syedzayyan/paper_mill_benchmark huggingface dataset:
Development of neurodegeneration in amyotrophic lateral sclerosis: from up or down?

Amyotrophic lateral sclerosis (als) is a fatal neurological disease associated with neurodegeneration and intracellular pathological 43-k da transactive response sequence dna-binding protein (tdp-43) positive inclusions.The various clinical symptoms, such as motor disorders and cognitive impairment, reflect the degeneration of certain areas of the nervous system.Since the discovery of the significance of pathological tdp-43 for human disease including als, there has been an increasing number of studies reporting on the distribution and severity of neurodegeneration.These have rekindled the old debate about whether the first or second motor neuron is the primary site of degeneration in als.To shed light on this question, the following is a review of the relevant neuropathological studies.

Journal: Journal of neural transmission (Vienna, Austria : 1996) (2020)
Publication types: Journal Article;Review
Astragalin and Isoquercitrin Isolated fromAster scaberSuppress LPS-Induced Neuroinflammatory Responses in Microglia and Mice.

The current study investigated the anti-neuroinflammatory effects and mechanisms of astragalin (ast) and isoquercitrin (que) isolated from chamchwi (aster scaber thunb.) in the lipopolysaccharide (lps)-activated microglia and hippocampus of lps induced mice.Lps induced increased cytotoxicity, nitric oxide (no) production, antioxidant activity, reactive oxygen species (ros), inducible nitric oxide synthase (i nos) expression, the release of pro-inflammatory cytokines, protein kinase b phosphorylation, and mitogen-activated protein kinases (mapk) phosphorylation in lps-treated microglial cells.Intraperitoneal injection of lps also induced neuroinflammatory effects in the murine hippocampus.Ast and que significantly reduced lps-induced production of no, i nos, and pro-inflammatory cytokines in the microglia and hippocampus of mice.Therefore, anti-inflammatory effects on mapk signaling pathways mediate microglial cell and hippocampus inflammation.In lps-activated microglia and hippocampus of lps-induced mice, ast or que inhibited mapk kinase phosphorylation by extracellular signal-regulated kinase, c-jun n-terminal kinase, and p38 signaling proteins.Ast and que inhibited lps-induced ros generation in microglia and increased 1,1-diphenyl-2-picrylhydrazyl radical scavenging.In addition, lps treatment increased the heme oxygenase-1 level, which was further elevated after ast or que treatments.Ast and que exert anti-neuroinflammatory activity by down-regulation of mapks signaling pathways in lps-activated microglia and hippocampus of mice.

Journal: Foods (Basel, Switzerland) (2022)
Publication types: Journal Article
Bone Preservation in Total Hip Arthroplasty.

Preserving bone stock in younger and more active patients after total hip arthroplasty (tha) is important for future revision.Newer prosthesis designs, including short femoral stems and isoelastic acetabular cups, are likely to preserve more bone stock.However, long-term follow-up studies on bone remodeling after short-stem tha with an isoelastic monoblock acetabular cup are few.Therefore, we evaluated bone preservation after tha using these prostheses at a 5-year follow-up.Methods this prospective observational study is a 5-year follow-up of our previously reported 2-year observational study on the same cohort of patients.We included 45 patients with primary osteoarthritis treated with a calcar-guided femoral short-stem prosthesis and a monoblock press-fit acetabular cup.We evaluated bone mineral density (bmd) around the prostheses using dual-energy x-ray absorptiometry and reported functional outcomes preoperatively and at 3, 12, 24, and 60 months postoperatively.All complications were recorded.Results at the final follow-up, the bmd was comparable with that at 24 months in gruen zones 3, 4, 5, 6, and 7, whereas it significantly differed in gruen zones 1 (p .05).Moreover, all measured clinical outcomes significantly improved (p < .001).One perioperative dislocation was reported.Conclusion patients undergoing tha with a calcar-guided femoral short-stem prosthesis and a monoblock acetabular cup can expect preservation of bone stock over a longer follow-up with excellent clinical outcomes and few complications.

