Childhood cancer data initiative: Status report.

In March 2023, over 800 researchers, clinicians, patients, survivors, and advocates from the pediatric oncology community met to discuss the progress of the National Cancer Institute's Childhood Cancer Data Initiative. We present here the status of the initiative's efforts in building its data ecosystem and updates on key programs, especially the Molecular Characterization Initiative and the planned Coordinated National Initiative for Rare Cancers in Children and Young Adults. These activities aim to improve access to childhood cancer data, foster collaborations, facilitate integrative data analysis, and expand access to molecular characterization, ultimately leading to the development of innovative therapeutic approaches.

Risk Factors and Moderators of Intimate Partner Violence Victimization Versus Perpetration Among Women in Spain.

Bidirectional intimate partner violence (IPV) appears highly prevalent, but the extant literature, which has been dominated by work in North America, has not adequately accounted for how victimization overlaps with perpetration and how potential resources may interact with risk factors. A community sample of Spanish women completed measures of IPV approval, mental health risk factors (psychological distress and problematic substance use), and interpersonal resources (partner and social satisfaction). Using Mplus accounting for victimization and perpetration overlap, findings indicate that greater psychological distress and substance use were associated with IPV perpetration, and lower IPV approval was linked to victimization. Stronger partner satisfaction did not serve a buffering role but rather interacted to increase IPV perpetration; low social support was associated with victimization and exacerbated risk of perpetration.

Psychosocial Resources Predicting Maternal and Paternal Positive Parenting and Lower Child Abuse Risk.

Young children have the highest victimization rates of physical abuse in their first year of life, making up nearly half of all child abuse-related fatalities. More effective prevention is needed to reduce child victimization, yet many risk reduction models rely on problematic inclusion criteria, only intervene after maltreatment has occurred, or focus only on mothers. More proactive prevention models that promote positive parenting practices early in the transition to parenthood could be key to reducing child maltreatment. The current study sought to assess how both mothers' and fathers' psychosocial resources (e.g., emotion regulation, coping, and social support) and empathy can predict positive parenting and predict lower child abuse risk across time in a cross-lagged model. Parenting and abuse risk were examined prenatally, through the transition into parenthood, until children were 4 years old. First time mothers and their partners were recruited in the third trimester of pregnancy and assessed again when children were 6 months, 18 months, and 4 years old. Separate path models for mothers and fathers analyzed whether psychosocial resources and empathy at earlier timepoints predicted their positive parenting and lower abuse risk by the time children were age 4. Findings demonstrated that mothers' earlier empathy predicted later positive parenting and earlier positive parenting predicted later empathy. Fathers' lower prenatal abuse risk predicted greater subsequent empathy. Both mothers' and fathers' psychosocial resources and empathy at earlier timepoints predicted later positive parenting. Parents' psychosocial resources can be integral assets in positive, effective parenting approaches both concurrently and longitudinally. Mothers' and fathers' resources are an important point of intervention prior to and during the transition into parenthood to support healthier families that would confer benefits to child functioning.

Enhanced Tolerance against a Fungal Pathogen and Insect Resistance in Transgenic Tobacco Plants Overexpressing an Endochitinase Gene from Serratia marcescens.

In this study we cloned a chitinase gene (SmchiC), from Serratia marcescens isolated from the corpse of a Diatraea magnifactella lepidopteran, which is an important sugarcane pest. The chitinase gene SmchiC amplified from the S. marcescens genome was cloned into the transformation vector p2X35SChiC and used to transform tobacco (Nicotiana tabacum L. cv Petit Havana SR1). The resistance of these transgenic plants to the necrotrophic fungus Botrytis cinerea and to the pest Spodoptera frugiperda was evaluated: both the activity of chitinase as well as the resistance against B. cinerea and S. frugiperda was significantly higher in transgenic plants compared to the wild-type.

Pre-Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients with Esophageal Cancer at High Risk for Radiation Pneumonitis.

PURPOSE: To examine the association between pre-radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). MATERIALS AND METHODS: In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%-95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. RESULTS: The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. CONCLUSION: The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP.

Postoperative Complications After Distal Pancreatectomy Performed During Cytoreductive Surgery for Gynecologic Malignancies.

