bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial image objects for classification of breast cancer biomarkers with transcriptome sequencing data and convolutional neural network algorithms
Authors: Chen Xiangning , Chen Daniel G. , Zhao Zhongming , Balko Justin M. , Chen Jingchun
Published: October 2021

Background

Transcriptome sequencing has been broadly available in clinical studies. However, it remains a challenge to utilize these data effectively for clinical applications due to the high dimension of the data and the highly correlated expression between individual genes.

Methods

We proposed a method to transform RNA sequencing data into artificial image objects (AIOs) and applied convolutional neural network (CNN) algorithms to classify these AIOs. With the AIO technique, we considered each gene as a pixel in an image and its expression level as pixel intensity. Using the GSE96058 (n = 2976), GSE81538 (n = 405), and GSE163882 (n = 222) datasets, we created AIOs for the subjects and designed CNN models to classify biomarker Ki67 and Nottingham histologic grade (NHG).

Results

With fivefold cross-validation, we accomplished a classification accuracy and AUC of 0.821 ± 0.023 and 0.891 ± 0.021 for Ki67 status. For NHG, the weighted average of categorical accuracy was 0.820 ± 0.012, and the weighted average of AUC was 0.931 ± 0.006. With GSE96058 as training data and GSE81538 as testing data, the accuracy and AUC for Ki67 were 0.826 ± 0.037 and 0.883 ± 0.016, and that for NHG were 0.764 ± 0.052 and 0.882 ± 0.012, respectively. These results were 10% better than the results reported in the original studies. For Ki67, the calls generated from our models had a better power for prediction of survival as compared to the calls from trained pathologists in survival analyses.

Conclusions

We demonstrated that RNA sequencing data could be transformed into AIOs and be used to classify Ki67 status and NHG with CNN algorithms. The AIO method could handle high-dimensional data with highly correlated variables, and there was no need for variable selection. With the AIO technique, a data-driven, consistent, and automation-ready model could be developed to classify biomarkers with RNA sequencing data and provide more efficient care for cancer patients.
Supine vs upright exercise in patients with hepatopulmonary syndrome and orthodeoxia: study protocol for a randomized controlled crossover trial
Authors: Parikh Harsh , Lui Eric , Faughnan Marie E. , Al-Hesayen Abdul , Segovia Stephanie , Gupta Samir
Published: October 2021

Background

The hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations and abnormal oxygenation. Liver transplantation is the only effective therapy for this disease. Patients with HPS have significant exercise limitations, impacting their quality of life and associated with poor liver transplant outcomes. Many patients with HPS exhibit orthodeoxia—an improvement in oxygenation in the supine compared to the upright position. We hypothesize that exercise capacity will be superior in the supine compared to the upright position in such patients.

Methods

We propose a randomized controlled crossover trial in patients with moderate HPS (PaO2< 80 mmHg) and orthodeoxia (supine to upright PaO2decrease > 4 mmHg) comparing the effect of supine vs upright position on exercise. Patients with pulmonary hypertension, FEV1/FVC ratio < 0.65, significant coronary artery disease, disorders preventing or contraindicating use of a cycle ergometer, and/or moderate or severe ascites will be excluded. Participants will be randomized to cycle ergometry in either the supine or upright position. After a short washout period (a minimum of 1 day to a maximum of 4 weeks), participants will crossover and perform an exercise in the alternate position. Exercise will be performed at a constant work rate of 70–85% of the predicted peak work rate until the “stopping time” is reached, defined by exhaustion, profound desaturation, or safety concerns (drop in systolic blood pressure or life-threatening arrhythmia). The primary outcome will be the difference in the stopping time between exercise positions, compared with a repeated measures analysis of variance method with a mixed effects model approach. The model will be adjusted for period effects.P< 0.05 will be considered statistically significant.

Discussion

HPS patients have hypoxemia leading to significant exercise limitations. If our study is positive, a supine exercise regimen could become a routine prescription for patients with HPS and orthodeoxia, enabling them to exercise more effectively. Future studies could explore the corresponding effects of a supine exercise training regimen on physiologic variables such as long-term exercise capacity, quality of life, dyspnea, and liver transplantation outcomes.

Trial registration

ClinicalTrials.govProtocol Registration and Results System (PRS)NCT04004104. Registered on 1 July 2019
Complementary feeding methods in the first year of life: a study protocol for a randomized clinical trial
Authors: Nunes Leandro Meirelles , Führ Jordana , Belin Christy Hannah Sanini , Moreira Paula Ruffoni , Neves Renata Oliveira , de Brito Mariana Lopes , Morando Lorenzo Andreazza , Mariath Adriela Azevedo Souza , Gomes Erissandra , Bernardi Juliana Rombaldi
Published: October 2021

Background

The traditional spoon-feeding approach to introduction of solid foods during the complementary feeding period is supported by consensus in the scientific literature. However, a method called Baby-Led Introduction to SolidS (BLISS) has been proposed as an alternative, allowing infants to self-feed with no adult interference. To date, there have been no trials in the Brazilian population to evaluate the effectiveness of BLISS in comparison to the traditional approach.