Journal: The Journal of arthroplasty (2022)
Publication types: Journal Article;Observational Study;Research Support, Non-U.S. Gov't
Objective evaluation for treat to target in Crohn's disease.

Crohn's disease (cd) is a chronic and destructive bowel disease; continued disease activity can lead to penetrating complications.With the recent advent of effective medications, the importance of using a treat-to-target approach to guide therapy is becoming important.Methods in this review, we reviewed the previous evidence for evaluating cd lesions.Results we describe ileocolonoscopy's role in assessing disease activity, as well as recent progress in modalities, such as balloon-assisted endoscopy, capsule endoscopy, magnetic resonance enterography, computed tomography enterography, and ultrasonography.Advances in modalities have changed cd assessment, with small-bowel involvement becoming more important.Conclusions proper optimization is necessary in clinical practice.

Journal: Journal of gastroenterology (2020)
Publication types: Journal Article;Review
It's the water! The open and shut case of drug-induced integrin activation.

Integrin receptors are established drug targets, but many of the drugs that have been developed act as partial agonists, inducing the receptor into a high-affinity, ligand-binding state.Lin et al.Discovered a general mechanism to circumvent this problem-stabilizing a key water molecule that prevents receptor activation.Their findings are likely to impact future therapeutic development.

Journal: Cell (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Comment
Combined MEK and STAT3 Inhibition Uncovers Stromal Plasticity by Enriching for Cancer-Associated Fibroblasts With Mesenchymal Stem Cell-Like Features to Overcome Immunotherapy Resistance in Pancreatic Cancer.

& aims we have shown that reciprocally activated rat sarcoma (ras)/mitogen-activated protein kinase/extracellular signal-regulated kinase (mek) and janus kinase/signal transducer and activator of transcription 3 (stat3) pathways mediate therapeutic resistance in pancreatic ductal adenocarcinoma (pdac), while combined mek and stat3 inhibition (meki+stat3i) overcomes such resistance and alters stromal architecture.We now determine whether meki+stat3i reprograms the cancer-associated fibroblast (caf) and immune microenvironment to overcome resistance to immune checkpoint inhibition in pdac.Methods caf and immune cell transcriptomes in meki (trametinib)+stat3i (ruxolitinib)-treated vs vehicle-treated ptf1a cre/+;lsl-kras g12d/+;tgfbr2flox/flox(pkt) tumors were examined via single-cell rna sequencing (sc rnaseq).Clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats associated protein 9 silencing of caf-restricted map2k1/mek1 or stat3, or both, enabled interrogation of caf-dependent effects on immunologic remodeling in orthotopic models.Tumor growth, survival, and immune profiling via mass cytometry by time-of-flight were examined in pkt mice treated with vehicle, anti-programmed cell death protein 1 (pd-1) monotherapy, and meki+stat3i combined with anti-pd1.Results meki+stat3i attenuates il6/cxcl1-expressing proinflammatory and lrrc15-expressing myofibroblastic caf phenotypes while enriching for ly6a/cd34-expressing cafs exhibiting mesenchymal stem cell-like features via sc rnaseq in pkt mice.This caf plasticity is associated with m2-to-m1 reprogramming of tumor-associated macrophages, and enhanced trafficking of cluster of differentiation 8+t cells, which exhibit distinct effector transcriptional programs.These meki+stat3i-induced effects appear caf-dependent, because caf-restricted mek1/stat3 silencing mitigates inflammatory-caf polarization and myeloid infiltration in vivo.Addition of meki+stat3i to pd-1 blockade not only dramatically improves antitumor responses and survival in pkt mice but also augments recruitment of activated/memory t cells while improving their degranulating and cytotoxic capacity compared with anti-pd-1 monotherapy.Importantly, treatment of a patient who has chemotherapy-refractory metastatic pdac with meki (trametinib), stat3i (ruxolitinib), and pd-1 inhibitor (nivolumab) yielded clinical benefit.Conclusions combined meki+stat3i mitigates stromal inflammation and enriches for caf phenotypes with mesenchymal stem cell-like properties to overcome immunotherapy resistance in pdac.

Journal: Gastroenterology (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Transient fetal atrioventricular block: A series of four cases and approach to management.

