Effect of genetic liability to migraine and its subtypes on breast cancer: a mendelian randomization study.

BACKGROUND: The relationship between migraine and breast cancer risk has generated conflicting findings. We attempted to assess the association between migraine and breast cancer risk using Mendelian randomization (MR) analysis. METHODS: We selected genetic instruments associated with migraine from a recently published genome-wide association studies (GWAS). Inverse variant weighted (IVW) analysis was adopted as the main method, and we also performed the weighted-median method and the MR‒Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR Robust Adjusted Profile Score (MR-RAPS) methods as supplements. RESULTS: Our MR suggested that any migraine (AM) was a risk factor for overall breast cancer (IVW: odds ratio (OR) = 1.072, 95% confidence intervals (CI) = 1.035-1.110, P = 8.78 × 10- 5, false discovery rate (FDR) = 7.36 × 10- 4) and estrogen receptor-positive (ER+) breast cancer (IVW: OR = 1.066, 95% CI = 1.023-1.111, P = 0.0024; FDR = 0.0108) but not estrogen receptor-negative (ER-) breast cancer. In its subtype analysis, women with a history of migraine without aura (MO) had an increased risk of ER- breast cancer (IVW: OR = 1.089, 95% CI = 1.019-1.163, P = 0.0118, FDR = 0.0354), and MO was suggestively associated with the risk of overall breast cancer (FDR > 0.05 and IVW P < 0.05). No significant heterogeneity or horizontal pleiotropy was found in the sensitivity analysis. CONCLUSION: This study suggested that women with AM have an increased risk of overall breast cancer and ER + breast cancer. MO was suggestively associated with the risk of overall breast cancer and ER- breast cancer.

Central nervous system involvement at initial diagnosis of extranodal NK/T-cell lymphoma: a retrospective study of a consecutive 12-year case series.

Patients with central nervous system (CNS) involvement at initial diagnosis of extranodal NK/T-cell lymphoma (ENKTL) are exceedingly rare, and the clinicopathologic features of CNS involvement have not been well characterized. In this study, we reviewed 662 patients with ENKTL from August 2008 to September 2019. Their clinical and pathological features, treatments, and survival outcomes were analyzed. The median follow-up time was 72 months. Nine of 662 (1.4%) patients were diagnosed with CNS involvement. Among them, the median age was 37 years, and seven patients were male. All patients had positive EBV-DNA, and three patients were asymptomatic at the time of diagnosis with CNS involvement. Common extranodal involved sites included bone, paranasal sinuses, breast, kidney, adrenal gland, and bone marrow. All patients were positive for cytoplasmic CD3ε, cytotoxic granule proteins, and EBER and negative for CD20. All patients received intrathecal chemotherapy and at least one cycle of systemic chemotherapy. Seven patients had died and two were still alive by the last follow-up. The median overall survival (OS) in patients with CNS involvement at initial diagnosis of ENKTL was 9 months, and the 1-year OS was 44.4%. Five patients achieved a complete response after asparaginase-based chemotherapy; two were still alive, one died of systemic progression, one died of ENKTL-associated hemophagocytic syndrome, and one died of treatment-related infections. In conclusion, CNS involvement at initial diagnosis of ENKTL is extremely rare with poor prognosis. There is no standard treatment, and asparaginase-based chemotherapy combined with intrathecal chemotherapy might yield good efficacy.

First-line LVDP (L-asparaginase, etoposide, dexamethasone, and cisplatin) regimen combined with radiotherapy is effective for early-stage extranodal natural killer/T-cell lymphoma, nasal type.

