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Abstract Exercise and mindfulness-based interventions have growing evidence for managing fatigue and comorbid symptoms; however, packaging them in a cohesive digital way for patients undergoing cancer treatment has not been evaluated. We conducted a randomized controlled trial to assess the impact of a 12 week digital integrative medicine program, Integrative Medicine at Home (IM@Home), versus enhanced usual care on fatigue severity (primary outcome), comorbid symptoms and acute healthcare utilization (secondary outcomes), in 200 patients with solid tumors experiencing fatigue during treatment. Fatigue severity decreased more in IM@Home than in the control (1.99 vs. 1.51 points; p = 0.04). IM@Home participants also had reduced symptom distress (p = 0.003), anxiety (p = 0.03), and depression (p = 0.02). Acute healthcare utilization was lower with IM@Home, with fewer emergency department visits (rate ratio 0.49; p = 0.04), hospitalizations (4% vs. 12.9%; p = 0.03), and shorter hospital stays (4.25 vs. 10 days; p

Purpose This study compared the three-dimensional (3D) morphology of the mandible, temporomandibular joint (TMJ), and condylar movement in skeletal Class II and Class III patients and investigated correlations between morphology and movement in each skeletal pattern.Materials and Methods This study included patients with skeletal Class II (Class II group, n = 23) and skeletal Class III (Class III group, n = 25). Computed tomography was used to perform 3D morphological measurements of the mandible, condyle, articular eminence, joint space, and condylar position. Condylar path length (CPL), sagittal condylar inclination (SCI), and transverse condylar inclination (TCI) during most protrusive mandibular movements were measured using computerized axiography. Each measurement was compared between the two groups using Mann – Whitney’s U test, and the correlation between morphological and movement measurements was examined in each group with Spearman’s rank correlation coefficient.Results The Class II group showed significantly smaller condylar length, ramus height, mandibular body length, and condylar volume, while larger articular eminence height and more anterior condylar position than the Class III group. As for the condylar movement, the Class II group had significantly larger values in CPL and SCI than the Class III group. The Class II group showed a significant correlation between articular eminence inclination and SCI, while the Class III group showed a significant correlation between superior joint space and CPL.Conclusion Patients with skeletal Class II and III exhibited different correlation patterns between TMJ morphology and condylar movement during mandibular protrusive movement.

Tianyuan Lei,1,2 Kai Yang,1,2 JinHyun Jun,1,2 Shujin Hu,1,2 Qinghao Yang,1,2 Xu Hong,3 Yonghua Cui1,2 1Department of Psychiatry, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Laboratory for Clinical Medicine, Capital Medical University, Beijing, People’s Republic of China; 3Cloud Services Innovation Laboratory, Institute of Intelligent Science and Technology, China Electronics Technology Group Corporation, Beijing, People’s Republic of ChinaCorrespondence: Yonghua Cui; Tianyuan Lei, Email cuiyonghua@bch.com.cn; tianyuanlei@bch.com.cnPurpose: Tic disorders are neurodevelopmental disorders characterized by movements or vocalizations, often accompanied by anxiety symptoms. However, the relationships between tic severity, age, and anxiety symptoms remain unclear. Here, we investigated the association between tic severity and age and examined how anxiety symptoms might influence this relationship.Patients and Methods: Paediatric patients with tic disorders were recruited from the outpatient clinic of the in Department of Psychiatry at Beijing Children’s Hospital, Capital Medical University. The final sample included 372 subjects (77 females, 295 males; mean age = 10.50 ± 2.70 years; age range: 6.33– 15.92 years). Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS), while anxiety symptoms were measured using the Screen for Child Anxiety Related Emotional Disorders (SCARED).Results: We found a significant positive correlation between both total and subscale anxiety scores and tic severity. Furthermore, anxiety symptoms, particularly separation anxiety, were found to be significantly correlated with age-related differences in tic severity. In the high anxiety group, tic severity increased significantly with age, mirroring the overall trend. Conversely, in the low anxiety group, tic severity remained relatively stable with age.Conclusion: Our findings highlight the role of anxiety in the progression of tic disorders and emphasize the importance of addressing anxiety in the clinical management of children with tic disorders.Keywords: tic disorders, anxiety symptom, development, children and adolescents

Kai Yang,1,2 Tianyuan Lei,1,2 JinHyun Jun,1,2 Qinghao Yang,1,2 Jingyi Li,1,2 Mengjiao Wang,1,2 Yonghua Cui1,2 1Department of Psychiatry, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2Laboratory for Clinical Medicine, Capital Medical University, Beijing, 100045, People’s Republic of ChinaCorrespondence: Tianyuan Lei; Yonghua Cui, Email tianyuanlei@bch.com.cn; cuiyonghua@bch.com.cnPurpose: Tic disorders (TD) are common neurodevelopmental disorders characterized by heterogeneous tic symptoms in children, making diagnostic classification difficult. This complexity requires accurate subtyping using data-driven computational methods to identify patterns within clinical data. This systematic review primarily summarizes the current evidence for the classification of TD using a data-driven approach.Patients and Methods: We conducted a systematic literature search on PubMed and Web of Science up to December 2023 and identified 16 publications analyzing 14 unique samples, totaling approximately 6000 subjects.Results: Nine studies classified different subtypes of TD based on symptoms and behavior. Seven studies identified novel factor structures based on TD and its complex comorbidity patterns. Seven studies highlighted associations between TD symptom patterns and genetics, reflecting the diversity of underlying genetic mechanisms underlying TD.Conclusion: This systematic review reveals significant variability in research on the classification of TD, which limits the application of findings for accurate diagnosis and guiding treatment strategies in pediatric psychiatry. Further research incorporating multidimensional information (such as genetic, neuroimaging, and environmental and social factors) is essential to improve the understanding of TD subtypes.Keywords: tic disorders, Tourette syndrome, subtype classification, cluster analysis

Abstract Background Cisplatin-induced ototoxicity (CIO), characterized by irreversible and progressive bilateral hearing loss, is a prevalent adverse effect of cisplatin chemotherapy. Alongside clinical risk factors, genetic variants contribute to CIO and genome-wide association studies (GWAS) have highlighted the polygenicity of this adverse drug reaction. Polygenic scores (PGS), which integrate information from multiple genetic variants across the genome, offer a promising tool for the identification of individuals who are at higher risk for CIO. Integrating large-scale hearing loss GWAS data with single cell omics data holds potential to overcome limitations related to small sample sizes associated with CIO studies, enabling the creation of PGSs to predict CIO risk. Results We utilized a large-scale hearing loss GWAS and murine inner ear single nuclei RNA-sequencing (snRNA-seq) data to develop two polygenic scores: a hearing loss PGS (PGSHL) and a biologically informed PGS for CIO (PGSCIO). The PGSCIO included only variants which mapped to genes that were differentially expressed within cochlear cells that showed differential abundance in the murine snRNA-seq data post-cisplatin treatment. Evaluation of the association of these PGSs with CIO in our target CIO cohort revealed that PGSCIO demonstrated superior performance (P = 5.54 × 10− 5) relative to PGSHL (P = 2.93 × 10− 3). PGSCIO was also associated with CIO in our test cohort (P = 0.04), while the PGSHL did not show a significant association with CIO (P = 0.52). Conclusion This study developed the first PGS for CIO using a large-scale hearing loss dataset and a biologically informed filter generated from cisplatin-treated murine inner ear snRNA-seq data. This innovative approach offers new avenues for developing PGSs for pharmacogenomic traits, which could contribute to the implementation of tailored therapeutic interventions. Further, our approach facilitated the identification of specific cochlear cells that may play critical roles in CIO. These novel insights will guide future research aimed at developing targeted therapeutic strategies to prevent CIO.

