syedzayyan/paper_mill_benchmark huggingface dataset:
The majority of β-catenin mutations in colorectal cancer is homozygous.

Β-catenin activation plays a crucial role for tumourigenesis in the large intestine but except for lynch syndrome (ls) associated cancers stabilizing mutations of β-catenin gene (ctnnb1) are rare in colorectal cancer (crc).Previous animal studies provide an explanation for this observation.They showed that ctnnb1 mutations induced transformation in the colon only when ctnnb1 was homozygously mutated or when membranous β-catenin binding was hampered by e-cadherin haploinsufficiency.We were interested, if these mechanisms are also found in human ctnnb1 mutated crcs.Results among 869 crcs stabilizing ctnnb1 mutations were found in 27 cases.Homo- or hemizygous ctnnb1 mutations were detected in 74% of ctnnb1 mutated crcs (13 microsatellite instabile (msi-h), 7 microsatellite stabile (mss)) but only in 3% (1/33) of extracolonic ctnnb1 mutated cancers.In contrast to mss crc, ctnnb1 mutations at codon 41 or 45 were highly selected in msi-h crc.Of the examined three crc cell lines, β-catenin and e-cadherin expression was similar in cell lines without or with hetereozygous ctnnb1 mutations (dld1 and hct116), while a reduced e-cadherin expression combined with cytoplasmic accumulation of β-catenin was found in a cell line with homozygous ctnnb1 mutation (ls180).Reduced expression of e-cadherin in human msi-h crc tissue was identified in 60% of investigated cancers, but no association with the ctnnb1 mutational status was found.Conclusions in conclusion, this study shows that in contrast to extracolonic cancers stabilizing ctnnb1 mutations in crc are commonly homo- or hemizygous indicating a higher threshold of β-catenin stabilization to be required for transformation in the colon as compared to extracolonic sites.Moreover, we found different mutational hotspots in ctnnb1 for msi-h and mss crcs suggesting a selection of different effects on β-catenin stabilization according to the molecular pathway of tumourigenesis.Reduced e-cadherin expression in crc may further contribute to higher levels of transcriptionally active β-catenin, but it is not directly linked to the ctnnb1 mutational status.

Journal: BMC cancer (2020)
Publication types: Journal Article
Mesenchymal Stem Cell Injection in Crohn's Disease Strictures: A Phase I-II Clinical Study.

And aim mesenchymal stem cells [mscs] have anti-inflammatory and anti-fibrotic properties and could be a potential therapy for crohn's disease [cd] strictures.In this phase i-ii pilot trial, we assessed safety and efficacy of local msc injection to treat cd strictures.Methods cd patients with a short [less than 5 cm in length] non-passable stricture accessible by ileocolonoscopy were included.Allogenic bone-marrow derived mscs were injected in the four quadrants of the stricture.Adverse events and clinical scores were evaluated at each follow-up visit and endoscopy and magnetic resonance enterography were performed at baseline, week [w]12 and w48.The main judgement criterion for efficacy was the complete [defined by the ability to pass the ileocolonoscope] or partial [defined by a diameter increase] resolution of the stricture at w12.Second efficacy criteria included assessment of the stricture at w48 and evolution of clinical scores at w12 and w48.Results we performed 11 msc injections in 10 cd patients [three primary and seven anastomotic strictures; one stricture injected twice].Msc injections were well tolerated but four hospitalisations for occlusion were reported.At w12, five patients presented a complete or partial resolution of the stricture [two complete and three partial].Seven patients were re-evaluated at w48 [one dilated, one operated, and one lost to follow-up] and four patients had a complete resolution.The evolution of clinical scores between w0, w12, and w48 was not statistically significant.Conclusions mscs injection in cd stricture was well tolerated and may offer a benefit.

