bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute granulomatous interstitial nephritis in a patient with metastatic melanoma on targeted therapy with dabrafenib and trametinib—A case report
Authors: Krelle Anna , Mathai Vinod Kalapurackal , Kirkland Geoff , Nott Louise , Jose Matthew D. , Whale Karen 
Published: August 2021

AbstractBackgroundCombination molecular targeted therapy with dabrafenib plus trametinib has been shown to improve progression‐free survival and overall survival in patients with BRAF V600 mutated unresectable or metastatic melanoma. In general, these agents are well tolerated. Kidney related adverse events are uncommon with only three case reports of acute interstitial nephritis and one case of a serious acute kidney injury. We report another case of interstitial nephritis related to these drugs.CaseA 37‐year‐old man diagnosed with metastatic melanoma (BRAF V600E mutation) who developed acute interstitial nephritis 5 years into his treatment with combination dabrafenib plus trametinib therapy. He presented with an asymptomatic acute kidney injury on routine surveillance pathology with a creatinine of 174 μmol/L (from baseline 80 μmol/L) and a corresponding estimated glomerular filtration rate (eGFR) of 42 ml/min/1.73 m2 (from a baseline >90 ml/min/1.73 m2) and microalbuminuria (albumin creatinine ratio [ACR] 8.5 mg/mmol). Renal biopsy revealed a granulomatous interstitial nephritis likely drug related. He was treated with prednisolone 1 mg/kg and ceased his targeted therapy with improvement in his renal function.ConclusionAlthough rare, recognition of acute interstitial nephritis, a possible serious adverse outcome due to dabrafenib and trametinib is important and needs to be incorporated into current Australian cancer therapy guidelines.
Polygenic score modifies risk for Alzheimer's disease in APOE ε4 homozygotes at phenotypic extremes
Authors: Huq Aamira J. , Fulton‐Howard Brian , Riaz Moeen , Laws Simon , Sebra Robert , Ryan Joanne ,   Alzheimer's Disease Genetics Consortium, Renton Alan E. , Goate Alison M. , Masters Colin L. , Storey Elsdon , Shah Raj C. , Murray Anne , McNeil John , Winship Ingrid , James Paul A. , Lacaze Paul 
Published: August 2021

AbstractIntroductionDiversity in cognition among apolipoprotein E (APOE) ε4 homozygotes can range from early‐onset Alzheimer's disease (AD) to a lifetime with no symptoms.MethodsWe evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy APOE ε4 homozygotes aged ≥75 years (n = 213) and early‐onset APOE ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity.ResultsThe PRS for AD was significantly higher in APOE ε4 homozygote AD cases compared to older cognitively healthy APOE ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0–35.2; P = .003). The difference in the same PRS between APOE ε3/ε3 extremes was not as significant (OR 3.13; CI 0.98–9.92; P = .053) despite similar numbers and power. There was no statistical difference in an educational attainment PRS between these age extreme case‐controls.DiscussionA PRS for AD contributes to modified cognitive expression of the APOE ε4/ε4 genotype at phenotypic extremes of risk.
Chrysin modulates protein kinase IKKε/TBK1, insulin sensitivity and hepatic fatty infiltration in diet‐induced obese mice
Authors: Amir Siddiqui Mohammad , Badruddeen  , Akhtar Juber , Uddin Shahab , Chandrashekharan Sidda Madappa , Ahmad Mohammad , Khan Mohammad Irfan , Khalid Mohammad 
Published: August 2021