Myonghwa Park,1 Keunyeob Oh,2 Hyungjun Kim,3 Jongkun Jun,4 Jooyoung Kim,5 Thi-Thanh-Tinh Giap,6 Rhayun Song1 1College of Nursing, Chungnam National University, Daejeon, Republic of Korea; 2College of Economics and Management, Chungnam National University, Daejeon, Republic of Korea; 3School of Business, Chungnam National University, Daejeon, Republic of Korea; 4Division of Global Business and Technology, Hankuk University of Foreign Studies, Yongin, Republic of Korea; 5School of Business and Technology Management, College of Business, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; 6College of Health Science, VinUniversity, Hanoi, VietnamCorrespondence: Rhayun Song, College of Nursing, Chungnam National University, Munwha-ro 266, Jung-Gu, Daejeon, 35015, Republic of Korea, Tel +82-10-3069-2214, Fax +82-42-580-8309, Email songry@cnu.ac.krPurpose: This study aims to explore how the relationship between information-seeking and infection-prevention behaviors through risk perception changes according to the level of trust in the media and government.Methods: The study is a secondary data analysis of data from a cross-sectional national survey of 700 adults living in the community, representing different age groups, genders, and geographic regions. A validated questionnaire was used to assess information-seeking behaviors, trust in media and government, and risk perception to explain infection-prevention behaviors in response to the COVID-19 pandemic. A conditional analysis was conducted using SPSS and PROCESS macro (Model 7) to identify the effect of moderated mediation.Results: The participants were fairly balanced by gender and age group. Most participants learned about COVID-19 through major broadcasts and television (56.7%) followed by internet media (21.7%). Information-seeking and risk perception together explained 17% of the variance in infection-prevention behaviors (F=63.95, p< 0.01). The standardized indirect effect (β=0.04, BootCI 0.02, 0.06) was significant at 95% CI. The moderated mediation index (M=− 0.04, CI − 0.05, − 0.01) indicates that trust in media and government influences the effect of information-seeking on risk perception and infection-prevention behavior even after controlling for age and gender.Conclusion: Information-seeking behaviors affect infection-prevention behaviors directly and indirectly through risk perception. Trust in media and government modulates this relationship, emphasizing the importance of establishing trust to promote effective risk communication and long-term public compliance with infection-prevention practices. Health authorities should focus on building trust through transparent risk communication and integrating diverse media perspectives. Further research is needed to explore the psychological and social mechanisms underlying trust in media and government through qualitative, cross-cultural comparisons.Keywords: conditional analysis, information-seeking, risk perception, protective behaviors, trust in media and government

Background: Reishi, a medicinal mushroom, is increasingly used for symptom control by cancer patients worldwide. However, data around patients' experiences with Reishi in oncology are lacking, limiting safe, effective clinical applications. We thus sought to evaluate patient reported benefits and harms of using Reishi. Methods: We conducted a cross-sectional survey among Chinese cancer patients using Reishi products, probing for symptom improvements and/or adverse events (AEs) after taking Reishi. Multivariable logistic regression models assessed whether socio-demographic or clinical factors, as well as duration of Reishi use or combination with other TCM herbs, were associated with being a “responder” – reporting “quite a bit” or “very much” symptom improvement. Results: Among 1374 participants, more than half of participants reported that nausea (55 %), fatigue (52 %), poor appetite (51 %), and depression (50 %) improved quite a bit or very much after taking Reishi. In multivariate analyses, age 5 years: AOR = 2.07, p < 0.001) were significantly associated with higher responder rates for symptom improvement. However, 125 (9.1 %) also reported a range of AEs, including dry mouth (5 %), constipation (4 %), insomnia (3 %), pruritus (3 %) and vertigo (3 %). Conclusion: While majority of cancer patients using Reishi reported symptom improvements, some reported adverse effects. This information can assist clinicians in advising cancer patients on safe and effective use of Reishi and help identify specific outcomes for assessment in future prospective clinical trials.

Abstract Defining genetic factors impacting chemotherapy failure can help to better predict response and identify drug resistance mechanisms. However, there is limited understanding of the contribution of inherited noncoding genetic variation on inter-individual differences in chemotherapy response in childhood acute lymphoblastic leukemia (ALL). Here we map inherited noncoding variants associated with treatment outcome and/or chemotherapeutic drug resistance to ALL cis-regulatory elements and investigate their gene regulatory potential and target gene connectivity using massively parallel reporter assays and three-dimensional chromatin looping assays, respectively. We identify 54 variants with transcriptional effects and high-confidence gene connectivity. Additionally, functional interrogation of the top variant, rs1247117, reveals changes in chromatin accessibility, PU.1 binding affinity and gene expression, and deletion of the genomic interval containing rs1247117 sensitizes cells to vincristine. Together, these data demonstrate that noncoding regulatory variants associated with diverse pharmacological traits harbor significant effects on allele-specific transcriptional activity and impact sensitivity to antileukemic agents.

Abstract Background Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. Methods A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. Results Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. Conclusion While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. Trial registration Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.

(1) Background: This pilot study evaluates the feasibility and preliminary effects of acupuncture for cancer-related cognitive dysfunction (CRCD) in cancer survivors. (2) Methods: A randomized trial comparing real acupuncture (RA) to sham acupuncture (SA) and waitlist control (WLC) among cancer survivors reporting cognitive difficulties. Interventions were delivered weekly over 10 weeks. Feasibility was evaluated by recruitment, treatment adherence, and assessment completion. Subjective CRCD was assessed by the Functional Assessment of Cancer Therapy-Cognitive Function—Perceived Cognitive Impairment subscale (FACT-Cog PCI) and objective CRCD was assessed by the Hopkins Verbal Learning Test—Revised (HVLT-R). (3) Results: 32 participants (57.1% of eligible patients) were enrolled. All participants in acupuncture groups completed ≥8 of 10 treatments. Assessment completion rate was 100% for all participants. From baseline to week 10, the RA group (n = 19) reported a clinically meaningful 17.3-point increase in FACT-Cog PCI (95% confidence interval [CI] 12.5 to 22.1), compared to 9.7 points (95% CI 2.8 to 16.7) in the SA group (n = 9), and 6.8 points (95% CI −3.7 to 17.2) in the WLC group (n = 4). In the subgroup analysis among patients with a below-average baseline HVLT-R (T-score < 50), the RA group (n = 8) increased FACT-Cog PCI scores by 20.4 (95% CI 13.6 to 27.3), compared to 11.1 points (95% CI 0.6 to 21.5) in the SA group (n = 5). The improvements from RA persisted through week 16 in both the total sample and the sub-group. Eleven mild adverse events were reported, with pain and bleeding at the needling sites being the most common. (4) Conclusions: The findings support the feasibility and safety of conducting a randomized, placebo-controlled trial to evaluate acupuncture for cognitive dysfunction in cancer survivors.

