Miracle-dz/UniFAR-FTUs huggingface dataset:
Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response

Objectives We aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission. Design Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015–2020, n=110; All India Institute of Medical Sciences, New Delhi 2018–2020, n=62). Results In the 2015–2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992–1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992–1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%–11%. Conclusions Emergency colectomy rates for ASC have halved in 25 years to 8%–15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.
Loss of p16 expression is a risk factor for recurrence in sinonasal inverted papilloma.

BACKGROUND The purpose of this study was to evaluate p16, p53, EGFR, pEGFR protein expression and HPV infection as possible markers of tumor progression in a series of sinonasal inverted papilloma (SNIP) and sinonasal squamous cell carcinoma (SNSCC). METHODS A series of 49 SNIP, 11 SNSCC associated with SNIP (SNIP-SNSCC) and 52 SNSCC not associated with SNIP were analyzed for p16, p53, EGFR, and phosphorylated EGFR (pEGFR) expression by immunohistochemistry. Human papillomavirus (HPV) infection status was evaluated by DNA-PCR. Results were correlated to clinical and follow-up data. RESULTS Reduced or loss of p16 expression was observed in 18% SNIP, 64% SNIP-SNSCC and 87% of SNSCC. Reduced or loss p16 staining in SNIP correlated with shorter recurrent SNIP-free follow-up. In contrast, p16 expression was not predictive of recurrent SNSCC in cases with SNIP-SNSCC and SNSCC. P53, EGFR, and pEGFR expression did not differ between the tumor groups, nor were they related to recurrent SNIP-free follow-up or recurrent SNSCC. Oncogenic HPV types 16 and 18 were detected in 5% of SNIP and 18% of SNIP-SNSCC, but not in SNSCC. There was no correlation between HPV infection and >70% p16 immunostaining. CONCLUSIONS HPV infection appears to play a minor role in SNIP and SNSCC and p16 immunostaining does not appear a valid surrogate marker for HPV. However, reduced or loss p16 expression may have prognostic value as a risk marker for recurrent SNIP.
The effect of forming implementation intentions on alcohol consumption: A systematic review and meta‐analysis

Abstract Issues Meta‐analysis was used to estimate the effect of forming implementation intentions (i.e., if‐then plans) on weekly alcohol consumption and heavy episodic drinking (HED). Sample type, mode of delivery, intervention format and timeframe were tested as moderator variables. Approach Cochrane, EThOS, Google Scholar, PsychArticles, PubMed and Web of Science were searched for relevant publications to 31 March 2021. Random‐effects meta‐analysis was used to estimate the effect size difference (d) between individuals forming versus not forming implementation intentions on weekly consumption and HED. Key Findings Sixteen studies were included in meta‐analyses. The effect size difference for forming implementation intentions on weekly alcohol consumption was d + = −0.14 confidence interval (CI) [−0.24; −0.03]. Moderator analyses highlighted stronger effects for: (i) community (d + = −0.38, CI [−0.58; −0.18]) versus university (d + = −0.04, CI [−0.13; 0.05]) samples; (ii) paper (d + = −0.26, CI [−0.43; −0.09]) versus online (d + = −0.04, CI [−0.14; 0.06]) mode of delivery; and (iii) volitional help sheet (d + = −0.34, CI [−0.60; −0.07]) versus implementation intention format (d + = −0.07, CI [−0.16; 0.02]). In addition, effects diminished over time (B = 0.02, SE = 0.01, CI [0.03; 0.01]). Forming implementation intentions had a null effect on HED, d + = −0.01 CI [−0.10; 0.08]. Implications Forming implementation intentions reduces weekly consumption but has no effect on HED. Conclusion This review identifies boundary conditions on the effectiveness of implementation intentions to reduce alcohol consumption. Future research should focus on increasing the effectiveness of online‐delivered interventions and integrating implementation intention and motivational interventions.
Epidemiology and treatment utilization for Canadian patients with migraine: a literature review

