Adolescent mobile phone addiction during the COVID-19 pandemic predicts subsequent suicide risk:a two-wave longitudinal study

Both the rate of mobile phone addiction and suicidality among adolescents have increased during the pandemic lockdown. However, the relationship between mobile phone addiction and suicide risk and the underlying psychological mechanisms remains unknown. This study examined the associations between mobile phone addiction in adolescents during the first month of lockdown and the suicide risk in the subsequent five months. A two-wave short-term longitudinal web-based survey was conducted on 1609 senior high school students (mean age = 16.53 years, SD = 0.97 years; 63.5% female). At Time 1 (T1), the severity of mobile phone addiction and basic demographic information was collected from Feb 24 to 28, 2020 in Sichuan Province, China (at the pandemic’s peak). Five months later, between July 11 and July 23 (Time 2, T2), mobile phone addiction, daytime sleepiness, depression, and suicidality were measured within the past five months. The regression analysis revealed that mobile phone addiction during quarantine directly predicted suicidality within the next five months, even after controlling for the effect of depression and daytime sleepiness. Meanwhile, mobile phone addiction at T1 also indirectly predicted suicidality at T2, with depression and daytime sleepiness mediating this association. Programs targeting improvement of daytime sleepiness and depressive symptoms may be particularly effective in reducing suicide risk among adolescents with mobile phone addiction

The Symptoms and Medications of Patients with Inflammatory Bowel Disease in Hubei Province after COVID-19 Epidemic

Objectives. The COVID-19 epidemic triggered by coronavirus SARS-CoV-2 is rapidly spreading around the globe. This study is aimed at finding out the suspected or confirmed SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD) in Hubei province, China. We also investigated symptoms, medications, life quality, and psychological issues of IBD patients under the ongoing pandemic. Methods. We conducted a self-reported questionnaire survey via an online survey platform. SARS-CoV-2 infection-related data was collected from IBD patients. The status quo of medications and symptoms of the subjects were investigated. Life quality, depression, and anxiety were measured by clinical questionnaires and rated on scoring systems. Results. A total of 204 IBD patients from Hubei province were included in this study. No suspected or confirmed SARS-CoV-2 infection case was found in this study. As a result of city shutdown, two-thirds of the patients (138/204) in our series reported difficulty in accessing medicines and nearly half of them (73/138) had to discontinue medications. Apart from gastrointestinal symptoms, systemic symptoms were common while respiratory symptoms were rare in the cohort. Though their quality of life was not significantly lowered, depression and anxiety were problems that seriously affected them during the COVID-19 epidemic. Conclusions. Inaccessibility to medications is a serious problem for IBD patients after city shutdown. Efforts have to be made to address the problems of drug withdrawal and psychological issues that IBD patients suffer from during the COVID-19 outbreak

Intratumor graph neural network recovers hidden prognostic value of multi-biomarker spatial heterogeneity

Cancer prognosis using multiregion sampling is costly and not completely reliable due to the required biomarker homogenisation step. Here, the authors develop an intratumor graph neural network for prognosis in multiregion cancer samples based on in situ biomarkers and gene expression that does not need homogenisation

Prognostic value of tumor necrosis based on the evaluation of frequency in invasive breast cancer

Abstract Background Tumor necrosis (TN) was associated with poor prognosis. However, the traditional classification of TN ignored spatial intratumor heterogeneity, which may be associated with important prognosis. The purpose of this study was to propose a new method to reveal the hidden prognostic value of spatial heterogeneity of TN in invasive breast cancer (IBC). Methods Multiphoton microscopy (MPM) was used to obtain multiphoton images from 471 patients. According to the relative spatial positions of TN, tumor cells, collagen fibers and myoepithelium, four spatial heterogeneities of TN (TN1-4) were defined. Based on the frequency of individual TN, TN-score was obtained to investigate the prognostic value of TN. Results Patients with high-risk TN had worse 5-year disease-free survival (DFS) than patients with no necrosis (32.5% vs. 64.7%; P < 0.0001 in training set; 45.8% vs. 70.8%; P = 0.017 in validation set), while patients with low-risk TN had a 5-year DFS comparable to patients with no necrosis (60.0% vs. 64.7%; P = 0.497 in training set; 59.8% vs. 70.8%; P = 0.121 in validation set). Furthermore, high-risk TN “up-staged” the patients with IBC. Patients with high-risk TN and stage I tumors had a 5-year DFS comparable to patients with stage II tumors (55.6% vs. 62.0%; P = 0.565 in training set; 62.5% vs. 66.3%; P = 0.856 in validation set), as well as patients with high-risk TN and stage II tumors had a 5-year DFS comparable to patients with stage III tumors (33.3% vs. 24.6%; P = 0.271 in training set; 44.4% vs. 39.3%; P = 0.519 in validation set). Conclusions TN-score was an independent prognostic factor for 5-year DFS. Only high-risk TN was associated with poor prognosis. High-risk TN “up-staged” the patients with IBC. Incorporating TN-score into staging category could improve its performance to stratify patients

Overcoming Target-Mediated Quinolone Resistance in Topoisomerase IV by Introducing Metal-Ion-Independent Drug–Enzyme Interactions

