Miracle-dz/UniFAR-FTUs huggingface dataset:
EGFR Amplification Induces Increased DNA Damage Response and Renders Selective Sensitivity to Talazoparib (PARP Inhibitor) in Glioblastoma

Purpose: Exploration of novel strategies to extend the benefit of PARP inhibitors beyond BRCA-mutant cancers is of great interest in personalized medicine. Here, we identified EGFR amplification as a potential biomarker to predict sensitivity to PARP inhibition, providing selection for the glioblastoma (GBM) patient population who will benefit from PARP inhibition therapy. Experimental Design: Selective sensitivity to the PARP inhibitor talazoparib was screened and validated in two sets [test set (n = 14) and validation set (n = 13)] of well-characterized patient-derived glioma sphere-forming cells (GSC). FISH was used to detect EGFR copy number. DNA damage response following talazoparib treatment was evaluated by γH2AX and 53BP1 staining and neutral comet assay. PARP–DNA trapping was analyzed by subcellular fractionation. The selective monotherapy of talazoparib was confirmed using in vivo glioma models. Results: EGFR-amplified GSCs showed remarkable sensitivity to talazoparib treatment. EGFR amplification was associated with increased reactive oxygen species (ROS) and subsequent increased basal expression of DNA-repair pathways to counterelevated oxidative stress, and thus rendered vulnerability to PARP inhibition. Following talazoparib treatment, EGFR-amplified GSCs showed enhanced DNA damage and increased PARP–DNA trapping, which augmented the cytotoxicity. EGFR amplification–associated selective sensitivity was further supported by the in vivo experimental results showing that talazoparib significantly suppressed tumor growth in EGFR-amplified subcutaneous models but not in nonamplified models. Conclusions: EGFR-amplified cells are highly sensitive to talazoparib. Our data provide insight into the potential of using EGFR amplification as a selection biomarker for the development of personalized therapy.
Nystagmus duration after caloric irrigations

Abstract Objective: To measure nystagmus duration after warm and cool caloric water irrigations, with the aim of providing preliminary evidence for the optimum interval between irrigation onsets; and to compare nystagmus durations between warm and cool irrigations, in addition to maximum slow phase velocity (SPV). Design: Participants underwent up to four caloric irrigations during routine appointments. Nystagmus was recorded to minimal levels (within 2°/s of subject’s baseline). The nystagmus duration and maximum SPV were measured. Study Sample: 52 vestibular assessment patients (99 ears). Results: The mean nystagmus duration was 183.9 s (seconds) (3:04 min) from irrigation onset, and nystagmus became minimal after 264.8 s (4:25 min) in 97.5% of this sample. The population mean is within ±6.7 s of the sample mean (p = <0.001). There was no significant difference between warm and cool irrigation durations, and correlation and linear regression analysis showed duration cannot reliably be predicted by maximum SPV. Conclusions: Mean nystagmus duration (3 min after irrigation onset) and nystagmus duration for 97.5% of patients (<4.5 min) were substantially less than the BSA recommended 7 min between irrigations. These findings provide preliminary evidence for shortening of intervals between stimulus onsets, regardless of irrigation temperature or maximum SPV, to reduce caloric testing time and improve clinical efficiency.
Association of volume of self-directed versus assigned interpretive work with diagnostic performance of radiologists: an observational study

Objectives To understand the sources of variability in diagnostic performance among experienced radiologists. Design All prostate MRI examinations performed between 2016 and 2018 were retrospectively reviewed. Setting University hospital in Japan. Participants Data derived from 334 pathology-proven cases (male, mean age: 70 years; range: 35–90 years) that were interpreted by 10 experienced radiologists were subjected to the analysis. Primary and secondary outcome measures Diagnostic performance measures of the radiologists were compared with candidate factors, including interpretive volume of prostate MRIs, volume of self-directed and assigned total annual interpretive work, and years of experience. The potential influence of fatigue was also evaluated by examining the effect of the report’s issue time. Results There were 186 prostate cancer cases. Performance was based on accuracy, sensitivity and specificity (86%, 85% and 84%, respectively). While performance was not correlated with the volume of prostate MRIs, per se (ρ=–0.15, p=0.69; ρ=–0.01, p=0.99; ρ=–0.33, p=0.36) or the total MRIs assigned for each radiologist (p>0.6) or years of experience (p>0.4), all measures were strongly correlated with voluntary work represented by the interpretive volume of abdominal CTs (r=0.79, p<0.01; r=0.80, p<0.01; r=0.64, p=0.048). The performance did not differ based on the issue time of the report (morning, afternoon and evening) (χ2(2)=3.65, p=0.16). Conclusions Greater autonomy, represented as enhanced self-directed interpretive work, was most significantly correlated with the performance of prostate MRI interpretation. The lack of a correlation between the performance and assigned volume confirms the complexity of human learning. Together, these findings support the hypothesis that successful promotion of internal drivers could have a pervasive positive impact on improving diagnostic performance.
Platelet-derived β2m regulates age related monocyte/macrophage functions

