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Purpose: Patients with rhabdomyosarcoma with metastatic disease have a poor prognosis despite therapy intensification. The aim of this study was to investigate the efficacy of whole lung irradiation (WLI) in patients with rhabdomyosarcoma and lung metastases., Methods: Patients with rhabdomyosarcoma with lung metastases enrolled on four Children's Oncology Group protocols (D9802, D9803, ARST08P1, ARST0431) were retrospectively reviewed. Event-free survival (EFS) and overall survival (OS) were compared between patients who received and did not receive WLI., Results: In 143 patients with rhabdomyosarcoma with lung metastases, 65 patients (45.5%) received WLI and 78 patients (54.5%) did not receive WLI despite protocol requirements. The 5-year EFS was 38.3% (95% CI, 24.8 to 51.8) in patients who received WLI and 25.2% (95% CI, 13.8 to 36.6) in patients who did not receive WLI ( P = .0496). The 5-year OS was 45.5% (95% CI, 31.8 to 59.3) in patients who received WLI and 32.4% (95% CI, 20.4 to 44.4) in patients who did not receive WLI ( P = .08). In exploratory subgroup analyses, the benefit of WLI on EFS and OS was significant in patients 10 years and older. Other clinical factors associated with EFS on univariable analysis included age, histology FOXO1 fusion status, number of metastatic sites, location of metastatic sites, and Oberlin Score., Conclusion: WLI is associated with improved EFS in patients with rhabdomyosarcoma with lung metastases. These results highlight the potential importance of WLI and need for more stringent protocol compliance for administering WLI.

Purpose: To develop a machine-learning algorithm to improve hepatic resection selection for metastatic colorectal cancer patients by predicting post-PVE outcomes., Material & Methods: This multicenter retrospective study (2000-2020) included 200 consecutive patients with CRC liver-metastases planned for PVE before surgery. Radiomic features and lab values were collected. Patient-specific eigenvalues for each liver shape were calculated using a statistical shape model approach. After semi-automatic segmentation and review by a board-certified radiologist, the data was split 70/30% for training and testing. Three machine learning algorithms predicting the total liver volume (TLV) after PVE, sufficient FLR%, and the kinetic growth rate % (KGR%) were trained with performance assessed using accuracy, sensitivty, specifity, AUC or RMSE. Significance between the internal and external test sets was assessed by the student's t-test. One institution was kept separate as an external testing set., Results: A total of 114 (76m; 56y ±12) and 37 (19m; 50y ±11) patients met the inclusion criteria for the internal and external validation. Prediction accuracy (SD) and AUC (SD) for sufficient FLR% or liver growth potential (KGR%> 0%) were high in the internal testing set 0.91 (±0.01), 85.81% (±1.01%) or 0.66 (±0.03), 87.44% (±0.10%)). Similar results occurred on the external testing set 0.88 (±0.00), 79.66% (±0.60%) or 0.69 (±0.01), 72.06% (±0.30%)). TLV prediction showed a discrepancy of 12.56% (95% CI: ±4.20%, p=0.86) internally and 13.57% (95% CI: ±3.76%, p=0.91) externally., Conclusion: These machine learning-based models can help predict the FLR%, KGR%, and TLV as metrics for successful PVE., (Copyright © 2024. Published by Elsevier Inc.)

Access to electricity is a key indicator of a country's development. In developing nations like Ethiopia, this metric is particularly crucial for assessing progress. Currently, about 45.8% of Ethiopia's population lacks access to electricity, with rural areas experiencing even higher rates, reaching 57.2%. The Southern Nations, Nationalities, and People's (SNNP) region faces the greatest challenge, with 62.1% of its population lacking electricity. Ethiopia aims to achieve universal electricity access by 2030, and microgrid (MG) development is expected to play a pivotal role in meeting this goal. This study employs a multi-tier framework (MTF) to categorize village households based on electricity access, considering factors like income level and willingness to pay, to support the MG development process. Three villages-Toba, Koza, and Womba-in the SNNP region were selected for optimal MG sizing. Sensitivity variables such as global horizontal irradiance (GHI) variation, photovoltaic (PV) and battery prices, battery usage limits, and capacity shortage levels were analyzed for their impact on net present cost (NPC), initial capital cost, and cost of energy (COE) using HOMER Pro software. For example, in the Toba MG, increasing the capacity shortage from 0 to 10% reduced the COE from 0.1195 $/kWh to 0.09104 $/kWh, a 23.82% decrease. Additionally, fluctuations in PV and battery prices had a direct impact on the system's NPC. The study also explored the impact of clustering the microgrids by interconnecting the three individual systems and conducting a techno-economic analysis. The comparison between standalone MG operation and clustered microgrids revealed that, despite the added cost of interconnection, the benefits in terms of technological, economic, and reliable operation of the clustered system were comparable to standalone microgrids. Finally, a feasibility study was conducted for the potential grid extension of the Toba MG, which is located 130 km from the nearest substation in Sawla., (© 2024. The Author(s).)

