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Background: The accurate evaluation of tumor response after locoregional therapy is crucial for adjusting therapeutic strategy and guiding individualized follow-up. Purpose: To determine the inter-reader agreement of the LR-TR algorithm for hepatocellular carcinoma treated with locoregional therapy among radiologists with different seniority. Material and Methods: A total of 275 treated observations on 249 MRI scans from 99 patients were retrospectively collected. Three readers of different seniorities (senior, intermediate, and junior with 10, 6, and 2 years of experience in hepatic imaging, respectively) analyzed the presence or absence of features (arterial-phase hyperenhancement and washout) and evaluated LR-TR category. Results: There were substantial inter-reader agreements for overall LR-TR categorization (kappa = 0.704), LR-TR viable (kappa = 0.715), and LR-TR non-viable (kappa = 0.737), but fair inter-reader agreement for LR-TR equivocal (kappa = 0.231) among three readers. The inter-reader agreement was substantial for arterial-phase hyperenhancement (kappa = 0.725), but moderate for washout (kappa = 0.443) among three readers. The inter-reader agreements between two readers were substantial for overall LR-TR categorization (kappa = 0.734, 0.727, 0.652), LR-TR viable (kappa = 0.719, 0.752, 0.678), and LR-TR non-viable (kappa = 0.758, 0.760, 0.694), which were at the same level as the inter-reader agreements among three readers. In addition, the inter-reader agreements between two readers were substantial for arterial-phase hyperenhancement (kappa = 0.733, 0.766, 0.678), but moderate for washout (kappa = 0.473, 0.422, 0.446), which were at the same level as the inter-reader agreements among three readers. Conclusion: LR-TR algorithm demonstrated overall substantial inter-reader agreement among radiologists with different seniority. [ABSTRACT FROM AUTHOR]

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Nasopharyngeal carcinoma (NPC) is a distinct type of cancer that affects the head and neck region, and it is notably linked to infection with the Epstein-Barr Virus (EBV), particularly in endemic regions such as Southeast Asia and Southern China. Despite advances in the conventional care for NPC, including radiation and chemotherapy, the prognosis remains poor for individuals with relapsed or metastatic stages of the disease. Immune checkpoint inhibitors (ICIs), particularly those targeting the PD-1/PD-L1 axis, have emerged as an optimistic therapeutic option. PD-L1 overexpression in NPC contributes to immune avoidance and correlates in relation to these immunotherapies. This review comprehensively explores PD-L1 expression in NPC and its role in tumor immune escape, along with a detailed analysis of clinical trials investigating PD-1/PD-L1 blockade. While PD-L1 overexpression is associated with better responses to ICIs, resistance mechanisms and the complex tumor microenvironment (TME) limit their overall efficacy. We will address these barriers and highlight future directions for improving outcomes, including combination therapies, novel biomarkers, and personalized approaches to treatment. With ongoing research and clinical trials, immune checkpoint inhibition holds great potential to revolutionize NPC therapy, offering hope for improved sustained survival rates and overall well-being for individuals.

Aims: To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment. Methods: Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue. Results: This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as CHL1 (false discovery rate (FDR) = 2.11 × 10-11), RIC8A (FDR = 7.05 × 10-4), and SOX12 (FDR = 1.43 × 10-3). Additionally, RIC8A and CHL1 were hypermethylated in responders, while SOX12 was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in TESPA1 and ATP11A exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells. Conclusion: Our study identified cell-specific changes in DNA methylation associated with chondroitin sulphate response in KBD patients. Cite this article: Bone Joint Res 2024;13(5):237–246.

Background: Conventional cytoreductive therapy for patients with chronic Philadelphia‐negative myeloproliferative neoplasms (MPNs) includes hydroxyurea (HU), interferon‐alpha2 (IFN), and anagrelide. HU is worldwide the most used cytoreductive agent, which lowers elevated blood cell counts within days in the large majority of patients. However, some patients may experience rebound cytosis when HU is reduced due to cytopenia, thereby potentially giving rise to fluctuating cell counts during therapy. Such rapid oscillations may be harmful and potentially elicit thrombosis. Treatment with IFN gradually lowers elevated cell counts within weeks and when the dosage is reduced, the cell counts do not rapidly increase but are sustained within the normal range in the large majority of patients. Conventional hematological response criteria are among others based upon single absolute cell count values and do not take into account the relative decreases toward normal for each cell count. Materials, Methods & Results: Using serial data from the Danish DALIAH trial, we herein describe a novel integrated biomarker index for the assessment of hematological and molecular (JAK2V617F) responses in patients with MPNs during treatment with IFN or HU. Discussion: This novel tool convincingly displays the superiority of IFN versus HU in normalizing elevated cell counts. Our results need to be validated in larger studies but already now call for studies of the safety and efficacy of combination therapy during the initial treatment of patients with MPNs. [ABSTRACT FROM AUTHOR]

