Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring

POGZ-related disorders (also known as White-Sutton syndrome) encompass a wide range of neurocognitive abnormalities and other accompanying anomalies. Disease severity varies widely among POGZ patients and studies investigating genotype-phenotype association are scarce. Therefore, our aim was to collect data on previously unreported POGZ patients and perform a large-scale phenotype-genotype comparison from published data. Overall, 117 POGZ patients′ genotype and phenotype data were included in the analysis, including 12 novel patients. A severity scoring system was developed for the comparison. Mild and severe phenotypes were compared with the types and location of the variants and the predicted presence or absence of nonsense-mediated RNA decay (NMD). Missense variants were more often associated with mild phenotypes (p = 0.0421) and truncating variants predicted to escape NMD presented with more severe phenotypes (p < 0.0001). Within this group, variants in the prolin-rich region of the POGZ protein were associated with the most severe phenotypes (p = 0.0004). Our study suggests that gain-of-function or dominant negative effect through escaping NMD and the location of the variants in the prolin-rich domain of the protein may play an important role in the severity of manifestations of POGZ–associated neurodevelopmental disorders.

MuTILs: explainable, multiresolution computational scoring of Tumor-Infiltrating Lymphocytes in breast carcinomas using clinical guidelines

Tumor-Infiltrating Lymphocytes (TILs) have strong prognostic and predictive value in breast cancer, but their visual assessment is subjective. We present MuTILs, a convolutional neural network architecture specifically optimized for the assessment of TILs in whole-slide image scans in accordance with clinical scoring recommendations. MuTILs is a concept bottleneck model, designed to be explainable and to encourage sensible predictions at multiple resolutions. Our computational scores match visual scores and have independent prognostic value in invasive breast cancers from the TCGA dataset.

Infantile acne is a medical problem that calls for therapy

Background: Acne vulgaris of infants is a well-recognized medical and cosmetic problem as it may cause severe scarring of the face. Hence medical treatment is essentially needed. Objective: To record all patients with infantile acne vulgaris and to do full demographic and clinical evaluation. Patients and methods:This is case series clinical descriptive study with interventional therapeutic trial that included all patients with infantile acne vulgaris that were seen during the period from Jan 2021 – September 2021 years. All demographic and clinical features were recorded. The clinical scoring of acne severity was done as follow:mild when the rash was mainly comedones,moderate mainly papules and pustules and severe mainly nodules and scarring. Any triggering factors were recorded including hormonal changes. Therapy was started by giving topical 2% clindamycin twice a day and oral trimethoprim-sulfamethoxazole suspension one teaspoonful twice a day for 1-2 months. Results: This study included 28 patients with infantile acne, with 19(67.86%) males and 9(32.14%) females with male to female ratio;2.1. The age of patients ranged from 1-24 months, with a mean 14.6 ±6.1.The duration of rash was ranged from 4-8 weeks. The commonest sites affected were cheeks in 27(96.4%) cases, followed by forehead in 8 (28.6%), then chin in 6 (23.1%), and nose 6 (23.1%) of the cases. Scoring of severity of acne showed moderate in 13(46.4%), followed by mild in 9 (32.1%), and sever in 6 (21.4%). The response to treatment was complete clearance in 15(53.6%) and partial response in 13(46.4%) of the patients while no adverse effects were observed. Conclusions: Infantile acne is not uncommon disease among infants where medical therapy is essentially needed especially in severe cases as to prevent facial scarring. Early diagnosis and treatment with oral trimethoprim-sulfamethoxazole suspension and topical 2% clindamycin lotion is an effective mode of therapy.

