syedzayyan/paper_mill_benchmark huggingface dataset:
Delineation of dominant and recessive forms of LZTR1-associated Noonan syndrome.

Noonan syndrome (ns) is characterised by distinctive facial features, heart defects, variable degrees of intellectual disability and other phenotypic manifestations.Although the mode of inheritance is typically dominant, recent studies indicate lztr1 may be associated with both dominant and recessive forms.Seeking to describe the phenotypic characteristics of lztr1-associated ns, we searched for likely pathogenic variants using two approaches.First, scrutiny of exomes from 9624 patients recruited by the deciphering developmental disorders (ddds) study uncovered six dominantly-acting mutations (p.r97l; p.y136c; p.y136h, p.n145i, p.s244c; p.g248r) of which five arose de novo, and three patients with compound-heterozygous variants (p.r210*/p.v579m; p.r210*/p.d531n; c.1149+1g>t/p.r688c).One patient also had biallelic loss-of-function mutations in neb, consistent with a composite phenotype.After removing this complex case, analysis of human phenotype ontology terms indicated significant phenotypic similarities (p = 0.0005), supporting a causal role for lztr1.Second, targeted sequencing of eight unsolved ns-like cases identified biallelic lztr1 variants in three further subjects (p.w469*/p.y749c, p.w437*/c.-38t>a and p.a461d/p.i462t).Our study strengthens the association of lztr1 with ns, with de novo mutations clustering around the kt1-4 domains.Although lztr1 variants explain ~0.1% of cases across the ddd cohort, the gene is a relatively common cause of unsolved ns cases where recessive inheritance is suspected.

Journal: Clinical genetics (2019)
Publication types: Case Reports;Journal Article;Research Support, Non-U.S. Gov't
Artemidubolides A-T, cytotoxic unreported guaiane-type sesquiterpenoid dimers against three hepatoma cell lines from Artemisia dubia.

A random bioassay revealed that the et oh extract and et oac fraction of artemisia dubia wall.(asteraceae) exhibited cytotoxic activity against hep g2 cells with inhibitory ratios of 57.1% and 84.2% at a concentration of 100.0 μg/m l.Bio-guided isolation combined by lc-ms-it-tof analyses of the active fractions led to the isolation of 20 previously undescribed guaiane-type sesquiterpenoid dimers named artemidubolides a-t (1-20).Their structures and the absolute configurations were determined by comprehensive spectral analyses, comparison of the experimental and calculated ecd spectra, and seven compounds (artemidubolides a, b, d, f, k, o and r) were confirmed unequivocally by single crystal x-ray diffraction analysis.Structurally, artemidubolides a-q were [4 + 2] diels-alder adducts of two monomeric guaianolides, and artemidubolides r-t were linked though an ester bond.All the isolated compounds were evaluated for their hepatomatic cytotoxicity against hep g2, huh7, and sk-hep-1 cell lines to demonstrate that 18 compounds exhibited obvious cytotoxicity against three tested hepatoma cell lines with ic50values in the range of 5.4-87.6 μm.Importantly, artemidubolides b, d, and m exhibited hepatoma cytotoxicity with ic50values of 5.4, 5.7, and 9.7 (hep g2), 8.2, 4.3, and 12.2 (huh7), and 13.4, 8.4, and 12.9 μm (sk-hep-1), respectively.Mechanism investigation in hep g2 cells suggested the most active artemidubolide d dose-dependently inhibited cell migration and invasion, induced g1/m cell cycle arrest by down-regulating proteins cdk4, cdk6 and cyclin d1 and up-regulating the level of protein p21; and induced apoptosis by down-regulated of parp-1 and bcl-2 expression and up-regulating bax and cleaved parp-1 levels.

Journal: Phytochemistry (2022)
Publication types: Journal Article
Morphology and molecular mechanisms of tail resorption during metamorphosis in Rana chensinensis tadpole (Anura: Ranidae).

