bluuebunny/crossref_metadata_2025 huggingface dataset:
Contextual differences considered in the Tunisian ADOLOPMENT of the European guidelines on breast cancer screening
Authors: Kahale Lara A. , Ouertatani Hella , Brahem Asma Ben , Grati Hela , Hamouda Mohammed Ben , Saz-Parkinson Zuleika , Akl Elie A.
Published: May 2021

Background

Breast cancer is a common disease in Tunisia and is associated with high mortality rates. The “Instance Nationale de l’Evaluation et de l’Accréditation en Santé” (INEAS) and the Tunisian Society of Oncology decided to develop practice guidelines on the subject. While the development of de novo guidelines on breast cancer screening is a demanding process, guideline adaptation appears more appropriate and context sensitive. The objective of this paper is to describe the adaptation process of the European Guidelines on Breast Cancer Screening and Diagnosis to the Tunisian setting in terms of the methodological process, contextual differences between the source and adoloped guideline, and changes in the recommendations.

Methods

We used the ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE)-ADOLOPMENT methodology to prioritize the topic, select the source guideline, and prioritize the questions and the outcomes. Once the source guideline was selected—the European Breast Cancer Guidelines—the European Commission´s Joint Research Centre shared with the project team in Tunisia all relevant documents and files. In parallel, the project team searched for local studies on the disease prevalence, associated outcomes’ baseline risks, patients’ values and preferences, cost, cost-effectiveness, acceptability, and feasibility. Then, the adoloping panel reviewed the GRADE evidence tables and the Evidence to Decision tables and discussed whether their own judgments were consistent with those from the source guideline or not. They based their judgments on the evidence on health effects, the contextual evidence, and their own experiences.

Results

The most relevant contextual differences between the source and adoloped guidelines were related to the perspective, scope, prioritized questions, rating of outcome importance, baseline risks, and indirectness of the evidence. The ADOLOPMENT process resulted in keeping 5 out of 6 recommendations unmodified. One recommendation addressing “screening versus no screening with ultrasound in women with high breast density on mammography screening” was modified from ‘conditional against’ to ‘conditional for either’ due to more favorable ratings by the adoloping panel in terms of equity and feasibility.

Conclusion

This process illustrates both the feasibility of GRADE-ADOLOPMENT approach and the importance of consideration of contextual evidence. It also highlights the value of collaboration with the organization that developed the source guideline.
METTL13 inhibits progression of clear cell renal cell carcinoma with repression on PI3K/AKT/mTOR/HIF-1α pathway and c-Myc expression
Authors: Liu Zhuonan , Sun Tianshui , Piao Chiyuan , Zhang Zhe , Kong Chuize
Published: May 2021

Background

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of renal malignancy. Methyltransferase like 13 (METTL13) functions as an oncogene in most of human cancers, but its function and mechanism in ccRCC remains unreported.

Methods

qRT-PCR, western blotting and immunohistochemistry were used to detect METTL13’s expression in tissues. The effects of METTL13 on ccRCC cells’ growth and metastasis were determined by both functional experiments and animal experiments. Weighted gene co-expression network analysis (WGCNA) was performed to annotate METTL13’s functions and co-immunoprecipitation (co-IP) was used to determine the interaction between METTL13 and c-Myc.

Results

METTL13 was underexpressed in ccRCC tissues compared to normal kidney tissues and its low expression predicted poor prognosis for ccRCC patients. The in vitro studies showed that knockdown and overexpression of METTL13 respectively led to increase and decrease in ccRCC cells’ proliferation, viability, migratory ability and invasiveness as well as epithelial-mesenchymal transition (EMT). The in vivo experiment demonstrated the inhibitory effect that METTL13 had on ccRCC cells’ growth and metastasis. Bioinformatic analyses showed various biological functions and pathways METTL13 was involved in. In ccRCC cells, we observed that METTL13 could negatively regulate PI3K/AKT/mTOR/HIF-1α pathway and that it combined to c-Myc and inhibited c-Myc protein expression.

Conclusions

In general, our finding suggests that high expression of METTL13 is associated with favorable prognosis of ccRCC patients. Meanwhile, METTL13 can inhibit growth and metastasis of ccRCC cells with participation in multiple potential molecular mechanisms. Therefore, we suggest METTL13 can be a new diagnostic and therapeutic target for ccRCC in the future.
Acute inflammatory profiles differ with sex and age after spinal cord injury
Authors: Stewart Andrew N. , Lowe John L. , Glaser Ethan P. , Mott Caitlin A. , Shahidehpour Ryan K. , McFarlane Katelyn E. , Bailey William M. , Zhang Bei , Gensel John C.
Published: May 2021

Background

Sex and age are emerging as influential variables that affect spinal cord injury (SCI) recovery. Despite a changing demographic towards older age at the time of SCI, the effects of sex or age on inflammation remain to be elucidated. This study determined the sex- and age-dependency of the innate immune response acutely after SCI.

Methods

Male and female mice of ages 4- and 14-month-old received T9 contusion SCI and the proportion of microglia, monocyte-derived macrophages (MDM), and neutrophils surrounding the lesion were determined at 3- and 7-day post-injury (DPI) using flow cytometry. Cell counts of microglia and MDMs were obtained using immunohistochemistry to verify flow cytometry results at 3-DPI. Microglia and MDMs were separately isolated using fluorescence-activated cell sorting (FACS) at 3-day post-injury (DPI) to assess RNA expression of 27 genes associated with activation, redox, and debris metabolism/clearance.

