jimnoneill/paper-to-field-training huggingface dataset:
Interim Long-term Safety and Efficacy of XEN1101, a Potent, Selective Potassium Channel Opener: Update from an Ongoing Open-label Extension of a Phase 2b Study (X-TOLE) in Adults with Focal Epilepsy (S19.005)

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Objective: \nTo report interim 18-month data from an ongoing, long-term, open-label extension (OLE) of a Phase 2b study (X-TOLE) of XEN1101 in adults with focal onset seizures (FOS). \nBackground: \nIn the double-blind period (DBP) of X-TOLE, XEN1101 (10, 20, and 25 mg QD with food) showed a dose-dependent, statistically significant, and rapid-onset reduction in seizure frequency. We report interim 18-month OLE safety and efficacy data. \nDesign/Methods: \nEligible patients enrolled in the 5-year OLE at 20 mg QD with food. Assessments occurred at week 3 in the OLE and at 3-month intervals thereafter. Safety assessments included treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Primary efficacy outcome was median percentage change (MPC) in monthly (28-day) FOS frequency from DBP baseline. \nResults: \n285 patients completed the DBP and 275 (96.5%) enrolled in the OLE. At the 18-month OLE interim analysis (April 12, 2023), 182 had been treated for ≥1 year and 170 for ≥18 months; 159 (57.8%) patients continued participation. The majority of TEAEs were mild or moderate. The most common TEAEs were dizziness, coronavirus infection, headache, fall, and somnolence. 20.7% reported TEAEs leading to dose reduction. In the OLE at 1 and 1.5 years, the mean (SD) weight gain was 1.1 (5.9) kg and 0.5 (7.1) kg, respectively. SAEs were reported in 33 (12%) patients, 6 patients (2.2%) reported treatment-related SAEs. One SAE led to death (sudden unexpected death in epilepsy, considered not treatment related). The MPC was –83.4% at 18 months in the OLE vs DBP baseline. Updated safety and efficacy analyses will be presented. \nConclusions: \nXEN1101 was generally well tolerated and demonstrated an OLE safety profile similar to that seen in the DBP and other antiseizure medications used in FOS treatment. No new safety signals emerged. These promising data suggest long-term efficacy of XEN1101 in a difficult-to-treat population.
Prognostic significance of Musashi 2 (MSI2) RNA-binding protein expression in precancerous polyps and during colorectal cancer (CRC) progression.

Field: Medicine (Health Sciences)

e16009 Background: The RNA-binding protein Musashi-2 (MSI2) controls the translation of proteins that support stem cell identity and lineage determination. Elevated expression of MSI2 plays an important role during progression, dissemination, and drug resistance in numerous solid and hematological malignancies. This study assessed MSI2 as potential clinical biomarker in colorectal cancer (CRC) and pre-malignant disorders of colon mucosa. Methods: This study included 125 patients, of whom 20 had tubulovillous adenomas (TAs) of the colon, and 105 had verified colorectal cancer. Of the 105 patients with CRC, 45 had locoregional invasion (stages I-III). The remaining 60 patients had liver metastases (mCRC), with 31 patients diagnosed with synchronous and 29 with metachronous metastases. We used immunohistochemical (IHC) approach to measure MSI2 expression in matching specimens of normal versus TA tissues, normal versus primary CRC tumor, and normal versus metastatic CRC, followed by correlative analysis in relation to clinical outcomes. In parallel, the biological effects of overexpressing or depleting MSI2 expression in human CRC cells were analyzed in vitro using qRT-PCR, western blot, proliferation and clonogenic assays. Results: MSI2 expression in patient samples was significantly elevated in TAs versus primary tissue (p < 0.002), and was further elevated in primary tumor, and in metastatic sites (p < 0.0001 versus normal tissue, p < 0.003 versus TAs). MSI2 expression positively correlated with decreased progression free survival (PFS) and overall survival (OS), lower tumor grade, and right-side localization (p = 0.004) of tumors. In vitro knockdown of MSI2 in CRC cells suppressed of proliferation, survival and clonogenic capacities of the cells. Conclusions: Elevated expression of MSI2 is associated with pre-cancerous polyps (TAs) in the colonic mucosa, indicating it is an early event in transformation. MSI2 is further elevated during, CRC progression, and associated with poor prognosis, and loss of MSI2 reduces multiple growth properties of CRC cell models. These data imply a causative role of MSI2 overexpression at multiple stages of CRC formation and progression.
Wavelet Domain Image Super-Resolution Reconstruction Based on Image Pyramid and Cycle-Spinning

