Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive Factors for the Survival Outcomes of Preoperative Chemotherapy in Patients with Resectable and Borderline Resectable Colorectal Cancer with Liver Metastasis

Background: Preoperative chemotherapy increases resectability in borderline resectable colorectal liver metastasis (CRLM) patients who undergo curative liver surgery. Most clinical risk scores and other predictive factors for survival have been extensively studied in patients who undergo upfront liver surgery. However, predictive factors of CRLM patients who received preoperative chemotherapy remains controversial. Methods: CRLM patients who received preoperative systemic therapy followed by curative liver surgery at our institution between 1/2012 and 12/2018 were included. This study aimed to investigate factors that predicted the outcomes of preoperative systemic treatment, optimal dose/duration, and toxicity in patients with CRLM. Outcomes: Ninety-eight patients were eligible for analysis. Most patients received oxaliplatin-based chemotherapy (72.7%), while 15.9% received both oxaliplatin and irinotecan. Biologic agents were administered in 48.9% of patients. Overall, chemotherapy-induced liver injury was observed in 38.5%. The median disease-free survival (DFS) and overall survival (OS) were 8.7 months and 3.6 years, respectively. Baseline, pre-surgery, and increased Fong scores after preoperative chemotherapy were significantly associated with DFS and OS. In multivariate analysis, a high Fong score at baseline (p=0.018) was significantly associated with shorter DFS, whereas male sex (p=0.040) and liver surgery (p=0.044) were related to longer OS. Conclusion: In our study, Fong clinical risk scores, female sex, and liver surgery as a part of liver-directed therapy were independent prognostic factors for survival in CRLM patients who received preoperative chemotherapy. These clinical factors should be considered as an option to guide physicians’ decisions in selecting patients with CRLM who may benefit most from curative liver-directed therapy.
Open-labeled Randomized Controlled Trial on Efficacy of Azithromycin Versus Doxycycline in Pediatric Scrub Typhus

Background: Doxycycline (DX) is the first-line therapeutic agent for scrub typhus. Macrolides, especially azithromycin (AZ), have been found to be equally efficacious as DX for treating scrub typhus in adults. We conducted this study to compare the efficacy of AZ versus DX in pediatric scrub typhus. Study design: Open-label randomized controlled trial. Methods: Children 1–14 years of age suffering from acute febrile illness of ≥5 days and with a positive scrub IgM serology were randomized to receive either DX (2.2 mg/kg/dose twice daily in <40 kg; 100 mg BD in >40 kg for 7 days) or AZ (10 mg/kg/day for 5 days). The primary outcome was defervescence within 7 days of DX or 5 days of AZ. Results: We had 75 children randomized and analyzed using an intention-to-treat approach and 60 children analyzed via per-protocol analysis. The proportion of children achieving defervescence was comparable in 2 groups [per-protocol analysis: 90.9% in the DX group vs. 96.3% in the AZ group, RR: 0.94 (95% CI: 0.83–1.08)]. On Kaplan–Meier curves, AZ showed a significantly higher probability of defervescence at any time point during treatment as compared with DX (log-rank test P value 0.035). Conclusion: AZ and DX had comparable rates of defervescence among children with scrub typhus. Trial registration No.: CTRI/2020/01/022991.
Potassium level changes in chronic kidney disease patients following balanced crystalloid administration in the emergency department

One common reason why clinicians are often hesitate to administer balanced crystalloids in the emergency department is the potential occurrence of unexpected hyperkalemia in patients with chronic kidney disease (CKD). In order to investigate the changes in potassium levels resulting from the administration of balanced crystalloids, specially Plasma Solution A (a generic version of Plasma-Lyte), to emergency department patients with CKD, we conducted an evaluation. A retrospective cohort study was conducted at a single academic hospital. Our study included patients with CKD who received intravenous Plasma Solution A and underwent electrolyte follow-up testing within 24 hours of administration. In total, there were 745 patients included in this study, of whom 87 had CKD. Through a 1:1 propensity score matching procedure for factors other than the estimated glomerular filtration rate, we matched 87 patients with normal kidney function to 87 CKD patients. For patients with CKD, the mean standard deviation SD administered volume of Plasma Solution A was 28.7 (21.0) mL/kg, and the mean SD administration duration was 13.2 (4.5) hours. The mean SD potassium level decreased from 4.3 (0.6) mmol/L to 4.1 (0.6) mmol/L (P = .029). Our study findings suggest that there may be no significant harmful increase in potassium levels or worsening of renal function within 24 hours after the intravenous administration of approximately 2 L of Plasma Solution A to patients with CKD.
Resource allocation decisions under pandemic conditions: A cross-sectional survey of Ontario physicians