Chemotherapy combined with radiotherapy could reduce the risk of recurrence in early-stage extranodal NK/T lymphoma (ENKTL). However, the optimal combined chemotherapy regimen is still unknown. Our previous study reported that LVDP (L-asparaginase, etoposide, dexamethasone, and cisplatin) combined with radiotherapy was a potentially effective and safe treatment regimen for early-stage ENKTL. This study further validated the efficacy and safety of LVDP chemotherapy combined with radiation for early-stage ENKTL with more patients and longer follow-up. We retrospectively studied 112 patients with early-stage ENKTL from September 2010 to September 2019. All patients received the LVDP regimen, and 101 of them received radiotherapy. The patients' characteristics, treatment responses, survival outcomes, prognostic factors, and toxicities were analyzed. The median follow-up was 60 months (range, 4 to 117). All patients received median 4 cycles of the LVDP chemotherapy. At the end of therapy, the objective response rate and complete response rate were 88.3% and 77.6%, respectively. The 3- and 5-year OS were 79.6% and 73.2%, and the 3- and 5-year PFS were 75.4% and 71.6%, respectively. Among them, the LVDP regimen combined with radiotherapy yielded more favorable treatment outcomes (the 3-year OS and PFS were 83.1% and 80.8%). The most common severe hematologic toxicity was leukopenia (25% grade 3/4), and the most common severe non-hematologic toxicity was increased transaminase (4.5% grade 3/4). No pancreatitis or treatment-related death occurred. The LVDP regimen combined with radiotherapy had a good therapeutic response and long-term survival with tolerable toxicity for patients with early-stage ENKTL.

The value of prognostic nutritional index in nasal-type, extranodal natural killer/T-cell lymphoma.

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive disorder with heterogeneous clinical characteristics and poor prognosis. The combined value of baseline serum albumin level and absolute peripheral lymphocyte count showed prognostic information in a variety of malignancies, but its evidence is limited in ENKTL. The purpose of this study is to evaluate the impact of prognostic nutritional index (PNI) in ENKTL, and to provide some nutritionally and immunologically relevant information for better risk stratification. We conducted a retrospective study in 533 patients newly diagnosed with ENKTL. The PNI was calculated as albumin (g/L) + 5 × lymphocyte count (109/L). The optimal cutoff values for serum albumin and lymphocyte count were 40.6 g/L and 1.18 × 109/L, respectively, and 47.3 for PNI. After a median follow-up of 70 months, the 5-year overall survival (OS) and progression-free survival (PFS) were 56.2% and 49.5%, respectively. Patients in low PNI group had more unfavorable clinical features, and tended to have worse 5-year OS and PFS compared with those in high PNI group. According PNI-associated prognostic score, patients were classified into different risk groups. Significant difference has been found in 5-year OS and PFS in different risk groups. When PNI and PNI-associated prognostic score were superimposed on the International Prognostic Index (IPI), prognostic index of natural killer lymphoma (PINK), or nomogram-revised risk index (NRI) categories, the PNI and PNI-associated prognostic score provided additional prognostic information. Therefore, PNI and PNI-associated prognostic score could be independent prognostic factors for ENKTL and may be useful for risk stratification and clinical decision-making.

Nomograms to predict progression of disease within 24 months in patients with localized natural killer/T-cell lymphoma.

Aims: Progression of disease within 24 months (POD24) is associated with poor survival in some subtypes of lymphoma.The aim is to identify high-risk patients with localized extranodal natural killer/T-cell lymphoma (ENKTL) and to define clinical factors associated with the risk of early recurrence after antitumor treatment. Methods: The authors retrospectively analyzed 330 cases with localized ENKTL, of which 89 experienced POD24. Results: The 5-year overall survival of the POD24 group was extremely inferior to that of the non-POD24 group. Risk factors for POD24 were Eastern Cooperative Oncology Group performance status ≥2, response evaluation (non-complete remission) after first-line treatment and elevated lactate dehydrogenase concentrations. Also, higher Epstein-Barr virus DNA titer was related to POD24. Based on these data with or without the availability of Epstein-Barr virus DNA, the authors conducted two nomograms to predict POD24, which showed good accuracy with high C statistics. Conclusion: The results showed that POD24 could serve as a marker to identify patients whose medical needs were unmet in ENKTL.

Ten-Year Change in Disorders of Consciousness: A Bibliometric Analysis.