Journal: Journal of Crohn's & colitis (2022)
Publication types: Clinical Trial, Phase I;Clinical Trial, Phase II;Journal Article
Cerebellar Activation During Simple and Complex Bimanual Coordination: an Activation Likelihood Estimation (ALE) Meta-analysis.

Bimanual coordination is an important part of everyday life and recruits a large neural network, including the cerebellum.The specific role of the cerebellum in bimanual coordination has not yet been studied in depth, although several studies indicate a differential role of the anterior and posterior cerebellum depending on the complexity of the coordination.An activation likelihood estimation (ale) meta-analysis was used combining the data of several functional mri studies involving bimanual coordination tasks with varying complexities to unravel the involvement of the different areas of the cerebellum in simple and complex bimanual coordination.This study confirms the general bimanual network as found by puttemans et al.(puttemans et al.In j neurosci 25:4270-4278, 2005) and highlights the differences between preferred in-phase (simultaneous movements of homologous muscle groups) and anti-phase movement conditions (alternating movements of homologous muscle groups), and more complex, non-preferred bimanual movements (e.g., out-of-phase movements).Our results show a differential role for the anterior and posterior vermis in bimanual coordination, with a role for the anterior vermis in anti-phase and complex bimanual coordination, and an exclusive role for the posterior vermis in complex bimanual movements.In addition, the way complexity was manipulated also seems to play a role in the involvement of the anterior and posterior vermis.We hypothesize that the anterior vermis is involved in sequential/spatial control, while the posterior vermis is involved in temporal control of (bimanual) coordination, though other factors such as (visual) feedback and continuity of the movement also seem to have an impact.More studies are needed to unravel the specific role of the cerebellar vermis in bimanual coordination.

Journal: Cerebellum (London, England) (2022)
Publication types: Meta-Analysis;Journal Article;Review
Lumbar spine surgery reduces postoperative opioid use in the veteran population.

The united states has been facing a worsening opioid epidemic over the past two decades.The veteran population represents a large and vulnerable group with a higher burden of mental health comorbidities.The purpose of this study was to analyze the impact of lumbar spine surgery on postoperative opioid usage in the united states veteran population.Methods a retrospective cohort study was conducted using the veterans affairs informatics and computing infrastructure database.Patients who underwent lumbar spine surgery were stratified into three groups by their preoperative opioid claims within 365 days of surgery.Postoperative cumulative morphine milligram equivalents (mme) were tracked for each group and the paired wilcoxon signed rank test was used to compare cumulative preoperative mme (days -365-0) to cumulative postoperative mme (days 91-455).Results at one year, 30.6% of patients in the high preoperative opioid group and 73.1% of patients in the low preoperative opioid group were no longer using opioids.In the opioid naive cohort, 10.0% of patients were still using opioids at one year.Among all patients, median cumulative postoperative mme was significantly less than median cumulative preoperative mme (p<0.001).High preoperative opioid usage of more than 3 claims was most significantly associated with continued postoperative opioid usage (odds ratio 12.55, p<0.001).From 2010 to 2020 the proportion of patients with preoperative opioid claims decreased (58.8% to 34.8%).Conclusions in the veteran population, lumbar spine surgery was effective in getting 50% of patients who were on opioids preoperatively to discontinue opioids postoperatively.Even minimal exposure to opioids preoperatively resulted in a 2.69-time increase in risk of being on opioids at one year versus opioid naive patients.This study affirms that despite being a high-risk population, the veteran population has a similar response to lumbar spine surgery as the general population in regards to opioid dependence.

Journal: Journal of spine surgery (Hong Kong) (2022)
Publication types: Journal Article
Protective effects of ThaiMucuna pruriens(L.) DC. var. pruriens seeds on sexual behaviors and essential reproductive markers in chronic unpredictable mild stress mice.

