syedzayyan/paper_mill_benchmark huggingface dataset:
Health-related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial.

In the phase 3 pollux trial, daratumumab in combination with lenalidomide and dexamethasone (d-rd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma (rrmm) compared with lenalidomide and dexamethasone (rd) alone.Here, we present patient-reported outcomes (pros) from pollux, assessed using the validated european organisation for research and treatment of cancer quality of life questionnaire core 30-item (eortc qlq-c30) and the euro qol 5-dimensional descriptive system (eq-5d-5l) questionnaires.Changes from baseline are presented as least-squares mean changes with 95% confidence intervals (cis) derived from a mixed-effects model.Pro assessment compliance rates were high and similar in both d-rd and rd groups through cycle 40 (week 156).In this on-treatment analysis, mean changes from baseline were significantly greater in eortc qlq-c30 global health status, physical functioning, and pain scores in the d-rd group versus the rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health-related quality of life (hrqo l).Subgroup results were similar to those in the overall population.In the pollux study, baseline hrqo l was maintained with prolonged d-rd treatment.These findings complement the sustained and significant improvement in progression-free survival observed with d-rd and supports its use in patients with rrmm.Clinical trial registration: nct02076009.

Journal: British journal of haematology (2021)
Publication types: Clinical Trial, Phase III;Journal Article;Multicenter Study;Randomized Controlled Trial;Research Support, Non-U.S. Gov't
Malignant Narcissism in Relation to Clinical Change in Borderline Personality Disorder: An Exploratory Study.

Normal and pathological narcissism have been the focus of considerable theoretical discussion and empirical research in recent years in personality psychology and psychopathology.Kernberg [ 1 - 4 ] has argued that there is a particularly dysfunctional and impairing variant of narcissistic disturbance known as malignant narcissism.This exploratory study sought to develop, using established assessment methods, a dimensional measure of malignant narcissism that incorporates the key features of grandiose narcissism, paranoid propensities, psychopathic features, and proclivity for a sadistic and aggressive interpersonal style.Method and sampling: this study examined 57 subjects, diagnosed with borderline personality disorder that were treated using 3 different empirically supported treatments in a previous study [ 5 ], for possible deviance on the proposed malignant narcissism index.It also evaluated 2 important clinical domains of change in relation to malignant narcissism.To wit, it was predicted, based on kernberg's [ 3 , 4 ] clinical model, that elevated levels of malignant narcissism would be significantly associated with slower rates of improvement in both general psychosocial/psychological functioning and anxiety among treated individuals.Results higher levels of malignant narcissism were associated, as predicted, with slower rates of improvement in both global functioning and anxiety.The proposed malignant narcissism index was a more powerful predictor of slowed improvement in global functioning than simple narcissistic personality disorder features.Conclusions the heuristic potential of the malignant narcissism construct is discussed and the utility of a dimensional approach to this construct is explored, especially in reference employing personality traits/processes to better understand pathological configurations and personality disturbance.

Journal: Psychopathology (2018)
Publication types: Journal Article
Expression of PDL1 and Her2neu in Gastric and Gastroesophageal Junction Adenocarcinoma.

The process of tumorigenesis in gastric carcinoma involves multiple genetic alterations including overexpression of pd-l1, amplification of her2neu, and mutation of p53.In the present study, the expressions of pd-l1 and her2neu were analyzed in relation to clinicopathological parameters including p53 in gastric and gastroesophageal junction adenocarcinoma.We examined 100 biopsy and resection samples of gastric and gastroesophageal junction carcinomas for pd-l1, her2neu, and p53 protein expressions using immunohistochemistry.Scorings were done based on intensity and percentage of tumor cells expressing the markers.Follow-up and survival analyses were done wherever data was available.Pd-l1 and her2neu were seen in 37% and 38% respectively.The analysis showed pd-l1 expression was significantly associated with depth of invasion (p= 0.0007), nodal metastasis (p= 0.0003), and ajcc staging (p= 0.0085).Her2neu negative including equivocal expression was significantly associated with histological grading (p= 0.0043), lauren classification (p= 0.0042), depth of invasion (p= 0.04), and nodal metastasis (p= 0.017).Combined analysis of pd-l1 and her2neu showed significant association with histological grading (p= 0.017), lauren classification (p= 0.005), depth of invasion (p= 0.0035), and nodal metastasis (p= 0.00073).Univariate cox regression analysis showed that depth of invasion, nodal metastasis, distant metastasis, ajcc staging, and p53 were negative prognostic factors for patients' overall survival.In multivariate analysis, distant metastasis and her2neu negativity including equivocal cases were independent prognostic factors.Pd-l1 positivity was seen in cases with advanced pathological features, which suggest its role in the tumorigenesis of gastric and gastroesophageal junction adenocarcinoma.Her2neu positivity showed no correlation with advanced pathological features as well as no prognostic significance, which could be attributed to tumor heterogeneity, endoscopic nature of the biopsies, and non-confirmation of equivocal cases by fluorescent in situ hybridization.