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten-eleven translocation (TET) enzymes, and can lead to global DNA hypermethylation. Here, we report patterns of hypermethylation in FH-mutant cell lines and tumor samples are associated with the silencing of nicotinate phosphoribosyl transferase (NAPRT), a rate-limiting enzyme in the Preiss-Handler pathway of NAD+ biosynthesis, in a subset of HLRCC cases. NAPRT is hypermethylated at a CpG island in the promoter in cell line models and patient samples, resulting in loss of NAPRT expression. We find that FH-deficient RCC models with loss of NAPRT expression, as well as other oncometabolite-producing cancer models that silence NAPRT, are extremely sensitive to nicotinamide phosphoribosyl transferase inhibitors (NAMPTi). NAPRT silencing was also associated with synergistic tumor cell killing with PARP inhibitors and NAMPTis, which was associated with effects on PAR-mediated DNA repair. Overall, our findings indicate that NAPRT silencing can be targeted in oncometabolite-producing cancers and elucidates how oncometabolite-associated hypermethylation can impact diverse cellular processes and lead to therapeutically relevant vulnerabilities in cancer cells. Implications: NAPRT is a novel biomarker for targeting NAD+ metabolism in FH-deficient HLRCCs with NAMPTis alone and targeting DNA repair processes with the combination of NAMPTis and PARP inhibitors., (©2024 The Authors; Published by the American Association for Cancer Research.)

Power electronic converters are widely implemented in many types of power applications such as microgrids. Power converters can make a physical connection between the power resources and the power application. To control a power converter, required data such as the voltage and the current of that should be measured to be used in a control application. Therefore, a communication-based structure including sensors and communication links can be used to measure the desired data and transmit that to the controllers. So, a power converter-based system can be considered as a type of cyber-physical system, and it can be vulnerable to cyber-attacks. Then, it can strongly be recommended to use a strategy for a power converter-based system to monitor the system and identify the existence of cyber-attack in the system. In this study, artificial intelligence (AI) is deployed to calculate the value of the false data (i.e., constant false data, and time-varying false data) and detect false data injection cyber-attacks on power converters. Besides, to have a precise technical evaluation of the proposed methodology, that is evaluated under other issues, i.e., noise, and communication link delay. In the case of noise, the proposed strategy is examined under noises with different signal-to-noise ratios . Further, for the case of the communication delay, the system is examined under both symmetrical (i.e., same communication delay on all inputs) and unsymmetrical communication delays (i.e., different communication delay/delays on the inputs). In this work, artificial neural networks are implemented as the AI-based application, and two types of the networks, i.e., feedforward (as a basic type) and long short-term memory (LSTM)-based network as a more complex network are tested. Finally, three important AI-based techniques (regression, classification, and clustering) are examined. Based on the obtained results, this work can properly identify and calculate the false data in the system., (© 2024. The Author(s).)

The challenge related to the coordination of overcurrent relays in a looped network, which is a highly constrained problem, is to find a more optimum solution and at the same time there is no miscoordination. In this problem, the utilized optimization algorithm has a direct effect on finding a more optimal solution. High exploration particle swarm optimization (HEPSO) algorithm, which utilizes multi-crossover mechanism of the genetic algorithm and the bee colony mechanism to increase the exploration capability, has been selected to solve the coordination problem. To validate the HEPSO algorithm, a new algorithm called turbulent flow of water-based optimization (TFWO) is also used, and their results are compared. A new approach to discretization of variables is presented, which prevents miscoordination in the relays coordination. It is a realistic assumption for all relay types, especially digital relays, in preventing miscoordination. Also, the outage of sub-transmission transformers is considered for determining pickup current, which is a practical aspect of power systems operation. The obtained results are compared with the results of other algorithms and methods such as metaheuristic, mathematical and analytical, and hybrid methods. The efficiency of the selected algorithm is proven through comprehensive comparisons. The results show more optimum solutions while there is no miscoordination. Finally, the performance of the selected algorithm and the proposed approaches are tested on IEEE 14 and 30-bus test systems. Since these test systems are large enough, the number of problem variables will increase significantly, effectively validating the power and robustness of the selected algorithm to tackle this complex and constrained problem. The outage of transformers in determining pickup currents had been implemented in this section., Competing Interests: 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., (© 2024 The Authors.)

Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma-related outcomes of short-term exposure to outdoor air pollutants (PM2.5, PM10, NO 2 , SO 2 , O 3 , and CO), heavy traffic, outdoor pesticides, and extreme temperatures. Additionally, the SR evaluated the impact of the efficacy of interventions reducing outdoor pollutants. The risk of bias was assessed using ROBINS-E tools and the certainty of the evidence by using GRADE. Short-term exposure to PM2.5, PM10, and NO 2 probably increases the risk of asthma-related hospital admissions (HA) and emergency department (ED) visits (moderate certainty evidence). Exposure to heavy traffic may increase HA and deteriorate asthma control (low certainty evidence). Interventions reducing outdoor pollutants may reduce asthma exacerbations (low to very low certainty evidence). Exposure to fumigants may increase the risk of new-onset asthma in agricultural workers, while exposure to 1,3-dichloropropene may increase the risk of asthma-related ED visits (low certainty evidence). Heatwaves and cold spells may increase the risk of asthma-related ED visits and HA and asthma mortality (low certainty evidence)., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

DNA damage is fundamental to tumorigenesis, and the inability to repair DNA damage is a hallmark of many human cancers. DNA is repaired via the DNA damage repair (DDR) apparatus, which includes five major pathways. DDR deficiencies in cancers give rise to potential therapeutic targets, as cancers harboring DDR deficiencies become increasingly dependent on alternative DDR pathways for survival. In this review, we summarize the DDR apparatus, and examine the current state of research efforts focused on identifying vulnerabilities in DDR pathways that can be therapeutically exploited in pediatric extracranial solid tumors. We assess the potential for synergistic combinations of different DDR inhibitors as well as combinations of DDR inhibitors with chemotherapy. Lastly, we discuss the immunomodulatory implications of targeting DDR pathways and the potential for using DDR inhibitors to enhance tumor immunogenicity, with the goal of improving the response to immune checkpoint blockade in pediatric solid tumors. We review the ongoing and future research into DDR in pediatric tumors and the subsequent pediatric clinical trials that will be critical to further elucidate the efficacy of the approaches targeting DDR.