Introduction fetal atrioventricular block (avb) is a failure of conduction from atria to ventricles.Immune- and nonimmune-mediated forms occur, especially in association with congenital heart disease.Second-degree (2°) avb may be reversible with dexamethasone and intravenous immunoglobulin in immune-mediated disease.However, once third-degree avb develops, it is deemed irreversible with need for a pacemaker and risk for cardiomyopathy.Rarely, 2° avb is a transient, benign phenomenon in the immature conduction system.Few case series of transient avb have been reported, but a management approach has not been defined.Methods/results/conclusion we report four patients with self-resolving, nonimmune fetal avb and outline a management strategy.

Journal: Journal of cardiovascular electrophysiology (2022)
Publication types: Case Reports;Journal Article
Mechanical Confinement and DDR1 Signaling Synergize to Regulate Collagen-Induced Apoptosis in Rhabdomyosarcoma Cells.

Fibrillar collagens promote cell proliferation, migration, and survival in various epithelial cancers and are generally associated with tumor aggressiveness.However, the impact of fibrillar collagens on soft tissue sarcoma behavior remains poorly understood.Unexpectedly, this study finds that fibrillar collagen-related gene expression is associated with favorable patient prognosis in rhabdomyosarcoma.By developing and using collagen matrices with distinct stiffness and in vivo-like microarchitectures, this study uncovers that the activation of ddr1 has pro-apoptotic and of integrin β1 pro-survival function, specifically in 3d rhabdomyosarcoma cell cultures.It demonstrates that rhabdomyosarcoma cell-intrinsic or extrinsic matrix remodeling promotes cell survival.Mechanistically, the 3d-specific collagen-induced apoptosis results from a dual ddr1-independent and a synergistic ddr1-dependent trpv4-mediated response to mechanical confinement.Altogether, these results indicate that dense microfibrillar collagen-rich microenvironments are detrimental to rhabdomyosarcoma cells through an apoptotic response orchestrated by the induction of ddr1 signaling and mechanical confinement.This mechanism helps to explain the preference of rhabdomyosarcoma cells to grow in and metastasize to low fibrillar collagen microenvironments such as the lung.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Large airway diseases in pediatrics: a pictorial essay.

"large airway diseases" is being used as an all-encompassing phrase to describe a broad spectrum of pathological entities, which involves the trachea, main, lobar, and segmental bronchi of up to 3 mm diameter.Imaging modalities such as radiography, computed tomography, and magnetic resonance imaging contribute to the identification and diagnosis of each entity.Knowledge of clinical information, normal cross-sectional anatomy, and imaging characteristics of large airway diseases is necessary for appropriate radiologic evaluation.This review provides information about congenital and acquired diseases of the large airways in the pediatric population.

Journal: Acta radiologica open (2020)
Publication types: Journal Article
A comparison of intracranial volume estimation methods and their cross-sectional and longitudinal associations with age.

Intracranial volume (icv) is frequently used in volumetric magnetic resonance imaging (mri) studies, both as a covariate and as a variable of interest.Findings of associations between icv and age have varied, potentially due to differences in icv estimation methods.Here, we compared five commonly used icv estimation methods and their associations with age.T1-weighted cross-sectional mri data was included for 651 healthy individuals recruited through the norment centre (mean age = 46.1 years, range = 12.0-85.8 years) and 2410 healthy individuals recruited through the uk biobank study (ukb, mean age = 63.2 years, range = 47.0-80.3 years), where longitudinal data was also available.Icv was estimated with free surfer (e tiv and sb tiv), spm12, cat12, and fsl.We found overall high correlations across icv estimation method, with the lowest observed correlations between fsl and e tiv (r = .87) and between fsl and cat12 (r = .89).Widespread proportional bias was found, indicating that the agreement between methods varied as a function of head size.Body weight, age, sex, and mean icv across methods explained the most variance in the differences between icv estimation methods, indicating possible confounding for some estimation methods.We found both positive and negative cross-sectional associations with age, depending on dataset and icv estimation method.Longitudinal icv reductions were found for all icv estimation methods, with annual percentage change ranging from -0.293% to -0.416%.This convergence of longitudinal results across icv estimation methods offers strong evidence for age-related icv reductions in mid- to late adulthood.

