Minimal clinically important difference of the EORTC QLQ-CIPN20 for worsening peripheral neuropathy in patients receiving neurotoxic chemotherapy.

Context/objectivesThis is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy.MethodsCancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score.ResultsThere was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p < 0.001 and r = - 0.518, p < 0.001, respectively; T3: r = - 0.699; p < 0.001 and r = - 0.523, p < 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = - 0.354, p < 0.001; T3: r = 0.286, p < 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5-5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6-5.0 (8.1%-15.6% of the subdomain score).ConclusionThe MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5-5.9 for the sensory subscale and 2.6-5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention

Directed evolution and predictive modelling of galactose oxidase towards bulky benzylic and unactivated secondary alcohols

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Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

Discovery of estrogen receptor α target genes and response elements in breast tumor cells

BACKGROUND: Estrogens and their receptors are important in human development, physiology and disease. In this study, we utilized an integrated genome-wide molecular and computational approach to characterize the interaction between the activated estrogen receptor (ER) and the regulatory elements of candidate target genes. RESULTS: Of around 19,000 genes surveyed in this study, we observed 137 ER-regulated genes in T-47D cells, of which only 89 were direct target genes. Meta-analysis of heterogeneous in vitro and in vivo datasets showed that the expression profiles in T-47D and MCF-7 cells are remarkably similar and overlap with genes differentially expressed between ER-positive and ER-negative tumors. Computational analysis revealed a significant enrichment of putative estrogen response elements (EREs) in the cis-regulatory regions of direct target genes. Chromatin immunoprecipitation confirmed ligand-dependent ER binding at the computationally predicted EREs in our highest ranked ER direct target genes, NRIP1, GREB1 and ABCA3. Wider examination of the cis-regulatory regions flanking the transcriptional start sites showed species conservation in mouse-human comparisons in only 6% of predicted EREs. CONCLUSIONS: Only a small core set of human genes, validated across experimental systems and closely associated with ER status in breast tumors, appear to be sufficient to induce ER effects in breast cancer cells. That cis-regulatory regions of these core ER target genes are poorly conserved suggests that different evolutionary mechanisms are operative at transcriptional control elements than at coding regions. These results predict that certain biological effects of estrogen signaling will differ between mouse and human to a larger extent than previously thought

Graphene-Based Nanocomposites for Energy Storage

Since the first report of using micromechanical cleavage method to produce graphene sheets in 2004, graphene/graphene-based nanocomposites have attracted wide attention both for fundamental aspects as well as applications in advanced energy storage and conversion systems. In comparison to other materials, graphene-based nanostructured materials have unique 2D structure, high electronic mobility, exceptional electronic and thermal conductivities, excellent optical transmittance, good mechanical strength, and ultrahigh surface area. Therefore, they are considered as attractive materials for hydrogen (H2) storage and high-performance electrochemical energy storage devices, such as supercapacitors, rechargeable lithium (Li)-ion batteries, Li–sulfur batteries, Li–air batteries, sodium (Na)-ion batteries, Na–air batteries, zinc (Zn)–air batteries, and vanadium redox flow batteries (VRFB), etc., as they can improve the efficiency, capacity, gravimetric energy/power densities, and cycle life of these energy storage devices. In this article, recent progress reported on the synthesis and fabrication of graphene nanocomposite materials for applications in these aforementioned various energy storage systems is reviewed. Importantly, the prospects and future challenges in both scalable manufacturing and more energy storage-related applications are discussed

Measurements of the branching fractions for B→K∗γB \to K^{*}\gamma decays at Belle II

This paper reports a study of $B \to K^{*}\gamma$ decays using $62.8\pm 0.6$ fb$^{-1}$ of data collected during 2019--2020 by the Belle II experiment at the SuperKEKB $e^{+}e^{-}$ asymmetric-energy collider, corresponding to $(68.2 \pm 0.8) \times 10^6$ $B\overline{B}$ events. We find $454 \pm 28$, $50 \pm 10$, $169 \pm 18$, and $160 \pm 17$ signal events in the decay modes $B^{0} \to K^{*0}[K^{+}\pi^{-}]\gamma$, $B^{0} \to K^{*0}[K^0_{\rm S}\pi^{0}]\gamma$, $B^{+} \to K^{*+}[K^{+}\pi^{0}]\gamma$, and $B^{+} \to K^{*+}[K^{+}\pi^{0}]\gamma$, respectively. The uncertainties quoted for the signal yield are statistical only. We report the branching fractions of these decays: $$\mathcal{B} [B^{0} \to K^{*0}[K^{+}\pi^{-}]\gamma] = (4.5 \pm 0.3 \pm 0.2) \times 10^{-5},$$ $$\mathcal{B} [B^{0} \to K^{*0}[K^0_{\rm S}\pi^{0}]\gamma] = (4.4 \pm 0.9 \pm 0.6) \times 10^{-5},$$ $$\mathcal{B} [B^{+} \to K^{*+}[K^{+}\pi^{0}]\gamma] = (5.0 \pm 0.5 \pm 0.4)\times 10^{-5},\text{ and}$$ $$\mathcal{B} [B^{+} \to K^{*+}[K^0_{\rm S}\pi^{+}]\gamma] = (5.4 \pm 0.6 \pm 0.4) \times 10^{-5},$$ where the first uncertainty is statistical, and the second is systematic. The results are consistent with world-average values

Measurement of the branching fraction for the decay B→K∗(892)ℓ+ℓ−B \to K^{\ast}(892)\ell^+\ell^- at Belle II

We report a measurement of the branching fraction of $B \to K^{\ast}(892)\ell^+\ell^-$ decays, where $\ell^+\ell^- = \mu^+\mu^-$ or $e^+e^-$, using electron-positron collisions recorded at an energy at or near the $\Upsilon(4S)$ mass and corresponding to an integrated luminosity of $189$ fb$^{-1}$. The data was collected during 2019--2021 by the Belle II experiment at the SuperKEKB $e^{+}e^{-}$ asymmetric-energy collider. We reconstruct $K^{\ast}(892)$ candidates in the $K^+\pi^-$, $K_{S}^{0}\pi^+$, and $K^+\pi^0$ final states. The signal yields with statistical uncertainties are $22\pm 6$, $18 \pm 6$, and $38 \pm 9$ for the decays $B \to K^{\ast}(892)\mu^+\mu^-$, $B \to K^{\ast}(892)e^+e^-$, and $B \to K^{\ast}(892)\ell^+\ell^-$, respectively. We measure the branching fractions of these decays for the entire range of the dilepton mass, excluding the very low mass region to suppress the $B \to K^{\ast}(892)\gamma(\to e^+e^-)$ background and regions compatible with decays of charmonium resonances, to be \begin{equation} {\cal B}(B \to K^{\ast}(892)\mu^+\mu^-) = (1.19 \pm 0.31 ^{+0.08}_{-0.07}) \times 10^{-6}, {\cal B}(B \to K^{\ast}(892)e^+e^-) = (1.42 \pm 0.48 \pm 0.09)\times 10^{-6}, {\cal B}(B \to K^{\ast}(892)\ell^+\ell^-) = (1.25 \pm 0.30 ^{+0.08}_{-0.07}) \times 10^{-6}, \end{equation} where the first and second uncertainties are statistical and systematic, respectively. These results, limited by sample size, are the first measurements of $B \to K^{\ast}(892)\ell^+\ell^-$ branching fractions from the Belle II experiment