AbstractNuclear factor kappa B cells (NF‐κB) activation causes induction of the noncanonical IκB kinases (I‐kappa‐B kinase epsilon (IKKε) and TANK‐binding kinase 1 (TBK1) in liver and fat after high fat diet which followed activating of cascade of counter‐inflammation that conserves energy storage. Chrysin (5,7‐dihydroxyflavone), a natural flavonoid, present in many plants, honey and propolis, used conventionally to treat numerous ailments. The present study was aimed to identify the protective role of chrysin on the glucose lowering and insulin sensitivity in diet induced obese (DIO) mice by regulating IKKε/TBK1. Chrysin administered therapeutically (60, 100, 200 mg/kg body weight) and preventive mode (200 mg/kg body weight) for 4 and 10 weeks respectively to DIO mice. At last fasting blood glucose, oral glucose tolerance test, serum lipid profile, as well as the expression level of IKKε/TBK1 and triglyceride in the liver tissue were assessed. DIO mice showed impaired glucose tolerance, reduced weight gain, elevated hepatic IKKε/TBK1 expression, fatty acid infiltration triglyceride and increased in plasma insulin and glucose. Chrysin in both therapeutic and preventive mode normalized the altered levels of the same. Overall chrysin improves glycemic control and insulin sensitivity through regulating expression of IKKε/TBK1 in liver of DIO mice.
Mouse models of patent ductus arteriosus (PDA) and their relevance for human PDA
Authors: Yarboro Michael T. , Gopal Srirupa H. , Su Rachel L. , Morgan Thomas M. , Reese Jeff 
Published: August 2021

AbstractThe ductus arteriosus (DA) is a unique fetal vascular shunt, which allows blood to bypass the developing lungs in utero. After birth, changes in complex signaling pathways lead to constriction and permanent closure of the DA. The persistent patency of the DA (PDA) is a common disorder in preterm infants, yet the underlying causes of PDA are not fully defined. Although limits on the availability of human DA tissues prevent comprehensive studies on the mechanisms of DA function, mouse models have been developed that reveal critical pathways in DA regulation. Over 20 different transgenic models of PDA in mice have been described, with implications for human DA biology. Similarly, we enumerate 224 human single‐gene syndromes that are associated with PDA, including a small subset that consistently feature PDA as a prominent phenotype. Comparison and functional analyses of these genes provide insight into DA development and identify key regulatory pathways that may serve as potential therapeutic targets for the management of PDA.
Successful treatment of COVID‐19 infection with convalescent plasma in B‐cell‐depleted patients may promote cellular immunity
Authors: Kremer Andreas E. , Kremer Anita N. , Willam Carsten , Völkl Simon , Verhagen Johan , Achenbach Susanne , van der Meijden Edith D. , Lang Vanessa , Aigner Michael , Maier Clara , Tenbusch Matthias , Korn Klaus , Lutzny‐Geier Gloria , Spoerl Silvia , Strauß Richard , Vetter Marcel , Überla Klaus , Neurath Markus F. , Mackensen Andreas , Schiffer Mario , Hackstein Holger 
Published: August 2021

AbstractTreatment with convalescent plasma has been shown to be safe in coronavirus disease in 2019 (COVID‐19) infection, although efficacy reported in immunocompetent patients varies. Nevertheless, neutralizing antibodies are a key requisite in the fight against viral infections. Patients depleted of antibody‐producing B cells, such as those treated with rituximab (anti‐CD20) for hematological malignancies, lack a fundamental part of their adaptive immunity. Treatment with convalescent plasma appears to be of general benefit in this particularly vulnerable cohort. We analyzed clinical course and inflammation markers of three B‐cell‐depleted patients suffering from COVID‐19 who were treated with convalescent plasma. In addition, we measured serum antibody levels as well as peripheral blood CD38/HLA‐DR‐positive T‐cells ex vivo and CD137‐positive T‐cells after in vitro stimulation with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐derived peptides in these patients. We observed that therapy with convalescent plasma was effective in all three patients and analysis of CD137‐positive T‐cells after stimulation with SARS‐CoV‐2 peptides showed an increase in peptide‐specific T‐cells after application of convalescent plasma.In conclusion, we here demonstrate efficacy of convalescent plasma therapy in three B‐cell‐depleted patients and present data that suggest that while application of convalescent plasma elevates systemic antibody levels only transiently, it may also boost specific T‐cell responses.
Experimental study on multi‐fuel combustion of lean coal and by‐product gas in a 75t/h tangentially‐fired boiler
Authors: Yi Zhengming , Hu Xuman , Zhou Zheng 
Published: August 2021