Journal: Indian journal of surgical oncology (2021)
Publication types: Journal Article
Leishmaniasis and tumor necrosis factor alpha antagonists in the Mediterranean basin. A switch in clinical expression.

Tumor necrosis factor alpha (tnf-α) blockers are recognized as a risk factor for reactivation of granulomatous infections.Leishmaniasis has been associated with the use of these drugs, although few cases have been reported.Methodology we performed a retrospective observational study including patients with confirmed leishmaniasis acquired in the mediterranean basin that were under tnf-α blockers therapy at the moment of the diagnosis.Patients diagnosed in our hospital from 2008 to 2018 were included.Moreover, a systematic review of the literature was performed and cases fulfilling the inclusion criteria were also included.Principal findings forty-nine patients were analyzed including nine cases from our series.Twenty-seven (55.1%) cases were male and median age was 55 years.Twenty-five (51%) patients were under infliximab treatment, 20 (40.8%) were receiving adalimumab, 2 (4.1%) etanercept, one (2%) golimumab and one (2%) a non-specified tnf-α blocker.Regarding clinical presentation, 28 (57.1%) presented as cutaneous leishmaniasis (cl), 16 (32.6%) as visceral leishmaniasis (vl) and 5 (10.2%) as mucocutaneous leishmaniasis (mcl).All vl and mcl patients were treated with systemic therapies.Among cl patients, 13 (46.4%) were treated with a systemic drug (11 received l-am b, one intramuscular antimonials and one miltefosine) while 14 (50%) patients were given local treatment (13 received intralesional pentavalent antimonials, and one excisional surgery).Tnf-α blockers were interrupted in 32 patients (65.3%).After treatment 5 patients (10.2%) relapsed.Four patients with a cl (3 initially treated with local therapy maintaining tnf-α blockers and one treated with miltefosine) and one patient with vl treated with l-am b maintaining tnf-α blockers.Conclusions this data supports the assumption that the blockage of tnf-α modifies clinical expression of leishmaniasis in endemic population modulating the expression of the disease leading to atypical presentations.According to the cases reported, the best treatment strategy would be a systemic drug and the discontinuation of the tnf-α blockers therapy until clinical resolution.

Journal: PLoS neglected tropical diseases (2019)
Publication types: Journal Article;Observational Study
Enhancing the Yield and Quality of Influenza Virus-like Particles (VLPs) Produced in Insect Cells by Inhibiting Cytopathic Effects of Matrix Protein M2.

To provide broader protection and eliminate the need for annual update of influenza vaccines, biomolecular engineering of influenza virus-like particles (vlps) to display more conserved influenza proteins such as the matrix protein m2 has been explored.However, achieving high surface density of full-length m2 in influenza vlps has been left unrealized.In this study, we show that the ion channel activity of m2 induces significant cytopathic effects in spodoptera frugiperda(sf9) insect cells when expressed using m2-encoding baculovirus.These effects include altered sf9 cell morphology and reduced baculovirus replication, resulting in impaired influenza protein expression and thus vlp production.On the basis of the function of m2, we hypothesized that blocking its ion channel activity could potentially relieve these cytopathic effects, and thus restore influenza protein expression to improve vlp production.The use of the m2 inhibitor amantadine indeed improves sf9 cellular expression not only of m2 (∼3-fold), but also of hemagglutinin (ha) (∼7-fold) and of matrix protein m1 (∼3-fold) when coexpressed to produce influenza vlps.This increased cellular expression of all three influenza proteins further leads to ∼2-fold greater vlp yield.More importantly, the quality of the resulting influenza vlps is significantly improved, as demonstrated by the ∼2-fold, ∼50-fold, and ∼2-fold increase in the antigen density to approximately 53 ha, 48 m1, and 156 m2 per influenza vlp, respectively.Taken together, this study represents a novel approach to enable the efficient incorporation of full-length m2 while enhancing both the yield and quality of influenza vlps produced by sf9 cells.

