Miracle-dz/UniFAR-FTUs huggingface dataset:
Population-based utility scores for HPV infection and cervical squamous cell carcinoma among Australian Indigenous women

Objective Working in partnership with Indigenous communities in South Australia, we aimed to develop, pilot test and estimate utility scores for health states relating to cervical cancer screening, precancer, and invasive cervical cancer and precancer/cancer treatment among Indigenous women. Methods Development and pilot testing of hypothetical cervical cancer health states, specifically through the lens of being an Indigenous Australian woman, was done with an Indigenous Reference Group in conjunction with five female Indigenous community members. Six health states were developed. These included: (1) Screened: cytology normal; (2) human papillomaviruses (HPV) positive with cytology normal; (3) low grade cytology (LSIL);(4) high grade cytology (HSIL); (5) early stage cervical cancer and; (6) later stage cervical cancer. Utility scores were calculated using a two-stage standard gamble approach among a large cohort of Indigenous Australian women taking part in a broader study involving oral HPV infection. The mean and standard deviation (SD) of the rank, percentage of respondents with a utility = 1 (perfect health) and utility score of each health state was summarised. Mean (SD) and medians and inter-quartile range (IQR) over 12 months and lifetime duration were calculated. Potential differences by age and residential location were assessed using the Wilcox Sum Rank test. Results Data was obtained from 513 Indigenous women aged 19+ years. Mean utility scores were higher for the four non-cancer health states than for invasive cervical cancer states (p-values <0.05). Lower mean utility scores were observed for late stage cervical cancer, with 0.69 at 12 months and 0.70 for lifetime duration (Intra-class correlation coefficients = 0.425). Higher utility scores were observed for the four non-cancer health states among non-metropolitan participants (ranged from 0.93 to 0.98) compared with metropolitan participants (ranged from 0.86 to 0.93) (p-values<0.05). Conclusion Among a large cohort of Indigenous Australian women, the reduction in quality of life (which utilities reflect) was perceived to be greater with increasing severity of cervical cancer health states. There were differences observed by geographic location, with positive cervical screening and precursor cancer-related quality of life being much higher among non-metropolitan-dwelling participants. These utility values, from one of the largest such studies ever performed in any population will be uniquely able to inform modelled evaluations of the benefits and costs of cervical cancer prevention interventions in Indigenous women.
Structural and functional brain alterations in anorexia nervosa:A multimodal meta‐analysis of neuroimaging studies

Anorexia nervosa (AN) is a complex psychiatric disorder with poorly understood etiology. Numerous voxel‐based morphometry (VBM) and resting‐state functional imaging studies have provided strong evidence of abnormal brain structure and intrinsic and functional activities in AN, but with inconsistent conclusions. Herein, a whole‐brain meta‐analysis was conducted on VBM (660 patients with AN, and 740 controls) and resting‐state functional imaging (425 patients with AN, and 461 controls) studies that measured differences in the gray matter volume (GMV) and intrinsic functional activity between patients with AN and healthy controls (HCs). Overall, patients with AN displayed decreased GMV in the bilateral median cingulate cortex (extending to the bilateral anterior and posterior cingulate cortex), and left middle occipital gyrus (extending to the left inferior parietal lobe). In resting‐state functional imaging studies, patients with AN displayed decreased resting‐state functional activity in the bilateral anterior cingulate cortex and bilateral median cingulate cortex, and increased resting‐state functional activity in the right parahippocampal gyrus. This multimodal meta‐analysis identified reductions of gray matter and functional activity in the anterior and median cingulate in patients with AN, which contributes to further understanding of the pathophysiology of AN.
PD-L1 detection on circulating tumor-derived extracellular vesicles (T-EVs) from patients with lung cancer