Results

Flow cytometry revealed that being female and older at the time of injury significantly increased MDMs relative to other phagocytes, specifically increasing the ratio of MDMs to microglia at 3-DPI. Cell counts using immunohistochemistry revealed that male mice have more total microglia within SCI lesions that can account for a lower MDM/microglia ratio. With NanoString analyses of 27 genes, only 1 was differentially expressed between sexes in MDMs; specifically, complement protein C1qa was increased in males. No genes were affected by age in MDMs. Only 2 genes were differentially regulated in microglia between sexes after controlling for false discovery rate, specifically CYBB (NOX2) as a reactive oxygen species (ROS)-associated marker as well as MRC1 (CD206), a gene associated with reparative phenotypes. Both genes were increased in female microglia. No microglial genes were differentially regulated between ages. Differences between microglia and MDMs were found in 26 of 27 genes analyzed, all expressed higher in MDMs with three exceptions. Specifically, C1qa, cPLA2, and CD86 were expressed higher in microglia.

Conclusions

These findings indicate that inflammatory responses to SCI are sex-dependent at both the level of cellular recruitment and gene expression.
Rupture of contralateral mainstem bronchus during uniportal video-assisted thoracoscopy surgery lobectomy and 3 successful cases of repair
Authors: Luo Zhilin , Wang Tianhu , Zhang Hong
Published: May 2021

Background

Our goal was to discuss the treatment for rupture of contralateral mainstem bronchus during uniportal video-assisted thoracoscopy surgery (uniportal VATS) lobectomy.

Case presentation

We analyzed clinical data of 3 cases of rupture of contralateral mainstem bronchus during uniportal VATS. Surgical repair was performed immediately under an uniportal VATS during operation, as a result, 3 cases of bronchial rupture all were repaired successfully, and we continued to complete lobectomy and systemic lymph node dissection. Reexamination was performed after 1 week, and no fistula was found in trachea and bronchi through a fiberoptic bronchoscopy. The time range for indwelling the chest tube is 6–9 days, and the hospital stay is 8–10 days. No abnormality was observed on chest radiography when the 3 patients returned to the hospital 1 month after the operation for the second reexamination.

Conclusions

Instant surgical repair is recommended to the treatment of bronchial rupture in thoracic surgery. It is safe and feasible to repair bronchial tear with uniportal VATS.
Calcium channelopathies and intellectual disability: a systematic review
Authors: Kessi Miriam , Chen Baiyu , Peng Jing , Yan Fangling , Yang Lifen , Yin Fei
Published: May 2021

Background

Calcium ions are involved in several human cellular processes including corticogenesis, transcription, and synaptogenesis. Nevertheless, the relationship between calcium channelopathies (CCs) and intellectual disability (ID)/global developmental delay (GDD) has been poorly investigated. We hypothesised that CCs play a major role in the development of ID/GDD and that both gain- and loss-of-function variants of calcium channel genes can induce ID/GDD. As a result, we performed a systematic review to investigate the contribution of CCs, potential mechanisms underlying their involvement in ID/GDD, advancements in cell and animal models, treatments, brain anomalies in patients with CCs, and the existing gaps in the knowledge. We performed a systematic search in PubMed, Embase, ClinVar, OMIM, ClinGen, Gene Reviews, DECIPHER and LOVD databases to search for articles/records published before March 2021. The following search strategies were employed: ID and calcium channel, mental retardation and calcium channel, GDD and calcium channel, developmental delay and calcium channel.

Main body

A total of 59 reports describing 159 cases were found in PubMed, Embase, ClinVar, and LOVD databases. Variations in ten calcium channel genes including CACNA1A, CACNA1C, CACNA1I, CACNA1H, CACNA1D, CACNA2D1, CACNA2D2, CACNA1E, CACNA1F, and CACNA1G were found to be associated with ID/GDD. Most variants exhibited gain-of-function effect. Severe to profound ID/GDD was observed more for the cases with gain-of-function variants as compared to those with loss-of-function. CACNA1E, CACNA1G, CACNA1F, CACNA2D2 and CACNA1A associated with more severe phenotype. Furthermore, 157 copy number variations (CNVs) spanning calcium genes were identified in DECIPHER database. The leading genes included CACNA1C, CACNA1A, and CACNA1E. Overall, the underlying mechanisms included gain- and/ or loss-of-function, alteration in kinetics (activation, inactivation) and dominant-negative effects of truncated forms of alpha1 subunits. Forty of the identified cases featured cerebellar atrophy. We identified only a few cell and animal studies that focused on the mechanisms of ID/GDD in relation to CCs. There is a scarcity of studies on treatment options for ID/GDD both in vivo and in vitro.

Conclusion

Our results suggest that CCs play a major role in ID/GDD. While both gain- and loss-of-function variants are associated with ID/GDD, the mechanisms underlying their involvement need further scrutiny.
Long-term renal outcome in methylmalonic acidemia in adolescents and adults
Authors: Dao Myriam , Arnoux Jean-Baptiste , Bienaimé Frank , Brassier Anaïs , Brazier François , Benoist Jean-François , Pontoizeau Clément , Ottolenghi Chris , Krug Pauline , Boyer Olivia , de Lonlay Pascale , Servais Aude
Published: May 2021

Background

Chronic kidney disease (CKD) is one of the main long-term prognosis factors in methylmalonic acidemia (MMA), a rare disease of propionate catabolism. Our objective was to precisely address the clinical and biological characteristics of long-term CKD in MMA adolescent and adult patients.