Targeting oncogenes at the genomic DNA level can open new avenues for precision medicine. Significant efforts are ongoing to target oncogenes using RNA-targeted and protein-targeted platforms, but no progress has been made to target genomic DNA for cancer therapy. Here, we introduce a gamma peptide nucleic acid (γPNA)-based genomic DNA-targeted platform to silence oncogenes in vivo. γPNAs efficiently invade the mixed sequences of genomic DNA with high affinity and specificity. As a proof of concept, we establish that γPNA can inhibit c-Myc transcription in multiple cell lines. We evaluate the in vivo efficacy and safety of genomic DNA targeting in three pre-clinical models. We also establish that anti-transcription γPNA in combination with histone deacetylase inhibitors and chemotherapeutic drugs results in robust antitumor activity in cell-line- and patient-derived xenografts. Overall, this strategy offers a unique therapeutic platform to target genomic DNA to inhibit oncogenes for cancer therapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

This work analyzes the stability and performance of an offshore solar-concentrated ocean thermal energy conversion system (SC-OTEC) tied to an onshore AC grid. The OTEC is a system where electricity is generated using small temperature differences between the warm surface and deep cold ocean water. Existing control methods for SC-OTEC systems lack coordination, hindering dynamic stability and effective damping for the synchronous generator (SG). These methods struggle to quickly adapt to sudden disturbances and lack the capability to adequately reject or compensate for such disturbances due to complex control constraints and computational demands. To this regard, a control strategy combining sliding mode control (SMC) and a power system stabilizer (PSS) to improve the SC-OTEC dynamic stability and damping features for the SG. Moreover, an auxiliary secondary automatic voltage regulator is assembled with a non-linear exciter system to provide damping features. The proposed PID-PSS and secondary AVR controller gains are adaptively tuned using a modified whale optimization algorithm with the balloon effect modulation. The studied SC-OTEC is tested through MATLAB/Simulink under a severe 3ϕ short-circuit fault, solar radiation variations, and a change in surface seawater temperature as well as changes in local loads. The final findings approved that the proposed control strategy preserves a strong performance and can mimic effectively the proposed SC-OTEC damping compared to the conventional system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Abubakr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To determine outcomes of children with rhabdomyosarcoma (RMS) with isolated lung metastases., Methods: Data were analyzed for 428 patients with metastatic RMS treated on COG protocols. Categorical variables were compared using Chi-square or Fisher's exact tests. Event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier method and compared using the log-rank test., Results: Compared with patients with other metastatic sites (n = 373), patients with lung-only metastases (n = 55) were more likely to be <10 years of age, have embryonal histology (embryonal rhabdomyosarcoma), have N0 disease, and less likely to have primary extremity tumors. Lung-only patients had significantly better survival outcomes than patients with all other sites of metastatic disease (p < .0001) with 5-year EFS of 48.1 versus 18.8% and 5-year OS of 64.1 versus 26.9%. Patients with lung-only metastases, and those with a single extrapulmonary site of metastasis, had better survival compared with patients with two or more sites of metastatic disease (p < .0001). In patients with ERMS and lung-only metastases, there was no significant difference in survival between patients ≥10 years and 1-9 years (5-year EFS: 58.3 vs. 68.2%, 5-year OS: 66.7 vs. 67.7%)., Conclusions: With aggressive treatment, patients with ERMS and lung-only metastatic disease have superior EFS and OS compared with patients with other sites of metastatic disease, even when older than 10 years of age. Consideration should be given to including patients ≥10 years with ERMS and lung-only metastases in the same group as those <10 years in future risk stratification algorithms., (© 2023 Wiley Periodicals LLC.)

