The Intolerance to Uncertainty Scale (IUS) was developed to measure a dispositional tendency to react negatively to uncertain events, regardless of the occurrence probability of those events. Recent ...evidence suggests a 2-factor structure underlying the IUS; 1 factor measuring a prospective aspect (i.e., desire for predictability) and the other assessing an inhibitory aspect (i.e., uncertainty paralysis). The factorial and construct validity of the IUS test scores among undergraduate students in Singapore were examined in the present research using exploratory (n = 565) and confirmatory (n = 898) factor analyses. Results indicated that a 2-factor model was preferred over a unitary-factor model. The construct validity of the IUS (and subscale) scores was examined using a comprehensive nomological network of psychopathology and personality/affectivity variables. Differential relations were observed for the prospective and inhibitory components, providing support that the 2 subscales assessed unique aspects of the intolerance of uncertainty construct. An 18-item modified version of IUS was also proposed and its test scores had stronger validity evidence than scores from the widely used 12-item version.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
The solution processing of optoelectronic active layers promises to usher in a new era of technologies, from rollable displays to smart textiles, but critical challenges remain in the processing of ...these materials. While solution-based deposition of these compounds, including organic small-molecules and polymers and metal–halide perovskites, is key to driving down manufacturing costs, the rapid, uncontrolled nature of solution processing invariably results in the formation of kinetically trapped films, with heterogeneities and defects spanning multiple length scales that degrade device performance. Given such finite time, usually on the order of seconds, for molecules to organize as solvent evaporates from the active layers, the use of nanoporous scaffolds to select for desired crystallization outcomes is a promising approach to addressing this critical issue. As the size of crystals decreases, their surface free energy plays an increasingly important role in dictating their morphology and structure. By confining crystallization within the sub-micrometer pores of scaffolds, such surface free energy effects can be exploited to select for specific polymorphs and crystal orientations. In this Perspective, we highlight the use of nanoporous scaffolds to stabilize high-performing polymorphs of metal-halide perovskites, as well as guide the orientation of organic semiconductor crystals both laterally and vertically for optimized in-plane and out-of-plane charge transport, respectively. Critically, examples of scalable solution-phase deposition methods using nanoporous scaffolds are highlighted as potential targets for commercialization.
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IJS, KILJ, NUK, PNG, UL, UM
As structure prediction methods are generating millions of publicly available protein structures, searching these databases is becoming a bottleneck. Foldseek aligns the structure of a query protein ...against a database by describing tertiary amino acid interactions within proteins as sequences over a structural alphabet. Foldseek decreases computation times by four to five orders of magnitude with 86%, 88% and 133% of the sensitivities of Dali, TM-align and CE, respectively.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
The liver is the most common site of metastatic disease
. Although this metastatic tropism may reflect the mechanical trapping of circulating tumour cells, liver metastasis is also dependent, at ...least in part, on the formation of a 'pro-metastatic' niche that supports the spread of tumour cells to the liver
. The mechanisms that direct the formation of this niche are poorly understood. Here we show that hepatocytes coordinate myeloid cell accumulation and fibrosis within the liver and, in doing so, increase the susceptibility of the liver to metastatic seeding and outgrowth. During early pancreatic tumorigenesis in mice, hepatocytes show activation of signal transducer and activator of transcription 3 (STAT3) signalling and increased production of serum amyloid A1 and A2 (referred to collectively as SAA). Overexpression of SAA by hepatocytes also occurs in patients with pancreatic and colorectal cancers that have metastasized to the liver, and many patients with locally advanced and metastatic disease show increases in circulating SAA. Activation of STAT3 in hepatocytes and the subsequent production of SAA depend on the release of interleukin 6 (IL-6) into the circulation by non-malignant cells. Genetic ablation or blockade of components of IL-6-STAT3-SAA signalling prevents the establishment of a pro-metastatic niche and inhibits liver metastasis. Our data identify an intercellular network underpinned by hepatocytes that forms the basis of a pro-metastatic niche in the liver, and identify new therapeutic targets.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
