bluuebunny/crossref_metadata_2025 huggingface dataset:
Anakinra: efficacy in the management of fever during neutropenia and mucositis in autologous stem cell transplantation (AFFECT-2)—study protocol for a multicenter randomized double-blind placebo-controlled trial
Authors: de Mooij Charlotte E. M. , van Groningen Lenneke F. J. , de Haan Anton F. J. , Biemond Bart J. , Bakker Martijn , van der Velden Walter J. F. M. , Blijlevens Nicole M. A.
Published: November 2020

Background

Since decades, fever and infections have been the most important complications of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic malignancies. Neutropenia has long been considered to be the most important risk factor for these complications. However, recent studies have shown that not neutropenia, but the development of mucositis is the most important cause of these complications. Currently, limited options for the prevention and treatment of mucositis are available, of which most are only supportive. The pro-inflammatory cytokine interleukin-1 (IL-1) plays a crucial role in the pathogenesis of mucositis. Pre-clinical studies of chemotherapy-induced mucositis have shown that recombinant human IL-1 receptor antagonist anakinra significantly ameliorated intestinal mucositis. In our pilot study AFFECT-1, we examined the safety and maximal tolerated dose of anakinra in patients with multiple myeloma, treated with high-dose melphalan (HDM) and autologous HSCT, selecting a dose of 300 mg daily for the phase IIb trial. The aim of the AFFECT-2 study is to determine the efficacy of anakinra in preventing fever during neutropenia (FN) and mucositis in this study population.

Methods/design

A multicenter, randomized, placebo-controlled, double-blind phase IIb trial will be conducted. Ninety patients with multiple myeloma scheduled for treatment with HDM and autologous HSCT will be included. Patients will be randomized between intravenous treatment with anakinra (300 mg) or placebo. Each group will be treated from day − 2 (day of HDM; day 0 is HSCT) up until day + 12. Outcome measures will be assessed at baseline, during admission, at discharge or day + 30, at day + 90, and + 1 year. The primary outcome will be reduction of FN. Secondary outcome measures include mucositis scores, bloodstream infections, citrulline levels, quality of life, and fatigue severity.

Discussion

The AFFECT-2 trial will examine the efficacy of anakinra in the management of fever during neutropenia and mucositis in patients with multiple myeloma treated with HDM and autologous HSCT. The results of this study may provide a new treatment option for these important complications. Also, this study will give us more insight in the pathophysiology of mucositis, including the role of IL-1 and the role of the microbiota in mucositis.

Trial registration

Clinicaltrials.gov NCT04099901. Registered on September 23, 2019. EudraCT: 2018-005046-10.
Oral corticosteroids for post-infectious cough in adults: study protocol for a double-blind randomized placebo-controlled trial in Swiss family practices (OSPIC trial)
Authors: Merlo Christoph , Essig Stefan , Brancati-Badarau D. Oana , Leuppi Jörg Daniel , Speich Benjamin , Erlanger Tobias E. , Hemkens Lars G. , Zeller Andreas
Published: November 2020

Background

Cough is a common reason for patients to visit general practices. So-called post-infectious cough is defined as lasting 3 to 8 weeks after an upper respiratory tract infection. It can be disabling in daily activities, with substantial impact on physical and psychosocial health, leading to impaired quality of life and increased health care costs. Recommendations for the management of post-infectious cough in primary care are scarce and incoherent. A systematic review and meta-analysis of randomized clinical trials (RCT) assessing patient-relevant benefits and potential harms of available treatments identified six eligible RCTs assessing different treatment regimens (i.e. inhaled fluticasone propionate, inhaled budesonide, salbutamol plus ipratropium-bromide, montelukast, nociception-opioid-1-receptor agonist, codeine, gelatine). No RCT found clear patient-relevant benefits and most had an unclear or high risk of bias.

Post-infectious cough is thought to be mediated by inflammatory processes that are also present in exacerbations of asthma or chronic obstructive pulmonary diseases for which there is strong evidence that oral corticosteroids provide patient-relevant benefit without relevant harm. We therefore plan to conduct the first RCT evaluating the effectiveness of oral corticosteroids for post-infectious cough.

Methods

We are conducting a triple-blinded randomized-controlled and multicentred superiority trial in primary health care practices in Switzerland. We will include 204 adult patients who consult their general practitioner (GP) for a cough lasting 3 to 8 weeks following an upper respiratory tract infection. Participants will be randomly allocated to either the 5-day treatment with oral corticosteroids or placebo. The primary outcome is cough-related quality of life assessed by the Leicester Cough Questionnaire score 14 days after randomization. Secondary outcomes include cough-related quality of life at several time points, overall cessation of cough and adverse events.

Discussion

This RCT will provide evidence on whether oral corticosteroids are beneficial and safe in patients with post-infectious cough. Results can have a substantial impact on the well-being and management of these patients in Switzerland and beyond. An evidence-based treatment for this condition may reduce re-consultations with GPs and spending for antitussive drugs, thus possibly having an impact on health care spending.

