Bereavement is a commonly experienced grief event; however, bereavement can also trigger a number of psychological consequences, such as prolonged grief disorder (PGD). At present, the differences in prolonged grief disorder symptoms (PGD symptoms) among various individuals and how those symptoms relate to cognitive variables are unclear. In the present study, 817 Chinese college students with bereavement experience were selected as participants. Based on the evaluation results of their irrational beliefs, bereavement-related irrational beliefs, basic world assumptions, and PGD symptoms, an individual-centered latent profile analysis was used to divide a group with PGD symptoms into several subgroups and comprehensively examine the relationships between these subgroups and cognitive variables. (1) The severity of PGD symptoms among Chinese college students can be categorized into three subgroups: mild, moderate, and severe. (2) Cognitive variables such as irrational beliefs and basic world assumptions were all found to correlate with the severity of PGD symptoms; bereavement-related irrational beliefs was the variable with the largest correlation. However, for the first time, this study found that different dimensions of basic world assumptions had different directions of correlation, based on the severity of the PGD symptoms. Justice, control, randomness, and self-control had significantly positive correlations. Conversely, benevolence of the world, benevolence of people, and worthiness of the self had significantly negative correlations. These results have important reference value for cognitive behavioral therapy (CBT) treatment and interventions for PGD issues in Chinese college students.

Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated. The variables relate to the engineering and function of the respective perfusion devices, such as the type of pump used, functional, like ventilation modes or physiological (e.g. perfusion solutions). This review reflects on the individual technical and fluid components relevant to EVLP and their respective impact on inflammatory response and outcome. We discuss key components of EVLP protocols and options for further improvement of EVLP in regard to PGD. This review offers an overview of available options for centers establishing an EVLP program and for researchers looking for ways to adapt existing protocols.

Advanced heart failure (AdvHF) can only be treated definitively by heart transplantation (HTx), yet problems such right ventricle dysfunction (RVD), rejection, cardiac allograft vasculopathy (CAV), and primary graft dysfunction (PGD) are linked to a poor prognosis. As a result, numerous biomarkers have been investigated in an effort to identify and prevent certain diseases sooner. We looked at both established biomarkers, such as NT-proBNP, hs-troponins, and pro-inflammatory cytokines, and newer ones, such as extracellular vesicles (EVs), donor specific antibodies (DSA), gene expression profile (GEP), donor-derived cell free DNA (dd-cfDNA), microRNA (miRNA), and soluble suppression of tumorigenicity 2 (sST2). These biomarkers are typically linked to complications from HTX. We also highlight the relationships between each biomarker and one or more problems, as well as their applicability in routine clinical practice.

Shidu parents refer to the couple who have lost their only child and have not given birth or adopted another child in China. The number of Shidu parents is increasing annually. The aim of this research was to examine the mediating role of anxiety and the moderating role of social support between perceived stress and prolonged grief disorder (PGD) among Chinese Shidu parents.
A cross-sectional study was carried out with 505 participants who completed a questionnaire including the Prolonged Grief Questionnair-3 (PG-13), the Perceived Stress Scale-10 (PSS-10), the Self-Rating Anxiety Scale (SAS) and the Duke-UNC Functional Social Support Questionnaire (FSSQ). SPSS PROCESS macro was employed to examine the mediating role of anxiety and the moderating role of social support.
The mediation analysis showed anxiety partially mediated the link between perceived stress and PGD, and the proportion of mediation of anxiety was 39.22%. The moderated mediation analysis revealed the second stage of mediating effects of anxiety on the link between perceived stress and PGD was moderated by social support. Specifically, compared with Shidu parents with higher social support, the association between anxiety and PGD was closer for those with lower social support.
The moderated mediation model can broaden our understanding of how and when perceived stress, anxiety and social support work together to affect PGD. The interventions aimed at improving mental health of Chinese Shidu parents need to work on reducing stress and enhancing social support.

Prolonged grief disorder, a condition characterized by severe, persistent, and disabling grief, is newly included in ICD-11 and DSM-5-TR. Prolonged grief symptoms can be effectively treated with face-to-face or internet-delivered cognitive behavioral therapy. Traumatic losses may elicit higher prevalence of severe grief reactions. While face-to-face cognitive behavioral therapy appears efficacious in treating prolonged grief symptoms in traumatically bereaved individuals, it is not yet clear if internet-based cognitive behavioral therapy is efficacious for this population. Therefore, we investigated the efficacy of a 12-week internet-delivered cognitive behavioral therapy for people bereaved through traffic accidents in a randomized waitlist-controlled trial (registration number: NL7497, Dutch Trial Register). Forty adults bereaved though a traffic accident were randomized to internet-based cognitive behavioral therapy (n = 19) or a waitlist control condition (n = 21). Prolonged grief, post-traumatic stress, and depression symptoms were assessed at baseline, post-treatment, and 8-week follow-up. Dropout in the treatment condition was relatively high (42%) compared to the control condition (19%). Nevertheless, multilevel analyses showed that internet-based cognitive behavioral therapy strongly reduced prolonged grief, post-traumatic stress, and depression symptoms relative to the control condition at post-treatment and follow-up. We conclude that internet-based cognitive behavioral therapy appears a promising treatment for traumatically bereaved adults.

