bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-creating a large-scale adolescent health survey integrated with access to digital health interventions
Authors: Peiris-John Roshini , Dizon Lovely , Sutcliffe Kylie , Kang Kristy , Fleming Theresa
Published: August 2020

Aim

This paper describes how we engaged with adolescents and health providers to integrate access to digital health interventions as part of a large-scale secondary school health and wellbeing survey in New Zealand.

Methods

We conducted nine participatory, iterative co-design sessions involving 29 adolescents, and two workshops with young people (n = 11), digital and health service providers (n = 11) and researchers (n = 9) to gain insights into end-user perspectives on the concept and how best to integrate digital interventions in to the survey.

Results

Students’ perceived integrating access to digital health interventions into a large-scale youth health survey as acceptable and highly beneficial. They did not want personalized/normative feedback, but thought that every student should be offered all the help options. Participants identified key principles: assurance of confidentiality, usability, participant choice and control, and language. They highlighted wording as important for ease and comfort, and emphasised the importance of user control. Participants expressed that it would be useful and acceptable for survey respondents to receive information about digital help options addressing a range of health and wellbeing topics.

Conclusion

The methodology of adolescent-practitioner-researcher collaboration and partnership was central to this research and provided useful insights for the development and delivery of adolescent health surveys integrated with digital help options. The results from the ongoing study will provide useful data on the impact of digital health interventions integrated in large-scale surveys, as a novel methodology. Future research on engaging with adolescents once interventions are delivered will be useful to explore benefits over time.
Ecocriticism: Locating the Animist Figurings in Remi Raji’s Sea of My Mind
Authors: Oluseye Abiodun Babatunde , Olaoluwa Senayon , Ogbulogo Charles
Published: August 2020

This article is an ecocritical reading of Remi Raji’s Sea of My Mind (2013). We argue that the collection is a fine illustration of the animist turn in ecocriticism. By engaging with the import of the natural elements that incarnate with the imagination of the sea, we discuss the various ways in which Raji’s poetic oeuvres address the environmental exigencies of the times. We also show how the centrality of natural elements in the work pinpoints the limits of human agency. We further argue that the concern of the collection serves to amplify, from the Nigerian perspective, the necessity of maintaining the delicate balance of relations between humans and the nonhuman others, while not losing sight of the imperative of mitigation to forestall catastrophes of the apocalyptic scale.
Osteochondritis Dissecans of the Tibial Plateau in Children and Adolescents: A Case Series
Authors: Croman Millicent , Kramer Dennis E. , Heyworth Benton E. , Kocher Mininder S. , Micheli Lyle J. , Yen Yi-Meng
Published: August 2020

Background:

Osteochondritis dissecans (OCD) of the knee is a relatively well-known condition, most commonly arising in the femoral condyle. Lesions arising in the tibial plateau are rarely described.

Purpose:

To present a case series of OCD lesions of the tibial plateau.

Study Design:

Case series; Level of evidence, 4.

Methods:

Medical records and diagnostic imaging of patients <20 years of age with confirmed diagnosis of OCD of the tibial plateau from a single institution were retrospectively reviewed. Characteristic and radiographic features as well as details of both nonoperative and surgical management were investigated. Lesion characteristics and treatment outcomes were also analyzed.

Results:

A total of 9 lesions were identified in 9 patients (5 females, 4 males) who fit the inclusion criteria. The mean age at diagnosis was 14.2 years (range, 9-17 years). Knee pain (8/9) of longer than 1 year in duration was the most common presenting symptom. All 9 lesions were located on the lateral tibial plateau, and concomitant lateral compartment pathology was present in 5 of 9 patients (4 lateral femoral condyle OCDs, 3 lateral meniscal tears [1 discoid], and 1 discoid meniscus). Only 2 lesions were visible on initial radiographs; all 9 were visible on magnetic resonance imaging. All patients underwent initial nonoperative treatment; 2 patients demonstrated resolution of symptoms. Two patients underwent surgery for concomitant pathology, and the OCD was not addressed surgically. A total of 5 patients continued to be symptomatic after nonoperative treatment, prompting surgical intervention, which consisted of microfracture and chondroplasty in all 5 cases. A total of 2 of the 5 microfracture patients had resolution of symptoms, while another 2 patients had continued symptoms ultimately responsive to steroid injection treatment. One patient had revision microfracture, followed by autologous chondrocyte implantation and an arthroscopic lysis of adhesions. At final follow-up, ranging from 7 months to 10 years, 8 patients were asymptomatic, while 1 patient had developed early osteoarthritis.

Conclusion:

OCD of the tibial plateau in young patients is rare, usually involves the lateral side, and may have significant long-term implications for knee function. Presenting symptoms are often vague, and lesions may not always be visible on initial radiographs, which may lead to delayed treatment and adversely affect outcomes.
Single-Leg Squat After Anterior Cruciate Ligament Reconstruction: An Analysis of the Knee Valgus Angle at 6 and 12 Months
Authors: Batty Lachlan M. , Feller Julian A. , Damasena Iswadi , Behrens Gerrit , Devitt Brian M. , Hartwig Taylor , McClelland Jodie A. , Webster Kate E.
Published: August 2020

Background:

Deficits in neuromuscular control are common after anterior cruciate ligament (ACL) reconstruction and may be associated with further knee injury. The knee valgus angle during a single-leg squat (SLS) is one measure of neuromuscular performance.