Methods/design

To evaluate and compare three different complementary feeding methods. Data on 144 mother-child pairs will be randomized into intervention groups by methods: (A) strict Parent-Led Weaning; (B) strict Baby-Led Introduction to SolidS; and (C) a mixed method. Prospective participants from Porto Alegre, Brazil, and nearby cities will be recruited through the Internet. The interventions will be performed by nutritionists and speech therapists, at 5.5 months of age of the child, at a private nutrition office equipped with a test kitchen where meals will be prepared according to the randomized method. The pairs will be followed up at 7, 9, and 12 months of age. Data will be collected through questionnaires designed especially for this study, which will include a 24h child food recall, questionnaires on the child’s and parents’ eating behavior, oral habits, eating difficulties, and choking prevalence. At 12 months of age, children will undergo blood collection to measure hemoglobin, ferritin, and C-reactive protein, saliva collection for analysis of genetic polymorphisms, and oral examination. Anthropometric parameters (child and maternal) will be measured at the baseline intervention, at a 9 month home visit, and at the end-of-study visit at the hospital. The primary outcome will be child growth and nutritional status z-scores at 12 months; secondary outcomes will include iron status, feeding behavior, acceptability of the methods, dietary variety, choking, eating behaviors, food preferences, acceptance of bitter and sweet flavors, suction, oral habits, oral hygiene behavior, dental caries, gingival health status, and functional constipation.

Discussion

The trial intends to ascertain whether there are potential advantages to the BLISS complementary feeding method in this specific population, generating data to support families and healthcare providers.

Trial registration

Brazilian Clinical Trials Registry (ReBEC): RBR- 229scm number U1111-1226-9516. Registered on September 24, 2019.
Clinical effectiveness and safety of baricitinib for the treatment of juvenile idiopathic arthritis-associated uveitis or chronic anterior antinuclear antibody-positive uveitis: study protocol for an open-label, adalimumab active-controlled phase 3 clinical trial (JUVE-BRIGHT)
Authors: Ramanan Athimalaipet V. , Guly Catherine M. , Keller Stuart Y. , Schlichting Douglas E. , de Bono Stephanie , Liao Ran , Quartier Pierre
Published: October 2021

Background

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and the most common systemic disorder associated with uveitis in childhood. Uveitis is more common in JIA patients who are antinuclear antibody (ANA)-positive, have an early-onset disease, and have oligoarticular arthritis. JIA-associated uveitis (JIA-uveitis) is typically anterior, chronic, bilateral, nongranulomatous, and asymptomatic. Visual outcomes in JIA-uveitis have improved with current screening and treatment options; however, many patients fail to respond or do not achieve long-lasting remission. Baricitinib, an oral selective Janus kinase (JAK)1 and 2 inhibitor, may impact key cytokines implicated in the pathogenesis of JIA-uveitis or ANA-positive uveitis, representing a potential novel treatment option for disease management.

Methods

The multicenter, phase 3 trial will be conducted using an open-label Bayesian design. The study will enroll at least 20 and up to 40 patients aged 2 to <18 years with active JIA-uveitis or chronic ANA-positive uveitis without systemic features. At least 20 patients who have had an inadequate response or intolerance to methotrexate (MTX-IR), but not biologic disease-modifying antirheumatic drugs (bDMARDs), will be randomized (1:1) to open-label baricitinib or adalimumab. Approximately 20 additional patients who are MTX-IR or bDMARD inadequate responders will receive baricitinib treatment. Patients will be treated with once daily oral baricitinib at a fixed dose by age group (4 mg for patients aged ≥6 to <18 years and 2 mg for patients <6 years) or adalimumab (20 mg for patients weighing <30 kg and 40 mg for patients ≥30 kg) as a subcutaneous injection every 2 weeks. Treatment with stable background conventional synthetic DMARDs, low-dose corticosteroids, and/or nonsteroidal anti-inflammatory drugs is allowed. The primary endpoint is the proportion of patients with response at week 24. Patients may continue treatment for up to 5 years.

Discussion

This is the first pediatric clinical trial to assess the clinical effectiveness and safety of a JAK inhibitor in JIA-uveitis or chronic ANA-positive uveitis. A novel Bayesian design is used to assess the efficacy of baricitinib, including an adalimumab reference arm, in this small patient population with unmet medical need.

Trial registration

EudraCT 2019-000119-10. Registered on January 4, 2019; NCT04088409. Registered on September 12, 2019
Effect of domperidone (leisguard®) on antibody titers, inflammatory markers and creatinine in dogs with leishmaniosis and chronic kidney disease
Authors: Cavalera Maria Alfonsa , Gernone Floriana , Uva Annamaria , D’Ippolito Paola , Roura Xavier , Paltrinieri Saverio , Zatelli Andrea
Published: October 2021

Background

Immunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of this pilot study (therapeutic, prospective and non-controlled) was to evaluate the effect of domperidone on serum antibody titers of Leishmania infantum, globulins, gamma globulins, acute-phase proteins (e.g. C-reactive protein [CRP]), big endothelin-1 (big ET-1), serum creatinine (SC) and proteinuria in dogs with leishmaniosis affected by chronic kidney disease (CKD).

Methods

Dogs were recruited if “exposed” to or “infected” with L. infantum and affected by CKD (IRIS stage 1 [proteinuric] or IRIS stage 2–3a [SC < 3.5 mg/dl; proteinuric or non-proteinuric]). After inclusion, an oral suspension of domperidone was administered, and the dogs were followed up for 180 days, with checks at 30, 60, 90 and 180 days after initial treatment.