Abstract Background Racial disparities in sleep are well‐documented. However, evidence‐based options for addressing these disparities are lacking in cancer populations. To inform future research on sleep interventions, this study aims to understand racial differences in treatment responses to acupuncture and cognitive behavioral therapy for insomnia (CBT‐I) among Black and White cancer survivors. Methods We conducted a secondary analysis of a comparative effectiveness trial evaluating acupuncture versus CBT‐I for insomnia in cancer survivors. We compared insomnia severity, sleep characteristics, and co‐morbid symptoms, as well as treatment attitudes, adherence, and responses among Black and White participants. Results Among 156 cancer survivors (28% Black), Black survivors reported poorer sleep quality, longer sleep onset latency, and higher pain at baseline, compared to White survivors (all p

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Background: Outcome expectancy is an important component of non-specific effect that may play an important role in pain research and clinical care. We sought to evaluate whether pretreatment expectancy predicts pain reduction in cancer survivors receiving electroacupuncture (EA) or battlefield acupuncture (BFA). Methods: We analyzed data from a randomized clinical trial that compared EA and BFA versus wait list control (WLC) for chronic musculoskeletal pain in cancer survivors. Expectancy was measured by the Acupuncture Expectancy Scale (AES) at baseline. Pain severity was assessed using the Brief Pain Inventory (BPI) at baseline and week 12. For each treatment arm, multivariable regression models were used to evaluate the association between pretreatment expectancy and week 12 pain severity, controlling for baseline pain severity, age, sex, race, and education. Results: Among 360 participants enrolled, the mean age was 62.1 years (SD 12.7), with 251 (69.7 %) women and 88 (24.4 %) non-white survivors. Pretreatment expectancy was similar for all groups at baseline (EA: 13.9 ± 3.6; BFA: 13.2 ± 3.7, WLC:12.8 ± 3.3, p = 0.14). Greater pretreatment expectancy was not significantly associated with greater pain reduction in any group, after adjusting for co-variates (EA: Coef. = -0.05, 95 % CI = -0.14 – 0.04, p = 0.28; BFA: Coef. = -0.07, 95 % CI = -0.16 – 0.02, p = 0.15; WLC: Coef. = -0.09, 95 % CI = -0.25 – 0.06, p = 0.23). Conclusions: Pretreatment expectancy did not predict pain reduction for either EA or BFA in cancer survivors. Our study contributes to the interpretation of analgesic effects of EA or BFA, beyond the notion of a mere 'placebo effect'.

Abstract A culturally tailored virtual program could meet the survivorship needs of Asian American women breast cancer survivors (AABC). This study aims to determine the efficacy of a culturally tailored virtual information and coaching/support program (TICAA) in improving AABC’s survivorship experience. A randomized clinical trial (NCT02803593) was conducted from January 2017 to June 2020 among 199 AABC. The intervention group utilized TICAA and the American Cancer Society [ACS] website while the control group used only ACS website for 12 weeks. The outcomes were measured using the SCNS-34SF (needs; primary), the MSAS-SF (symptoms; secondary), and the FACT-B (quality of life; secondary). The data were analyzed using an intent-to-treat approach. The intervention group showed significant reductions in their needs from the baseline (T0) to post 4 weeks (T1) and to post 12 weeks (T2). Although the changes were not statistically significant, the intervention group had decreased symptoms from T0 to T2 while the control group had an increase in their symptoms. The intervention group had a significant increase in their quality of life from T0 to T2. A culturally tailored virtual program could therefore improve quality of life in AABC patients. Trial Registration: To Enhance Breast Cancer Survivorship of Asian Americans (TICAA), NCT02803593, https://clinicaltrials.gov/ct2/show/NCT02803593?titles=TICAA&draw=2&rank=1

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

Abstract Background Patients with local gastric cancer experience a decline of Health-related quality of life (HRQOL) during adjuvant chemotherapy following gastrectomy. Our previous pilot study has indicated the potential of acupuncture to improve HRQOL and control cancer-related symptoms burden. This full-scale trial will focus on confirming the effect of acupuncture for patients with gastric cancer. Methods A multicenter, open-label, three-arm randomized controlled trial with 249 patients will be conducted in China. Patients will be randomly assigned, in a ratio of 1:1:1, to receive high-dose acupuncture (HA, 7 times each chemo-cycle for 3 cycles), low-dose acupuncture (LA, 3 times each chemo-cycle for 3 cycles), or no acupuncture. The acupoints prescription consisted of bilateral ST36, PC6, SP4, DU20, EX-HN3, and selected Back-shu points. Patients-reported Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) and modified Edmonton Symptom Assessment Scale (mESAS) during the therapy will be recorded. Area under curve (AUC, 21 days/cycle × 3 cycles) and average trajectory of FACT-Ga and mESAS will be calculated. The primary outcome will be the differences in AUC of the FACT-Ga Trial Outcome Index (TOI) between HA and LA versus control groups. Secondary outcomes include AUCs and average trajectory of other FACT-Ga subscales and mESAS scores. Discussion This study aims to assess the effect of acupuncture and to compare the difference between LA and HA groups on HRQOL and symptom burden controlling in gastric cancer patients by an adequately powered trial. Trial registration This study was approved by the Ethics Committee of the Guangdong Provincial Hospital of Traditional Chinese Medicine (approval number: BF2018-118) with registration at ClinicalTrials.gov (identifier: NCT04360577).

