Miracle-dz/UniFAR-FTUs huggingface dataset:
The first PET glimpse of a proton FLASH beam

We demonstrate the first ever recorded positron-emission tomography (PET) imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a cylindrical poly-methyl methacrylate (PMMA) phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.8 MeV and an intensity of about 3.5 × 1010 protons that were extracted over 101.5 ms-long spills. The radiation environment was characterized by cadmium–zinc–telluride and plastic scintillator counters. Preliminary results indicate that the PET technology used in our tests can efficiently record FLASH beam events. The instrument yielded informative and quantitative imaging and dosimetry of beam-activated isotopes in a PMMA phantom, as supported by Monte Carlo simulations. These studies open a new PET modality that can lead to improved imaging and monitoring of FLASH proton therapy.
Zinc improves sexual and erectile function in HAART-treated rats via the upregulation of erectogenic enzymes and maintenance of redox balance

Abstract Purpose HAART has been shown to impair sexual function and penile erection via perturbation of penile redox balance, while zinc has been established to exert antioxidant activity. Therefore, this study focused on the role and associated molecular mechanism of zinc in HAART-induced sexual and erectile dysfunction. Materials and methods Twenty male Wistar rats were randomly grouped into four (n = 5 rats per group); the control, zinc-treated, HAART-treated, and HAART + zinc-treated groups. Treatments were per os daily for eight weeks. Results Zinc co-administration significantly improved HAART-induced increase in the latencies of mount, intromission, and ejaculations. Zinc also attenuated HAART-induced reduction in the motivation to mate, penile reflex/erection, and frequencies of mount, intromission, and ejaculations. In addition, zinc co-treatment improved HAART-induced decline in penile NO and cGMP, dopamine, and serum testosterone. More so, zinc prevented HAART-induced rise in penile activities of monoamine oxidase, acetylcholinesterase, phosphodiesterase-5, and arginase. Furthermore, concomitant treatment with zinc ameliorated HAART-induced penile oxidative stress and inflammation. Conclusion In conclusion, our present findings show that zinc improves sexual and erectile function in HAART-treated rats by upregulating erectogenic enzymes via the maintenance of penile redox balance.
Dependence of the Physical Properties of GaZnO/Polyethersulfone on the Ar Gas Flow Rate During Sputtering Deposition Process

The effects of Ar gas flow rate during the sputtering deposition of Ga-doped ZnO thin films, which were grown on polyethersulfone substrates, on their physical properties were investigated. For measurements of X-ray diffraction, samples deposited under higher Ar gas flux showed the relevant ZnO (002) peak while samples deposited under lower Ar gas flux revealed ZnGa2O4 (311) secondary phase. The samples showed a quite strong dependency of the electrical resistivity on the Ar gas flux; i . e. , samples deposited under higher Ar gas flux showed a lower resistivity, but samples deposited under lower Ar gas flux showed a quite high resistivity. This result was confirmed to originate from the insulating behavior of the unexpectedly formed ZnGa2O4 spinels. The formation of ZnGa2O4 spinels might result from the generation of metastable radicals during the sputtering process because supplying an unduly insufficient amount of Ar gas gives rise to a bombardment of metastable species from the target material.
A novel oncogene trigger transposable element derived‐1 promotes oral squamous cell carcinoma progression via evoking immune inhibition