The objective of this narrative review was to identify real-world evidence regarding the burden of migraine in Canada. We conducted a literature search in MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for studies published between August 2010 and August 2020. Of the 3269 publications identified, 29 studies were included. Prevalence estimates varied widely across Canada, and mental health comorbidities were common. Individuals with migraine have a lower quality of life, detrimental impact on workforce productivity, and higher rates of health care resource utilization (HCRU), with HCRU and costs highest among those with chronic migraine. We found inconsistencies in care, including underutilization of medications such as triptans, and varied utilization of over-the-counter and prescription medications. Increased medication use was identified among those with chronic migraine, and only a small number of patients used migraine preventive medications. The burden of migraine in Canada is substantial. Reduced quality of life and workforce productivity, increased HCRU and costs, and underutilization of triptans and migraine preventive medications highlight an important need for more effective management of individuals with migraine.
Searches for electroweak production of supersymmetric gauginos and sleptons with the ATLAS detector

Many supersymmetry models feature gauginos and also sleptons with masses below a few hundred GeV. These can give rise to direct pair production rates at the LHC that can be observed in the data sample recorded by the ATLAS detector. The talk presents results from searches for gaugino and slepton pair production in final states with leptons.
Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential anti-tumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathione-dependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.
Draft Genome Sequence of Shewanella indica Isolated from a Marine Sponge (Callyspongia diffusa)

The draft genome sequence of Shewanella indica strain MMRF542, which was isolated from a marine sponge (Callyspongia diffusa), is reported. The genome sequence provides insight into the ecological relevance and biotechnological potential of Shewanella species. ABSTRACT The draft genome sequence of Shewanella indica strain MMRF542, which was isolated from a marine sponge (Callyspongia diffusa), is reported. The genome sequence provides insight into the ecological relevance and biotechnological potential of Shewanella species.
Coinfection of Two Rickettsia Species in a Single Tick Species Provides New Insight into Rickettsia-Rickettsia and Rickettsia-Vector Interactions

The rickettsiae are a group of obligate intracellular Gram-negative bacteria that include human pathogens causing an array of clinical symptoms and even death. There is an important question in the field, that is whether one infection can block the superinfection of other rickettsiae. ABSTRACT Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses. There is an ongoing debate as to whether established infections by one Rickettsia species preclude the maintenance of the second species in ticks. Here, we identified two Rickettsia species in inoculum from Haemaphysalis montgomeryi ticks and subsequently obtained pure isolates of each species by plaque selection. The two isolates were classified as a transitional group and spotted fever group rickettsiae and named Rickettsia hoogstraalii str CS and Rickettsia rhipicephalii str EH, respectively. The coinfection of these two Rickettsia species was detected in 25.6% of individual field-collected H. montgomeryi. In cell culture infection models, R. hoogstraalii str CS overwhelmed R. rhipicephalii str EH with more obvious cytopathic effects, faster plaque formation, and increased cellular growth when cocultured, and R. hoogstraalii str CS seemed to polymerize actin tails differently from R. rhipicephalii str EH in vitro. This work provides a model to investigate the mechanisms of both Rickettsia-Rickettsia and Rickettsia-vector interactions. IMPORTANCE The rickettsiae are a group of obligate intracellular Gram-negative bacteria that include human pathogens causing an array of clinical symptoms and even death. There is an important question in the field, that is whether one infection can block the superinfection of other rickettsiae. This work demonstrated the coinfection of two Rickettsia species in individual ticks and further highlighted that testing the rickettsial competitive exclusion hypothesis will undoubtedly be a promising area as methods for bioengineering and pathogen biocontrol become amenable for rickettsiae.
Accurate detection of benign and malignant renal tumor subtypes with MethylBoostER: An epigenetic marker–driven learning framework