Results

Of the 14 recruited dogs, nine showed a statistically significant reduction in SC (χ2 = 9.1, df = 3, P = 0.028), but not in the urine protein/creatinine ratio (χ2 = 6.43, df = 3, P = 0.092). All dogs showed a significant reduction in antibody titers for L. infantum (χ2 = 9.56, df = 2, P = 0.008), globulins (χ2 = 11.08, df = 3, P = 0.011) and gamma globulins (χ2 = 12.38, df = 3, P = 0.006) during the study period. There was also a statistically significant reduction in CRP (χ2 = 16.7,
df = 3, P = 0.001), but not in big ET-1 (χ2 = 2.04, df = 3, P = 0.563).

Conclusions

This study provides preliminary results on the ability of domperidone to improve SC and reduce anti-L. infantum antibody titers, globulins, gamma globulins and CRP in dogs with leishmaniosis and CKD.

Graphical abstract
Model-based assessment of the safety of community interventions with primaquine in sub-Saharan Africa
Authors: van Beek Stijn W. , Svensson Elin M. , Tiono Alfred B. , Okebe Joseph , D’Alessandro Umberto , Gonçalves Bronner P. , Bousema Teun , Drakeley Chris , ter Heine Rob
Published: October 2021

Background

Single low-dose primaquine (SLD-PQ) is recommended in combination with artemisinin-based combination therapy to reduce Plasmodium falciparum transmission in areas threatened by artemisinin resistance or aiming for malaria elimination. SLD-PQ may be beneficial in mass drug administration (MDA) campaigns to prevent malaria transmission but uptake is limited by concerns of hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The aim of this study was to improve the evidence on the safety of MDA with SLD-PQ in a sub-Saharan African setting.

Methods

A nonlinear mixed-effects model describing the pharmacokinetics and treatment-induced hemolysis of primaquine was developed using data from an adult (n = 16, G6PD deficient) and pediatric study (n = 38, G6PD normal). The relationship between primaquine pharmacokinetics and hemolysis was modeled using an established erythrocyte lifespan model. The safety of MDA with SLD-PQ was explored through Monte Carlo simulations for SLD-PQ at 0.25 or 0.4 mg/kg using baseline data from a Tanzanian setting with detailed information on hemoglobin concentrations and G6PD status.

Results

The predicted reduction in hemoglobin levels following SLD-PQ was small and returned to pre-treatment levels after 25 days. G6PD deficiency (African A- variant) was associated with a 2.5-fold (95% CI 1.2–8.2) larger reduction in hemoglobin levels. In the Tanzanian setting where 43% of the population had at least mild anemia (hemoglobin < 11–13 g/dl depending on age and sex) and 2.73% had severe anemia (hemoglobin < 7–8 g/dl depending on age and sex), an additional 3.7% and 6.0% of the population were predicted to develop at least mild anemia and 0.25% and 0.41% to develop severe anemia after 0.25 and 0.4 mg/kg SLD-PQ, respectively. Children < 5 years of age and women ≥ 15 years of age were found to have a higher chance to have low pre-treatment hemoglobin.

Conclusions

This study supports the feasibility of MDA with SLD-PQ in a sub-Saharan African setting by predicting small and transient reductions in hemoglobin levels. In a setting where a substantial proportion of the population had low hemoglobin concentrations, our simulations suggest treatment with SLD-PQ would result in small increases in the prevalence of anemia which would most likely be transient.

Graphical abstract
Use of continuous glucose monitoring system in patients with type 2 mellitus diabetic during hemodialysis treatment
Authors: Hissa Marcelo Rocha Nasser , Hissa Priscilla Nogueira Gomes , Guimarães Sérgio Botelho , Hissa Miguel Nasser
Published: October 2021

Background

Studies highlight the inaccuracy of glycated hemoglobin (HbA1c) for the assessment of glycemic control in dialysis diabetics and suggest the use of continuous glucose monitoring (CGM) as an alternative. Of the CGMs, FreeStyle Libre® is the most used in worldwide, but there is still no consensus on its use in dialysis.

Method

A 3-week prospective study was performed with 12 patients comparing capillary and interstitial glucose during dialysis.

Results

Comparing capillary and interstitial measurements, similar values were observed in pre-dialysis in the 1st week (184.1 ± 69.5 mg/dl and 173.1 ± 78.9 mg/dl, respectively, p = 0.303), in patients with body mass index less than 24.9 kg/m2 (214.2 ± 72.2 mg/dl and 201.3 ± 77.0 mg/dl respectively, p = 0.466), in those dialysis fluid loss less than 2 l (185.5 ± 82.6 mg/dl and 183.1 ± 94.0 mg/dl respectively and p = 0.805) and in those with hemoglobin greater than 12 g/dl (152.0 ± 35, 5 mg/dl and 129.5 ± 47.4 mg/dl respectively, p = 0.016). In the correlation of the capillary measurement with the interstitial sensor, it was observed that the proportions in the Clarke Error Grid of zone A, zone B, zone C, zone D and zone E were 62.5%, 27.1%, 0.0%, 10.4% and 0.0% respectively and in the Parkes error grid in zone A, zone B, zone C, zone D and zone E were 80.6%, 9.7%, 9.7% 0.0% and 0.0%, respectively.