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck squamous cell carcinomas (HNSCC) globally. Its incidence rate is rapidly increasing, and its 5‐year survival rate remains at 50%, despite advances in medical science. Trigger transposable element‐derived 1 (TIGD1) has been found to be upregulated in various cancer types. However, its biological function in OSCC requires further investigation. We searched the Cancer Genome Atlas database using CIBERSORT and TIMER 2.0 to predict the significance of TIGD1 and evaluate its effect on immune cell infiltration. Gene set enrichment analysis was performed to determine the biological functions of TIGD1. Gain/loss of function techniques were used to explore the biological behavior of TIGD1 in Cal27 and HSC4 cells. Finally, flow cytometry was used to detect dendritic cell markers in an OSCC and dendritic cell co‐culture model. Our results show that TIGD1 is upregulated significantly in OSCC and is closely associated with tumor progression and prognosis. TIGD1 functions as an oncogene by increasing cells proliferation, inhibiting apoptosis, promoting cell invasion and migration. TIGD1 is also involved in tumor immune cell infiltration. Its overexpression can inhibit dendritic cell maturation, leading to immune suppression and tumor progression. High TIGD1 expression, which promotes OSCC progression, might be related to decreased dendritic cell maturation and activation. These findings suggest that TIGD1‐specific small interfering RNA synthesized in vitro could be a new target for OSCC immunotherapy.
The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer

Abstract Background Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. Materials and Methods Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. Results The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). Conclusion These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.
Long-term outcome of thoracoscopic ablation and radiofrequency catheter ablation for persistent atrial fibrillation as a de novo procedure

Abstract Aims Limited data are available regarding the efficacy of thoracoscopic ablation as the first procedure for persistent atrial fibrillation (AF). We sought to compare the long-term efficacy of thoracoscopic ablation vs. radiofrequency (RF) catheter ablation as the first procedure for persistent AF. Methods and results Between February 2011 and December 2020, 575 patients who underwent ablation for persistent AF were studied. Among them, thoracoscopic ablation was performed in 281 patients, RF catheter ablation in 228, and hybrid ablation in 66. Rhythm, clinical, and safety outcomes during 7-year follow-up were compared. The patients who underwent thoracoscopic ablation were older, had a higher prevalence of stroke, and had a larger left atrial volume than those who underwent RF catheter ablation. In the propensity score-matched population (n = 306), incidences of atrial tachyarrhythmia recurrence were 51.4% in the thoracoscopic ablation group and 62.5% in the RF catheter ablation group [adjusted hazard ratio (HR) 0.869, 95% confidence interval (CI) 0.618–1.223, P = 0.420]. Stroke and total procedural adverse events were not significantly different between thoracoscopic and RF catheter ablation (2.7 vs. 2.5%, P = 0.603, and 7.1 vs. 4.8%, P = 0.374, respectively). The hybrid ablation group showed similar rhythm outcomes compared with both the thoracoscopic and the RF catheter ablation groups. At the redo procedure, pulmonary vein gaps were more frequently observed in the RF catheter ablation group (32.6%) than in the thoracoscopic ablation group (7.9%) and in the hybrid ablation group (8.8%) (P < 0.001). Conclusion As a first procedure in persistent AF, thoracoscopic ablation and RF catheter ablation showed comparable efficacy, clinical, and safety outcomes during long-term follow-up.
PAI‐1 mediates TGF‐β1‐induced myofibroblast activation in tenocytes via mTOR signaling

Transforming growth factor‐beta (TGF‐β1) induces plasminogen activator inhibitor 1 (PAI‐1) to effect fibrotic pathologies in several organs including tendon. Recent data implicated PAI‐1 with inhibition of phosphatase and tensin homolog (PTEN) suggesting that PAI‐1‐induced adhesions involves phosphoinositide 3‐kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling. Ergo, we investigated effects of TGF‐β1, PAI‐1, and mTOR signaling crosstalk on myofibroblast activation, senescence, and proliferation in primary flexor tenocytes from wild‐type (WT) and PAI‐1 knockout (KO) mice. PAI‐1 deletion blunted TGF‐β1‐induced myofibroblast activation in murine flexor tenocytes and increased the gene expression of Mmp‐2 to confer protective effects against fibrosis. While TGF‐β1 significantly reduced phosphorylation of PTEN in WT cells, PAI‐1 deletion rescued the activation of PTEN. Despite that, there were no differences in TGF‐β1‐induced activation of mTOR signaling (AKT, 4EBP1, and P70S6K) in WT or KO tenocytes. Phenotypic changes in distinct populations of WT or KO tenocytes exhibiting high or low mTOR activity were then examined. TGF‐β1 increased alpha‐smooth muscle actin abundance in WT cells exhibiting high mTOR activity, but this increase was blunted in KO cells exhibiting high 4EBP1 activity but not in cells exhibiting high S6 activity. DNA damage (γH2AX) was increased with TGF‐β1 treatment in WT tenocytes but was blunted in KO cells exhibiting high mTOR activity. Increased mTOR activity enhanced proliferation (Ki67) in both WT and KO tenocytes. These findings point to a complex nexus of TGF‐β1, PAI‐1, and mTOR signaling in regulating proliferation, myofibroblast differentiation, and senescence in tenocytes, which could define therapeutic targets for chronic tendon adhesions and other fibrotic pathologies.
Assessing the astigmatism-reducing effect of toric intraocular lenses in eyes with low astigmatism: randomized masked bilateral comparison