BackgroundKRAS is commonly mutated in non-small cell lung cancer (NSCLC); however, the prognostic and predictive impact of each G12 substitution has not been fully elucidated. The approval of specific G12C inhibitors has modified the idea of KRAS “undruggability”, and although the first-line standard consists of immune checkpoint inhibitors (ICIs) with or without chemotherapy, as suggested at ASCO 2022, the outcome in KRAS-mutated population is still controversial.MethodsWe retrospectively described the clinical and pathological characteristics of a homogeneous G12 mutated cohort of 219 patients treated in four Italian oncologic units. We evaluated the outcome (PFS at 18 months and OS at 30 months) of those who underwent standard first-line treatment according to PD-L1 status, focusing on differences across single mutations.ResultsIn the study population, 47.9% of patients harbor the KRAS G12C mutation; 20.5%, G12V; 17.4%, G12D; and 8.2%, G12A. Smoking was a common behavior of patients harboring transversions and transition mutations. PD-L1 expression does not show particular distribution in the case series, although we recorded a prevalence of PD-L1

The therapeutic outcomes in major depressive disorder (MDD), one of the most common and heterogeneous mental illnesses, are affected by factors that remain unclear and often yield unsatisfactory results. Herein, we characterized the composition and metabolic function of the gut microbiota of patients with MDD during antidepressant treatment, based on 16S rRNA sequencing and metabolomics. The microbial signatures at baseline differed significantly between responder and non-responder groups. The gut microbiota of the non-responder group was mainly characterized by increased relative abundances of the phylum Actinobacteria, families Christensenellaceae and Eggerthellaceae, and genera Adlercreutzia and Christensenellaceae R7 group compared to that of the responder group. Additionally, the gut microbiota composition of the responder and non-responder groups differed significantly before and after treatment, especially at the genus level. Moreover, 20 differential metabolites between the responder and non-responder groups were identified that were mainly involved in lipid metabolism (cholestane steroids and steroid esters). Eggerthellaceae and Adlercreutzia displayed strong co-occurrence relationships with certain metabolites, suggesting alternations in the gut microbiome, and associated metabolites may be potential mediators of successful antidepressant treatment. Overall, our study demonstrates that alterations in gut microbiota composition and metabolic function might be relevant to the response to antidepressants, thereby providing insight into mechanisms responsible for their efficacy. [ABSTRACT FROM AUTHOR]

Abstract Background Osteopontin (OPN) is closely related to tumor occurrence and metastasis. This study explored the clinical value of serum OPN levels in small cell lung cancer (SCLC) patients. Methods The ELISA method was used to determine the OPN level of 96 SCLC patients before and after first-line chemotherapy, and compared with 60 healthy controls. Results The serum OPN level of SCLC patients before treatment was significantly higher than that of the healthy control (P

Abstract Background An accumulation of evidence has revealed the important role of epigenetic factors in explaining the etiopathogenesis of human diseases. Several empirical studies have successfully incorporated methylation data into models for disease prediction. However, it is still a challenge to integrate different types of omics data into prediction models, and the contribution of methylation information to prediction remains to be fully clarified. Results A stratified drug-response prediction model was built based on an artificial neural network to predict the change in the circulating triglyceride level after fenofibrate intervention. Associated single-nucleotide polymorphisms (SNPs), methylation of selected cytosine-phosphate-guanine (CpG) sites, age, sex, and smoking status, were included as predictors. The model with selected SNPs achieved a mean 5-fold cross-validation prediction error rate of 43.65%. After adding methylation information into the model, the error rate dropped to 41.92%. The combination of significant SNPs, CpG sites, age, sex, and smoking status, achieved the lowest prediction error rate of 41.54%. Conclusions Compared to using SNP data only, adding methylation data in prediction models slightly improved the error rate; further prediction error reduction is achieved by a combination of genome, methylation genome, and environmental factors.

In human cells, three closely related RAS genes, termed HRAS, KRAS, and NRAS, encode four highly homologous proteins. RAS proteins are small GTPases involved in a broad spectrum of key molecular and cellular activities, including proliferation and survival among others. Gain-of-function missense mutations, mostly located at codons 12, 13, and 61, constitutively activate RAS proteins and can be detected in various types of human cancers. KRAS is the most frequently mutated, followed by NRAS and HRAS. However, each isoform exhibits distinctive mutation frequency at each codon, supporting the hypothesis that different RAS mutants may lead to distinct biologic manifestations. This review is focused on the differences in signaling and phenotype, as well as on transcriptomics, proteomics, and metabolomics profiles related to individual RAS-mutated variants. Additionally, association of these mutants with particular targeted outcomes and rare mutations at additional RAS codons are discussed.