Purpose:

To determine whether the knee valgus angle during SLS changes between 6 and 12 months after ACL reconstruction and to assess how the operative knee valgus angle compares with that of the contralateral side.

Study Design:

Case series; Level of evidence, 4.

Methods:

A cohort of 100 patients with uninjured contralateral knees were assessed at 6 and 12 months after primary hamstring autograft ACL reconstruction. Participants performed the SLS on each leg, and the knee valgus angle was measured via frame-by-frame video analysis at 30° of flexion and at each patient’s maximum knee flexion angle.

Results:

For the operative limb at 30° of flexion, a small but statistically significant reduction was noted in the valgus angle between 6 and 12 months (5.46° vs 4.44°; P = .002; effect size = 0.24). At 6 months, a slightly higher valgus angle was seen in the operative limb compared with the nonoperative limb (5.46° vs 4.29°; P = .008; effect size = 0.27). At maximum flexion, no difference was seen between limbs in the valgus angle at either 6 or 12 months, and no change was seen in the operative limb between 6 and 12 months. At 6 months and 30° of knee flexion, 13 patients had a valgus angle greater than 10°. This group also had a higher mean valgus angle in the contralateral limb compared with the contralateral limb in the other 87 patients (8.5° vs 3.65°; P < .001).

Conclusion:

During a controlled SLS, the knee valgus angle remained essentially constant, and minimal limb asymmetries were present over the 6- to 12-month postoperative period, a time when athletes typically increase their activity levels. Whether changes or asymmetries will be seen with more dynamically challenging tasks remains to be determined. When present, high valgus angles were commonly bilateral.
Staging Antiquity: A Comparison of Five Greek Cultural Heritage Sites and The Construction of Their Authenticity
Authors: Karlsson Håkan , Gustafsson Anders
Published: August 2020

The text consists of an analysis of how the classical Greek sites of Marathon, Thermopylae, Delphi, Olympia and Mycenae are staged and presented to the public. This analysis is focused upon how the cultural heritage management views the authenticity of these sites and their physical remains, (i.e., as genuine) phenomenon firmly, and solely, belonging to the past, and how these attitudes are materialized in the form of presentations at information boards and in the physical staging of the sites. The materialization of this attitude constitutes the conditions for the public’s physical and imaginative access to the sites and for the public’s possibility to reflect critically around them. Thus, the sites are products of the past, but their authenticity is in parallel also a product of its role in present negotiations of interpretive supremacy, control, power and politics. The article further stresses that a changed attitude towards authenticity is crucial also for a development of a constructive relationship between heritage management and the public. In accordance with this, the article also presents a reconstructed view of authenticity—as the cultural process constituting both humans and material remains.
Targeting the Otub1/c-Maf axis for the treatment of multiple myeloma
Authors: Xu Yujia , Xu Min , Tong Jiefei , Tang Xiaowen , Chen Jinhao , Chen Xuehan , Zhang Zubin , Cao Biyin , Stewart A. Keith , Moran Michael F. , Wu Depei , Mao Xinliang
Published: August 2020

The oncogenic transcription factor c-Maf has been proposed as an ideal therapeutic target for multiple myeloma (MM), but how to achieve it is still elusive. In the present study, we found the Otub1/c-Maf axis could be a potential target. Otub1, an OTU family deubiquitinase, was found to interact with c-Maf by mass spectrometry. Otub1 abrogates c-Maf K48-linked polyubiquitination, thus preventing its degradation and enhancing its transcriptional activity. Specifically, this deubiquitinating activity depends on its Lys71 and the N terminus but is independent of UBE2O, a known E2 of c-Maf. Otub1 promotes MM cell survival and MM tumor growth. In contrast, silence of Otub1 leads to c-Maf degradation and c-Maf-expressing MM cell apoptosis. Therefore, the Otub1/c-Maf axis could be a therapeutic target of MM. In order to explore this concept, we performed a c-Maf recognition element–driven luciferase-based screen against US Food and Drug Administration–approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf deubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf. Consequently, LanC inhibits c-Maf transcriptional activity, induces c-Maf-expressing MM cell apoptosis, and suppresses MM growth and prolongs overall survival of model mice, but without apparent toxicity. Therefore, the present study identifies Otub1 as a novel deubiquitinase of c-Maf and establishes that the Otub1/c-Maf axis is a potential therapeutic target for MM.
Approval of tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm
Authors: Pemmaraju Naveen , Konopleva Marina
Published: August 2020

