Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison between patient-reported and clinician-reported outcomes: Validation of the Japanese version of the Integrated Palliative care Outcome Scale for staff

Abstract Objectives The goal of palliative and supportive care is to improve patients’ quality of life (QoL). Patient-reported outcome measures (PROMs) are the gold standard for the assessment of QoL and symptoms; however, when self-reporting is complicated, PROMs are often substituted with proxy-reported outcome measures, such as clinician-reported outcome measures. The objective of this study was to assess the validity and reliability of the Japanese version of the Integrated Palliative care Outcome Scale (IPOS) for staff (IPOS-Staff). Methods This multicenter, cross-sectional observational study was conducted concurrently with the validation of the IPOS for patients (IPOS-Patient). Japanese adult patients with cancer and their staff were recruited. We assessed the characteristics of the patients and staff members, missing values, prevalence, and total IPOS scores. For the analysis of criterion validity, intra-rater, and inter-rater reliability, we calculated intraclass correlations (ICCs). Results One hundred and forty-three patients completed the IPOS-Patient, and 79 medical staff members completed the IPOS-Staff. The most common missing values from IPOS-Staff were Family Anxiety (3.5%) and Sharing Feelings (3.5%). Over half of the patients scored themselves moderate or worse for Poor Mobility, Anxiety, and Family Anxiety, while staff members scored patients moderate or worse for Weakness, Anxiety, and Family Anxiety. For criterion validity (patient–staff agreement) as well as intra-rater and inter-rater reliability, ICCs ranged from 0.114 (Sharing Feelings) to 0.826 (Nausea), 0.720 (Anxiety) to 0.933 (Nausea), and −0.038 (Practical Problems) to 0.830 (Nausea), respectively. Significance of results The IPOS-Staff is easy to respond to; it has fair validity and reliability for physical items but poor for psycho-social items. By defining the context and objectives of its use and interpretation, the IPOS-Staff can be a useful tool for measuring outcomes in adult patients with cancer who cannot complete self-evaluations.
Genomic predictions for yield traits in US Holsteins with unknown parent groups.

The objective of this study was to assess the reliability and bias of estimated breeding values (EBV) from traditional BLUP with unknown parent groups (UPG), genomic EBV (GEBV) from single-step genomic BLUP (ssGBLUP) with UPG for the pedigree relationship matrix (A) only (SS_UPG), and GEBV from ssGBLUP with UPG for both A and the relationship matrix among genotyped animals (A22; SS_UPG2) using 6 large phenotype-pedigree truncated Holstein data sets. The complete data included 80 million records for milk, fat, and protein yields from 31 million cows born since 1980. Phenotype-pedigree truncation scenarios included truncation of phenotypes for cows born before 1990 and 2000 combined with truncation of pedigree information after 2 or 3 ancestral generations. A total of 861,525 genotyped bulls with progeny and cows with phenotypic records were used in the analyses. Reliability and bias (inflation/deflation) of GEBV were obtained for 2,710 bulls based on deregressed proofs, and on 381,779 cows born after 2014 based on predictivity (adjusted cow phenotypes). The BLUP reliabilities for young bulls varied from 0.29 to 0.30 across traits and were unaffected by data truncation and number of generations in the pedigree. Reliabilities ranged from 0.54 to 0.69 for SS_UPG and were slightly affected by phenotype-pedigree truncation. Reliabilities ranged from 0.69 to 0.73 for SS_UPG2 and were unaffected by phenotype-pedigree truncation. The regression coefficient of bull deregressed proofs on (G)EBV (i.e., GEBV and EBV) ranged from 0.86 to 0.90 for BLUP, from 0.77 to 0.94 for SS_UPG, and was 1.00 ± 0.03 for SS_UPG2. Cow predictivity ranged from 0.22 to 0.28 for BLUP, 0.48 to 0.51 for SS_UPG, and 0.51 to 0.54 for SS_UPG2. The highest cow predictivities for BLUP were obtained with the most extreme truncation, whereas for SS_UPG2, cow predictivities were also unaffected by phenotype-pedigree truncations. The regression coefficient of cow predictivities on (G)EBV was 1.02 ± 0.02 for SS_UPG2 with the most extreme truncation, which indicated the least biased predictions. Computations with the complete data set took 17 h with BLUP, 58 h with SS_UPG, and 23 h with SS_UPG2. The same computations with the most extreme phenotype-pedigree truncation took 7, 36, and 15 h, respectively. The SS_UPG2 converged in fewer rounds than BLUP, whereas SS_UPG took up to twice as many rounds. Thus, the ssGBLUP with UPG assigned to both A and A22 provided accurate and unbiased evaluations, regardless of phenotype-pedigree truncation scenario. Old phenotypes (before 2000 in this data set) did not affect the reliability of predictions for young selection candidates, especially in SS_UPG2.
Google search volume trends for cancer screening terms during the COVID-19 pandemic

