Miracle-dz/UniFAR-FTUs huggingface dataset:
Vasoactive intestinal peptide regulates ileal goblet cell production in mice

Innervation of the intestinal mucosa has gained more attention with demonstrations of tuft and enteroendocrine cell innervation. However, the role(s) these fibers play in maintaining the epithelial and mucus barriers are still poorly understood. This study therefore examines the proximity of mouse ileal goblet cells to neuronal fibers, and the regulation of goblet cell production by vasoactive intestinal peptide (VIP). An organotypic intestinal slice model that maintains the cellular diversity of the intestinal wall ex vivo was used. An ex vivo copper‐free click‐reaction to label glycosaminoglycans was used to identify goblet cells. Pharmacological treatment of slices was used to assess the influence of VIP receptor antagonism on goblet cell production and neuronal fiber proximity. Goblet cells were counted and shown to have at least one peripherin immunoreactive fiber within 3 µm of the cell, 51% of the time. Treatment with a VIP receptor type I and II antagonist (VPACa) resulted in an increase in the percentage of goblet cells with peripherin fibers. Pharmacological treatments altered goblet cell counts in intestinal crypts and villi, with tetrodotoxin and VPACa substantially decreasing goblet cell counts. When cultured with 5‐Ethynyl‐2’‐deoxyuridine (EdU) as an indicator of cell proliferation, colocalization of labeled goblet cells and EdU in ileal crypts was decreased by 77% when treated with VPACa. This study demonstrates a close relationship of intestinal goblet cells to neuronal fibers. By using organotypic slices from mouse ileum, vasoactive intestinal peptide receptor regulation of gut wall goblet cell production was revealed.
Impact of the BioFire FilmArray gastrointestinal panel on patient care and infection control

Objectives Conventional routine PCR testing for gastrointestinal infections is generally based on pathogen related panels specifically requested by clinicians and can be erroneous and time consuming. The BioFire FilmArray gastrointestinal (GI) panel combines 22 pathogens into a single cartridge-based test on a random-access system, thereby reducing the turnaround time to less than 2 hours. We described the clinical impact of implementing the BioFire FilmArray on patients with gastroenteritis in our hospital. Methods Patients attending a Dutch tertiary care center (Radboud University Medical Center), from whom stool samples were obtained, were eligible for inclusion. The clinicians selected one or a combination of different routinely performed PCR panels (bacterial panel, viral panel, clostridium testing, and three parasitic panels) based on clinical history and symptoms. All samples were in parallel tested with the FilmArray. We retrospectively collected patient data regarding infection control and patient management to assess the potential impact of implementing the FilmArray. Results In total 182 patients were included. Routine PCR detected one or more pathogens in 52 (28.6%) patients compared to 72 (39.6%) using the FilmArray. Turnaround time (including transport) decreased from median 53 hours for the routine PCR to 16 hours for the FilmArray. Twenty-six patients could have been removed from isolation 29 hours sooner, 3.6 antibiotic days could have been saved and in five patients additional imaging testing (including colonoscopies) could have been prevented. Conclusion The theoretical implementation of the BioFire FilmArray GI panel in patients with clinical suspicion of gastroenteritis resulted in a significant better patient management.
Early experience of Sacubitril–Valsartan in heart failure with reduced ejection fraction in real‐world clinical setting

Sacubitril/Valsartan (Sac/Val) was proven more effective than enalapril for symptomatic patients with heart failure (HF) with reduced ejection fraction (HFrEF). This study aimed to investigate eligibility, titration, and tolerability for Sac/Val in a real‐world clinical setting.
Building Resources in Caregivers: Feasibility of a Brief Writing Intervention to Increase Benefit Finding in Caregivers