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically challenging hematologic malignancy with dismal outcomes. With a median age of ∼70 years, the majority of patients with BPDCN have experienced historically suboptimal responses with intensive chemotherapy regimens. The major scientific breakthrough in this field was the recognition of overexpression of a surface receptor, CD123/interleukin 3 (IL-3) receptor α, in all patients. Importantly, a novel therapeutic agent consisting of a truncated diphtheria toxin (DT) payload fused to recombinant human IL-3 was being developed, one that targeted CD123, initially known as DT-IL-3 (later known as SL401; tagraxofusp; tagraxofusp-erzs [Elzonris]). The identification of this agent, and subsequent clinical trials specifically dedicated to patients with BPDCN (including a pilot study, followed by a larger phase 1/2 multicenter study [90% overall response rate [ORR] in frontline and 67% ORR in relapsed/refractory setting]), in part led to approval of tagraxofusp-erzs on 21 December 2018. Tagraxofusp-erzs was the first agent approved for BPDCN (for patients ages 2 years and older), and importantly, established this drug as the first CD123-targeted agent ever approved. The most notable toxicity of tagraxofusp-erzs is occurrence of the capillary leak syndrome, which occurs frequently at all grades, and has also been observed to be life-threatening, appropriately leading to a US Food and Drug Administration “black box” warning in the package insert. The preclinical and clinical aspects of drug development of tagraxofusp-erzs as monotherapy leading to drug approval are reviewed herein, with discussion of future directions of this novel agent, including consideration for rational combinations in BPDCN and beyond.
Platelets mediate serological memory to neutralize viruses in vitro and in vivo
Authors: Schrottmaier Waltraud C. , Salzmann Manuel , Badrnya Sigrun , Mussbacher Marion , Kral-Pointner Julia B. , Morava Susanne , Pirabe Anita , Brunnthaler Laura , Yaiw Koon C. , Heber Ulrike M. , Pereyra David , Andersen Jan T. , Bergthaler Andreas , Söderberg-Nauclér Cecilia , Karlsson Mikael C. I. , Assinger Alice , Forsell Mattias N. E.
Published: August 2020

Key Points

Platelets contain virus-specific IgGs that potently diminish viral infection in vitro and in vivo. Release of platelet IgG is more efficient at virus neutralization than equal amounts of plasma IgG.
Guideline-based indicators for adult patients with myelodysplastic syndromes
Authors: Stojkov Kristina , Silzle Tobias , Stussi Georg , Schwappach David , Bernhard Juerg , Bowen David , Čermák Jaroslav , Dinmohamed Avinash G. , Eeltink Corien , Eggmann Sabrina , Fenaux Pierre , Germing Ulrich , Haschke Manuel , Hellstrom-Lindberg Eva , Heger Monika , van de Loosdrecht Arjan A. , Passweg Jakob , Pfeilstöcker Michael , Platzbecker Uwe , Malcovati Luca , de Almeida António Medina , Mittelman Moshe , Morgenthaler Christine , Steensma David P. , Santini Valeria , Stauder Reinhard , Symeonidis Argiris , Schär Sämi , Maddox Charlotte , de Witte Theo , Bohlius Julia , Bonadies Nicolas
Published: August 2020

Myelodysplastic syndromes (MDSs) represent a heterogeneous group of hematological stem cell disorders with an increasing burden on health care systems. Evidence-based MDS guidelines and recommendations (G/Rs) are published but do not necessarily translate into better quality of care if adherence is not maintained in daily clinical practice. Guideline-based indicators (GBIs) are measurable elements for the standardized assessment of quality of care and, thus far, have not been developed for adult MDS patients. To this end, we screened relevant G/Rs published between 1999 and 2018 and aggregated all available information as candidate GBIs into a formalized handbook as the basis for the subsequent consensus rating procedure. An international multidisciplinary expert panel group (EPG) of acknowledged MDS experts (n = 17), health professionals (n = 7), and patient advocates (n = 5) was appointed. The EPG feedback rates for the first and second round were 82% (23 of 28) and 96% (26 of 27), respectively. A final set of 29 GBIs for the 3 domains of diagnosis (n = 14), therapy (n = 8), and provider/infrastructural characteristics (n = 7) achieved the predefined agreement score for selection (>70%). We identified shortcomings in standardization of patient-reported outcomes, toxicity, and geriatric assessments that need to be optimized in the future. Our GBIs represent the first comprehensive consensus on measurable elements addressing best practice performance, outcomes, and structural resources. They can be used as a standardized instrument with the goal of assessing, comparing, and fostering good quality of care within clinical development cycles in the daily care of adult MDS patients.
The management of venous thromboembolism in hospitalized patients with COVID-19
Authors: Spyropoulos Alex C.
Published: August 2020