The COVID-19 pandemic has forced physicians to confront difficult choices regarding the allocation of scarce resources, such as ventilators and critical care beds. Developing policies to guide the allocation of such resources has proven challenging. An understanding of physicians’ attitudes and beliefs surrounding resource allocation could help inform policymaking. As a replication and extension of a survey of Ottawa physicians conducted in 2020, we surveyed physicians across Ontario, Canada in April 2021. This survey examined physicians’ sense of preparedness to allocate critical care resources during the pandemic, attitudes concerning resource allocation policy, and approaches to resource allocation decision-making. Of the 253 responses included for analysis, the majority (67%) of respondents indicated feeling “somewhat” or “a little prepared” to make resource allocation decisions, while 20% indicated feeling “not at all prepared. ” Most respondents (86%) agreed that a policy to guide resource allocation in the event of scarcity should exist. Physicians overwhelmingly agreed that important factors to consider when making resource allocation decisions included the patient likelihood of survival, frailty index, comorbidities, and cognitive status. Responses from the province-wide survey conducted in 2021 resemble the results of an analogous survey of Ottawa physicians conducted in 2020. Physicians generally felt underprepared to make resource allocation decisions and agreed that official policies should guide such decisions. Identification of factors relevant to resource allocation was remarkably consistent across this sample and that taken in 2020.
'I don't want to impose on anybody': Older people and their families discuss their perceptions of risk, cause and care in the context of falls.

BACKGROUND Falls in hospitalised patients remain an ongoing challenge for healthcare systems internationally. Limited research exists on the perspectives of older people on falls risk, cause and care. OBJECTIVES This study explored the experiences of patients and their families after a fall in a healthcare facility. METHODS Semi-structured interviews were conducted with patients and families to explore the experience of having a fall. Data were analysed thematically. RESULTS The themes that emerged from the 14 interviews included the following: explanations; physical environment; communication; experiences of care; perceptions of risk; ageism; feelings towards the fall; and independence and dignity. CONCLUSIONS This research emphasises the diversity in older people's experiences after experiencing a fall. Falls prevention should be incorporated as one part of healthy, dignified ageing. IMPLICATIONS FOR PRACTICE Falls prevention and management strategies should be multifactorial, including enhanced communication with the patient and their families. When engaging in education and awareness, falls prevention should be positioned as one component of independent and dignified healthy ageing.
Eruption dynamics and magma withdrawal during the Plinian Phase of the Bishop Tuff Eruption, Long Valley Caldera

Variations in eruption column height, magma discharge (intensity), and geochemistry have been documented for the plinian phase of the Bishop Tuff eruption from the Long Valley caldera, California. Although exposures of the complete Bishop fall deposit are sparse, their widespread relationships, knowledge of the plinian vent location, and a reasonable estimate of the main dispersal axis allow for the construction of minimum clast isopleths. Column height and intensity are estimated to have increased from 23 km and 7×107 kg s−1 to a peak of 45 km and 7.5×108 kg s−1 at the end of the plinian phase. Variations in geochemistry of the plinian deposit reveal complex magma withdrawal processes during the Bishop plinian phase. Concentrations of many incompatible trace elements increase from the base to midlevel and then decrease to the top of the plinian deposit. This trend is mirrored by the variation in pumice density, which in turn reflects vesicularity. Based on the physical volcanology and compositional variations in the plinian deposit, a model is proposed for the temporal progression of magma withdrawal during the plinian phase. Relatively less-evolved magma was first tapped by the plinian phase from the side of the magma chamber, with the conduit location being controlled by the Hilton Creek fault system. As eruption intensity increased, more-evolved magma from the chamber roof was drawn down and tapped. Less-evolved magma was again tapped for the duration of the plinian phase, possibly as withdrawal from the roof zone became less efficient. Renewed eruption of slightly more evolved magma by the first post-plinian ignimbrites suggests that the vent migrated along the ring fault system to an area that had not experienced previous magma withdrawal.
Longshore current and wave height modulation at tidal frequency inside the surf zone

Data were acquired continuously during the 19-day DELILAH nearshore experiment with a specific objective of examining variability of the longshore current at tidal frequencies. It is hypothesized that breaking wave heights inside the surf zone are strong functions of the depth which are modulated by the tidal variations, and since radiation stress is a function of the wave height, longshore currents are forced at the tidal frequency inside the surf zone. The measured longshore current variations at tidal frequency are the same order of magnitude as the mean longshore current variations for moderate wave height conditions, indicating that the tide is a dominant mechanism associated with longshore current variability. Simulations of the magnitude and phase of the longshore current variability with tide elevation using the model by Thornton and Guza (1986) are used to explain observations. The measured tidal elevation and longshore current are in phase in the inner surf zone and out of phase in the outer surf zone as predicted by the model, verifying the hypothesis.
Preemptive Action: Measuring Presidential Assertiveness in Foreign Policy Lawmaking