Trial registration

ClinicalTrials.gov NCT04232449. Prospectively registered on 18 January 2020.
Effects of Keluoxin capsule combined with losartan potassium on diabetic kidney disease: study protocol for a randomized double-blind placebo-controlled multicenter clinical trial
Authors: Wu Rui , Wei Fan , Qu Lianlian , Bai Litao , Li Jun , Li Fei , Yan Weitian , Wang Qiuhong , Wei Junping
Published: November 2020

Background

Diabetic kidney disease (DKD) is one of the most important microvascular complications of diabetes, and its prevalence has increased dramatically in the past few decades. DKD is responsible for considerable morbidity and mortality of patients with diabetes. Keluoxin capsule (KLX) is a Chinese patent medicine that has been used in the clinic to control DKD for years. Previous studies have shown that KLX appears to reduce proteinuria, but the study protocols as well as the primary outcome need to be improved. Thus, we aim to evaluate whether losartan potassium combined with KLX is more effective than losartan potassium in DKD treatment and to provide validated evidence for the application of KLX in the treatment of DKD.

Methods

We will conduct a randomized double-blind placebo-controlled multicenter clinical trial. A total of 252 participants diagnosed with DKD recruited from 18 institutions will be randomly allocated to either a losartan potassium plus KLX (n = 126) or a losartan potassium plus placebo group (n = 126). The participants will be administered KLX or placebo in addition to losartan potassium for 24 weeks. The primary outcome measure will be the decline in estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2/year) from baseline within 24 weeks, and the secondary outcomes will be the incidence of serum creatinine doubling, the incidence of end-stage renal disease (ESRD), the proportion of subjects with a progressive decline in eGFR > 30%, the percent change in 24 h urinary total protein (UTP), the change in the urinary albumin/creatinine ratio (UACR), and the total effective rate of the traditional Chinese medicine (TCM) syndrome scale scores. Comparison of the differences in the variables between groups will be performed according to the data revealed by independent t tests, chi-squared tests, Fisher’s exact tests, or Wilcoxon’s tests. All statistical tests will be two-sided, and significance will be considered for p values < 0.05.

Discussion

This study will be the first randomized clinical trial to evaluate the efficacy and safety of KLX versus the placebo for the treatment of patients with DKD. The outcome of this trial will provide a basis for prescribing KLX to patients with DKD.

Trial registration

Chinese Clinical Trial Registry (www.chictr.org.cn) ChiCTR1900021113. Registered on January 29, 2019.
Intralipid postconditioning in patients of cardiac surgery undergoing cardiopulmonary bypass (iCPB): study protocol for a randomized controlled trial
Authors: Yuan Yuan , Xiong Hui , Zhang Yan , Yu Hong , Zhou Rong-Hua
Published: November 2020

Background

Intralipid is a necessary fatty acid carrier that has been safely used as an energy supplier in the clinic. It has played an important role in rescuing the cardiac arrest caused by local anesthetic toxicity. In recent years, experimental studies have shown that intralipid postconditioning (ILPC) could reduce myocardial ischemic/reperfusion (I/R) injuries. Our research group has innovatively conducted a pilot randomized controlled trial (RCT), and the results showed that ILPC could reduce the release of cTnT and CK-MB, biomarkers of myocardial I/R injury, in valve replacement surgery. However, the potential effects of ILPC on the clinical outcome of adult cardiac surgery patients are unclear. Intralipid postconditioning in patients of cardiac surgery undergoing cardiopulmonary bypass (iCPB) trial is aimed to further study whether ILPC could improve short-term and long-term clinical outcome, as well as cardiac function in adult cardiac surgery patients.

Methods

The iCPB trial is an ongoing, single-center, prospective, double-blinded, large sample RCT. In total, 1000 adults undergoing cardiac surgery will be randomly allocated to either the ILPC group or the control group. The intervention group received an intravenous infusion of 2 mL/kg of 20% intralipid (medium-chain and long-chain fat emulsion injection C6~C24, Pharmaceutical) within 10 min before aortic cross-unclamping, and the control group received an equivalent volume of normal saline. The primary endpoints are complex morbidity of major complications during hospitalization and all-cause mortality within 30 days after surgery. The secondary endpoints include (1) all-cause mortality 6 months and 1 year postoperatively; (2) the quality of life within 1 year after surgery, using the QoR-15 questionnaire; (3) the postoperative cardiac function evaluated by LVEF, LVEDS, and LVEDD, and the myocardial injury evaluated by CK-MB, cTnT, and BNP; and (4) short-term clinical outcomes during hospitalization and total cost are also detailed evaluated.

Discussion

The iCPB trial is the first to explore ILPC on the clinical outcome of adult cardiac surgery patients. The results are expected to provide potential evidences about whether ILPC could reduce the morbidity and mortality and improve the cardiac function and quality of life. Therefore, the results will provide a rationale for the evaluation of the potentially clinically relevant benefit of intralipid therapy.

Trial registration

Chictr.org.cn ChiCTR1900024387. Prospectively registered on 9 July 2019.
Parents’ understanding and motivation to take part in a randomized controlled trial in the field of adolescent mental health: a qualitative study
Authors: O’Keeffe Sally , Weitkamp Katharina , Isaacs Danny , Target Mary , Eatough Virginia , Midgley Nick
Published: November 2020

Background

Little is known about why parents agree to take part in randomized controlled trials for adolescent mental health. This study aimed to investigate parents’ perspectives on participating in a trial for psychological treatment of depression. The study explored parents’ motivations, understanding of the trial and perspectives on the acceptability of the trial.