The high incidence of thromboembolic disease, and in particular venous thromboembolism (VTE), has emerged as an important consideration in hospitalized and critically ill patients with coronavirus disease 2019 (COVID-19). The coagulopathy of COVID-19 is postulated to result from interactions of the inflammatory and immune systems with the coagulation system, manifesting as a cytokine storm associated with hyperinflammation and coagulation and platelet activation. Unique characteristics of VTE in hospitalized and critically ill patients with COVID-19 include the high incidence of VTE (and especially pulmonary embolism) when compared with historical controls; the finding of in situ pulmonary embolism associated with microthrombi, which suggests a thrombotic microangiopathic process in addition to classic macrovessel disease; and, most important from a clinical perspective, the unusually high rate of VTE that has been reported despite standard thromboprophylaxis. This raises the possibility that intermediate or weight-based heparin dosing may be more effective than fixed dosing for thromboprophylaxis in high-risk subsets of patients hospitalized with COVID-19. There have been several guidance statements focusing on the management of VTE in hospitalized and critically ill patients with COVID-19, including the most recent statement by the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis, which includes comprehensive guidance on the diagnosis, prevention, and treatment of VTE in this patient population. Ongoing randomized trials that address key clinical questions, especially more intense thromboprophylactic strategies and novel antithrombotic approaches, have the potential to reduce the morbidity and mortality from VTE in hospitalized and critically ill patients with COVID-19.
Procedural sedation for direct current cardioversion: a feasibility study between two management strategies in the emergency department
Authors: Stronati Giulia , Capucci Alessandro , Dello Russo Antonio , Adrario Erica , Carsetti Andrea , Casella Michela , Donati Abele , Guerra Federico
Published: August 2020

Background

A cardiologist-only approach to procedural sedation with midazolam in the setting of elective cardioversion (DCC) for AF has already been proven as safe as sedation with propofol and anaesthesiologist assistance. No data exist regarding the safety of such a strategy during emergency procedures. The aim of this study is to compare the feasibility of sedation with midazolam, administered by a cardiologist, to an anaesthesiologist-assisted protocol with propofol in emergency DCC.

Methods

Single centre, prospective, open blinded, randomized study including all consecutive patients admitted to the Emergency Department requiring urgent or emergency DCC. Patients were randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the midazolam group were managed by the cardiologist only, while patients treated with propofol group underwent DCC with anaesthesiologist assistance.

Results

Sixty-nine patients were enrolled and split into two groups. Eighteen patients (26.1%) experienced peri-procedural adverse events (bradycardia, severe hypotension and severe hypoxia), which were similar between the two groups and all successfully managed by the cardiologist. No deaths, stroke or need for invasive ventilation were registered. Patients treated with propofol experienced a greater decrease in systolic and diastolic blood pressure when compared with those treated with midazolam.

As the procedure was shorter when midazolam was used, the median cost of urgent/emergency DCC with midazolam was estimated to be 129.0 € (1st-3rd quartiles 114.6–151.6) and 195.6 € (1st-3rd quartiles 147.3–726.7) with propofol (p < .001).

Conclusions

Procedural sedation with midazolam given by the cardiologist alone was feasible, well-tolerated and cost-effective in emergency DCC.
Measuring clinical uncertainty and equipoise by applying the agreement study methodology to patient management decisions
Authors: Fahed Robert , Darsaut Tim E. , Farzin Behzad , Chagnon Miguel , Raymond Jean
Published: August 2020

Background

Clinical uncertainty and equipoise are vague notions that play important roles in contemporary problems of medical care and research, including the design and conduct of pragmatic trials. Our goal was to show how the reliability study methods normally used to assess diagnostic tests can be applied to particular management decisions to measure the degree of uncertainty and equipoise regarding the use of rival management options.

Methods

We first use thrombectomy in acute stroke as an illustrative example of the method we propose. We then review, item by item, how the various design elements of diagnostic reliability studies can be modified in order to measure clinical uncertainty.

Results

The thrombectomy example shows sufficient disagreement and uncertainty to warrant the conduct of additional randomized trials. The general method we propose is that a sufficient number of diverse individual cases sharing a similar clinical problem and covering a wide spectrum of clinical presentations be assembled into a portfolio that is submitted to a variety of clinicians who routinely manage patients with the clinical problem.

Discussion

Clinicians are asked to independently choose one of the predefined management options, which are selected from those that would be compared within a randomized trial that would address the clinical dilemma. Intra-rater agreement can be assessed at a later time with a second evaluation. Various professional judgments concerning individual patients can then be compared and analyzed using kappa statistics or similar methods. Interpretation of results can be facilitated by providing examples or by translating the results into clinically meaningful summary sentences.

Conclusions

Measuring the uncertainty regarding management options for clinical problems may reveal substantial disagreement, provide an empirical foundation for the notion of equipoise, and inform or facilitate the design/conduct of clinical trials to address the clinical dilemma.
Osteopontin promoter polymorphisms and risk of urolithiasis: a candidate gene association and meta-analysis study
Authors: Amar Ali , Afzal Ayesha , Hameed Athar , Ahmad Mumtaz , Khan Abdul Rafay , Najma Humaira , Abid Aiysha , Khaliq Shagufta
Published: August 2020

Background

Urolithiasis is a worldwide urological problem with significant contribution of genetic factors. Pakistan, which resides within the Afro-Asian stone belt, has a high reported prevalence (12%) of urolithiasis. Osteopontin (SPP1) is a urinary macromolecule with a suggested critical role in modulating renal stone formation, genetic polymorphisms of which may determine individual risk of developing urolithiasis. However, results of previous studies regarding SPP1 polymorphisms and susceptibility to urolithiasis have apparent inconsistencies with no data available for local population.