Patients and methods

In this retrospective study, we included MMA patients older than 13 years who had not received kidney and/or liver transplantation. We explored tubular functions, with special attention to proximal tubular function. We measured glomerular filtration rate (mGFR) by iohexol clearance and compared it to estimated glomerular filtration rate (eGFR) by Schwartz formula and CKD-EPI.

Results

Thirteen patients were included (M/F = 5/8). Median age was 24 years (13 to 32). Median mGFR was 57 mL/min/1.73 m2 (23.3 to 105 mL/min/1.73 m2). Ten out of 13 patients had mGFR below 90 mL/min/1.73 m2. No patient had significant glomerular proteinuria. No patient had complete Fanconi syndrome. Only one patient had biological signs suggestive of incomplete proximal tubulopathy. Four out of 13 patients had isolated potassium loss, related to a non-reabsorbable anion effect of urinary methylmalonate. Both Schwartz formula and CKD-EPI significantly overestimated GFR. Bias were respectively 16 ± 15 mL/min/1.73 m2 and 37 ± 22 mL/min/1.73 m2.

Conclusion

CKD is a common complication of the MMA. Usual equations overestimate GFR. Therefore, mGFR should be performed to inform therapeutic decisions such as dialysis and/or transplantation. Mild evidence of proximal tubular dysfunction was found in only one patient, suggesting that other mechanisms are involved.
AKT-mediated phosphorylation of Sox9 induces Sox10 transcription in a murine model of HER2-positive breast cancer
Authors: Al-Zahrani Khalid N. , Abou-Hamad John , Pascoal Julia , Labrèche Cédrik , Garland Brennan , Sabourin Luc A.
Published: May 2021

Background

Approximately 5–10% of HER2-positive breast cancers can be defined by low expression of the Ste20-like kinase, SLK, and high expression of SOX10. Our lab has observed that genetic deletion of SLK results in the induction of Sox10 and significantly accelerates tumor initiation in a HER2-induced mammary tumor model. However, the mechanism responsible for the induction of SOX10 gene expression in this context remains unknown.

Methods

Using tumor-derived cell lines from MMTV-Neu mice lacking SLK and biochemical approaches, we have characterized the signaling mechanisms and relevant DNA elements driving Sox10 expression.

Results

Biochemical and genetic analyses of the SOX10 regulatory region in SLK-deficient mammary tumor cells show that Sox10 expression is dependent on a novel −7kb enhancer that harbors three SoxE binding sites. ChIP analyses demonstrate that Sox9 is bound to those elements in vivo. Our data show that AKT can directly phosphorylate Sox9 in vitro at serine 181 and that AKT inhibition blocks Sox9 phosphorylation and Sox10 expression in SLK(-/-) tumor cells. AKT-mediated Sox9 phosphorylation increases its transcriptional activity on the Sox10 −7kb enhancer without altering its DNA-binding activity. Interestingly, analysis of murine and human mammary tumors reveals a direct correlation between the levels of active phospho-Sox9 S181 and Sox10 expression.

Conclusions

Our results have identified a novel Sox10 enhancer and validated Sox9 as a direct target for AKT. As Sox10 is a biomarker for triple-negative breast cancers (TNBC), these findings might have major implications in the targeting and treatment of those cancers.
Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways
Authors: Lu Jiansen , Zhang Hongbo , Pan Jianying , Hu Zhiqiang , Liu Liangliang , Liu Yanli , Yu Xiao , Bai Xiaochun , Cai Daozhang , Zhang Haiyan
Published: May 2021

Background

To investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (OA) development.

Methods

Ten-week-old male C57BL/6 mice were randomized and assigned to vehicle, collagenase-induced OA (CIOA), or CIOA with intra-articular fargesin treatment groups. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International (OARSI) score. Immunostaining and western blot analyses were conducted to detect relative protein. Raw264.7 cells were treated with LPS or IL-4 to investigate the role of polarized macrophages. ADTC5 cells were treated with IL-1β and conditioned medium was collected to investigate the crosstalk between chondrocytes and macrophages.

Results

Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by downregulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Conditioned medium (CM) from M1 macrophages treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen and increased Col2a1 and SOX9 in OA chondrocytes, but fargesin alone did not affect chondrocyte catabolic processes. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling.

Conclusions

This study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by downregulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.
Qualitative ultrastructural analysis of the submandibular salivary glands after administration of khat: in vivo study
Authors: Al-Qadhi Gamilah , Mubarak Rabab
Published: May 2021

Objective

Khat (Catha edulis Forssk) plant has been widely chewed for its psychostimulatory effects in the African and Arabian Peninsula, particularly in Yemen. Considering the khat leaves are gradually chewed without swallowing, while its active constituents are extracted into saliva, studying the effect of khat on salivary glands is necessary. This work is an extension of the previously published work that studied the effect of khat extract on the rats' submandibular salivary glands in terms of histological and immunohistochemical evaluations. The current research note aimed to better understand this effect on the ultrastructure of submandibular salivary gland cells by using transmission electron microscope.

