Miracle-dz/UniFAR-FTUs huggingface dataset:
Fiber Intake and Survival After Colorectal Cancer Diagnosis

Importance Although high dietary fiber intake has been associated with a lower risk of colorectal cancer (CRC), it remains unknown whether fiber benefits CRC survivors. Objective To assess the association of postdiagnostic fiber intake with mortality. Design, Setting, and Participants A total of 1575 health care professionals with stage I to III CRC were evaluated in 2 prospective cohorts, Nurses’ Health Study and Health Professionals Follow-up Study. Colorectal cancer–specific and overall mortality were determined after adjusting for other potential predictors for cancer survival. The study was conducted from December 23, 2016, to August 23, 2017. Exposures Consumption of total fiber and different sources of fiber and whole grains assessed by a validated food frequency questionnaire between 6 months and 4 years after CRC diagnosis. Main Outcomes and Measures Hazard ratios (HRs) and 95% CIs of CRC-specific and overall mortality after adjusting for other potential predictors for cancer survival. Results Of the 1575 participants, 963 (61.1%) were women; mean (SD) age was 68.6 (8.9) years. During a median of 8 years of follow-up, 773 deaths were documented, including 174 from CRC. High intake of total fiber after diagnosis was associated with lower mortality. The multivariable HR per each 5-g increment in intake per day was 0.78 (95% CI, 0.65-0.93; P = .006) for CRC-specific mortality and 0.86 (95% CI, 0.79-0.93; P < .001) for all-cause mortality. Patients who increased their fiber intake after diagnosis from levels before diagnosis had a lower mortality, and each 5-g/d increase in intake was associated with 18% lower CRC-specific mortality (95% CI, 7%-28%; P = .002) and 14% lower all-cause mortality (95% CI, 8%-19%; P < .001). According to the source of fiber, cereal fiber was associated with lower CRC-specific mortality (HR per 5-g/d increment, 0.67; 95% CI, 0.50-0.90; P = .007) and all-cause mortality (HR, 0.78; 95% CI, 0.68-0.90; P < .001); vegetable fiber was associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.96; P = .009) but not CRC-specific mortality (HR, 0.82; 95% CI, 0.60-1.13; P = .22); no association was found for fruit fiber. Whole grain intake was associated with lower CRC-specific mortality (HR per 20-g/d increment, 0.72; 95% CI, 0.59-0.88; P = .002), and this beneficial association was attenuated after adjusting for fiber intake (HR, 0.77; 95% CI, 0.62-0.96; P = .02). Conclusions and Relevance Higher fiber intake after the diagnosis of nonmetastatic CRC is associated with lower CRC-specific and overall mortality. Increasing fiber consumption after diagnosis may confer additional benefits to patients with CRC.
Alpha 2u-globulins in the urine of male rats: a reliable indicator for alpha 2u-globulin accumulation in the kidney.

Increases in kidney-type-alpha 2u-globulin (alpha G-K, molecular weight approximately 16 kDa) were detected in the urine of male adult rats treated with d-limonene by immunoblotting analysis using an antiserum which distinguishes native-type-alpha 2u-globulin (alpha G-N, molecular weight approximately 19 kDa) from alpha G-K. When male adult rats received d-limonene by gavage (0-300 mg/kg/day) for 14 consecutive days, dose-dependent increases in urinary excretion of alpha G-K were observed at a dosage level of more than 30 mg/kg/day. This was found to be directly correlated with alterations in the concentration of renal alpha G-K as well as the accumulation of hyaline droplets in proximal convoluted tubule (PCT) epithelial cells in the kidneys. Marked elevation of urinary alpha G-K was also noted following oral treatment of adult male rats with 2,2,4-trimethylpentane (TMP), 1,4-dichlorobenzene (DCB), decalin and isophorone (ISP) by gavage (1.5 mmol/kg/day) for 7 consecutive days, again in association with increased concentrations of renal alpha G-K and hyaline droplet accumulation in renal PCT epithelial cells. However, no such increases in urinary alpha G-K were observed for male adult rats treated with nephrotoxic chemicals such as puromycin aminonucleoside (PAN) (15 mg/kg/day, s.c., 14 consecutive days) or hexachloro-1,3-butadiene (HCBD) (100 mg/kg/day, p.o., 5 consecutive days), lacking the ability to cause kidney accumulation of the hyaline droplets and alpha G-K. The findings in this study thus indicate that measurement of urinary alpha G-K can give a reliable estimates not only of the potential to cause renal accumulation of alpha 2u-globulin but also of its magnitude.
Adaptive Hierarchical Clustering Using Ordinal Queries