Platelets have central roles in both immune responses and development. Stimulated platelets express leukocyte adhesion molecules and release numerous immune modulatory factors that recruit and activate leukocytes, both at the sites of activation and distantly. Monocytes are innate immune cells with dynamic immune modulatory functions that change during the aging process, a phenomenon termed “inflammaging”. We have previously shown that platelets are a major source of plasma beta-2 microglobulin (β2M) and that β2M induced a monocyte pro-inflammatory phenotype. Plasma β2M increases with age and is a pro-aging factor. We hypothesized that platelet derived β2M regulates monocyte phenotypes in the context of aging. Using wild-type (WT) and platelet specific β2M knockout mice (Plt-β2M-/-) mice, we found that plasma β2M increased with age and correlated with increased circulating Ly6CHi monocytes. However, aged Plt-β2M-/- mice had significantly fewer Ly6CHi monocytes compared to WT mice. Quantitative real-time PCR of circulating monocytes showed that WT mouse monocytes were more “pro-inflammatory” with age, while Plt-β2M-/- derived monocytes adopted a “pro-reparative” phenotype. Older Plt-β2M-/- mice had a significant decline in heart function compared to age matched WT mice, as well as increased cardiac fibrosis and pro-fibrotic markers. These data suggest that platelet-derived β2M regulates age associated monocyte polarization, and a loss of platelet derived β2M shifted monocytes and macrophages to a pro-reparative phenotype and increased pro-fibrotic cardiac responses. Platelet regulation of monocyte phenotypes via β2M may maintain a balance between inflammatory and reparative signals that affects age related physiologic outcomes.
Effect of local bee honey on dihydrofolate reductase enzyme inhibitor-induced mucositis: A histological study on albino wistar rats

Introduction: Mucositis is a common complication in around 40% of patients receiving chemotherapy which profoundly impact the quality of life. Despite the availability of many therapeutic agents that claim to prevent or reduce the severity of oral mucositis, no intervention that is completely successful at preventing oral mucositis exists. The present study aimed to demonstrate the effect of local honey on methotrexate-induced mucositis of the tongue. Materials and Methods: The study was done in albino rats (n = 24), divided into four groups: honey-normal saline group (H/NS), distilled water-NS group (DW/NS), DW-methotrexate group (DW/MTX), and H/MTX group. Local honey was given (2.5 g/kg) twice a daily for 8 days. NS or methotrexate (60 mg/kg) interrupted the experiment procedure on day 4. At day 8, rats were sacrificed and middle third of tongue was removed for preparation of histological slides. Slides were examined for inflammatory cell infiltration (ICI), cell vacuolization (CV), congested blood vessels (CBV), thickness of epithelium (both dorsal and ventral mucosa), and thickness keratin. Results: Statistically significant association was found between the groups for ICI and CV, χ2 (3) = 11.97, P= 0.003 for ICI, and χ2 (3) = 8.307, P= 0.023 for CV. Mean number of CBV per microscopic filed was 0.445, 0.389, 1.28, and 0.5 for H/NS, DW/NS, DW/MTX, and DW/H groups, respectively. Mean value of dorsal epithelial thickness (μm) was 96.78 ± 13.59, 100.50 ± 9.75, 75.53 ± 9.24, and 98.75 ± 10.92 for H/NS, DW/NS, DW/MTX, and DW/H groups, respectively. Mean value of ventral epithelial thickness (μm) was 70.45 ± 13.60, 58.38 ± 14.26, 37.04 ± 5.37, and 52.80 ± 7.97 for H/NS, DW/NS, DW/MTX, and DW/H groups, respectively. The thickness of epithelium of DW/MTX group was significantly different from other groups (P < 0.05). Conclusion: The present study demonstrated the palliative effect of local honey over the mucositis induced by the chemotherapeutic drug (methotrexate).
Effect of Hemodiafiltration on Self-Reported Sleep Duration: Results from a Randomized Controlled Trial