IMPORTANCE: During hospitalization for hematopoietic stem cell transplantation (HCT), patients receive high-dose chemotherapy before transplantation and experience significant physical and ...psychological symptoms and poor quality of life (QOL). OBJECTIVE: To assess the effect of inpatient palliative care on patient- and caregiver-reported outcomes during hospitalization for HCT and 3 months after transplantation. DESIGN, SETTING, AND PARTICIPANTS: Nonblinded randomized clinical trial among 160 adults with hematologic malignancies undergoing autologous/allogeneic HCT and their caregivers (n = 94). The study was conducted from August 2014 to January 2016 in a Boston hospital; follow-up was completed in May 2016. INTERVENTIONS: Patients assigned to the intervention (n=81) were seen by palliative care clinicians at least twice a week during HCT hospitalization; the palliative intervention was focused on management of physical and psychological symptoms. Patients assigned to standard transplant care (n=79) could be seen by palliative care clinicians on request. MAIN OUTCOMES AND MEASURES: Primary: change in patient QOL from baseline to week 2; secondary: patient-assessed mood, fatigue, and symptom burden scores at baseline, 2 weeks, and 3 months after HCT and caregiver-assessed QOL and mood at baseline and 2 weeks after HCT. RESULTS: Among 160 enrolled patients (mean age, 60 SD, 13.3 years; 91 women 56.9%; median hospital stay, 21 days) and 94 caregivers, 157 (98.1%) and 89 (94.7%), respectively, completed 2-week follow-up, and 149 patients (93.1%) completed 3-month follow-up. Patients in the intervention group reported a smaller decrease in QOL from baseline to week 2 (mean baseline score, 110.26; week 2 score, 95.46; mean change, −14.72) compared with patients in the control group (mean baseline score, 106.83; week 2 score, 85.42; mean change, −21.54; difference between groups, −6.82; 95% CI, −13.48 to −0.16; P = .045). Among the secondary outcomes, from baseline to week 2, patients in the intervention group vs those in the control group had less increase in depression (mean, 2.43 vs 3.94; mean difference, 1.52; 95% CI, 0.23-2.81; P = .02), lower anxiety (mean, −0.80 vs 1.12; mean difference, 1.92; 95% CI, 0.83-3.01; P < .001), no difference in fatigue (mean, −10.30 vs −13.65; mean difference, −3.34; 95% CI, −7.25 to 0.56; P = .09), and less increase in symptom burden (mean, 17.35 vs 23.14; mean difference, 5.80; 95% CI, 0.49-11.10; P = .03). At 3 months after HCT, intervention patients vs control patients had higher QOL scores (mean, 112.00 vs 106.66; mean difference, 5.34; 95% CI, 0.04-10.65; P = .048) and less depression symptoms (mean, 3.49 vs 5.19; mean difference, −1.70; 95% CI, −2.75 to −0.65; P = .002) but no significant differences in anxiety, fatigue, or symptom burden. From baseline to week 2 after HCT, caregivers of patients in the intervention group vs caregivers of patients in the control group reported no significant differences in QOL or anxiety but had a smaller increase in depression (mean, 0.25 vs 1.80; mean difference, 1.55; 95% CI, 0.14-2.96; P = .03). CONCLUSIONS AND RELEVANCE: Among adults at a single institution undergoing HCT for hematologic malignancy, the use of inpatient palliative care compared with standard transplant care resulted in a smaller decrease in QOL 2 weeks after transplantation. Further research is needed for replication and to assess longer-term outcomes and cost implications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02207322
The effect of nanoconfinement on the crystallization of methylammonium lead iodide (MAPbI3) was systematically studied using two-dimensional X-ray diffraction (2D XRD). Nanoconfined crystals were ...prepared by spin coating a cosolution of lead iodide (PbI2) and methylammonium iodide (MAI) dissolved in N,N-dimethylformamide or dimethyl sulfoxide onto anodized aluminum oxide (AAO) templates with uniaxially aligned pores ranging from 20–200 nm in diameter. Upon spin coating, a metastable crystalline phase incorporating solvent molecules was observed. Analysis of 2D XRD patterns using refined lattice parameters revealed that these crystals adopt a preferential orientation with alternating sheets of PbI2 and solvent molecules lying parallel to the long axis of the pores. Upon thermal annealing at temperatures up to 130 °C, the oriented PbI2/solvent crystals converted to randomly oriented MAPbI3 crystals, with the extent of conversion dependent on the characteristic pore diameter of the AAO template. Nanoconfinement was further observed to affect the stability of MAPbI3 crystals exposed to air. Unconfined MAPbI3 crystals degraded to PbI2 within a period of 2 weeks of air exposure, accompanied by a significant change in crystal morphology. In contrast, MAPbI3 crystals confined in AAO templates with a characteristic pore size of 100 nm were stable over the same period.