Journal: ACS synthetic biology (2019)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, Non-P.H.S.
A possible unique ecosystem in the endoglacial hypersaline brines in Antarctica.

Here, we present the results related to a new unique terrestrial ecosystem found in an englacial hypersaline brine found in northern victoria land (antarctica).Both the geochemistry and microbial (prokaryotic and fungal) diversity revealed an unicity with respect to all the other known antarctic brines and suggested a probable ancient origin mainly due a progressive cryoconcentration of seawater.The prokaryotic community presented some peculiarities, such as the occurrence of sequences of patescibacteria (which can thrive in nutrient-limited water environments) or few spirochaeta, and the presence of archaeal sequences of methanomicrobia closely related to methanoculleus, a methanogen commonly detected in marine and estuarine environments.The high percentage (35%) of unassigned fungal taxa suggested the presence of a high degree of undiscovered diversity within a structured fungal community (including both yeast and filamentous life forms) and reinforce the hypothesis of a high degree of biological uniqueness of the habitat under study.

Journal: Scientific reports (2023)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
METTL14 facilitates global genome repair and suppresses skin tumorigenesis.

Global genome repair (ggr), a subpathway of nucleotide excision repair, corrects bulky helix-distorting dna lesions across the whole genome and is essential for preventing mutagenesis and skin cancer.Here, we show that mettl14 (methyltransferase-like 14), a critical component of the n6-methyladenosine (m6a) rna methyltransferase complex, promotes ggr through regulating m6a m rna methylation-mediated ddb2 translation and suppresses ultraviolet b (uvb) radiation-induced skin tumorigenesis.Uvb irradiation down-regulates mettl14 protein through nbr1-dependent selective autophagy.Mettl14 knockdown decreases ggr and ddb2 abundance.Conversely, overexpression of wild-type mettl14 but not its enzymatically inactive mutant increases ggr and ddb2 abundance.Mettl14 knockdown decreases m6a methylation and translation of the ddb2 transcripts.Adding ddb2 reverses the ggr repair defect in mettl14 knockdown cells, indicating that mettl14 facilitates ggr through regulating ddb2 m6a methylation and translation.Similarly, knockdown of ythdf1, an m6a reader promoting translation of m6a-modified transcripts, decreases ddb2 protein levels.Both mettl14 and ythdf1 bind to the ddb2 transcript.In mice, skin-specific heterozygous mettl14 deletion increases uvb-induced skin tumorigenesis.Furthermore, mettl14 as well as ddb2 is down-regulated in human and mouse skin tumors and by chronic uvb irradiation in mouse skin, and mettl14 level is associated with the ddb2 level, suggesting a tumor-suppressive role of mettl14 in uvb-associated skin tumorigenesis in association with ddb2 regulation.Taken together, these findings demonstrate that mettl14 is a target for selective autophagy and acts as a critical epitranscriptomic mechanism to regulate ggr and suppress uvb-induced skin tumorigenesis.

Journal: Proceedings of the National Academy of Sciences of the United States of America (2021)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Ictal Theta Power as an Electroconvulsive Therapy Safety Biomarker: A Pilot Study.