AbstractBy‐product gas is used as an alternative energy for steel mills to relieve the pressure of the fossil fuel crisis. In order to study the influence of blending by‐product gas on boiler operation, the multi‐fuel combustion experiments on the mixture of coke oven gas (COG), blast furnace gas (BFG), and lean coal were carried out in a 75t/h multi‐fuel combustion boiler so as to determine the most balanced fuel formula. The results indicated that the mixed combustion of COG and lean coal could improve the boiler efficiency. However, the balance of by‐product gas utilization in steel mills was destroyed for not using BFG. Although mixed combustion of BFG and COG improved the boiler efficiency, the boiler could only be operated under low load because of lower furnace temperature. After applying the most balanced flue ratio of BFG, COG, and lean coal, with heat value rations of 35%, 35%, and 30%, respectively, the efficiency of the boiler became 77.21%. The flue gas temperature lowered 4.5°C and the carbon content of fly ash and boiler slag were reduced by 1.06% and 1.09%, respectively. As a result, the stand coal consumption of the boiler decreased by 226.1 kg/h with the ratio of coal saving being 3.3%.
Effect of saffron supplementation on oxidative stress parameters: A systematic review and meta‐analysis of randomized placebo‐controlled trials
Authors: Morvaridzadeh Mojgan , Agah Shahram , Dulce Estêvão M. , Hosseini Ava Sadat , Heydari Hafez , Toupchian Omid , Abdollahi Shima , Persad Emma , Abu‐Zaid Ahmed , Rezamand Gholamreza , Heshmati Javad 
Published: August 2021

AbstractOxidative stress (OS), the absence of equilibrium between prooxidants and antioxidants in the body, has been shown to play a pivotal role in the initiation and progression of many diseases. Saffron has been noted for its antioxidant capacity and can be used to improve OS parameters in unhealthy patients. Our aim was to evaluate the efficacy of saffron supplementation on OS parameters in unhealthy patients in randomized controlled trials (RCTs). We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science without language restrictions for RCTs up until April 2021. Studies were included if they compared any form of saffron supplementation to placebo or no supplementation on OS parameters in unhealthy patients. Using a random‐effects model with calculated standardized mean difference (SMD) and 95% confidence intervals (CI), we quantitatively synthesized the data. Heterogeneity was assessed using Cochrane's I2 values. Ten randomized controlled trials were eligible for this review. Seven were included in the meta‐analysis and indicated an association between saffron intake and a statistically significant decrease in malondialdehyde (MDA) levels (SMD: −0.40; 95% CI: −0.63, −0.17; I2 = 32.6%) and a significant increase in total antioxidant capacity (TAC, SMD: 0.24; 95% CI: 0.05, 0.42; I2 = 00.0%). Saffron intake was shown to significantly impact MDA and TAC, indicating its beneficial properties in improving OS in unhealthy patients. However, additional RCTs are required to evaluate the effect on other OS parameters.
Genomic Testing, Unexpected Consanguinity, and Adolescent Parents
Authors: McGowan Michelle , Brown Teneille , Biller Aimee B. , deSante‐Bertkau Jennifer 
Published: August 2021

AbstractThis case study about an infant with epidermolysis bullosa and his fourteen‐year‐old mother involves pediatric genomic testing and concerns about the adolescent parent's decision‐making capacity. Four commentaries explore ethics issues in the case, including the following challenges: The current ethics guidelines regarding informed decision‐making for genomic testing and return of results have been relatively silent on how to involve parents who are minors in decision‐making on behalf of their children. This lack of guidance can be particularly difficult for physicians when genetic test results revealing consanguinity raise concerns about sexual abuse of a minor, provoking questions about mandatory reporting requirements. Finally, medical teams may find themselves having to evaluate an adolescent parent's capacity in making medical decisions for her child while questioning the role and relationship of her support person.
Putting the local back into planning‐experiences and perceptions of state and district health functionaries of seven aspirational districts in India on an innovative planning capacity building approach
Authors: Sarin Enisha , Bisht Nitin , Mohanty Jaya Swarup , Chandra Joshi Naresh , Kumar Arvind , Dey Surajit , Kumar Harish 
Published: August 2021

