bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of ketogenic diet in CDKL5-related epilepsy: a single arm meta-analysis
Authors: Zhang Jie , Ma Jiayi , Chang Xuting , Wu Pengxia , Li Shangru , Wu Ye
Published: October 2022

Background

Drug-resistant epilepsy is one of the most important features of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder. The ketogenic diet (KD) may be effective for patients with CDKL5-related epilepsy, but there is little high-quality evidence to confirm the efficacy. This meta-analysis investigated the efficacy and safety of KD in CDKL5-related epilepsy.

Methods

The PubMed, Embase, Web of Science, Cochrane Library, WanFang, CNKI and VIP databases were searched for relevant studies published up to January 1, 2022. Two reviewers independently screened the literature according to inclusion and exclusion criteria and evaluated the bias risk of the included studies. Meta-analysis was performed using Review Manager 5.3 software.

Results

A total of 12 retrospective studies involving 193 patients met the inclusion criteria. Meta-analysis revealed that the definite responder rate to KD in the treatment of CDKL5-related epilepsy was 18.0% [95% CI (0.07, 0.67)], with no statistical heterogeneity among studies (I2 = 0%, P = 0.45). The clinical responder rate was 50.5% [95% CI (0.75, 1.39)], and there was no statistical heterogeneity among all studies (I2 = 46%, P = 0.05). Subgroup analysis showed that there was no significant difference in the clinical responder rate between the two groups with seizure onset age before and after 1 month (P = 0.14). Only one study mentioned adverse reactions, and the incidence of adverse reactions was 78.3% (18/23). Constipation and vomiting were the main manifestations, implying a high incidence of gastrointestinal adverse reactions.

Conclusions

The definite responder rate to KD in CDKL5-related epilepsy was 18%, and the gastrointestinal adverse reactions were probably common in these patients. All the studies included in the meta-analysis were retrospective, and most of them had small sample sizes. Additional high-quality studies are needed to confirm the efficacy and tolerance of KD in CDKL5-related epilepsy.
PV-IRES-Cre mouse line targets excitatory granule neurons in the cerebellum
Authors: Wang Wendy Xueyi , Qiao Julia , Lefebvre Julie L.
Published: October 2022

Parvalbumin-expressing inhibitory neurons (PV-INs) are critical for the balance and fine-tuning of complex neuronal circuits. Studies of PV-IN biology require tools for their specific labeling, targeting and manipulation. Among these, the Cre/LoxP system is the most popular in mice, with the two commonly used PV-Cre lines cited over 5600 times. Here we report in the mouse cerebellar cortex that PV-Cre activity is not restricted to inhibitory neurons. Imaging of Cre-activated reporters demonstrated recombination in excitatory granule cells. We present evidence that PV-Cre recombination is: (1) spatially regulated and lobule specific; (2) detected in granule cells in the external and internal granule cell layers arising from strong, but transient Pvalb expression in progenitors between E13-E15; and (3) delayed in a subset of inhibitory interneurons, asynchronous with PV protein expression. Together, our findings establish the spatio-temporal patterns PV-Cre activation in the mouse cerebellum, raising considerations for conditional targeting of Pvalb-expressing inhibitory populations.
Phase II trial of daratumumab with DCEP in relapsed/refractory multiple myeloma patients with extramedullary disease
Authors: Byun Ja Min , Min Chang-Ki , Kim Kihyun , Bang Soo-Mee , Lee Je-Jung , Kim Jin Seok , Yoon Sung-Soo , Koh Youngil
Published: October 2022

Extramedullary multiple myeloma (EMD) is an aggressive subentity of multiple myeloma (MM) with poor prognosis. As more innovative therapeutic approaches are needed for the treatment of MM with EMD, we conducted this multicenter, non-randomized phase II trial of daratumumab in combination with dexamethasone, cyclophosphamide, etoposide and cisplatin (DARA-DCEP). A total of 32 patients (median age 59, range 35–73) were treated with DARA-DCEP. Based on the best response during the study, the complete remission (CR) rate was 35.5% and overall response rate (ORR) 67.7%. During the median follow-up of 11 months, the median progression-free survival (PFS) was 5 months and median overall survival (OS) 10 months. There were 7 long-term responders whose median PFS was not reached. The most common grade ≥ 3 hematologic AE was thrombocytopenia. The most common non-hematologic AE was nausea (22.6%), followed by dyspepsia, diarrhea and stomatitis (all 12.9%). Grade ≥ 3 daratumumab infusion-related reaction was noted in 9.7% of the patients. Except for the planned 30% dose adjustment in cycle 1, only 2 patients required DCEP dose reduction. This is one of the very few prospective trials focusing on EMD and we successfully laid grounds for implementing immunochemotherapy in MM treatment.
Effects of rapid fluid infusion on hemoglobin concentration: a systematic review and meta-analysis
Authors: Quispe-Cornejo Armin A. , Alves da Cunha Ana L. , Njimi Hassane , Mongkolpun Wasineenart , Valle-Martins Ana L. , Arébalo-López Mónica , Creteur Jacques , Vincent Jean-Louis
Published: October 2022

Background

Rapid fluid administration may decrease hemoglobin concentration (Hb) by a diluting effect, which could limit the increase in oxygen delivery (DO2) expected with a positive response to fluid challenge in critically ill patients. Our aim was to quantify the decrease in Hb after rapid fluid administration.