Electroconvulsive therapy (ect) remains the benchmark for treatment resistant depression, yet its cognitive adverse effects have a negative impact on treatment.A predictive safety biomarker early in ect treatment is needed to identify patients at cognitive risk to maximize therapeutic outcomes and minimize adverse effects.We used ictal electroencephalography frequency analysis from suprathreshold treatments to assess the relationships between ect dose, ictal power across different frequency domains, and cognitive outcomes.Methods seventeen subjects with treatment resistant depression received right unilateral ect.Structural magnetic resonance imaging was obtained pre-ect for electric field modeling to assess ect dose.Serial assessments with 24-lead electroencephalography captured ictal activity.Clinical and cognitive assessments were performed before and after ect.The primary cognitive outcome was the change in delis kaplan executive function verbal fluency letter fluency.Results ictal theta (4-8 hz) power in the fp1/fp2 channels was associated with both whole-brain electric field strength (t(2,12) = 19.5, p = 0.007)/(t(2,10) = 21.85, p = 0.02) and delis kaplan executive function verbal fluency letter fluency scores (t(2,12) = -2.05, p = 0.05)/(t(2,10) = -2.20, p = 0.01).Other frequency bands (beta, alpha, delta, and gamma) did not demonstrate this relationship.Conclusions this pilot data identify ictal theta power as a potential safety biomarker in ect and is related to the strength of the ect dose.Ictal theta power could prove to be a convenient and powerful tool for clinicians to identify those patients most susceptible to cognitive impairment early in the treatment series.Additional studies are needed to assess the role of longitudinal changes in ictal theta power throughout the ect series.

Journal: The journal of ECT (2022)
Publication types: Journal Article
The Clinical Diagnostic Utility of Array CGH in Children with Syndromic Microcephaly.

A prospective study using array cgh in children with syndromic microcephaly from a tertiary pediatric healthcare centre in india.Aim to identify the copy number variations causative of microcephaly detected through chromosomal array cgh.Patients and methods of the 60 patients, 33 (55%) males and 27 (45%) females who consulted the rare disease clinic at department of pediatrics, sms medical college, jaipur, with developmental delay/facial dysmorphism/congenital anomalies in combination with microcephaly were included.Exclusion criteria children with acquired or non-genetic causes of microcephaly, craniosynostosis, metabolic diseases, known chromosomal aneuploidy such as trisomy 21, 13, and 18 and abnormal karyotype were excluded.The cohort was analyzed by array cgh in order to identify potentially pathogenic copy number variants (cnvs).Results clinically relevant pathogenic or likely pathogenic copy number variations (cnvs) were identified in 20/60 (33.3%) patients, variant of uncertain significance (vous) in 4/60 (6.6%) cases and benign cnvs in 3/60 (5%) of total cases.Out of 20 cases with pathogenic cnvs, 12 (60%) patients detected with a deletion, five (25%) patients with duplication and three (15%) patients resulted with a complex chromosomal rearrangement.Twelve cases present cnvs containing genes known to be implicated in microcephaly etiology.Conclusion this research highlights the contribution of submicroscopic chromosomal changes in the etiology of microcephaly in combination with developmental delay/facial dysmorphism/congenital anomalies (syndromic microcephaly).Our studies provide more insights into the benefits derived by using array cgh analysis in patients with syndromic microcephaly.

Journal: Annals of Indian Academy of Neurology (2022)
Publication types: Journal Article
Is there a change in P300 evoked potential after 6 months in cochlear implant users?

There are few studies on long-latency auditory evoked potential (p300) in people with hearing loss who use a cochlear implant.Central auditory system evaluation with behavioral and electrophysiological tests is believed to help understand the neuroplasticity mechanisms involved in auditory functioning after cochlear implant surgery.This study investigated the electrophysiological processing of cortical level acoustic signals in a group of 21 adult individuals with postlingual bilateral severe-to-profound hearing loss who were submitted to cochlear implant surgery.Methods data were collected in three phases: pre-cochlear implant surgery, at cochlear implant activation, and 6 months after surgery.P300 measures were also registered during all phases.Tone-burst and speech stimuli were used to elicit p300 and were presented in free field.Results mean p3 component latency with tone-burst and speech stimuli were 352.9 and 321.9 ms in the pre-cochlear implant phase, 364.9 and 368.7 ms in the activation phase, 336.2 and 343.6 ms 6 months after the surgery.The p3 component mean latency values using tone-burst at activation were significantly different from those 6 months after cochlear implant.They were also significantly different using speech, between pre-cochlear implant and activation phases.Lower p3 component latency occurred 6 months after cochlear implant activation with tone-burst and pre-cochlear implant with speech stimulus.There was a weak correlation between mean p3 component latency with speech stimulus and time of hearing loss.There was no difference in amplitude between phases or in the comparison with the other variables.Conclusion there were changes in p3 component latency during the period assessed, for both speech and pure-tone stimuli, with increased latency in the activation phase and similar lower results in the two other phases, pre-ci and 6 months after ci use.Mean amplitude measures did not vary in the three phases.