Introduction: Dialysis patients suffer from poor sleep duration and quality. We examined the self-reported sleep duration in patients randomized to either high-volume hemodiafiltration (HDF) or high flux hemodialysis (HD). Methods: Patients from 13 Brazilian dialysis clinics were enrolled in the HDFIT randomized controlled trial (RCT) investigating the impact of HDF on physical activity and self-reported outcomes. Self-reported sleep duration was taken from patient diaries recording sleep start and end time over a week during baseline, months 3 and 6, respectively. Sleep duration was analyzed by shift and nights relative to dialysis. Results: The HDFIT study enrolled 197 patients; sleep data were available in 173 patients (87 HD; 86 HDF). Patients’ age was 53 ± 15 years, 57% were white, 72% were male, 34% had diabetes, Kt/V was 1.54 ± 0.40, and albumin 3.97 ± 0.36 g/dL. Most patients reported sleeping 510–530 min/night. At 3 months, HDF patients slept 513 ± 71 min/night, HD patients 518 ± 76 min/night. At 6 months, HDF patients slept 532 ± 74 min/night, HD patients 519 ± 80 min/night. At baseline, 1st shift patients slept 406 ± 86 min the night before HD, 534 ± 64 min the night after HD, and 496 ± 99 min the night between 2 non-HD days. Compared to patients in the 2nd and 3rd shifts, patients dialyzed in the 1st shift slept less in the night before dialysis. Similar patterns were seen after 3 and 6 months. Conclusion: In our RCT, the dialysis modality (HDF vs. HD) had no effect on self-reported sleep duration. In both groups, dialysis in the 1st shift adversely affected self reported sleep duration.
Comparison of 2 Different Fixation Implants for Operative Treatment of Mid-Shaft Clavicle Fractures: A Retrospective Study

Background This retrospective analysis was designed to compare the outcomes of mid-shaft clavicle fracture operative treatment using bridge combined fixation system (BCFS) versus clavicular locking plate (CLP). Material/Methods Operative surgeries performed between January 2016 and July 2018 were included in the analysis. The surgical internal fixation implants were chosen according to surgeon preference and the choice of patients between the BCFS and CLP. Functional outcomes, fracture union, complications, pain, and patient satisfaction post-operation were assessed at a follow-up of 12 to 24 months. Results Two hundred and seventeen (217) patients, aged 21–79 years, were operated, 87 using BCFS and 130 using CLP. The operation time of the BCFS group was significantly less than the CLP group (P<0.01). We also found that BCFS group had higher degree of satisfaction (100% vs. 97%, P<0.03) and less VAS scale (0.25±0.18 vs. 0.35±0.21, P<0.001) compared with the CLP group, but the significance could only be obtained during the follow-up at 3 months after surgery. No significant differences were observed between the 2 groups when compared for fracture unions, functional scores, or complications. Conclusions BCFS significantly reduced the operation time when compared with CLP. No significant differences were observed for functional outcomes, including fracture union and complications, and there was less pain and higher patient satisfaction. Both methods appeared to be safe in terms of complications. However, the effectiveness and safety of BCFS in treating comminuted multi-fragmentary mid-shaft clavicle fractures (AO/OTA 15-2C classification) need further confirmation.
HL301 versus Umckamin in the treatment of acute bronchitis: a phase III, randomized, controlled, double-blind, multicenter study

