She was initiated on topical and intravitreal steroids which led to decreased intraocular inflammation and dry maculae.Five months after presentation, her visual acuity remained unchanged with no light perception in both eyes.We conclude that ocular echinococcosis, although rare, can lead to severe visual impairment as there are no known definite treatment modalities for intraocular hydatid disease.Reports on co-infections with hiv and echinococcusare limited with a potential scope for research.

Journal: SAGE open medical case reports (2022)
Publication types: Case Reports;Journal Article