The tail resorption process was an inevitable and pivotal transformation during amphibian metamorphosis.The present study investigated the mechanisms of tail resorption through histological and transcriptome analysis in rana chensinensis.The results showed that tail resorption was initiated before the onset of metamorphic climax, and dramatically regressed after metamorphic climax by external-morphology measurement.The drastic disintegration of tail muscle and notochord occurred at gs42-44, which were consistent with the trend of thyroid follicular cell height.Besides, expression level analysis and functional annotation of degs (differentially expressed genes) were conducted through rna-seq analysis of the tail.Our study also analyzed the expression of genes related to oxidative stress, autophagy, apoptosis and degradation of cellular components in the tail of r.Chensinensis.This study enriched the r.Chensinensis transcriptome database and laid the foundation of further analysis of tail resorption.

Journal: Comparative biochemistry and physiology. Part D, Genomics & proteomics (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Common Orthopaedic Injuries in CrossFit Athletes.

Cross fit is a high-intensity exercise program that has gained popularity over the past few decades.Cross fit combines movements from olympic weight lifting, gymnastics, powerlifting, and high-intensity interval training.As cross fit continues to expand, knowledge of the associated orthopaedic injuries to aid providers in diagnosis, treatment, and prevention will be increasingly important.The most common cross fit injuries occur in the shoulder (25% of all injuries), spine (14%), and knee (13%).Male athletes are markedly more likely to experience injuries than female athletes, and injuries occur markedly less when there is supervised coaching of the athletes.The most common causes of injury in cross fit include improper form and exacerbation of a prior injury.The purpose of this article was to review the literature to aid clinicians in identifying and treating common orthopaedic injuries in cross fit athletes.Understanding the injury patterns, treatment, and prevention options is important for a successful recovery and return to sport.

Journal: The Journal of the American Academy of Orthopaedic Surgeons (2023)
Publication types: Review;Journal Article
Cardiac Startle Response and Clinical Outcomes in Preschool Children With Fragile X Syndrome and Autism Spectrum Disorder.

Poor physiological regulation in response to threat is linked to multiple negative developmental outcomes including anxiety, which is highly prevalent and impairing in young children with neurodevelopmental disabilities like fragile x syndrome (fxs) and autism spectrum disorder (asd).The present study contrasted cardiac startle response in pre-school-aged children with fxs, with and without asd, to children with non-syndromic asd (ns asd) and neurotypical controls (nt).The relationship of cardiac startle to non-verbal mental age (nvma), asd severity, and parent-reported anxiety was also examined.method:four age-matched groups of pre-school children participated including those with fxs without asd (fxs-only,n= 21), fxs with asd (fxs+asd,n= 17), ns asd (n= 42), and nt children (n= 27).Participants viewed a silent movie during which a single 200 ms 98-decibel white noise burst occurred.Cardiac activity was analyzed for pre-stimulus respiratory sinus arrhythmia (rsa) and the inter-beat intervals (ibi) at the auditory stimulus and 10 s post-stimulus.The spence pre-school anxiety scale, autism diagnostic observation schedule-2nd edition, and mullen scales of early learning were examined in relation to startle response.results:the ns asd group demonstrated heightened cardiac activity at the auditory stimulus and 10 s post-stimulus compared to the nt controls.Neither of the fxs groups showed differences from any other group.Higher pre-stimulus rsa was associated with reduced cardiac response across groups, while the relationship between cognitive ability and asd severity to cardiac response varied between groups.Parent-reported anxiety was not associated with cardiac response for any group.conclusion:these findings demonstrate group distinctions in cardiac responses to auditory startle.Although fxs and asd share behavioral characteristics, the ns asd group showed a heightened cardiac startle response compared to the nt group that was not present in the fxs groups with or without asd.Non-verbal mental age was associated with greater stimulus or post-stimulus reactivity for all groups except the fxs+asd group, which showed no association between startle response and any clinical outcomes.Increased understanding of the relationship between physiological regulation and clinical outcomes will assist in identifying the timing and targets for effective interventions for individuals with neurodevelopmental disabilities.

Journal: Frontiers in psychiatry (2021)
Publication types: Journal Article
Further Extension of Lifespan byUnc-43/CaMKIIandEgl-8/PLCβMutations in Germline-DeficientCaenorhabditis elegans.