Opinion Statement: Primary malignant central nervous (CNS) tumors are a devastating group of diseases with urgent need for improved treatment options. Surgery, radiation, and cytotoxic chemotherapy remain the primary standard treatment modalities, with molecularly targeted therapies having proven efficacy in only small subsets of cases. Poly(ADP-ribose) polymerase (PARP) inhibitors, which have had immense success in the treatment of extracranial cancers with homologous recombination deficiency (HRD), are emerging as a potential targeted treatment for various CNS tumors. Although few primary CNS tumors display canonical BRCA gene defects, preclinical evidence suggests that PARP inhibitors may benefit certain CNS tumors with functional HRD or elevated replication stress. In addition, other preclinical studies indicate that PARP inhibitors may synergize with standard therapies used for CNS tumors including radiation and alkylating agents and may prevent or overcome drug resistance. Thus far, initial clinical trials with early-generation PARP inhibitors, typically as monotherapy or in the absence of selective biomarkers, have shown limited efficacy. However, the scientific rationale remains promising, and many clinical trials are ongoing, including investigations of more CNS penetrant or more potent inhibitors and of combination therapy with immune checkpoint inhibitors. Early phase trials are also critically focusing on determining active drug CNS penetration and identifying biomarkers of therapy response. In this review, we will discuss the preclinical evidence supporting use of PARP inhibitors in primary CNS tumors and clinical trial results to date, highlighting ongoing trials and future directions in the field that may yield important findings and potentially impact the treatment of these devastating malignancies in the coming years., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Loss-of-function mutations in genes encoding the Krebs cycle enzymes Fumarate Hydratase ( FH ) and Succinate Dehydrogenase ( SDH ) induce accumulation of fumarate and succinate, respectively and predispose patients to hereditary cancer syndromes including the development of aggressive renal cell carcinoma (RCC). Fumarate and succinate competitively inhibit αKG-dependent dioxygenases, including Lysine-specific demethylase 4A/B (KDM4A/B), leading to suppression of the homologous recombination (HR) DNA repair pathway. In this study, we have developed new syngeneic Fh1 - and Sdhb -deficient murine models of RCC, which demonstrate the expected accumulation of fumarate and succinate, alterations in the transcriptomic and methylation profile, and an increase in unresolved DNA double-strand breaks (DSBs). The efficacy of poly ADP-ribose polymerase inhibitors (PARPis) and temozolomide (TMZ), alone and in combination, was evaluated both in vitro and in vivo . Combination treatment with PARPi and TMZ results in marked in vitro cytotoxicity in Fh1 - and Sdhb -deficient cells. In vivo , treatment with standard dosing of the PARP inhibitor BGB-290 and low-dose TMZ significantly inhibits tumor growth without a significant increase in toxicity. These findings provide the basis for a novel therapeutic strategy exploiting HR deficiency in FH and SDH-deficient RCC with combined PARP inhibition and low-dose alkylating chemotherapy., Competing Interests: CONFLICTS OF INTEREST R.S.B. is a co-founder and consultant for Cybrexa Therapeutics and founder of Athena Therapeutics and co-founder of Aztek Bio. None of these companies has any conceptual or financial connection to this manuscript. DU, JCV, AS, JL, JVD, RS, SF, RC, SO, XB, HE, KB, RRH, JD, PB, BS declare no potential conflicts of interest., (Copyright: © 2022 Ueno et al.)

A Microgrid (MG), like any other smart and interoperable power system, requires device-to-device (D2D) communication structures in order to function effectively. This communication system, however, is not immune to intentional or unintentional failures. This paper discusses the effects of communication link failures on MG control and management and proposes solutions based on enhancing message content to mitigate their detritus impact. In order to achieve this goal, generation and consumption forecasting using deep learning (DL) methods at the next time steps is used. The architecture of an energy management system (EMS) and an energy storage system (ESS) that are able to operate in coordination is introduced and evaluated by simulation tests, which show promising results and illustrate the efficacy of the proposed methods. It is important to mention that, in this paper, three dissimilar topics namely MG control/management, DL-based forecasting, and D2D communication architectures are employed and this combination is proven to be capable of achieving the aforesaid objective.

Exatecan and deruxtecan are antineoplastic camptothecin derivatives in development as tumor-targeted-delivery warheads in various formulations including peptides, liposomes, polyethylene glycol nanoparticles, and antibody-drug conjugates. Here, we report the molecular pharmacology of exatecan compared with the clinically approved topoisomerase I (TOP1) inhibitors and preclinical models for validating biomarkers and the combination of exatecan with ataxia telangiectasia and Rad3-related kinase (ATR) inhibitors. Modeling exatecan binding at the interface of a TOP1 cleavage complex suggests two novel molecular interactions with the flanking DNA base and the TOP1 residue N352, in addition to the three known interactions of camptothecins with the TOP1 residues R364, D533, and N722. Accordingly, exatecan showed much stronger TOP1 trapping, higher DNA damage, and apoptotic cell death than the classical TOP1 inhibitors used clinically. We demonstrate the value of SLFN11 expression and homologous recombination (HR) deficiency (HRD) as predictive biomarkers of response to exatecan. We also show that exatecan kills cancer cells synergistically with the clinical ATR inhibitor ceralasertib (AZD6738). To establish the translational potential of this combination, we tested CBX-12, a clinically developed pH-sensitive peptide-exatecan conjugate that selectively targets cancer cells and is currently in clinical trials. The combination of CBX-12 with ceralasertib significantly suppressed tumor growth in mouse xenografts. Collectively, our results demonstrate the potency of exatecan as a TOP1 inhibitor and its clinical potential in combination with ATR inhibitors, using SLFN11 and HRD as predictive biomarkers., (©2022 American Association for Cancer Research.)

Mutations in the isocitrate dehydrogenase-1 and -2 (IDH1/2) genes were first identified in glioma and acute myeloid leukemia (AML), and subsequently found in multiple other tumor types. These neomorphic mutations convert the normal product of enzyme, α-ketoglutarate (αKG), to the oncometabolite 2-hydroxyglutarate (2HG). Our group recently demonstrated that 2HG suppresses the high-fidelity homologous recombination (HR) DNA repair pathway, resulting in a state referred to as 'BRCAness', which confers exquisite sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. In this study, we sought to elucidate sensitivity of IDH1/2-mutant cells to DNA damage response (DDR) inhibitors and, whether combination therapies could enhance described synthetic lethal interactions. Here, we report that ATR (ataxia telangiectasia and Rad3-related protein kinase) inhibitors are active against IDH1/2-mutant cells, and that this activity is further potentiated in combination with PARP inhibitors. We demonstrate this interaction across multiple cell line models with engineered and endogenous IDH1/2 mutations, with robust anti-tumor activity in vitro and in vivo . Mechanistically, we found ATR and PARP inhibitor treatment induces premature mitotic entry, which is significantly elevated in the setting of IDH1/2-mutations. These data highlight the potential efficacy of targeting HR defects in IDH1/2-mutant cancers and support the development of this combination in future clinical trials., (© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Cancer.)