Objectives: Disorders of consciousness (DoC) is a dynamic and challenging discipline, presenting intriguing challenges to clinicians and neurorehabilitation specialists for the lack of reliable assessment methods and interventions. Understanding DoC keeps pace with scientific research is urgent to need. We quantitively analyzed publications on DoC over the recent 10 years via bibliometrics analysis, to summarize the intellectual structure, current research hotspots, and future research trends in the field of DoC. Methods: Literature was obtained from the Science Citation Index Expanded of Web of Science Core Collection (WoSCC). To illustrate the knowledge structure of DoC, CiteSpace 5.8.R3 was used to conduct a co-occurrence analysis of countries, institutions, and keywords, and a co-citation analysis of references and journals. Also, Gephi 0.9.2 contributed to the author and co-cited author analysis. We found the most influential journals, authors, and countries and the most talked about keywords in the last decade of research. Results: A total of 1919 publications were collected. Over the past 10 years, the total number of annual publications has continued to increase, with the largest circulation in 2018. We found most DoC research and close cooperation originated from developed countries, e.g., the USA, Canada, and Italy. Academics from Belgium appear to have a strong presence in the field of DoC. The most influential journals were also mainly distributed in the USA and some European countries. Conclusions: This bibliometric study sheds light on the knowledge architecture of DoC research over the past decade, reflecting current hotspots and emerging trends, and providing new insights for clinicians and academics interested in DoC. The hot issues in DoC were diagnosing and differentiating the level of consciousness, and detecting covert awareness in early severe brain-injured patients. New trends focus on exploring the recovery mechanism of DoC and neuromodulation techniques.

A comprehensive and clinical-oriented evaluation criteria based on DVH information and gamma passing rates analysis for IMRT plan 3D verification.

PURPOSE: To accomplish the 3D dose verification to IMRT plan by incorporating DVH information and gamma passing rates (GPs) (DVH_GPs) so as to better correlate the patient-specific quality assurance (QA) results with clinically relevant metrics. MATERIALS AND METHODS: DVH_GPs analysis was performed to specific structures of 51 intensity-modulated radiotherapy (IMRT) treatment plans (17 plans each for oropharyngeal neoplasm, esophageal neoplasm, and cervical neoplasm) with Delta4 3D dose verification system. Based on the DVH action levels of 5% and GPs action levels of 90% (3%/2 mm), the evaluation results of DVH_GPs analysis were categorized into four regions as follows: the true positive (TP) (%DE> 5%, GPs < 90%), the false positive (FP) (%DE ≤ 5%, GPs < 90%), the false negative (FN) (%DE> 5%, GPs ≥ 90%), and the true negative (TN) (%DE ≤ 5%, GPs ≥ 90%). Considering the actual situation, the final patient-specific QA determination was made based on the DVH_GPs evaluation results. In order to exclude the impact of Delta4 phantom on the DVH_GPs evaluation results, 5 cm phantom shift verification was carried out to structures with abnormal results (femoral heads, lung, heart). RESULTS: In DVH_GPs evaluation, 58 cases with FN, 5 cases with FP, and 2 cases with TP were observed. After the phantom shift verification, the extremely abnormal FN of both lung (%DE = 21.52%±8.20%) and heart (%DE = 19.76%) in the oropharyngeal neoplasm plans and of the bilateral formal heads (%DE = 26.41%±13.45%) in cervical neoplasm plans disappeared dramatically. DVH_GPs analysis was performed to all evaluation results in combination with clinical treatment criteria. Finally, only one TP case from the oropharyngeal neoplasm plans and one FN case from the esophageal neoplasm plans did not meet the treatment requirements, so they needed to be replanned. CONCLUSION: The proposed DVH_GPs evaluation method first make up the deficiency of conventional gamma analysis regarding intensity information and space information. Moreover, it improves the correlation between the patient-specific QA results and clinically relevant metrics. Finally, it can distinguish the TP, TN, FP, and FN in the evaluation results. They are affected by many factors such as the action levels of DVH and GPs, the feature of the specific structure, the QA device, etc. Therefore, medical physicist should make final patient-specific QA decision not only by taking into account the information of DVH and GPs, but also the practical situation.