Reduction of insulin/insulin-like growth factor 1 (igf1) signaling (iis) promotes longevity across species.In the nematode caenorhabditis elegans, ablation of germline stem cells (gscs) and activity changes of the conserved signaling mediatorsunc-43/ca mkii(calcium/calmodulin-dependent kinase type ii) andegl-8/plcβ(phospholipase cβ) also increase lifespan.Like iis, these pathways depend on the conserved transcription factordaf-16/foxofor lifespan extension, but how they functionally interact is unknown.Here, we show that alteredunc-43/egl-8activity further increases the lifespan of long-lived gsc-deficient worms, but not of worms that are long-lived due to a strong reduction-of-function mutation in the insulin/igf1-like receptordaf-2.Additionally, we provide evidence forunc-43and, to a lesser extent,egl-8modulating the expression of certain collagen genes, which were reported to be dispensable for longevity of these particulardaf-2mutant worms, but not for other forms of longevity.Together, these results provide new insights into the conditions and potential mechanisms by which ca mkii- and plcβ-signals modulate c.Eleganslifespan.

Journal: Cells (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Research Support, N.I.H., Extramural
Survey Results on Pathologic Aspects of Endocervical Adenocarcinoma by the International Society of Gynecological Pathologists.

The international society of gynecological pathologists (isgy p) undertook a project to provide evidence-based recommendations for pathologic reporting of all aspects of endocervical adenocarcinoma.The first step in the process was the design of an extensive survey to collect baseline information on existing practices regarding grossing, processing, diagnosing, and reporting of endocervical adenocarcinoma among the members of the society.The web-based survey of 98 questions was emailed to all members of isgy p and there were 175 respondents (38.5% of isgy p members).The responses, as expected, revealed areas of uniformity but also areas of substantial variation.The results of the survey are presented herein and assisted in developing the recommendations presented in the other reviews in this issue.

Journal: International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists (2021)
Publication types: Journal Article
Abrupt bilateral blindness as a rare post-acute demyelinating consequence of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (sars-co v-2) could prompt various neurological complications.Abrupt visual disturbance was reported as a rare severe manifestation of post-coronavirus disease 2019 (covid-19).Autoimmune conditions were assumed to have an undeniable role in creation of such circumstances.This report presents a 69-year-old woman with sudden bilateral blindness three weeks after recovering from a sars-co v-2 infection.Demyelination due to covid-19-related autoimmune disorder of the central nervous system (crad-c) was considered to be the etiology of her bilateral blindness.Due to her progressive demyelination, immunosuppressive treatments were administered, which resulted in stabilizing post-covid-19 demyelinating lesions.Accordingly, in the case of covid-19-related neurological deficits, especially the acute and progressive symptoms, there should be great consideration of autoimmune response to prevent serious complications; hence early diagnosis, treatment, and long-term assessment of patients are necessitated.

Journal: eNeurologicalSci (2022)
Publication types: Case Reports;Journal Article
The relation between narcissism and aggression: A meta-analysis.

Narcissism is a complex, hierarchical construct that can be studied at the one, two, or three factor levels with different components within each level having their own unique nomological networks.The manner in which narcissism-both broadly and narrowly construed-is linked to aggression is important to understand given longstanding clinical and empirical observations of a link between the two and the critical implications of aggression.Methods the current preregistered meta-analysis (k = 118) took a novel methodological approach in exploring the association between the three levels of narcissism (i.e., global construct level, dual-dimension level, trifurcated level) and three indices of aggression (i.e., general, proactive, reactive).Results results revealed that the global construct of narcissism shows a moderate positive association with different indices of aggression.Vulnerable narcissism associated strongly and positively with reactive aggression and general aggression.At the trifurcated level, interpersonal antagonism associated positively with all indices of aggression, agentic extraversion associated negatively with all indices of aggression, and narcissistic neuroticism associates positively with general and reactive aggression.Conclusion the study highlighted the importance of studying narcissism, and potentially other personality profiles, at a finer-grained level to better understand crucial psychological processes associated with the construct of interest.

Journal: Journal of personality (2022)
Publication types: Journal Article;Meta-Analysis
Doxorubicin effect is enhanced by sphingosine-1-phosphate signaling antagonist in breast cancer.