We study the impact of the mixing (LR mixing) between the standard model W boson and its hypothetical, heavier right-handed parter W&#95;{R} on the neutrinoless double beta decay (0νββ decay) rate. Our study is done in the minimal left-right symmetric model assuming a type-II dominance scenario with charge conjugation as the left-right symmetry. We then show that the 0νββ decay rate may be dominated by the contribution proportional to this LR mixing, which at the hadronic level induces the leading-order contribution to the interaction between two pions and two charged leptons. The resulting long-range pion exchange contribution can significantly enhance the decay rate compared to previously considered short-range contributions. Finally, we find that even if future cosmological experiments rule out the inverted hierarchy for neutrino masses, there are still good prospects for a positive signal in the next generation of 0νββ decay experiments.

Current management of childhood leukemia is tailored based on disease risk determined by clinical features at presentation. Whether properties of the host immune response impact disease risk and outcome is not known. Here, we combine mass cytometry, single cell genomics, and functional studies to characterize the BM immune environment in children with B cell acute lymphoblastic leukemia and acute myelogenous leukemia at presentation. T cells in leukemia marrow demonstrate evidence of chronic immune activation and exhaustion/dysfunction, with attrition of naive T cells and TCF1+ stem-like memory T cells and accumulation of terminally differentiated effector T cells. Marrow-infiltrating NK cells also exhibit evidence of dysfunction, particularly in myeloid leukemia. Properties of immune cells identified distinct immune phenotype-based clusters correlating with disease risk in acute lymphoblastic leukemia. High-risk immune signatures were associated with expression of stem-like genes on tumor cells. These data provide a comprehensive assessment of the immune landscape of childhood leukemias and identify targets potentially amenable to therapeutic intervention. These studies also suggest that properties of the host response with depletion of naive T cells and accumulation of terminal-effector T cells may contribute to the biologic basis of disease risk. Properties of immune microenvironment identified here may also impact optimal application of immune therapies, including T cell-redirection approaches in childhood leukemia.

Statement: Communication and teamwork are important aspects of medicine and have been a recent focus of resuscitation. Culture can influence communication and teamwork, and these effects have not been studied in low-resource settings. Using a case study and the TEAM scale, we evaluated how culture influences teamwork and communication during resuscitation simulations, in addition to examining other challenges of simulation research in low-resource settings. We observed lower scores in leadership and communication skills than have been seen in other studies using the TEAM scale, which led us to evaluate the possible role of culture in influencing these skills. The high power distance and collectivism in Latin America can make communication difficult, especially during debriefing. Furthermore, in a male-biased medical hierarchy, female nurses may be less likely to voice concerns. Ultimately, this commentary provides advice for taking the influences of culture into account when planning future simulation training in low-resource settings.

Background: Helping Babies Breathe (HBB), a basic neonatal resuscitation curriculum, improves early neonatal mortality in low-resource settings. Our goal was to determine retention of resuscitation skills by different cadres of providers using the approved HBB Spanish translation in a rural clinic and community hospital in Honduras., Methods: Twelve clinic and 37 hospital providers were trained in 1 d HBB workshops and followed from July 2012 to February 2014. Resuscitation skills were evaluated by objective structured clinical evaluations (OSCEs) at regular intervals. Clinic providers practiced monthly, whereas hospital providers were randomized to monthly practice for 6 months vs three consecutive practices at 3, 5 and 6 months., Results: In the rural clinic, follow-up OSCE assessment showed rapid loss of skills by 1 month after HBB training. For all providers, repeated monthly testing resulted in improvements and maintenance of OSCE performance. In the community hospital, over all time points, the group with monthly OSCEs had 2.9 greater odds of passing compared with the group who practiced less frequently. Physicians were found to have 4.3 times greater odds of passing compared with nurses., Conclusions: Rapid loss of resuscitation skills occurs after an initial training. Repeated practice leads to retention of skills in all types of providers. Further investigation is warranted to determine the clinical correlation of neonatal outcomes after HBB training.

We report a case of a child with pre-B cell acute lymphoblastic leukemia undergoing maintenance chemotherapy with 6-mercaptopurine and methotrexate (MTX) who developed sinusoidal obstruction syndrome after being treated with ciprofloxacin for BK viremia. This case represents a rare complication of maintenance therapy with MTX and 6-mercaptopurine, and suggests a drug interaction between ciprofloxacin and MTX.

Background: To evaluate changes in neonatal resuscitation and postnatal care following Helping Babies Breathe (HBB) training at a community hospital in rural Honduras. We hypothesized that HBB training would improve resuscitation and essential newborn care interventions., Methods: Direct observation and video recording of delivery room care spanned before and after an initial HBB workshop held in August 2013. Rates of essential newborn care interventions were compared in resuscitations performed by individuals who had and had not received HBB training, and run charts recording performance of newborn care practices over time were developed., Results: Ten percent of deliveries (N=250) were observed over the study period, with 156 newborn resuscitations performed by individuals without HBB training, compared to 94 resuscitations performed by HBB trainees. After HBB training, significant improvements were seen in skin-to-skin care, breastfeeding within 60 min of age, and delayed cord clamping after 1 min (all P<0.01). More babies cared for by HBB trainees received basic neonatal resuscitation such as drying and stimulation. Run charts tracking these practices over time showed significant improvements after HBB training that were sustained during the study period, but remained below ideal goals. With improvement in drying/stimulation practices, fewer babies required bag/mask ventilation., Conclusion: In a rural Honduran community hospital, improvements in basic neonatal resuscitation and postnatal essential newborn care practices can be seen after HBB training. Further improvements in newborn care practices may require focused quality improvement initiatives for hospitals to sustain high quality care.