Methods

A total of 235 urolithiasis patients and 243 healthy controls, all of Pakistani ancestry, underwent genotyping for six SPP1 genetic polymorphisms in an effort to investigate potential association with urolithiasis using indigenous candidate gene association study design. Further, a comprehensive meta-analysis following a systematic literature search was also done to ascertain an evidence based account of any existent association regarding SPP1 promoter polymorphisms and risk of developing urolithiasis.

Results

Three SPP1 promoter polymorphisms, rs2853744:G > T, rs11730582:T > C and rs11439060:delG>G, were found to be significantly associated with risk of urolithiasis in indigenous genetic association study (OR = 3.14; p = 0.006, OR = 1.78; p = 0.006 and OR = 1.60; p = 0.012, respectively). We also observed a 1.68-fold positive association of a tri-allelic haplotype of these SPP1 promoter polymorphisms (G-C-dG) with risk of urolithiasis (OR = 1.68; p = 0.0079). However, no association was evident when data were stratified according to gender, age at first presentation, stone recurrence, stone multiplicity, parental consanguinity and family history of urolithiasis. The overall results from meta-analysis, which included 4 studies, suggested a significant association of SPP1 rs2853744:G > T polymorphism with susceptibility of urolithiasis (OR = 1.37; p = 0.004), but not for other SPP1 polymorphic variants analyzed.

Conclusions

In conclusion, we report significant association of 3 SPP1 polymorphisms with urolithiasis for the first time from South Asia, however, this association persisted only for SPP1 rs2853744:G > T polymorphism after meta-analysis of pooled studies. Further studies with a larger sample size will be required to validate this association and assess any potential usefulness in diagnosis and prognosis of renal stone disease.
Factors affecting the relationship between ionized and corrected calcium levels in peritoneal dialysis patients: a retrospective cross-sectional study
Authors: Morishita Masamitsu , Maruyama Yukio , Nakao Masatsugu , Matsuo Nanae , Tanno Yudo , Ohkido Ichiro , Ikeda Masato , Yokoo Takashi
Published: August 2020

Background

Chronic kidney disease-mineral and bone disorder (CKD-MBD) management in patients with end-stage renal disease is important owing to the risk of cardiovascular diseases. In clinical practice, we manage patients not by monitoring the levels of biologically active ionized calcium (iCa) but by monitoring total serum calcium or corrected calcium (cCa). We previously reported that iCa/cCa ratio was different between patients with hemodialysis and those with peritoneal dialysis (PD). In PD patients, several factors are expected to affect iCa/cCa ratio. Therefore, modifying the strategy to achieve better CKD-MBD management might be necessary; however, no reports have studied this to date. Therefore, we investigated the factors influencing iCa/cCa ratio in PD patients.

Methods

This retrospective cross-sectional study examined background and laboratory data, including iCa, collected at routine outpatient visits. The patients were divided into the first, second, and third tertile of iCa/cCa ratio groups to compare patient background and laboratory data. Multiple regression analysis was used to investigate the factors influencing iCa/cCa ratio. We used multiple imputation to deal with missing covariate data.

Results

In total, 169 PD patients were enrolled. In PD patients with lower iCa/cCa ratio, PD duration was longer and pH was higher. Urine volume and weekly renal Kt/V were lower in the patients with lower iCa/cCa ratio than in those with higher iCa/cCa ratio. iCa/cCa ratio and weekly renal Kt/V were directly correlated (r = 0.41, p < 0.01), and weekly renal Kt/V and pH were independent factors affecting iCa/cCa ratio (t = 2.86, p < 0.01 and t = − 5.42, p < 0.01, respectively).

Conclusions

iCa levels were lower in PD patients with lower residual renal function (RRF) even though their cCa levels were equal to those with maintained RRF, warranting caution in the assessment and management of CKD-MBD in PD patients.
Lens-induced myopization and intraocular pressure in young guinea pigs
Authors: Dong Li , Li Yi Fan , Wu Hao Tian , Di Kou Hai , Lan Yin Jun , Wang Ya Xing , Jonas Jost B. , Wei Wen Bin
Published: August 2020

Background

Intraocular pressure (IOP) is an important physiological measure of the eye and is associated with some ocular disorders. We aimed to assess the influence of topical beta blocker-induced IOP reduction on lens-induced axial elongation in young guinea pigs.

Methods

The experimental study included 20 pigmented guinea pigs (age: 2–3 weeks). Myopia was induced in the right eyes for 5 weeks with − 10 diopter lenses. The right eyes additionally received either one drop of carteolol 2% (study group,n = 10) or one drop of artificial tears daily (control group,n = 10), while the contralateral eyes of all animals remained untouched. The outcome parameter was axial elongation during the follow-up period. The mean of all IOP measurements taken during the study was referred to as mean IOP.