Methods

Sixty-five parents took part in this qualitative study. Their adolescent children had been randomly allocated to one of three active psychological treatments for depression as part of the IMPACT trial and were interviewed about their experiences of participating in the study. Semi-structured interviews were analysed using framework analysis.

Results

For seven of the sixty-five parents, their experience of taking part in the trial was not covered in their interview so they were excluded from the analysis. The analysis was therefore based on the data from the parents of 58 adolescents taking part in the trial. The most commonly cited motivation for taking part in the study reported by parents was a desire to help others going through similar difficulties. Parents generally reported finding trial participation acceptable, although there were aspects that some reported finding less acceptable, including randomization and the burden of research assessments. Others spoke positively about the experience of trial participation and found it enjoyable or even therapeutic. Importantly, some did not appear to have a good understanding of the trial design, including randomization and treatment allocation.

Conclusions

This study indicates that trial participation can be a positive experience for parents, yet it raises concerns about how trialists can ensure that consent is fully informed, given that some parents appeared to have a poor understanding of the trial. Future studies should seek to explore how communication with trial participants can be improved, to ensure that trial participation is fully informed. Patient and public involvement will be crucial in ensuring this communication is accessible to stakeholders.

Trial registration

ISRCTN registry ISRCTN83033550. Registered on 15 October 2009
The impact of the fipronil crisis on the financial performance of Dutch laying hen farms
Authors: Sok Jaap , van Horne Peter , Meuwissen Miranda
Published: November 2020

Background

Illegal use of fipronil as an insecticide in 2017 has caused substantial damage to Dutch laying hen farms. We assessed how the fipronil crisis has affected the financial performance of affected farms as well as unaffected farms. While affected farms faced culling their flocks and lost revenue, unaffected farms benefitted from temporary high egg prices.

Methods

A three-step normative modelling approach is taken using financial statements and a partial budget. The estimations are for a 50,000 laying hen farm facing the fipronil crisis for 5 months. First, a baseline is created by generating an income statement of this laying hen farm representing a ‘normal year’. Second, incremental costs and revenue as a result of the fipronil crisis are estimated. Third, the baseline income statement is updated with the outcomes of the partial budget. This results in two additional income statements that report the net operating result of this farm being unaffected and affected by the fipronil crisis.

Results

While in a normal year this average-sized farm has a net operating result of around 18,000 euros, profitability was estimated to be − 369,000 euros and + 169,000 euros for the affected and unaffected farm due to the crisis respectively. For affected farms, impacts were especially high as there was no government compensation or insurance.

Conclusions

As Dutch farms typically operate as independent family farms, there was also no compensation from other chain actors. The affected farms therefore likely have faced financial distress and have had to increase debt or use their financial reserves for household consumption and restarting the business. Outcomes contribute to discussions around liability claims and cost-benefit assessments of measures to improve the chain food safety and rapid alert systems.

Graphical Abstract
Detection of Leishmania infantum DNA in Pintomyia evansi and Lutzomyia longipalpis in Honduras
Authors: Sosa-Ochoa Wilfredo , Varela Amador Javier , Lozano-Sardaneta Yokomi , Rodriguez Segura Gabriela , Zúniga Valeriano Concepcion , Araujo Gabriela Venicia , Sandoval Pacheco Carmen María , Laurenti Márcia Dalastra , Galvis-Ovallos Fredy
Published: November 2020

Background

The two most abundant sand fly species on the Honduran Pacific coast are Lutzomyia (Lutzomyia) longipalpis and Pintomyia (Pifanomyia) evansi. Both species are known vectors of Leishmania (Leishmania) infantum, the etiological agent of visceral leishmaniasis (VL) in the Americas. Although VL and non-ulcerative cutaneous leishmaniasis (NUCL) are endemic on the Pacific versant of the Central American Pacific, the latter is the most frequent manifestation of leishmaniasis there. We evaluated the circulation of Leishmania spp. in the sand fly species on El Tigre Island, an endemic area of NUCL.

Results

We collected 222 specimens of six sand fly species. Lu. longipalpis (180 specimens; 81%) and Pif. (Pi.) evansi (35 specimens; 16%) were the most abundant species. L. (L.) infantum DNA was detected in nine of the 96 specimens analyzed; seven of these specimens were identified as Lu. longipalpis, and the remaining two were Pi.evansi, with an infection rate of 9.4% and 2.7%, respectively.

Conclusion

We present the first record of L. (L.) infantum DNA in Pi.evansi from a NUCL endemic region of Central America. Our results suggest that Pi. evansi could be a secondary vector of L. (L.) infantum in the transmission cycle of leishmaniasis. The detection of natural infections of L. (L.) infantum in sand flies in this region contributes to an understanding of the epidemiology of leishmaniasis in Honduras.