Journal: Brazilian journal of otorhinolaryngology (2022)
Publication types: Journal Article
Multicenter Randomized Sham Controlled Study of Genicular Artery Embolization for Knee Pain Secondary to Osteoarthritis.

To assess the safety and efficacy of genicular artery embolization (gae) compared with a sham procedure in the treatment of knee pain secondary to mild to moderate osteoarthritis (oa).Materials and methods a multicenter, single-blinded, randomized controlled trial was conducted to evaluate knee oa symptom reduction after gae versus sham procedure.Subjects (n = 21) with mild to moderate oa and intractable knee pain were randomized 2:1 to either gae or a sham procedure.Subjects who were randomized to the sham procedure and did not report clinical improvement in both the total western ontario and mc master universities osteoarthritis index (womac) and visual analog scale (vas) scores were unblinded and able to crossover to treatment at 1 month.Longitudinal data were collected for 12 months, and subjects were excluded if they required additional analgesics at follow-up.Reductions in the vas and total womac scores were compared using mixed-effects linear regression models.Results all subjects in the sham group failed to show significant improvements at 1 month and crossed over to the treatment arm.There was a statistically significantly greater pain reduction in the treatment group than in the sham group at 1 month (vas, 50.1 mm; standard error [se], 10.6; 95% confidence interval [ci], 29.0, 72.3; p<.01).Disability improvement was also significantly greater in the treatment group (womac, 24.7 points; se, 10.4; 95% ci, 3.5, 45.9; p=.02).Only minor adverse events were reported.Five subjects were excluded after increased analgesic use.Sensitivity analysis with all excluded patients confirmed significant improvements at 1 and 12 months.Conclusion in patients with mild to moderate knee oa, gae results in symptomatic improvement greater than the sham procedure with clinically significant reduction in pain and disability.

Journal: Journal of vascular and interventional radiology : JVIR (2022)
Publication types: Journal Article;Multicenter Study;Randomized Controlled Trial
The effects of Helicobacter pylori eradication therapy on salivary pepsin concentration in patients with laryngopharyngeal reflux.

To investigate the effect of helicobacter pylori (hp) eradication therapy on salivary pepsin concentration in laryngopharyngeal reflux (lpr) patients with hp infection.Materials and methods a total of 477 patients with suspected lpr were enrolled from june 2020 to september 2021.Reflux symptom index, reflux finding score, the positive rates and disintegrations per minute values of hp infection detected by14c urea breath test and salivary pepsin concentrations analyzed using enzyme-linked immunosorbent assay were compared in lpr patients and non-lpr patients with or without hp infection.Hp-positive patients were treated with hp eradication therapy while hp-negative patients with ppi therapy.Results the scores of nagging cough (0.88 vs.0.50, p = 0.035), erythema or hyperemia (1.93 vs.1.78, p = 0.035) and vocal fold edema (1.04 vs.0.85, p = 0.025) were higher in the lpr (+) hp (+) subgroup than in lpr (+) hp (-) subgroup.The concentrations of salivary pepsin in the hp (+) subgroup were higher than in the hp (-) subgroup either in lpr patients (75.24 ng/ml vs.61.39 ng/ml, p = 0.005) or the non-lpr patients (78.42 ng/ml vs.48.96 ng/ml, p = 0.024).Compared to baseline (before treatment), scores of nagging cough (0.35 vs.0.84, p = 0.019) and erythema or hyperemia (1.50 vs.1.83, p = 0.039) and the concentrations of salivary pepsin (44.35 ng/ml vs.74.15 ng/ml, p = 0.017) in lpr patients with hp infection decreased after hp treatment; yet, this was not observed for the lpr patients without hp infection treated with ppi only (p > 0.05).Conclusion hp infection may aggravate the symptoms and signs of lpr patients, partly by increasing their salivary pepsin concentration.

Journal: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery (2022)
Publication types: Journal Article