The Building Resources in Caregivers (BRiC) is a pilot feasibility trial that compared the effects of a 2‐week benefit finding writing expressive intervention to a control intervention, who wrote about the weather. Caregivers completed primary (benefit finding) and secondary (quality of life, depression and anxiety) outcome measures at pre (t1), immediately post‐test (t2) and 1 month later (t3). They also completed measures relating to trial feasibility, difficulty, and acceptance. Using complete case analysis only, analysis revealed no effect of the intervention for primary or secondary outcomes. Despite this, there were no differences between the intervention and control groups on key feasibility measures. Caregivers in the control condition were less likely to recommend this to other caregivers. Moreover, qualitative commentary provided by caregivers suggested that not everyone enjoyed the writing, some found it stressful, offering up some explanation for our findings. Our pilot trial suggests that any future benefit‐finding writing intervention would require several procedure modifications including tailoring to a specific cohort of caregivers, in particular those who like writing, before it has some utility as a psychosocial intervention.
Fifteen-week window for recurrent muscle strains in football: a prospective cohort of 3600 muscle strains over 23 years in professional Australian rules football

Objectives To determine the rates of muscle strain injury recurrence over time after return to play in Australian football and to quantify risk factors. Methods We analysed Australian Football League player data from 1992 to 2014 for rates of the four major muscle strain injury types (hamstring, quadriceps, calf and groin) diagnosed by team health professionals. Covariates for analysis were: recent history (≤8 weeks) of each of the four muscle strains; non-recent history (>8 weeks) of each; history of hip, knee anterior cruciate ligament, knee cartilage, ankle sprain, concussion or lumbar injury; age; indigenous race; match level and whether a substitute rule was in place. Results 3647 (1932 hamstring, 418 quadriceps, 458 calf and 839 groin) muscle strain injuries occurred in 272 759 player matches. For all muscle strains combined, the risk of injury recurrence gradually reduced, with recurrence risks of 9% (hamstring), 5% (quadriceps), 2% (calf) and 6% (groin) in the first match back and remaining elevated for 15 weeks after return to play. The strongest risk factor for each muscle injury type was a recent history of the same injury (hamstring: adjusted OR 13.1, 95% CI 11.5 to 14.9; calf OR 13.3, 95% CI 9.6 to 18.4; quadriceps: OR 25.2, 95% CI 18.8 to 33.8; groin OR 20.6, 95% CI 17.0 to 25.0), followed by non-recent history of the same injury (hamstring: adjusted OR 3.5, 95% CI 3.2 to 3.9; calf OR 4.4, 95% CI 3.6 to 5.4; quadriceps OR 5.2, 95% CI 4.2 to 6.4; groin OR 3.5, 95% CI 3.0 to 4.0). Age was an independent risk factor for calf muscle strains (adjusted OR 1.6, 95% CI 1.3 to 2.0). Recent hamstring injury increased the risk of subsequent quadriceps (adjusted OR 1.8, 95% CI 1.2 to 2.7) and calf strains (OR 1.8, 95% CI 1.2 to 2.6). During the ‘substitute rule’ era (2011–2014), hamstring (adjusted OR 0.76, 95% CI 0.67 to 0.86), groin (OR 0.78, 95% CI 0.65 to 0.93) and quadriceps (OR 0.70, 95% CI 0.53 to 0.92) strains were less likely than outside of that era but calf (OR 1.6, 95% CI 1.3 to 1.9) strains were more likely than before the substitute rule era. Conclusion Recent injury is the greatest risk factor for the four major muscle strains, with increased risk persisting for 15 weeks after return to play.
Characterization and Application of an Alginate Lyase, Aly1281 from Marine Bacterium Pseudoalteromonas carrageenovora ASY5

Alginate extracted from widely cultured brown seaweed can be hydrolyzed by alginate lyase to produce alginate oligosaccharides (AOS) with intriguing biological activities. Herein, a novel alginate lyase Aly1281 was cloned from marine bacterium Pseudoalteromonas carrageenovora ASY5 isolated from mangrove soil and found to belong to polysaccharide lyase family 7. Aly1281 exhibited maximum activity at pH 8.0 and 50 °C and have broad substrate specificity for polyguluronate and polymannuronate. Compared with other alginate lyases, Aly1281 exhibited high degradation specificity and mainly produced di-alginate oligosaccharides which displayed good antioxidant function to reduce ferric and scavenge radicals such as hydroxyl, ABTS+ and DPPH. Moreover, the catalytic activity and kinetic performance of Aly1281 were highly improved with the addition of salt, demonstrating a salt-activation property. A putative conformational structural feature of Aly1281 was found by MD simulation analysis for understanding the salt-activation effect.
Moderate but not severe hypothermia causes pro-arrhythmic changes in cardiac electrophysiology