Graphical Abstract
Cyr61 synthesis is induced by interleukin-6 and promotes migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis
Authors: Choi Changmin , Jeong Wooseong , Ghang Byeongzu , Park Yonggeun , Hyun Changlim , Cho Moonjae , Kim Jinseok
Published: November 2020

Background

Interleukin-6 (IL-6) is involved in fibroblast-like synoviocyte (FLS) activation and promotes pannus formation and bone and cartilage destruction in rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61) protein regulates cell proliferation, migration, and differentiation. The aim of this study was to investigate the role of Cyr61 in RA-FLS migration and invasion after IL-6 stimulation.

Methods

Western blotting, immunohistochemistry, reverse transcription-polymerase chain reaction, and real time-polymerase chain reaction were used to examine protein and mRNA levels of Cyr61, matrix metalloproteinases (MMPs), and other signalling proteins. Knockdown of gene expression was performed with siRNA, and RNA sequencing was performed for differential gene analysis. Migration and invasion were assessed by wound healing and Boyden chamber assays.

Results

Cyr61 levels were elevated in FLSs from RA patients compared to those in osteoarthritis patients. Control and IL-6-treated FLSs showed differential gene expression. IL-6 stimulated protein synthesis of Cyr61, which was attenuated by the extracellular signal-related kinase 1/2 (ERK 1/2) inhibitor, PD98059, and knockdown of early growth response 3 (EGR3), but not of JUN. IL-6-induced Cyr61 protein synthesis increased expression of MMP2. Cyr61 promoted FLS migration and invasion in an autocrine manner. Knockdown of CYR61 and a neutralising antibody attenuated Cyr61 synthesis and IL-6-induced FLS migration.

Conclusions

By modulating the ERK/EGR3 pathway, IL-6 stimulated Cyr61 production and in turn increased invasiveness of FLS. Our data suggest that Cyr61 might be a potential target to prevent the progression of joint damage in RA.
Gut microbiota and the human gut physiological changes
Authors: Bajinka Ousman , Darboe Alansana , Tan Yurong , Abdelhalim Khalid A. , Cham Lamin B.
Published: November 2020

Background

The human gut can be colonized by number of microorganisms. The most studied are bacteria, which changes from birth to newborn born into adult-like gut microbiota. Much is known about the effects of dietary, medications, and lifestyles on the bacterial composition. However, the host physiological changes influencing the gut microbiota, the immediate consequences, and the possible gut microbiota therapy are not studied at length. This review is based profoundly on animal model studies through experimentation and some human clinical trials for the past 20 years.

Forward

The physiological factors studied to influences gut microbiota are bacterial mucosal receptors, mucin glycosylation, mucus, epithelial microvilli, and tight junction. Host secretions and immune response such as immunity, secretory A (sIgA), inflammasome, innate immunity, immune response, glycans, bile acids, peristalsis, microRNA, and adhesion to intestinal glycans are as well found to confer variety of alterations on gut microbial flora.

Conclusion

Despite the resilience of the gut microbiota in response to changes, chain of events causes the imbalance microbiota. Increased pro-inflammatory potential with the help of cell barriers, host secretions, and immune response mediate gut recovery.
Assessing diagnostic radiology knowledge among Syrian medical undergraduates
Authors: Alchallah Mhd Obai , Ismail Hlma , Dia Tala , Shibani Mosa , Alzabibi Mhd Amin , Mohsen Fatema , Turkmani Khaled , Sawaf Bisher
Published: November 2020

Background

The role of radiology in medicine and healthcare is rapidly expanding worldwide, but awareness about this field among medical students is poor. This is the first study to assess Syrian medical students’ knowledge and attitude regarding radiology.

Methods

This is a cross-sectional study conducted at the Syrian Private University, on November 8, 2019, on the International Day of Radiology during the war crisis. Data were collected through self-administered surveys and analyzed using the Statistical Package for Social Sciences version 25.0 (SPSS Inc., Chicago, IL, USA).

Results

The questionnaire was completed by 269 students whose ages ranged between 17 and 30 years old. Males constituted 63.6% of the respondents. The results revealed adequate knowledge about the basics of radiology. 73.6% of the students had previously heard about interventional radiology. There were slight misconceptions with certain points in each section, especially those pertaining to the radiation exposure of each imaging method. Finally, the students expressed low interest in radiology as a future career (24.5%).

Conclusions

The level of awareness can affect a student’s decision in considering radiology as a future career. Further evaluation of the methods of teaching, input from medical boards, curriculum advisors, and guidance from radiologists is required.
Selective deletion of endothelial mineralocorticoid receptor protects from vascular dysfunction in sodium-restricted female mice
Authors: Faulkner Jessica L. , Lluch Emily , Kennard Simone , Antonova Galina , Jaffe Iris Z. , Belin de Chantemèle Eric J.
Published: November 2020

Background

Recent evidence by our laboratory demonstrates that women and female mice endogenously express higher endothelial mineralocorticoid receptor (ECMR) than males. Mounting clinical evidence also indicates that aldosterone production is higher in pathological conditions in females compared to males. However, the role for increased activation of ECMR by aldosterone in the absence of a comorbid condition is yet to be explored. The current study hypothesized that increased ECMR activation induced by elevated aldosterone production predisposes healthy female mice to endothelial dysfunction.