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IJS, KILJ, NUK, PNG, UL, UM
Homologous recombination deficiency (HRD) stands as a clinical indicator for discerning responsive outcomes to platinum-based chemotherapy and poly ADP-ribose polymerase (PARP) inhibitors. One of the ...conventional approaches to HRD prognostication has generally centered on identifying deleterious mutations within the BRCA1/2 genes, along with quantifying the genomic scars, such as Genomic Instability Score (GIS) estimation with scarHRD. However, the scarHRD method has limitations in scenarios involving tumors bereft of corresponding germline data. Although several RNA-seq-based HRD prediction algorithms have been developed, they mainly support cohort-wise classification, thereby yielding HRD status without furnishing an analogous quantitative metric akin to scarHRD. This study introduces the expHRD method, which operates as a novel transcriptome-based framework tailored to n-of-1-style HRD scoring. The prediction model has been established using the elastic net regression method in the Cancer Genome Atlas (TCGA) pan-cancer training set. The bootstrap technique derived the HRD geneset for applying the expHRD calculation. The expHRD demonstrated a notable correlation with scarHRD and superior performance in predicting HRD-high samples. We also performed intra- and extra-cohort evaluations for clinical feasibility in the TCGA-OV and the Genomic Data Commons (GDC) ovarian cancer cohort, respectively. The innovative web service designed for ease of use is poised to extend the realms of HRD prediction across diverse malignancies, with ovarian cancer standing as an emblematic example. Our novel approach leverages the transcriptome data, enabling the prediction of HRD status with remarkable precision. This innovative method addresses the challenges associated with limited available data, opening new avenues for utilizing transcriptomics to inform clinical decisions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Processing of concentrated lignocellulosic biomass suspensions typically involves the conversion of the cellulose into sugars and sugars into ethanol. Biomass is usually pretreated via methods like ...comminution or steam explosion to form fine cellulosic fibers to be dispersed into an aqueous phase for further treatment. The resulting cellulose suspensions need to be pressurized and pumped into and out of various processing vessels without allowing the development of flow instabilities that are typically associated with “demixing”, that is, the segregation of the cellulosic biomass from the aqueous phase via the formation of mats of cellulosic fibers and the filtration of the aqueous phase. Such demixing can prevent continuous processing at high rates. Here, the development of flow instabilities via the demixing effect for cellulose suspensions is demonstrated using capillary and compressive squeeze flows. It is shown that the use of a gelation agent, hydroxypropyl guar gum, at the critical concentration of 0.5 wt% or higher significantly affects the viscoelastic material functions of cellulosic suspensions, improves the dispersive mixing of the fibers within the aqueous phase, and results in the elimination of the flow instabilities and associated demixing effects that are ubiquitously observed during the pressurization and processing of cellulosic suspensions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This study examined the intergenerational transmission of parental invalidation and whether parental difficulties in emotion regulation mediated the association between past experiences of ...invalidation and current invalidating parenting practices. We also aimed to investigate whether gender might influence the transmission of parental invalidation. We recruited a community sample of 293 dual-parent families (adolescent and their parents) based in Singapore. Parents and adolescents each completed measures of childhood invalidation, whereas parents additionally reported on their difficulties in emotion regulation. Results based on path analyses demonstrated that past parental invalidation experienced by fathers positively predicted current perceived invalidation by their children. The association between mothers' childhood invalidation and current invalidating practices was fully mediated by mothers' difficulties with emotion regulation. Further analyses revealed that parents' current invalidating behaviors were not predicted by their past experiences of paternal or maternal invalidation. These findings point to the importance of considering the family invalidating environment as a whole when examining the influence of past experienced parental invalidation on emotion regulation and invalidating behaviors of second-generation parents. Our study provides empirical support for the intergenerational transmission of parental invalidation and highlights the need to address childhood experiences of parental invalidation in parenting programs.
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