Effects of land vs water jump exercise: Implications for exercise design targeting bone health.

PURPOSE: To quantify ground reaction force (GRF), osteogenic index (OI), muscle activity, and blood lactate levels during continuous jumping performed in water and on land. METHODS: Thirteen post-menopausal women (59.5 ± 6.8 years) performed two bouts of jumping, on land (LND) and in water at a depth of 1 m (WEX). Each 10-minute, 40-second bout consisted of 2 consecutive sets of squat, lunge, jumping jax, countermovement, and single legged jumps as intervals: 10 seconds maximal effort and 60 seconds recovery at 50% of heart rate reserve (HRR). Pre- and post-exercise lower extremity rate of perceived exertion (RPE) was recorded, and 10-µL earlobe blood samples were collected to assess lactate concentration. During exercise, data were collected for electromyography, GRF, and heart rate. Total GRF (TGRF) and total muscular activity (TMA) during each 10 seconds of jumping were measured. OI for one bout of continued jumps was determined by averaging GRF·ln (number of jumps + 1). RESULTS: There were no differences between WEX and LND for percent HRR and RPE. TGRF, OI, TMA, and lactate concentration on LND jumps were significantly higher than WEX. CONCLUSION: At similar cardiorespiratory and RPE levels, the lower impact loading of 10 minutes 40 seconds of interval continuous jumping exercise in 1-m depth was less osteogenic than on land. However, one daily bout of water jumping, 5 days per week resulted in a similar OI as 3 days of jumping on land. WEX might substitute or provide an adjunct to LND exercise to promote bone health.

Primary and Orthotopic Murine Models of Nasopharyngeal Carcinoma Reveal Molecular Mechanisms Underlying its Malignant Progression.

Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein-Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV- (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC-associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene-edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV-coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV- and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.

Radiomics-guided checkpoint inhibitor immunotherapy for precision medicine in cancer: A review for clinicians.

Immunotherapy using immune checkpoint inhibitors (ICIs) is a breakthrough in oncology development and has been applied to multiple solid tumors. However, unlike traditional cancer treatment approaches, immune checkpoint inhibitors (ICIs) initiate indirect cytotoxicity by generating inflammation, which causes enlargement of the lesion in some cases. Therefore, rather than declaring progressive disease (PD) immediately, confirmation upon follow-up radiological evaluation after four-eight weeks is suggested according to immune-related Response Evaluation Criteria in Solid Tumors (ir-RECIST). Given the difficulty for clinicians to immediately distinguish pseudoprogression from true disease progression, we need novel tools to assist in this field. Radiomics, an innovative data analysis technique that quantifies tumor characteristics through high-throughput extraction of quantitative features from images, can enable the detection of additional information from early imaging. This review will summarize the recent advances in radiomics concerning immunotherapy. Notably, we will discuss the potential of applying radiomics to differentiate pseudoprogression from PD to avoid condition exacerbation during confirmatory periods. We also review the applications of radiomics in hyperprogression, immune-related biomarkers, efficacy, and immune-related adverse events (irAEs). We found that radiomics has shown promising results in precision cancer immunotherapy with early detection in noninvasive ways.

Multiple sclerosis and breast cancer risk: a meta-analysis of observational and Mendelian randomization studies.

Background: Several observational studies have explored the relationships between multiple sclerosis (MS) and breast cancer; however, whether an association exists remains unknown. Methods: We conducted a meta-analysis of observational studies and Mendelian randomization (MR) based on genetic variants to identify the relationship between MS and breast cancer. The observational studies were searched from PubMed, Embase, Web of Science, and Scopus to assess the relationship between MS and breast cancer from inception to 07 Nov 2022. Moreover, we explored the association between genetically pre-disposed MS and breast cancer risk based on an MR study. The summary analysis for MS from two separate databases [International Multiple Sclerosis Genetics Consortium (IMSGC), FinnGen] and the summary analysis for breast cancer from Breast Cancer Association Consortium. Results: Fifteen cohort studies involving 173,565 female MS patients were included in this meta-analysis. The correlation between MS and breast cancer was not statistically significant [relative ratio (RR) = 1.08, 95% confidence interval (CI) = 0.99-1.17]. In the MR analysis, we did not observe causal associations of genetically determined MS with breast cancer and its subtypes from both the IMSGC and FinnGen datasets. Conclusion: The meta-analysis of observational and MR based on genetic variants does not support the correlation between MS and breast cancer.