Method

Vascular reactivity was assessed in aortic rings from wild-type (WT) and ECMR KO (KO) mice fed either a normal salt (NSD, 0.4% NaCl) or sodium-restricted diet (SRD, 0.05% NaCl) for 28 days.

Results

SRD elevated plasma aldosterone levels as well as adrenal CYP11B2 and angiotensin II type 1 receptor (AT1R) expressions in female, but not male, WT mice. In baseline conditions (NSD), endothelial function, assessed by vascular relaxation to acetylcholine, was higher while vascular contractility to phenylephrine, serotonin, and KCl lower in female than male WT mice. SRD impaired endothelial function and increased vascular contractility in female, but not male, WT mice effectively ablating the baseline sex differences. NOS inhibition with LNAME ablated endothelial relaxation to a higher extent in male than female mice on NSD and ablated differences in acetylcholine relaxation responses between NSD- and SRD-fed females, indicating a role for NO in SRD-mediated endothelial function. In association, SRD significantly reduced vascular NOX4 expression in female, but not male, mice. Lastly, selective deletion of ECMR protected female mice from SRD-mediated endothelial dysfunction and increased vascular contractility.

Conclusion

Collectively, these data indicate that female mice develop aldosterone-induced endothelial dysfunction via endothelial MR-mediated reductions in NO bioavailability. In addition, these data support a role for ECMR to promote vascular contractility in female mice in response to sodium restriction.
Fanconi Bickel syndrome: clinical phenotypes and genetics in a cohort of Sudanese children
Authors: Musa Salwa A. , Ibrahim Areej A. , Hassan Samar S. , Johnson Matthew B , Basheer Asmahan T. , Arabi Ali M. , Abdullah Mohamed A.
Published: November 2020

Background

Fanconi-Bickel syndrome (FBS) is a rare condition of carbohydrate metabolism, caused by a recessive defect in the facilitative glucose transporter GLUT2 encoded by theSLC2A2gene and characterized by a wide spectrum of phenotypical features. There is a paucity of reported data on FBS from Sub-Saharan Africa. Here, we describe the clinical, biochemical and genetic characteristics of our patients with FBS from Sudan, a country with a high consanguinity rate.

Patients & methods

Eleven patients from ten unrelated Sudanese families were included. Clinical & biochemical data were documented and imaging studies done including bone survey and abdominal ultrasound. Liver biopsy was done to confirm the pathological diagnosis in 45% of cases and molecular genetics was performed through contribution with the Exeter genomics laboratory for ten patients.

Results

Reported consanguinity was 70% among our patients. Growth was significantly impaired at presentation with mean weights of (-5.3 ± 1.8) SD and heights (-5.4 ± 2.5) SD. Severe chest deformity was present in (27%) and all patients showed features of rickets at presentation. Three patients had neonatal diabetes requiring insulin therapy of which one has been reported before. Six families lost undiagnosed siblings with similar clinical presentations. We identified a total of four homozygous pathogenicSLC2A2variants in our patients, one of whom had a novel mutation.

Conclusions

FBS is not uncommon in Sudan where there is a high rate of consanguinity. Many cases are likely missed because of variable presentation and lack of public and professionals’ awareness. This is the first series to describe this condition from Sub-Saharan Africa.
Data processing scheme based on blockchain
Authors: Fu Jinhua , Xu Mixue , Huang Yongzhong , Si Xueming , Yuan Chao
Published: November 2020

In the white paper written on Bitcoin, a chain of blocks was proposed by Satoshi Nakamoto. Since then, blockchain has been rapidly developed. Blockchain is not only limited to the field of cryptocurrency but also has been extensively applied to the Internet of Things, supply chain finance, electronic evidence storage, data sharing, and e-government fields. Both the public chain and the alliance chain have been extensively developed. In the data processing field, blockchain has a particularly good application potential. The Square Kilometre Array (SKA) is a proposal consisting of a joint venture of more than ten countries, resulting in the world’s largest synthetic aperture radio telescope. In the SKA, the processing scale of the data is large, and it consists of several data processing nodes. The data will be processed in the cloud computing mode. Taking the SKA under consideration, this report proposes a data processing scheme based on blockchain for the anti-counterfeiting, anti-tampering and traceability of data. Furthermore, the authenticity and integrity of the data are assured. The primary aspects include data distribution, data operation and data sharing, which correspond to the data reception, data algorithm processing and result sharing of data operation in the SKA. With this process, the integrity, reliability and authenticity of the data are guaranteed. Additionally, smart contracts, homomorphic hashing, secure containers, aggregate signatures and one-way encrypted channels are implemented to ensure the intelligence, security and high performance of the process.
Generalized trapezium-type inequalities in the settings of fractal sets for functions having generalized convexity property
Authors: Khan Zareen A. , Rashid Saima , Ashraf Rehana , Baleanu Dumitru , Chu Yu-Ming
Published: November 2020

In the paper, we extend some previous results dealing with the Hermite–Hadamard inequalities with fractal sets and several auxiliary results that vary with local fractional derivatives introduced in the recent literature. We provide new generalizations for the third-order differentiability by employing the local fractional technique for functions whose local fractional derivatives in the absolute values are generalized convex and obtain several bounds and new results applicable to convex functions by using the generalized Hölder and power-mean inequalities.