Background Recent breakthroughs in therapies with immune checkpoint inhibitors (ICIs) have revolutionized the treatment of lung cancer. However, only 15–25% of patients respond to the ICIs therapy, and methods to identify those responsive patients are currently a hot research topic. PD-L1 expression measured on tumor tissues using immunohistochemistry (IHC) was approved as one of the companion diagnostic methods, but it is invasive and cannot be used to monitor dynamic changes in PD-L1 expression during treatments. Methods In this study, we developed an Epcam-PD-L1 extracellular vesicle (EV) detection prototype using the Simoa platform. This assay detected PD-L1 expression levels on tumor-derived exosomes from the lung cancer cell lines A549 and SK-MES1. In addition, 35 plasma samples from patients with lung cancer were tested with this assay and the results were compared to the tissue PD-L1 expression levels represented by the tumor proportion score (TPS). Results PD-L1 TPS-positive patients (≥1% IHC TPS) had significantly higher Simoa Epcam-PD-L1 signals than TPS-negative patients (<1% IHC TPS, P=0.026). The Simoa Epcam-PD-L1 area under curve (AUC) reached 0.776, with a sensitivity of 92.86% and a specificity of 71.43%. When PD-L1 TPS-positive patients were defined as having an IHC TPS ≥10%, the greatest difference in Epcam-PD-L1 signals was observed between IHC TPS-positive and IHC TPS-negative groups (P=0.0024) and the Simoa Epcam-PD-L1 AUC reached 0.832. Finally, the Spearman’s correlation coefficient showed a significant correlation between the TPS and Simoa Epcam-PD-L1 signals (0.428, P=0.0104). Conclusions Based on our results, our Simoa Epcam-PD-L1 EV detection assay is a potential liquid biopsy method to predict the PD-L1 expression level in patients with lung cancer.
Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021

We measured COVID-19 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection at primary care/outpatient level among adults ≥ 65 years old using a multicentre test-negative design in eight European countries. We included 592 SARS-CoV-2 cases and 4,372 test-negative controls in the main analysis. The VE was 62% (95% CI: 45–74) for one dose only and 89% (95% CI: 79–94) for complete vaccination. COVID-19 vaccines provide good protection against COVID-19 presentation at primary care/outpatient level, particularly among fully vaccinated individuals.
Effect of social order, perch, and dust-bath allocation on behavior in laying hens

Objective The objective of this study was to determine the effects of different social ranking order (SRO) and the enrichments (perch and dust-bath) allocation (EA) on behavior of laying hens in furnished cages. Methods Total experimental period was 4 weeks. There were 216 Hy-line brown layers beak-trimmed at 1 d of age and selected randomly at 14 weeks of age from a commercial farm, and randomly divided into 36 cages with 6 hens in each cage. High enrichments (perch and dust-bath) allocation (HEA) and low enrichments (perch and dust-bath) allocation (LEA) were provided. Video observations of behavior were obtained from the focal hens between 14 and 18 weeks of age and perching, dust-bathing and other general behaviors of the hens with different social orders were measured. Results Perching behavior of high SRO hens (HSR) were significantly higher than that of medium SRO hens (MSR), and that of the MSR were significantly higher than that of low SRO hens (LSR) (p<0.01), except for lying on perch (p>0.05). The hens in the high EA cage (HEAC) showed more lying behavior on perch than those in the low EA cage (LEAC) (p< 0.01). The different SRO and EA did not affect dust-bathing behavior except vertical wing-shaking behavior (p<0.05). The LEA did not affect general behaviors (p>0.05), except standing and preening behaviors (p<0.01 and p<0.05), of which the hens in the HEAC showed less standing (p<0.01) and more preening behavior than the hens in the LEAC. Conclusion The SRO of laying hens has a significant effect on the perching behaviors, but SRO and EA have little effect on dust-bathing and general behaviors.
Upregulation of miR-128 inhibits neuronal cell apoptosis following spinal cord injury via FasL downregulation by repressing ULK1

Spinal cord injury (SCI) is characterized by permanent motor deficits followed by inflammation and oxidative stress, causing neuronal cell death. The present study aimed to investigate the role of microRNA (miR)-128 in neuronal cell apoptosis and its underlying mechanism. Targeting relationships among miR-128 and Unc-51 like autophagy activating kinase 1 (ULK1) and Fas ligand (FasL) were verified using dual-luciferase reporter assay and ChIP assays. Loss- and gain-of-function assays were conducted in rat models of SCI to determine the roles of miR-128 and ULK1 in neuronal cell apoptosis, inflammation, and motor function. Apoptosis, motor function and expression of inflammatory factors were respectively determined by Terminal deoxynucleotidyl transferase-mediated dUTp nick end-labeling, Basso, Beattie and Bresnahan (BBB) score and enzyme-linked immunosorbent assay. Hematoxylin and eosin staining, Nissl staining and immunofluorescence were respectively performed to observe morphological changes and number of neurons and nestin-positive cells. The neuronal cells were isolated from neuron injury models and cultured in vitro. MTT and flow cytometry was conducted to determine the neuronal cell viability and apoptosis respectively. miR-128 was downregulated whereas ULK1 was upregulated in rats with SCI. Overexpression of miR-128 or downregulation of ULK1 inhibited neuronal cell apoptosis and inflammation as evidenced by an increased BBB score and more neurons and nestin-positive cells, but reduced expression of inflammatory and apoptosis-related factors. ULK1 was negatively regulated by miR-128, whereas FasL was positively regulated by ULK1. In vitro experiments validated the roles of miR-128 and ULK1 in neuronal cell differentiation and apoptosis. In conclusion, the upregulation of miR-128 depresses neuronal cell apoptosis by downregulating ULK1, thereby attenuating SCI via the downregulation of FasL.
Fatigue-related reductions in movement smoothness during a lateral shuffle and side-cutting movement