The COVID-19 pandemic has led to delays in cancer diagnosis, in part due to postponement of cancer screening. We used Google Trends data to assess public attention to cancer screening during the first peak of the COVID-19 pandemic. Search volume for terms related to established cancer screening tests (“colonoscopy,” “mammogram,” “lung cancer screening,” and “pap smear”) showed a marked decrease of up to 76% compared to the pre-pandemic period, a significantly greater drop than for search volume for terms denoting common chronic diseases. Maintaining awareness of cancer screening during future public health crises may decrease delays in cancer diagnosis.
Direct enantioselective gradient reversed-phase ultra-high performance liquid chromatography - tandem mass spectrometry method for 3-hydroxy alkanoic acids in lipopeptides on immobilized 1.6 μm amylose-based chiral stationary phase.

3-Hydroxy fatty acids are important chiral building blocks of lipopeptides and metabolic intermediates of fatty acid oxidation, respectively. The analysis of the stereochemistry of such biomolecules has significant practical impact to elucidate and assign the enzymatic specificity of the biosynthesis machinery. In this work, a new MS compatible direct chiral UHPLC separation method for 3-hydroxy fatty acids without derivatization is presented. The application of amylose tris(3,5-dimethylphenyl carbamate) based polysaccharide chiral stationary phase immobilized on 1.6 μm silica particles (CHIRALPAK IA-U) allows the enantioseparation of 3-hydroxy fatty acids under generic ESI-MS friendly RP gradient elution conditions. Adequate separation factors were achieved with both acetonitrile and methanol as organic modifiers, covering hydrocarbon chain lengths between C6 and C14 . Elution orders were derived from rhamnolipid (R-95) of which enantiomerically pure or enriched (R)-3-hydroxy fatty acids were recovered after ester hydrolysis. The S-configured acids consistently eluted before the respective R-enantiomers. The method was successfully applied for the elucidation of the absolute configuration of 3-hydroxy fatty acids originating from a novel lipopeptide with unknown structure. The work furthermore demonstrates that gradient elution is a viable option also in enantioselective (U)HPLC, even for analytes with modest separation factors, although less commonly exploited. This article is protected by copyright. All rights reserved.
Visual field defects in temporal lobe epilepsy surgery