Risperidone has been used to treat the symptoms of schizophrenia and to reduce its relapse. However, the responses to treatment show great variability among patients. The potassium channel has been reported as an effective target for antipsychotics. KCNH7, a member of the voltage-gated K+ channel Kv11 family, is primarily expressed in the brain. Here, we assessed the genetic association of KCNH7 with risperidone responses in 393 schizophrenia patients. The patients were treated with risperidone for 6 weeks. The reduction rates of Positive and Negative Syndrome Scale (PANSS) scores were determined to quantify drug response. We also examined the associations between six single-nucleotide polymorphisms (SNPs) of KCNH7 and the risperidone responses for a total of 6 weeks. The SNP rs77699177 (C > T) in the KCNH7 gene intron was significantly associated with the treatment response reflected by the PANSS reduction rate (CC, 55.8 ± 23.0; TC, 70.9 ± 20.3, P = 0.000110), indicating that patients with the TC genotype have better efficacy for antipsychotic therapy. The rs2241240 SNP also showed a significant association with treatment responses after 6 weeks of treatment (P = 0.00256). The findings indicate that the voltage-gated K+ channel KCNH7 is a potential functional marker for the identification of the response to risperidone treatment in schizophrenia patients.Note: The study was registered under clinical trial number ChiCTR-RNC-09000522 (http://www.chictr.org/).

Abstract Background Glutathione S‐transferases (GSTs) polymorphisms may impact on chronic myeloid leukemia (CML) risk or heterogeneous responses to Imatinib mesylate (IM). The aim of this study was to evaluate the correlation between GSTs polymorphisms and CML risk, treatment response. Methods We genotyped GSTM1, GSTT1 null deletion polymorphisms, and GSTP1 Ile105Val polymorphism by PCR methods and BCR‐ABL transcripts were analyzed by qRT‐PCR in 104 CML patients and 104 sex‐ and age‐matched healthy individuals. Results Individual analysis showed significant association of GSTM1 (p = 0.008; OR = 0.46; 95% CI: 0.26–0.82) and GSTP1 genes (p = 0.04; OR = 1.56; 95% CI: 1.016–2.423) with CML risk. The combined analysis indicated that GSTM1 null/GSTT1 present, GSTM1‐null/GSTP1M*(AG/GG) as well as GSTT1 present/ GSTP1M* genotype were associated with CML risk (ORg(‐):2.28; 95% CI: 1.29–4.04; ORgg: 2.85; 95% CI: 1.36–5.97; OR(‐)g: 1.75; 95% CI: 0.99–3.06, respectively). The proportion of CML cancer attributable to the interaction of smoking and GSTM1 null, GSTT1null, and GSTP1 M* was 42%, 39%, and 13%, respectively. Patients with GSTM1‐null and GSTP1 AG/GG genotype had significantly a lower rate of MMR achievement (p = 0.00; p = 0.009 respectively). Event‐free survival (EFS) percentage was similar between GSTM1 null and GSTM1 present patients (p = 0.21). Conclusion Our study suggests the influence of GSTM1 and GSTP1 polymorphisms on CML risk and treatment response. The interaction between GSTs polymorphisms and smoking plays a significant role on CML susceptibility.

Glutathione S-transferase P1 (GSTP1) has gradually become a promising target for cancer prevention and treatment. However, subtle variations in GSTP1 can lead to the occurrence of single nucleotide polymorphisms (SNPs). The correlation between specific genotypes of GSTP1 and the clinical outcome of the disease has been extensively investigated, demonstrating a significant area of research in this field. However, their impact on the responses to GSTP1 inhibitor treatment remains to be elucidated. Among the various SNPs of GSTP1, I105V polymorphisms is the most widely studied. In this study, a silico model of GSTP1 I105V polymorphism was successfully established to predict the changes of binding model and binding affinity between GSTP1 I105(WT) or GSTP1 V105 and ethacrynic acid via molecular docking and molecular dynamics, and ultimately further evaluated for its anticancer effects. The result demonstrated that the binding capacity of ethacrynic acid decreases with the I105V mutation of GSTP1, indicating the changes in its anticancer activities. Cancer cells expressing GSTP1 V105 may exhibit greater tolerance to ethacrynic acid-induced toxicity compared to other genotypes. In summary, this study provides the first evidence that the GSTP1 I105V polymorphism may impact cancer cell sensitivity to its inhibitor through theoretical prediction. Furthermore, a comprehensive understanding of the correlation between GSTP1 I105V polymorphisms and responses to GSTP1 inhibitor treatment would offer valuable insights for future drug development targeting GSTP1 in cancer-related diseases.Communicated by Ramaswamy H. Sarma.