ABSTRACT Although movement smoothness is considered a hallmark of well-coordinated motor tasks, it is unknown whether markers of movement smoothness can be used to assess the quality of neuromuscular control in athletes. As a first step into this direction, the purpose of this study was to test whether movement smoothness is reduced following a fatiguing lateral shuffle protocol due to fatigue-related adaptations in neuromuscular control. Sixteen healthy adults (7 females) completed a submaximal 3-minute lateral shuffle trial and a maximal fatiguing shuffle trial until task failure. The movement of the pelvis and feet was determined using 3D motion capture at 250 Hz. Movement smoothness was quantified using the log-dimensionless jerk, which represents how often and abruptly the segment acceleration changes over time. Pelvis and foot movement smoothness along with spatiotemporal variables characterizing the shuffling pattern were compared between the beginning and end of the fatiguing shuffle trial using Wilcoxon signed-rank tests (α = 0.05). Pelvis movement smoothness was significantly reduced in all movement directions (p ≤ 0.005, strong effects) while foot movement smoothness was predominantly reduced in the shuffle direction (p ≤ 0.018, moderate to strong effects). Reductions in movement smoothness coincided with a lower peak pelvis speed in shuffle direction (p = 0.007, strong effect) and shorter contact times when changing direction (p = 0.049, moderate effect). These reductions in movement smoothness may be explained by a change in the overall shuffle pattern characterized by “harder” side-cuts as well as by a muscle fatigue-related decline in the ability to precisely plan and execute foot trajectories.
Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acetaminophen-induced acute liver failure through activating ERK and IGF-1R/PI3K/AKT signaling pathway.

This study aimed to investigate the therapeutic potential of human umbilical cord mesenchymal stem cells derived exosomes (hUCMSC-Exo) in acute liver failure (ALF) in mice as well as its underlying mechanism. We found that a single tail vein administration of hucMSC-Exo effectively enhanced the survival rate, inhibited apoptosis in hepatocytes, and improved liver function in APAP-induced mouse model of ALF. Furthermore, the deletion of glutathione (GSH) and superoxide dismutase (SOD), generation of malondialdehyde (MDA), and the over production of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP were also inhibited by hucMSC-Exo, indicating that hucMSC-Exo inhibited APAP-induced apoptosis of hepatocytes by reducing oxidative stress. Moreover, hucMSC-Exo significantly down-regulated the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in APAP-treated livers. Western blot showed that hucMSC-Exo significantly promoted the activation of ERK1/2 and IGF-1R/PI3K/AKT signaling pathways in APAP-injured LO2 cells, resulting in the inhibition of apoptosis of LO2 cells. Importantly, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 could reverse the function of hucMSC-Exo on APAP-injured LO2 cells in some extent. Our results suggest that hucMSC-Exo offer antioxidant hepatoprotection against APAP in vitro and in vivo by inhibitiing oxidative stress-induced apoptosis via upregulation of ERK1/2 and PI3K/AKT signaling pathways.
MicroRNA-139-5p Regulates Fibrotic Potentials via Modulation of Collagen Type 1 and Phosphorylated p38 MAPK in Uterine Leiomyoma