Conclusion

The mean absolute relative difference in dialysis patients is higher than the general population without end-stage renal disease. However, clinical decision-making based on the values measured by the system can be made with a good margin based on the correlation between interstitial and capillary measurements.
Activation of mTOR mediates hyperglycemia-induced renal glomerular endothelial hyperpermeability via the RhoA/ROCK/pMLC signaling pathway
Authors: Chen Xiaolin , Chen Jianhui , Li Xianfan , Yu Zengpu
Published: October 2021

Objective

Hyperglycemia is associated with albuminuria and renal glomerular endothelial dysfunction in patients with diabetic nephropathy. The mTOR and RhoA/ROCK signaling pathways are involved in glomerular filtration barrier (GFB) regulation, but their role in high glucose (HG)-induced GFB dysfunction in human renal glomerular endothelial cells (HRGECs) has not been investigated. This study aimed to investigate the mechanisms of HG-induced GFB dysfunction in vitro.

Materials and methods

HRGECs were cultured in vitro and exposed to HG. The horseradish peroxidase–albumin leakage and transendothelial electrical resistance of the endothelial monolayer were measured after HG treatment with or without rapamycin preincubation. A fluorescence probe was used to study the distribution of F-actin reorganization. The phosphorylation levels of myosin light chain (MLC) and mTOR were measured via western blotting. RhoA activity was evaluated via GTPase activation assay. The effects of blocking mTOR or the RhoA/ROCK pathway on endothelial permeability and MLC phosphorylation under HG conditions were observed.

Results

HG exposure induced F-actin reorganization and increased MLC phosphorylation, leading to EC barrier disruption. This effect was attenuated by treatment with rapamycin or Y-27632. Phospho-MLC (pMLC) activation in HRGECs was mediated by RhoA/ROCK signaling. mTOR and RhoA/ROCK inhibition or knockdown attenuated pMLC activation, F-actin reorganization and barrier disruption that occurred in response to HG exposure.

Conclusions

Our results revealed that HG stimulation upregulated RhoA expression and activity through an mTOR-dependent pathway, leading to MLC-mediated endothelial cell cytoskeleton rearrangement and glomerular endothelial barrier dysfunction.
Metabolites of gut microbiome are associated with glucose metabolism in non-diabetic obese adults: a Chinese monozygotic twin study
Authors: Yu Ke , Yu Cai-Guo , Yin Xing-Qi , Wang Zong-Wei , Wang Xiao-Bo , Wang Li-Li , Guo Shuang , An Ya-Xin , Zhao Dong
Published: October 2021

Background

Evidence suggests gut microbiome is associated with diabetes. However, it’s unclear whether the association remains in non-diabetic participants. A Chinese monozygotic twin study, in which the participants are without diabetes, and are not taking any medications, was conducted to explore the potential association.

Methods

Nine pairs of adult monozygotic twins were enrolled and divided into two twin-pair groups (a and b). Clinical and laboratory measurements were conducted. Visceral adipose tissue (VAT) was assessed. Fecal samples were collected to analyze the microbiome composition by 16S rDNA gene amplicon sequencing. Liquid chromatography mass spectrometry was performed to detect the metabolites.

Results

The participants aged 53 years old averagely, with 8 (88.9%) pairs were women. All the participants were obese with VAT higher than 100 cm2 (152.2 ± 31.6). There was no significant difference of VAT between the twin groups (153.6 ± 30.4 cm2 vs. 150.8 ± 29.5 cm2, p = 0.54). Other clinical measurements, including BMI, lipid profiles, fasting insulin and blood glucose, were also not significantly different between groups (p ≥ 0.056), whereas HbA1c level of group a is significantly higher than group b (5.8 ± 0.3% vs. 5.6 ± 0.2%, p = 0.008). The number and richness of OTUs are relatively higher in group a, and 13 metabolites were significantly different between two groups. Furthermore, several of the 13 metabolites could be significantly linked to special taxons. The potential pathway involved drug metabolism-other enzymes, Tryptophan metabolism and Citrate cycle.

Conclusions

Gut microbiome composition and their metabolites may modulate glucose metabolism in obese adults without diabetes, through Tryptophan metabolism, Citrate cycle and other pathways.
Considerations for transition from subcutaneous to oral prophylaxis in the treatment of hereditary angioedema
Authors: Gower Richard G. , Wilber Mary
Published: October 2021

Background

Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable localized episodes of edema, which is frequently managed with long-term prophylactic medications. Until recently, long-term prophylaxis has predominantly required regular intravenous or subcutaneous administration, however the recent approval of berotralstat (Orladeyo™) offers an orally administered prophylactic which may be associated with a lower burden of treatment compared to injectable options for some patients.

Case presentation

This report describes four participants in the APeX-S trial who transitioned from subcutaneously administered lanadelumab (Takhzyro®) to daily oral berotralstat for long-term HAE prophylaxis. Lanadelumab dosing continued after berotralstat commencement in all patients and was tapered before discontinuation in three of the four patients. No substantial increases in HAE attack rates were observed after the transition to berotralstat monotherapy. One patient experienced a treatment-related adverse event (dyspepsia), which was mild and self-resolving.

Conclusions

All four patients described in this case series successfully transitioned from lanadelumab to berotralstat monotherapy for long-term prophylaxis without significant complications and without the use of a complex transition protocol. The decision to transition to berotralstat monotherapy and how the transition should be achieved was discussed between patient and physician, ensuring that the comfort and perspectives of the patients were considered during the treatment transition. This report highlights the importance of individualization of HAE management plans to address both the disease and treatment burdens of HAE, and thus to provide the best possible quality of life for each patient.
Isotretinoin-associated exercise-induced anaphylaxis in a patient with birch pollinosis and soybean sensitization: case presentation and literature review
Authors: Bamidis Anna , Hofmann Silke C.
Published: October 2021

Background

Peanut and soybean allergies are listed as contraindication in the package leaflet of isotretinoin, a widely used treatment of acne vulgaris. Cross-reactivity between PR10-proteins in peanut, tree nuts, and soybean is particularly common in patients with birch pollinosis and may lead to anaphylactic reactions in sensitized patients after intake of soybean oil containing isotretinoin capsules.