Children with cancer and their caregivers face physical and psychosocial challenges during and after treatment. Dance/movement therapy (DMT) has been used to improve well-being, promote healthy coping, and mitigate the impact of illness, but limited knowledge exists regarding DMT utilization, delivery, and outcomes in pediatric oncology. This retrospective study aimed to identify reasons for referral to DMT, DMT visit characteristics, key DMT techniques and processes, and clinician-reported outcomes. We examined the electronic medical records of 100 randomly selected pediatric patients (resulting in 1160 visits) who received DMT services between 2011 and 2021. Sociodemographic, clinical, and visit characteristics, referral reasons, and clinician-reported outcomes were reported as frequency and proportions. Qualitative thematic analysis was used to identify key DMT techniques and processes. Among 100 patients (63% female, aged 0–27 years), 77.9% were referred for psychological distress and 19.6% for pain. Two distinct DMT approaches were used during visits: a traditional DMT approach (77%) and a multisensory DMT approach (23%). The most common visit length was 15–25 min (41.6%), followed by sessions of 30–45 min (22.5%) and ≤10 min (18.1%). A total of 61.9% of DMT visits were inpatient and 38.1% outpatient. Of all visits, 8.8% were new and 91.2% were follow-ups. Caregivers were engaged in treatment in 43.7% of visits, and 5.5% of visits focused entirely on the work with the caregiver. DMT intervention focused on self-expression, emotional self-regulation, coping strategies, socialization, and caregiver–child interaction. Clinician-reported outcomes included enhanced coping with hospital experience (58%), improved pain management (27%), improved self-regulation (21%), and increased physical activation (13.2%). The results suggest DMT as a supportive intervention for psychological distress and pain management in pediatric oncology patients and provide insights into DMT practices and outcomes to guide intervention development and future research.

Background: Prehabilitation before thoracic surgery has been found to improve outcomes in patients with cancer; however, COVID-19 presented challenges to access on-site programs. We describe the development, implementation, and evaluation of a synchronous, virtual mind-body prehabilitation program developed in response to COVID-19. Methods: Eligible participants were patients seen at a thoracic oncology surgical department of an academic cancer center, aged 18 years or older with a diagnosis of thoracic cancer and referred at least 1 week before surgery. The program offered 2 45-minute preoperative mind-body fitness classes each week delivered via Zoom (Zoom Video Communications, Inc). We collected data for referrals, enrollment, participation, and evaluated patient-reported satisfaction and experience. We conducted brief semistructured interviews about participants’ experience. Results: Among 278 patients referred, 260 were approached, and of those 197 (76%) patients agreed to participate. Among participants, 140 (71%) attended at least 1 class, with an average of 11 attendees per class. The majority of participants reported being extremely satisfied (97.8%), extremely likely to recommend the classes to others (91.2%), and indicated that classes were very much helpful in preparing for surgery (90.8%). Patients also reported that the classes helped reduce anxiety/stress (94.2%), fatigue (88.5%), pain (80.7%), and shortness of breath (86.5%). Qualitative data further suggest that the program made participants feel stronger, more connected to their peers, and better prepared for surgery. Conclusions: This virtual mind-body prehabilitation program was well received with high satisfaction and benefits and is highly feasible to implement. This approach may help overcome some of the challenges to in-person participation.

IntroductionBattlefield Acupuncture (BFA), a standardized auricular acupuncture protocol, is widely used for pain in the military but is not well-studied in oncology. This study examined cancer survivors who received BFA for pain.MethodsThis is a secondary analysis of a randomized trial that compared the effectiveness of BFA and electroacupuncture vs. usual care for chronic musculoskeletal pain in cancer survivors. This study focused on participants randomized to BFA. Participants received 10 weekly treatments. Needles were placed until one of these stop conditions were satisfied: ten needles were administered; pain severity decreased to ≤1 out of 10; patient declined further needling, or vasovagal reaction was observed. Pain severity was assessed using Brief Pain Inventory. Responders were those with ≥30% pain severity reduction. We examined pain location, BFA stop reason, and pain reduction of participants during the first session. We also examined which factors predicted responder status after the first session (week 1) or the full treatment (week 12).ResultsAmong 143 randomized to BFA, most common pain locations were lower back (30.8%) and knee/leg (18.2%). Of 138 who initiated treatment, 41 (30.0%) received ten needles; 81 (59.1%) achieved pain ≤1; 14 (10.2%) declined further needling; and 1 (0.7%) had vasovagal reaction. BFA reduced pain severity by 2.9 points (95% CI 2.6 to 3.2) after the first session (P

Abstract Background Second malignant neoplasms (SMNs) are one of the most severe late complications after pediatric cancer treatment. However, the effect of genetic variation on SMNs remains unclear. In this study, we revealed germline genetic factors that contribute to the development of SMNs after treatment of pediatric solid tumors. Methods We performed whole‐exome sequencing in 14 pediatric patients with SMNs, including three brain tumors. Results Our analysis revealed that five of 14 (35.7%) patients had pathogenic germline variants in cancer‐predisposing genes (CPGs), which was significantly higher than in the control cohort (p

Oncogenic gene fusions are frequent in childhood cancers but remain poorly understood and untargeted. Here, the authors identify 272 oncogenic fusions in transcriptomics data from 5190 childhood cancer patients, revealing their possible etiologies, their links with tumor progression and evolution, and their potential as therapeutic targets.

Background: Family caregivers of people with cancer report high levels of psychological distress. Yoga, with well-documented mental health benefits, could be a useful intervention to address distress in this population. However, little is known about yoga practices among cancer caregivers. The present study evaluates their interest in and barriers to yoga practice. Methods: We conducted a cross-sectional survey study of family caregivers of cancer patients at five suburban satellite locations of an academic cancer center. Survey items and statistical analyses focused on yoga usage as well as interest in and barriers to yoga practice. Results: Among 539 participants, most were females (64.8%), white (84.2%), and caring for a spouse or partner (54.7%). Interest in practicing yoga among study participants was 42.3%. Increased interest was independently associated with being females (odds ratio [OR] = 3.30, 95% confidence interval [CI] = 1.98–5.51, P < 0.001) and employed (part-time: OR = 2.58, 95% CI = 1.1–6.18, P = 0.03; full-time: OR = 1.77, 95% CI = 1.1–2.01, P = 0.02). Few participants (6.3%) were currently practicing yoga, although 31% had done so in the past. Sixty-one percent of those who had practiced before their loved one's diagnosis stopped practicing yoga afterward. Commonly cited barriers to yoga practice included time constraints (37.3%) and psychological obstacles (33.6%). About a quarter of those who had never practiced yoga lacked awareness of yoga's benefits (26.6%). Conclusion: Despite the low use of yoga, interest in practicing was moderately high, especially among women and employed caregivers. As caregivers face numerous barriers to yoga practice, strategies are needed to overcome these barriers and help them access yoga's health benefits.