Results

Oral administration of khat extract produced degenerative changes in the secretory and ductal cells of rats' submandibular salivary glands. These changes involved irregular boundaries of variable sized-nuclei, dilated RER, cytoplasmic vacuoles as well as swollen and degenerated mitochondria.
De novo transcriptome analysis for examination of the nutrition metabolic system related to the evolutionary process through which stick insects gain the ability of flight (Phasmatodea)
Authors: Sakamoto Takuma , Sasaki Shunya , Yamaguchi Nobuki , Nakano Miho , Sato Hiroki , Iwabuchi Kikuo , Tabunoki Hiroko , Simpson Richard J. , Bono Hidemasa
Published: May 2021

Objective

Insects are the most evolutionarily successful groups of organisms, and this success is largely due to their flight ability. Interestingly, some stick insects have lost their flight ability despite having wings. To elucidate the shift from wingless to flying forms during insect evolution, we compared the nutritional metabolism system among flight-winged, flightless-winged, and flightless-wingless stick insect groups.

Results

Here, we report RNA sequencing of midgut transcriptome of Entoria okinawaensis, a prominent Japanese flightless-wingless stick insect, and the comparative analysis of its transcriptome in publicly available midgut transcriptomes obtained from seven stick insect species. A gene enrichment analysis for differentially expressed genes, including those obtained from winged vs wingless and flight vs flightless genes comparisons, revealed that carbohydrate metabolic process-related genes were highly expressed in the winged stick insect group. We also found that the expression of the mitochondrial enolase superfamily member 1 transcript was significantly higher in the winged stick insect group than in the wingless stick insect group. Our findings could indicate that carbohydrate metabolic processes are related to the evolutionary process through which stick insects gain the ability of flight.
Early lactate and glucose kinetics following return to spontaneous circulation after out-of-hospital cardiac arrest
Authors: Freire Jorge Pedro , Boer Rohan , Posma Rene A. , Harms Katharina C. , Hiemstra Bart , Bens Bas W. J. , Nijsten Maarten W.
Published: May 2021

Objective

Lactate has been shown to be preferentially metabolized in comparison to glucose after physiological stress, such as strenuous exercise. Derangements of lactate and glucose are common after out-of-hospital cardiac arrest (OHCA). Therefore, we hypothesized that lactate decreases faster than glucose after return-to-spontaneous-circulation (ROSC) after OHCA.

Results

We included 155 OHCA patients in our analysis. Within the first 8 h of presentation to the emergency department, 843 lactates and 1019 glucoses were available, respectively. Lactate decreased to 50% of its initial value within 1.5 h (95% CI [0.2–3.6 h]), while glucose halved within 5.6 h (95% CI [5.4–5.7 h]). Also, in the first 8 h after presentation lactate decreases more than glucose in relation to their initial values (lactate 72.6% vs glucose 52.1%). In patients with marked hyperlactatemia after OHCA, lactate decreased expediently while glucose recovered more slowly, whereas arterial pH recovered at a similar rapid rate as lactate. Hospital non-survivors (N = 82) had a slower recovery of lactate (P = 0.002) than survivors (N = 82). The preferential clearance of lactate underscores its role as a prime energy substrate, when available, during recovery from extreme stress.
Anaphylaxis caused by artisanal honey in a child: a case report
Authors: Di Costanzo Margherita , De Paulis Nicoletta , Peveri Silvia , Montagni Marcello , Berni Canani Roberto , Biasucci Giacomo
Published: May 2021

Background

Honey is a rare cause of food allergy, especially in children, but it can cause severe systemic allergic reactions. In the pediatric age group, only a few cases have been reported in the literature. Honey allergy may be caused by pollen content or bee-derived proteins. A role for Compositae has been suggested among pollen allergens. Allergology workup of a patient with suspected honey allergy is not well defined. Here we describe a rare case of anaphylaxis in a 5-year-old boy, sensitized to Compositae pollen (ragweed and mugwort), after the ingestion of artisanal honey.

Case presentation

The Slavic patient was referred to our hospital emergency department for generalized urticaria and breathing impairment. All the symptoms occurred approximately 30 minutes after the ingestion of a meal containing salmon and artisanal honey. The allergology workup revealed that a skin prick-by-prick test with the implicated artisanal honey was positive, while a variety of different commercial honey and salmon products yielded negative results. Skin prick test and serum-specific immunoglobulin E (IgE) results were also positive for Compositae pollen (ragweed and mugwort). Patients sensitized to weed pollens who ingest bee products may experience an immediate allergic reaction because of the cross-reaction between weed pollens and Compositae bee product pollen. In this case, primary sensitization may be due to airborne Compositae pollen. Commercial honey is heavily processed due to pasteurization and filtration, which removes most of the pollen. These observations highlight the role of Compositae pollen in the observed allergic reaction and suggest that the different pollen content in the artisanal honey relative to commercial honey was responsible for the allergic reaction in our patient.