Field: Computer Science (Physical Sciences)

On the base of the analysis of single image super-resolution reconstruction, wavelet domain super-resolution reconstruction based on image Pyramid and cycle-spinning is proposed in the paper. The algorithm consists of the following parts: the predictive high-resolution image are obtained by a LR image based on laplacian pyramid method; the discrete wavelet transform is used for predictive high-resolution image to obtain the high-frequency wavelet coefficients; a high-resolution image is obtained by the inverse wavelet transform; Finally the cycle-spinning method is used to reduce ringing. The proposed algorithm avoids the application of iterative method, reduces the complexity of calculation and applies to large dimension low-resolution images. The results show the proposed approach has succeeded in obtaining a high-resolution image with a high peak signal-to-noise ratio and good visual quality.
EFFICACY OF AN ACCELERATED COLONOSCOPY TRAINING WEEK: AUDIT FROM ONE NATIONAL COLONOSCOPY TRAINING CENTER IN THE UK

Field: Health Professions (Health Sciences)

Background: Poor performance and inadequate training in colonoscopy in the UK has been reported. Several centers across the UK run intensive hands‐on training courses but their efficacy has not been established. Methods: To assess the benefit of the accelerated colonoscopy training course, an audit was conducted for the 50 trainees who individually attended the course. The course objectives were to increase core knowledge and improve the basic hand skills required for colonoscopy on a one‐to‐one basis. This includes three microteaching, two computer simulator and four hands‐on training sessions within 4 days. They performed two multiple‐choice question (MCQ) papers. Performance parameters measured at the beginning and end of the course were the Direct Observation of Procedural Skills (DOPS) using visual analog scales for all aspects of colonoscopy technique. Results: The MCQ score significantly increased: mean score 57% vs 66% ( P < 0.0001). DOPS demonstrated an improvement in clinical skills. Pre‐ and post‐course mean scores were: general approach 75 vs 81 ( P = 0.007), basic handling technique 59 vs 67 ( P = 0.002), understanding and control of looping 54 vs 67 ( P < 0.0001), cecal/ileal intubation 61 vs 76 ( P < 0.0001) and extubation technique 65 vs 77 ( P < 0.0001), respectively. All trainees had a high level of satisfaction and found the hands‐on training most beneficial. Conclusion: This intensive course improves core knowledge and clinical skills in colonoscopy, which maximizes hands‐on training, which may accelerate the learning curve.
Recent applications of multivariate data analysis methods in the authentication of rice and the most analyzed parameters: A review

Field: Agricultural and Biological Sciences (Life Sciences)

Rice is one of the most important staple foods around the world. Authentication of rice is one of the most addressed concerns in the present literature, which includes recognition of its geographical origin and variety, certification of organic rice and many other issues. Good results have been achieved by multivariate data analysis and data mining techniques when combined with specific parameters for ascertaining authenticity and many other useful characteristics of rice, such as quality, yield and others. This paper brings a review of the recent research projects on discrimination and authentication of rice using multivariate data analysis and data mining techniques. We found that data obtained from image processing, molecular and atomic spectroscopy, elemental fingerprinting, genetic markers, molecular content and others are promising sources of information regarding geographical origin, variety and other aspects of rice, being widely used combined with multivariate data analysis techniques. Principal component analysis and linear discriminant analysis are the preferred methods, but several other data classification techniques such as support vector machines, artificial neural networks and others are also frequently present in some studies and show high performance for discrimination of rice.
Clinical Case Report: Digital Emboli and Aneurysm of a Trapped Brachial Artery

Field: Medicine (Health Sciences)

We present an original case study of an adult patient with thrombo-embolic ischeamia of the fingers in relation to an aneurysm of a trapped brachial artery. The entrapment was within an abnormally high insertion of the pronator terres muscle above the humeral epicondyles. The clinic treatment and a brief overview of the literature available on the subject are presented.
Two Genomic Regions of Chromosomes 1 and 18 Explain Most of the Stroke Susceptibility Under Salt Loading in Stroke-Prone Spontaneously Hypertensive Rat/Izm