Abstract Background Investigating the morphological and functional effects on mandibular asymmetry (MA) is important not only to understand the developmental process of masticatory dysfunction, but also to provide suggestions for evidence-based occlusal treatment. Aim To evaluate three-dimensional temporomandibular joint (TMJ) morphology and its relationship to asymmetrical condylar movement in MA patients. Materials and methods Fifty subjects were divided into MA and control groups (n = 25 each) according to a menton deviation of 4 mm from the mid-sagittal plane. TMJ morphology (condyle, glenoid fossa and TMJ spaces) were evaluated using a three-dimensional analysis programme. Three-dimensional condylar movements (from the sagittal and horizontal planes) were recorded and measured by computerized axiography on protrusion. Side-to-side asymmetry was measured for each parameter. The asymmetry index value was calculated to assess the correlation between TMJ morphology and condylar movement. For the statistical analysis, Wilcoxon’s signed-ranked test, the Mann–Whitney U test, and Spearman’s rank correlation were used. Results Glenoid fossa volume, surface area, anteroposterior length, and condylar volume were significantly smaller, and articular eminence angle, glenoid fossa, and condylar axial angle were significantly larger, on the shifted side of the MA group when compared with those on the non-shifted side and the mean values of the control group (P

Different molecular subtypes defined by specific gene rearrangements have been described for acute lymphoblastic leukaemia (ALL). Here, the authors show that ZNF384 fusion activates FLT3 expression conferring a therapeutic vulnerability for ZNF384- rearranged ALL subtype.

Abstract The current distributions of organisms have been shaped by both current and past geographical barriers. However, it remains unclear how past geographical factors—currently cryptic on the sea floor—affected the current distributions of terrestrial animals. Here, we examined the effects of currently cryptic ancient rivers on current genetic differentiation of the large Japanese wood mouse, Apodemus speciosus, which inhabits islands in the Seto Inland Sea, Japan. Genome-wide polymorphisms were identified by GRAS-Di (Genotyping by Random Amplicon Sequencing, Direct) analysis of 92 A. speciosus individuals. Maximum-likelihood analysis was performed with 94,142 single nucleotide polymorphisms (SNPs) identified by GRAS-Di analyses. Ancient rivers were visualized by Geographic Information System (GIS) channel analysis. Maximum-likelihood analysis showed strong support for the monophyly of each population in the islands in the Seto Inland Sea; it also showed close relationships between Innoshima-Ikuchijima, Ohmishima-Hakatajima-Oshima, Ohmishima-Hakatajima, Ohsakikamijima-Ohsakishimojima, Kamikamagarijima-Shimokamagarijima, and Kurahashijima-Etajima islands. The principal component analyses of the SNPs also supported these relationships. Furthermore, individuals from islands located on the east and west sides of the main stream of the ancient river were clustered on each side with strong support. These phylogenetic relationships were completely congruent with the paleogeographic relationships inferred from ancient rivers. In conclusion, the findings demonstrated that the current distribution of genetically distinct island lineages was shaped by ancient rivers that are currently submerged beneath the Seto Inland Sea, Japan.

Notch1 is frequently activated promoting T-cell acute lymphoblastic leukaemia (T-ALL). Here, the authors show that Notch1 induces oxidative phosphorylation dependency in T-ALL and synergism when inhibiting both mitochondrial complex I and glutaminolysis in preclinical murine and human xenograft models.

Background: Sleep disturbances are common and bothersome among cancer and noncancer populations. Suanzaoren ( Ziziphi Spinosae Semen ) is commonly used to improve sleep, yet its efficacy and safety are unclear. Methods: We systematically searched PubMed, Cochrane Library, and EMBASE from inception through October 5, 2021, to identify randomized trials of Suanzaoren . We included randomized trials comparing Suanzaoren to placebo, medications, cognitive behavioral therapy (CBT), or usual care for improving sleep outcomes in cancer and noncancer patients with insomnia or sleep disturbance. We performed a risk of bias analysis following Cochrane guidelines. Depending on heterogeneity, we pooled studies with similar comparators using fixed- and random-effects models. Results: We included participants with insomnia disorder (N = 785) or sleep disturbance (N = 120) from 9 trials. Compared with placebo, Suanzaoren led to significant subjective sleep quality improvements in participants with insomnia and patients with sleep disturbance combined (standard mean difference −0.58, 95% CI −1.04, −0.11; P

BackgroundCancer survivors represent one of the fastest growing populations in the United States. Unfortunately, nearly 1 in 3 survivors experience anxiety symptoms as a long-term consequence of cancer and its treatment. Characterized by restlessness, muscle tension, and worry, anxiety worsens the quality of life; impairs daily functioning; and is associated with poor sleep, depressed mood, and fatigue. Although pharmacological treatment options are available, polypharmacy has become a growing concern for cancer survivors. Music therapy (MT) and cognitive behavioral therapy (CBT) are evidence-based, nonpharmacological treatments that have demonstrated effectiveness in treating anxiety symptoms in cancer populations and can be adapted for remote delivery to increase access to mental health treatments. However, the comparative effectiveness of these 2 interventions delivered via telehealth is unknown. ObjectiveThe aims of the Music Therapy Versus Cognitive Behavioral Therapy for Cancer-related Anxiety (MELODY) study are to determine the comparative effectiveness of telehealth-based MT versus telehealth-based CBT for anxiety and comorbid symptoms in cancer survivors and to identify patient-level factors associated with greater anxiety symptom reduction for MT and CBT. MethodsThe MELODY study is a 2-arm, parallel-group randomized clinical trial that aims to compare the effectiveness of MT versus CBT for anxiety and comorbid symptoms. The trial will enroll 300 English- or Spanish-speaking survivors of any cancer type or stage who have experienced anxiety symptoms for at least 1 month. Participants will receive 7 weekly sessions of MT or CBT delivered remotely via Zoom (Zoom Video Communications, Inc) over 7 weeks. Validated instruments to assess anxiety (primary outcome), comorbid symptoms (fatigue, depression, insomnia, pain, and cognitive dysfunction), and health-related quality of life will be administered at baseline and at weeks 4, 8 (end of treatment), 16, and 26. Semistructured interviews will be conducted at week 8 with a subsample of 60 participants (30 per treatment arm) to understand individual experiences with the treatment sessions and their impact. ResultsThe first study participant was enrolled in February 2022. As of January 2023, 151 participants have been enrolled. The trial is expected to be completed by September 2024. ConclusionsThis study is the first and largest randomized clinical trial to compare the short- and long-term effectiveness of remotely delivered MT and CBT for anxiety in cancer survivors. Limitations include the lack of usual care or placebo control groups and the lack of formal diagnostic assessments for psychiatric disorders among trial participants. The study findings will help guide treatment decisions for 2 evidence-based, scalable, and accessible interventions to promote mental well-being during cancer survivorship. International Registered Report Identifier (IRRID)DERR1-10.2196/46281

Background: Fatigue is a troublesome symptom in cancer survivors that often results from disrupted sleep. We sought to assess whether two insomnia-focused non-pharmacological interventions are also effective for improving fatigue. Methods: We analyzed data from a randomized clinical trial comparing cognitive behavioral therapy for insomnia (CBT-I) versus acupuncture for insomnia among cancer survivors. Participants were 109 patients who reported insomnia and moderate or worse fatigue. Interventions were delivered over eight weeks. Fatigue was evaluated at baseline, week 8, and week 20 using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). We used both mediation analysis and t-tests to explore the extent to which fatigue reduction was attributable to insomnia response. Results: Compared to baseline, both CBT-I and acupuncture produced significant reductions in total MFSI-SF scores at week 8 (−17.1 points; 95% confidence interval [CI]: −21.1 to −13.1, and −13.2 points; 95% CI: -17.2 to -9.2, respectively, all p