Purpose of review Surgery can provide a robust long-standing seizure remission in drug-refractory mesial temporal lobe epilepsy (MTLE). Despite this, a significant proportion of postoperative patients are ineligible to gain a driving licence due to the size of the subsequent visual field defect (VFD). The amygdala and hippocampus are intimately related to several important white fibre association tracts and damage to the optic radiation results in a contralateral superior quadrantanopia. For this reason, several different modifications to established surgical approaches and novel techniques have recently been applied to mitigate or prevent damage to the optic radiation. There is still no consensus on which operative technique results in optimal outcomes regarding seizure remission, neuropsychological sequelae and VFD rates. We explore contemporary surgical approaches to the mesial temporal lobe and describe the intraoperative use of tractography and iMRI in preventing VFDs. Recent findings Established approaches for the surgical treatment of MTLE include standardized approaches in the form of anterior temporal lobectomies, selective approaches and various modifications thereof. Recent advancements in microsurgical techniques have seen numerous modifications to these approaches to spare the optic radiation as well as the introduction of minimally invasive alternatives such as laser interstitial thermal therapy (LITT) and stereotactic radiosurgery (SRS). The intraoperative use of optic radiation tractography through overlays in the operative microscope and interventional MRI suites to correct for brain shift have been shown to reduce VFDs. Summary VFDs following the surgical treatment of drug-refractory MTLE can have a significant impact on the quality of life. Each of the surgical techniques carries a risk to the visual pathways but the use of minimally invasive techniques as well as surgical adjuncts may reduce or prevent acquired VFDs.
CDK4/6 and PI3K inhibitors: A new promise for patients with HER2‐positive breast cancer

HER2‐positive (HER2+) breast cancer represents a heterogeneous breast cancer subtype, including both oestrogen receptor (ER) positive and negative tumours. A deeper understanding of the crosstalk between ER and HER2 receptor pathways has led to the development of treatment strategies consisting of a simultaneous blockade of both signalling pathways, as a reasonable approach to prevent the onset of mechanisms of resistance.
Perspectives of Pregnant and Breastfeeding Women on Participating in Longitudinal Mother-Baby Studies Involving Electronic Health Records: Qualitative Study

Background Electronic health records (EHRs) hold great potential for longitudinal mother-baby studies, ranging from assessing study feasibility to facilitating patient recruitment to streamlining study visits and data collection. Existing studies on the perspectives of pregnant and breastfeeding women on EHR use have been limited to the use of EHRs to engage in health care rather than to participate in research. Objective The aim of this study is to explore the perspectives of pregnant and breastfeeding women on releasing their own and their infants’ EHR data for longitudinal research to identify factors affecting their willingness to participate in research. Methods We conducted semistructured interviews with pregnant or breastfeeding women from Alachua County, Florida. Participants were asked about their familiarity with EHRs and EHR patient portals, their comfort with releasing maternal and infant EHR data to researchers, the length of time of the data release, and whether individual research test results should be included in the EHR. The interviews were transcribed verbatim. Transcripts were organized and coded using the NVivo 12 software (QSR International), and coded data were thematically analyzed using constant comparison. Results Participants included 29 pregnant or breastfeeding women aged between 22 and 39 years. More than half of the sample had at least an associate degree or higher. Nearly all participants (27/29, 93%) were familiar with EHRs and had experience accessing an EHR patient portal. Less than half of the participants (12/29, 41%) were willing to make EHR data available to researchers for the duration of a study or longer. Participants’ concerns about sharing EHRs for research purposes emerged in 3 thematic domains: privacy and confidentiality, transparency by the research team, and surrogate decision-making on behalf of infants. The potential release of sensitive or stigmatizing information, such as mental or sexual health history, was considered in the decisions to release EHRs. Some participants viewed the simultaneous use of their EHRs for both health care and research as potentially beneficial, whereas others expressed concerns about mixing their health care with research. Conclusions This exploratory study indicates that pregnant and breastfeeding women may be willing to release EHR data to researchers if researchers adequately address their concerns regarding the study design, communication, and data management. Pregnant and breastfeeding women should be included in EHR-based research as long as researchers are prepared to address their concerns.
Physiological determinants of biogeography: The importance of metabolic depression to heat tolerance