Current gold standard diagnostic strategies are unable to accurately differentiate malignant from benign small renal masses preoperatively; consequently, 20% of patients undergo unnecessary surgery. Devising a more confident presurgical diagnosis is key to improving treatment decision-making. We therefore developed MethylBoostER, a machine learning model leveraging DNA methylation data from 1228 tissue samples, to classify pathological subtypes of renal tumors (benign oncocytoma, clear cell, papillary, and chromophobe RCC) and normal kidney. The prediction accuracy in the testing set was 0.960, with class-wise ROC AUCs >0.988 for all classes. External validation was performed on >500 samples from four independent datasets, achieving AUCs >0.89 for all classes and average accuracies of 0.824, 0.703, 0.875, and 0.894 for the four datasets. Furthermore, consistent classification of multiregion samples (N = 185) from the same patient demonstrates that methylation heterogeneity does not limit model applicability. Following further clinical studies, MethylBoostER could facilitate a more confident presurgical diagnosis to guide treatment decision-making in the future.
Survival of scalar zero modes in warped extra dimensions

Models with an extra dimension generally contain background scalar fields in a non-trivial con- figuration, whose stability must be ensured. With gravity present, the extra dimension is warped by the scalars, and the spin-0 degrees of freedom in the metric mix with the scalar perturbations. Where possible, we formally solve the coupled Schrodinger equations for the zero modes of these spin-0 perturbations. When specialising to the case of two scalars with a potential generated by a superpotential, we are able to fully solve the system. We show how these zero modes can be used to construct a solution matrix, whose eigenvalues tell whether a normalisable zero mode exists, and how many negative mass modes exist. These facts are crucial in determining stability of the corresponding background configuration. We provide examples of the general analysis for domain- wall models of an infinite extra dimension and domain-wall soft-wall models. For 5D models with two scalars constructed using a superpotential, we show that a normalisable zero mode survives, even in the presence of warped gravity. Such models, which are widely used in the literature, are therefore phenomenologically unacceptable.
A comprehensive review of pancreatic cancer and its therapeutic challenges

Pancreatic cancer is a devastating and lethal human malignancy with no curable chemo-treatments available thus far. More than 90% of pancreatic tumors are formed from ductal epithelium as pancreatic ductal adenocarcinoma (PDAC), which often accompany with the expression of mutant K-ras. The incidences of pancreatic cancer are expected to increase rapidly worldwide in the near future, due to environmental pollution, obesity epidemics and etc. The dismal prognosis of this malignancy is contributed to its susceptibility to tumor micro-metastasis from inception and the lack of methods to detect precursor lesions at very early stages of the onset until clinical symptoms occur. In recent years, basic and clinical studies have been making promising progresses for discovering markers to determine the subtypes or stages of this malignancy, which allow effectively implementing personalized therapeutic interventions. The purpose of this review is to discuss the existing knowledge of the molecular mechanisms of pancreatic cancer and the current state of treatment options with the emphasis on targeting therapeutic approaches. The specific focuses are on the molecular mechanisms of the disease, identifications of drug resistance, establishment of immune escaping mechanisms as well as potential of targeting identified pathways in combinations with existing chemo-drugs.
Interspecies Chimeric Barriers for Generating Exogenic Organs and Cells for Transplantation

A growing need for organs and novel cell-based therapies has provided a niche for approaches like interspecies chimeras. To generate organs from one donor species in another host species requires techniques such as blastocyst complementation and gene editing to successfully create an embryo that has cells from both the donor and the host. However, the task of developing highly efficacious and competent interspecies chimeras is met by many challenges. These interspecies chimeric barriers impede the formation of chimeras, often leading to lower levels of chimeric competency. The barriers that need to be addressed include the evolutionary distance between species, stage-matching, temporal and spatial synchronization of developmental timing, interspecies cell competition and the survival of pluripotent stem cells and embryos, compatibility of ligand–receptor signaling between species, and the ethical concerns of forming such models. By overcoming the interspecies chimera barriers and creating highly competent chimeras, the technology of organ and cellular generation can be honed and refined to develop fully functioning exogenic organs, tissues, and cells for transplantation.
Noise-induced synchronization and regularity in feed-forward-loop motifs