A neutrophil/lymphocyte Ratio as a Significant Predictor for Patients with low-risk and early-stage Extranodal NK-T-cell Lymphoma.

Purpose: The neutrophil/lymphocyte ratio (NLR) is a novel prognostic marker in several malignancies, whereas its function in patients with early-stage extranodal NK-T-cell lymphoma (ENKTL) hasn't been explored. Therefore, we expolored the predictive value of NLR for early-stage ENKTL in this study. Methods: We evaluated the prognostic value of NLR in 132 patients with early-stage ENKTL based on L-asparaginase-containing regimens. Their characteristics, treatment responses, survival outcomes, prognostic factors, and the prognostic value of NLR were analyzed. Results: All patients were followed up for median 54 months. The optimal NLR cutoff value was 3.77 by receiver operating curve(ROC). For all patients, the complete response (CR) and the overall response rate (ORR) were 74.2% and 85.6%. Patients with NLR < 3.77 had higher CR and ORR than patients with NLR ≥ 3.77(CR, 81% vs. 53.1%; ORR, 90% vs. 71.9%). For all patients, the 3-year overall survival (OS) and progression-free survival (PFS) based on L-asparaginase-containing chemotherapy were 80.4% and 76%. Patients with NLR < 3.77 had better survival outcomes than patients with NLR ≥ 3.77(3-year OS, 86.9% vs. 60.3%, p = 0.002; 3-year PFS, 81.8% vs. 54.5%, p = 0.001). By univariate and multivariate analyses, NLR ≥ 3.77 was an independent poor prognostic factor for both OS and PFS. Additionally, NLR ≥ 3.77 was associated with poor survival outcomes in patients with low-risk International Prognostic Index (IPI) and Prognostic Index of Natural Killer lymphoma with Epstein-Barr virus (PINK-E). Conclusion: A high NLR is a poor prognostic marker of survival in patients with early-stage ENKTL, and could be applied to risk-stratify for low-risk patients.

Prognostic significance of the systemic immune-inflammation index in patients with extranodal natural killer/T-cell lymphoma.

Background: The systemic immune-inflammation index (SII) is based on the neutrophil, platelet, and lymphocyte counts, and has been identified as a prognostic marker in multiple types of cancer. However, the potential value of the SII for predicting survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTCL) has not been investigated thus far. Method: This study included 382 patients with ENKTCL treated with asparaginase-base regimens from 2021 to 2017 in West China Hospital (Chengdu, China). Clinical and demographic variables, as well as the prognostic value of the SII, were analyzed using Cox proportional hazards regression analysis. Results: The complete and objective response rates were 55.8% and 74.9%, respectively. Patients with high SII were associated with a lower rate of complete response, higher rate of B symptoms, and serum lactate dehydrogenase levels above or equal to the upper limits of normal (p < 0.01). Patients with low SII were linked to better overall survival and progression-free survival than those with high SII (p < 0.01). Patients with early-stage disease or prognostic model for natural killer lymphoma with Epstein-Barr virus, defined as the low-risk group, could be further stratified according to the SII (p < 0.01). Negative prognostic factors were determined using the Cox proportional hazards regression analysis, which identified four variables: Eastern Cooperative Oncology Group performance status score ≥2, Stage III/IV disease, positivity for Epstein-Barr virus DNA in plasma, and high SII. Predictive nomograms for the prediction of 3- and 5-year overall survival, as well as progression-free survival, were constructed based on those four variables. The nomograms demonstrated favorable discriminating power. Conclusion: The SII is a novel prognostic marker for ENKTCL, which may be used for the prediction of poorer survival in low-risk patients.