Journal: Human brain mapping (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Detection of Thioarsenates in Rice Grains and Rice Products.

Inorganic and methylated thioarsenates have recently been reported to contribute substantially to arsenic (as) speciation in paddy-soil pore waters.Here, we show that thioarsenates can also accumulate in rice grains and rice products.For their detection, a method was developed using a pepsin-pancreatin enzymatic extraction followed by chromatographic separation at p h 13.From 54 analyzed commercial samples, including white, parboiled and husked rice, puffed rice cakes, and rice flakes, 50 contained dimethylmonothioarsenate (dmmta) (maximum 25.6 μg kg-1), 18 monothioarsenate (mta) (maximum 5.6 μg kg-1), 14 dimethyldithioarsenate (dmdta) (maximum 2.8 μg kg-1), and 5 dithioarsenate (dta) (maximum 2.3 μg kg-1).Additionally, we show that the commonly used nitric acid extraction transforms mta to arsenite and dmmta and dmdta to dimethylarsenate (dma).Current food guidelines do not require an analysis of thioarsenates in rice and only limit the contents of inorganic oxyarsenic species (including acid-extraction-transformed mta), but not dma (including acid-extraction-transformed dmmta and dmdta).

Journal: Journal of agricultural and food chemistry (2021)
Publication types: Journal Article
Critical weaknesses in shielding strategies for COVID-19.

The covid-19 pandemic, caused by the coronavirus sars-co v-2, has led to a wide range of non-pharmaceutical interventions being implemented around the world to curb transmission.However, the economic and social costs of some of these measures, especially lockdowns, has been high.An alternative and widely discussed public health strategy for the covid-19 pandemic would have been to 'shield' those most vulnerable to covid-19 (minimising their contacts with others), while allowing infection to spread among lower risk individuals with the aim of reaching herd immunity.Here we retrospectively explore the effectiveness of this strategy using a stochastic seir framework, showing that even under the unrealistic assumption of perfect shielding, hospitals would have been rapidly overwhelmed with many avoidable deaths among lower risk individuals.Crucially, even a small (20%) reduction in the effectiveness of shielding would have likely led to a large increase (>150%) in the number of deaths compared to perfect shielding.Our findings demonstrate that shielding the vulnerable while allowing infections to spread among the wider population would not have been a viable public health strategy for covid-19 and is unlikely to be effective for future pandemics.

Journal: PLOS global public health (2022)
Publication types: Journal Article
Integrated Transcriptome and Histone Modification Analysis Reveals NDV Infection Under Heat Stress Affects Bursa Development and Proliferation in Susceptible Chicken Line.

Two environmental factors, newcastle disease and heat stress, are concurrently negatively impacting poultry worldwide and warrant greater attention into developing genetic resistance within chickens.Using two genetically distinct and highly inbred layer lines, fayoumi and leghorn, we explored how different genetic backgrounds affect the bursal response to a treatment of simultaneous newcastle disease virus (ndv) infection at 6 days postinfection (dpi) while under chronic heat stress.The bursa is a primary lymphoid organ within birds and is crucial for the development of b cells.We performed rna-seq and ch ip-seq targeting histone modifications on bursa tissue.Differential gene expression revealed that leghorn, compared to fayoumi, had significant down-regulation in genes involved in cell proliferation, cell cycle, and cell division.Interestingly, we also found greater differences in histone modification levels in response to treatment in leghorns than fayoumis, and biological processes enriched in associated target genes of h3k27ac and h3k4me1 were similarly associated with cell cycle and receptor signaling of lymphocytes.Lastly, we found candidate variants between the two genetic lines within exons of differentially expressed genes and regulatory elements with differential histone modification enrichment between the lines, which provides a strong foundation for understanding the effects of genetic variation on ndv resistance under heat stress.This study provides further understanding of the cellular mechanisms affected by ndv infection under heat stress in chicken bursa and identified potential genes and regulatory regions that may be targets for developing genetic resistance within chickens.