Methods

Our protocol was registered in PROSPERO (CRD42020165146). We searched PubMed, the Cochrane Database, and Embase from inception until February 15, 2022. We selected studies that reported Hb before and after rapid fluid administration (bolus fluid given over less than 120 min) with crystalloids and/or colloids in adults. Exclusion criteria were studies that included bleeding patients, or used transfusions or extracorporeal circulation procedures. Studies were divided according to whether they involved non-acutely ill or acutely ill (surgical/trauma, sepsis, circulatory shock or severe hypovolemia, and mixed conditions) subjects. The mean Hb difference and, where reported, the DO2 difference before and after fluid administration were extracted. Meta-analyses were conducted to assess differences in Hb before and after rapid fluid administration in all subjects and across subgroups. Random-effect models, meta-regressions and subgroup analyses were performed for meta-analyses. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic.

Results

Sixty-five studies met our inclusion criteria (40 in non-acutely ill and 25 in acutely ill subjects), with a total of 2794 participants. Risk of bias was assessed as “low” for randomized controlled trials (RCTs) and ‘low to moderate’ for non-RCTs. Across 63 studies suitable for meta-analysis, the Hb decreased significantly by a mean of 1.33 g/dL [95% CI − 1.45 to − 1.12; p < 0.001; I2 = 96.88] after fluid administration: in non-acutely ill subjects, the mean decrease was 1.56 g/dL [95% CI − 1.69 to − 1.42﻿; p < 0.001; I2 = 96.71] and in acutely ill patients 0.84 g/dL [95% CI − 1.03 to − 0.64; p = 0.033; I2 = 92.91]. The decrease in Hb was less marked in patients with sepsis than in other acutely ill patients. The DO2 decreased significantly in fluid non-responders with a significant decrease in Hb.

Conclusions

Hb decreased consistently after rapid fluid administration with moderate certainty of evidence. This effect may limit the positive effects of fluid challenges on DO2 and thus on tissue oxygenation.
Efficacy and safety of Jiu-Wei-Xi-Feng granules for treating tic disorders in children: study protocol for a randomized controlled equivalence trial
Authors: Guo Sheng-xuan , Li Rui-ben , Hu Si-yuan , Cai Qiu-han , Zhong Cheng-liang , Hao Rui-min
Published: October 2022

Background

Tic disorders (TD) is a neuropsychiatric disease with twitch as the main manifestation in childhood. Jiu-Wei-Xi-Feng granules has been marketed in China for treating children with TD. As Long Gu (Os Draconis) in the composition of this Chinese patent medicine is a rare and expensive medicinal material protected by the Chinese government, therefore, we consider replacing it with Mu Li (Concha Ostreae) that has the same effect and is cheaper. This study is designed to evaluate the clinical equivalence between Jiu-Wei-Xi-Feng granules (Os Draconis replaced by Concha Ostreae) (JWXFD) and Jiu-Wei-Xi-Feng granules (original formula) (JWXFO) in children with TD (consumption of renal yin and liver wind stirring up internally syndrome).

Methods/design

This is a multicenter, randomized, double-blind, equivalence trial comparing the efficacy and safety of JWXFD and JWXFO in treating Children with tic disorders (consumption of renal yin and liver wind stirring up internally syndrome). A total of 288 patients will be recruited and randomly assigned to two groups in a 1:1 ratio. The treatment course is 6 weeks, with a 2 weeks follow-up. The primary outcome is the mean change value from baseline to 6th week by the Yale Global Tic Severity Scale total tic score (YGTSS-TTS). Secondary outcomes include total effective rate of tic, Yale Global Tic Severity Scale (YGTSS) scores and its factor scores (the degree of motor tics, phonic tics and social function damage), Clinical Global Impression-Severity scale, and TCM syndrome efficacy.

Discussion

The design of this study refers to a large number of similar research design points, and asked for opinions of peer experts, and finally reached a consensus. This trial will provide high-quality evidence on the clinical equivalence between JWXFD and JWXFO and provide a basis for the marketing of JWXFD.

Trial registration

ChiCTR2000032312

Registered on 25 April 2020, http://www.chictr.org.cn/showproj.aspx?proj=52630
The use of 3D ceramic block graft compared with autogenous block graft for rehabilitation of the atrophic maxilla: a randomized controlled clinical trial
Authors: de Almeida Malzoni Carolina Mendonça , Gonçalves Victor , Possari Juliana , Junior Elcio Marcantonio
Published: October 2022

Background

Dental implant placement may require a bone graft for vertical and horizontal alveolar ridge augmentation. Due to its osteoconduction, osteoinductive, and osteogenesis, autogenous bone graft characteristics are considered the standard gold treatment. However, autografts can promote postoperative morbidity and implicate difficulties concerning the graft adaptation to the recipient's bone since it can eventually avoid gaps. To overcome these issues, this trial will compare the performance of Plenum® Oss 3Dβ fit, an alloplastic graft, and a 3D-printed patient-specific graft based on β-tricalcium phosphate to the autograft procedure.