The effect of cyberbullying victimization and traditional bullying victimization on suicidal ideation among Chinese female college students: The role of rumination and insomnia.

BACKGROUND: The issue of college student suicide has emerged as a significant global public health concern. To date, there has been a lack of extensive research on the effects of distinct forms of bullying victimization (traditional bullying victimization and cyberbullying victimization) on suicidal ideation, as well as the differences between them. The present study aimed to investigate the relationship between two forms of bullying victimization and suicidal ideation among female college students, while also considering the potential mediating effects of rumination and insomnia. METHODS: A total of 2106 female college students from Southern China participated in this study. The participants had a mean age of 19.83 years (SD = 1.04 years). Participants completed the MINI-C questionnaire, School Bullying Behavior Questionnaire, Cyberbullying Inventory (CBI), Ruminative Responses Scale (RRS), and Insomnia Severity Index (ISI). The mediation models were conducted using Model 4 and Model 6 of the Process macro program in SPSS. RESULTS: The results showed that (1) the mediating effect of rumination in the relationship between different forms of bullying victimization and suicidal ideation was significant; (2) The mediating effect of insomnia in the relationship between traditional bullying victimization and suicidal ideation was not significant; the mediating effect between cyberbullying victimization and suicidal ideation was significant. (3) The chain mediating effect of rumination and insomnia in the relationship between different forms of bullying victimization and suicidal ideation were both significant. CONCLUSION: This study endeavor represents the first attempt to investigate the relationship between two forms of bullying victimization and suicidal ideation.

A controlling nutritional status score is an independent predictor for patients with newly diagnosed nasal-type extranodal NK/T-cell lymphoma based on asparaginase-containing regimens.

BACKGROUND: The controlling nutritional status (CONUT) score is a nutritional index that combines serum albumin, total cholesterol, and lymphocyte counts. The potential value of CONUT score for predicting clinical outcomes in patients with nasal-type extranodal NK/T-cell lymphoma (ENKTL) has not been explored. METHODS: This study included 374 ENKTL patients treated with asparaginase-containing regimens from September 2012 to September 2017. Clinical characteristics, treatment efficacy, prognostic factors, and the predictive value of CONUT score were analyzed. RESULTS: The complete response (CR) and overall response rate (ORR) were 54.8% and 74.6%, respectively. Patients with CONUT scores <2 had higher CR and ORR compared to patients with scores ≥2 (69.1% vs. 48.9% for CR, p = 0.001; 90.0% vs. 74.6% for ORR, p < 0.001). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 61.9% and 57.3%, respectively. Patients with CONUT scores <2 had better survival outcomes than those with scores ≥2 (5-year OS, 76.1% vs. 56.0%, p < 0.001; 5-year PFS, 74.4% vs. 50.1%, p < 0.001). CONUT score ≥2 was identified as an independent poor prognostic factor for both OS and PFS. A CONUT score ≥2 was also associated with poorer survival outcomes in low-risk ENKTL patients. CONCLUSION: A CONUT score ≥2 is a prognostic marker for poor survival in patients with ENKTL and could be used to stratify risk in low-risk patients.