Quinolones, which target gyrase and topoisomerase IV, are the most widely prescribed antibacterials worldwide. Unfortunately, their use is threatened by the increasing prevalence of target-mediated drug resistance. Greater than 90% of mutations that confer quinolone resistance act by disrupting enzyme–drug interactions coordinated by a critical water–metal ion bridge. Quinazolinediones are quinolone-like drugs but lack the skeletal features necessary to support the bridge interaction. These compounds are of clinical interest, however, because they retain activity against the most common quinolone resistance mutations. We utilized a chemical biology approach to determine how quinazolinediones overcome quinolone resistance in <i>Bacillus anthracis</i> topoisomerase IV. Quinazolinediones that retain activity against quinolone-resistant topoisomerase IV do so primarily by establishing novel interactions through the C7 substituent, rather than the drug skeleton. Because some quinolones are highly active against human topoisomerase IIα, we also determined how clinically relevant quinolones discriminate between the bacterial and human enzymes. Clinically relevant quinolones display poor activity against topoisomerase IIα because the human enzyme cannot support drug interactions mediated by the water–metal ion bridge. However, the inclusion of substituents that allow quinazolinediones to overcome topoisomerase IV-mediated quinolone resistance can cause cross-reactivity against topoisomerase IIα. Therefore, a major challenge in designing drugs that overcome quinolone resistance lies in the ability to identify substituents that mediate strong interactions with the bacterial, but not the human, enzymes. On the basis of our understanding of quinolone–enzyme interactions, we have identified three compounds that display high activity against quinolone-resistant <i>B. anthracis</i> topoisomerase IV but low activity against human topoisomerase IIα

Giant photon-drag-induced ultrafast photocurrent in diamond for nonlinear photonics

Diamond is emerging as an attractive third-generation wide-bandgap semiconductor for future on-chip nonlinear photonics and quantum optics due to its unique thermal, optical, and mechanical properties. However, the light-driven current under below-bandgap excitation from the second-order nonlinear optical effect in diamond is still challenging. Herein, a giant second-order nonlinear photocurrent is observed in the chemical vapor deposition (CVD) diamond by utilizing terahertz (THz) emission spectroscopy. This ultrafast photocurrent originates from the photon drag effect (PDE), during which the momentum transfer from the incident photons to the charge carriers at the rich grain boundaries of the CVD diamond after the exclusive subgap {\pi}-{\pi}* transition upon femtosecond laser excitation. Especially, the interplay between circular and linear PDE to the THz generation has been clarified and distinguished under elliptically polarized light excitation. Furthermore, the picosecond ultrafast dynamics of these charge carriers are also verified by the infrared spectroscopy. Owing to the giant photon-drag-induced ultrafast photocurrent, the CVD diamond presents the highest THz emission efficiency compared with the reported carbon allotropes, which expands the new functionality of diamond nonlinear photonics into on-chip THz devices

Activity of Quinolone CP-115,955 Against Bacterial and Human Type II Topoisomerases Is Mediated by Different Interactions

CP-115,955 is a quinolone with a 4-hydroxyphenyl at C7 that displays high activity against both bacterial and human type II topoisomerases. To determine the basis for quinolone cross-reactivity between bacterial and human enzymes, the activity of CP-115,955 and a series of related quinolones and quinazolinediones against <i>Bacillus anthracis</i> topoisomerase IV and human topoisomerase IIα was analyzed. Results indicate that the activity of CP-115,955 against the bacterial and human enzymes is mediated by different interactions. On the basis of the decreased activity of quinazolinediones against wild-type and resistant mutant topoisomerase IV and the low activity of quinolones against resistant mutant enzymes, it appears that the primary interaction of CP-115,955 with the bacterial system is mediated through the C3/C4 keto acid and the water–metal ion bridge. In contrast, the drug interacts with the human enzyme primarily through the C7 4-hydroxyphenyl ring and has no requirement for a substituent at C8 in order to attain high activity. Despite the fact that the human type II enzyme is unable to utilize the water–metal ion bridge, quinolones in the CP-115,955 series display higher activity against topoisomerase IIα <i>in vitro</i> and in cultured human cells than the corresponding quinazolinediones. Thus, quinolones may be a viable platform for the development of novel drugs with anticancer potential

AutoFibroNet: A deep learning and multi-photon microscopy-derived automated network for liver fibrosis quantification in MAFLD

Background: liver fibrosis is the strongest histological risk factor for liver-related complications and mortality in metabolic dysfunction-associated fatty liver disease (MAFLD). Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) is a powerful tool for label-free two-dimensional and three-dimensional tissue visualisation that shows promise in liver fibrosis assessment.Aim: to investigate combining multi-photon microscopy (MPM) and deep learning techniques to develop and validate a new automated quantitative histological classification tool, named AutoFibroNet (Automated Liver Fibrosis Grading Network), for accurately staging liver fibrosis in MAFLD.Methods: AutoFibroNet was developed in a training cohort that consisted of 203 Chinese adults with biopsy-confirmed MAFLD. Three deep learning models (VGG16, ResNet34, and MobileNet V3) were used to train pre-processed images and test data sets. Multi-layer perceptrons were used to fuse data (deep learning features, clinical features, and manual features) to build a joint model. This model was then validated in two further independent cohorts.Results: AutoFibroNet showed good discrimination in the training set. For F0, F1, F2 and F3-4 fibrosis stages, the area under the receiver operating characteristic curves (AUROC) of AutoFibroNet were 1.00, 0.99, 0.98 and 0.98. The AUROCs of F0, F1, F2 and F3-4 fibrosis stages for AutoFibroNet in the two validation cohorts were 0.99, 0.83, 0.80 and 0.90 and 1.00, 0.83, 0.80 and 0.94, respectively, showing a good discriminatory ability in different cohorts.Conclusion: AutoFibroNet is an automated quantitative tool that accurately identifies histological stages of liver fibrosis in Chinese individuals with MAFLD.<br/