Voluntary wheel running behaviour as a tool to assess the severity in a mouse pancreatic cancer model

Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore, performed an evidence-based severity assessment of experimental procedures used in a pancreatic cancer model including surgical tumour induction and subsequent chemotherapeutic treatment via repeated intraperitoneal injections. Cancer cell injection into the pancreas was performed during a laparotomy under general anaesthesia. After a four-day recovery phase, mice received either drug treatment (galloflavin and metformin) or the respective vehicle substances via daily intraperitoneal injections. In addition to clinical scoring, an automated home-cage monitoring system was used to assess voluntary wheel running (VWR) behaviour as an indicator of impaired well-being. After surgery, slightly elevated clinical scores and minimal body weight reductions, but significantly decreased VWR behaviour were observed. During therapy, body weight declined in response to chemotherapy, but not after vehicle substance injection, while VWR activity was decreased in both cases. VWR behaviour differed between treatment groups and revealed altered nightly activity patterns. In summary, by monitoring VWR a high impact of repeated injections on the well-being of mice was revealed and substance effects on well-being were distinguishable. However, no differences in tumour growth between treatment groups were observed. This might be due to the severity of the procedures uncovered in this study, as exaggerated stress responses are potentially confounding factors in preclinical studies. Finally, VWR was a more sensitive indicator of impairment than clinical scoring in this model.

Heparin-induced Thrombocytopenia: Perioperative Diagnosis and Management

Heparin-induced thrombocytopenia is a severe prothrombotic disease. Timely diagnosis and treatment are essential. Application of diagnostic algorithms based on validated clinical scoring tools and rapid, specific laboratory assays may improve outcomes.

Use of Thoracic Ultrasonography to Improve Disease Detection in Experimental BRD Infection

Bovine respiratory disease (BRD) is caused by complex interactions between viral and bacterial pathogens, host immune status, and environmental stressors. In both clinical and research settings, current methods for detecting BRD in calves commonly focus on visual indicators such as attitude, nasal discharge, and cough, in addition to vital signs such as rectal temperature and respiration rate. Recently, thoracic ultrasonography (TUS) has become more commonly used in clinical settings, in addition to physical examination to diagnose BRD. To assess the value of performing TUS during experimental BRD infection, 32 calves were challenged with bovine respiratory syncytial virus, to mimic a viral infection, and 30 calves were infected with Mannheimia haemolytica, to mimic a bacterial infection. TUS was performed at regular intervals using a standardized method and scoring system in addition to daily clinical scoring. Although overall correlations between clinical scores and TUS scores were generally weak (maximum R2 = 0.3212), TUS identified calves with abnormal lung pathology that would have otherwise been misclassified on the basis of clinical scoring alone, both on arrival and throughout the studies. In addition, TUS had an increased correlation with gross lung pathology on necropsy (maximum R2 = 0.5903), as compared to clinical scoring (maximum R2 = 0.3352). Our results suggest that TUS can provide additional information on calf health at enrollment and throughout a study and may provide an alternative to terminal studies, due to the high correlation with lung pathology at necropsy.

A COMBINED ULTRASOUND AND CLINICAL SCORING MODEL FOR THE PREDICTION OF PERIPARTUM COMPLICATIONS IN PREGNANCIES COMPLICATED BY PLACENTA PREVIA

Introduction: Patients with placenta previa are at an increased risk of uncontrolled hemorrhage. Various clinical and ultrasound parameters can predict the risk of bleeding in these patients. Hence, the objective of our study is to develop a combined ultrasound and clinical scoring model for the prediction of peripartum complications in pregnancies complicated by placenta previa. Methods: Fifty singleton pregnant women with placenta previa who underwent cesarean delivery in our hospital were included in the study. We collected clinical and ultrasound data prospectively, and the score was given to each parameter, and total score correlated with the occurrence of peripartum complications. Clinical parameters included age, parity, history of dilatation and evacuation, previous cesarean delivery, history of placenta previa, antepartum hemorrhage, and ultrasound parameters included type of previa, no. of lacunae in placenta, uteroplacental hypervascularity. The peripartum complications noted were the need for blood transfusion, uterine artery ligation, and cesarean hysterectomy. Results: According to the composite scoring done, uterine artery ligation was needed in more than 50% of patients at a score of 9–10. It increased to 100% as the score increased to ≥11. At a score of ≥12, hysterectomy was needed in around 75% of patients, and 100% of patients needed a blood transfusion. Univariate analysis using the Pearson Chi-square test was also done to know whether individual parameters and peripartum complications were significantly related that is p<0.05 with one another. Conclusion: The scoring system may serve to predict peripartum complications in pregnancies complicated by placenta previa.