Methods

This is a split-mouth randomized clinical study designed to evaluate the performance of personalized (patient-specific) bioceramic bone grafts (Plenum® Oss 3Dβ fit) for bone augmentation of the atrophic anterior maxilla in comparison to the autogenous bone graft. We hypothesize that the gain and maintenance of the grafted area volume and the quality of the newly formed bone tissue after eight months postoperative with the synthetic patient-specific graft will be superior to the autogenous bone graft. To assess the quantity and the quality of bone neoformation, volumetric and histological analyses will be performed.

Discussion

The fabrication of medical devices by additive manufacturing presents advantages over conventional manufacturing processes, mostly related to the precision of geometry and anatomy. Additionally, the osteoconductive proprieties of β-tricalcium phosphate enable this synthetic bone substitute as an alternative solution over autogenous graft for bone defect reconstruction. Thus, patient-specific bone grafts can potentially improve patient satisfaction, reducing the need for autogenous bone grafts, consequently avoiding implications related to this type of treatment, such as patient morbidity.

Trial registration

This study is registered in REBEC (Registro Brasileiro de Ensaios Clínicos): RBR-76wmm3q; UTN: U1111-1272-7773. Registration date: 14 September 2021.
Ecological drivers of dog heartworm transmission in California
Authors: Couper Lisa I. , Mordecai Erin A.
Published: October 2022

Background

Effectively controlling heartworm disease—a major parasitic disease threatening animal health in the US and globally—requires understanding the local ecology of mosquito vectors involved in transmission. However, the key vector species in a given region are often unknown and challenging to identify. Here we investigate (i) the key vector species associated with transmission of the parasite, Dirofilaria immitis, in California and (ii) the climate and land cover drivers of vector presence.

Methods

To identify key mosquito vectors involved in transmission, we incorporated long-term, finely resolved mosquito surveillance data and dog heartworm case data in a statistical modeling approach (fixed-effects regression) that rigorously controls for other unobserved drivers of heartworm cases. We then used a flexible machine learning approach (gradient boosted machines) to identify the climate and land cover variables associated with the presence of each species.

Results

We found significant, regionally specific, positive associations between dog heartworm cases and the abundance of four vector species: Aedes aegypti (Central California), Ae. albopictus (Southern California), Ae. sierrensis (Central California), and Culiseta incidens (Northern and Central California). The proportion of developed land cover was one of the most important ecological variables predicting the presence or absence of the putative vector species.

Conclusion

Our results implicate three previously under-recognized vectors of dog heartworm transmission in California and indicate the land cover types in which each putative vector species is commonly found. Efforts to target these species could prioritize surveillance in these land cover types (e.g. near human dwellings in less urbanized settings for Ae. albopictus and Cs. incidens) but further investigation on the natural infection prevalence and host-biting rates of these species, as well as the other local vectors, is needed.

Graphical Abstract
Effective treatment of a child with adenoidal hypertrophy and severe asthma by omalizumab: a case report
Authors: Sui Haijing , Zhang Huishan , Ding Wei , Zhao Zuotao , Mo Jiali , Yuan Jiexin , Ye Leping
Published: October 2022

Background

Childhood adenoid hypertrophy (AH) is common and is often associated with allergic asthma, resulting in complications like obstructive sleep apnea syndrome (OSAS). Management of the disease and its complications is often challenging.

Case presentation

We report here a case of a 10-year-old boy who suffered from severe allergic asthma and rhinitis and was treated with omalizumab. Before the treatment, the childhood asthma control test (C-ACT, 14), visal analog scale (VAS, 7) and lung function (mild obstructive ventilation dysfunction and moderate to severe dysfunction in ventilation in small airway) were seriously affected. Polysomnography showed OSAS (apnea hypopnea index, AHI, 6.4), low hypooxia saturation (lowest pulse oxygen saturation, LoSpO2, 70%), and adenoid hypertrophy (at grade III). After treating with omalizumab for 4 weeks (once treatment), the ventilation function, symptoms of asthma and allergic rhinitis (C-ACT, 24; VAS, 2), and OSAS (AHI: 1.8 and LoSpO2: 92.6%) were all improved, and the adenoids size was also significantly reduced to grade II. And during the following 3 times of treatment, the allergic symptoms continued improving, and the size of adenoid was reduced to grade I. Even 6.5 months after cessation of omalizumab, the size of adenoid remained at grade I.

Conclusion

This is the first documented case that childhood adenoid hypertrophy can be significantly improved by omalizumab.
Heparin-induced thrombocytopenia following Shiga-toxin-associated hemolytic uremic syndrome: a case report
Authors: Rigamonti Elia , Bonora Tecla , Ventresca Mariangela , Cippà Pietro
Published: October 2022

Background

Up to 50% of cases of Shiga-toxin-producingEscherichia colihemolytic uremic syndrome occur in adults, and the clinical presentation is variable. Microbiological analyses must be performed in all patients with thrombotic microangiopathy to identify Shiga-toxin-producingEscherichia coli, even in the absence of diarrhea.

Case presentation

A 79-year-old Caucasian woman was admitted to hospital because of severe proctitis. In the following days, the patient’s level of consciousness declined, and she developed acute kidney injury, thrombocytopenia, and hemolytic anemia. Shiga-toxin-producingEscherichia coliwas found in fecal cultures, suggesting the diagnosis of hemolytic uremic syndrome. In the following days, her clinical conditions improved, but thrombocytopenia worsened, and the patient developed posterior tibial vein thrombosis. The discordant evolution of thrombocytopenia compared with other clinical and laboratory parameters prompted a new evaluation of its causes. Diagnosis of heparin-induced thrombocytopenia was confirmed by heparin-induced platelet aggregation assay and positive antibodies to platelet factor 4.