Conclusions

This is the first reported pediatric case of honey-induced anaphylaxis in a child under 6 years of age sensitized to Compositae pollen. Pediatricians should be aware of the potential risk of severe allergic reactions upon ingestion of honey and bee products, especially in patients sensitized to weed pollens. To diagnose honey allergy, obtaining a proper clinical history is essential. In addition, skin prick-by-prick tests are helpful, and may represent a simple method to screen for honey allergy in patients sensitized to Compositae pollen, in light of the potential risk.
Effects of organic acid, Enterococcus faecalis strain EC-12 and sugar cane extract in feed against enterotoxigenic Escherichia coli-induced diarrhea in pigs
Authors: Matsumoto Hiroki , Miyagawa Masashi , Yin Yizhe , Oosumi Takayuki
Published: May 2021

Diarrhea can lead to mortality and delayed growth in pigs and is a major economic loss in the pig industry. In this study, we evaluated non-antimicrobial materials that can prevent diarrhea to infection by enterotoxigenic Escherichia coli (ETEC) in weaned pigs and investigated biological changes. We confirmed the efficacy of fumaric acid, lactic acid, Enterococcus faecalis strain EC-12 (EC12) and sugar cane extract (SCE) in inhibiting diarrhea and investigated the biological changes by analyzing gut microbiota and plasma metabolites. Administration of EC12 (0.1%, w/w) and SCE (1.0%, w/w) groups had reduced score of diarrhea. Furthermore, the combination of EC12 and SCE was effective at reducing the fecal score of diarrhea even at low concentrations. Administration of either EC12 or SCE greatly reduced the relative abundance of Enterobacteriaceae in pigs. EC12 and SCE were most effective in suppressing ETEC-induced diarrhea in weaned pigs. Furthermore, we were able to identify biological changes in pigs when EC12 and SCE were administered to pigs. These feeds may have prevented infection by ETEC in weaned pigs and may improve pig productivity and reduce the use of antimicrobial agents.
Melittin as a promising anti-protozoan peptide: current knowledge and future prospects
Authors: Memariani Hamed , Memariani Mojtaba
Published: May 2021

Protozoan diseases such as malaria, leishmaniasis, Chagas disease, and sleeping sickness still levy a heavy toll on human lives. Deplorably, only few classes of anti-protozoan drugs have thus far been developed. The problem is further compounded by their intrinsic toxicity, emergence of drug resistance, and the lack of licensed vaccines. Thus, there is a genuine exigency to develop novel anti-protozoan medications. Over the past years, melittin, the major constituent in the venom of European honeybee Apis mellifera, has gathered the attention of researchers due to its potential therapeutic applications. Insofar as we are aware, there has been no review pertinent to anti-protozoan properties of melittin. The present review outlines the current knowledge about anti-protozoan effects of melittin and its underlying mechanisms. The peptide has proven to be efficacious in killing different protozoan parasites such as Leishmania, Plasmodium, Toxoplasma, and Trypanosoma in vitro. Apart from direct membrane-disruptive activity, melittin is capable of destabilizing calcium homeostasis, reducing mitochondrial membrane potential, disorganizing kinetoplast DNA, instigating apoptotic cell death, and induction of autophagy in protozoan pathogens. Emerging evidence suggests that melittin is a promising candidate for future vaccine adjuvants. Transmission-blocking activity of melittin against vector-borne pathogens underscores its potential utility for both transgenic and paratransgenic manipulations. Nevertheless, future research should focus upon investigating anti-microbial activities of melittin, alone or in combination with the current anti-protozoan medications, against a far broader spectrum of protozoan parasites as well as pre-clinical testing of the peptide in animal models.
Simplified frontal EEG in adults under veno-arterial extracorporeal membrane oxygenation
Authors:   The DINAMO Study Group, Touchard Cyril , Cartailler Jérôme , Vellieux Geoffroy , de Montmollin Etienne , Jaquet Pierre , Wanono Ruben , Reuter Jean , Para Marylou , Bouadma Lila , Timsit Jean-François , d’Ortho Marie-Pia , Kubis Nathalie , Rouvel Tallec Anny , Sonneville Romain
Published: May 2021

Background

EEG-based prognostication studies in intensive care units often rely on a standard 21-electrode montage (stdEEG) requiring substantial human, technical, and financial resources. We here evaluate whether a simplified 4-frontal electrode montage (4-frontEEG) can detect EEG patterns associated with poor outcomes in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

Methods

We conducted a reanalysis of EEG data from a prospective cohort on 118 adult patients under VA-ECMO, in whom EEG was performed on admission to intensive care. EEG patterns of interest included background rhythm, discontinuity, reactivity, and the Synek’s score. They were all reassessed by an intensivist on a 4-frontEEG montage, whose analysis was then compared to an expert’s interpretation made on stdEEG recordings. The main outcome measure was the degree of correlation between 4-frontEEG and stdEEG montages to identify EEG patterns of interest. The performance of the Synek scores calculated on 4-frontEEG and stdEEG montage to predict outcomes (i.e., 28-day mortality and 90-day Rankin score $${\ge {4}}$$

≥
4

) was investigated in a secondary exploratory analysis.