Results

Greater axial elongation was associated with a shorter axial length at baseline (P < 0.001; standardized regression coefficient beta: − 0.54) and lens-induced myopization (P < 0.001; beta: 0.55). In the multivariable model, axial elongation was not significantly correlated with the IOP at study end (P = 0.59), the mean IOP during the study period (P = 0.12), the mean of all IOP measurements (P = 0.17), the difference between the IOP at study end and baseline IOP (P = 0.38), the difference between the mean IOP during the study period and the baseline IOP (P = 0.11), or the application of carteolol eye drops versus artificial tears eye drops (P = 0.07). The univariate analysis of the relationships between axial elongation and the IOP parameters yielded similar results. The inter-eye difference between the right eye and the left eye in axial elongation was significantly associated with the inter-eye difference in baseline axial length (P = 0.001; beta:-0.67) but not significantly correlated with the inter-eye difference in any of the IOP-related parameters (allP > 0.25).

Conclusions

In young guinea pigs with or without lens-induced axial elongation, neither the physiological IOP nor the IOP reduced by carteolol, a topical beta-blocker, was associated with the magnitude of axial elongation. These results suggest that IOP, regardless of whether it is influenced by carteolol, does not play a major role in axial elongation in young guinea pigs.
A clinical prediction model for complicated appendicitis in children younger than five years of age
Authors: Feng Wei , Zhao Xu-Feng , Li Miao-Miao , Cui Hua-Lei
Published: August 2020

Background

No reliably specific method for complicated appendicitis has been identified in children younger than five years of age. This study aimed to analyze the independent factors for complicated appendicitis in children younger than five years of age, develop and validate a prediction model for the differentiation of simple and complicated appendicitis.

Methods

A retrospective study of 382 children younger than five years of age with acute appendicitis from January 2007 to December 2016 was conducted with assessments of demographic data, clinical symptoms and signs, and pre-operative laboratory results. According to intraoperative findings and postoperative pathological results, acute appendicitis was divided into simple and complicated appendicitis. Univariate and multivariate analyses were used to screen out the independent factors of complicated appendicitis, and develop a prediction model for complicated appendicitis. Then 156 such patients from January 2017 to December 2019 were collected as validation sample to validate the prediction model. Test performance of the prediction model was compared with the ALVARADO score and Pediatric Appendicitis Score (PAS).

Results

Of the 382 patients, 244 (63.9%) had complicated appendicitis. Age, white blood cell count, and duration of symptoms were the independent factors for complicated appendicitis in children younger than five years of age. The final predication model for complicated appendicitis included factors above. In validation sample, the prediction model exhibited a high degree of discrimination (area under the curve [AUC]: 0.830; 95% confidence interval [CI]: 0.762–0.885) corresponding to a optimal cutoff value of 0.62, and outperformed the PAS (AUC: 0.735; 95% CI: 0.658–0.802), ALVARADO score (AUC: 0.733; 95% CI: 0.657–0.801).

Conclusion

Age, white blood cell count, and duration of symptoms could be used to predict complicated appendicitis in children younger than five years of age with acute appendicitis. The prediction model is a novel but promising method that aids in the differentiation of acute simple and complicated appendicitis.
The state of child nutrition in Ethiopia: an umbrella review of systematic review and meta-analysis reports
Authors: Mohammed Shimels Hussien , Habtewold Tesfa Dejenie , Arero Amanuel Godana , Esmaillzadeh Ahmad
Published: August 2020

Background

Malnutrition remains to be a major public health problem in developing countries, particularly among children under-5 years of age children who are more vulnerable to both macro and micro-nutrient deficiencies. Various systematic review and meta-analysis (SRM) studies were done on nutritional statuses of children in Ethiopia, but no summary of the findings was done on the topic. Thus, this umbrella review was done to summarize the evidence from SRM studies on the magnitude and determinants of malnutrition and poor feeding practices among under-5 children in Ethiopia.

Methods

PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Google Scholar were searched for SRM studies on magnitude and risk factors of malnutrition and child feeding practice indicators in Ethiopia. The methodological quality of the included studies was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. The estimates of the included SRM studies on the prevalence and determinants of stunting, wasting, underweight, and poor child feeding practices were pooled and summarized with random-effects meta-analysis models.

Result

We included nine SRM studies, containing a total of 214,458 under-5 children from 255 observation studies. The summary estimates of prevalence of stunting, underweight, and wasting were 42% (95%CI = 37–46%), 33% (95%CI = 27–39%), and 15% (95%CI = 12–19%), respectively. The proportion of children who met the recommendations for timely initiation of breastfeeding, exclusive breastfeeding during the first 6 months, and timely initiation of complementary feeding were 65, 60, and 62%, respectively. The proportion of children who met the recommendations for dietary diversity and meal frequency were 20, and 56%, respectively. Only 10% of children fulfilled the minimum criteria of acceptable diet. There was a strong relationship between poor feeding practices and the state of malnutrition, and both conditions were related to various health, socio-economic, and environmental factors.