As an application, numerous novel cases can be obtained from our outcomes. To ensure the feasibility of the proposed method, we present two examples to verify the method. It should be pointed out that the investigation of our findings in fractal analysis and inequality theory is vital to our perception of the real world since they are more realistic models of natural and man-made phenomena.
Malaria elimination in Malaysia and the rising threat of Plasmodium knowlesi
Authors: Chin Abraham Zefong , Maluda Marilyn Charlene Montini , Jelip Jenarun , Jeffree Muhammad Saffree Bin , Culleton Richard , Ahmed Kamruddin
Published: November 2020

Background

Malaria is a major public-health problem, with over 40% of the world’s population (more than 3.3 billion people) at risk from the disease. Malaysia has committed to eliminate indigenous human malaria transmission by 2020. The objective of this descriptive study is to understand the epidemiology of malaria in Malaysia from 2000 through 2018 and to highlight the threat posed by zoonotic malaria to the National Malaria Elimination Strategic Plan.

Methods

Malaria is a notifiable infection in Malaysia. The data used in this study were extracted from the Disease Control Division, Ministry of Health Malaysia, contributed by the hospitals and health clinics throughout Malaysia. The population data used in this study was extracted from the Department of Statistics Malaysia. Data analyses were performed using Microsoft Excel. Data used for mapping are available at EPSG:4326 WGS84 CRS (Coordinate Reference System). Shapefile was obtained from igismap. Mapping and plotting of the map were performed using QGIS.

Results

Between 2000 and 2007, human malaria contributed 100% of reported malaria and 18–46 deaths per year in Malaysia. Between 2008 and 2017, indigenous malaria cases decreased from 6071 to 85 (98.6% reduction), while during the same period, zoonoticPlasmodium knowlesicases increased from 376 to 3614 cases (an 861% increase). The year 2018 marked the first year that Malaysia did not report any indigenous cases of malaria caused by human malaria parasites. However, there was an increasing trend ofP. knowlesicases, with a total of 4131 cases reported in that year. Although the increased incidence ofP. knowlesicases can be attributed to various factors including improved diagnostic capacity, reduction in human malaria cases, and increase in awareness ofP. knowlesi, more than 50% ofP. knowlesicases were associated with agriculture and plantation activities, with a large remainder proportion linked to forest-related activities.

Conclusions

Malaysia has entered the elimination phase of malaria control. Zoonotic malaria, however, is increasing exponentially and becoming a significant public health problem. Improved inter-sectoral collaboration is required in order to develop a more integrated effort to control zoonotic malaria. Local political commitment and the provision of technical support from the World Health Organization will help to create focused and concerted efforts towards ensuring the success of the National Malaria Elimination Strategic Plan.
Low-frequency oscillations of finger skin blood flow during the initial stage of cold-induced vasodilation at different air temperatures
Authors: Sera Toshihiro , Kohno Taiki , Nakashima Yusuke , Uesugi Musashi , Kudo Susumu
Published: November 2020

Background

Cold-induced vasodilation (CIVD) is known to be influenced by the ambient temperature. Frequency analysis of blood flow provides information on physiological regulation of the cardiovascular system, such as myogenic, neurogenic, endothelial nitric oxide (NO) dependent, and NO-independent activities. In this study, we hypothesized that the major origin of CIVD occurs prior to the CIVD event and investigated finger skin blood flow during the initial stage of CIVD at different ambient temperatures using frequency analysis.

Methods

Eighteen healthy volunteers immersed their fingers in 5 °C water at air temperatures of 20 °C and 25 °C. Finger skin blood flow was measured using laser Doppler flowmetry and analyzed using Morlet mother wavelet. We defined the time when the rate of blood flow increased dramatically as the onset of CIVD, and defined three phases as the periods from the onset of cooling to minimum blood flow (vasoconstriction), from minimum blood flow to the onset of CIVD (prior to CIVD), and from the onset of CIVD to maximum blood flow (CIVD).

Results

The increment ratio of blood flow at CIVD was significantly higher at 20 °C air temperature. In particular, at 20 °C air temperature, arteriovenous anastomoses (AVAs) might be closed at baseline, as finger skin temperature was much lower than at 25 °C air temperature, and endothelial NO-independent activity was significantly higher and neurogenic activity significantly lower during vasoconstriction than at baseline. Additionally, the differences in both activities between vasoconstriction and prior to CIVD were significant. On the other hand, there were no significant differences in endothelial NO-dependent activity between baseline and all phases at both air temperatures.