Results

The detection of EEG patterns using 4-frontEEG was statistically similar to that of stdEEG for background rhythm (Spearman rank test, ρ = 0.66, p < 0.001), discontinuity (Cohen’s kappa, $$\kappa$$
κ
 = 0.955), reactivity ($$\kappa$$
κ
 = 0.739) and the Synek’s score (ρ = 0.794, p < 0.001). Using the Synek classification, we found similar performances between 4-frontEEG and stdEEG montages in predicting 28-day mortality (AUC 4-frontEEG 0.71, AUC stdEEG 0.68) and for 90-day poor neurologic outcome (AUC 4-frontEEG 0.71, AUC stdEEG 0.66). An exploratory analysis confirmed that the Synek scores determined by 4 or 21 electrodes were independently associated with 28-day mortality and poor 90-day functional outcome.

Conclusion

In adult patients under VA-ECMO, a simplified 4-frontal electrode EEG montage interpreted by an intensivist, detected common EEG patterns associated with poor outcomes, with a performance similar to that of a standard EEG montage interpreted by expert neurophysiologists. This simplified montage could be implemented as part of a multimodal evaluation for bedside prognostication.
Even-order differential equation with continuous delay: nonexistence criteria of Kneser solutions
Authors: Muhib Ali , Khashan M. Motawi , Moaaz Osama
Published: May 2021

In this paper, we study even-order DEs where we deduce new conditions for nonexistence Kneser solutions for this type of DEs. Based on the nonexistence criteria of Kneser solutions, we establish the criteria for oscillation that take into account the effect of the delay argument, where to our knowledge all the previous results neglected the effect of the delay argument, so our results improve the previous results. The effectiveness of our new criteria is illustrated by examples.
Converging or diverging trajectories of mortality under one year of age in the Baltic States: a comparison with the European Union
Authors: Genowska Agnieszka , Strukcinskiene Birute , Villerusa Anita , Konstantynowicz Jerzy
Published: May 2021

Background

Information about trends in perinatal and child health inequalities is scarce, especially in the Eastern Europe. We analyzed how mortality under 1 year of age has been changing in the Baltic States and the European Union (EU) over 25 years, and what associations occurred between changes in macroeconomic factors and mortality.

Methods

Data on fetal, neonatal, infant mortality, and macroeconomic factors were extracted from WHO database. Joinpoint regression analysis was performed to analyze time trajectories of mortality over 1990–2014. We also investigated how the changes in health expenditures and Gross Domestic Product (GDP) contributed to the changes in mortality.

Results

The reduction of fetal, neonatal and infant mortality in the Baltic countries led to convergence with the EU. In Estonia this process was the fastest, and then the rates tended to diverge. The strongest effect in reduction of neonatal mortality was related to the annual increase in health expenditure and GDP which had occurred in the same year, and a decrease in fetal mortality associated with an increase in health expenditure and GDP in the 4th and 5th year, respectively, following the initial change.

Conclusions

These findings outlined convergences and divergences in mortality under 1 year of age in the Baltic States compared with the patterns of the EU. Our data highlighted a need to define health policy directions aimed at the implementation of effective intervention modalities addressing reduction of risks in prenatal and early life.
Pars plana vitrectomy with/without encircling scleral band for treatment of retinal detachment associated with buphthalmos
Authors: Ghoraba Hammouda Hamdy , El Gouhary Sameh Mohamed , Ghali Ali Ahmed Ali , Abdelhafez Mohamed Ahmed , Zaky Adel Galal , Leila Mahmoud , Heikal Mohamed Amin , Mansour Hosam Othman
Published: May 2021

Background

To evaluate the results of pars plana vitrectomy (PPV) and silicone oil (SO) tamponade with or without encircling scleral band for repair of rhegmatogenous retinal detachment (RRD) in children with buphthalmos.

Patients and methods

Retrospective comparative nonrandomized interventional case series including consecutive patients who underwent PPV with or without encircling band and SO tamponade for RRD associated with buphthalmos.

Results

The study included 19 eyes of 19 children. Mean age was 8 years, range 3–16 years. Mean follow-up period was 28 months, range 19–63 months. Globe survival has been achieved in 15 out of 19 eyes (79%). Phthisis bulbi was reported in four cases (22%). Eight patients (42%) achieved ambulatory vision. Most eyes initially achieved anatomical success.

Conclusion

Despite the poor visual and anatomical results of RRD repair in eyes with buphthalmos, globe survival might be the rationale for surgery in such cases. Globe preservation could avoid the psychological and social consequences of phthisis bulbi in non-operated children.
Inferring multi-period optimal portfolios via detrending moving average cluster entropy(a)
Authors: Murialdo P. , Ponta L. , Carbone A.
Published: May 2021

Despite half a century of research, there is still no general agreement about the optimal approach to build a robust multi-period portfolio. We address this question by proposing the detrended cluster entropy approach to estimate the weights of a portfolio of high-frequency market indices. The information measure gathered from the markets produces reliable estimates of the weights at varying temporal horizons. The portfolio exhibits a high level of diversity, robustness and stability as not affected by the drawbacks of traditional mean-variance approaches.
Enhanced Forman curvature and its relation to Ollivier curvature
Authors: Tee Philip , Trugenberger C. A.
Published: May 2021