This study explores the impacts of multiple factors (noise, intra-motif coupling, and critical bifurcation parameter) on noise-induced motif synchrony and output regularity in three-node feed-forward-loops (FFLs), distinguishing between coherent FFLs with purely excitatory connections and incoherent FFLs formed by transitioning the intermediate layer to inhibitory connections. Our model utilizes the normal form of Hopf bifurcation (HB), which captures the generic structure of excitability observed in real systems. We find that the addition of noise can optimize motif synchrony and output regularity at the intermediate noise intensities. Our results also suggest that transitioning the excitatory coupling between the intermediate and output layers of the FFL to inhibitory coupling—i.e., moving from the coherent to the incoherent FFL—enhances output regularity but diminishes motif synchrony. This shift towards inhibitory connectivity highlights a trade-off between motif synchrony and output regularity and suggests that the structure of the intermediate layer plays a pivotal role in determining the motif’s overall dynamics. Surprisingly, we also discover that both motifs achieve their best output regularity at a moderate level of intra-motif coupling, challenging the common assumption that stronger coupling, especially of the excitatory type, results in improved regularity. Our study provides valuable insights into functional differences in network motifs and offers a direct perspective relevant to the field of complex systems as we consider a normal-form model that pertains to a vast number of individual models experiencing HB.
Simple and Efficient 3D-Printed Superfusion Chamber for Electrophysiological and Neuroimaging Recordings In Vivo

Visual Abstract In vitro and in vivo experimentation in the central nervous system are effective approaches to study its functioning. Manipulations in vitro are characterized by easy experimental control and stable experimental conditions. However, transferring these advantages to in vivo research remains technically and ethically challenging, preventing many research teams from acquiring critical recordings in their animal models. In order to transfer the benefits of in vitro experimentation to in vivo experimentation, we developed a suite of 3D-printed tools (a superfusion chamber with an independent brain presser and animal stand). Using the immature rat barrel cortex as a model, we show that our set of tools (further “superfusion preparation”) provides stable conditions for electrophysiological and neuroimaging recordings in the neonatal rat neocortex in vivo. Highly correlated intracellular and extracellular activity was recorded during spontaneous and evoked cortical activity, supporting the possibility of simultaneous long-lasting electrophysiological recordings from a single cortical column in vivo. The optical intrinsic signal of evoked cortical responses was also recorded from the skull-free neocortex, suggesting the effective combination of the superfusion preparation with neuroimaging approaches. Modulation of immature activity by epicortical application of pharmacological agents via superfusion equally supports the use of the superfused cortex preparation in pharmacological screening. In addition to high efficiency (in affordability, reliability, and ease of use in vivo), the 3D-printed set of tools developed should reduce animal use, supporting the 3Rs principle (Replacement, Reduction, and Refinement) of ethical use of animals.
Dobbs: Navigating the New Quagmire and Its Impacts on Abortion and Reproductive Health Care

On June 24, 2022, the U.S. Supreme Court issued its decision on Dobbs v. Jackson Women’s Health Organization. By voting to uphold Mississippi’s law banning most abortions after 15 weeks, the Court overturned Roe v. Wade, eliminating the federal standard protecting a woman’s right to abortion and reversing nearly 50 years of legal precedent. The ruling returned regulation of abortion to the states, which are responding by implementing bans or protecting access to abortion. As political and legal conflicts escalate and individual horror stories emerge, the dangerous mirage presented by this misguided legal fix to a long-standing vexing issue will come into sharper relief. The Dobbs ruling is creating a new uncertain and treacherous landscape for women and health care professionals to navigate.
A physics-based model of electrical conduction decrease with time in amorphous Ge2Sb2Te5

The time-stability of the electrical characteristics of chalcogenide materials is one of the most important issues for their use in nonvolatile solid state memory applications. In particular the electrical conduction of the glassy phase evolves with time due to two different physical phenomena: the crystallization and the so-called low conductivity drift. Despite the physics of crystallization having been extensively studied in literature, the latter is mainly described by phenomenological relationships, and its physical comprehension is still under discussion. In this paper we study the amorphous phase low-field conductivity drift and its dependence on the temperature experienced by the device. We developed an experimental procedure able to separate the reversible change in the electrical conductivity with temperature due to the material semiconductorlike behavior from the nonreversible one related to the drift mechanism. A drift model explaining such nonreversible conductivity change as a band diagram m.