And aims chronic stress is a major common cause of male infertility.Many species of velvet beans are shown to be rich in l-dopa.In thai folklore medicine, seeds of mucuna pruriens(l.) dc.Var.Pruriens (thai mhamui or t-mp) have been used for treating erectile dysfunction.This study aimed to determine l-dopa levels in t-mp seed extract and investigate its preventive on sexual behaviors and reproductive parameter damages including essential proteins in chronic unpredictable mild stress (cums) mice.Experimental procedure mice were divided into 4 groups: (i) control, (ii) cums, (iii) t-mp300 + cums, and (iv) t-mp600 + cums.Groups i and ii received dw while groups iii and iv were pretreated with the seed extracts (300 and 600 mg/kg bw) for 14 consecutive days before co-treatment with a randomly different cums/day (from 12 mild stressors) for 43 days.Results and conclusion t-mp seed extract contained l-dopa approximately 10% of total dried weight.A dose of 600 mg/kg improved sexual performances and degenerative seminiferous epithelium in cums mice.Sperm qualities and testosterone level were elevated while corticosterone was decreased in co-treatment groups.T-mp-cums cotreated groups also improved expressions of akap4, ar, and tyr pho proteins in testis, epididymis, and sperm.T-mp increased st ar and cyp11a1 expressions in testis.It also suppressed testicular apoptosis via decreased expressions of hsp70, caspases 3, and 9.T-mp seeds containing l-dopa could improve sexual behaviors and essential reproductive proteins caused by cums.Section natural products.Taxonomy classification by evise traditional herbal medicine; animal model; histopathology.

Journal: Journal of traditional and complementary medicine (2022)
Publication types: Journal Article
The emerging role of ubiquitin-specific protease 20 in tumorigenesis and cancer therapeutics.

As a critical member of the ubiquitin-specific proteolytic enzyme family, ubiquitin-specific peptidase 20 (usp20) regulates the stability of proteins via multiple signaling pathways.In addition, usp20 upregulation is associated with various cellular biological processes, such as cell cycle progression, proliferation, migration, and invasion.Emerging studies have revealed the pivotal role of usp20 in the tumorigenesis of various cancer types, such as breast cancer, colon cancer, lung cancer, gastric cancer and adult t cell leukemia.In our review, we highlight the different mechanisms of usp20 in various tumor types and demonstrate that usp20 regulates the stability of multiple proteins.Therefore, regulating the activity of usp20 is a novel tumor treatment.However, the clinical significance of usp20 in cancer treatment merits more evidence.Finally, different prospects exist for the continued research focus of usp20.

Journal: Cell death & disease (2022)
Publication types: Journal Article;Review;Research Support, Non-U.S. Gov't
Acupuncture for oligospermia and asthenozoospermia: A systematic review and meta-analysis.

Acupuncture is widely used for oligospermia and asthenozoospermia in china, but its effect is unclear.We aimed to determine the effectiveness and safety of acupuncture in treating oligospermia and asthenozoospermia.Methods an electronic search for randomized controlled trials evaluating acupuncture treatment in patients with oligospermia and asthenozoospermia published from database inception to october 2018 was conducted in pub med, embase, the chinese biomedical literature database, the chinese scientific journal database (vip database), the wan-fang database, the china national knowledge infrastructure and the cochrane library.We established search terms related to 3 areas (oligospermia, asthenozoospermia, and acupuncture).Two authors independently screened all identified citations and extracted the data.The methodological quality of the included trials was assessed using the cochrane criteria.Results seven studies with a total of 527 subjects were screened according to inclusion and exclusion standards, and most of the studies had significant methodological weaknesses.Seven randomized controlled trials tested the effects of acupuncture compared with placebo acupuncture and conventional medications in patients with oligospermia and asthenozoospermia.The results of this study suggest that acupuncture alone has no clear superiority in improving sperm motility (standard mean difference [smd] = 1.13, 95% confidence interval [ci]: -0.64 to 2.89), the sperm concentration (smd = 0.32, 95% ci: 0.27-0.92) or semen volume compared with placebo acupuncture.No significant difference was found between acupuncture alone and conventional medications in improving sperm motility (smd = -0.53, 95% ci: -2.54 to 1.48), the sperm concentration (smd = -1.10, 95% ci: -1.48 to -0.72) or semen volume.However, adjuvant acupuncture may enhance the effect of medications on improving sperm motility (smd = 4.10, 95% ci: 1.09-7.12) and the sperm concentration (smd = 1.07, 95% ci: 0.739-1.40), but the study heterogeneity was too high to establish robust conclusions.Conclusion these results suggest that the current evidence does not support acupuncture as an effective treatment for oligospermia and asthenozoospermia; therefore, acupuncture is not currently recommended as a treatment for these conditions.However, owing to the high risk of bias among the included studies, the evidence is limited, and more large-scale, high-quality clinical trials are needed in the future.Trial registration number prospero crd42018083885.