Recent advances in emergent geometry and discretized approaches to quantum gravity have relied upon the notion of a discrete measure of graph curvature. We focus on the two main measures that have been studied, the so-called Ollivier-Ricci and Forman-Ricci curvatures. These two approaches have a very different origin, and both have advantages and disadvantages. In this work we study the relationship between the two measures for a class of graphs that are important in quantum gravity applications. We discover that under a specific set of circumstances they are equivalent, opening up the possibility of replacing the more fundamental Ollivier-Ricci curvature by the computationally more accessible Forman-Ricci curvature in certain applications to models of emergent spacetime and quantum gravity.
High-quality Fano resonances and multispectral perfect absorption in mushroom-type dielectric metamaterials with a silver nanofilm
Authors: Li Hongju , Zhang Yu , Qin Meng , Wang Lingling , Chai Yifeng
Published: May 2021

Dielectric metamaterials with high refractive index have drawn intensive attention owing to their advantages of confinement and guiding of light in practical photonic devices. Here, we propose a hybrid nanostructure, consisting of mushroom-type dielectric nanoarrays and plasmonic nanofilms, towards the goal of achieving multispectral perfect absorption of light and high-quality Fano resonance. Our studies reveal that the proposed structure indeed possesses the expected properties of light harvest and Fano resonance, which is induced by the coupling between plasmonic and Mie-type resonant modes. Furthermore, the resonant field distributions inside the nanostructure and the effects of modifying the parameters of dielectric nanoarrays on resonant modes are systematically investigated. Our findings of nearly total absorption in silicon and high-quality sensing of the combined system will greatly benefit the applications of solar energy transition and sensors.
Fish scales: Primitive basis for modern metamaterials
Authors: Ebrahimi Hossein , Ali Hessein , Stephen Jeremy , Ghosh Ranajay
Published: May 2021

Scales are a path breaking evolutionary adaptation that accompanied vertebrate evolution for the past 500 million years. Inherently lightweight with diverse shapes, sizes, materials, and distribution, they provide remarkable architecture-material enhancement, typical of metamaterials. Here we provide a perspective on mechanical behavior of fish scale inspired structures and explain the origins of some of their striking mechanical properties that include directional nonlinearity, interlocking behavior, and multiple penetration modes. We outline and explain the progress in understanding the complexities of these structures in global and local deformation modes and conclude by offering future perspectives and challenges.
Magnetic phase transition in the ground-state phase diagram of binary bose gases in optical lattices
Authors: de Forges de Parny Laurent , Rousseau Valéry
Published: May 2021

We investigate the ground-state phase diagram of interacting binary Bose gases trapped in two-dimensional optical lattices by means of quantum Monte Carlo simulations. Our simulations reveal a magnetic phase transition from a

ferromagnetic-order to a spin insulator inside the Mott insulating phase with two particles per site for quasi-balanced on-site inter- and intra-particle interactions, i.e.,

. This 3D-XY transition is characterized by the establishment of a finite local magnetic moment along the z-axis, ferromagnetic correlations in the

plane and by counterflow superfluidity inside the Mott phase. When decreasing

, this transition merges with the Mott-superfluid transition and becomes first order. The merging of the two transitions is investigated with respect to the

parameter.
The Validity of Serum Alkaline Phosphatase to Identify Nutritional Rickets in Nigerian Children on a Calcium-Deprived Diet
Authors: Thacher Tom D , Sempos Christopher T , Durazo-Arvizu Ramon A , Fischer Philip R , Munns Craig F , Pettifor John M
Published: May 2021

Context

Nutritional rickets results from the interaction of low vitamin D status and limited calcium intake. Serum alkaline phosphatase (AP) activity is a biomarker of impaired mineralization in rickets.

Objective

To assess the performance of serum AP activity in identifying nutritional rickets in calcium-deprived Nigerian children.

Methods

We reanalyzed data from a case-control study of children with active rickets and matched control subjects without rickets, using a multivariate logistic regression to assess the odds of rickets associated with AP activity, adjusting for age, sex, and weight-for-age z-score.

Results

A total of 122 children with rickets and 119 controls were included. Rachitic children had a mean (±SD) age of 54 ± 29 months, and 55 (45.1%) were male. Cases and controls had low dietary calcium intakes (216 ± 87 and 214 ± 96 mg/day, respectively). Serum AP activity levels in cases and controls were 812 ± 415 and 245 ± 78 U/L, respectively (P < 0.001). AP was negatively associated with 25-hydroxyvitamin D values (r = −0.34; P < 0.001). In the adjusted model, the odds ratio (95% CI) receiver operating characteristic curve was 0.978. AP > 350 U/L identified nutritional rickets in Nigerian children with sensitivity 0.93, specificity 0.92, positive likelihood ratio 11.3, and negative likelihood ratio 0.07.

Conclusion

An AP > 350 U/L effectively discriminated between Nigerian children with and without nutritional rickets. AP is a low-cost biochemical test that could be used to screen for nutritional rickets, but cutoff values require validation in other populations, and laboratory values need to be standardized for widespread population studies.
New Horizon: Exercise and a Focus on Tissue-Brain Crosstalk
Authors: Townsend Logan K , MacPherson Rebecca E K , Wright David C
Published: May 2021

The world population is aging, leading to increased rates of neurodegenerative disorders. Exercise has countless health benefits and has consistently been shown to improve brain health and cognitive function. The purpose of this review is to provide an overview of exercise-induced adaptations in the brain with a focus on crosstalk between peripheral tissues and the brain. We highlight recent investigations into exercise-induced circulating factors, or exerkines, including irisin, cathepsin B, GPLD1, and ketones and the mechanisms mediating their effects in the brain.
“Seropedagogy”
Authors: Franco Robert
Published: May 2021