OBJECTIVES: To investigate the incidence of pancreatic leak and other postoperative complications after distal pancreatectomy performed during debulking surgery for gynecologic malignancies. METHODS: All patients who underwent distal pancreatectomy during their debulking surgery from 2010 to 2014 were identified. Postoperative complications within 30 days and pancreatic leak within 120 days after surgery were included. RESULTS: Eighteen patients met the inclusion criteria. The median age was 62 years (36-78 years). Four patients (22%) were admitted to the intensive care unit, and the average length of hospital stay was 10 days. Nine patients developed postoperative complications within 30 days after surgery (50%) with no perioperative mortality up to 90 days after surgery. No patients required reexploration. The median time from surgery to initiation of chemotherapy was 39.5 days. Two patients developed pancreatic leak (11%). Among the patients who developed pancreatic leak, the average length of hospital stay was 11.5 days and time to initiation of chemotherapy was 75 days. Conservative management was successful in both cases. CONCLUSION: In this series, the rate of pancreatic leak was lower than previously reported with no perioperative mortality or surgical reexploration. However, the time to initiation of chemotherapy was delayed in those who developed pancreatic leak. These data are important in patient counseling and decision making at the time of debulking surgery. Gynecologic oncologists considering distal pancreatectomy should be familiar with perioperative management of these patients.

Erythrasma: Pathogenesis and Diagnostic Challenges.

Erythrasma is a common chronic superficial bacterial infection caused by Corynebacterium minutissimum, a lipophilic, diphtheroid, filamentous, gram-positive bacillus and normal inhabitant of the skin flora. Commonly found in intertriginous spaces, this bacterium releases a porphyrin that causes lesions to fluoresce under a Wood's lamp, aiding diagnosis. Despite its clinical relevance, the pathogenesis remains understudied. We present a case of a 43-year-old woman with a history of hypertension, type 2 diabetes mellitus, and obesity who exhibited an erythematous eczematous plaque with characteristic coral-red fluorescence under Wood's lamp. The diagnosis was confirmed through negative skin scrapings for candidiasis and dermatophytosis. A two-week course of topical clindamycin resulted in complete resolution. Given the condition's frequent coexistence with other pathologies, accurate diagnosis and effective treatment are essential. Topical treatments are usually more convenient. The hypothesis that hydrophobic and lipophilic interactions in intertriginous areas contribute to the pathogenesis of erythrasma requires further experimental validation.

Eczema Herpeticum: Clinical Insights and Pathogenesis Hypotheses on Basolateral Adhesion Proteins.

Eczema herpeticum (EH) is a severe viral complication caused by the herpes simplex virus (HSV) that occurs in individuals with compromised skin barriers, such as those with atopic dermatitis (AD). EH is characterized by the rapid spread of HSV across skin lesions, potentially leading to systemic involvement. Although commonly observed in the context of AD, EH can also arise in various dermatological conditions, necessitating prompt recognition and management by healthcare providers. This case report details the diagnosis and treatment of EH in a five-year-old girl with a history of AD who presents with fever and painful skin lesions. Despite the absence of confirmatory tests initially, a positive IgM anti-HSV-1 serology, combined with clinical presentation, supported the diagnosis of EH. The patient received intravenous aciclovir, resulting in significant improvement within 48 hours. This case highlights the importance of early diagnosis and treatment, particularly when confirmatory tests are not available. The report discusses the clinical presentation of EH, which includes vesicular lesions, fever, and rapid progression. The differential diagnosis includes chickenpox, impetigo, eczema vaccinatum, and contact dermatitis. Understanding the epidemiology and pathogenesis of EH, especially in relation to AD, is crucial for effective management. The case also introduces a novel hypothesis linking structural protein alterations to immune dysfunction in EH, suggesting a need for further research. Acyclovir remains the gold standard for treating EH, and timely intervention is essential. This case underscores the necessity of a diagnostic algorithm in the absence of guidelines and highlights the role of IgM serology and clinical judgment in managing suspected EH cases.

Acquired Bilateral Nevus of Ota-Like Macules: A Case Report.

Facial melanoses (FM) present complex diagnostic and therapeutic challenges, particularly in the setting of dermal melanocytoses (DM). We present a case that illustrates these challenges as it does not fit within existing classification frameworks. Initially considered as Ota nevus, characterized by blue or dark pigmentation and scleral involvement, histopathological findings suggested acquired bilateral nevus of Ota-like macules (ABNOM). While ABNOM, more common in Asians, rarely affects the sclera or children, recent studies indicate that it may be underdiagnosed in these groups. Differential diagnosis ruled out other FM causes due to mucosal involvement. Correct classification is essential for epidemiological accuracy and treatment decisions, especially given varying responses to Q-switched laser therapy and melanoma risks associated with Ota nevus and ABNOM. While the pathogenesis remains unclear, a two-hit model involving shared melanoma mutations in melanocytes has been proposed and warrants further molecular study.