Conclusions

A discordant evolution of platelet count in patients with thrombotic microangiopathy requires a systematic reevaluation of the thrombocytopenia.
Myocytic androgen receptor overexpression does not affect sex differences in adaptation to chronic endurance exercise
Authors: Barsky Sabrina Tzivia , Monks Douglas Ashley
Published: October 2022

Muscle-specific androgen receptor (AR) overexpression (HSAAR transgene) in sedentary male rats results in reduced adiposity, increased mitochondrial enzyme activity, and selective increase in Type 2b myofiber size. Here, we tested chronic endurance exercise interactions with this phenotype in both sexes. Across 9 weeks, rats ran 5×/week on motorized running wheels at increasing speeds and durations. Exercise reduced fat mass in all groups, but sex affected endurance exercise outcomes such that absolute lean mass increased only in females and total body mass decreased only in males. Expected sex differences were observed with males exhibiting greater total body and lean mass; absolute and relative fat mass; bone mineral density; extensor digitorum longus (EDL) myofiber size and glycolytic proportion; but lesser Type 2a and Type 1 myosin expression in tibialis anterior. Observed HSAAR outcomes were not altered by sex, with transgenic rats having greater lean mass, Type 2a myosin expression in soleus, and glycolytic myofiber size in EDL. Tibialis AR content was independently affected by sex, HSAAR, and exercise. No sex differences were observed in tibialis AR expression in wild-type rats, although HSAAR males had greater AR content than HSAAR females. We identified a moderate correlation between AR expression and glycolytic myofiber size, but not whole-body composition. Overall, results suggest myocytic AR overexpression and chronic exercise, despite sharing a similar phenotype to adaptation, are mediated by distinct mechanisms. Further, this study illustrates sex differences in adaptation to chronic endurance exercise, and suggests sex-similarity in the relationship between muscle AR and exercise response.
Effect of progesterone administration in male and female smokers on nicotine withdrawal and neural response to smoking cues: role of progesterone conversion to allopregnanolone
Authors: Novick Andrew M. , Duffy Korrina A. , Johnson Rachel L. , Sammel Mary D. , Cao Wen , Strasser Andrew A. , Sofuoglu Mehmet , Kuzma Alexandra , Loughead James , Morrow A. Leslie , Epperson C. Neill
Published: October 2022

Background

Progesterone administration has therapeutic effects in tobacco use disorder (TUD), with females benefiting more than males. Conversion of progesterone to the neurosteroid allopregnanolone is hypothesized to partly underlie the therapeutic effects of progesterone; however, this has not been investigated clinically.

Methods

Smokers (n = 18 males, n = 21 females) participated in a randomized, double-blind, placebo-controlled crossover study of 200 mg progesterone daily across 4 days of abstinence. The ratio of allopregnanolone:progesterone was analyzed in relationship to nicotine withdrawal, smoking urges, mood states, subjective nicotine effects, and neural response to smoking cues.

Results

Allopregnanolone:progesterone ratio interacted with sex to predict withdrawal symptoms (p = 0.047), such that females with higher allopregnanolone:progesterone ratios reported lower withdrawal severity (b = − 0.98 [− 1.95, − 0.01]; p = 0.048). In addition, allopregnanolone:progesterone ratio interacted with sex to predict confusion (p = 0.014) and fatigue (p = 0.034), such that females with higher allopregnanolone:progesterone ratios reported less confusion (b = − 0.45 [− 0.78, − 0.12]; p = 0.008) and marginally lower fatigue (b = − 0.50 [− 1.03, 0.02]; p = 0.062. Irrespective of sex, higher ratios of allopregnanolone:progesterone were associated with stronger “good effects” of nicotine (b = 8.39 [2.58, 14.20]); p = 0.005) and weaker “bad effects” of nicotine (b = − 7.13 [− 13.53, − 0.73]; p = 0.029).

Conclusions

Conversion of progesterone to allopregnanolone correlated with smoking-related outcomes in both sex-dependent and sex-independent ways. Sex-dependent effects suggest that conversion of progesterone to allopregnanolone may contribute to greater therapeutic benefits in females but not males with TUD.

Trial registration Clinicaltrials.gov registration, retrospectively registered: NCT01954966; https://clinicaltrials.gov/ct2/show/NCT01954966\
Bile acid distributions, sex-specificity, and prognosis in colorectal cancer
Authors: Cai Yuping , Shen Xinyi , Lu Lingeng , Yan Hong , Huang Huang , Gaule Patricia , Muca Engjel , Theriot Casey M. , Rattray Zahra , Rattray Nicholas J. W. , Lu Jun , Ahuja Nita , Zhang Yawei , Paty Philip B. , Khan Sajid A. , Johnson Caroline H.
Published: October 2022

Background

Bile acids are known to be genotoxic and contribute to colorectal cancer (CRC). However, the link between CRC tumor bile acids to tumor location, patient sex, microbiome, immune-regulatory cells, and prognosis is not clear.