Doxorubicin is one of the most commonly used chemotherapeutic drugs for breast cancer; however, its use is limited by drug resistance and side effects.We hypothesized that adding fty720, a sphingosine-1-phosphate (s1p) receptor functional antagonist, to doxorubicin would potentiate its effects by suppression of drug-induced inflammation.Materials and methods the cancer genome atlas, gene expression omnibus data sets, and national cancer institute-60 panel were used for gene expressions and gene set enrichment analysis.E0771 syngeneic mammary tumor cells were used.Ob/ob mice fed with western high-fat diet were used as an obesity model.Results stat3 expression was significantly increased after doxorubicin treatment in human breast cancer that implicates that doxorubicin evokes inflammation.Expression of sphingosine kinase 1, the enzyme that produces s1p and links inflammation and cancer, tended to be higher in doxorubicin-resistant human cancer and cell lines.In a murine breast cancer model, sphingosine kinase 1, s1p receptor 1, interleukin 6, and stat3 were overexpressed in the doxorubicin-treated group, whereas all of them were significantly suppressed with addition of fty720.Combination therapy synergistically suppressed cancer growth both in vitro and in vivo.Furthermore, combination therapy showed higher efficacy in an obesity breast cancer model, where high body mass index demonstrated trends toward worse disease-free and overall survival, and high-serum s1p levels in human patients and volunteers.Conclusions we found that fty720 enhanced the efficacy of doxorubicin by suppression of drug-induced inflammation, and combination therapy showed stronger effect in obesity-related breast cancer.

Journal: The Journal of surgical research (2017)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Research Support, N.I.H., Extramural
Determination of Biological Age: Geriatric Assessment vs Biological Biomarkers.

Of review biological age is the concept of using biophysiological measures to more accurately determine an individual's age-related risk of adverse outcomes.Grading of the degree of frailty and measuring biomarkers are distinct methods of measuring biological age.This review compares these strategies for estimating biological age for clinical purposes.Recent findings the degree of frailty predicts susceptibility to adverse outcomes independently of chronological age.The utility of this approach has been demonstrated across a range of clinical contexts.Biomarkers from various levels of the biological aging process are improving in accuracy, with the potential to identify aberrant aging trajectories before the onset of clinically manifest frailty.Grading of frailty is a demonstrably, clinically, and research-relevant proxy estimate of biological age.Emerging biomarkers can supplement this approach by identifying accelerated aging before it is clinically apparent.Some biomarkers may even offer a means by which interventions to reduce the rate of aging can be developed.

Journal: Current oncology reports (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Review
Benign pituitary adenoma with multiple intracranial metastases-a case report and review of the literature.

Metastatic benign pituitary adenomas (pas), also known as pituitary carcinomas (pcs), represent 0.1-0.2% of all intracranial lesions.They are rare and challenging pathologies.We present the case of a 34-year-old female, who presented to the clinic with headache and visual loss.She was diagnosed with pa with multiple extra-axial metastases.Debulking and biopsy of the lesions was done.Postoperatively, there was gross residual disease, and the patient's visual disturbances did not improve.Only 165 cases of pcs have been reported in the current literature.Existing consensus on management of these uncommon lesions is based on trial and previously published case reports and surgery appears to be the only definitive treatment.Further research regarding any non-surgical expectant management is warranted.

Journal: Journal of surgical case reports (2022)
Publication types: Case Reports;Journal Article
Diagnosis and treatment of hand tumors.

Hand tumors are a very common problem in hand surgery.While these lesions are most often benign, malignant lesions often have an atypical presentation and are discovered late, very often during an inappropriate treatment.To optimize the care of hand tumors and to reduce diagnostic and treatment errors, we will review the broad diagnostic and therapeutic principles and the most common clinical presentations.

Journal: Orthopaedics & traumatology, surgery & research : OTSR (2022)
Publication types: Journal Article;Review
Molecular characterization of 23 Y chromosomal STR markers in the Gurjar population of National Capital Region (NCR), India.