AbstractDistrict functionaries have ostensibly a major responsibility to develop evidence based plans. However, this responsibility is not commensurate with skills and expertise among functionaries in many Indian states. Vriddhi project‐technical partner of the government, developed a planning tool for maternal and neonatal health programmes, called RMNCH + A Action Agenda using Strategic Approach (RAASTA), which was introduced in a workshop format in two states and attended by program officers. Qualitative feedback was obtained from selected participants to understand their experience of the workshop and of the planning tool. It emerged that previous planning process had little application of local evidence based solutions. Participants appreciated the alternative approach as RAASTA equipped them to use local evidence. Several action plans derived at the workshop were included in the state plan. At the same time, apprehension was expressed by participants about translating their learnings to practical application as planning was not a central priority in their scheme of duties and tasks. Enhanced support from states in refreshing district planners' skills would be an important step. One state government has scaled up the RAASTA tool while an electronic version is being developed for future use as it demonstrates great potential to equip and aid district officials in developing evidence based plans.
Impact of focused cardiac ultrasound in vascular surgery patients: A prospective observational study
Authors: Mensel Camilla , Eldrup Nikolaj , Guldbrand Vibeke , Juhl‐Olsen Peter 
Published: August 2021

AbstractPurposeWe aimed to evaluate the diagnostic and logistical consequences of routine preoperative focused cardiac ultrasound (FOCUS) in patients scheduled for elective vascular surgery.MethodsIn a prospective, observational study, FOCUS was performed in all patients seen in the vascular surgery outpatient clinic from January 14 to May1, 2019, unless a full echocardiography had been conducted in the preceding 12 months or the patient was already referred to an echocardiography by the vascular surgeons. FOCUS followed a stringent protocol and referrals for a full echocardiography followed predefined criteria.ResultsPreoperative FOCUS was performed in 55 (60%) patients. Of these, 12 patients (22%) revealed cardiac pathology and were referred to a full echocardiography. Coronary angiography was subsequently performed in one of these patients but was without a further consequence. All patients underwent surgery.ConclusionFOCUS disclosed cardiac pathology in the outpatient clinic but with little clinical consequence. This study does not support routine FOCUS as a part of the preoperative patient cardiovascular assessment before vascular surgery. However, larger studies are warranted to further evaluate the relevance of preoperative FOCUS in a larger sample size.
Low‐dose oxytocin as an adjunct to Foley catheter for cervical ripening in nulliparous women at MTRH, Eldoret, Kenya: A randomized controlled trial
Authors: Omondi Patrick , Nyongesa Paul , Chemalan Bett Kipchumba , Itsura Peter 
Published: August 2021

AbstractObjectiveTo investigate whether the addition of oxytocin to cervical ripening with a Foley catheter (FC) among nulliparous women shortens the time to delivery.MethodsIn this double‐blinded randomized trial conducted at Moi Teaching and Referral Hospital, 220 women were randomly assigned to FC plus low‐dose oxytocin as treatment or FC plus placebo as controls in a 1:1 ratio. A modified intention‐to‐treat analysis was performed using SPSS v24. The protocol was approved by the institutional ethics committee and registered at www.ctr.pharmacyboardkenya.org; ECCT/19/08/02.ResultsBaseline characteristics were similar. Time to delivery was shorter by 3 h in the treatment group compared with the controls (25.4 versus 28.4 h, P = 0.002). The treatment group had a 22% increased likelihood of delivery within 24 h compared with the controls (53.3% versus 43.1%, relative risk [RR] 1.22, 95% confidence interval [CI] 0.938–1.579, P = 0.135). The controls were however twice more likely to deliver by cesarean section than the treatment group (39% versus 21%, RR 2.32, 95% CI 1.16–2.73, P = 0.006). There were no significant differences in neonatal or other maternal outcomes.ConclusionFC with adjunctive oxytocin for cervical ripening in nulliparous women results in a shorter time to delivery and reduced cesarean deliveries when compared with FC alone.
Cover Image
Authors: Hoffmann Malte , Abaci Turk Esra , Gagoski Borjan , Morgan Leah , Wighton Paul , Tisdall Matthew Dylan , Reuter Martin , Adalsteinsson Elfar , Grant Patricia Ellen , Wald Lawrence L. , van der Kouwe André J. W. 
Published: August 2021

The cover image is based on the Original Article Rapid head‐pose detection for automated slice prescription of fetal‐brain by Malte Hoffmann et al., https://doi.org/10.1002/ima.22563.
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Family awareness and the diagnosis of diabetes
Authors: Wearmouth EM 
Published: August 2021