Methods

We conducted bile acid analysis using targeted liquid chromatography–mass spectrometry (LC–MS) on tumor tissues from CRC patients (n = 228) with survival analysis. We performed quantitative immunofluorescence (QIF) on tumors to examine immune cells.

Results

Twelve of the bile acids were significantly higher in right-sided colon tumors compared to left-sided colon tumors. Furthermore, in male patients, right-sided colon tumors had elevated secondary bile acids (deoxycholic acid, lithocholic acid, ursodeoxycholic acid) compared to left-sided colon tumors, but this difference between tumors by location was not observed in females. A high ratio of glycoursodeoxycholic to ursodeoxycholic was associated with 5-year overall survival (HR = 3.76, 95% CI = 1.17 to 12.1, P = 0.026), and a high ratio of glycochenodeoxycholic acid to chenodeoxycholic acid was associated with 5-year recurrence-free survival (HR = 3.61, 95% CI = 1.10 to 11.84, P = 0.034). We also show correlation between these bile acids and FoxP3 + T regulatory cells.

Conclusions

This study revealed that the distribution of bile acid abundances in colon cancer patients is tumor location-, age- and sex-specific, and are linked to patient prognosis. This study provides new implications for targeting bile acid metabolism, microbiome, and immune responses for colon cancer patients by taking into account primary tumor location and sex.
Sparse convolutional array for DOA estimation
Authors: Wang Zikai , Liu Yun , Song Ruiliang , Liu Ning , Liang Qilian
Published: October 2022

Array signal processing plays an important role in many areas. Besides the Uniform Linear Array, there are many sparse array that have been proposed, for example, Minimum-redundancy array, Co-prime array, nested array, etc. However, most of the array structures have certain disadvantages. A new type of nonlinear sparse sensor array called sparse convolutional array is illustrated which can reduce the number of physical sensors while remain a decent performance in DOA estimation. The sparse convolutional array contains three groups of physical sensors and is able to form a hole-free difference co-array. By adding sensors on two sides instead of the center, the proposed array shows improved performance compared to some other approaches while reminds few physical sensors. The array geometrical structure is illustrated, and the numerical result is provided. We also extended this array structure to two-dimensional case, and the performance is illustrated.
Convolutional neural networks for the classification of guitar effects and extraction of the parameter settings of single and multi-guitar effects from instrument mixes
Authors: Hinrichs Reemt , Gerkens Kevin , Lange Alexander , Ostermann Jörn
Published: October 2022

Guitar effects are commonly used in popular music to shape the guitar sound to fit specific genres, or to create more variety within musical compositions. The sound not only is determined by the choice of the guitar effect, but also heavily depends on the parameter settings of the effect. Previous research focused on the classification of guitar effects and extraction of their parameter settings from solo guitar audio recordings. However, more realistic is the classification and extraction from instrument mixes. This work investigates the use of convolution neural networks (CNNs) for the classification and parameter extraction of guitar effects from audio samples containing guitar, bass, keyboard, and drums. The CNN was compared to baseline methods previously proposed, like support vector machines and shallow neural networks together with predesigned features. On two datasets, the CNN achieved classification accuracies $$1-5\,\%$$

1
-
5

%

above the baseline accuracy, achieving up to $$97.4\, \%$$

97.4

%

accuracy. With parameter values between 0.0 and 1.0, mean absolute parameter extraction errors of below 0.016 for the distortion, below 0.052 for the tremolo, and below 0.038 for the slapback delay effect were achieved, matching or surpassing the presumed human expert error of 0.05. The CNN approach was found to generalize to further effects, achieving mean absolute parameter extraction errors below 0.05 for the chorus, phaser, reverb, and overdrive effect. For sequentially applied combinations of distortion, tremolo, and slapback delay, the mean extraction error slightly increased from the performance for the single effects to the range of 0.05 to 0.1. The CNN was found to be moderately robust to noise and pitch changes of the background instrumentation suggesting that the CNN extracted meaningful features.
Classified 3D mapping and deep learning-aided signal power estimation architecture for the deployment of wireless communication systems
Authors: Egi Yunus , Eyceyurt Engin
Published: October 2022

The traditional wireless communication systems deployment models require expensive and time-consuming procedures, including environment selection (rural, urban, and suburban), drive test data collection, and analysis of the raw data. These procedures mainly utilize stochastic and deterministic approaches for signal strength prediction to locate the optimum cellular tower (eNodeB) position for 4G and 5G systems. Since environment selection is limited by urban, suburban, and rural areas, they do not cover complex macro and micro variations, especially buildings and tree canopies having a higher impact on signal fading due to scattering and absorption. Therefore, they usually end up with high prediction errors. This article proposes an efficient architecture for the deployment of communication systems. The proposed method determines the effect of the environment via extracting tree and building properties by using a classified 3D map and You Only Look Once (YOLO) V5, which is one of the most efficient deep learning algorithms. According to the results, the mean average precision (mAP) 0.5% and mAP 0.95% accuracies are obtained as 0.96 and 0.45, and image color classification (ICC) findings indicate 77.6% accuracy on vegetation detection, especially for tree canopies. Thus, the obtained results significantly improved signal strength prediction with a 3.96% Mean Absolute Percentage Error (MAPE) rate, while other empirical models’ prediction errors fall in the range of 6.07–15.26%.
Bond-based peridynamics, a survey prospecting nonlocal theories of fluid-dynamics
Authors: Dimola Nunzio , Coclite Alessandro , Fanizza Giuseppe , Politi Tiziano
Published: October 2022