Journal: Frontiers in genetics (2020)
Publication types: Journal Article
Learning Representations for Facial Actions From Unlabeled Videos.

Facial actions are usually encoded as anatomy-based action units (aus), the labelling of which demands expertise and thus is time-consuming and expensive.To alleviate the labelling demand, we propose to leverage the large number of unlabelled videos by proposing a twin-cycle autoencoder (tae) to learn discriminative representations for facial actions.Tae is inspired by the fact that facial actions are embedded in the pixel-wise displacements between two sequential face images (hereinafter, source and target) in the video.Therefore, learning the representations of facial actions can be achieved by learning the representations of the displacements.However, the displacements induced by facial actions are entangled with those induced by head motions.Tae is thus trained to disentangle the two kinds of movements by evaluating the quality of the synthesized images when either the facial actions or head pose is changed, aiming to reconstruct the target image.Experiments on au detection show that tae can achieve accuracy comparable to other existing au detection methods including some supervised methods, thus validating the discriminant capacity of the representations learned by tae.Tae's ability in decoupling the action-induced and pose-induced movements is also validated by visualizing the generated images and analyzing the facial image retrieval results qualitatively and quantitatively.

Journal: IEEE transactions on pattern analysis and machine intelligence (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
COVID-19 mRNA Vaccination Mimicking Heart Attack in a Healthy 56-Year-Old Physician.

We report our experience regarding a 56-year-old physician who developed severe symptoms mimicking a heart attack a few days after receiving the second dose of the new m rna vaccine of pfizer-bio ntech for covid-19 protection.The patient is a healthy individual with no comorbidities and a normal clinical and laboratory profile.Five days after receiving the second dose on his left shoulder, he manifested sudden, severe pain on the whole left arm which lasted for about one hour, gradually intensifying and migrating to the chest and presenting as severe angina or heart attack.All work-up, however, was negative, with no evidence of ischemic heart attack or myocarditis.Severe acute symptoms lasted for about 20 h and completely resolved after 36 h.Although myocarditis as a potential side effect of the vaccine with associated heart pain has been identified, chest pain mimicking heart attack with otherwise normal workup has not been reported.Physicians must consider this likely rare and self-resolving symptom in order to increase awareness and prevent themselves and their patients from increased anxiety and unnecessary laboratory investigations.

Journal: Infectious disease reports (2022)
Publication types: Case Reports;Journal Article
A novel supervised learning method to generate CT images for attenuation correction in delayed pet scans.

And objectives attenuation correction is important for pet image reconstruction.In clinical pet/ct scans, the attenuation information is usually obtained by ct.However, additional ct scans for delayed pet imaging may increase the risk of cancer.In this paper, we propose a novel ct generation method for attenuation correction in delayed pet imaging that requires no additional ct scans.Methods as only pet raw data is available for the delayed pet scan, routine image registration methods are difficult to use directly.To solve this problem, a reconstruction network is developed to produce pseudo pet images from raw data first.Then a second network is used to generate the ct image through mapping pet/ct images from the first scan to the delayed scan.The inputs of the second network are the two pseudo pet images from the first and delayed scans, and the ct image from the first scan.The labels are taken from the ground truth ct image in the delayed scan.The loss function contains an image similarity term and a regularization term, which reflect the anatomy matching accuracy and the smoothness of the non-rigid deformation field, respectively.Results we evaluated the proposed method with simulated and clinical pet/ct datasets.Standard uptake value was computed and compared with the gold standard (with coregistered ct for attenuation correction).The results show that the proposed supervised learning method can generate pet images with high quality and quantitative accuracy.For the test cases in our study, the average mae and rmse of the proposed supervised learning method were 4.61 and 22.75 respectively, and the average psnr between the reconstructed pet image and the ground truth pet image was 62.13 d b.Conclusions the proposed method is able to generate accurate ct images for attenuation correction in delayed pet scans.Experiments indicate that the proposed method outperforms traditional methods with respect to quantitative pet image accuracy.

Journal: Computer methods and programs in biomedicine (2020)
Publication types: Journal Article