Therapies targeting immune checkpoints are effective in tumors with a high mutation burden that express multiple neo-antigens. However, glial tumors including those seen in children carry fewer mutations and there is an unmet need to identify new antigenic targets of anti-tumor immunity. SOX2 is an embryonal stem cell antigen implicated in the biology of glioma initiating cells. Expression of SOX2 by pediatric glial tumors and the capacity of the immune system in these patients to recognize SOX2 has not been previously studied. We examined the expression of SOX2 on archived paraffin-embedded tissue from pediatric glial tumors. The presence of T-cell immunity to SOX2 was examined in both blood and tumor-infiltrating T-cells in children and young adults with glioma. The nature of tumor-infiltrating immune cells was analyzed with a 37-marker panel using single-cell mass cytometry. SOX2 is expressed by tumor cells but not surrounding normal tissue in pediatric gliomas of all grades. T-cells against this antigen can be detected in blood and tumor tissue in glioma patients. Glial tumors are enriched for CD8/CD4 T-cells with tissue resident memory (T RM ; CD45RO + , CD69 + , CCR7 - ) phenotype, which co-express multiple inhibitory checkpoints including PD-1, PD-L1 and TIGIT. Tumors also contain natural killer cells with reduced expression of lytic granzyme. Our data demonstrate immunogenicity of SOX2, which is specifically overexpressed on pediatric glial tumor cells. Harnessing tumor immunity in glioma will likely require the combined targeting of multiple inhibitory checkpoints.

Introduction: Helping Babies Breathe (HBB) is a simulation-based neonatal resuscitation curriculum designed for low-resource settings. At the completion of the workshop, learners complete the following four assessments: a multiple-choice question (MCQ) test, bag-mask ventilation (BMV) checklist, and two objective structured clinical examinations (OSCEs). Objective structured clinical examinations are clinical performance assessments that evaluate learners' skills in simulated scenarios. The aims of this study were (1) to evaluate the validity and reliability of the OSCEs used in the HBB curriculum, (2) to conduct an itemized analysis of the OSCEs to identify specific deficits in knowledge and performance, and to identify areas of improvement for future versions of HBB., Methods: Seventy physicians and nurses completed an HBB workshop conducted in Spanish at a Honduran community hospital. Validity and reliability were examined using an item analysis of item difficulty, discrimination, correlation, and internal consistency/reliability., Results: Posttest scores were higher for all assessments. Most items on the OSCEs were of low difficulty and low discrimination. Item agreement was lowest for multistep items., Conclusions: As summative and formative assessments of performance in simulated neonatal resuscitation, the HBB OSCEs are effective because most learners were able to perform the skills correctly after an HBB workshop. On the basis of our results, we recommend changes to future editions of HBB, including the following: simplification of multistep items to single tasks, use of a global rating scale, provision of additional scenarios, and specific instructions to raters on how to grade OSCEs and promote self-reflection to enhance debriefings/feedback. Further validation and study of the OSCEs in the second edition of HBB would enhance their quality and translation into clinical performance.