Microsporum canis-Induced Tinea Capitis: A Rapid Screening Algorithm.

Tinea capitis is a common fungal infection of the scalp, primarily affecting children, and caused by fungi like Trichophyton and Microsporum. Its pathogenesis is influenced by both host-specific and environmental factors, resulting in various clinical presentations including hair loss and scaling of the scalp. We present the case of an eight-year-old male with tinea capitis, characterized by itching and hair loss in the occipital area. Examination revealed characteristic findings on trichoscopy, and direct examination of hair confirmed parasitization. Treatment with terbinafine was initiated, leading to the resolution of symptoms. Epidemiological variations in the etiology of tinea capitis exist globally, with Trichophyton predominating in some regions and Microsporum in others. Trichoscopy is a valuable diagnostic tool for differentiating fungal infections, guiding treatment decisions. Despite the efficiency of direct skin and hair examination, the common occurrence of tinea and the lack of mycological centers in many clinics pose challenges. To address this, we propose integrating trichoscopy and epidemiological and clinical data for a quick in-office decision tool.

An Immune-Based Therapeutical Approach in an Elderly Patient With Fixed Cutaneous Sporotrichosis.

Sporotrichosis is a subcutaneous fungal infection caused by thermally dimorphic fungi from the Sporothrix genus, primarily prevalent in tropical regions of Latin America, Africa, and Asia. Mexico's Jalisco state is an endemic hotspot with a remarkable prevalence rate of 54.4%. Clinical presentation varies based on immune status and virulence. The most common form is cutaneous-lymphangitic (67%), with fixed cutaneous cases accounting for 28%. This case study explores a traditional therapeutic approach for fixed cutaneous sporotrichosis but introduces a distinct immunological perspective.

Evaluation of prostate cancer detection using micro-ultrasound versus MRI through co-registration to whole-mount pathology.

Micro-ultrasound has recently been introduced as a low-cost alternative to multi-parametric MRI for imaging prostate cancer. Early clinical studies have demonstrated promising results; however, robust validation via comparison with whole-mount pathology has yet to be achieved. Due to micro-ultrasound probe design and tissue deformation during scanning, it is difficult to accurately correlate micro-ultrasound imaging planes with ground truth whole-mount pathology slides. In this study, we developed a multi-step methodology to co-register micro-ultrasound and MRI to whole-mount pathology. The three-step process had a registration error of 3.90 ± 0.11 mm and consists of: (1) micro-ultrasound image reconstruction, (2) 3D landmark registration of micro-ultrasound to MRI, and (3) 2D capsule registration of MRI to whole-mount pathology. This process was then used in a preliminary reader study to compare the diagnostic accuracy of micro-ultrasound and MRI in 15 patients who underwent radical prostatectomy for prostate cancer. Micro-ultrasound was found to have equivalent performance to retrospective MRI review for index lesion detection (91.7% vs. 80%), while demonstrating an increased detection of tumor extent (52.5% vs. 36.7%) with similar false positive regions-of-interest (38.3% vs. 40.8%). Prospective MRI review had reduced detection of index lesions (73.3%) and tumor extent (18.9%) but improved false positive regions-of-interest (22.7%) relative to micro-ultrasound and retrospective MRI. Further evaluation is needed with a larger sample size.

Cognitive Rehabilitation: Mild Traumatic Brain Injury and Relevance of OTPF.

There is increased awareness of the long-term cognitive sequelae of mild traumatic brain injury (mTBI). Therefore, researchers and clinicians have developed and tested cognitive training protocols to address these challenges. The current review summarized literature that examined existing cognitive rehabilitation/training programs. Specifically, the review listed the impact of these programs on functional domains informed by the Occupational Therapy Practice Framework (OTPF). Literature between the years 2008 and 2022 was gathered from nine databases. Results indicate that several cognitive rehabilitation programs have proven to positively influence domains of occupation, client factors, performance, and context. Occupational therapy practitioners have an opportunity to engage in mTBI management. Furthermore, adopting domains of OTPF may guide assessments, treatment planning, and long-term follow-up.

Focal therapy of prostate cancer: Assessment with prostate-specific membrane antigen (PSMA) imaging.