Abstract Pain and insomnia often co-occur and impair the quality of life in cancer survivors. This study evaluated the effect of acupuncture versus cognitive behavioral therapy for insomnia (CBT-I) on pain severity among cancer survivors with comorbid pain and insomnia. Using data from the CHOICE trial that compared acupuncture versus CBT-I for insomnia among cancer survivors, we analyzed the effect of interventions on pain outcomes in 70 patients with moderate to severe baseline pain. Interventions were delivered over eight weeks. We assessed average pain severity (primary outcome) and pain interference at baseline, week 8, and week 20. We further defined insomnia and pain responders as patients who achieved clinically meaningful improvement in insomnia and pain outcomes, respectively, at week 8. We found that compared with baseline, the between-group difference (-1.0, 95% CI -1.8 to -0.2) was statistically significant favoring acupuncture for reduced pain severity at week 8 (-1.4, 95% CI -2.0 to -0.8) relative to CBT-I (-0.4, 95% CI-1.0 to 0.2). Responder analysis showed that 1) with acupuncture, insomnia responders reported significantly greater pain reduction from baseline to week 4, compared with insomnia non-responders (-1.5, 95% CI -2.7 to -0.3); 2) with CBT-I, pain responders reported significantly greater insomnia reduction at week 8, compared with pain non-responders (-4.7, 95% CI -8.7 to -1.0). These findings suggest that among cancer survivors with comorbid pain and insomnia, acupuncture led to rapid pain reductions, which contributed to a decrease in insomnia, whereas CBT-I had a delayed effect on pain, possibly achieved by insomnia improvement.

Introduction Pain, comorbid fatigue and sleep disturbances are common and distressing symptoms for patients with advanced cancer, negatively impacting their quality of life. Clinical guidelines recommend non-pharmacological interventions, including acupuncture and massage, for pain management in adult patients with cancer in adjunct to conventional care. However, high-quality evidence about the comparative effectiveness and long-term durability of these therapies for symptom management is limited.Methods and analysis We describe the design of a two-arm, parallel group, multicentre randomised controlled trial that investigates the use of acupuncture versus massage for musculoskeletal pain among 300 patients with diverse types of advanced cancer. The primary aim is to evaluate the long-term effectiveness (26 weeks from randomisation) of acupuncture vs massage for pain (primary outcome) and comorbid symptoms (fatigue, sleep disturbance and quality of life). The secondary aim is to identify patient-level demographic characteristics (eg, sex, race, age), clinical factors (eg, insomnia, pain severity) and psychological attributes that are associated with a greater reduction in pain for either acupuncture or massage. Patients will receive weekly acupuncture or massage treatments for 10 weeks, followed by monthly booster sessions up to 26 weeks. The primary endpoint will be the change in worst pain intensity score from baseline to 26 weeks. We will collect validated patient-reported outcomes at multiple time points over 26 weeks.Ethics and dissemination The Institutional Review Board at Memorial Sloan Kettering Cancer Center in New York approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. Our findings will help patients and healthcare providers make informed decisions about incorporating non-pharmacological treatments to manage pain for patients with advanced cancer.Trial registration number NCT04095234.

Nucleoside analogs (NNA), such as acyclovir (ACV) and ganciclovir (GCV), are widely used as anti-virals to treat herpes virus infection. Here, Nishii et al. show that diphosphatase NUDT15 hydrolyzes ACV and GCV, therewith reducing NNA activity in vitro and link NUDT15 variation to inter-patient variability in ACV and GCV therapeutic effects.

There is growing evidence for an inherited basis of susceptibility to childhood acute lymphoblastic leukemia. Genomewide association studies by us and others have identified non-coding acute lymphoblastic leukemia risk variants at the ARID5B gene locus, but the molecular mechanisms linking ARID5B to normal and malignant hematopoiesis remain largely unknown. Using a Vav1-driven transgenic mouse model, we characterized the role of Arid5b in hematopoiesis in vivo. Arid5b overexpression resulted in a dramatic reduction in the proportion of circulating B cells, immature, and mature Bcell fractions in the peripheral blood and the bone marrow, and also a decrease of follicular B cells in the spleen. There were significant defects in B-cell activation upon Arid5b overexpression in vitro with hyperactivation of B-cell receptor signaling at baseline. In addition, increased mitochondrial oxygen consumption rate of naïve or stimulated B cells of Arid5b-overexpressing mice was observed, compared to the rate of wild-type counterparts. Taken together, our results indicate that ARID5B may play an important role in B-cell development and function.

Purpose: Many cancer survivors experience cancer-related cognitive impairment (CRCI). We conducted a randomized controlled pilot trial of 2 types of yoga practice and evaluated their effects on participants’ objective cognitive function. Methods: Sedentary breast or ovarian cancer survivors were randomized to practice either restorative yoga (with more meditative practice and minimal physical exertion) or vigorous yoga (with considerable physical exertion and minimal meditative practice) in 60-minute supervised sessions 3 times a week for 12 weeks, followed by 12 weeks of home practice. We used the NIH Toolbox Cognition Domain to evaluate participants at baseline, week 12, and week 24. Results: We enrolled 35 participants. For women in the restorative yoga group, overall cognitive function was statistically significantly improved at weeks 12 and 24 compared to baseline ( P = .03 and 0.004; Cohen’s D = 0.3 and 0.5). Fluid cognitive function also significantly improved at weeks 12 and 24 ( P = .02 and 0.0007; Cohen’s D = 0.3 and 0.6), whereas improvements in crystallized cognition were not significant. For women in the vigorous yoga group, significant improvement was only seen in tasks of crystallized cognition at week 24 ( P = .03; Cohen’s D = 0.5). Between-group comparisons showed that at week 24, women in the restorative yoga group had significantly higher scores on fluid cognition tasks. Conclusions: Patients who participated in yoga practice demonstrated improvement in objective cognitive function over time. Restorative yoga may be more effective in improving fluid cognitive function at week 24 when compared to vigorous yoga. These promising findings should be confirmed in definitive studies. Trial registration: Clinicaltrials.gov; NCT02305498 (Date Registered: December 2, 2014)

Rearrangements that drive ectopic MEF2C expression have recurrently been found in patients with human early thymocyte progenitor acute lymphoblastic leukemia (ETP-ALL). Here, we show high levels of MEF2C expression in patients with ETP-ALL. Using both in vivo and in vitro models of ETP-ALL, we demonstrate that elevated MEF2C expression blocks NOTCH-induced T cell differentiation while promoting a B-lineage program. MEF2C activates a B cell transcriptional program in addition to RUNX1, GATA3, and LMO2; upregulates the IL-7R; and boosts cell survival by upregulation of BCL2. MEF2C and the Notch pathway, therefore, demarcate opposite regulators of B- or T-lineage choices, respectively. Enforced MEF2C expression in mouse or human progenitor cells effectively blocks early T cell differentiation and promotes the development of biphenotypic lymphoid tumors that coexpress CD3 and CD19, resembling human mixed phenotype acute leukemia. Salt-inducible kinase (SIK) inhibitors impair MEF2C activity and alleviate the T cell developmental block. Importantly, this sensitizes cells to prednisolone treatment. Therefore, SIK-inhibiting compounds such as dasatinib are potentially valuable additions to standard chemotherapy for human ETP-ALL.