Case presentation

Here, we describe a young man with hazelnut and birch pollen allergy, who experienced exercise-induced anaphylaxis after isotretinoin intake on the third day of treatment. A complete allergy work-up was carried out, and sensitization to both peanut and soybean PR10-proteins was confirmed. However, oral provocation with isotretinoin remained negative in the absence of intense physical activity and longterm treatment was well tolerated.

Conclusion

To our knowledge, this is the first report of an exercise-induced anaphylaxis due to isotretinoin therapy. Our literature review to assess tolerability of isotretinoin in patients allergic to peanut, tree nuts or soybean revealed only one other case of anaphylaxis in a cashew-nut allergic patient sensitized to soybean PR10-protein Gly m 4. While there are no reports on soybean allergic patients treated with isotretinoin, the vast majority of peanut or tree nut allergic patients tolerated isotretinoin. Therefore, we conclude that sensitization to soybean, peanut or tree nuts should not preclude isotretinoin therapy. Particular caution is however warranted in patients with soybean sensitization. Pre-treatment oral challenges with isotretinoin may be recommended and physicians should be aware of the potential role of cofactors.
Exploration of parent-reported food allergy symptoms via breastmilk exposures and likelihood to develop tolerance
Authors: Lang Abigail , Patel Shrey , Rychlik Karen , Caruso Deanna , Wang Xiaobin , Pongracic Jacqueline A. , Kumar Rajesh
Published: October 2021

Background

Knowledge is limited about the relationship between clinical reactivity to foods through breastfeeding and long-term food allergy outcomes. We explored parent-perceived symptoms of food allergy via breastfeeding and the association with future tolerance.

Methods

Subjects identified from the Chicago Food Allergy Study (2005–2011) were categorized by parent-reported reactions to maternally ingested foods via breastfeeding (50/898 peanut-allergic, 69/620 egg-allergic, and 153/589 milk-allergic). The primary outcome was tolerance [passed oral food challenge (OFC) or consumption of previously implicated food]. Secondary outcomes included severe reactions (anaphylaxis and/or cardiovascular/respiratory symptoms) and additional concomitant food allergies. Univariate chi-square analyses were performed to assess for association between variables, followed by logistic regression models.

Results

Of the 50 subjects with parent-reported peanut-associated symptoms with breastfeeding, none gained tolerance. There were no significant associations between parent-reported breastfeeding symptoms and development of tolerance for egg and milk (egg: OR 0.46, 95% CI 0.21–1.01, p = 0.053; milk: OR 1.13, 95% CI 0.70–1.81, p = 0.614). All egg-allergic subjects with parent-perceived symptoms while breastfeeding also reported multiple food allergies (n = 69), but milk- and peanut-allergic subjects were not more likely to have multiple allergies (milk: OR 1.89, 95% CI 0.88–4.02, p = 0.10; peanut: OR 2.36, 95% CI 0.72–7.76, p = 0.16). There were no significant associations between parent-reported breastfeeding symptoms and subsequent reaction severity.

Conclusions

A significant proportion of parents perceive symptoms of food allergy attributable to indirect breastfeeding exposures. Our exploratory analysis suggests that infants with parent-perceived clinical reactivity to peanut via breastmilk may be less likely to gain tolerance. Infants with parent-reported reactivity to egg via breastmilk exposure were more likely to report multiple food allergies. Further rigorous prospective studies are needed to clarify the true prevalence of IgE-mediated food allergy symptoms attributable to indirect breastfeeding exposures and the association with development of tolerance.
Potential therapeutic approach of intravenous immunoglobulin against COVID-19
Authors: Kolahchi Zahra , Sohrabi Hanye , Ekrami Nasab Sara , Jelodari Mamaghani Hesan , Keyfari Alamdari Maryam , Rezaei Nima
Published: October 2021

Since the outbreak of the novel coronavirus disease (COVID-19), the therapeutic and management options to reduce the burden of the COVID-19 disease are under investigation. IVIG therapy is used as an effective treatment for immunodeficient patients and patients with inflammatory or autoimmune conditions. The therapeutic effect of IVIG in COVID-19 patients has been investigated. But, the results are controversial and some studies reported no benefit of IVIG therapy. More clinical trials on the effect of IVIG therapy in COVID-19 patients should be performed to establish a certain conclusion about IVIG effectiveness.
Orbital myeloid sarcoma misdiagnosed for subperiostal hematoma: a case report
Authors: Razem Bahaa , Raiteb Mohamed , El Mrini Sanaa , Slimani Faiçal
Published: October 2021

Background

Myeloid sarcoma is a solid tumor that consists of immature myeloid cells occurring at an extramedullary site. It can present before, concurrent with, or after the diagnosis of acute myeloid leukemia or other myeloproliferative diseases, and a proportion of patients never develop bone marrow infiltration. Only a few isolated cases of pediatric orbital myeloid sarcoma have been reported, and they are often associated with a high misdiagnosis rate.