In human cells, three closely related RAS genes, termed HRAS, KRAS , and NRAS , encode four highly homologous proteins. RAS proteins are small GTPases involved in a broad spectrum of key molecular and cellular activities, including proliferation and survival among others. Gain-of-function missense mutations, mostly located at codons 12, 13, and 61, constitutively activate RAS proteins and can be detected in various types of human cancers. KRAS is the most frequently mutated, followed by NRAS and HRAS. However, each isoform exhibits distinctive mutation frequency at each codon, supporting the hypothesis that different RAS mutants may lead to distinct biologic manifestations. This review is focused on the differences in signaling and phenotype, as well as on transcriptomics, proteomics, and metabolomics profiles related to individual RAS-mutated variants. Additionally, association of these mutants with particular targeted outcomes and rare mutations at additional RAS codons are discussed. [ABSTRACT FROM AUTHOR]

Risperidone has been used to treat the symptoms of schizophrenia and to reduce its relapse. However, the responses to treatment show great variability among patients. The potassium channel has been reported as an effective target for antipsychotics. KCNH7 , a member of the voltage-gated K+ channel Kv11 family, is primarily expressed in the brain. Here, we assessed the genetic association of KCNH7 with risperidone responses in 393 schizophrenia patients. The patients were treated with risperidone for 6 weeks. The reduction rates of Positive and Negative Syndrome Scale (PANSS) scores were determined to quantify drug response. We also examined the associations between six single-nucleotide polymorphisms (SNPs) of KCNH7 and the risperidone responses for a total of 6 weeks. The SNP rs77699177 (C > T) in the KCNH7 gene intron was significantly associated with the treatment response reflected by the PANSS reduction rate (CC, 55.8 ± 23.0; TC, 70.9 ± 20.3, P = 0.000110), indicating that patients with the TC genotype have better efficacy for antipsychotic therapy. The rs2241240 SNP also showed a significant association with treatment responses after 6 weeks of treatment (P = 0.00256). The findings indicate that the voltage-gated K+ channel KCNH7 is a potential functional marker for the identification of the response to risperidone treatment in schizophrenia patients. Note: The study was registered under clinical trial number ChiCTR-RNC-09000522 (http://www.chictr.org/). [ABSTRACT FROM AUTHOR]

A review of the article "Can genetic studies predict treatment response in antineutrophil cytoplasmic antibody-associated vasculitis?", is presented.

In this paper, we investigate what can be learned about average counterfactual outcomes as well as average treatment effects when it is assumed that treatment response functions are smooth. We obtain a set of new partial identification results for both the average treatment response and the average treatment effect. In particular, we find that the monotone treatment response and monotone treatment selection bound of Manski and Pepper, 2000 can be further tightened if we impose the smoothness conditions on the treatment response. Since it is unknown in practice whether the imposed smoothness restriction is met, it is desirable to conduct a sensitivity analysis with respect to the smoothness assumption. We demonstrate how one can carry out a sensitivity analysis for the average treatment effect by varying the degrees of smoothness assumption. We illustrate our findings by reanalyzing the return to schooling example of Manski and Pepper, 2000 and also by measuring the effect of the length of job training on the labor market outcomes. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutation is an important predictor for response to personalized treatments of patients with advanced non‑small‑cell lung cancer (NSCLC). However its usage is limited due to the difficult of obtaining tissue specimens. A novel prediction system using matrix assisted laser desorption ionization‑time of flight mass spectrometry (MALDI‑TOF MS) has been reported to be a perspective tool in European countries to identify patients who are likely to benefit from EGFR tyrosine kinase inhibitor (TKI) treatment. In the present study, MALDI‑TOF MS was used on pretreatment serum samples of patients with advanced non‑small‑cell lung cancer to discriminate the spectra between disease control and disease progression groups in one cohort of Chinese patients. The candidate features for classification were subsequently validated in a blinded fashion in another set of patients. The correlation between plasma EGFR mutation status and the intensities of representative spectra for classification was evaluated. A total of 103 patients that were treated with EGFR‑TKIs were included. It was determined that 8 polypeptides peaks were significant different between the disease control and disease progression group. A total of 6 polypeptides were established in the classification algorithm. The sensitivity of the algorithm to predict treatment responses was 76.2% (16/21) and the specificity was 81.8% (18/22). The accuracy rate of the algorithm was 79.1% (34/43). A total of 3 polypeptides were significantly correlated with EGFR mutations (P=0.04, P=0.03 and P=0.04, respectively). The present study confirmed that MALDI‑TOF MS analysis can be used to predict responses to EGFR‑TKI treatment of the Asian population where the EGFR mutation status differs from the European population. Furthermore, the expression intensities of the three polypeptides in the classification model were associated with EGFR mutation. [ABSTRACT FROM AUTHOR]