In many applications of clustering (for example, ontologies or clusterings of animal or plant species), hierarchical clusterings are more descriptive than a flat clustering. A hierarchical clustering over n elements is represented by a rooted binary tree with n leaves, each corresponding to one element. The subtrees rooted at interior nodes capture the clusters. In this paper, we study active learning of a hierarchical clustering using only ordinal queries. An ordinal query consists of a set of three elements, and the response to a query reveals the two elements (among the three elements in the query) which are "closer" to each other than to the third one. We say that elements x and x' are closer to each other than x" if there exists a cluster containing x and x', but not x". When all the query responses are correct, there is a deterministic algorithm that learns the underlying hierarchical clustering using at most n log2 n adaptive ordinal queries. We generalize this algorithm to be robust in a model in which each query response is correct independently with probability [Equation], and adversarially incorrect with probability 1 − p. We show that in the presence of noise, our algorithm outputs the correct hierarchical clustering with probability at least 1 − Δ, using O(n log n + n log(1/Δ)) adaptive ordinal queries. For our results, adaptivity is crucial: we prove that even in the absence of noise, every non-adaptive algorithm requires Ω(n3) ordinal queries in the worst case.
Synthetic genome engineering gets infectious

Since the start of this century, a handful of research groups have pursued the synthesis and large-scale engineering of genomes. Work on synthetic genomes has seen the field scale-up from the full synthesis of the small poliovirus genome (2002) (1), to a complete working synthetic bacterial genome (2010) (2), and more recently to the construction and validation of multiple rewritten eukaryote chromosomes for the model organism Saccharomyces cerevisiae (2014, 2017) (3⇓⇓⇓⇓–8). The costs and time-scales for assembling entire bacterial genomes and eukaryotic chromosomes mean that synthetic genome engineering is not yet a routine approach to manipulating cells for research or biotechnology. However, by stepping down a scale from bacteria to viruses, opportunities quickly arise, even for those viruses with comparatively large genomes, like the double-stranded DNA herpes simplex virus (HSV) type 1 genome, over 150 kb in length. In PNAS, Oldfield et al. (9) engineer the HSV KOS strain genome, leveraging synthetic genomic cloning approaches to rapidly construct HSV variants with combinatorial mutations for functional evaluation. Large-scale genomic engineering has been achieved by a handful of groups taking different approaches, but broadly the strategies employed fall into two categories: multiplexed editing and hierarchical assembly. For editing, new technologies, such as multiplex automated genome engineering-based targeted mutation (10) and the new genome editing tools of CRISPR-Cas9 allow existing genomes to be extensively modified toward a target sequence over several generations within their host cells (11). This can be an efficient approach if the cell grows fast and is easy to manipulate with molecular biology methods. For the alternative hierarchical assembly strategy, a designed or modified target genome sequence is instead put together gradually from smaller subgenomic fragments that are linked together by various DNA assembly methods. Depending on the size of the genome or chromosome … [↵][1]1To whom correspondence should be addressed. Email: t.ellis{at}imperial.ac. uk. [1]: #xref-corresp-1-1
A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non–Small Cell Lung Cancer

Purpose: Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated patients with non–small cell lung cancer (NSCLC). Experimental Design: Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m2 ganetespib by intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until disease progression. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies. Results: Ninety-nine patients with a median of 2 prior systemic therapies were enrolled; 98 were assigned to cohort A (n = 15), B (n = 17), or C (n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively. Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n = 1) or PCR-based assays (n = 3), in crizotinib-naïve patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The most common AEs were diarrhea, fatigue, nausea, and anorexia. Conclusions: Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement. Clin Cancer Res; 19(11); 3068–77. ©2013 AACR.
The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model

&NA; The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh‐driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.
Newborn Brain Function Is Affected by Fetal Exposure to Maternal Serotonin Reuptake Inhibitors