Case report

We report a rare case of pediatric orbital myeloid sarcoma associated with blunt trauma in a 3-year-old Caucasian male patient, which was clinically and radiologically misdiagnosed for orbital subperiostal hematoma. The patient underwent a surgical intervention to drain the hematoma when an orbital mass was found. The microscopic, immunologic, and genetic features of the tumor and the myelogram were in favor of LAM2, and the patient was started with chemotherapy with a favorable evolution within 18 months follow-up.

Conclusion

Orbital myeloid sarcoma usually exhibits clinical and radiological features that can be easily misleading, especially if it happensde novoor as the first manifestation of acute myeloid leukemia. Only a few isolated cases have reported and proposed trauma as a trigger event of the onset of this type of tumor proliferation, but further investigations and evidence are needed to support this hypothesis.
Cesarean scar pregnancy treatment: a case series
Authors: Heidar Zahra , Zadeh Modarres Shahrzad , Abediasl Zhila , Khaghani Arezo , Salehi Ensieh , Esfidani Tayebeh
Published: October 2021

Background

Cesarean scar pregnancy is a complicated and potentially life-threatening type of ectopic pregnancy. This study reports two women with cesarean scar pregnancy who were successfully treated with systemic methotrexate administration, and two other women who needed local re-administration of methotrexate after systemic injection.

Case presentation

Four Iranian pregnant women aged 29–34 years who were between 5  to 7 gestational weeks with cesarean scar pregnancy diagnosis are described. After a single dose of systemic methotrexate injection, the level of serum beta-human chorionic gonadotropin decreased in two of the women, while fetal activity was observed in the other two women. In the latter patients, methotrexate was injected under transvaginal ultrasound guidance into the gestational sac. As a result, the serum beta-human chorionic gonadotropin level first increased and then decreased in these patients. During the follow-up period, all the patients were stable and no complications were observed. Serum beta-human chorionic gonadotropin levels reached the non-pregnancy range from 4 to 9 weeks after treatment.

Conclusion

When diagnosed at early gestation, cesarean scar pregnancy can be treated successfully with methotrexate administration alone. The clinicians should be aware that the beta-human chorionic gonadotropin level may initially increase after methotrexate injection in some patients. However, the final outcome will be promising if the patients remain stable.
Fulminant H1N1 and severe acute respiratory syndrome coronavirus-2 infections with a 4-year interval without an identifiable underlying cause: a case report
Authors: Katzenstein Terese L. , Jørgensen Sofie E. , Mortensen Jann , Helleberg Marie , Kalhauge Anna , Mogensen Trine H.
Published: October 2021

Background

The clinical presentation of severe acute respiratory syndrome coronavirus-2 infection is highly variable from asymptomatic infection to fulminant disease. The reasons for the variation are only starting to unravel, with risk factors including age and certain comorbidities as well as genetic defects causing immunological perturbations in the interferon pathways.

Case presentation

We report the case of an otherwise healthy Caucasian man, who at ages 60 and 64 years suffered from severe H1N1 influenza virus infection and severe acute respiratory syndrome coronavirus-2 infections, respectively. In both cases, there were acute kidney impairment and the need for intensive care unit admission as well as mechanical ventilation. Fortunately, after both infections there was full clinical recovery. The severity of the infections indicates an underlying impairment in the ability to control these kinds of infections. Challenge of patient peripheral blood mononuclear cells showed impaired type I and III antiviral interferon responses and reduced interferon-stimulated gene expression. However, despite investigation of patient samples by whole exome sequencing and enzyme-linked immunosorbent assay, no known disease-causing genetic variants related to interferon pathways were found, nor were interferon autoantibodies demonstrated. Thus, any underlying immunological cause of this unusual susceptibility to severe viral infections remains unresolved.

Conclusion

The patient experienced very similar severe clinical pictures triggered by H1N1 and severe acute respiratory syndrome coronavirus-2 infections, indicating an underlying inability to contain these infections. We were unable to show that the patient had any of the currently known types of immune incompetence but identified genetic changes possibly contributing to the severe course of both infections. Further analyses to delineate contribution factors are needed.
The impact of a coronavirus disease 2019 pandemic-related interruption of regular physical rehabilitation on functional abilities in a patient with two chronic neurological diseases: a case report
Authors: Braun Tobias , Weidmann Raphael , Möller Jens Carsten , Ammann Anissa , Marks Detlef
Published: October 2021

Background

Regular outpatient rehabilitation is prescribed for many patients with chronic neurological disorders, such as Parkinson’s disease or multiple sclerosis, to constantly support patients and their proxies in disease management. Due to the coronavirus disease 2019 pandemic, federal institutions and governments worldwide have directed local or nationwide lockdowns. During these times, the provision of regular outpatient rehabilitation service is drastically limited, making it actually impossible for community-dwelling patients with neurological disorders to receive prescribed rehabilitation interventions.

Case presentation

A 67-year-old White Swiss man with two chronic neurological diseases, Parkinson’s disease and multiple sclerosis, underwent a 4-week inpatient rehabilitation in our hospital. The main rehabilitation goals were related to improvements of mobility and a decrease in the risk of falls. The patient gained significant functional improvements that he maintained over the following months, supported by the continuation of physiotherapy in the domestic environment. Due to a coronavirus disease 2019 pandemic-related interruption of the regular ambulatory rehabilitation for several weeks during the first coronavirus disease 2019 wave in Switzerland, the patient’s functional abilities decreased significantly. Thus, the patient was again referred to our hospital for intensive inpatient rehabilitation to regain his physical functioning and mobility capacity. At hospital discharge, the patient improved most of his physical functioning to a prepandemic level.