Continued enlargement of the aneurysm sac after thoracic endovascular aortic repair (TEVAR) is a known risk after endovascular treatment of thoracic aortic aneurysms. For this reason, periodic outpatient follow-up is required to identify situations that require repair. Here, we describe an aortobronchial fistula (ABF) in a patient lost to follow-up, that presented 3 years after an elective TEVAR done for a primary, descending thoracic aortic aneurysm. Our patient arrived in extremis and suffered massive hemoptysis leading to her demise. Computed tomography (CT) angiogram near the time of her death demonstrated a bleeding ABF immediately distal to her previous TEVAR repair. Aortic aneurysmal disease remains life threatening even after repair. Improved endovascular techniques and devices have resulted in decreased need for reintervention. However, this case demonstrates the risk of thoracic aortic disease progression and highlights the importance of establishing consistent, long-term follow-up after TEVAR., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We present a rare late complication after inferior vena cava filter (IVC) placement. A 52-year-old woman with an IVC presented with sudden onset of chest pain. Cardiac catheterisation and echocardiography revealed an embolised IVC filter strut penetrating the right ventricle. Endovascular retrieval was considered but deemed unsafe due to proximity to the right coronary artery and concern for migration to pulmonary circulation. Urgent removal of the strut was performed via sternotomy. The postoperative course was uneventful. Two weeks later, she was asymptomatic. Minimally invasive approaches have been described for retrieval of intact IVC filters that have migrated to the right heart but not for embolised filter fragments. We recommend traditional sternotomy as the preferred method of retrieval as it limits the likelihood of further migration or trauma., (Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Pericardial effusions compress the heart, decrease cardiac output, and lead to haemodynamic collapse. Ultrasound (US)-guided pericardiocentesis is the gold standard for treating pericardial effusions. Recently, the incorporation of computed tomography (CT) guidance has increased patient safety while entering the pericardium. Despite the superior performance of CT-guided pericardiocentesis in smaller, complex effusions, this procedure is not routinely performed by cardiologists and surgeons. Unlike those with an intact pericardium, patients with mediastinal trauma, pericardial adhesions, temporary pacing wires, and vascular conduits are high risk for pericardiocentesis. Tamponade physiology also increases patient susceptibility to the hypotensive effects of anaesthesia during surgical drainage. Here we illustrate the technique of CT-guided pericardiocentesis and demonstrate its application in specific clinical scenarios. We conclude that CT-guided pericardiocentesis provides a useful, alternative strategy for treating cardiac tamponade in high risk patients., (Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objectives: Helping Babies Breathe is an evidence-based curriculum designed to teach basic neonatal resuscitation in low-resource countries. The purpose of this study was to evaluate the acquisition of knowledge and skills following this training and correlation of learner characteristics to performance in a Spanish-speaking setting., Methods: Thirty-one physicians and 39 nurses completed Helping Babies Breathe training at a Honduran community hospital. Trainee knowledge and skills were evaluated before and after the training using a multiple-choice questionnaire, bag-mask ventilation skills test, and two objective structured clinical exams (OSCEs). Linear mixed-effects models were used to analyze assessment scores pre- and post-training by profession (physician or nurse) while controlling for covariates., Results: Helping Babies Breathe training resulted in significant increases in mean scores for the multiple-choice question test, bag-mask ventilation skills test, and OSCE B. Time to initiation of effective bag-mask ventilation decreased from a mean of 74.8 to 68.4 s. Despite this improvement in bag-mask ventilation, only 42 % of participants were able to initiate effective bag-mask ventilation within the Golden Minute. Although physicians scored higher on the pre-test multiple-choice questions and bag-mask ventilation, nurses demonstrated a greater mean difference in scores after training. OSCE B scores pre- and post-training increased similarly between professions. Nurses' and physicians' performance in simulation was not significantly different after the training. Assessment scores and course feedback indicated a need for more skills practice, particularly with bag-mask ventilation., Conclusions: When evaluated immediately after an initial workshop, Helping Babies Breathe training resulted in significant gains in neonatal resuscitation knowledge and skills. Following training, nurses, who commonly do not perform these skills in real-life situations, were able to perform at a similar level to physicians. Further studies are necessary to determine how to sustain this knowledge and skills over time, tailor the course to learner characteristics, and whether this training translates into improvements in clinical practice.

Iatrogenic intraoperative tracheal injuries are rare in cardiac operations. Management of this complication is not well described because of the low incidence and lack of reported cases. We present an 82-year-old woman who sustained a tracheal injury during aortic valve replacement. Soft tissue coverage of the trachea was obtained, the original cardiac operation was completed, and she was otherwise managed conservatively. She recovered without further complication and was discharged home 1 week after the surgical procedure., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Neuronal networks in rodent barrel cortex are characterized by stable low baseline firing rates. However, they are sensitive to the action potentials of single neurons as suggested by recent single-cell stimulation experiments that reported quantifiable behavioral responses in response to short spike trains elicited in single neurons. Hence, these networks are stable against internally generated fluctuations in firing rate but at the same time remain sensitive to similarly-sized externally induced perturbations. We investigated stability and sensitivity in a simple recurrent network of stochastic binary neurons and determined numerically the effects of correlation between the number of afferent ("in-degree") and efferent ("out-degree") connections in neurons. The key advance reported in this work is that anti-correlation between in-/out-degree distributions increased the stability of the network in comparison to networks with no correlation or positive correlations, while being able to achieve the same level of sensitivity. The experimental characterization of degree distributions is difficult because all pre-synaptic and post-synaptic neurons have to be identified and counted. We explored whether the statistics of network motifs, which requires the characterization of connections between small subsets of neurons, could be used to detect evidence for degree anti-correlations. We find that the sample frequency of the 3-neuron "ring" motif (1→2→3→1), can be used to detect degree anti-correlation for sub-networks of size 30 using about 50 samples, which is of significance because the necessary measurements are achievable experimentally in the near future. Taken together, we hypothesize that barrel cortex networks exhibit degree anti-correlations and specific network motif statistics.

Objectives: To describe the preoperative, intraoperative and postoperative characteristics of patients with left-sided heart valve disease treated in the thoracic and cardiovascular surgery service of a national reference hospital; as well as to describe the occurrence of thromboembolic and bleeding events in these patients., Materials and Methods: A retrospective longitudinal study was carried out, which included 185 patients who underwert surgery between 1999 and 2006 at the Hospital Nacional Dos de Mayo (Lima, Peru). The patients were divided into 4 groups: patients with mitral commissurotomy; with aortic valve replacement; with mitral valve replacement and with double valve replacement. T-student test, Chi-square test, analysis of variance and Bonferroni test were used. The survival analysis took into account the severe thromboembolic and bleeding events and a follow-up period of 7 years was set., Results: The average durations of disease was 4.6 years. The most frequent etiology was rheumatic valve disease (74.6%). Hospital mortality was 3.8%, the most frequent cause of death was low cardiac output syndrome associated to multiple organ failure. The incidence of ischemic events (thrombosis or embolization) in patients who had a long-term valve replacement (more than 6 months) was 3.2%, and the incidence of bleeding events was 4.3%., Conclusions: The results of surgical treatment for left-sided heart valve disease in Peru are favorable. The rate of complications and hospital mortality rate, as well as the long-term thromboembolic and bleeding events are comparable to those reported in the world literature.

