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The function of spargel/dPGC-1 in Drosophila oogenesis has been unequivocally established. Here, we sought to assess whether Spargel protein or RNA is essential for developmentally competent eggs. The trans-heterozygotic combination of two spargel mutant alleles allowed us to decrease Spargel expression to very low levels. Using this model, we now demonstrated the requirement for Spargel in eggshell patterning and embryonic development, which led us to establish that spargel is a maternal effect gene. Further examination of Spargel's potential mechanism of action in eggshell biogenesis revealed that low levels of Spargel in the adult ovary cause diminished Cyclin E activity, resulting in reduced chorion gene amplification levels, leading to eggshell biogenesis defects. Thus, another novel role for spargel/dPGC-1 is exposed whereby, through Cyclin E activity, this conserved transcriptional coactivator regulates the chorion gene amplification process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Infantile colic diagnostic criteria were established by Rome IV. A universally accepted management remains to be established. We aimed to evaluate diagnostic criteria, management strategies, and perceived regional prevalence of infantile colic in Pakistan, as well as its effect on physicians and parents., Methods: A questionnaire was distributed amongst 1,256 physicians., Results: We received 800 replies. Wessel and Rome IV criteria were used by most physicians for diagnosis; however, the response "any infant who cries a lot" was selected by older physicians (48% of those over 60 years), physicians in rural areas (32%), physicians practicing in private clinics (27%), and general physicians (30%). Estimated prevalence of infantile colic ranges from 21-40%. Reassurance was the most widely recommended management strategy followed by herbal teas (51%), switching to a different formula (49%), probiotics (28%) and antibiotics (26%), discontinuation of breastfeeding (14%), elimination of dairy products from the breastfeeding mothers' diet (6%), and the administration of colic drops (1%). Most physicians considered the negative impact of colic on their personal lives and the parents as mild-to-moderate. Notably, 38% of percent of physicians routinely screened for maternal depression, and 45% of physicians were aware of the association between infantile colic and shaken baby syndrome., Conclusion: Most physicians in Pakistan diagnose and manage infantile colic according to the established guidelines. However, the guidelines pertaining to treatment planning are not followed. Educational efforts directed toward general physicians and doctors practicing in rural areas and clinics must be implemented to avoid unnecessary testing and treatment burden., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Background: An obesity paradox, whereby patients with higher body mass index (BMI) experience improved outcomes, has been described for ischemic stroke. It is unclear whether this applies to patients undergoing mechanical thrombectomy (MT) for large vessel occlusion (LVO)., Methods: Mechanical thrombectomies for anterior circulation LVO between 2015 and 2021 at a single institution were reviewed. Multivariable logistic regressions were used to determine the association between BMI and favorable functional outcome (90-day modified Rankin Scale 0-2), intracranial hemorrhage, and malignant middle cerebral infarction. A systematic review was performed to identify studies reporting the effect of BMI on outcomes among patients receiving MT for LVO. The data from the systematic review were combined with the institutional data by using a random effects model., Results: The institutional cohort comprised 390 patients with a median BMI of 27 kg/m 2 . Most patients were obese [36.7% (BMI ≥ 30 kg/m 2 )], followed by overweight [30.5% (BMI ≥ 25 and < 30 kg/m 2 )], normal [27.9% (BMI ≥ 18.5 and < 25 kg/m 2 )], and underweight [4.9% (BMI < 18.5 kg/m 2 )]. As a continuous variable, BMI was not associated with any of the outcomes. When analyzing BMI ordinally, obesity was associated with lower odds of favorable 90-day modified Rankin Scale (odds ratio 0.42, 95% confidence interval 0.20-0.86). The systematic review identified three eligible studies comprising 1,348 patients for a total of 1,738 patients. In the random effects model, there was no association between obesity and favorable outcome (odds ratio 0.89, 95% confidence interval 0.63-1.24)., Conclusions: Obesity is not associated with favorable outcomes in patients undergoing MT for LVO., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: Mechanical thrombectomy (MT) improves outcomes in patients with LVO but many still experience mortality or severe disability. We sought to develop machine learning (ML) models that predict 90-day outcomes after MT for LVO., Methods: Consecutive patients who underwent MT for LVO between 2015-2021 at a Comprehensive Stroke Center were reviewed. Outcomes included 90-day favorable functional status (mRS 0-2), severe disability (mRS 4-6), and mortality. ML models were trained for each outcome using prethrombectomy data (pre) and with thrombectomy data (post)., Results: Three hundred and