Conclusion

Child malnutrition and poor feeding practices are highly prevalent and of significant public health concern in Ethiopia. Only a few children are getting proper complementary feeding. Multi-sectoral efforts are needed to improve children’s feeding practices and reduce the high burden of malnutrition in the country.
Epigenetic silencing of long non-coding RNA BM742401 in multiple myeloma: impact on prognosis and myeloma dissemination
Authors: Li Zhenhai , Kumar Shaji , Jin Dong-Yan , Calin George A. , Chng Wee-Joo , Siu Kam-Leung , Poon Ming-Wai , Chim Chor Sang
Published: August 2020

Background

Long non-coding RNA (lncRNA) BM742401 is a tumor suppressor in gastric cancer and chronic lymphocytic leukemia. As the promoter and coding region of BM742401 are fully embedded in a CpG island, we hypothesized that BM742401 is a tumor suppressor lncRNA epigenetically silenced by promoter DNA methylation in multiple myeloma.

Methods

Methylation-specific PCR and quantitative bisulfite pyrosequencing were performed to detect the methylation of BM742401 in normal plasma cells, myeloma cell lines and primary myeloma samples. The expression of BM742401 was measured by qRT-PCR. The function of BM742401 in multiple myeloma cells was analyzed by lentivirus transduction followed by migration assay.

Results

BM742401 methylation was detected in 10 (66.7%) myeloma cell lines but not normal plasma cells, and inversely correlated with expression of BM742401. In primary samples, BM742401 methylation was detected in 3 (12.5%) monoclonal gammopathy of undetermined significance, 9 (15.8%) myeloma at diagnosis and 8 (17.0%) myeloma at relapse/progression. Moreover, BM742401 methylation at diagnosis was associated with inferior overall survival (median OS: 25 vs. 39 months; P = 0.0496). In myeloma cell line JJN-3, stable overexpression of BM742401 by lentivirus transduction resulted in reduced cell migration (P = 0.0001) but not impacting cell death or proliferation.

Conclusions

This is the first report of tumor-specific methylation-mediated silencing of BM742401 in myeloma, which is likely an early event in myelomagenesis with adverse impact on overall survival. Moreover, BM742401 is a tumor suppressor lncRNA by inhibiting myeloma cell migration, hence implicated in myeloma plasma cell homing, metastasis and disease progression.
CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET
Authors: Wang Shuyang , Qiu Junfeng , Liu Lei , Su Cailin , Qi Lu , Huang Chengmei , Chen Xiaoning , Zhang Yaxin , Ye Yaping , Ding Yanqing , Liang Li , Liao Wenting
Published: August 2020

Background

cAMP responsive element binding protein 5 (CREB5) is a transcriptional activator in eukaryotic cells that can regulate gene expression. Previously, we found that CREB5 was involved in the occurrence and development of colorectal cancer (CRC) using bioinformatics analysis. However, the biological roles and underlying regulatory mechanism of CREB5 in CRC remain unclear.

Methods

Real-time PCR, western blotting, and immunohistochemistry were used to examine CREB5 expression. In vitro experiments including migration assay, wound-healing assay, chicken chorioallantoic membrane assay, and human umbilical vein endothelial cells tube formation assay were used to investigate the effects of CREB5 on CRC cell migration and tumor angiogenesis ability. Additionally, an orthotopic implantation assay was performed in nude mice to confirm the effects of CREB5 in vivo. Furthermore, gene set enrichment analysis was performed to explore the potential mechanism of CREB5 in CRC.

Results

We found that CREB5 expression was highly upregulated in CRC. CREB5 overexpression was positively correlated with advanced WHO stages and TNM stages and shorter survival in CRC patients. Moreover, CREB5 overexpression promoted while CREB5 silencing reduced the invasiveness and metastatic capacity of CRC cells both in vitro and in vivo. Furthermore, CREB5 directly interacted with the MET promoter and activated the hepatocyte growth factor-MET signalling pathway. Importantly, inhibition of MET reduced the invasion and metastasis of CREB5-overexpressing CRC cells, suggesting that CREB5 promotes metastasis mainly through activation of MET signalling.

Conclusion

Our study demonstrates a crucial role for CREB5 in CRC metastasis by directly upregulating MET expression. CREB5 may be both a potential prognostic marker and a therapeutic target to effectively overcome metastasis in CRC.
A lactate-targeted resuscitation strategy may be associated with higher mortality in patients with septic shock and normal capillary refill time: a post hoc analysis of the ANDROMEDA-SHOCK study
Authors: Kattan Eduardo , Hernández Glenn , Ospina-Tascón Gustavo , Valenzuela Emilio Daniel , Bakker Jan , Castro Ricardo ,   The ANDROMEDA-SHOCK Study Investigators and the Latin America Intensive Care Network (LIVEN)
Published: August 2020

Background

Capillary refill time (CRT) may improve more rapidly than lactate in response to increments in systemic flow. Therefore, it can be assessed more frequently during septic shock (SS) resuscitation. Hyperlactatemia, in contrast, exhibits a slower recovery in SS survivors, probably explained by the delayed resolution of non-hypoperfusion-related sources. Thus, targeting lactate normalization may be associated with impaired outcomes. The ANDROMEDA-SHOCK trial compared CRT- versus lactate-targeted resuscitation in early SS. CRT-targeted resuscitation associated with lower mortality and organ dysfunction; mechanisms were not investigated. CRT was assessed every 30 min and lactate every 2 h during the 8-h intervention period, allowing a first comparison between groups at 2 h (T2). Our primary aim was to determine if SS patients evolving with normal CRT at T2 after randomization (T0) exhibited a higher mortality and organ dysfunction when allocated to the LT arm than when randomized to the CRT arm. Our secondary aim was to determine if those patients with normal CRT at T2 had received more therapeutic interventions when randomized to the LT arm. To address these issues, we performed a post hoc analysis of the ANDROMEDA-SHOCK dataset.