Toric lenses effectively reduce low-range corneal astigmatism in a range starting at 0.75 D and allow patients to achieve better UDVA postoperatively. Purpose: To evaluate the astigmatism-reducing effect of toric intraocular lenses (IOLs) for low amounts of corneal astigmatism. Setting: Hanusch Hospital, Vienna, Austria. Design: Randomized, masked, controlled trial with bilateral comparison. Methods: Patients scheduled for bilateral cataract surgery and a corneal astigmatism in both eyes between 0.75 diopters (D) and 1.5 D were included in this study. The first eye was randomized to receive either a toric IOL or a nontoric IOL, and the contralateral eye received the other type of IOL. At the follow-up visits, optical biometry, corneal measurements with tomography and topography, autorefraction, subjective refraction, corrected and uncorrected distance visual acuity (CDVA/UDVA) with ETDRS charts and a questionnaire were performed. Results: 58 eyes were included in the study. Postoperative median UDVA was 0.00 (logMAR) in the toric eyes and 0.10 in the nontoric eyes (P = .03). The median CDVA was 0.00 in both groups (P = .60). Median residual astigmatism determined by subjective refraction and autorefraction in the toric eyes was 0.25 D and 0.50 D, respectively (P = .04), and 0.50 D and 1.00 D in the nontoric eyes, respectively (P < .001). Conclusions: The use of a toric IOL appears to be appropriate from a threshold value of approximately 0.75 D preoperative corneal astigmatism. Further studies in a larger patient population are needed to confirm these results.
Efficacy of eye movement desensitization and reprocessing therapy for fear of cancer recurrence among cancer survivors: a randomized single-case experimental design

ABSTRACT Background: Fear of cancer recurrence (FCR) is one of the greatest problems with which cancer survivors have to deal. High levels of FCR are characterized by intrusive thoughts about cancer-related events and re-experiencing these events, avoidance of reminders of cancer, and hypervigilance, similar to post-traumatic stress disorder (PTSD). Eye movement desensitization and reprocessing (EMDR) therapy focuses on these images and memories. It is effective in reducing PTSD and may be effective in reducing high levels of FCR. Objective: The aim of the present study is to investigate the effectiveness of EMDR for severe FCR in breast and colorectal cancer survivors. Method: A multiple-baseline single-case experimental design (n = 8) was used. Daily repeated measurements for FCR were taken during the baseline phase and treatment phase, post-treatment, and at the 3 month follow-up. Participants answered the Cancer Worry Scale (CWS) and the Fear of Cancer Recurrence Inventory, Dutch version (FCRI-NL) five times, i.e. at the start and at the end of each phase (baseline, treatment, post-treatment, and follow-up). The study was prospectively registered at clinicaltrials.gov (NL8223). Results: Visual analysis and effect size calculation by Tau-U were executed for the daily questionnaire on FCR. The weighted average Tau-U score was . 63 (p < .01) for baseline versus post-treatment, indicating large change, and . 53 (p < .01) between baseline and follow-up, indicating moderate change. The scores on the CWS and FCRI-NL-SF decreased significantly from baseline to follow-up. Conclusion: The results seem promising for EMDR therapy as a potentially effective treatment for FCR. Further research is recommended. HIGHLIGHTS Patients who experience high fear of cancer recurrence (FCR) often have intrusive memories and images about (future) cancer-related events. Eye movement desensitization and reprocessing (EMDR) therapy can focus on these intrusions. EMDR therapy is found to be a promising therapy for patients experiencing high FCR.
Factors Influencing the Experience of Breast and Cervical Cancer Screening Among Women in Low- and Middle-Income Countries: A Systematic Review