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

To clarify the genetic mechanisms of stroke susceptibility in the stroke-prone spontaneously hypertensive rat (SHRSP), a quantitative trait locus (QTL) analysis was performed. Using 295 F2 rats of a cross between SHRSP/Izm and SHR/Izm, 2 major QTLs for stroke latency under salt loading were identified on chromosomes (chr) 1 and 18. Evaluation of 6 reciprocal single and double congenic rats for these QTLs showed that substitution of the SHRSP for the SHR fragment at the chr 1 and 18 QTLs increased the relative risk for stroke by 8.4 and 5.0, respectively. The combined effect of the 2 QTLs was 10× greater than that of the background genome (by Cox hazard model). Blood pressure monitoring by radio telemetry indicated that the combination of the 2 QTLs had a clear effect on the salt-dependent blood pressure increase, suggesting an important role for the salt-sensitive blood pressure increase in the susceptibility of SHRSP to stroke. A haplotype analysis of 11 substrains of SHRSP and SHR using 340 simple sequence repeat markers in the chr 1 QTL suggested that the 7-Mbp fragment between D1Rat260 and D1Rat178 was most likely to harbor the responsible gene(s), which was confirmed by a study of additional subcongenic strains. This study indicated a major role for 2 QTLs on chr 1 and 18 in stroke susceptibility in SHRSP under salt loading. The salt-sensitive blood pressure increase was implied to play a key role in the stroke susceptibility.
Synthesis, characterization and catalytic studies of bimetallic heteronuclear complexes for the reduction of nitroaromatic compounds

Field: Chemistry (Physical Sciences)

Four mixed-ligand complexes were prepared and formulated as [Ln(H2OBA)(H2PZDC)] and [Ln(H2OBA)(H2PDC)] {Ln = La & Gd; H2OBA = 4,4-oxybisbenzoic acid; H2PDC = 2,3-pyridinedicarboxylic acid; H2PZDC = 2,3-pyrazinedicarboxylic acid}. The complexes were modified by a nickel/cobalt impregnation method to generate bimetallic complexes 1–8. Fourier transform infrared (FTIR) spectroscopy analysis of the bimetallic complexes indicated that the carboxylate coordinated to the lanthanide ion via the OH- group while the Ni2+ and Co2+ ions were preferentially bonded to the nitrogen donor ligand via the N- group. Complete catalytic reduction of 4-nitrophenol to 4-aminophenol by the Ni@ complexes gave a maximum reduction time of 37 minutes for complex 1 while complex 7 gave a reduction time of 21 minutes. The rate constants were observed to increase with an increase in temperature up to 50 °C for complexes 3, 5, and 7.
Playing the double: Pirandello's disjunctive effects on dramaturgy in liberal and fascist Italy (1860--1936)

Field: Arts and Humanities (Social Sciences)

This study examines how contents and structures of Luigi Pirandello's theatre subvert hegemonic discourses circulating in bourgeois, regional and nationalist dramatic production from the years of the Liberal State (1860-1922) to Fascist Italy (1922-1936). As part of the "disciplinary" project of the new Italian State, such production elaborates a stable model of gender, ethnic, and national subjects. Based on identification techniques, this model shapes the theatre of the adultery, the regional production of verismo, and nationalist drama. By way of a number of alienating devices, including meta-theatrical reflexivity, parodic doubling, and paradigmatic repetition, Pirandello disrupts essentialist visions of gender, Sicilian-ness, and collective models of national identity. Pirandello's alienating devices, which are the product of a dynamic relation between social and structural elements, constitute a repertoire of disjunctive figures that shape four distinct groups of plays: grotesque (La morsa, La ragione degli altri, Come prima, meglio di prima, L'uomo, la bestia, la virtù, La signora Morli, una e due, Come to mi vuoi); regional ('A birritta cu' i ciancianeddi, Liolà, 'A patenti, Pensaci Giacuminu!); metatheatrical (Sei personaggi in cerca di autore, Questa sera si recita a soggetto, Ciascuno a suo modo ); "mythical" (La nuova colonia, Lazzaro, I giganti della montagna). ^ The first chapter focuses on the subversion of bourgeois morality that is encoded in the staging of the adulterine love triangle of the grotesque plays. Pirandello fragments the unity of character in a conflict of different roles, thereby breaking the model of a stable family based upon marital authority, female subordination, and the double standard that ensues from the rigidity of such gender roles. ^ The second chapter addresses Pirandello's Sicilian theatre and focuses on the dramatist's use of parodic doubles as means to question national stereotypes of Sicily as an archive of tradition and the essence of Italian-ness. ^ Pirandello's meta-theatrical reflexivity, as opposed to both Fascist ritual theatricality and D'Annunzio's dramaturgy, is analyzed in chapter three. Meta-theatre becomes the means to prompt the audience to espouse a position of critical distance that was discouraged by the consensual structure that shaped Fascist collective performances. ^ The fourth and last chapter, devoted to Pirandello's "myths", challenges critical opinion that in this production the dramatist falls prey to the lure of Fascist mythical thought. This chapter examines how the assertive and optimist mythical structure of Fascist dramatic practices are questioned in the unveiling of the ideology that informs them: the nationalist desire for a colonial empire, the alignment of the Catholic Church with the regime, and art's loss of autonomy towards the totalitarian regime. ^
IDDF2024-ABS-0229 Early diagnosis and prognosis prediction of gastric cancer by high-performance serum lipidome fingerprints: a multi-cohort study