Focal therapy of prostate cancer (PCa) is currently of great interest, but a metric of success. other than biopsy, is not yet available. In a patient with a repeatedly negative MRI and negative systematic biopsies, a scan employing the radioisotope 68Ga-PSMA-11 PET/CT identified a PSMA-avid hotspot in the prostate. PSMA-guided biopsy confirmed the diagnosis of a clinically-significant PCa. Following ablation of the lesion with high-intensity focused ultrasound (HIFU), the PSMA-avid lesion disappeared and targeted biopsy confirmed a fibrotic scar with no residual cancer. PSMA imaging may have a role in guiding diagnosis, focal ablation, and follow-up of men with PCa.

Cryotherapy for partial gland ablation of prostate cancer: Oncologic and safety outcomes.

BACKGROUND: Partial gland ablation (PGA) is a new option for treatment of prostate cancer (PCa). Cryotherapy, an early method of PGA, has had favorable evaluations, but few studies have employed a strict protocol using biopsy endpoints in men with clinically significant prostate cancer (csPCa). METHODS: 143 men with unilateral csPCa were enrolled in a prospective, observational trial of outpatient PGA-cryotherapy. Treatment was a 2-cycle freeze of the affected prostate part. Participants were evaluated with MRI-guided biopsy (MRGB) at baseline and at 6 months and 18 months after treatment. Absence of csPCa upon MRGB was the primary endpoint; quality-of-life at baseline and at 6 months after treatment was assessed by EPIC-CP questionnaires in the domains of urinary and sexual function. RESULTS: Of the 143 participants, 136 (95%) completed MRGB at 6 months after treatment. In 103/136 (76%), the biopsy revealed no csPCa. Of the 103, 71 subsequently had an 18-month comprehensive biopsy; of the 71 with 18-month biopsies, 46 (65%) were found to have no csPCa. MRI lesions became undetectable in 96/130 (74%); declines in median serum PSA levels (6.9 to 2.5 ng/mL), PSA density (0.15 to 0.07), and prostate volume (42 to 34cc) were observed (all p < 0.01). Neither lesion disappearance on MRI nor PSA decline correlated with biopsy outcome. Urinary function was affected only slightly and sexual function moderately. CONCLUSION: In the near to intermediate term, partial gland ablation with cryotherapy was found to be a safe and moderately effective treatment of intermediate-risk prostate cancer. Eradication of cancer was better determined by MRI-guided biopsy than by MRI or PSA.

Mediators between Positive and Negative Parenting and Child Depressive and Anxious Symptoms: Findings from a Diverse, At-Risk Sample.

BACKGROUND: Although children's depressive and anxious symptoms have been broadly construed as internalizing problems, the current study sought to identify factors that may differentially contribute to these two mental health problems in a high-risk sample. Prior research has not adequately tested both depressive versus anxious symptoms simultaneously, nor has it adequately considered the role of negative versus positive parenting simultaneously, thereby neglecting the potential overlap in both sets of constructs. Overlooking such potential statistical overlap obfuscates how factors may differentially contribute to either depressive versus anxious symptoms. Existing research has also focused on lower-risk community samples. METHOD: The present study investigated whether children's negative self-concept or maladaptive attributional style mediated the link between both negative and positive parenting in a racially diverse, at-risk sample of 65 primary school-age children recruited from mental health agencies. RESULTS: When tested together, more negative parenting, but not less positive parenting, retained direct effects on both depressive and anxious symptoms. Both negative self-concept and maladaptive attributional style fully mediated the association between less positive parenting and children's depressive symptoms, whereas positive self-concept, but not attributional style, mediated between less positive parenting and anxious symptoms. CONCLUSIONS: The current findings underscore potential differential intervention targets for these two internalizing problems and highlight the need for future research to consider both depressive and anxious symptoms, and related predictors, simultaneously to control for their shared variance.

Partial Gland Ablation of Prostate Cancer: Effects of Repeat Treatment.