Peridynamic (PD) theories have become widespread in various research areas due to the ability of modeling discontinuity formation and evolution in materials. Bond-based peridynamics (BB-PD), notwithstanding some modeling limitations, is widely employed in numerical simulations due to its easy implementation combined with physical intuitiveness and stability. In this paper, we review and investigate several aspects of bond-based peridynamic models. We present a detailed description of peridynamics theory, applications, and numerical models. We display the employed BB-PD integral kernels together with their differences and commonalities; then we discuss some consequences of their mathematical structure. We critically analyze and comment on the kinematic role of nonlocality, the relation between kernel structure and material impenetrability, and the role of PD kernel nonlinearity in crack formation prediction. Finally, we propose and present the idea of extending BB-PD to fluids in the framework of fading memory material, drawing some perspectives for a deeper and more comprehensive understanding of the peridynamics in fluids.
Serverless computing: a security perspective
Authors: Marin Eduard , Perino Diego , Di Pietro Roberto
Published: October 2022

In this article we review the current serverless architectures, abstract and categorize their founding principles, and provide an in-depth security analysis. In particular, we: show the security shortcomings of the analyzed serverless architectural paradigms; point to possible countermeasures; and, highlight several research directions for practitioners, Industry, and Academia.
SDG 8 and the food–energy–water nexus: a two-country dynamic computable general equilibrium CGE model
Authors: Schlör Holger , Schubert Stefanie A.
Published: October 2022

Background

In the twenty-first century, the success story of the Post-World-War-II World has been called into question by climate change and other challenges. De-growth or zero economic growth are discussed as possible solutions for mitigating climate change. The traditional economic growth model is increasingly challenged by the demand for sustained economic growth expressed in United Nations Sustainable Development Goal 8 “sustained economic growth” (UN-SDG 8) and supported by the European Green Deal. The aim of this paper is to contribute to the general understanding of characteristics, effects and challenges of new economic growth ideas as well as their interlinkages with the food–energy–water (FEW) nexus.

Methods

To address these challenges, a stylized dynamic General Equilibrium Model (GEM) was developed, which consists of two countries: an emerging, developing European country A and a developed European country B. Country A is assumed to grow, while country B shrinks. The model is based on artificial data sets. This approach was chosen to prevent the blurring of counterfactual comparison by country-specific effects of economic turbulences such as the Lehman crash or the economic break-in during the Covid-19 pandemic.

Results

The gross output of the emerging European country increases, whereas the output of the developed European country decreases according to the different growth strategies. The analysis reveals that a constantly widening gap between the emerging and the developed country is created. It can further be shown how this influences the relevant economic indicators (CO2emissions, household budget, trade balance, utility and social welfare).

Conclusions

The analysis of the two-country stylized GE model makes distortions visible: insignificant gaps in the values and development of analyzed economic indicators become prevalent. The welfare gap affects the core of the traditional socio-economic system, because the development of the utility of the households is central for the stability of political processes. A sufficiency and subsistence sector may be an option to even out the welfare losses from the de-growth strategy of the traditional economic system to avoid that the de-growth gaps are perceived by the community as welfare losses which can endanger the realization of UN-SDG 8.
Attitudes and training related to substance use in pediatric emergency departments
Authors: Hoch Ariel M. , Schoenberger Samantha F. , Boyle Tehnaz P. , Hadland Scott E. , Gai Mam Jarra , Bagley Sarah M.
Published: October 2022

Background

In recent years, pediatric emergency departments (PED) have seen an increase in presentations related to substance use among their adolescent patient population. We aimed to examine pediatric emergency medicine (PEM) physicians’ knowledge, attitudes, and beliefs on caring for adolescents with substance use.

Methods

We conducted a cross-sectional online survey of PEM physicians through the American Academy of Pediatrics Pediatric Emergency Medicine Collaborative Research Committee (PEM-CRC) listserv. The 41-item survey contained the following domains: demographics, current protocols and education for managing adolescent substance use, and attitudes about treatment of substance use. We calculated descriptive statistics for each variable within the domains.

Results

Of 177 respondents (38.2% response rate), 55.4% were female, 45.2% aged ≥ 50 years, 78% worked in a children’s hospital, and 50.8% had > 15 years clinical practice. Overall, 77.8% reported caring for adolescents with a chief complaint related to non-opioid substance use and 26.0% opioid use at least once a month. Most (80.9%) reported feeling comfortable treating major medical complications of substance use, while less than half were comfortable treating withdrawal symptoms. 73% said that they were not interested in prescribing buprenorphine.