Recent experimental animal studies have shown that fetal exposure to serotonin reuptake inhibitors (SRIs) affects brain development. Modern recording methods and advanced computational analyses of scalp electroencephalography (EEG) have opened a possibility to study if comparable changes are also observed in the human neonatal brain. We recruited mothers using SRI during pregnancy (n = 22) and controls (n = 62). Mood and anxiety of mothers, newborn neurology, and newborn cortical function (EEG) were assessed. The EEG parameters were compared between newborns exposed to drugs versus controls, followed by comparisons of newborn EEG features with maternal psychiatric assessments. Neurological assessment showed subtle abnormalities in the SRI-exposed newborns. The computational EEG analyses disclosed a reduced interhemispheric connectivity, lower cross-frequency integration, as well as reduced frontal activity at low-frequency oscillations. These effects were not related to maternal depression or anxiety. Our results suggest that antenatal serotonergic treatment might change newborn brain function in a manner compatible with the recent experimental studies. The present EEG findings suggest links at the level of neuronal activity between human studies and animal experiments. These links will also enable bidirectional translation in future studies on the neuronal mechanisms and long-term neurodevelopmental effects of early SRI exposure.
Un système de types pragmatique pour la vérification déductive des programmes. ( A Pragmatic Type System for Deductive Verification)

This thesis is conducted in the framework of deductive software verification. is aims to formalize some concepts that are implemented in the verification tool Why3. The main idea is to explore solutions that a type system based approach can bring to deductive verification. First, we focus our attention on the notion of ghost code, a technique that is used in most of modern verification tools and which consists in giving to some parts of specification the appearance of operational code. Using ghost code correctly requires various precautions since the ghost code must never interfere with the operational code. The first chapter presents a type system with e ects illustrating how ghost code can be used in a way which is both correct and expressive. The second chapter addresses some questions related to verification of programs with pointers in the presence of aliasing, i.e. when several pointers handled by a program denote a same memory cell. Rather than moving towards to approaches that address the problem in all its complexity to the costs of abandoning the framework of Hoare logic, we present a type system with e ects and singleton regions which resolves aliasing issues by performing a static control of aliases even before the proof obligations are generated. Although our system is limited to pointers whose identity must be known statically, we observe that it fits for most of the code we want to verify. Finally, we focus our attention on a situation where there exists an abstraction barrier between the user’s code and the one of the libraries which it depends on. That means that libraries provide the user a set of functions and of data structures, without revealing details of their implementation. When programs are developed in a such modular way, verification must be modular itself. It means that the verification of user’s code must take into account only function contracts supplied by libraries while the verification of libraries must ensure that their implementations refine correctly the exposed entities. The third chapter extends the system presented in the previous chapter with these concepts of modularity and data refinement. We conclude our work by a case study in which we illustrate how solutions exposed in this thesis can be combined for verifying a non trivial implementation of hash tables called “cuckoo hashing”.
Tooth loss and metabolic syndrome in middle-aged Japanese adults.

AIM Metabolic syndrome is associated with periodontal disease and dental caries; however, little attention has been given to the association between metabolic syndrome and tooth loss, which is the endpoint of these two diseases. This study examined this association in middle-aged adults over a 5-year period. METHODS A retrospective study was performed in 2107 participants (1718 males and 389 females) aged 35-60 years who underwent annual dental check-ups, to evaluate tooth loss and metabolic components, including obesity, elevated triglycerides, blood pressure, fasting glucose, and reduced high-density lipoprotein. Logistic regression analysis was performed to evaluate the association between metabolic syndrome (≥3 components) at the baseline examination and tooth loss. RESULTS Over a 5-year period, 10.8% of the participants lost at least one tooth. Compared to those with no metabolic components, participants with ≥3 components had an increased risk of tooth loss (odds ratio = 1.54; 95% confidence interval: 1.01-2.37), adjusting for age, gender, dental caries experience, attachment loss, oral hygiene status, number of teeth, tooth brushing frequency, smoking, and occupational status. CONCLUSIONS Metabolic syndrome was associated with the incidence of tooth loss among middle-aged adults.
Proper division plane orientation and mitotic progression together allow normal growth of maize

Significance Speculation about the role of division plane orientation in the growth of a plant has hinged on two conflicting ideas. The first idea is that the plant body is specified at the tissue level and cells divide merely to fill in the space, making the orientation of division unimportant to the overall growth. The second idea is that the orientation of the division plane is critical for tissue-level patterning and therefore also impacts growth. This study suggests that misorientation of the division plane together with cell-cycle delays cannot be compensated for. Therefore, division plane orientation is a critical but potentially indirect factor for growth. How growth, microtubule dynamics, and cell-cycle progression are coordinated is one of the unsolved mysteries of cell biology. A maize mutant, tangled1, with known defects in growth and proper division plane orientation, and a recently characterized cell-cycle delay identified by time-lapse imaging, was used to clarify the relationship between growth, cell cycle, and proper division plane orientation. The tangled1 mutant was fully rescued by introduction of cortical division site localized TANGLED1-YFP. A CYCLIN1B destruction box was fused to TANGLED1-YFP to generate a line that mostly rescued the division plane defect but still showed cell-cycle delays when expressed in the tangled1 mutant. Although an intermediate growth phenotype between wild-type and the tangled1 mutant was expected, these partially rescued plants grew as well as wild-type siblings, indicating that mitotic progression delays alone do not alter overall growth. These data indicate that division plane orientation, together with proper cell-cycle progression, is critical for plant growth.
Randomized controlled clinical study evaluating effectiveness and safety of a volume-stable collagen matrix compared to autogenous connective tissue grafts for soft tissue augmentation at implant sites.