Conclusions

Our results indicated that the increase of endothelial NO-independent activity and the decrease of neurogenic activity may contribute to the high increment ratio of blood flow at CIVD at 20 °C air temperature.
Neuroglia infection by rabies virus after anterograde virus spread in peripheral neurons
Authors: Potratz Madlin , Zaeck Luca M. , Weigel Carlotta , Klein Antonia , Freuling Conrad M. , Müller Thomas , Finke Stefan
Published: November 2020

The highly neurotropic rabies virus (RABV) enters peripheral neurons at axon termini and requires long distance axonal transport and trans-synaptic spread between neurons for the infection of the central nervous system (CNS). Recent 3D imaging of field RABV-infected brains revealed a remarkably high proportion of infected astroglia, indicating that highly virulent field viruses are able to suppress astrocyte-mediated innate immune responses and virus elimination pathways. While fundamental for CNS invasion, in vivo field RABV spread and tropism in peripheral tissues is understudied. Here, we used three-dimensional light sheet and confocal laser scanning microscopy to investigate the in vivo distribution patterns of a field RABV clone in cleared high-volume tissue samples after infection via a natural (intramuscular; hind leg) and an artificial (intracranial) inoculation route. Immunostaining of virus and host markers provided a comprehensive overview of RABV infection in the CNS and peripheral nerves after centripetal and centrifugal virus spread. Importantly, we identified non-neuronal, axon-ensheathing neuroglia (Schwann cells, SCs) in peripheral nerves of the hind leg and facial regions as a target cell population of field RABV. This suggests that virus release from axons and infected SCs is part of the RABV in vivo cycle and may affect RABV-related demyelination of peripheral neurons and local innate immune responses. Detection of RABV in axon-surrounding myelinating SCs after i.c. infection further provided evidence for anterograde spread of RABV, highlighting that RABV axonal transport and spread of infectious virus in peripheral nerves is not exclusively retrograde. Our data support a new model in which, comparable to CNS neuroglia, SC infection in peripheral nerves suppresses glia-mediated innate immunity and delays antiviral host responses required for successful transport from the peripheral infection sites to the brain.
Big data actionable intelligence architecture
Authors: Ma Tian J. , Garcia Rudy J. , Danford Forest , Patrizi Laura , Galasso Jennifer , Loyd Jason
Published: November 2020

The amount of data produced by sensors, social and digital media, and Internet of Things (IoTs) are rapidly increasing each day. Decision makers often need to sift through a sea of Big Data to utilize information from a variety of sources in order to determine a course of action. This can be a very difficult and time-consuming task. For each data source encountered, the information can be redundant, conflicting, and/or incomplete. For near-real-time application, there is insufficient time for a human to interpret all the information from different sources. In this project, we have developed a near-real-time, data-agnostic, software architecture that is capable of using several disparate sources to autonomously generate Actionable Intelligence with a human in the loop. We demonstrated our solution through a traffic prediction exemplar problem.
From anaerobic to aerobic treatment: upcycling of digestate as a moisturizing agent for in-vessel composting process
Authors: Chaher Nour El Houda , Hemidat Safwat , Chakchouk Mehrez , Nassour Abdallah , Hamdi Moktar , Nelles Michael
Published: November 2020

In Tunisia, there are crucial challenges facing both urban and rural areas, the most prominent of which are the production of organic waste, the need for waste treatment, the demand for water and energy and the need for a circular economy. To this end, the study was designed to develop a technical concept on closed cycle ‘biowaste to bioenergy’ treating, basically food waste (FW) through combined biological processes. In this approach, the generated digestate from FW anaerobic reactors was used successfully as a moisturizing agent for FW in-vessel composting. Four types of digestate were examined to be used as moisturizing agent (MA). The selection of the appropriate MA was achieved based on technical criteria; moisture content (MC), C:N ratio and heavy metals concentrations. The findings showed that the digestate obtained from anaerobic co-digestion of food waste and wheat straw (D1) was the most efficient AD-effluent to be added. In terms of composting process performance, the thermophilic phase of the amended reactor (A1) lasted 16 days and reached higher temperatures of about 72 °C, while the unamended one (A1) was characterized by a thermophilic temperature of around 66 °C indicating that the end products were of a pathogen-free compost. When it comes to the physico-chemical factors examined demonstrating that the biological conditions were sufficiently developed. The findings showed overall decreasing profiles during the composting period for moisture, C:N ratio as well as nitrification index (NI). From the quality-point of view, it was found that heavy metal concentrations had lower limits than those values set by German standards. Moreover, all the compost samples appeared to be stable and classified as class IV and V end product.
FLAIR hyperintensity along the brainstem surface in leptomeningeal metastases: a case series and literature review
Authors: Mitsuya Koichi , Nakasu Yoko , Deguchi Shoichi , Shirata Kensei , Asakura Koiku , Nakashima Kazuaki , Endo Masahiro , Takahashi Toshiaki , Hayashi Nakamasa
Published: November 2020

Background

The incidence of leptomeningeal metastasis (LM) is underestimated because of its non-specific signs and the low sensitivity of clinical diagnostic modalities. Cerebrospinal magnetic resonance (MR) imaging with and without contrast enhancement (CE) is a gold standard for the neuroradiological assessment of patients with suspected LM. Previous studies suggested that some LM cases show changes of the brainstem surface on non-contrast MR images without or before the appearance of abnormalities on CE images. We assessed the features of this non-contrast MR finding in a cohort of LM patients in this retrospective single-institution study.