Effects of 10 Hz individualized repetitive transcranial magnetic stimulation on patients with disorders of consciousness: a study protocol for an exploratory double-blind crossover randomized sham-controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive brain stimulation technique, has shown potentials for consciousness recovery of patients with disorders of consciousness (DoC), as, to a certain extent, it is effective in regulating the excitability of central nervous system. However, it is difficult to achieve satisfactory effect with "one size fits all" rTMS treatment due to different clinical conditions of patients. There is an urgent need to develop individualized strategy to improve the effectiveness of rTMS on patients with DoC. METHODS: Our protocol is a randomized double-blind sham-controlled crossover trial that includes 30 DoC patients. Each patient will received 20 sessions, in which 10 sessions will be rTMS-active stimulus, and the other 10 sessions will be sham stimulus, separated by no less than 10 days' washout period. The rTMS-active will include 10 Hz rTMS over the individualized-targeted selection area for each patient according to the different insult regions of the brain. Coma Recovery Scale-Revised (CRS-R) will be used as primary outcome at baseline, after the first stage of stimulation, at the end of the washout period, and after the second stage of stimulation. Secondary outcomes will be measured at the same time, including efficiency, relative spectral power, and functional connectivity of high-density electroencephalograph (EEG). Adverse events will be recorded during the study. DISCUSSION: rTMS has obtained grade A evidence in treating patients with several central nervous system diseases, and there has been some evidence showing partial improvement on level of consciousness in DoC patients. However, the effectiveness of rTMS in DoC is only 30~36%, mostly due to the non-specific target selection. In this protocol, we present a double-blind crossover randomized sham-controlled trial based on the individualized-targeted selection strategy that aims to study the effectiveness of rTMS therapy for DoC, and the result may provide new insights to non-invasive brain stimulation. TRIAL REGISTRATION: ClinicalTrials.gov : NCT05187000. Registered on January 10, 2022.

Cybervictimization and non-suicidal self-injury among Chinese adolescents: The effect of depression and school connectedness.

Cybervictimization has been shown in many studies to be a risk factor for adolescent non-suicidal self-injurious behavior (NSSI). In this study we tested the roles of depression and school connectedness in this association. The Integrative Model of NSSI, Emotion Regulation and Interpersonal Relationship Model of NSSI, and Integrative Model of Social Media and Suicide provided the conceptual framework for the study. A sample of 1106 adolescents (M age = 13.17; SD = 0.69; 51.78% girls) completed anonymous questionnaires in their classrooms. The results of structural equation modeling showed that the positive association between cybervictimization and adolescent NSSI was mediated by depression. Moreover, this indirect link was stronger for adolescents with low vs. high school connectedness. The results have implications for intervention programs aimed at reducing NSSI among adolescents.

Comparison of the clinical efficacies of two L-asparaginase-based chemotherapy regimens for newly diagnosed nasal-type extranodal NK/T-cell lymphoma.

BACKGROUND: Nasal-type extranodal natural killer (NK)/T cell lymphoma (ENKTL) is a rare and aggressive type of lymphoma. The optimal chemotherapy regimen for ENKTL has not yet been established. In this study, we compared the LVDP (L-asparaginase, etoposide, dexamethasone, and cisplatin) and GLIDE (gemcitabine, L-asparaginase, ifosfamide, dexamethasone, and etoposide) chemotherapy regimens for the treatment of ENKTL. METHODS: A total of 267 patients with newly diagnosed ENKTL were included in this retrospective study. Propensity score matching (PSM) was used to adjust for confounders between the LVDP and GLIDE groups. Treatment responses, survival outcomes, and toxicities between the two groups were compared before and after PSM. RESULTS: At the end of therapy, the objective response rate (ORR) and complete response (CR) were 83.5% and 62.2%, respectively, for all patients. The ORR and CR were 85.5% and 62.2% for the LVDP group compared with 79.3% and 62.2% for the GLIDE group, respectively, and no differences between the two groups were found (ORR, p = 0.212; CR, p = 0.996). With a median 71 months follow-up, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 64.3% and 68.5%, respectively. The 5-year PFS and OS were 65.6% and 70.1% for the LVDP group compared with 61.6% and 64.6% for the GLIDE group, respectively (PFS, p = 0.478; OS, p = 0162). After PSM, no significant differences in short-term efficacy (ORR, p = 0.696; CR, p = 0.264) or long-term efficacy (PFS, p = 0.794; OS, p = 0.867) between the two groups were identified. However, treatment-related toxicities were milder in the LVDP group compared to the GLIDE group, even after adjusting for confounders via PSM. CONCLUSION: In conclusion, both LVDP and GLIDE regimens are effective for the treatment of ENKTL. However, the LVDP regimen is safer than the GLIDE regimen, with milder treatment-related toxicities. Therefore, the LVDP regimen could be a preferable option for patients with ENKTL.