Journal: Medicine (2021)
Publication types: Journal Article;Meta-Analysis;Systematic Review
The opioid system in depression.

Opioid receptors are widely distributed throughout the brain and play an essential role in modulating aspects of human mood, reward, and well-being.Accumulating evidence indicates the endogenous opioid system is dysregulated in depression and that pharmacological modulators of mu, delta, and kappa opioid receptors hold potential for the treatment of depression.Here we review animal and clinical data, highlighting evidence to support: dysregulation of the opioid system in depression, evidence for opioidergic modulation of behavioural processes and brain regions associated with depression, and evidence for opioidergic modulation in antidepressant responses.We evaluate clinical trials that have examined the safety and efficacy of opioidergic agents in depression and consider how the opioid system may be involved in the effects of other treatments, including ketamine, that are currently understood to exert antidepressant effects through non-opioidergic actions.Finally, we explore key neurochemical and molecular mechanisms underlying the potential therapeutic effects of opioid system engagement, that together provides a rationale for further investigation into this relevant target in the treatment of depression.

Journal: Neuroscience and biobehavioral reviews (2022)
Publication types: Journal Article;Review;Research Support, Non-U.S. Gov't;Research Support, N.I.H., Extramural
Chromogenicity of aerobic spore-forming bacteria of the Bacillaceae family isolated from different ecological niches and physiographic zones.

To determine the distribution patterns of pigmented bacteria of the bacilaceae family in different physiographic zones and ecological niches, we recovered 787 isolates from 185 environmental samples (including the areas with radiation pollution).Among the strains obtained, 149 pigmented representatives were detected, which synthesized intracellular and extracellular pigments of yellow, red, pink, and dark colors.In compliance with physiological, biochemical, and chemotaxonomic features, the isolates were identified as 7 species of the bacilaceae family.We demonstrated that the ability to synthesize pigments significantly depended on the culture medium composition.According to the color of the colonies, the absorption spectra of pigment extracts, their physicochemical properties, and the implementation of several qualitative tests, the pigmented isolates were divided into ten groups.The relative number of pigmented strains in the physiographic zone was consistent with the total level of solar radiation for the year.Most pigmented members of the bacillaceae family were recovered from deserts and semi-deserts, and fewest of them originated from mixed forests.We show that among the studied ecological niches, pigmented strains were most often isolated from the phyllosphere and aquatic environment and least often from soils.However, the isolates from soils and aquatic environments exhibited a greater diversity of pigmentation, and a lesser variety of colored strains was obtained from the phyllosphere and the gastrointestinal tract of animals.We established that the quantitative and qualitative composition of pigmented isolates from the areas with radiation contamination differed significantly from those coming from the natural radiation background.

Journal: Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] (2022)
Publication types: Journal Article
Pediatric Noninfectious Uveitis in a Tertiary Referral Center in Jordan: Clinical Spectrum and Immunomodulatory Treatment.