Field: Medicine (Health Sciences)

Background

Early detection is warranted to improve the prognosis of gastric cancer (GC), but it remains challenging. Liquid biopsy combined with machine learning will provide new insights into the diagnostic strategies of GC. Lipid metabolism reprogramming plays a crucial role in the initiation and development of tumors. Therefore, we aimed to map the lipid metabolism landscape of GC and develop novel lipid-based tools of liquid biopsy for early diagnosis and risk stratification of GC.

Methods

This cohort study enrolled 944 participants, including 440 patients with GC, 71 patients with gastric precancerous lesions and 433 healthy donors (IDDF2024-ABS-0229 Figure 1. Study design). Based on the lipid detection of the serums from participants by ultra-performance liquid chromatography-mass spectrometry, the serum lipid metabolic landscape of GC was depicted. Linear discriminant analysis and clustering analysis were employed to establish and validate the serum lipid metabolic signature (SLMS) and the gastric cancer prognostic subtype (GCPS), which were applied for the diagnosis and prognosis prediction of GC, respectively. Besides, multi-omics analysis was performed to further interpret the lipid metabolism disturbance in GC tissues and demonstrate the reliability of SLMS and GCPS.

Results

The SLMS, consisting of 19 lipids (IDDF2024-ABS-0229 Figure 2. 19 lipids in the serum lipid metabolic signature), showed excellent performances in discriminating between GC patients and healthy donors (training cohort, AUC=0.993; testing cohort, AUC=0.989; external validation cohort, AUC=0.965; predictive cohort, AUC=0.978; (IDDF2024-ABS-0229 Figure 3. The diagnostic performance of SLMS in identifying GC)). Importantly, the SLMS could efficiently distinguish early-stage GC (stage I/II) patients from healthy donors (training cohort, AUC=0.992; testing cohort, AUC=0.996; external cohort, AUC=0.975; predictive cohort, AUC=0.963; (IDDF2024-ABS-0229 Figure 4. The efficacy of SLMS in diagnosing early SATGE GE)). Moreover, the GCPS effectively predicted high-risk GC patients with poor overall survival, especially patients with advanced GC (stage III/IV, (IDDF2024-ABS-0229 Figure 5. The GCPS can predict the survival of GC patients)). Finally, the alteration of lipid metabolism in GC and the metabolic heterogeneity between two prognostic subtypes were verified in situ while some potential gene targets for GCPS were identified (IDDF2024-ABS-0229 Figure 6. Multi-omics revealed the lipid metabolism disturbance in GC).

Conclusions

Lipid metabolic reprogramming arose along with the development of gastric cancer. We could efficiently screen GC patients and predict their survival through the SLMS and GCPS.
Effect of glucocorticoid receptor (GR) blockade on endotoxemia in rats.