Conclusions

Among this national sample of PEM physicians, 3 of 4 physicians managed substance-related visits monthly, but 52% lacked comfort in managing withdrawal symptoms and 73.1% were not interested in prescribing buprenorphine. Almost all PEM physician identified substance use-related education is important but lacked access to faculty expertise or educational content. Expanded access to education and training for PEM physicians related to substance use is needed.
Utilization of Basaltic Quarry Dust as a Partial Replacement of Cement for Hollow Concrete Block Production
Authors: Mitikie Bahiru Bewket , Alemu Yohannis Lemma , Reda Shumet Getahun
Published: October 2022

This research was conducted to examine the potential of basaltic crusher dust as a partial replacement for Portland Pozzolana cement in hollow concrete block (HCB) production. Quarry dust is one of the waste materials abundantly available and pozzolanic material in the quarry industry. In doing so, physical tests of cement pastes and hollow concrete blocks of different classes, i.e., A, B, and C, were produced by partially replacing the cement content with 10%, 20%, 30%, and 40% by weight of basaltic crusher dust using vibrating block molding machine. The units without basaltic crusher dust (0%) serve as a control variable. The cement pastes were examined for consistency and setting time, and the blocks produced were tested to determine their compressive strength, water absorption rate, and density. Furthermore, the possible cost advantages of using basaltic crusher dust as a partial replacement of cement in the hollow concrete block were analyzed. The result indicates that the experimental HCB of classes A and C surpassed the required standard of compressive strength, water absorption, and density specified by the Ethiopian standard ES 596:2001; whereas, the compressive strength of class B fails at 40% cement replacement. It was concluded that hollow concrete blocks of classes A and C with up to 40% replacement and class B with up to 30% replacement can be used for load-bearing walls and save the e cost of hollow concrete blocks with comparable properties.
The long way to innovation adoption: insights from precision agriculture
Authors: Masi Margherita , De Rosa Marcello , Vecchio Yari , Bartoli Luca , Adinolfi Felice
Published: October 2022

The adoption of innovations may boost the transition to sustainable agricultural models. Among these innovations, precision farming offers a fundamental contribution to sustainable soil management and the improvement in product quality. The work is set against this background and aims to analyse the rate of introducing precision farming tools and the variables that prevent/facilitate this adoption. Although adoption rates in Italy remain relatively low, it is vital to underline the obstacles that limit the broader use of precision agricultural technologies inside farms. To this end, the literature has highlighted various elements of complexity (farm characteristics, socio-economic and psychological), which can hinder or generate perceived complexity and significantly reduce the potential for technology adoption. In this context emerges the increasing importance of public and private activities related to knowledge transfer. The paper focuses on agricultural knowledge and innovation systems, which are also relevant in light of the recent proposal for the new regulation on rural development. The awareness–knowledge–adoption–product (AKAP) sequence was used to reveal the gap between the potential and actual adoption of innovation on Italian farms to comprehend the adoption process and identify relevant barriers and the role knowledge systems played. Empirical findings show that AKIS has a critical mediating function in promoting innovation uptake. Strengthening knowledge systems, acting on the different phases of the AKAP sequence, could allow a greater understanding of precision agriculture techniques and bottlenecks to adoption.
Dexmedetomidine alleviates inflammatory response and oxidative stress injury of vascular smooth muscle cell via α2AR/GSK-3β/MKP-1/NRF2 axis in intracranial aneurysm
Authors: Zhang Ze , Mu Xiue , Zhou Xiaohui
Published: October 2022

Vascular smooth muscle cell (VSMC) phenotypic modulation regulates the initiation and progression of intracranial aneurysm (IA). Dexmedetomidine (DEX) is suggested to play neuroprotective roles in patients with craniocerebral injury. Therefore, we investigated the biological functions of DEX and its mechanisms against IA formation and progression in the current study. The rat primary VSMCs were isolated from Sprague–Dawley rats. IA and superficial temporal artery (STA) tissue samples were obtained from patients with IA. Flow cytometry was conducted to identify the characteristics of isolated VSMCs. Hydrogen peroxide (H2O2) was used to mimic IA-like conditions in vitro. Cell viability was detected using CCK-8 assays. Wound healing and Transwell assays were performed to detect cell motility. ROS production was determined by immunofluorescence using DCFH-DA probes. Western blotting and RT-qPCR were carried out to measure gene expression levels. Inflammation responses were determined by measuring inflammatory cytokines. Immunohistochemistry staining was conducted to measure α2-adrenergic receptor levels in tissue samples. DEX alleviated the H2O2-induced cytotoxicity, attenuated the promoting effects of H2O2on cell malignancy, and protected VSMCs against H2O2-induced oxidative damage and inflammation response. DEX regulated the GSK-3β/MKP-1/NRF2 pathway via the α2AR. DEX alleviates the inflammatory responses and oxidative damage of VSMCs by regulating the GSK-3β/MKP-1/NRF2 pathway via the α2AR in IA.
Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma
Authors: Joshkon Ahmad , Tabouret Emeline , Traboulsi Wael , Bachelier Richard , Simoncini Stéphanie , Roffino Sandrine , Jiguet-Jiglaire Carine , Badran Bassam , Guillet Benjamin , Foucault-Bertaud Alexandrine , Leroyer Aurelie S. , Dignat-George Françoise , Chinot Olivier , Fayyad-Kazan Hussein , Bardin Nathalie , Blot-Chabaud Marcel
Published: October 2022

Rationale

Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis. The U.S. food and drug administration approved the use of the anti-VEGF antibody bevacizumab in recurrent GBM. However, resistance to this treatment is frequent and fails to enhance the overall survival of patients. In this study, we aimed to identify novel mechanism(s) responsible for bevacizumab-resistance in CD146-positive glioblastoma.