We present a method to estimate Gibbs distributions with spatio-temporal constraints on spike trains statistics. We apply this method to spike trains recorded from ganglion cells of the salamander retina, in response to natural movies. Our analysis, restricted to a few neurons, performs more accurately than pairwise synchronization models (Ising) or the 1-time step Markov models (Marre et al., 2009) to describe the statistics of spatio-temporal spike patterns and emphasizes the role of higher order spatio-temporal interactions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We present a patient with aortoesophageal fistula that occurred years after an acute type B aortic dissection that was treated medically. This patient developed aneurysmal dilatation of the chronically dissected aorta, which finally eroded into the esophagus. Endovascular management with the placement of a stent graft was performed, but the patient ultimately died of multiorgan failure and possible myocardial infarction.

Patients with central venous occlusion who are ''tunneled catheter dependent'' are a challenge for hemodialysis access. A relatively new option for them is the hemodialysis reliable outflow (HeRO) device that can be totally implanted subcutaneously. However, patients still require a tunneled hemodialysis catheter that is used until the HeRO device is mature, 4 to 6 weeks later. Here, we describe a conversion of an existing tunneled hemodialysis catheter into a HeRO device, which was combined with a ''self-sealing'' Flixene graft. This allowed almost immediate use of the HeRO device without the need for placement of a catheter.

The Hemodialysis Reliable Outflow (HeRO) device is a novel alternative for dialysis access in patients with no suitable veins in the upper extremities. We placed a HeRO device in a 67-year-old woman with end-stage renal disease and 2 months later, it was being used for hemodialysis. After 1 month of uneventful use, the device thrombosed and it was rescued with a percutaneous endovascular approach. The device remains patent 6 months after the intervention.

Aneurysms of the iliac vein are rare. They can occur in association with arteriovenous fistulae located elsewhere. Here, we present a 30-year-old man who developed a large left external iliac vein aneurysm in association with a chronic traumatic arteriovenous fistula in the left thigh. Less than 25 cases of iliac vein aneurysms have been reported in the last 40 years. The presentation and treatment of this condition has been heterogeneous. We suggest that adequate surgical treatment can be offered in a staged approach: aneurysm resection with reconstruction should be done first, followed by closure of the arteriovenous fistula 6 months later.

Cystectomy without capitonnage is a widely used surgical technique for liver hydatid disease. A residual cavity can be left during the procedure, which can turn into an abscess. We report the case of a patient who developed right pleural empyema as a late complication of this procedure. She was successfully managed with antibiotics and a right thoracotomy.

Background: The upsurge of gastric bypass procedures has been accompanied by an increase in anastomotic strictures and marginal ulcers. According to the reported literature, the gastrojejunostomy strictures in 3-31% and ulcerates in 1-16% of cases. Several anastomotic techniques are used, however no study has specifically addressed whether choice of reinforcing suture affects rates of stricture or ulcer. We reviewed our case series to determine if a protocol change in suture choice altered the incidence of anastomotic strictures and marginal ulcers., Methods: We performed a retrospective review of a prospectively collected database for 315 primary Roux-en-Y gastric bypass patients (7/2008 to 3/2008). Nearly all patients had a 25-mm circular stapled anastomosis with an outer suture layer for reinforcement. Before 5/31/06, interrupted permanent suture was used in 231 patients, and after 6/1/06 interrupted absorbable suture was used in 84 patients. We compared overall rates of stricture, marginal ulceration, and aggregate gastrojejunostomy complications between the two suture groups using a proportional hazards model and log-rank statistic. A p-value < 0.05 was used to assign statistical significance., Results: We found statistically fewer gastrojejunostomy complications in the absorbable suture group (4.7%) than the permanent suture group (19.9%). Subgroup analysis showed that anastomotic strictures were less common in the absorbable suture group, but the difference was short of statistical confirmation. Use of absorbable suture did result in statistically fewer marginal ulcers (2.3%) compared with absorbable suture (13.4%)., Conclusions: Use of absorbable reinforcing sutures is associated with fewer gastrojejunostomy complications. We recommend absorbable sutures for the outer layer of stapled gastrojejunal anastomoses when performing isolated Roux-en-Y gastric bypass.

Background: Lung hydatid cyst caused by Echinococcus granulosus is endemic in many areas of the world. We aimed to compare the outcome of surgical treatment in intact and ruptured (infected or noninfected) cysts., Methods: We reviewed the medical records of 115 patients with lung hydatid disease who were surgically treated between 2001 and 2005 in a tertiary hospital in Lima, Peru. Patients were divided into 3 groups based on cyst characteristics: intact cysts (n = 41), ruptured noninfected cysts (n = 47) and ruptured infected cysts (n = 27). If a patient had more than one type of cyst, the most severe form of disease was recorded. Data related to symptoms, morbidity and mortality were recorded and compared. We also calculated direct patient costs., Results: Mean age of patients was 23.6 +/- 15.1 years old. Ruptured cysts were present in 64 % of patients and giant cysts (> 10 cm diameter) were present in 26 % of patients. Hemoptysis was present in 47.0 % of patients and was more frequent in patients with ruptured infected cysts. Lung resection was performed in 58 % of patients. The most common postoperative complication was infection of the operative wound (6.08 %). Perioperative mortality was zero. Patients with ruptured cysts had a longer hospitalization time and higher total cost (12.28 +/- 0.92 days, US$ 890.34 +/- 303.35) than patients with intact cysts (10.17 +/- 0.79 days, US$ 724.81 +/- 14.38)., Conclusion: Surgical treatment of lung hydatid disease is safe, with a good outcome and a low mortality rate. The lung resection rate was higher than most published series and reflects the relatively high proportion of patients with giant and ruptured infected cysts.