A quantitative understanding of physiological thermal responses is vital for forecasting species distributional shifts in response to climate change. Many studies have focused on metabolic rate as a global metric for analyzing the sublethal effects of changing environments on physiology. Thermal performance curves (TPCs) have been suggested as a viable analytical framework, but standard TPCs may not fully capture physiological responses, due in part to failure to consider the process of metabolic depression. We derived a model based on the nonlinear regression of biological temperature‐dependent rate processes and built a heart rate data set for 26 species of intertidal molluscs distributed from 33°S to ~40°N. We then calculated physiological thermal performance limits with continuous heating using T1/2H , the temperature at which heart rate is decreased to 50% of the maximal rate, as a more realistic measure of upper thermal limits. Results indicate that heat‐induced metabolic depression of cardiac performance is a common adaptive response that allows tolerance of harsh environments. Furthermore, our model accounted for the high inter‐individual variability in the shape of cardiac TPCs. We then used these TPCs to calculate physiological thermal safety margins (pTSM), the difference between the maximal operative temperature (95th percentile of field temperatures) and T1/2H of each individual. Using pTSMs, we developed a physiological species distribution model (pSDM) to forecast future geographic distributions. pSDM results indicate that climate‐induced species range shifts are potentially less severe than predicted by a simple correlative SDM. Species with metabolic depression below the optimum temperature will be more thermal resistant at their warm trailing edges. High intraspecific variability further suggests that models based on species‐level vulnerability to environmental change may be problematic. This multi‐scale, mechanistic understanding that incorporates metabolic depression and inter‐individual variability in thermal response enables better predictions about the relationship between thermal stress and species distributions.
Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths

Synthesis of acetylcholine by group 2 innate lymphoid cells is important for optimal immune responses to helminth infection. Acetylcholine versus helminth infection Group 2 innate lymphoid cells (ILC2s) play a role in mucosal immune responses during allergy or helminth infection, and different neurotransmitters can regulate ILC2 function. Roberts et al. now show that pulmonary ILC2s can develop a cholinergic phenotype and up-regulate the synthesis and release of acetylcholine (ACh) during infection with the helminth Nippostrongylus brasiliensis. This cholinergic phenotype was associated with ILC2 activation and could also be induced by exposure to Alternaria alternata extracts or the alarmin cytokines IL-33 and IL-25. Genetic disruption of ACh synthesis in ILC2s was associated with greater parasite burdens and reduced lung and gut barrier immunity to N. brasiliensis infection. These results highlight a role for ACh production by ILC2 in protective immune responses against helminth infection. Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated. Group 2 ILCs (ILC2s) are shown here to synthesize and release acetylcholine (ACh) during parasitic nematode infection. The cholinergic phenotype of pulmonary ILC2s was associated with their activation state, could be induced by in vivo exposure to extracts of Alternaria alternata or the alarmin cytokines interleukin-33 (IL-33) and IL-25, and was augmented by IL-2 in vitro. Genetic disruption of ACh synthesis by murine ILC2s resulted in increased parasite burdens, lower numbers of ILC2s, and reduced lung and gut barrier responses to Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in the expansion of ILC2s for maximal induction of type 2 immunity.
Response to Comment on “Increased growing-season productivity drives earlier autumn leaf senescence in temperate trees”

Our study showed that increases in seasonal productivity drive earlier autumn senescence of temperate trees. Norby argues that this finding is contradicted by observations from free-air CO2 enrichment (FACE) experiments, where elevated CO2 has been found to delay senescence in some cases. We provide a detailed answer showing that the results from FACE studies are in agreement with our conclusions.
Letter transpositions and morphemic boundaries in the second language processing of derived words: An exploratory study of individual differences