Abstract Aims Treatment of arrhythmias evoked by hypothermia/rewarming remains challenging, and the underlying mechanisms are unclear. This in vitro experimental study assessed cardiac electrophysiology in isolated rabbit hearts at temperatures occurring in therapeutic and accidental hypothermia. Methods and results Detailed ECG, surface electrogram, and panoramic optical mapping were performed in isolated rabbit hearts cooled to moderate (31°C) and severe (17°C) hypothermia. Ventricular activation was unchanged at 31°C while action potential duration (APD) was significantly prolonged (176.9 ± 4.2 ms vs. 241.0 ± 2.9 ms, P < 0.05), as was ventricular repolarization. At 17°C, there were proportionally similar delays in both activation and repolarization. These changes were reflected in the QRS and QT intervals of ECG recordings. Ventricular fibrillation threshold was significantly reduced at 31°C (16.3 ± 3.1 vs. 35 ± 3.5 mA, P < 0.05) but increased at 17°C (64.2 ± 9.9, P < 0.05). At 31°C, transverse conduction was relatively unchanged by cooling compared to longitudinal conduction, but at 17°C both transverse and longitudinal conduction were proportionately reduced to a similar extent. The gap junction uncoupler heptanol had a larger relative effect on transverse than longitudinal conduction and was able to restore the transverse/longitudinal conduction ratio, returning ventricular fibrillation threshold to baseline values (16.3 ± 3.1 vs. 36.3 ± 4.3 mA, P < 0.05) at 31°C. Rewarming to 37°C restored the majority of the electrophysiological parameters. Conclusions Moderate hypothermia does not significantly change ventricular conduction time but prolongs repolarization and is pro-arrhythmic. Further cooling to severe hypothermia causes parallel changes in ventricular activation and repolarization, changes which are anti-arrhythmic. Therefore, relative changes in QRS and QT intervals (QR/QTc) emerge as an ECG-biomarker of pro-arrhythmic activity. Risk for ventricular fibrillation appears to be linked to the relatively low temperature sensitivity of ventricular transmural conduction, a conclusion supported by the anti-arrhythmic effect of heptanol at 31°C.
Policy statement of enteral nutrition for preterm and very low birthweight infants

For preterm and very low birthweight infants, the mother’s own milk is the best nutrition. Based on the latest information for mothers who give birth to preterm and very low birthweight infants, medical staff should encourage and assist mothers to pump or express and provide their own milk whenever possible. If the supply of maternal milk is insufficient even though they receive adequate support, or the mother’s own milk cannot be given to her infant for any reason, donor human milk should be used. Donors who donate their breast milk need to meet the Guideline of the Japan Human Milk Bank Association. Donor human milk should be provided according to the medical needs of preterm and very low birthweight infants, regardless of their family’s financial status. In the future, it will be necessary to create a system to supply an exclusive human milk‐based diet (EHMD), consisting of human milk with the addition of a human milk‐derived human milk fortifier, to preterm and very low birthweight infants.
Mutation Analysis of Colorectal and Gastric Carcinomas Originating from Adenomas: Insights into Genomic Evolution Associated with Malignant Progression