To what extent and under which conditions do presidents challenge foreign policy legislation through Statements of Administration Policy (SAPs)? While the presidents’ use of executive orders and signing statements has been studied extensively, this paper argues that SAPs are a subtler and less politically costly tool that is more important than scholars realized. Delivered at a crucial intervention point along the legislative process, these communications provide a key gateway for assertive presidential challenges. Relying on a novel assertiveness-score, this paper finds that SAPs target legislative content more aggressively over time and that the composition of government predicts executive assertiveness particularly well. Next to that, I show that presidents are more assertive when their term comes to an end. These insights contribute to our understanding of spiking interbranch tensions in American Politics.
Geometry of triple junctions related to San Andreas Transform

Understanding the evolution of the San Andreas transform is a key not only to broad aspects of regional geology but also to the development of specific structural provinces. Though stable in the regional sense, the paired triple junctions at the ends of the transform have had transient unstable configurations wherever the trends of the prior trench and the newly developing transform were locally not collinear. The resulting instabilities were mainly of kinds inferred to induce extensional tectonics within a nearby region. Passage of the Mendocino fault-fault-trench triple junction northward along the central California coast coincided well with pulses of initial subsidence in Neogene sedimentary basins near the continental margin and with eruptions at local volcanic centers in the Coast Ranges. Passage of the Rivera ridge-trench-fault triple junction southward was associated with the rifting events that formed the California Continental Borderland and the Gulf of California.
Keeping the Freedom to Build Idealized Climate Models

I would like to add more fuel to the point of view of Nof [2008], who initiated a Forum to promote the study of simplified climate models. Aside from the problem of subgrid-scale uncertainties and the associated amplification of errors in a nonlinear system, there are two other issues to bear in mind when discussing the solutions of complex climate models. The first concerns their initialization. The present generation of models is for the most part initialized from the observations of a given climate. However, initialization from climatological data is not a good test of the models because the solution that is desired is put into the system at the beginning! Then the task evolves into one of minimizing the drift away from these initial conditions. Results, then, become self-fulfilling.
A reinforcement learning model with choice traces for a progressive ratio schedule

The progressive ratio (PR) lever-press task serves as a benchmark for assessing goal-oriented motivation. However, a well-recognized limitation of the PR task is that only a single data point, known as the breakpoint, is obtained from an entire session as a barometer of motivation. Because the breakpoint is defined as the final ratio of responses achieved in a PR session, variations in choice behavior during the PR task cannot be captured. We addressed this limitation by constructing four reinforcement learning models: a Simple Q- learning model, an Asymmetric model with two learning rates, a Perseverance model with choice traces, and a Perseverance model without learning. These models incorporated three behavioral choices: reinforced and non-reinforced lever presses and void magazine nosepokes (MNPs), because we noticed that mice performed frequent MNPs during PR tasks. The best model was the Perseverance model, which predicted a gradual reduction in amplitudes of reward prediction errors (RPEs) upon void MNPs. We confirmed the prediction experimentally with fiber photometry of extracellular dopamine (DA) dynamics in the ventral striatum of mice using a fluorescent protein (genetically encoded GPCR activation-based DA sensor: GRABDA2m). We verified application of the model by acute intraperitoneal injection of low-dose methamphetamine (METH) before a PR task, which increased the frequency of MNPs during the PR session without changing the breakpoint. The Perseverance model captured behavioral modulation as a result of increased initial action values, which are customarily set to zero and disregarded in reinforcement learning analysis. Our findings suggest that the Perseverance model reveals effects of psychoactive drugs on choice behaviors during PR tasks.
Evaluation of petrogenetic models for Lachlan Fold Belt granitoids: Implications for crustal architecture and tectonic models

The restite (one source‐component) model suggests that granitoids are derived from contrasting source rocks and that the typical linear chemical variation of Lachlan Fold Belt granitoids is produced by restite separation. However, it cannot explain the general chemical and isotopic similarity of S‐ and I‐type granitoids in the eastern Lachlan Fold Belt, the similarity of zircon inheritance patterns between the two granite types, nor their apparently simple eNd‐Sr isotopic array. A two source‐component mixing model, based on the eNd‐Sr isotopic array, suggests that linear chemical variation of the granitoids reflects variable incorporation of deeply buried Ordovician sedimentary rocks and basaltic magmas. However, isotopically defined mixes do not match the predicted chemical mixes. Also systematic and sympathetic isotopic and chemical variations are observed for both the felsic and mafic granites within suites across the Bega Batholith. For a simple two‐component model to apply, both the crustal and mantl.
Bed Nucleus of the Stria Terminalis (BNST) neurons containing the serotonin 5HT2c receptor modulate operant alcohol self-administration behavior in mice