Abstract Objective: HL301 is a combination product of seven medicinal plants that has been proven effective in acute bronchitis by two phase II studies. In the present study, its efficacy and safety compared with those of Umckamin in the treatment of acute bronchitis were evaluated in phase III, randomized, controlled, double-blind, multicenter trial design. Methods: A total of 246 acute bronchitis patients were randomized to receive either HL301 (600 mg/day) or Umckamin (333 mg/day) for seven days. The primary outcome was the difference in their baseline (visit 2) and end of treatment (visit 3) bronchitis severity score (BSS). Other efficacy variables included the change in each BSS component (cough, sputum, dyspnea, chest pain, and crackle), response rate, improvement rate, and satisfaction rate with treatment. Results: A full analysis set and per protocol set analysis of both groups revealed that the difference of BSS between visit 2 and visit 3 in the HL301 and Umckamin group was not significantly different (4.58 ± 1.79 versus 4.29 ± 1.88, p = .37 and 4.60 ± 1.81 versus 4.33 ± 1.88, p = .42, respectively). The change in five BSS components (cough, sputum, dyspnea, chest pain, and crackle) of the HL301 and Umckamin groups did not differ after treatment. HL301 or Umckamin treated participants showed an equal level of response, improvement, and satisfaction rates with treatment. Both the HL301 group and Umckamin group showed the same safety profile. Conclusions: HL301 (600 mg/day) was as effective and safe as Umckamin (333 mg/day) in treating acute bronchitis.
Ultra-rapid brain uptake of subcutaneous sumatriptan in the rat: Implication for cluster headache treatment

Background In spite of the substantial therapeutic efficacy of triptans, their site of action is still debated. Subcutaneous sumatriptan is the most efficacious symptomatic treatment for cluster headache (CH) patients, showing therapeutic onset within a few minutes after injection even in migraine patients. However, whether subcutaneous sumatriptan is able to reach the CNS within this short time frame is currently unknown. Methods Here, by means of liquid chromatography/mass spectrometry, we investigated peripheral and brain distribution of subcutaneous sumatriptan soon after injection in rats at a dose equivalent to that used in patients. Tissue sumatriptan contents were compared to those of oxazepam, a prototypical lipophilic, neuroactive drug. Results We report that sumatriptan accumulated within brain regions of relevance to migraine and CH pathogenesis such as the hypothalamus and the brainstem as soon as 1 and 5 minutes after injection. Notably, sumatriptan brain distribution was faster than that of oxazepam, reaching concentrations exceeding its reported binding affinity for 5HT1B/D receptors, and in the range of those able to inhibit neurotransmitter release in vivo. Conclusion Our findings indicate that sumatriptan distributes within the CNS soon after injection, and are in line with prompt pain relief by parenteral sumatriptan in CH patients.
Risk factors of death in patients with cerebral infarction at 6 months: study of Nanjing First Hospital stroke registry

Objective To study the risk factors of death in patients with cerebral infarction at 6 month and to provide evidence for early intervention. Methods According to Nanjing First Hospital stroke registry,patients with cerebral infarction was prospectively registered from 2004 to 2008. Clinical characteristics of patients were recorded in detail. The follow-up was conducted at 90 d by interviewing patients or their relatives after hospital discharge. Clinical events and time of occurrence were recorded; mRS was used to evaluate the outcome after cerebral infarction. Logistic regression model was used to analysis the relationship between risk factors and death at 6 months. Results A total of1833 patients with cerebral infarction were included in the study. And 283 patients were dead at 6 months,the death rate was 15. 4%. Multivariate logistic regression analysis indicated that age( OR = 1. 028,95% CI: 1. 014- 1. 043),atrial fibrillation( OR = 2. 000,95% CI: 1. 272- 3. 145),previous stroke( OR = 1. 524,95% CI: 1. 000- 2. 321),moderate to severe neurologic deficits( OR = 5. 933,95% CI: 4. 126- 8. 530),renal function injury( OR = 1. 987,95% CI: 1. 150- 3. 435),pneumonia( OR = 3. 869,95% CI: 2. 727- 5. 489) and gastrointestinal bleeding( OR =0. 464,95% CI: 0. 217- 0. 995) were the independent risk factors of death for cerebral infarction at 6 months( all P≤0. 05). Conclusion Age,atrial fibrillation,previous stroke,moderate to severe neurologic deficit,renal function injury,pneumonia and gastrointestinal bleeding are the independent risk factors of death at 6 months after cerebral infarction.
Variability of concentric angle-specific isokinetic torque and impulse assessments of the knee extensors