The pentose phosphate pathway (PPP) is an important mechanism by which tumour cells resist stressful environments and maintain malignant proliferation. However, the mechanism by which the PPP regulates these processes in colorectal cancer (CRC) remains elusive.
Closely related PPP genes were obtained from the TCGA and GEO databases. The effect of ATP13A2 on CRC cell proliferation was evaluated by performing in vitro assays. The connection between the PPP and ATP13A2 was explored by assessing proliferation and antioxidative stress. The molecular mechanism by which ATP13A2 regulates the PPP was investigated using chromatin immunoprecipitation and dual luciferase experiments. The clinical therapeutic potential of ATP13A2 was explored using patient-derived xenograft (PDX), patient-derived organoid (PDO) and AOM/DSS models.
We identified ATP13A2 as a novel PPP-related gene. ATP13A2 deficiency inhibited CRC growth and PPP activity, as manifested by a decrease in the levels of PPP products and an increase in reactive oxygen species levels, whereas ATP13A2 overexpression induced the opposite effect. Mechanistically, ATP13A2 regulated the PPP mainly by affecting phosphogluconate dehydrogenase (PGD) mRNA expression. Subsequent studies showed that ATP13A2 overexpression promoted TFEB nuclear localization by inhibiting the phosphorylation of TFEB, thereby enhancing the transcription of PGD and ultimately affecting the activity of the PPP. Finally, ATP13A2 knockdown inhibited CRC growth in PDO and PDX models. ATP13A2- /- mice had a lower CRC growth capacity than ATP13A2+/+ in the AOM/DSS model.Our findings revealed that ATP13A2 overexpression-driven dephosphorylation of TFEB promotes PPP activation by increasing PGD transcription, suggesting that ATP13A2 may serve as a potential target for CRC therapy.

Adversarial training, especially projected gradient descent (PGD), has proven to be a successful approach for improving robustness against adversarial attacks. After adversarial training, gradients of models with respect to their inputs have a preferential direction. However, the direction of alignment is not mathematically well established, making it difficult to evaluate quantitatively. We propose a novel definition of this direction as the direction of the vector pointing toward the closest point of the support of the closest inaccurate class in decision space. To evaluate the alignment with this direction after adversarial training, we apply a metric that uses generative adversarial networks to produce the smallest residual needed to change the class present in the image. We show that PGD-trained models have a higher alignment than the baseline according to our definition, that our metric presents higher alignment values than a competing metric formulation, and that enforcing this alignment increases the robustness of models.

Retinoblatoma is now the pediatric cancer with the highest cure rate. More than any other ocular malignancy the approach to this cancer has changed dramatically in the past 10 years. Most of the things taught to the majority of all Ophthalmology residents is out of date. Because few Ophthalmologists deal with retinoblastoma they are not aware of these seismic changes so this summary of my Curtin lectures outlines some of the major changes all Ophthalmologists should be familiar with.

Procreative obligations are often discussed by evaluating only the consequences of reproductive actions or omissions; less attention is paid to the moral role of intentions and attitudes. In this paper, I assess whether intentions and attitudes can contribute to defining our moral obligations with regard to assisted reproductive technologies already available, such as preimplantation genetic diagnosis (PGD), and those that may be available in future, such as reproductive genome editing and ectogenesis, in a way compatible with person-affecting constraints. I propose the parent-child relationship argument, which is based on the moral distinction between creating and parenting a child. Hence, I first argue that intentions and attitudes can play a role in defining our moral obligations in reproductive decisions involving PGD. Second, I maintain that if we accept this and recognize reproductive genome editing and ectogenesis as person-affecting procedures, we should be committed to arguing that prospective parents may have moral reasons to prefer reproduction via such techniques than via sexual intercourse. In both cases, I observe an extension of our procreative responsibility beyond what is proposed by the consequentialist person-affecting morality.

Bereaved ICU family surrogates are at risk of comorbid prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depression. Knowledge about temporal relationships between PGD, PTSD, and depression is limited by a lack of relevant studies and diverse or inappropriate assessment time frames given the duration criterion for PGD. We aimed to determine the temporal reciprocal relationships between PGD, PTSD, and depressive symptoms among ICU decedents\' family surrogates during their first 2 bereavement years with an assessment time frame reflecting the PGD duration criterion.
This prospective, longitudinal, observational study examined PGD, PTSD, and depressive symptoms among 303 family surrogates of ICU decedents from two academic hospitals using 11 items of the Prolonged Grief Disorder-13, the Impact of Event Scale-Revised, and the depression subscale of the Hospital Anxiety and Depression Scale, respectively, at 6, 13, 18, and 24 months post-loss. Cross-lagged panel modeling was conducted: autoregressive coefficients indicate variable stability, and cross-lagged coefficients indicate the strength of reciprocal relationships among variables between time points.
Symptoms (autoregressive coefficients) of PGD (0.570-0.673), PTSD (0.375-0.687), and depression (0.591-0.655) were stable over time. Cross-lagged standardized coefficients showed that depressive symptoms measured at 6 months post-loss predicted subsequent symptoms of PGD (0.146) and PTSD (0.208) at 13 months post-loss. PGD symptoms did not predict depressive symptoms. PTSD symptoms predicted subsequent depressive symptoms in the second bereavement year (0.175-0.278). PGD symptoms consistently predicted subsequent PTSD symptoms in the first 2 bereavement years (0.180-0.263), whereas PTSD symptoms predicted subsequent PGD symptoms in the second bereavement year only (0.190-0.214). PGD and PTSD symptoms are bidirectionally related in the second bereavement year.
PGD, PTSD, and depressive symptoms can persist for 2 bereavement years. Higher PGD symptoms at 6 months post-loss contributed to the exacerbation of PTSD symptoms over time, whereas long-lasting PTSD symptoms were associated with prolonged depression and PGD symptoms beyond the first bereavement year. Identification and alleviation of depression and PGD symptoms as early as 6 months post-loss enables bereaved surrogates to grieve effectively and avoid the evolution of those symptoms into long-lasting PGD, PTSD, and depression.