Background One genomic breakpoint can result in variable BCR - ABL1 transcript types due to alternative splicing. The influence of different BCR - ABL1 transcript types on clinical outcome is still controversial. Aim of the study The objective of this analysis was to determine the impact of transcript type on response, clinical outcome, recurrence risk after treatment with Imatinib mesylate in Chronic Myeloid Leukemia (CML) patients. Methods Sixty CML patients in chronic phase were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and banding standard protocols. Results There was a significant difference in collective incidence of complete cytogenetic response (CCR) between the e14a2 and e13a2 groups ( P = 0.04). The median time to achieve CCR was shorter in e14a2 patients than to e13a2 ( P = 0.01). This finding is paralleled by the molecular response where the median of the BCR - ABL1 / ABL1 expression levels were significantly lower in e14a2 transcript compared to e13a2 type at 3, 6, 9 and 12 months from the start of therapy ( P < 0.01). The probability of recurrence after treatment discontinuation was 9.33 fold higher in e13a2 transcript, that is reported here for the first time ( χ 2 = 5.49; P = 0.01; OR: 9.33; 95% CI: 1.59, 54.67). No significant difference was observed regarding overall survival (OS), although Patients with e14a2 transcript displayed a significant tendency toward a higher event free survival (EFS) ratio ( P = 0.03). Conclusion We found that patients with the e14a2 transcript achieved better and faster responses to Imatinib mesylate. In this study, parallel data regarding molecular and cytogenetic responses, impact of transcript type on the probability of recurrence might suggest a general outcome that the type of transcript can be used as a prognostic marker at diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Mitochondrial genome maintenance exonuclease 1 (MGME1) is associated with DNA depletion, deletion, duplication, and rearrangement. However, the function of MGME1 in tumors, especially lower-grade gliomas (LGGs), has not been established., Methods: Pan-cancer analysis was used to define the expression patterns and prognostic value of MGME1 in various cancers. Subsequently, we systematically determined the associations between MGME1 expression and clinicopathological characteristics, prognosis, biological functions, immune characteristics, genomic mutations, and therapeutic responses of LGGs based on their expression patterns. The expression level and specific functions of MGME1 in LGGs was detected by conducting in vitro experiments., Results: Abnormally enhanced and high MGME1 expressions were associated with poor prognoses of various tumors, including LGG. Multivariate and univariate Cox regression analyses manifested that MGME1 expression was an independent prognostic biomarker for LGG. The immune-related signatures, infiltration of immune cells, immune checkpoint genes (ICPGs), copy number alteration (CNA), tumor mutation burden (TMB), and treatment responses of LGG patients were associated with the expression of MGME1. The in vitro experiments affirmed that MGME1 was elevated and tightly connected with the cell proliferation and cell cycle in LGG., Conclusions: MGME1 is an independent prognostic biomarker and closely related to the cell proliferation in LGG.