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

To study the clinical significance of the decrease of glucocorticoid receptor (GR) in stress and shock, GR was blocked about 80% by mifepristone (RU38486), and the effects of the blockade on the pathological changes of endotoxemia were studied in rats. The results revealed that GR blockade may exacerbate the pathological and pathophysiological changes of endotoxemia: (1) the more rapid drop in arterial blood pressure, (2) the more severe pathological changes involving multiple organs, especially the lung and small intestine, (3) the increase of leukocyte adherence in venules and more pronounced rheological changes in the mesenteric microcirculation, and (4) the striking elevation of serum acid phosphatase (ACP), phospholipase A2 (PLA2) activity, and lipoperoxide (LPO). The changes of serum ACP, PLA2, and LPO in the rats with 80% GR blockade were more marked than in those with 50% GR blockade. Based on these findings, we propose that the decrease in GR during stress and shock might be a contributing factor in the pathogenesis of shock and multiple organ failure (MOF). The possible mechanisms of the above noted findings are discussed.
Vibration of membrane modules for low pressure membrane process

Field: Chemical Engineering (Physical Sciences)

Vibrating process in submerged membrane system has the potential to overcome limitations such as fouling potentiality and high energy consumption. However, vibration mechanism is not widely understood and especially so in the filtration process of yeast solution. The main aim of this project study is to investigate the efficiency of vibration in the filtration process of yeast suspension. Different amplitudes and frequencies, degree of tightness of membrane fibers were operating parameters used in the filtration system in the laboratory. With unwashed yeasts, increment in amplitudes had a better fouling control than increment in frequencies. With washed yeast, however with increment in frequency, the fouling rate was better reduced. Without the presence of potential fouling agents, washed yeasts fouling rates were reduced significantly coupled with an increase in frequency. Vibration effectiveness in bentonite, unwashed and washed yeast solutions was proven to be achievable with increase in frequency and amplitude. However, more run tests will have to be conducted for yeast suspension. Experiments conducted to investigate the supporting frame for membrane fibers, which was suspected to introduce turbulence into the feed solution and enhance the hydrodynamic condition, had shown that the frame had negligible effect. It is evident that the vibration technique with optimize frequency and amplitude can reduce fouling rates in both organic and inorganic solutions. However, further understanding of fouling mechanism in organic solutions has to be studied for its full applicability in vibration membrane system.
Synthesis, characterization, and mechanical properties of nanoporous foams

Field: Materials Science (Physical Sciences)

Nanoporous (NP) metal foams, including Au, Cu, Ag, and Pd, have been successfully synthesized using different processes, such as free corrosion, electrochemically driven dealloying, and subsequent heat treatments. To investigate the effect of the synthesis processes on the yield strength and microstructure, the hardness of NP Au, Cu, Ag, and Pd foams with ligament sizes ranging from 20-220 nm was measured using nanoindentation and micro Vickers hardness testing, while the morphology and ligament sizes were determined by scanning electron microscopy (SEM). The results demonstrate that for all these materials, the yield strength of the NP foams was higher than that predicted by macroporous foam scale equations. In addition, combining the results with previous data for NP Au, it was observed that the yield strength of foams increases as ligament size decreases, which emphasizes the significant effect of the ligament size. The results were also compared to several predictions for foam deformation models, including elastic buckling and plastic collapse models. Overall, the deformation mode, regardless of the type of metal, seems to more closely follow the plastic collapse models. Deviations from the models are attributed to irregular cell geometry and relative density estimations. ? Additionally, the effect of oxide formation in relation to the NP foam structure for Cu and Ag was investigated as a function of heat treatments. The formation of oxide was characterized using X-ray diffraction (XRD) and Raman spectroscopy. The variations in ligament size, morphology and yield strength were investigated for all heat treated foams. For NP Cu foams, the results demonstrate that the formation of oxides was observed after any heat treatments above 200 �C under argon. These Cu oxides initiated at the surface layer and can grow in thickness with increasing heat treatment temperature, leading to a complete oxide foam. It was determined that the yield strength of Cu oxide foams increased ~ 40 times upon heat treatments, as compared to Cu foams. For the NP Ag foams, oxidation was observed after heat treatments in argon, but was limited to only a surface layer. This thin oxide layer decomposed into silver and oxygen at 600 �C. Furthermore, NP Ag foams appear to show relatively high thermal stability compared to other metal foams. The heat treatments on NP Ag foams were not as effective at changing the ligament size as the use of different electrolytes. However, the results demonstrated that both Cu and Ag foams retain their structural integrity even after oxidation.