Abstract Research into nonnative (L2) morphological processing has produced largely conflicting findings. To contribute to the discussions surrounding the contradictory findings in the literature, we examined L2 morphological priming effects along with a transposed-letter (TL) methodology. Critically, we also explored the potential effects of individual differences in the reading networks of L2 speakers using a test battery of reading proficiency. A masked primed lexical decision experiment was carried out in which the same target (e.g., ALLOW) was preceded by a morphological prime (allowable), a TL-within prime (allwoable), an substituted letter (SL)-within prime (allveable), a TL-across prime (alloawble), an SL-across prime (alloimble), or an unrelated prime (believable). The average data yielded morphological priming but no significant TL priming. However, the results of an exploratory analysis of the potential effects of individual differences suggested that individual variability mediated the group-level priming patterns in L2 speakers. TL-within and TL-across priming effects were obtained only when the performance of participants on nonword reading was considered, while the magnitude of the morphological priming effects diminished as the knowledge of vocabulary expanded. The results highlight the importance of considering individual differences while testing L2 populations.
Shape optimisation for faster washout in recirculating flows

Abstract How to design an optimal biomedical flow device to minimise trapping of undesirable biological solutes/debris and/or enhance their washout is a pertinent but complex question. While biomedical devices often utilise externally driven flows to enhance washout, the presence of vortices – arising as a result of fluid flows within cavities – hinder washout by trapping debris. Motivated by this, we solve the steady, incompressible Navier–Stokes equations for flow through channels into and out of a two-dimensional cavity. In endourology, the presence of vortices – enhanced by flow symmetry breaking – has been linked to long washout times of kidney stone dust in the renal pelvis cavity, with dust transport modelled via advection and diffusion of a passive tracer (Williams et al., J. Fluid Mech., vol. 902, 2020, A16). Here, we determine the inflow and outflow channel geometries that minimise washout times. For a given flow field $\boldsymbol {u}$, vortices are characterised by regions where $\det \boldsymbol {\nabla }\boldsymbol {u} > 0$ (Jeong & Hussain, J. Fluid Mech., vol. 285, 1995, pp. 69–94). Integrating a smooth form of $\max (0, \det \boldsymbol {\nabla }\boldsymbol {u})$ over the domain provides an objective to minimise recirculation zones (Kasumba & Kunisch, Comput. Optim. Appl., vol. 52, 2012, pp. 691–717). We employ adjoint-based shape optimisation to identify inflow and outflow channel geometries that reduce this objective. We show that a reduction in the vortex objective correlates with reduced washout times. We additionally show how multiple solutions to the flow equations lead to solution branch switching during the optimisation routine by characterising the change in solution bifurcation structure with the change in inflow/outflow channel geometry.
Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation

Nicotinic signaling regulates top-down circuit maturation and restores attention deficits in mouse model of fragile X syndrome. Cognitive function depends on frontal cortex development; however, the mechanisms driving this process are poorly understood. Here, we identify that dynamic regulation of the nicotinic cholinergic system is a key driver of attentional circuit maturation associated with top-down frontal neurons projecting to visual cortex. The top-down neurons receive robust cholinergic inputs, but their nicotinic tone decreases following adolescence by increasing expression of a nicotinic brake, Lynx1. Lynx1 shifts a balance between local and long-range inputs onto top-down frontal neurons following adolescence and promotes the establishment of attentional behavior in adulthood. This key maturational process is disrupted in a mouse model of fragile X syndrome but was rescued by a suppression of nicotinic tone through the introduction of Lynx1 in top-down projections. Nicotinic signaling may serve as a target to rebalance local/long-range balance and treat cognitive deficits in neurodevelopmental disorders.
Engineered glycomaterial implants orchestrate large-scale functional repair of brain tissue chronically after severe traumatic brain injury

Engineered glycomaterial implants orchestrate large-scale repair after severe traumatic brain injury. Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brain’s poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery chronically after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely after sTBI significantly enhanced cellular repair and gross motor function recovery when compared to controls 20 weeks after sTBI. Animals subjected to M2 region injuries followed by eCS matrix implantations demonstrated the significant recovery of “reach-to-grasp” function. This was attributed to enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity. These findings indicate that eCS matrices implanted acutely after sTBI can support complex cellular, vascular, and neuronal circuit repair chronically after sTBI.