OBJECTIVE: To evaluate the near-term clinical and pathological effects of repeat partial gland ablation (PGA) in men with intermediate-risk prostate cancer (PCa). MATERIALS AND METHODS: One hundred seventy men with focal lesions of PCa (all GG2 or GG3) underwent PGA with high-intensity focused ultrasound (HIFU) or cryotherapy (CRYO) in prospective trials. Residual PCa in or near the ablation zone was found in 37 men after a first PGA; 30 went on to receive a second PGA and were the subjects of study. At 3 timepoints, baseline and 6 months after first and second ablations, quality-of-life (QOL) questionnaires (IIEF, IPSS) and MRI-guided biopsies (MRGB) were performed. Biopsies were targeted and systematic at baseline and in follow-up, comprehensively about the ablation zone. RESULTS: All 30 patients completed QOL questionnaires and 26 had MRGB at the 3 timepoints. Mean QOL scores were not significantly different from the baseline after the first or second PGA. No operative complications were encountered; and "decisional regret" was reported in only 2/29 men after the repeat ablation. A decrease in semen volume was reported by 25% of patients. Repeat ablation was successful (absence of csPCa on MRGB) in 14/26 (53%) of men. PSA levels decreased and MRI lesions resolved after ablations, but neither was a reliable predictor of biopsy outcomes. CONCLUSION: When initial PGA fails, repeat PGA is a reasonable consideration, because in near-term follow-up, secondary procedures appear to be safe, causing only minimal detriment to urinary and sexual function, with csPCa becoming undetectable by MRGB in approximately half the patients.

Development and psychometric characteristics of analog measures of parental empathy.

Despite substantial literature on the effect of empathy on parenting, empathy research has historically suffered from definitional and methodological limitations. Parental empathy can be characterized as parents' ability to recognize, take the perspective of, and appropriately react to children's emotions. Current parental empathy assessment largely relies on self-report measures of dispositional empathy, but many argue parental empathy is distinct from dispositional empathy. Despite efforts to measure parental empathy implicitly, such analog approaches are labor intensive. The current report describes the preliminary development of the Empathy Measure for Parents Analog Task (EMPAT), two novel analog measures of parental empathy: one EMPAT analog uses audio stimuli and a second version uses written evocative scripts. After piloting with a sample of undergraduate students (Study 1), the measures were then administered to a sample of 212 parents (Study 2). For each study, the accuracy of the audio and script stimuli were first confirmed by examination of frequency distributions, then exploratory factor analyses were conducted to determine factor structure for each emotion subscale (i.e., Happy, Mad, Sad, Scared), and finally the composition of each emotion subscale was confirmed with scale reliability analyses. Correlations between each EMPAT version and measures of dispositional empathy, parental empathy, and positive parenting indicators were examined to assess the initial validity of the EMPAT measures. The new analog tasks demonstrated good reliability as well as preliminary evidence of validity, with potential utility in assessing cognitive elements of empathy in particular. With continued efforts to examine measure validity, the implications of these studies suggest the EMPAT tasks show promise in providing improved implicit, efficient assessments of child-directed empathy, which may be important for understanding positive and problematic parenting.

Eicosapentaenoic Acid Improves Hepatic Metabolism and Reduces Inflammation Independent of Obesity in High-Fat-Fed Mice and in HepG2 Cells.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, concurrent with increased obesity. Thus, there is urgent need for research that can lead to effective NAFLD prevention/treatment strategies. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA), improve inflammation- and dyslipidemia-related metabolic disorders; however, mechanisms mediating the benefits of n-3 PUFAs in NAFLD treatment are less understood. We previously reported that EPA reversed obesity-induced hepatic steatosis in high-fat (HF)-fed B6 mice. Utilizing a combination of biochemical analyses of liver tissues from HF and HF-EPA-fed mice and a series of in vitro studies in tumor necrosis factor-alpha (TNF-α)-stimulated HepG2 cells, we dissect the mechanistic effects of EPA in reducing hepatic steatosis, including the role of EPA-targeted microRNAs (miRNA). With EPA, hepatic lipid metabolism was improved in HF-EPA mice, as indicated by decreased protein and messenger RNA (mRNA) levels of fatty acid synthase (FASN) and acetyl-CoA carboxylase (Acaca) gene, and increased mRNA levels for the peroxisome proliferator activated receptor-α (Pparα), and carnitine palmitoyltransferase (Cpt) 1a and 2 genes in the HF-EPA mice. Additionally, inflammation was reduced, as shown by decreased tumor necrosis factor-alpha (Tnfα) gene expression. Accordingly, EPA also significantly reduced FASN and ACACA mRNAs in human HepG2 cells. Glycolysis, estimated by extracellular acidification rate, was significantly reduced in HepG2 cells treated with EPA vs. vehicle. Furthermore, we identified several miRNAs that are regulated by EPA in mouse liver, including miR-19b-3p, miR-21a-5p, and others, which target lipid metabolism and inflammatory pathways. In conclusion, our findings provide novel mechanistic evidence for beneficial effects of EPA in NAFLD, through the identification of specific genes and miRNAs, which may be further exploited as future NAFLD therapies.