fifty seven patients met the inclusion criteria. After model screening and hyperparameter tuning the top performing ML model for each outcome and timepoint was random forest (RF). Using only prethrombectomy features, the AUCs for the RF pre models were 0.73 (95% CI 0.62-0.85) for favorable functional status, 0.77 (95% CI 0.65-0.86) for severe disability, and 0.78 (95% CI 0.64-0.88) for mortality. All of these were better than a standard statistical model except for favorable functional status. Each RF model outperformed Pre, SPAN-100, THRIVE, and HIAT scores (P < 0.0001 for all). The most predictive features were premorbid mRS, age, and NIHSS. Incorporating MT data, the AUCs for the RF post models were 0.80 (95% CI 0.67-0.90) for favorable functional status, 0.82 (95% CI 0.69-0.91) for severe disability, and 0.71 (95% CI 0.55-0.84) for mortality., Conclusions: RF models accurately predicted 90-day outcomes after MT and performed better than standard statistical and clinical prediction models., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Energy metabolism in vertebrates is controlled by three members of the PGC-1 (PPAR γ- coactivator 1) family, transcriptional coactivators that shape responses to physiological stimuli by interacting with the nuclear receptors and other transcription factors. Multiple evidence now supports that Spargel protein found in insects and ascidians is the ancestral form of vertebrate PGC-1's. Here, we undertook functional analysis of srl gene in Drosophila, asking about the requirement of Spargel per se during embryogenesis and its RNA binding domains. CRISPR- engineered srl gene deletion turned out to be an amorphic allele that is late embryonic/early larval lethal and Spargel protein missing its RNA binding domain (SrlΔRRM) negatively affects female fertility. Overexpression of wild-type Spargel in transgenic flies expedited the growth of egg chambers. On the other hand, oogenesis is blocked in a dominant-negative fashion in the presence of excess Spargel lacking its RRM domains. Finally, we observed aggregation of Notch proteins in egg chambers of srl mutant flies, suggesting that Spargel is involved in intracellular transport of Notch proteins. Taken together, we claim that these new mutant alleles of spargel are emerging powerful tools for revealing new biological functions for Spargel, an essential transcription coactivator in both Drosophila and mammals., Competing Interests: Conflicts of interest The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Background: We evaluated how systolic blood pressure (SBP) and mean arterial pressure (MAP) parameters between presentation and reperfusion influence functional status and intracranial hemorrhage (ICH)., Methods: All patients who underwent MT for LVO at a single institution were reviewed. Independent variables included SBP and MAP measurements obtained on presentation, between presentation and reperfusion (pre-reperfusion), and between groin puncture and reperfusion (thrombectomy). Mean, minimum, maximum, and standard deviations (SD) for SBP and MAP were calculated. Outcomes included 90-day favorable functional status, radiographic ICH (rICH), and symptomatic ICH (sICH)., Results: 305 patients were included. Higher pre-reperfusion SBP max was associated with rICH (OR 1.41, 95% CI 1.08-1.85) and sICH (OR 1.84, 95% CI 1.26-2.72). Higher SBP SD was also associated with rICH (OR 1.38, 95% CI 1.06-1.81) and sICH (OR 1.59, 95% CI 1.12-2.26). Greater SBP max (OR 0.64, 95% CI 0.47-0.86), MAP max (OR 0.72, 95% CI 0.52-0.97), SBP SD (OR 0.63, 95% CI 0.46-0.86), and MAP SD (0.63, 95% CI 0.45-0.84) during thrombectomy were associated with lower odds of 90-day favorable functional status. In a subgroup analysis, these associations were primarily limited to patients with intact collateral circulation. Optimal SBP max cutoffs for predicting rICH were 171 (pre-reperfusion) and 179 mmHg (thrombectomy). Cutoffs for predicting sICH were 178 (pre-reperfusion) and 174 mmHg (thrombectomy)., Conclusion: Greater maximum BP and variability in BP during the pre-reperfusion period are associated with unfavorable functional status and ICH after MT for anterior circulation LVO., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Prediction of malignant middle cerebral artery infarction (MMI) could identify patients for early intervention. We trained and internally validated a ML model that predicts MMI following mechanical thrombectomy (MT) for ACLVO., Methods: All patients who underwent MT for ACLVO between 2015 - 2021 at a single institution were reviewed. Data was divided into 80% training and 20% test sets. 10 models were evaluated on the training set. The top 3 models underwent hyperparameter tuning using grid search with nested 5-fold CV to optimize the area under the receiver operating curve (AUROC). Tuned models were evaluated on the test set and compared to logistic regression., Results: A total of 381 patients met the inclusion criteria. There were 50 (13.1%) patients who developed MMI. Out of the 10 ML models screened on the training set, the top 3 performing were neural network (median AUROC 0.78, IQR 0.72 - 0.83), support vector machine ([SVM] median AUROC 0.77, IQR 0.72 - 0.83), and random forest (median AUROC 0.75, IQR 