In the present study, dna samples of 202 unrelated male individuals of gurjar population were evaluated for the molecular diversity at 23 y chromosomal y-str markers.Out of selected individuals, results showed 143 unique haplotypes.Highest degree of gene diversity (gd), polymorphic information content (pic), and power of discrimination (pd) was observed as 0.7941, 0.7590, and 0.7902, respectively, for the locus dys385a/b.Haplotype diversity (hd), gene diversity (gd), polymorphic information content (pic), and power of discrimination (pd) was found to be 0.7079, 0.999999999989, 0.9999999996, and 0.999999999986, respectively, for the studied 23 y-str markers.Allele 11 of locus dys392 was found to be the most frequent allele with the frequency of 0.762.In inter-population relationship, studied population showed genetic relatedness with the population of jammu and kashmir, india, and ladakh, india.The haplotype data of the present study will not only enrich the existing indian y-str data but will also be useful for forensic dna application.

Journal: International journal of legal medicine (2022)
Publication types: Journal Article
The electrocardiogram characteristics and pacing parameters of permanent left bundle branch pacing: a systematic review and meta-analysis.

Recent advances in conduction system pacing have led to the use of left bundle branch pacing (lbbp), which has potential advantages over his bundle pacing (hbp).For example, lbbp engages the electrical activation through the left bundle branch, produces ventricular electrical synchrony, and avoids the weakness of hbp such as lead instability, higher threshold, and early battery depletion.This pacing modality has been considered an attractive mode to achieve normal physiological pacing.However, as a new technology, lbbp is still in the stage of clinical exploration and lacks adequate evaluation.This study aims to investigate the electrocardiogram characteristics, pacing parameters, the safety, and the effectiveness of lbbp.Methods a computerized search of pub med, embase, and the cochrane library for the effects of lbbp was done.The baseline characteristics of patients, successful rate of implantation, capture threshold, r-wave amplitude, pacing impedance, qrs duration, and follow-up date were extracted and summarized.Results thirteen studies including 712 patients were included in this analysis.The overall successful rate for implantation was 92.9%.The main indications for lbbp were atrioventricular block (avb), sinus node dysfunction (snd), atrial fibrillation (af) with slow ventricular rate, and cardiac resynchronization therapy (crt) candidates.For patients with qrs duration>120 ms, permanent lbbp resulted in narrower qrs duration compared to that before implantation (p = 0.05).Qrs duration and capture threshold of lbbp remained stable during follow-up.Moreover, there was higher r-wave amplitude and lower pacing impedance at follow-up compared to those at implantation (p = 0.01 and p < 0.00001, respectively).Conclusions permanent lbbp has shown promising results for pacemaker-indicated patients in small observational studies.Good electrical synchronization, high success rates, and stable pacemaker lead parameters suggested significant advantages of lbbp in physiological pacing.Randomized controlled trials are needed to assess the efficacy of lbbp in patients.

Journal: Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing (2022)
Publication types: Journal Article;Meta-Analysis;Review;Systematic Review
Is adherence to the Mediterranean diet associated with good sleep duration in primary-school children?

The mediterranean diet (md) contributes to preventing numerous chronic diseases and has benefits on cognitive development.Adherence to the md is associated with sleep quality and duration in adults and adolescents, but this association seems to have been little investigated in primary-school children.The aim of this cross-sectional study was to verify whether good sleep duration was associated with adherence to the md.Design the study enrolled a sample of italian primary school children.Their mothers were asked to answer an anonymous, self-administered questionnaire investigating the children's adherence to the md (using the kid med score) and variables related to their lifestyles, behavioral traits and socio-economic factors.Logistic regression models were developed to analyze the association between adherence to the md, entered as the dependent variable, and adequacy of sleep duration.Setting primary schools in padova, italy.Subjects 267 italian 6-year-olds in their first year of primary school.Results the multivariate analysis showed an association between adherence to the md and hours of sleep: for children with a good sleep duration, the odds ratio of a poor-to-moderate adherence to the md was 0.282 (95% ci, 0.109-0.681,p< 0.05).Conclusion ensuring an adequate sleep duration may be an important strategy for enhancing adherence to the md.Sleep and dietary education should be included in future health promotion programs.

Journal: Frontiers in pediatrics (2022)
Publication types: Journal Article