Repetitive transcranial magnetic stimulation over the posterior parietal cortex improves functional recovery in nonresponsive patients: A crossover, randomized, double-blind, sham-controlled study.

Background: Recent studies have shown that patients with disorders of consciousness (DoC) can benefit from repetitive transcranial magnetic stimulation (rTMS) therapy. The posterior parietal cortex (PPC) is becoming increasingly important in neuroscience research and clinical treatment for DoC as it plays a crucial role in the formation of human consciousness. However, the effect of rTMS on the PPC in improving consciousness recovery remains to be studied. Method: We conducted a crossover, randomized, double-blind, sham-controlled clinical study to assess the efficacy and safety of 10 Hz rTMS over the left PPC in unresponsive patients. Twenty patients with unresponsive wakefulness syndrome were recruited. The participants were randomly divided into two groups: one group received active rTMS treatment for 10 consecutive days (n = 10) and the other group received sham treatment for the same period (n = 10). After a 10-day washout period, the groups crossed over and received the opposite treatment. The rTMS protocol involved the delivery of 2000 pulses/day at a frequency of 10 Hz, targeting the left PPC (P3 electrode sites) at 90% of the resting motor threshold. The primary outcome measure was the JFK Coma Recovery Scele-Revised (CRS-R), and evaluations were conducted blindly. EEG power spectrum assessments were also conducted simultaneously before and after each stage of the intervention. Result: rTMS-active treatment resulted in a significant improvement in the CRS-R total score (F = 8.443, p = 0.009) and the relative alpha power (F = 11.166, p = 0.004) compared to sham treatment. Furthermore, 8 out of 20 patients classified as rTMS responders showed improvement and evolved to a minimally conscious state (MCS) as a result of active rTMS. The relative alpha power also significantly improved in responders (F = 26.372, p = 0.002) but not in non-responders (F = 0.704, p = 0.421). No adverse effects related to rTMS were reported in the study. Conclusions: This study suggests that 10 Hz rTMS over the left PPC can significantly improve functional recovery in unresponsive patients with DoC, with no reported side effects. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05187000.

Olfactory response is a potential sign of consciousness: electroencephalogram findings.

Objective: This study aimed to explore whether olfactory response can be a sign of consciousness and represent higher cognitive processing in patients with disorders of consciousness (DoC) using clinical and electroencephalogram data. Methods: Twenty-eight patients with DoC [13 vegetative states (VS)/unresponsive wakefulness syndrome (UWS) and 15 minimally conscious states (MCS)] were divided into two groups: the presence of olfactory response (ORES) group and the absence of olfactory response (N-ORES) group according to behavioral signs from different odors, i.e., vanillin, decanoic acid, and blank stimuli. We recorded an olfactory task-related electroencephalogram (EEG) and analyzed the relative power and functional connectivity at the whole-brain level in patients with DoC and healthy controls (HCs). After three months, the outcomes of DoC patients were followed up using the coma recovery scale-revised (CRS-R). Results: A significant relationship was found between olfactory responses and the level of consciousness (χ2(1) = 6.892, p = 0.020). For olfactory EEG, N-ORES patients showed higher theta functional connectivity than ORES patients after stimulation with vanillin (p = 0.029; p = 0.027). Patients with N-ORES showed lower alpha and beta relative powers than HCs at the group level (p = 0.019; p = 0.033). After three months, 62.5% (10/16) of the ORES patients recovered consciousness compared to 16.7% (2/12) in the N-ORES group. The presence of olfactory response was significantly associated with an improvement in consciousness (χ2(1) = 5.882, p = 0.023). Conclusion: Olfactory responses should be considered signs of consciousness. The differences in olfactory processing between DoC patients with and without olfactory responses may be a way to explore the neural correlates of olfactory consciousness in these patients. The olfactory response may help in the assessment of consciousness and may contribute to therapeutic orientation.