Methods

We reviewed head MR images and clinical data of 142 consecutive patients in whom the final diagnosis was LM.

Results

We found that 11 of these 142 patients (7.7%) with LM had band-like hyperintensity on the brainstem surface on non-enhanced FLAIR images, which looked like bloomy rind on cheese. Three of seven patients who were examined using diffusion-weighted imaging showed restricted diffusion in the corresponding lesion site. The above-mentioned 11 patients included 10 women and 1 man, with a median age of 61 years. All 11 patients had primary lung adenocarcinoma. Seven patients had symptomatic hydrocephalus. Ten patients had EGFR-mutated and one had ALK-rearrangement adenocarcinomas. Before the diagnosis of LM, 10 patients had undergone systemic therapy with EGFR-TKI or pemetrexed, and 1 patient with ALK inhibitor and bevacizumab.

Conclusions

We present a series of patients with bloomy rind sign that is non-enhancing LM reliably detected by FLAIR hyperintensity on the brainstem surface. This finding is rare, but may reflect the spread of cancer cells in both the leptomeningeal membrane and the surface of the brain parenchyma specifically in patients with lung adenocarcinomas. Further study is needed to determine the clinical significance of this sign, and the pathophysiological factors associated with it may be clarified by analyzing serial MR images in a larger cohort of patients treated for LM.
Assessment of population-based input functions for Patlak imaging of whole body dynamic 18F-FDG PET
Authors: Naganawa Mika , Gallezot Jean-Dominique , Shah Vijay , Mulnix Tim , Young Colin , Dias Mark , Chen Ming-Kai , Smith Anne M. , Carson Richard E.
Published: November 2020

Background

Arterial blood sampling is the gold standard method to obtain the arterial input function (AIF) for quantification of whole body (WB) dynamic18F-FDG PET imaging. However, this procedure is invasive and not typically available in clinical environments. As an alternative, we compared AIFs to population-based input functions (PBIFs) using two normalization methods: area under the curve (AUC) and extrapolated initial plasma concentration (CP*(0)). To scale the PBIFs, we tested two methods: (1) the AUC of the image-derived input function (IDIF) and (2) the estimatedCP*(0). The aim of this study was to validate IDIF and PBIF for FDG oncological WB PET studies by comparing to the gold standard arterial blood sampling.

Methods

The Feng18F-FDG plasma concentration model was applied to estimate AIF parameters (n= 23). AIF normalization used either AUC(0–60 min) orCP*(0), estimated from an exponential fit.CP*(0) is also described as the ratio of the injected dose (ID) to initial distribution volume (iDV).iDVwas modeled using the subject height and weight, with coefficients that were estimated in 23 subjects. In 12 oncological patients, we computed IDIF (from the aorta) and PBIFs with scaling by the AUC of the IDIF from 4 time windows (15–45, 30–60, 45–75, 60–90 min) (PBIFAUC) and estimatedCP*(0) (PBIFiDV). The IDIF and PBIFs were compared with the gold standard AIF, using AUC values and PatlakKivalues.

Results

The IDIF underestimated the AIF at early times and overestimated it at later times. Thus, based on the AUC andKicomparison, 30–60 min was the most accurate time window for PBIFAUC; later time windows for scaling underestimatedKi(− 6 ± 8 to − 13 ± 9%). Correlations of AUC between AIF and IDIF, PBIFAUC(30–60), and PBIFiDVwere 0.91, 0.94, and 0.90, respectively. The bias ofKiwas − 9 ± 10%, − 1 ± 8%, and 3 ± 9%, respectively.

Conclusions

Both PBIF scaling methods provided good mean performance with moderate variation. Improved performance can be obtained by refining IDIF methods and by evaluating PBIFs with test-retest data.
Improved PET/MRI attenuation correction in the pelvic region using a statistical decomposition method on T2-weighted images
Authors: Wallstén Elin , Axelsson Jan , Jonsson Joakim , Karlsson Camilla Thellenberg , Nyholm Tufve , Larsson Anne
Published: November 2020

Background

Attenuation correction of PET/MRI is a remaining problem for whole-body PET/MRI. The statistical decomposition algorithm (SDA) is a probabilistic atlas-based method that calculates synthetic CTs from T2-weighted MRI scans. In this study, we evaluated the application of SDA for attenuation correction of PET images in the pelvic region.

Materials and method

Twelve patients were retrospectively selected from an ongoing prostate cancer research study. The patients had same-day scans of [11C]acetate PET/MRI and CT. The CT images were non-rigidly registered to the PET/MRI geometry, and PET images were reconstructed with attenuation correction employing CT, SDA-generated CT, and the built-in Dixon sequence-based method of the scanner. The PET images reconstructed using CT-based attenuation correction were used as ground truth.

Results

The mean whole-image PET uptake error was reduced from − 5.4% for Dixon-PET to − 0.9% for SDA-PET. The prostate standardized uptake value (SUV) quantification error was significantly reduced from − 5.6% for Dixon-PET to − 2.3% for SDA-PET.

Conclusion

Attenuation correction with SDA improves quantification of PET/MR images in the pelvic region compared to the Dixon-based method.