Since the beginnings of the HIV/AIDS pandemic, pedagogy has been a crucial survival strategy, especially when government agencies failed to prevent mass deaths. However, contemporary sex education on HIV/AIDS—if taught to undergraduates before they arrive on campus—often does not account for the disproportionate effects of the pandemic on racial minorities and global South countries. In this teaching essay, the author describes how his course on the history of HIV/AIDS takes a global approach to highlight that the AIDS crisis is not over. Starting with histories of HIV/AIDS in the United States, Haiti, China, and elsewhere that sought to find a scapegoat for the pandemic, the course then turns to the global power of the pharmaceutical industry. It examines the marketing and lobbying strategies of companies such as Gilead, which use the stigma of HIV/AIDS to transform impoverished global South countries into new markets for research and capital extraction. Finally, it also highlights how the AIDS crisis remains an ongoing struggle against racial disparities in health care that prevent access to life-saving treatments and preventative drugs such as Truvada and Descovy for pre-exposure prophylaxis (PrEP). Using a range of materials from podcasts to pills, the author introduces students to the globalizing forces that take the bodies of the poor, women, and Black, Latinx, trans, and global South citizens as expendable in the fight against HIV/AIDS.
“Qué Bonita Mi Tierra”
Authors: Esparza René
Published: May 2021

Employing an anticolonial and anticapitalist approach to HIV/AIDS, the activists of the Latina/o Caucus of ACT UP/NY pushed beyond a biomedical framework of “drugs into bodies” that tended to dominate the larger organization. As US queer racialized/colonial subjects, Latinx AIDS activists enacted a queer and feminist decolonial activism that looked past the continental United States to the global South. In Puerto Rico, Latinx AIDS activists helped establish the first chapter of ACT UP in a Spanish-speaking country. Together, the Latina/o Caucus and ACT UP/Puerto Rico spearheaded a campaign against the colonial policies of the United States, the corporate greed of island-based pharmaceutical firms, and the heteropatriarchal investments of church and commonwealth officials—conditions that exacerbated the disproportionate rates of HIV/AIDS among Puerto Rican island and diasporic communities. Through these efforts, Latinx AIDS activists transformed the domestic and global fight against AIDS into a queer, feminist, and decolonial endeavor.
Who Gets to Be a #TruvadaWhore
Authors: Betts Devon
Published: May 2021

In 2012 the FDA’s approval of Truvada as a type of HIV preventative health care (PrEP) generated a considerable amount of criticism. This discourse was exemplified by the #TruvadaWhore campaign, in which gay men used the hashtag to reclaim this derogatory term and made information on PrEP more accessible. Although this campaign is queer in its rejection of heteronormative logics, it also highlights the limitations of queer identity politics. The #TruvadaWhore campaign masks differences of power and privilege among MSM. It presumed that a critique of slut shaming could function universally across race, despite the racial myths about Black hypersexuality that have existed throughout modernity, and undergird the ongoing regulation of Black bodies, both queer and straight. Ultimately, this article calls for a queering and reimagining of such activism as an intersectional and coalitional project through an exploration of the question: who gets to be a #TruvadaWhore?
Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs
Authors: Aztekin Can , Hiscock Tom W. , Gurdon John , Jullien Jerome , Marioni John , Simons Benjamin David
Published: May 2021

Absence of a specialized wound epidermis is hypothesized to block limb regeneration in higher vertebrates. However, the factors preventing its formation in regeneration-incompetent animals are poorly understood. To characterize the endogenous molecular and cellular regulators of specialized wound epidermis formation in Xenopus laevis tadpoles, and the loss of their regeneration competency during development, we used single-cell transcriptomics and ex vivo regenerating limb cultures. Transcriptomic analysis revealed that the specialized wound epidermis is not a novel cell state, but a re-deployment of the apical-ectodermal-ridge (AER) programme underlying limb development. Enrichment of secreted inhibitory factors, including Noggin, a morphogen expressed in developing cartilage/bone progenitor cells, are identified as key inhibitors of AER cell formation in regeneration-incompetent tadpoles. These factors can be overridden by Fgf10, which operates upstream of Noggin and blocks chondrogenesis. These results indicate that manipulation of the extracellular environment and/or chondrogenesis may provide a strategy to restore regeneration potential in higher vertebrates.
Implications of the new FIGO staging and the role of imaging in cervical cancer
Authors: Kido Aki , Nakamoto Yuji
Published: May 2021

International Federation of Gynecology and Obstetrics (FIGO) staging, which is the fundamentally important cancer staging system for cervical cancer, has changed in 2018. New FIGO staging includes considerable progress in the incorporation of imaging findings for tumour size measurement and evaluating lymph node (LN) metastasis in addition to tumour extent evaluation. MRI with high spatial resolution is expected for tumour size measurements and the high accuracy of positron emmision tomography/CT for LN evaluation. The purpose of this review is firstly review the diagnostic ability of each imaging modality with the clinical background of those two factors newly added and the current state for LN evaluation. Secondly, we overview the fundamental imaging findings with characteristics of modalities and sequences in MRI for accurate diagnosis depending on the focus to be evaluated and for early detection of recurrent tumour. In addition, the role of images in treatment response and prognosis prediction is given with the development of recent technique of image analysis including radiomics and deep learning.