Methods

The study was performed using sera from GBM patients and human GBM cell lines in culture or xenografted in nude mice.

Results

We found that an increase in sCD146 concentration in sera of GBM patients after the first cycle of bevacizumab treatment was significantly associated with poor progression free survival and shorter overall survival. Accordingly, in vitro treatment of CD146-positive glioblastoma cells with bevacizumab led to a high sCD146 secretion, inducing cell invasion. These effects were mediated through integrin αvβ3 and were blocked by mucizumab, a novel humanized anti-sCD146 antibody. In vivo, the combination of bevacizumab with mucizumab impeded CD146 + glioblastoma growth and reduced tumor cell dissemination to an extent significantly higher than that observed with bevacizumab alone.

Conclusion

We propose sCD146 to be 1/ an early biomarker to predict and 2/ a potential target to prevent bevacizumab resistance in patients with glioblastoma.
High-resolution transcriptomics informs glial pathology in human temporal lobe epilepsy
Authors: Pai Balagopal , Tome-Garcia Jessica , Cheng Wan Sze , Nudelman German , Beaumont Kristin G. , Ghatan Saadi , Panov Fedor , Caballero Elodia , Sarpong Kwadwo , Marcuse Lara , Yoo Jiyeoun , Jiang Yan , Schaefer Anne , Akbarian Schahram , Sebra Robert , Pinto Dalila , Zaslavsky Elena , Tsankova Nadejda M.
Published: October 2022

The pathophysiology of epilepsy underlies a complex network dysfunction between neurons and glia, the molecular cell type-specific contributions of which remain poorly defined in the human disease. In this study, we validated a method that simultaneously isolates neuronal (NEUN +), astrocyte (PAX6 + NEUN–), and oligodendroglial progenitor (OPC) (OLIG2 + NEUN–) enriched nuclei populations from non-diseased, fresh-frozen human neocortex and then applied it to characterize the distinct transcriptomes of such populations isolated from electrode-mapped temporal lobe epilepsy (TLE) surgical samples. Nuclear RNA-seq confirmed cell type specificity and informed both common and distinct pathways associated with TLE in astrocytes, OPCs, and neurons. Compared to postmortem control, the transcriptome of epilepsy astrocytes showed downregulation of mature astrocyte functions and upregulation of development-related genes. To gain further insight into glial heterogeneity in TLE, we performed single cell transcriptomics (scRNA-seq) on four additional human TLE samples. Analysis of the integrated TLE dataset uncovered a prominent subpopulation of glia that express a hybrid signature of both reactive astrocyte and OPC markers, including many cells with a mixed GFAP + OLIG2 + phenotype. A further integrated analysis of this TLE scRNA-seq dataset and a previously published normal human temporal lobe scRNA-seq dataset confirmed the unique presence of hybrid glia only in TLE. Pseudotime analysis revealed cell transition trajectories stemming from this hybrid population towards both OPCs and reactive astrocytes. Immunofluorescence studies in human TLE samples confirmed the rare presence of GFAP + OLIG2 + glia, including some cells with proliferative activity, and functional analysis of cells isolated directly from these samples disclosed abnormal neurosphere formation in vitro. Overall, cell type-specific isolation of glia from surgical epilepsy samples combined with transcriptomic analyses uncovered abnormal glial subpopulations with de-differentiated phenotype, motivating further studies into the dysfunctional role of reactive glia in temporal lobe epilepsy.
Reversal of cancer gene expression identifies repurposed drugs for diffuse intrinsic pontine glioma
Authors: Zhao Guisheng , Newbury Patrick , Ishi Yukitomo , Chekalin Eugene , Zeng Billy , Glicksberg Benjamin S. , Wen Anita , Paithankar Shreya , Sasaki Takahiro , Suri Amreena , Nazarian Javad , Pacold Michael E. , Brat Daniel J. , Nicolaides Theodore , Chen Bin , Hashizume Rintaro
Published: October 2022

Diffuse intrinsic pontine glioma (DIPG) is an aggressive incurable brainstem tumor that targets young children. Complete resection is not possible, and chemotherapy and radiotherapy are currently only palliative. This study aimed to identify potential therapeutic agents using a computational pipeline to perform an in silico screen for novel drugs. We then tested the identified drugs against a panel of patient-derived DIPG cell lines. Using a systematic computational approach with publicly available databases of gene signature in DIPG patients and cancer cell lines treated with a library of clinically available drugs, we identified drug hits with the ability to reverse a DIPG gene signature to one that matches normal tissue background. The biological and molecular effects of drug treatment was analyzed by cell viability assay and RNA sequence. In vivo DIPG mouse model survival studies were also conducted. As a result, two of three identified drugs showed potency against the DIPG cell lines Triptolide and mycophenolate mofetil (MMF) demonstrated significant inhibition of cell viability in DIPG cell lines. Guanosine rescued reduced cell viability induced by MMF. In vivo, MMF treatment significantly inhibited tumor growth in subcutaneous xenograft mice models. In conclusion, we identified clinically available drugs with the ability to reverse DIPG gene signatures and anti-DIPG activity in vitro and in vivo. This novel approach can repurpose drugs and significantly decrease the cost and time normally required in drug discovery.