Conclusions

The interruption of a rehabilitation service due to a pandemic-related lockdown can significantly impact the functional abilities of patients with chronic neurological diseases. This case report supports the claim for continuous access to rehabilitation services for all people with rehabilitation needs.
Mesenchymal stem cells derived from human induced pluripotent stem cells improve the engraftment of myogenic cells by secreting urokinase-type plasminogen activator receptor (uPAR)
Authors: Elhussieny Ahmed , Nogami Ken’ichiro , Sakai-Takemura Fusako , Maruyama Yusuke , Takemura Natsumi , Soliman Wael Talaat , Takeda Shin’ichi , Miyagoe-Suzuki Yuko
Published: October 2021

Background

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disease caused by mutations in the dystrophin gene. Transplantation of myogenic stem cells holds great promise for treating muscular dystrophies. However, poor engraftment of myogenic stem cells limits the therapeutic effects of cell therapy. Mesenchymal stem cells (MSCs) have been reported to secrete soluble factors necessary for skeletal muscle growth and regeneration.

Methods

We induced MSC-like cells (iMSCs) from induced pluripotent stem cells (iPSCs) and examined the effects of iMSCs on the proliferation and differentiation of human myogenic cells and on the engraftment of human myogenic cells in the tibialis anterior (TA) muscle of NSG-mdx4Cv mice, an immunodeficient dystrophin-deficient DMD model. We also examined the cytokines secreted by iMSCs and tested their effects on the engraftment of human myogenic cells.

Results

iMSCs promoted the proliferation and differentiation of human myogenic cells to the same extent as bone marrow-derived (BM)-MSCs in coculture experiments. In cell transplantation experiments, iMSCs significantly improved the engraftment of human myogenic cells injected into the TA muscle of NSG-mdx4Cv mice. Cytokine array analysis revealed that iMSCs produced insulin-like growth factor-binding protein 2 (IGFBP2), urokinase-type plasminogen activator receptor (uPAR), and brain-derived neurotrophic factor (BDNF) at higher levels than did BM-MSCs. We further found that uPAR stimulates the migration of human myogenic cells in vitro and promotes their engraftment into the TA muscles of immunodeficient NOD/Scid mice.

Conclusions

Our results indicate that iMSCs are a new tool to improve the engraftment of myogenic progenitors in dystrophic muscle.
Non-stem bladder cancer cell-derived extracellular vesicles promote cancer stem cell survival in response to chemotherapy
Authors: Chung Wei-Min , Molony Ryan D. , Lee Yi-Fen
Published: October 2021

Background

Chemosenstive non-stem cancer cells (NSCCs) constitute the bulk of tumors and are considered as part of the cancer stem cell (CSC) niche in the tumor microenvironment (TME). Tumor-derived extracellular vesicles (EVs) mediate the communication between tumors and the TME. In this study, we sought to investigate the impacts of EVs released by NSCCs on the maintenance of CSC properties and chemoresistance.

Methods

We employed murine MB49 bladder cancer (BC) sub-lines representing CSCs and NSCCs as a model system. Chemotherapy drugs were used to treat NSCCs in order to collect conditioned EVs. The impacts of NSCC-derived EVs on CSC progression were evaluated through sphere formation, cytotoxicity, migration, and invasion assays, and by analyzing surface marker expression on these BC cells. Differential proteomic analyses were conducted to identify cargo protein candidates involved in the EV-mediated communication between NSCCs and CSCs.

Results

NSCC-derived EVs contained cargo proteins enriched in proteostasis-related functions, and significantly altered the development of CSCs such that they were more intrinsically chemoresistant, aggressive, and better able to undergo self-renewal.

Conclusions

We thus identified a novel communication mechanism whereby NSCC-EVs can alter the relative fitness of CSCs to promote disease progression and the acquisition of chemoresistance.
Reduced-complexity decoding implementation of QC-LDPC codes with modified shuffling
Authors: Hasani Alireza , Lopacinski Lukasz , Kraemer Rolf
Published: October 2021

Layered decoding (LD) facilitates a partially parallel architecture for performing belief propagation (BP) algorithm for decoding low-density parity-check (LDPC) codes. Such a schedule for LDPC codes has, in general, reduced implementation complexity compared to a fully parallel architecture and higher convergence rate compared to both serial and parallel architectures, regardless of the codeword length or code-rate. In this paper, we introduce a modified shuffling method which shuffles the rows of the parity-check matrix (PCM) of a quasi-cyclic LDPC (QC-LDPC) code, yielding a PCM in which each layer can be produced by the circulation of its above layer one symbol to the right. The proposed shuffling scheme additionally guarantees the columns of a layer of the shuffled PCM to be either zero weight or single weight. This condition has a key role in further decreasing LD complexity. We show that due to these two properties, the number of occupied look-up tables (LUTs) on a field programmable gate array (FPGA) reduces by about 93% and consumed on-chip power by nearly 80%, while the bit error rate (BER) performance is maintained. The only drawback of the shuffling is the degradation of decoding throughput, which is negligible for low values of$$E_b/N_0$$Eb/N0until the BER of 1e−6.
A characterization of cortisol level and adrenal reservation in human cardiopulmonary arrest: systematic review and meta-analysis
Authors: Sahebnasagh Adeleh , Nejad Paria Soltani , Salehi-Abargouei Amin , Dehghani Mohammad Hossein , Saghafi Fatemeh
Published: October 2021

Background

Cardiopulmonary arrest (CPA) is an urgency, which is associated with high mortality. This systematic review evaluated the relationship between baseline cortisol level and the outcome of resuscitated CPA patients.