Abstract Chronic inflammation has been a proposed mechanism of resistance to aromatase inhibitors in breast cancer. Stratifying by HER2 status, a matched case-control study from the Wellness After Breast Cancer-II cohort was performed to assess whether or not elevated serum inflammatory biomarkers (C-Reactive protein [CRP], interleukin-6 [IL-6], and serum amyloid A [SAA]) and/or the presence of a high-risk IL-6 promoter genotype were associated with recurrence of hormone receptor positive (HR+) early breast cancer. Estrogen levels were also measured and correlated with biomarkers and disease outcomes. CRP and SAA were significantly associated with an increased risk of recurrence in the HR+/HER2− group, but not the HR+/HER2+ group. Mean serum estrogen levels were non-significantly elevated in patients who relapsed vs. non-relapsed patients. Surprisingly, high-risk IL-6 promoter polymorphisms were strongly associated with HER2+ breast cancer relapse, which has potential therapeutic implications, as elevated intracellular IL-6 has been associated with trastuzumab resistance in pre-clinical models.

Chronic pain is common and debilitating in cancer survivors. Tibetan herbal pain-relieving plaster is used as an external analgesic to treat musculoskeletal pain in China; however, its safety and efficacy have not been evaluated via clinical trials in cancer survivors. We designed this Phase II randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04916249) to assess the efficacy and safety of the pain-relieving plaster for temporary pain relief among cancer survivors with chronic musculoskeletal pain. Under ethical approval from the Institutional Review Board at the Memorial Sloan Kettering Cancer Center, we will enroll eligible cancer survivors who have a clinical diagnosis of moderate to severe chronic musculoskeletal pain in this study. We use a central randomization system to allocate the eligible participants to either the treatment or the control group in a 1:1 ratio, with stratification by baseline opioid use. We will instruct the participants to apply the herbal patch (Tibetree Pain-Relieving Plaster, Tibet Cheezheng Tibetan Medicine Co. Ltd., Tibet, China) or placebo patch daily at the focal area with worst pain for 14 consecutive days. Study physician, participant, outcome assessor, and biostatistician are blinded to the group allocation. The primary outcome is pain severity measured by the Brief Pain Inventory on Days 2–7. Secondary outcomes include changes in insomnia, anxiety, depression, fatigue, pressure pain threshold, pain medication use, and global impression of change. We will also monitor the adverse events throughout the study period. Statistical analysis will follow the intention-to-treat principle and linear mixed modeling will be used. With rigorous design and implementation, this randomized, placebo-controlled trial will provide the initial evidence on the efficacy and safety of the pain-relieving plaster for pain relief among cancer survivors with chronic musculoskeletal pain.

Background: Shenling Baizhu San (SBS), a well-known Chinese medicine herbal formula, has been widely used for treating chronic diarrhea for thousands of years. However, the efficacy and safety of SBS in treating chronic diarrhea have not been fully assessed. Objective: This study evaluates the efficacy and safety of the herbal formula SBS in symptomatic relief of chronic diarrhea. Methods: English and Chinese language databases (PubMed, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Data, and SinoMed electronic databases) were searched through April 2020 for relevant randomized controlled trials (RCTs). The outcomes in these RCTs included stool frequency, stool consistency, patient-reported satisfaction of chronic diarrhea treatment, quality of life and adverse events. Paired reviewers independently extracted data and conducted qualitative and quantitative analyses. The Cochrane revised risk of bias RoB-2 tool was applied to assess the risk of bias for each trial whereas the RevMan 5.3 software was used for outcomes data synthesis and meta-analysis. Mean difference (MD) and the 95% confidence interval (CI) were used to measure continuous data. The dichotomous data were analyzed via the relative risk (RR) with 95% CIs. Results: Fourteen RCTs including 1158 participants (54% males) with chronic diarrhea were included. Shenling Baizhu San combined with or without conventional medicine (CM) was associated with greater patient-reported satisfaction than CM alone. There was no increased risk of adverse events (AEs) during treatment. Conclusion: Treatment with SBS was associated with significant improvement in patient-reported satisfaction, irrespective of conventional medicine use. Rigorous and powered RCTs with objective outcome measures are needed to confirm the effects of SBS in specific gastrointestinal disease populations with chronic diarrhea symptoms. Systematic review registration number (PROSPERO): CRD42020178073

Background: Arthralgia is a common and debilitating toxicity of aromatase inhibitors (AI) that leads to premature drug discontinuation. We sought to evaluate the clinical and genetic risk factors associated with AI-associated arthralgia (AIAA). Methods: We performed a cross-sectional study among postmenopausal women with stage 0-III breast cancer who were prescribed a third-generation AI for adjuvant therapy. The primary outcome was patient-reported AIAA occurrence. We extracted and assayed germline DNA for single nucleotide polymorphisms (SNPs) of genes implicated in estrogen and inflammation pathways. Multivariable logistic regression models examined the association between demographic, clinical, and genetic factors and AIAA. Analyses were restricted to White participants. Results: Among 1049 White participants, 543 (52%) reported AIAA. In multivariable analyses, women who had a college education [Adjusted Odds Ratio (AOR) 1.49, 95% Confidence Interval (CI) 1.00–2.20], had a more recent transition into menopause (

B-cell acute lymphoblastic leukaemia (B-ALL) is a common childhood cancer. Here, the authors conducted a meta-analysis with four genome-wide association studies, totalling 5,321 cases and 16,666 controls of European descent, identifying B-ALL risk loci, whose integration with epigenomic profiling indicates cell-cycle and B-cell development deregulation as central mechanisms in B-ALL susceptibility, often in a subtype-specific fashion.