0.68 - 0.81). On the test set, random forest (median AUROC 0.78, IQR 0.73 - 0.83) and neural network (median AUROC 0.78, IQR 0.73 - 0.83) were the top performing models, followed by SVM (median AUROC 0.77, IQR 0.70 - 0.83). These scores were significantly better than those for logistic regression (AUROC 0.72, IQR 0.66 - 0.78), individual risk factors, and the Malignant Brain Edema score (p < 0.001 for all)., Conclusion: ML models predicted MMI with good discriminative ability. They outperformed standard statistical techniques and individual risk factors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The transcranial approach for direct middle meningeal artery (MMA) access to embolize dural arteriovenous fistulas (dAVF) has been described, but limited information regarding the setup, equipment, and technique is available. We present the details of this hybrid approach in the setting of a ruptured Cognard grade IV tentorial dAVF (Video 1). The patient was an adult female who presented with nausea, vomiting, and dizziness and was found to have a cerebellar hemorrhage. Catheter angiography revealed a tentorial dAVF fed by bilateral middle meningeal, left posterior meningeal, and left occipital arteries. Attempted transarterial embolizations through each of these were unsuccessful. The left MMA was a primary source of supply, but distal microcatheter placement was not possible due to proximal tortuosity. Therefore transcranial MMA access distal to this tortuosity was pursued. The MMA was localized using roadmap angiography and a temporal craniectomy was completed over the artery. A 4-French sheath was placed, and super selective angiography was performed, demonstrating the fistula. A microcatheter was navigated to the fistula and it was embolized with Onyx. Postoperative angiogram demonstrated fistula occlusion. The patient remained at her neurologic baseline and was discharged home. Transcranial MMA access is a useful technique to overcome tortuosity that cannot be navigated with traditional endovascular techniques., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Myeloperoxidase (MPO) is a heme peroxidase with microbicidal properties. MPO plays a role in the host's innate immunity by producing reactive oxygen species inside the cell against foreign organisms. However, there is little functional evidence linking missense mutations to human diseases. We utilized in silico saturation mutagenesis to generate and analyze the effects of 10,811 potential missense mutations on MPO stability. Our results showed that ~71% of the potential missense mutations destabilize MPO, and ~8% stabilize the MPO protein. We showed that G402W, G402Y, G361W, G402F, and G655Y would have the highest destabilizing effect on MPO. Meanwhile, D264L, G501M, D264H, D264M, and G501L have the highest stabilization effect on the MPO protein. Our computational tool prediction showed the destabilizing effects in 13 out of 14 MPO missense mutations that cause diseases in humans. We also analyzed putative post-translational modification (PTM) sites on the MPO protein and mapped the PTM sites to disease-associated missense mutations for further analysis. Our analysis showed that R327H associated with frontotemporal dementia and R548W causing generalized pustular psoriasis are near these PTM sites. Our results will aid further research into MPO as a biomarker for human complex diseases and a candidate for drug target discovery.

Background: Intractable nasal and oropharyngeal hemorrhage may be treated with endovascular embolization, but limited data are available. We sought to evaluate the efficacy, safety, and factors associated with rebleeding., Methods: A retrospective analysis of consecutive embolizations for nasal and oropharyngeal hemorrhage over a 10-year period at a single institution was performed. Outcomes included procedural success (defined as cessation of hemorrhage in the immediate postoperative period), rebleeding requiring an additional intervention, and procedural complications., Results: A total of 47 embolizations on 39 patients were included. The mean age was 60 years (standard deviation 16.1), 23.1% of patients were women, and 21 (53.8%) patients had a previously diagnosed head/neck malignancy. Bleeding sites were the nose in 20 patients and oropharynx in 21 (two patients presented with both nasal and oral bleeding). Immediate procedural success was achieved in 45 (95.7%) embolizations. Rebleeding requiring an additional intervention occurred after 11 (23.4%) embolizations at a median of one day after the procedure. In the multivariate analysis, preoperative hypotension (odds ratio 4.78, 95% confidence interval 1.04-24.61) and the use of coils (odds ratio 6.09, 95% confidence interval 1.24-46.69) were associated with rebleeding requiring repeat intervention. Complications included two watershed strokes that were anticipated due to occlusion of the internal carotid artery., Conclusions: In our experience endovascular embolization was a safe and effective treatment option for stopping oral and nasal hemorrhage. However, rebleeding was present after 23.4% of treatments and was associated with preoperative hypotension and the use of coils. Further study in a large multi-institutional cohort is warranted.