Methods

We searched the following databases: PubMed, Scopus, ISI Web of Science, and Google Scholar. Relevant observational and controlled trials were explored from inception by April 2020. The quality of the articles was assessed using the Newcastle-Ottawa Scale (NOS).

Results

Finally, five cohort studies (n = 201 participants in total) were eligible for including in the meta-analysis. The results of this meta-analysis showed that although the baseline serum cortisol levels were higher in survivors of cardiac arrest compared with non-survivors, the differences between groups do not reach a significance level (Hedges’ g = 0.371, 95% CI, −0.727, 1.469, P value = 0.508). Between-study heterogeneity was statistically significant (Cochrane Q test: P value < 0.001, I2 = 89.323).

Conclusions

The result of the present meta-analysis was suggestive of a higher baseline serum cortisol levels in survivors of CPA. Future randomized controlled studies with a large sample size will determine the exact relationship between adrenal reservation and the eventual outcome of patients with CPA.

Systematic review registration

PROSPERO CRD42018085468
Do continuous forms of intra-operative ultrafiltration enhance recovery after adult cardiac surgery with cardiopulmonary bypass? A protocol for systematic review and meta-analysis of randomized controlled trials
Authors: Bierer Joel , Horne David , Stanzel Roger , Henderson Mark , Boulos Leah , Hayden Jill
Published: October 2021

Background

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a systemic inflammatory syndrome that adversely impacts cardiopulmonary function and can contribute to prolonged postoperative recovery. Intra-operative ultrafiltration during CPB is a strategy developed by pediatric cardiac specialists, aiming to dampen the inflammatory syndrome by removing circulating cytokines and improving coagulation profiles during the cardiac operation. Although ultrafiltration is commonly used in the pediatric population, it is not routinely used in the adult population. This study aims to evaluate if randomized evidence supports the use of continuous intra-operative ultrafiltration to enhance recovery for adults undergoing cardiac surgery with CPB.

Methods

This systematic review and meta-analysis will include randomized controlled trials (RCT) that feature continuous forms of ultrafiltration during adult cardiac surgery with CPB, specifically assessing for benefit in mortality rates, invasive ventilation time and intensive care unit length of stay (ICU LOS). Relevant RCTs will be retrieved from databases, including MEDLINE, Embase, CENTRAL and Scopus, by a pre-defined search strategy. Search results will be screened for inclusion and exclusion criteria by two independent persons with consensus. Selected RCTs will have study demographics and outcome data extracted by two independent persons and transferred into RevMan. Risk of bias will be independently assessed by the Revised Cochrane Risk-of-Bias (RoB2) tool and studies rated as low-, some-, or high- risk of bias. Meta-analyses will compare the intervention of continuous ultrafiltration against comparators in terms of mortality, ventilation time, ICU LOS, and renal failure. Heterogeneity will be measured by the χ2 test and described by the I2 statistic. A sensitivity analysis will be completed by excluding included studies judged to have a high risk of bias. Summary of findings and certainty of the evidence, determined by the GRADE approach, will display the analysis findings.

Discussion

The findings of this systematic review and meta-analysis will summarize the evidence to date of continuous forms of ultrafiltration in adult cardiac surgery with CPB, to both inform adult cardiac specialists about this technique and identify critical questions for future research in this subject area.

Systematic review registration

This systematic review and meta-analysis is registered in PROSPERO CRD42020219309 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020219309).
Multi-resolution wavelet basis for solving steady forced Korteweg–de Vries model
Authors: Utudee Somlak , Maleewong Montri
Published: October 2021

A steady forced Korteweg–de Vries (fKdV) model which includes gravity, capillary, and pressure distributions is solved numerically using the wavelet Galerkin method. The anti-derivatives of Daubechies wavelets are developed as the basis of the solution subspaces for the mixed boundary condition type. Accuracy of numerical solutions can be improved by increasing the number of wavelet levels in the multi-resolution analysis. The theoretical result of convergence rate is also shown. The problem can be viewed as gravity-capillary wave flows over an applied pressure distribution. The flow regime can be characterized by subcritical, supercritical, and critical flows depending on the value of the Froude number. Trapped depression and elevation waves are found over the pressure distribution. For a near-critical flow regime, a generalized solitary wave with ripples is presented. This shows a capillary effect in balance to gravity and the pressure force on the free surface.
A new structure to n-dimensional trigonometric cubic B-spline functions for solving n-dimensional partial differential equations
Authors: Raslan K. R. , Ali Khalid K. , Mohamed Mohamed S. , Hadhoud Adel R.
Published: October 2021

In this paper, we present a new structure of the n-dimensional trigonometric cubic B-spline collocation algorithm, which we show in three different formats: one-, two-, and three-dimensional. These constructs are critical for solving mathematical models in different fields. We illustrate the efficiency and accuracy of the proposed method by its application to a few two- and three-dimensional test problems. We use other numerical methods available in the literature to make comparisons.