S this study aims to describe the clinical, etiological, and treatment features of noninfectious uveitis in jordanian children in a single center.Methods a retrospective, observational analysis of medical records of pediatric patients who were diagnosed with noninfectious uveitis from 2015 to 2020 at pediatric rheumatology and ophthalmology clinics at queen rania children's hospital, amman, jordan, was conducted.All patients were below 14 years of age at diagnosis.The collected data included age at diagnosis, anatomical location of uveitis, laterality, associated systemic disease, and used medications.Results overall, 96 patients were included in this cohort (41 males and 55 females), with a mean age at diagnosis of 8.4±2.4 years.Anterior uveitis (44.8%) was the commonest anatomical location.Based on laterality, bilateral uveitis was reported in 59.3% of all patients.Idiopathic uveitis (46.9%) and juvenile idiopathic arthritis-associated uveitis (jiau) (35.5%) were the most common diagnoses.Of the children with idiopathic uveitis, 47% had panuveitis, while 61.7% of the children with jiau had chronic anterior uveitis.Posterior synechiae were the most common complication (12.5%).Patients with refractory uveitis received infliximab (29.1%) and adalimumab (4.1%).Conclusion to the best of our knowledge, this is the first report on noninfectious uveitis in jordanian children.Compared with other regional and international published reports, jiau and idiopathic uveitis were the most common diagnoses.To obtain more details on noninfectious uveitis characteristics, a population-based rather than a single-center study is needed in jordan.

Journal: Cureus (2022)
Publication types: Journal Article
Insights into Trace Metal Metabolism in Health and Disease from PET: "PET Metallomics".

Essential trace metals such as copper, zinc, iron, and manganese perform critical functions in cellular and physiologic processes including catalytic, regulatory, and signaling roles.Disturbed metal homeostasis is associated with the pathogenesis of diseases such as dementia, cancer, and inherited metabolic abnormalities.Intracellular pathways involving essential metals have been extensively studied but whole-body fluxes and transport between different compartments remain poorly understood.The growing availability of pet scanners and positron-emitting isotopes of key essential metals, particularly64cu,63zn, and52mn, provide new tools with which to study these processes in vivo.This review highlights opportunities that now present themselves, exemplified by studies of copper metabolism that are in the vanguard of a new research front in molecular imaging: "pet metallomics."

Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (2018)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Review
Nanomaterials-Incorporated Chemically Modified Gelatin Methacryloyl-Based Biomedical Composites: A Novel Approach for Bone Tissue Engineering.

Gelatin methacryloyl (gel ma)-based composites are evolving three-dimensional (3d) networking hydrophilic protein composite scaffolds with high water content.These protein composites have been devoted to biomedical applications due to their unique abilities, such as flexibility, soft structure, versatility, stimuli-responsiveness, biocompatibility, biodegradability, and others.They resemble the native extracellular matrix (ecm) thanks to their remarkable cell-adhesion and matrix-metalloproteinase (mmp)-responsive amino acid motifs.These favorable properties promote cells to proliferate and inflate within gel ma-protein scaffolds.The performance of gel ma composites has been enriched using cell-amenable components, including peptides and proteins with a high affinity to harmonize cellular activities and tissue morphologies.Due to their inimitable merits, gel ma systems have been used in various fields such as drug delivery, biosensor, the food industry, biomedical, and other health sectors.The current knowledge and the role of gel ma scaffolds in bone tissue engineering are limited.The rational design and development of novel nanomaterials-incorporated gel ma-based composites with unique physicochemical and biological advantages would be used to regulate cellular functionality and bone regeneration.Substantial challenges remain.This review focuses on recent progress in mitigating those disputes.The study opens with a brief introduction to bone tissue engineering and gel ma-based composites, followed by their potential applications in bone tissue engineering.The future perspectives and current challenges of gel ma composites are demonstrated.This review would guide the researchers to design and fabricate more efficient multifunctional gel ma-based composites with improved characteristics for their practical applications in bone tissue engineering and biomedical segments.

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