Objective: Length-tension relationships are widely reported in research, rehabilitation and performance settings; however, several isometric contractions at numerous angles are needed to understand these muscular outputs. Perhaps a more efficient way to determine torque-angle characteristics is via isokinetic dynamometry; however, little is known about the variability of isokinetic measurements besides peak torque and optimal angle. This paper examines the variability of angle-specific isokinetic torque and impulse measures. Approach: Three sessions of concentric (60°·s−1) knee extensions were performed by both limbs of 32 participants. Assessments were repeated on three occasions, separated by 5–8 d. To quantify variability, the standardized typical error of measurement (TEM) was doubled and thresholds of 0.2–0.6 (small), 0.6–1.2 (moderate), 1.2–2.0 (large), 2.0–4.0 (very large) and >4.0 (extremely large) were applied. Additionally, variability was deemed large when the intraclass correlation coefficient (ICC) was <0.67 and coefficient of variation (CV) > 10%; moderate when ICC > 0.67 or CV < 10% (but not both); and small when both ICC > 0.67 and CV < 10%. Main results: Isokinetic torque and angular impulse show small to medium variability (ICC = 0.75–0.96, CV = 6.4%–15.3%, TEM = 0.25–0.53) across all but the longest (100°) and shortest (10°) muscle lengths evaluated. However, moderate to large variability was found for the optimal angle (ICC = 0.58–0.64, CV = 7.3%–8%, TEM = 0.76–0.86), and torque and impulse at the beginning and end of the range of motion (ICC = 0.57–0.85, CV = 11–42.9%, TEM = 0.40–0.89). Intersession variability of isokinetic torque and impulse were small to moderate at medium (90–20°) joint angles. Significance: Researchers and practitioners can examine the muscle torque-angle relationship and activity-specific torque outputs within these ranges, without resorting to more strenuous and time-consuming isometric evaluations.
Prenatal attachment in pregnancy following assisted reproductive technology: a literature review

ABSTRACT Objective: To summarise the literature on prenatal attachment in pregnancies following Assisted Reproductive Technology (ART). Background: Prenatal attachment can predict the quality of the postpartum parent–infant relationship and is linked to perinatal mental health of the parents and their adjustment to the parental role. It might be expected prenatal attachment will be influenced by fertility treatment such as ART, but there are contradictory results. Methods: In this review, studies with a cross-sectional and longitudinal design, published in 1990–2019 were included. A search was conducted in MEDLINE/PubMed, EMbase, Web of Science and Scopus, and using the Google Scholar search engine. A total of 17 articles were found which met the inclusion criteria and after these articles were reviewed using the STROBE-checklist, 15 articles were included in the study. Results: In most couples who conceived following ART, the level of prenatal attachment was either similar to or higher than in couples who conceive without ART. Conclusions: The findings challenge the idea that infertility problems affect attachment in pregnancies following ART. However, ART- couples may be more susceptible to anxiety due to pregnancy loss and support may be better focused on the pregnancy-related anxiety in these couples rather than any attachment intervention.
IL (Interleukin)-6 Contributes to Deep Vein Thrombosis and Is Negatively Regulated by miR-338-5p

Supplemental Digital Content is available in the text. Objective: Deep venous thrombosis (DVT), one of the most common venous thromboembolic disorders, is closely linked with pulmonary embolism and post-thrombotic syndrome, both of which have a high mortality. However, the factors that trigger DVT formation are still largely unknown. Elevated expression of IL (interleukin)-6—an important inflammatory cytokine—has been linked with DVT formation. However, the molecular mechanisms leading to the elevated IL-6 in DVT remain unclear. Here, we proposed that epigenetic modification of IL-6 at the post-transcriptional level may be a crucial trigger for IL-6 upregulation in DVT. Approach and Results: To explore the association between microRNAs and IL-6 in DVT, we performed microRNA microarray analysis and experiments both in vitro and in vivo. Microarray and quantitative real-time polymerase chain reaction results showed that IL-6 expression was increased while miR-338-5p level was decreased substantially in peripheral blood mononuclear cells of patients with DVT, and there was significant negative correlation between miR-338-5p and IL-6. Experiments in vitro showed that overexpressed miR-338-5p reduced IL-6 expression, while miR-338-5p knockdown increased IL-6 expression. Moreover, our in vivo study found that mice with anti–IL-6 antibody or agomiR-338-5p delivery resulted in decreased IL-6 expression and alleviated DVT formation, whereas antagomiR-338-5p acted inversely. Most of miR-338-5p was found located in cytoplasm by fluorescence in situ hybridization. Dual-luciferase reporter assay identified direct binding between miR-338-5p and IL-6. Conclusions: Our results suggest that decreased miR-338-5p promotes DVT formation by increasing IL-6 expression.