The serotonin 5HT2c receptor has been widely implicated in the pathophysiology of alcohol use disorder (AUD), particularly alcohol seeking and the affective consequences of chronic alcohol consumption. However, little is known about the brain sites in which 5HT2c exerts its effects on specific alcohol-related behaviors, especially in females. Here, we investigated the effects of site-specific manipulation of the 5HT2c receptor system in the BNST on operant alcohol self-administration behaviors in adult mice of both sexes, including the acquisition and maintenance of fixed-ratio responding, motivation for alcohol (progressive ratio), and quinine-adulterated responding for alcohol on a fixed-ratio schedule (punished alcohol seeking). Knockdown of 5HT2c in the BNST did not affect the acquisition or maintenance of operant alcohol self-administration, nor did it affect progressive ratio responding for alcohol. This manipulation had only a subtle effect on responding for quinine alcohol selectively in females. On the other hand, chemogenetic inhibition of BNST 5HT2c-containing neurons (BNST5HT2c) increased operant alcohol self-administration behavior in both sexes on day 2, but not day 9, of testing. It also increased operant responding for 1000 μM quinine-adulterated alcohol selectively in males. Importantly, chemogenetic inhibition of BNST5HT2c did not alter operant sucrose responding or motivation for sucrose in either sex. We then performed cell-type specific anterograde tracing, which revealed that BNST5HT2c project to similar regions in males and females, many of which have been previously implicated in AUD. We next used chemogenetics and quantification of the immediate early gene cFos to characterize the functional influence of BNST5HT2c inhibition on vlPAG activity. We show that chemogenetic inhibition of BNST5HT2c reduces vlPAG cFos in both sexes, but that this reduction is more robust in males. Together these findings suggest that BNST5HT2c neurons, and to a small extent the BNST 5HT2c receptor, serve to promote aversive responses to alcohol consumption, potentially through sex-dependent disinhibition of vlPAG neurons.
Oculomotor routines for perceptual judgments

In everyday life we frequently make simple visual judgments about object properties, e.g., how big or wide is a certain object? Our goal is to test whether there are also task specific oculomotor routines which support perceptual judgments, similar to the well-established exploratory routines for haptic perception. In a first study, observers saw different scenes with two objects presented in a photorealistic virtual reality environment. Observers were asked to judge which of two objects was taller or wider while gaze was tracked. All tasks were performed with the same set of virtual objects in the same scenes, so that we can compare spatial characteristics of exploratory gaze behavior to quantify oculomotor routines for each task. Width judgments showed fixations around the center of the objects with larger horizontal spread. In contrast, for height judgments, gaze was shifted towards the top of the objects with larger vertical spread. These results suggest specific strategies in gaze behavior that presumably are used for perceptual judgments. To test the causal link between oculomotor behavior and perception, in a second study, observers either could freely gaze at the object or we introduced a gaze contingent set up forcing observers to fixate specific positions on the object. Discrimination performance was similar between free gaze and the gaze contingent conditions for width and height judgments. These results suggest that although gaze is adapted for different tasks, performance seems to be based on a perceptual strategy, independent of potential cues that can be provided by the oculomotor system.
Absolute number of three populations of interneurons and all GABAergic synapses in the human hippocampus

The human hippocampus plays a central role in learning and memory functions and is implicated in several neurological and psychiatric disorders linked to different subpopulations of its neurons. Understanding the complex workings of the human hippocampus requires computational models with accurate quantitative neuronal data. Although the total number of different hippocampal neurons and their synapses have been extensively described in rodents, most of these data are not available for the human hippocampus. All hippocampal functions are tightly regulated by different classes of local GABAergic interneurons. Therefore, here we used unbiased stereological methods to estimate the density and total number of three major GABAergic cell groups: the parvalbumin (PV)-expressing interneurons, the somatostatin (SOM)-positive interneurons and the calretinin (CR)-positive interneurons. We found that there are approximately 45600 PV-positive, 134500 SOM-positive and 228000 CR-positive interneurons per hippocampal hemisphere. Compared to rodent data, the higher proportion of CR-positive -typically interneuron selective-cells may contribute to a more robust regulation of local interneurons. We also used 3-dimensional electron microscopy to estimate the total number of GABAergic boutons and synapses in the different layers of the hippocampus, and we also quantified those originating from PV-positive neurons. We estimated that there are at least about 1.82 * 1010 GABAergic synapses in one hippocampal hemisphere, of which about 2.77 * 109 are PV-positive, representing about 15.2% of the total GABAergic synapses of local or afferent neurons.