Small malignant tumor foci arising from benign lesions are rare but offer a unique opportunity to investigate the genomic evolution that occurs during malignant transformation. In this study, we analyzed 11 colorectal and 10 gastric adenoma–carcinoma pairs, each of which represented malignant tumors (carcinomas) embedded in benign lesions (adenomas) found in the same patient. Whole-exome sequencing revealed that mutation abundance was variable across different cases, but comparable between adenoma–carcinoma pairs. When mutations were classified as adenoma-specific, carcinoma-specific, or common, adenoma-specific mutations were more enriched with subclonal mutations than were carcinoma-specific mutations, indicative of a perturbation in mutational subclonal architecture (such as selective sweep) during malignant transformation. Among the recurrent mutations in colorectal cancers, APC and KRAS mutations were common between adenomas and carcinomas, indicative of their early occurrence during genomic evolution. TP53 mutations were often observed as adenoma-specific and therefore likely not associated with the emergence of malignant clones. Clonality-based enrichment analysis revealed that subclonal mutations of extracellular matrix genes in adenomas are more likely to be clonal in carcinomas, indicating potential roles for these genes in malignant transformation. Compared with colorectal cancers, gastric cancers showed more lesion-specific mutations than common mutations and higher levels of discordance in copy number profiles between matched adenomas and carcinomas, which may explain the elevated evolutionary dynamics and heterogeneity of gastric cancers compared to colorectal cancers. Taken together, this study demonstrates that co-existing benign and malignant lesions enable the evolution-based categorization of genomic alterations that may reveal clinically important biomarkers in colorectal and gastric cancers.
Diagnosis and Management of Non-Variceal Gastrointestinal Hemorrhage: A Review of Current Guidelines and Future Perspectives

Non-variceal gastrointestinal bleeding (GIB) is a significant cause of mortality and morbidity worldwide which is encountered in the ambulatory and hospital settings. Hemorrhage form the gastrointestinal (GI) tract is categorized as upper GIB, small bowel bleeding (also formerly referred to as obscure GIB) or lower GIB. Although the etiologies of GIB are variable, a strong, consistent risk factor is use of non-steroidal anti-inflammatory drugs. Advances in the endoscopic diagnosis and treatment of GIB have led to improved outcomes. We present an updated review of the current practices regarding the diagnosis and management of non-variceal GIB, and possible future directions.
Dynamics of carving runs in alpine skiing. I. The basic centrifugal pendulum

ABSTRACT We studied perfect carving turns of alpine skiing using the simple model of an inverted pendulum which is subject to the gravity force and the force mimicking the centrifugal force emerging in the turns. Depending on the turn speed the model describes two different regimes. In the subcritical regime, there exist three equilibrium positions of the pendulum where the total torque applied to the pendulum vanishes—the marginally stable vertical position and two unstable tilted positions on both sides of the vertical. The tilted equilibria correspond to the ski turns executed in perfect balance. The vertical equilibrium corresponds to gliding down the fall line without turns. In the supercritical regime, the tilted equilibria disappear. In addition to the equilibria, the model allows fall-rise solutions, where the pendulum (skier) rises from the ground on one side and hits the ground on the other side, and solutions describing oscillations about the vertical equilibrium. These oscillations correspond to the so-called dynamic skiing where the skier never settles to a balanced position in the turn. Analysis of the available data on World Cup races shows that elite racers ski mostly in the supercritical regime.
Contaminant Degradation by •OH during Sediment Oxygenation: Dependence on Fe(II) Species.

It has been documented that contaminants could be degraded by hydroxyl radicals (•OH) produced upon oxygenation of Fe(II)-bearing sediments. However, the dependence of contaminant degradation on sediment characteristics, particularly Fe(II) species, remains elusive. Here we assessed the impact of the abundance of Fe(II) species in sediments on contaminant degradation by •OH during oxygenation. Three natural sediments with different Fe(II) contents and species were oxygenated. During 10 h oxygenation of 200 g/L sediment suspension, 2 mg/L phenol was negligibly degraded for sandbeach sediment (Fe(II): 9.11 mg/g), but was degraded by 41% and 52% for lakeshore (Fe(II): 9.81 mg/g) and farmland (Fe(II): 19.05 mg/g) sediments, respectively. •OH produced from Fe(II) oxygenation was the key reactive oxidant. Sequential extractions, X-ray diffraction, Mössbauer and X-ray absorption spectroscopy suggest that surface-adsorbed Fe(II) and mineral structural Fe(II) contributed predominantly to •OH production and phenol degradation. Control experiments with specific Fe(II) species and coordination structure analysis collectively suggest the likely rule that Fe(II) oxidation rate and its competition for •OH increase with the increase in electron-donating ability of the atoms (i.e., O) complexed to Fe(II), while •OH yield decreases accordingly. The Fe(II) species with a moderate oxidation rate and •OH yield is most favorable for contaminant degradation.
The Role of Executive Functions in Socioeconomic Attainment Gaps: Results From a Randomized Controlled Trial.