AIM To test whether or not the use of a collagen matrix (VCMX) results in short-term soft tissue volume increase at implant sites non-inferior to an autogenous subepithelial connective tissue graft (SCTG), and to evaluate safety and tissue integration of VCMX and SCTG. METHODS In 20 patients with a volume deficiency at single-tooth implant sites, soft tissue volume augmentation was performed randomly allocating VCMX or SCTG. Soft tissue thickness, patient-reported outcome measures (PROMs), and safety were assessed up to 90 days (FU-90). At FU-90 (abutment connection), tissue samples were obtained for histological analysis. Descriptive analysis was computed for both groups. Non-parametric tests were applied to test non-inferiority for the gain in soft tissue thickness at the occlusal site. RESULTS Median soft tissue thickness increased between BL and FU-90 by 1.8 mm (Q1:0.5; Q3:2.0) (VCMX) (p = 0.018) and 0.5 mm (-1.0; 2.0) (SCTG) (p = 0.395) (occlusal) and by 1.0 mm (0.5; 2.0) (VCMX) (p = 0.074) and 1.5 mm (-2.0; 2.0) (SCTG) (p = 0.563) (buccal). Non-inferiority with a non-inferiority margin of 1 mm could be demonstrated (p = 0.020); the difference between the two group medians (1.3 mm) for occlusal sites indicated no relevant, but not significant superiority of VCMX versus SCTG (primary endpoint). Pain medication consumption and pain perceived were non-significantly higher in group SCTG up to day 3. Median physical pain (OHIP-14) at day 7 was 100% higher for SCTG than for VCMX. The histological analysis revealed well-integrated grafts. CONCLUSIONS Soft tissue augmentation at implant sites resulted in a similar or higher soft tissue volume increase after 90 days for VCMX versus SCTG. PROMs did not reveal relevant differences between the two groups.
Cellulose Nanocrystal Stabilized Emulsions for Conformance Control and Fluid Diversion in Porous Media

Nanoparticle stabilized emulsions have drawn increasing attention for applications in various industries including enhanced oil recovery (EOR). Unlike surfactants, nanoparticles provide long-term stability to the emulsions and significantly higher viscoelastic response. However, the flow behavior of nanoparticle stabilized emulsions in porous media has not been explored much. Cellulose Nanocrystals (CNCs) have gained attention in the past few years since they are an abundant renewable biomass-derived material. This study investigates the flow behavior and stability of oil in water emulsions stabilized by CNCs in unconsolidated porous media and the application of these emulsions in EOR and conformance control. Confocal Microscopy coupled with Cryo-SEM enabled us to precisely characterize the emulsion microstructure and correlate it to the rheological behavior of the emulsions. The rheological measurements revealed that a strong droplet network forms within the emulsions over time. Importantly, we show that the same network forms when the emulsions occupy pore space in a granular material. Emulsions were injected through a sandpack with a porosity of 35% and average pore diameter of 54 μm. The injected emulsions were aged inside the porous media for 24 hours. Thorough experimental assessment of the collected effluent samples revealed that the emulsion was stable. The porous medium was then subjected to a gradually increasing pressure gradient of either water or oil. Gradients greatly exceeding typical near-well values (>300 psi/ft) were required to establish flow, and the resulting flow rate exhibited a pressure gradient three orders of magnitude higher than in an untreated water saturated sandpack. Interestingly, a significantly larger gradient was needed for water to flow than for oil, raising the possibility of using this class of emulsions for selective phase blocking, and perhaps as relative permeability modifiers. Moreover, emulsions stabilized with other material allowed water to flow at very small gradients, confirming that the network formation is critical for this application. This study revealed the potential application of a naturally occurring biodegradable nanomaterial for conformance control and for curbing excessive water production where zonal isolation is difficult to achieve.