BackgroundPer- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that have become globally ubiquitous in humans and the environment. In utero PFAS exposure is associated with neurodevelopmental effects; however, the mechanism is poorly understood. Brain-derived neurotrophic factor (BDNF) signaling is critical to fetal neurodevelopment during pregnancy and maintains important regulatory roles later in life. This study aims to characterize placental BDNF signaling and investigate whether PFAS exposure disrupts the signaling pathway in placental trophoblast cells.MethodsThe expression and localization of BDNF receptors–p75NTR and TrkB–in first trimester and term human placentas and trophoblast cells were investigated by immunofluorescence staining. To assess the effects of PFAS exposure on the BDNF pathway, BeWo cells were treated with PFAS mixtures that mimicked blood levels in a highly exposed population and major PFAS compounds in the mixture at 0.01, 0.1, 1, and 10 µM concentrations. Changes in pro-BDNF levels and phosphorylation of TrkB receptors were examined by Western blot.ResultsIn first trimester human placentas, TrkB and p75NTR receptors were primarily localized to syncytiotrophoblast and cytotrophoblast cells. At term, TrkB and p75NTR receptors were primarily observed in the placental villous stroma. TrkB receptor staining in trophoblasts was reduced at term, while p75NTR receptor staining was negative. TrkB receptors were confined to the nuclear and perinuclear spaces, and phosphorylation occurred at the Tyr816 residue in BeWo cells. Exposure to PFOS, PFOA, PFBS, and the six-PFAS mixture did not significantly affect BDNF levels or activation (phosphorylation) of TrkB. Treating cells with 1 μM and 10 μM of PFNA resulted in increased TrkB phosphorylation compared to unexposed controls, but BDNF levels were unchanged.ConclusionsBDNF receptors are present in different regions of human placental villi, indicating diverse functions of BDNF signaling in placental development. Our findings suggest that the BDNF pathway in placental trophoblast cells is not disrupted by exposures to PFOS, PFOA, PFBS, and a PFAS mixture, but may be affected by PFNA exposures. Further investigation is needed on how PFAS affects other critical signaling pathways during fetal neurodevelopment.

Chemotherapy dosages are often compromised, but most reports lack data on dosages that are actually delivered. In two consecutive acute lymphoblastic leukemia trials that differed in their asparaginase formulation, native E. coli L-asparaginase in St. Jude Total 15 (T15, n=365) and pegaspargase in Total 16 (T16, n=524), we tallied the dose intensities for all drugs on the low-risk or standard-risk arms, analyzing 504,039 dosing records. The median dose intensity for each drug ranged from 61-100%. Dose intensities for several drugs were more than 10% higher on T15 than on T16: cyclophosphamide (P

Introduction: Spleen Deficiency Syndrome (SDS) is recognized as one of the most common Traditional Chinse Medicine (TCM) syndromes in patients with colorectal cancer (CRC). However so far there is no existing patient-reported outcome (PRO) to evaluate SDS. Our study aimed to develop and validate a PRO TCM-SDS scale for CRC in China. Methods: We developed an initial 8-item TCM-SDS scale for CRC based on literature review and consultation with experts. We then pilot tested the scale ( n = 40) and performed item revision. We conducted a survey study among CRC patients from oncology clinics at a TCM Hospital to further determine the reliability and validity of the scale. Results: Among 100 patients finally enrolled and analyzed in the survey study, 46% were female with median age of 60 years old, 77% had left side tumors and 23% had stage IV disease. Factor loading indicated that there were three domains within TCM-SDS scale. The final TCM-SDS scale involves 5 items including “ I feel loss of appetite,” “I feel abdomen fullness,” “I feel my arms and legs lack strength,” “I feel short of breath when talking,” and “My stool is formless” (Cronbach’s alpha coefficient 0.76). We calculated the total score of the scale by summing the 5 individual items and normalizing them to a value maximum of 10, with higher scores indicating greater burden of spleen deficiency syndrome. The average spleen deficiency score for all patients was 3.55 ± 1.54. Among them, those who had stage IV disease had higher scores than stage I-III patients (4.30 vs 3.38, P = .015). Test-retest reliability after 2 weeks showed Pearson coefficient of 0.67 and all items were highly related ( P

Background: Musculoskeletal pain is a common and debilitating condition for cancer patients. Existing therapies for these pain conditions have substantial limitations. To identify an integrative approach to pain management, we conducted a systematic review to evaluate the safety and efficacy of a Tibetan herbal-based topical agent, CheeZheng Pain Relieving Plaster (PRP), for the treatment of osteoarthritis (OA) pain. Methods: We extracted citations from PubMed and Chinese databases (CNKI, WanFang Data, and CQVIP). We included randomized clinical trials evaluating the effectiveness and safety of CheeZheng PRP compared to conventional OA pain treatments. Results: Twenty-two randomized clinical trials (n = 2556 participants) compared CheeZheng PRP against nonsteroidal anti-inflammatory drugs (11), glucosamine (2), intraarticular corticosteroid (2), hyaluronic acid injections (6), and acetaminophen (1). Ten studies found a statistically greater effectiveness (assessed by ≥30% reduction in symptom severity) of CheeZheng PRP in improving OA pain (measured by the Visual Analogue Scale), stiffness, and function compared to control. Ten studies reported that 4.8% of participants experienced application site skin irritation that resolved after discontinuing the plaster. Randomization was not sufficiently described in most studies, and no placebo-controlled trials were identified. Conclusions: There is promising evidence for the safety and clinical effectiveness of CheeZheng PRP to treat OA; however, lack of placebo control and unclear descriptions of randomization increase the potential risk for bias. Future randomized, placebo-controlled trials are needed to establish the safety and efficacy of CheeZheng PRP for pain management in oncology settings.

Background: Cancer patients often experience decreased quality of life during chemotherapy. This study aimed to determine the preliminary efficacy and safety of Reishi & Privet Formula (RPF) for maintaining quality of life among patients with non–small cell lung cancer (NSCLC) undergoing chemotherapy. Methods: We conducted a phase II randomized, double-blind, placebo-controlled clinical trial in China. Adults with NSCLC scheduled to receive chemotherapy were randomly assigned (3:1 ratio) to receive oral RPF (3.36 g/day) or placebo daily for 6 weeks. The main outcome was the Functional Assessment of Cancer Therapy–Lung (FACT-L). We evaluated RPF’s safety profile using the Common Terminology Criteria for Adverse Events and assessed changes in outcome measures from baseline to weeks 3 and 6 using a linear mixed effects model. Results: We enrolled 82 participants across 8 cancer centers in China. The median age was 59 years, 56 (68%) had advanced cancer. Compared with the placebo group, the RPF group had nonstatistically significant higher quality of life as measured by the FACT-L total score ( P = .086) over 2 cycles of chemotherapy. The RPF group was associated with a nonsignificant better general health ( P = .050) and emotional well-being ( P = .090) than the placebo group. Adverse events rates did not differ between groups. Conclusions: This study demonstrated preliminary safety and suggests a promising trend in RPF’s effect on maintaining quality of life and emotional well-being among NSCLC patients undergoing chemotherapy. Future adequately powered randomized-controlled trials are needed to verify the efficacy and safety of RPF in cancer patients undergoing chemotherapy.