PURPOSE The persistent high morbidity and mortality from breast and cervical cancer in low- and middle-income countries (LMICs) may be influenced by global disparities in the uptake of screening services. This review sought to synthesize existing evidence to determine factors that influence the experience of women relating to breast and cervical screening in LMICs. METHODS A qualitative systematic review of the literature identified through Global Health, Embase, PsycInfo, and MEDLINE. Eligible studies included those outlining primary qualitative research or mixed-method studies with reporting of qualitative findings, detailing women's experiences of involvement with programs for breast or cervical cancer screening. Framework synthesis was used to explore and organize findings from primary qualitative studies and the Critical Appraisal Skills Programme checklist used for quality assessment. RESULTS Database searches yielded 7,264 studies for title and abstract screening and 90 full-text articles for screening, with qualitative data from 17 studies and a total of 722 participants included in this review. Four stages influencing experiences of women were generated across both breast and cervical cancer screening approaches, with individual (eg, knowledge of cancer), social (eg, religion, cultural beliefs), and health system (eg, accessibility) factors identified that influence women's initial and subsequent engagement. CONCLUSION This study synthesizes existing evidence of factors that influence engagement with breast and cervical cancer screening in LMICs. Evidence-informed recommendations are proposed that may improve the experience of cancer screening in LMICs, with further research necessary to explore their operationalization and impact on cancer care delivery.
Fraternity of old‐timers: How ubiquitin regulates miRNA functions

miRNA‐mediated gene repression and ubiquitin‐dependent processes are among the oldest and most versatile mechanisms that control multiple molecular pathways, rather than just protein turnover. These systems were discovered decades ago and have become among the most studied. All systems within cells are interconnected, and these two are no exception: the plethora of studies have demonstrated that the activity of the miRNAs system depends on players of the ubiquitin‐centered universe of processes, and vice versa. This review focuses on recent progress that highlights that very similar mechanisms of regulation of miRNAs by ubiquitin‐related processes are likely to be found in distantly related species, including animals, plants, and viruses. Most of them occur through the ubiquitination of Argonaute proteins, but some of the other miRNA system factors are also regulated. This suggests that their regulatory relationships are either ancient evolutionary acquisitions or have arisen independently in different kingdoms.
Systematic analysis of YFP traps reveals common mRNA/protein discordance in neural tissues

A survey of intracellular localization of 200 mRNAs and encoded proteins in the Drosophila larval nervous system. Post-transcriptional regulation is the norm and ∼10% of transcripts localize at tips of glia/neurons, with potentially important functions. A novel browsable resource of ∼1,300 figures is provided.
Astrocytoma and glioblastoma IDH1-wildtype cells colonize tumor vessels and deploy vascular mimicry