Background: GD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1) burden based on bone, hematologic and visceral domains. We investigated this disease severity scoring system (DS3) methodology for initial assessment, long-term follow-up and evaluation of treatment responses. Methods: We enrolled 133 treated adult GD1 patients. Baseline DS3 scores were calculated near the initial treatment date and patients stratified by severity as marked (DS3 6.00-19.00), moderate (DS3 3.00-5.99), mild (DS3 < 3.00). Follow-up scores were calculated annually. Minimal clinically important improvement (MCII), is defined as ΔDS3 of -3.1. Results: Patient characteristics: N370S was the most common allele (118 patients had at least one), 52 were N370S/N370S (48/52 were Ashkenazi Jews), N370S/L444P was the most common genotype among non-Jews. Median age of treatment: 45 years; median follow-up: 14 years. Baseline DS3 scores: Patients with marked disease (N = 58; median 7.84) were least likely to be N370S homozygous (19 %) and most likely to have had splenectomy (53 %), early age at diagnosis (median 18 years) and major pre-treatment bone pathology (76 %). Among patients with moderate disease (N = 53; median 4.33), 49 % were N370S/N370S, 15.1 % had splenectomy and 17 % had major bone disease. Median age at diagnosis: 32 years. No patient with mild disease (N = 22; median 2.4) had splenectomy or major skeletal disease. Median age at diagnosis: 40 years. 68 % were N370S homozygous. Response to treatment: Health-state transitions occurred primarily during the early treatment years. At Year 5, among 48 evaluable patients with marked baseline disease, eight were unchanged in severity status whereas 40 had MCII of varying degrees with 11 scored as mild. Among 42 evaluable moderate patients, none worsened, 16 remained moderate and 26 improved to mild. Among 16 evaluable mild patients, 14 remained so and 2 had DS3 scores in the low moderate range. Conclusions: DS3 is effective for assessing disease burden in GD1 and for monitoring response. ERT was associated with MCII in DS3 scores in patients with high severity. Nevertheless, despite better DS3 scores with treatment, GD1 patients especially those with splenectomy and pre-treatment bone pathology, continued to have bone complications. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine heritability estimates of treatment responses to a 10% hydrogen peroxide strip-based whitening system in twins. Eighty-five twin pairs were randomly assigned to 10% hydrogen peroxide whitening strips or placebo strips without peroxide. Both twins (monozygotic or dizygotic) received the same treatment. Maxillary teeth were treated for 30 minutes twice daily for 7 days. Efficacy was measured objectively as L* (light–dark), a* (red–green), and b* (yellow–blue) color change from digital images at baseline (∆) and day 8. Heritability estimates for tooth whitening treatment responses for changes from day 8 to baseline were obtained using variance-component methodologies. Whitening treatment responses were highly heritable (h2 = 71.0) for ∆b* and ∆a*(p < .0001), but not for ∆L* (h2 = 27.0), which was essentially modulated by environmental factors. This study has demonstrated that both genetic and environmental factors significantly contributed to seven-day whitening treatment responses achieved with 10% hydrogen peroxide strips. [ABSTRACT FROM PUBLISHER]

Background: KRAS is commonly mutated in non-small cell lung cancer (NSCLC); however, the prognostic and predictive impact of each G12 substitution has not been fully elucidated. The approval of specific G12C inhibitors has modified the idea of KRAS "undruggability", and although the first-line standard consists of immune checkpoint inhibitors (ICIs) with or without chemotherapy, as suggested at ASCO 2022, the outcome in KRAS-mutated population is still controversial., Methods: We retrospectively described the clinical and pathological characteristics of a homogeneous G12 mutated cohort of 219 patients treated in four Italian oncologic units. We evaluated the outcome (PFS at 18 months and OS at 30 months) of those who underwent standard first-line treatment according to PD-L1 status, focusing on differences across single mutations., Results: In the study population, 47.9% of patients harbor the KRAS G12C mutation; 20.5%, G12V; 17.4%, G12D; and 8.2%, G12A. Smoking was a common behavior of patients harboring transversions and transition mutations. PD-L1 expression does not show particular distribution in the case series, although we recorded a prevalence of PD-L1 <1% in G12V (51.4%) compared to G12A (26.7%). ICIs alone was the clinician's choice in 32.7% of patients, and the chemo-immune combination in 17.3% of patients. We described the independent prognostic role of young age ( p = 0.007), female gender ( p = 0.016), and an ICI-based regimen ( p = 0.034) regardless of mutations. Overall, our data confirm the worst prognostic value of G12V mutation apart from treatment choice unlike the other major mutations (C, D, and A) that showed a favorable trend in PFS., Conclusions: KRAS G12 mutations are confirmed to have different characteristics, and the outcome is influenced by ICI first-line regimen. This study provides valuable information for further analysis in the future., Competing Interests: The authors declare that the research was conducted in the absence of commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fancelli, Caliman, Mazzoni, Paglialunga, Gatta Michelet, Lavacchi, Berardi, Mentrasti, Metro, Birocchi, Delmonte, Priano, Comin, Castiglione, Bartoli, Voltolini, Pillozzi and Antonuzzo.)

The therapeutic outcomes in major depressive disorder (MDD), one of the most common and heterogeneous mental illnesses, are affected by factors that remain unclear and often yield unsatisfactory results. Herein, we characterized the composition and metabolic function of the gut microbiota of patients with MDD during antidepressant treatment, based on 16S rRNA sequencing and metabolomics. The microbial signatures at baseline differed significantly between responder and non-responder groups. The gut microbiota of the non-responder group was mainly characterized by increased relative abundances of the phylum Actinobacteria, families Christensenellaceae and Eggerthellaceae, and genera Adlercreutzia and Christensenellaceae R7 group compared to that of the responder group. Additionally, the gut microbiota composition of the responder and non-responder groups differed significantly before and after treatment, especially at the genus level. Moreover, 20 differential metabolites between the responder and non-responder groups were identified that were mainly involved in lipid metabolism (cholestane steroids and steroid esters). Eggerthellaceae and Adlercreutzia displayed strong co-occurrence relationships with certain metabolites, suggesting alternations in the gut microbiome, and associated metabolites may be potential mediators of successful antidepressant treatment. Overall, our study demonstrates that alterations in gut microbiota composition and metabolic function might be relevant to the response to antidepressants, thereby providing insight into mechanisms responsible for their efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Shen, Hao, Li, Xu, Yin and Kuang.)