The socioeconomic attainment gap in mathematics starts early and increases over time. This study aimed to examine why this gap exists. Four-year-olds from diverse backgrounds were randomly allocated to a brief intervention designed to improve executive functions (N = 87) or to an active control group (N = 88). The study was preregistered and followed CONSORT guidelines. Executive functions and mathematical skills were measured at baseline, 1 week, 3 months, 6 months, and 1 year posttraining. Executive functions mediated the relation between socioeconomic status and mathematical skills. Children improved over training, but this did not transfer to untrained executive functions or mathematics. Executive functions may explain socioeconomic attainment gaps, but cognitive training directly targeting executive functions is not an effective way to narrow this gap.
Imaging and Imaging-Based Management of Pediatric Thyroid Nodules

Thyroid nodules are less frequent in children than adults. Childhood thyroid nodules carry specific features, including a higher risk of malignancy than nodules in adults, rendering them unique in terms of management. Subsequently, they should be considered a distinct clinical entity with specific imaging recommendations. Initial evaluation requires a thorough workup, including clinical examination, and a detailed personal and familial history to determine the presence of possible risk factors. Laboratory and radiologic evaluation play an integral part in the diagnostic algorithm, with ultrasonography (US) being the first diagnostic test in all patients. US elastography has been recently introduced as an incremental method, reducing the subjectivity of the clinical diagnosis of nodule firmness associated with increased malignancy risk. However, fine-needle aspiration biopsy (FNAB) remains the mainstay in the diagnostic work-up of thyroid nodules and is documented to be best method for differentiating benign from malignant thyroid nodules. In addition, thyroid scintigraphy provides functional imaging information, which has a role both in the diagnostic management of thyroid nodules and during follow up in malignancies. Finally, despite providing additional information in certain clinical scenarios, 18F-fludeoxyglucose Positron Emission Tomography (18F-FDG-PET), computed tomography (CT), and magnetic resonance imaging (MRI) imaging are not routinely recommended for the evaluation of patients with newly detected thyroid nodules or in all cases of thyroid cancer. The objective of this review is to summarize the concepts in imaging and imaging-based management of nodular thyroid disease in the pediatric population, acknowledging the unique features that this patient group carries and the specific approach it requires.
Solution conformations explain the chameleonic behaviour of macrocyclic drugs.

It has been hypothesized that drugs in the chemical space beyond the rule of 5 (bRo5) must behave as molecular chameleons to combine otherwise conflicting properties, including aqueous solubility, cell permeability and target binding. Evidence for this has, however, been limited to the cyclic peptide cyclosporin A. Herein we show that the non-peptidic and macrocyclic drugs roxithromycin, telithromycin and spiramycin behave as molecular chameleons, with rifampicin showing a less pronounced behavior. In particular roxithromycin, telithromycin and spiramycin display a marked, yet limited flexibility and populate significantly less polar and more compact conformational ensembles in an apolar than in a polar environment. In addition to balancing of membrane permeability and aqueous solubility, this flexibility also allows binding to targets that vary in structure between species. The drugs' passive cell permeability correlates to their 3D polar surface area and corroborate two theoretical models for permeability, developed for cyclic peptides. We conclude that molecular chameleonicity should be incorporated in the design of orally administered drugs in the bRo5 space.