ABSTRACT Gliomas are the most prevalent type of malignant brain tumors with a very dismal prognosis. Angiogenesis in glioma has recently gotten more attention and its molecular aspects have been published; however, these were not complemented with ultrastructural evidence. Our ultrastructural examination of glioma vessels reveals several unique and critical features related to their mechanisms of progression and metastasis strategy. The detailed ultrastructural survey of 18 isocitrate dehydrogenase-wildtype (IDH1-wt) glioblastomas and 12 isocitrate dehydrogenase-mutant (IDH1-mt) High-grade gliomas indicated that tumor vessels of both types had undergone deformities such as the thickening of the vessel wall (VW) and proliferation of the basement membrane, contour distortions, abnormal and discontinuous basal lamina, tumor cells’ invasion and colonization of VW, disappearance of endothelial cells (ECs), pericytes, and smooth muscle cells, as well as the formation of a continuous ring of tumor cells attached to the luminal side of VW in numerous cases. The latter feature is a clear sign of vascular mimicry (VM) that was previously suggested in gliomas but never shown by TEM. Additionally, the vascular invasion was carried out by a large number of tumor cells and was accompanied by the accumulation of tumor lipids in the vessels’ lumina and VWs; these two features are distinct for gliomas and may alter the course of the clinical presentation and overall prognosis. This raises the issue of how to specifically target tumor cells involved in vascular invasion in order to optimize prognosis and overcome these mechanisms employed by the tumor cells.
Feed withdrawal influences egg production, egg quality and antioxidant variables in White Leghorn layers reared during the tropical summer season

ABSTRACT 1. An experiment was conducted with White Leghorn layers (Babcock BV 300) to optimise the feed withdrawal schedule for egg-laying hens (67 to 80 weeks) reared in open-sided poultry houses during the tropical summer season. 2. Four feeding schedules (1. ad libitum access to the layer feed, 2. feed withdrawal from 9 AM-5 PM, 3. 11 AM-5 PM, and 4. 1 PM-5 PM followed by free access to the layer feed) were examined. Each feeding schedule was offered to 12 replicates consisting of 12 layers housed in four adjacent cages (45.7 × 35.6 × 43.2 cm). 3. Fasting the layers from 1-5 pm reduced egg production compared to layers fasting from 9 or 11 am. The FI/egg or unit egg mass was highest in layers fasted from 1-5 pm. In the 9 am-5 pm fasted group, the cloacal temperature (CT) increased significantly at 11 am and gradually reduced at 3 pm. In the 1-5 pm fasted group, the CT remained higher at 3 pm and 5 pm. 4. The cell-mediated immune response in layers fasted from 9 am or 11 am was higher than those fed ad libitum or 1-5 pm fasted group. Lipid peroxidation was higher in layers 1-5 pm fasted group, and significantly lower LP was found in groups that fasted from 9 am or 11 am. In general, the activities of serum antioxidant enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase) were higher in layers that fasted from 9 am or 11 am compared to those that had ad libitum feed or fasted from 1-5 pm. 5. It was concluded that the feed withdrawal should be initiated during the forenoon (9 AM/11 am-5 pm) for optimum production and to reduce oxidative stress in egg-laying hens reared during summer in the tropical region.
5. Syntactic and prosodic integration and disintegration in peripheral adverbial clauses and in right dislocation/afterthought

In this paper we bring together two lines of research. This is the work on peripheral adverbial clauses (PACs) by Frey (2011, 2012) and the work on right dislocation and afterthought by Truckenbrodt (to appear). Both relate to syntactic integration, to root clauses, to intonation phrases and sentence stress. In this paper we would like to integrate them into a single set of analytical assumptions that relate to the notion of integrationby Reis (1997) and Holler (2008) and simultaneously the notion of root sentence (unembedded root clause), which according to B. Downing (1970), henceforth Downing (1970), triggers obligatory pauses (intonation phrase boundaries). The combined account involves minor adjustments of the preceding independent accounts, and it brings out similarities and differences among the phenomena investigated here. In the remainder of this section we introduce notions of syntactic integration, root sentences, and their consequences for information structure and prosody. In Section 5.2 we discuss peripheral adverbial clauses. In Section 5.3 we address right dislocation and afterthought. Peripheral clauses and dislocated constituents in the right periphery are compared in a summary of the results in Section 5.4.