Background & Aims: The diagnostic scoring systems for autoimmune hepatitis categorize some patients as having probable disease; this designation can affect treatment strategies and recruitment to clinical studies. A retrospective study was performed to determine the bases for the classification of probable autoimmune hepatitis and its clinical importance. Methods: The study included 185 adult patients who had been assessed at presentation for findings common to both international diagnostic scoring systems. Results: Seventeen patients (9%) were graded as probable autoimmune hepatitis by the revised original scoring system, and 28 patients (15%) were similarly designated by the simplified scoring system. These patients were distinguished from those designated as definite autoimmune hepatitis by male sex, concurrent immune diseases, lower serum γ-globulin and immunoglobulin G levels, and lower titers of autoantibody. Patients with definite or probable designations by either scoring system responded similarly to conventional corticosteroid regimens during comparable intervals of treatment. Full, partial, or nonresponses and treatment dependence were evident in all diagnostic categories with similar frequencies. Twenty-seven patients designated as probable autoimmune hepatitis by one system were designated as definite autoimmune hepatitis by the other system. Conclusions: The designation of probable autoimmune hepatitis by the international scoring systems is based on differences in clinical manifestations and does not reflect differences in the validity of the diagnosis or its treatment response. Large multicenter prospective studies are necessary to establish these observations. [Copyright &y& Elsevier]

The purpose of the present study was to determine if a 5-HT6 receptor polymorphism is associated with antidepressant treatment response in major depressive disorder (MDD). Ninety-one patients with MDD, compared with 127 normal control subjects, were evaluated after an 8-week treatment period. An association analysis revealed no differences in genotype and allele distribution between patients with MDD and normal control subjects. However, there were significant differences in the treatment response in some Hamilton Depression Rating Scale (HAM-D) scores (sleep, activity, somatic anxiety, and total) between genotypes. Moreover, the heterozygote group (CT genotype) had significantly better treatment response than the homozygote group (CC + TT genotypes), especially in the somatic-anxiety subcategory and the total score of HAM-D. These findings imply that a 5-HT6 receptor polymorphism (C267T) is associated with treatment response in MDD. [ABSTRACT FROM AUTHOR]

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently defined autoimmune meningoencephalomyelitis, associated with GFAP-IgG antibody. A pooled analysis of 324 cases from published literature and a retrospective single-center study were performed, firstly reveals the possibility that patients with myelitic lesions respond better to initial immunotherapy, but are prone to relapse, suggesting a more aggressive and long-term immunosuppressive medication for them. Moreover, our results showed using tacrolimus at maintenance stage exhibited a less tendency to relapse, providing a possibly new choice to future clinical treatments. [Display omitted] • GFAP astrocytopathy with myelitic lesions respond better to initial therapy. • GFAP astrocytopathy with myelitic lesions are more prone to relapse. • Using tacrolimus at maintenance stage exhibited a less tendency to relapse. [ABSTRACT FROM AUTHOR]

Background: Glutathione S‐transferases (GSTs) polymorphisms may impact on chronic myeloid leukemia (CML) risk or heterogeneous responses to Imatinib mesylate (IM). The aim of this study was to evaluate the correlation between GSTs polymorphisms and CML risk, treatment response. Methods: We genotyped GSTM1, GSTT1 null deletion polymorphisms, and GSTP1 Ile105Val polymorphism by PCR methods and BCR‐ABL transcripts were analyzed by qRT‐PCR in 104 CML patients and 104 sex‐ and age‐matched healthy individuals. Results: Individual analysis showed significant association of GSTM1 (p = 0.008; OR = 0.46; 95% CI: 0.26–0.82) and GSTP1 genes (p = 0.04; OR = 1.56; 95% CI: 1.016–2.423) with CML risk. The combined analysis indicated that GSTM1 null/GSTT1 present, GSTM1‐null/GSTP1M*(AG/GG) as well as GSTT1 present/ GSTP1M* genotype were associated with CML risk (ORg(‐):2.28; 95% CI: 1.29–4.04; ORgg: 2.85; 95% CI: 1.36–5.97; OR(‐)g: 1.75; 95% CI: 0.99–3.06, respectively). The proportion of CML cancer attributable to the interaction of smoking and GSTM1 null, GSTT1null, and GSTP1 M* was 42%, 39%, and 13%, respectively. Patients with GSTM1‐null and GSTP1 AG/GG genotype had significantly a lower rate of MMR achievement (p = 0.00; p = 0.009 respectively). Event‐free survival (EFS) percentage was similar between GSTM1 null and GSTM1 present patients (p = 0.21). Conclusion: Our study suggests the influence of GSTM1 and GSTP1 polymorphisms on CML risk and treatment response. The interaction between GSTs polymorphisms and smoking plays a significant role on CML susceptibility. [ABSTRACT FROM AUTHOR]