Purpose This study aimed to elucidate whether microRNA-139-5p is involved in the pathogenesis of uterine leiomyoma. Materials and Methods Human leiomyoma and matched human smooth muscle samples were obtained from 10 women who underwent hysterectomy for uterine leiomyoma. MicroRNA (miRNA) expression was analyzed by quantitative real-time polymerase chain reaction. To assess the effects of miR-139-5p on cultured leiomyoma cells, cell migration, collagen gel contraction, wound healing, and the expression levels of hallmark proteins were evaluated in cells transfected with a miR-139-5p mimic. Results The expression of miR-139-5p was significantly lower in leiomyoma tissues than in matched smooth muscle tissues. Restored miR-139-5p expression in miR-139-5p mimic-transfected human leiomyoma cells resulted in decreased contractility of the ECM and cell migration. In addition, upregulation of miR-139-5p decreased the protein expression of collagen type 1 and phosphorylated p38 MAPK. Conclusion Expression of miR-139-5p is downregulated in leiomyoma cells and modulation of miR-139-5p may be involved inthe pathogenesis of leiomyomas through the regulation of collagen type 1 and phosphorylated p38 MAPK. Therefore, miR-139-5p is a potential therapeutic target for leiomyoma.
Auditory processing in schizophrenia: Behavioural evidence of abnormal spatial awareness

ABSTRACT Spatial processing deficits are the reason for many daily life problems of schizophrenia (SCZ) patients. In this study, we aimed to examine the possibility of abnormal bias to one hemifield, in form of hemispatial neglect and extinction, in auditory modality in SCZ. Twenty-five SCZ patients and 25 healthy individuals were compared on speech tasks to study the auditory neglect and extinction, as well as an auditory localization task for studying neglect. In the speech tasks, participants reproduced some nonsense syllables, played from one or two speakers on the right and/or left sides. On the localization task, examinees discriminated the subjective location of the noise stimuli presented randomly from five speakers. On the speech task, patients had significantly lower hit rates for the right ear compared with controls (p = 0.01). While healthy controls showed right ear advantage, SCZs showed a left ear priority. In the localization task, although both groups had a left-side bias, this bias was much more prominent for the patients (all p < 0.05). SCZ could potentially alter the auditory spatial function, which may appear in the form of auditory neglect and extinction on the right side, depending on the characteristics of patient population.
Differential responses of the sunn4 and rdn1-1 super-nodulation mutants of Medicago truncatula to elevated atmospheric CO2.

BACKGROUND AND AIMS Nitrogen fixation in legumes requires tight control of carbon and nitrogen balance. Thus, legumes control nodule numbers via an autoregulation mechanism. 'Autoregulation of nodulation' mutants super-nodulate and are thought to be carbon-limited due to the high carbon-sink strength of excessive nodules. This study aimed to examine the effect of increasing carbon supply on the performance of super-nodulation mutants. METHODS We compared the responses of Medicago truncatula super-nodulation mutants (sunn-4 and rdn1-1) and wild type to five CO2 levels (300-850 μmol mol -1). Nodule formation and N2 fixation were assessed in soil-grown plants at 18 and 42 days after sowing. KEY RESULTS Shoot and root biomass, nodule number and biomass, nitrogenase activity and fixed-N per plant of all genotypes increased with increasing CO2 concentration and reached the maximum around 700 μmol mol -1. While the sunn-4 mutant showed strong growth-retardation compared to wild-type plants, elevated CO2 increased shoot biomass and total N content of rdn1-1 mutant up to two-fold. This was accompanied by a four-fold increase in nitrogen fixation capacity in the rdn1-1 mutant. CONCLUSIONS These results suggest that the super-nodulation phenotype per se did not limit growth. The additional nitrogen fixation capacity of the rdn1-1 mutant may enhance the benefit of elevated CO2 on plant growth and N2 fixation.
Ultrasound‐guided injection of intralesional steroids in acute hidradenitis suppurativa lesions: A prospective study