Between 1982 and 1990, 101 children between the ages of one and 15 years were admitted with newly diagnosed insulin‐dependent diabetes (IDDM). Patients with a family history of IDDM or knowledge of diabetes symptoms from other sources (grouped together as ‘family awareness‘) were significantly less acidotic (mean bicarbonate 21.5 vs 18.1 mmol/l) and had a shorter in‐patient stay (10.2 days vs 12.4 days) than those with no such family awareness. However there was no difference in the mean length of symptoms (3.97 vs 3.66 weeks), mean plasma glucose (25.2 vs 26.9 mmol/l) or percentage receiving intravenous rehydration (33.0% vs 36.6%).There was a consistent downward trend in the length of in‐patient stay despite no trends in mean length of symptoms, plasma glucose or bicarbonate. It is concluded that family awareness does not reduce the mean length of symptoms in newly diagnosed diabetic children but may be associated with reduced in‐patient stay. The trend for earlier hospital discharge reflects changing attitudes to community‐based management of chronic disease rather than earlier diagnosis or improved in‐patient treatment.
Capillary‐size flow of human blood plasma: Revealing hidden elasticity and scale dependence
Authors: Windberger Ursula , Baroni Patrick , Noirez Laurence 
Published: August 2021

AbstractThe dynamical mechanical analysis of blood generally uses models inspired by conventional flows, assuming scale‐independent homogeneous flows and without considering fluid–surface boundary interactions. The present experimental study highlights the relevance of using an approach in line with physiological reality providing a strong interaction between the fluid and the boundary interface. New dynamic properties of human blood plasma are found: a finite shear elastic response (solid‐like property) is identified in nearly static conditions, which also depends on the scale (being reinforced at small scales). The elastic behavior is confirmed by the induction, without heat transfer, of local hot and cold thermodynamic states evidencing a thermo‐mechanical coupling in blood plasma so far known only in elastic materials. This finding opens new routes for medical diagnosis and device fabrication.
Cover Image, Volume 96, Issue 9
Authors: Ornelas‐González Alonso , Chairez‐Cantu Karolina , Ortiz‐Martínez Margarita , González‐González Mirna , Rito‐Palomares Marco 
Published: August 2021

The cover image is based on the Review Stem cell culture media enriched with plant‐derived compounds: Cell proliferation enhancement by Alonso Ornelas‐González et al., https://doi.org/10.1002/jctb.6794.
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Cadmium retention and microbial response in volcanic soils along gradients of soil age and climate on the Galápagos Islands
Authors: Rechberger Maria V. , Roberti Daniela , Phillips Avion , Zehetner Franz , Keiblinger Katharina M. , Kandeler Ellen , Gerzabek Martin H. 
Published: August 2021

AbstractThe behavior of trace metals may vary strongly in the course of volcanic soil development. Cadmium retention in soils is specifically important for some Galápagos islands where agriculture is leading to anthropogenic Cd contamination. To assess the influence of soil development factors on soil Cd retention and toxicity, we performed Cd sorption–desorption experiments with volcanic topsoils from the Galápagos Islands sampled along gradients of (a) substrate age (chronosequence, 1.5–1,070 ka) and (b) climate (elevation sequence, 47–866 m asl) ranging from arid lowland areas to humid highland areas. Additionally, the effects of Cd toxicity on the soil microbial community composition were evaluated for two soils of the chronosequence. In young volcanic soils, the sorption capacity was very high but decreased rapidly with soil age and increasing elevation. These trends were coupled with decreases in soil weathering indicators (e.g., electrical conductivity, pH, and effective cation exchange capacity) as well as changes in soil mineralogy. Cadmium addition did not influence total phospholipid fatty acids and basal respiration in most soils. However, with increasing Cd concentration, a pronounced reduction in the Gram‐negative/Gram‐positive bacteria ratio (from 0.32 to 0.12) occurred in an old, highly weathered soil with low Cd retention capacity. Our results show that up to 60% of added Cd was only weakly sorbed in old volcanic soils. As a consequence, the old volcanic soils of Galápagos bear the potential risk that the mobile Cd fraction is taken up by soil microorganisms, transferring this element into the food chain.