The article argues on the third generation neuroimaging in translation psychiatry to improve and create therapeutic options for psychiatric diseases, including autism spectrum disorder, suicidal behavior, and schizophrenia.

The death receptor 5 (DR5) is a member of the tumor necrosis factor receptor superfamily that can transduce the apoptosis signal in cells. This study assessed serum levels of soluble death receptor 5 (sDR5) in small-cell lung cancer (SCLC) patients compared with those in healthy controls. Clinicopathological features of patients, treatment responses, and overall survival of patients were also recorded and analyzed. The sDR5 levels were analyzed using ELISA in 50 healthy controls and 82 SCLC patients before and after first-line chemotherapy. The statistical data showed that pre-treatment levels of serum sDR5 in SCLC patients were higher than those of healthy controls (P<0.001). Pre-treatment levels of serum sDR5 were significantly associated with smoking history of patients, Veterans Administration Lung Study Group (VALSG) stage, tumor size, and lymph node (N) metastasis (P=0.028, 0.001, 0.028, and 0.01, respectively). After treatment with the first-line chemotherapy, the post-treatment levels of serum sDR5 were obviously decreased (P<0.001), and correlated with treatment responses (P<0.001), although there was no significant difference in their pretreatment sDR5 levels (P=0.62). Cox proportional hazard analysis demonstrated that the post-treatment levels of serum sDR5, VALSG stage, and PS status were all independent predictors for overall survival of patients. The results from the current study indicate that serum level of sDR5 could be further confirmed as a biomarker to predict treatment responses and survival of SCLC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Despite the high prevalence and socioeconomic impact of chronic low back pain (cLBP), treatments for cLBP are often unsatisfactory, and effectiveness varies widely across patients. Recent neuroimaging studies have demonstrated abnormal resting-state functional connectivity (rsFC) of the default mode, salience, central executive, and sensorimotor networks in chronic pain patients, but their role as predictors of treatment responsiveness has not yet been explored. In this study, we used machine learning approaches to test if pre-treatment rsFC can predict responses to both real and sham acupuncture treatments in cLBP patients. Fifty cLBP patients participated in 4 weeks of either real (N = 24, age = 39.0 ± 12.6, 16 females) or sham acupuncture (N = 26, age = 40.0 ± 13.7, 15 females) treatment in a single-blinded trial, and a resting-state fMRI scan prior to treatment was used in data analysis. Both real and sham acupuncture can produce significant pain reduction, with those receiving real treatment experiencing greater pain relief than those receiving sham treatment. We found that pre-treatment rsFC could predict symptom changes with up to 34% and 29% variances for real and sham treatment, respectively, and the rsFC characteristics that were significantly predictive for real and sham treatment differed. These results suggest a potential way to predict treatment responses and may facilitate the development of treatment plans that optimize time, cost, and available resources., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Lung cancer is the most common cancer in both the developing and developed countries, which has an unoptimistic outcome. As a result of high rates in mortality and considerable difficulties in treatment, early detection of lung cancer is thought as one of the potential solutions for this stigma. Tissue biopsy has been widely used for cancer diagnosis, but the invasive nature limits their application, especially when repeated biopsies are needed. Liquid biopsy, a minimally invasive procedure aiming to primarily analyze circulating tumor cells (CTCs) and/or circulating tumor DNA (ctDNA) for diagnosing and profiling cancer, has gained interest from oncologists and basic researchers. A great number of achievements in the field of liquid biopsy has been developed, thus liquid biopsy is more feasible in clinical practice than before. More importantly, liquid biopsy is being used, in addition to the diagnosis of lung cancer, to predict prognosis according to genetic alterations and monitor disease based on signature molecular markers. In this review, we briefly summarize techniques in liquid biopsy and focus on its applications in disease diagnosis, prognosis prediction, and condition monitoring of lung cancer., Competing Interests: None.

The value of radiotherapy for palliation is well known to oncologists but not necessarily to other physicians. Using terms such as symptom improvement ratio (sir) and number needed to treat (nnt) rather than traditional response rates might be more appropriate in describing the benefits of palliative radiotherapy to other health care professionals.