The management of hidradenitis suppurativa (HS) flares with intralesional steroids lacks strong scientific evidence but limited data suggest that it may be useful. The objective of this study is to assess the clinical and ultrasound responses of HS flares to ultrasound‐guided injections of intralesional triamcinolone (40 mg/ml) with a dilution 1:4 versus 1:2 at 30‐day (t1), 60‐day (t2), and 90‐day (t3) follow‐up. We recruited patients with ≤3 acute lesions, unresponsive to topical therapy. At baseline we assessed lesions clinically and by ultra‐high frequency ultrasound (48 or 70 MHz) and randomly performed an ultrasound‐guided injection of triamcinolone. Assessments were repeated at t1, t2, and t3 follow‐up, re‐injecting the lesion in the case of no or partial response. We treated 49 lesions: 38.8% showed improvements at t1; 46.9% at t2; 6% at t3; and 8.3% showed no clinical and ultrasound improvements. Long‐term follow‐up data confirmed a statistically significant reduction in Visual Analogue Scale (VAS)‐pain, Dermatology Life Quality Index (DLQI), and HS‐Physician Global Assessment (HS‐PGA), as well as edema and vascular signals. No adverse effects were reported. Our study suggests that ultrasound‐injections with a 1:2 dilution are beneficial for HS flares that do not respond to topical treatment and should be included in the therapeutic algorithm.
US Trends in Opioid Access Among Patients With Poor Prognosis Cancer Near the End-of-Life

PURPOSE Heightened regulations have decreased opioid prescribing across the United States, yet little is known about trends in opioid access among patients dying of cancer. METHODS Among 270,632 Medicare fee-for-service decedents with poor prognosis cancers, we used part D data to examine trends from 2007 to 2017 in opioid prescription fills and opioid potency (morphine milligram equivalents per day [MMED]) near the end-of-life (EOL), defined as the 30 days before death or hospice enrollment. We used administrative claims to evaluate trends in pain-related emergency department (ED) visits near EOL. RESULTS Between 2007 and 2017, the proportion of decedents with poor prognosis cancers receiving ≥ 1 opioid prescription near EOL declined 15.5% (relative percent difference [RPD]), from 42.0% (95% CI, 41.4 to 42.7) to 35.5% (95% CI, 34.9 to 36.0) and the proportion receiving ≥ 1 long-acting opioid prescription declined 36.5% (RPD), from 18.1% (95% CI, 17.6 to 18.6) to 11.5% (95% CI, 11.1 to 11.9). Among decedents receiving opioids near EOL, the mean daily dose fell 24.5%, from 85.6 MMED (95% CI, 82.9 to 88.3) to 64.6 (95% CI, 62.7 to 66.6) MMED. Overall, the total amount of opioids prescribed per decedent near EOL (averaged across those who did and did not receive an opioid) fell 38.0%, from 1,075 morphine milligram equivalents per decedent (95% CI, 1,042 to 1,109) to 666 morphine milligram equivalents per decedent (95% CI, 646 to 686). Simultaneously, the proportion of patients with pain-related ED visits increased 50.8% (RPD), from 13.2% (95% CI, 12.7 to 13.6) to 19.9% (95% CI, 19.4 to 20.4). Sensitivity analyses demonstrated similar declines in opioid utilization in the 60 and 90 days before death or hospice, and suggested that trends in opioid access were not confounded by secular trends in hospice utilization. CONCLUSION Opioid use among patients dying of cancer has declined substantially from 2007 to 2017. Rising pain-related ED visits suggests that EOL cancer pain management may be worsening.
The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

Background Evidence of the clinical impact of programmed death-ligand 1 (PD-L1) expression in small cell lung cancer (SCLC) is scarce and conflicting, even though atezolizumab became the first PD-L1 inhibitor approved by the US Food and Drug Administration (FDA) in recent years for the initial treatment of extensive-stage (ES)-SCLC. Methods We investigated PD-L1 expression in SCLC tumors using the three validated PD-L1 immunohistochemistry (IHC) assays (SP263, SP142, and 22C3) and assessed the correlation between PD-L1 expression and clinicopathological factors to determine the prognostic value of PD-L1 expression. The three PD-L1 IHC analyses were prospectively used to assess tumor samples of patients with SCLC at diagnosis. Results Of the total of 59 patients, 47 patients received the active treatment beyond platinum-based chemotherapy at our institution. PD-L1 expression was positive in 39.0% with SP263, 37.3% with SP142, and 22.0% with 22C3. In a univariate analysis, the positive result of at least one of the three PD-L1 assays and the positive result of the SP142 assay were associated with longer overall survival (OS). A multivariable analysis confirmed that performance status, stage, and the SP142 assay were independent predictors of OS. In subgroup analysis, these results revealed more significant prognostic factors in ES than in limited-stage (LS). In patients with SCLC, especially those with ES, the expression of the SP142 assay is a significant independent prognostic factor. Conclusions Although these results need to be further validated in larger cohorts, this information will benefit clinicians and patients in determining the immunotherapy for patients with ES-SCLC.