Results

Patients randomized to the lactate arm at T0, evolving with normal CRT at T2 exhibited significantly higher mortality than patients with normal CRT at T2 initially allocated to CRT (40 vs 23%, p = 0.009). These results replicated at T8 and T24. LT arm received significantly more resuscitative interventions (fluid boluses: 1000[500–2000] vs. 500[0–1500], p = 0.004; norepinephrine test in previously hypertensive patients: 43 (35) vs. 19 (19), p = 0.001; and inodilators: 16 (13) vs. 3 (3), p = 0.003). A multivariate logistic regression of patients with normal CRT at T2, including APACHE-II, baseline lactate, cumulative fluids administered since emergency admission, source of infection, and randomization group) confirmed that allocation to LT group was a statistically significant determinant of 28-day mortality (OR 3.3; 95%CI[1.5–7.1]); p = 0.003).

Conclusions

Septic shock patients with normal CRT at baseline received more therapeutic interventions and presented more organ dysfunction when allocated to the lactate group. This could associate with worse outcomes.
First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens
Authors: Fokam Joseph , Takou Desire , Semengue Ezechiel Ngoufack Jagni , Teto Georges , Beloumou Grace , Dambaya Beatrice , Santoro Maria-Mercedes , Mossiang Leonella , Billong Serge Clotaire , Cham Fatim , Sosso Samuel Martin , Temgoua Edith Saounde , Nanfack Aubin Joseph , Moudourou Sylvie , Kamgaing Nelly , Kamgaing Rachel , Ngako Pamen Joelle Nounouce , Etame Mireille Mpoudi Ngole , Bissek Anne-Cecile Z.-K. , Elat Jean-Bosco N. , Moussi Emmanuel Eben , Colizzi Vittorio , Perno Carlo-Federico , Ndjolo Alexis ,   On behalf of the VIROFORUM
Published: August 2020

Background

Sub-Saharan African countries are transitioning to dolutegravir-based regimens, even for patients with extensive previous drug exposure, including first-generation integrase strand-transfer inhibitors (INSTI) such as raltegravir. Such exposure might have implications on cross-resistance to dolutegravir-based antiretroviral therapies (ART).

Case presentation

We report a 65 years old Cameroonian, previously exposed to raltegravir, and failing on third-line treatment with multi-drug resistance to darunavir/r and dolutegravir. Genotypic resistance testing (GRT) and viral tropism were performed during monitoring time points. The patient initiated ART in August 2007. At the time point of the first (29.04.2010), second (01.12.2017) and third (08.08.2019) GRT, prior ART exposure included 3TC, d4T, NVP and EFV; additionally TDF, DRV/r and RAL; and additionally ABC and DTG respectively. First GRT revealed mutations associated with resistance only to first-generation Non-nucleoside reverse transcriptase inhibitors (NNRTI). Second GRT revealed mutations associated with high-level resistance to all NRTIs, first generation NNRTIs, all ritonavir boosted protease inhibitors (PI/r), and all INSTI, while viral tropism (using geno2pheno) revealed a CCR5-tropic virus with a false positive rate (FPR) of 60.9% suggesting effectiveness of maraviroc (MRV). The third GRT showed high-level resistance to NRTI, NNRTI, all PI and all INSTI, with additional mutations (H221HY for NNRTI and S147G for INSTI), and a CCR5-tropic virus with a slightly reduced FPR (57.0%). Without any locally available active therapeutic option, the patient has been on a maintenance therapy with “DRV/r (600mg x 2/day)+TDF+3TC” and patient/family-centered adherence has been reinforced. Since the first viral load (VL) measurement in 2010, the patient has had 12 VL tests with the VL ranging from 4.97 Log to 6.44 Log copies/mL and the CD4 count never exceeded 200 cells/μL.

Conclusions

As African countries transition to dolutegravir-based regimens, prior raltegravir-exposure may prompt selection (and potential transmission) of dolutegravir-resistance, supporting case surveillance.
Correction to: Diet induced the change of mtDNA copy number and metabolism in Angus cattle
Authors: Bai Ying , Carrillo José A. , Li Yaokun , He Yanghua , Song Jiuzhou
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Delay in seeking treatment before emergent heart failure readmission and its association with clinical phenotype
Authors: Takei Makoto , Harada Kazumasa , Shiraishi Yasuyuki , Matsuda Junya , Iwasaki Yoichi , Yamamoto Yoshiya , Matsushita Kenichi , Miyazaki Tetsuro , Miyamoto Takamichi , Iida Kiyosi , Tanimoto Shuzo , Nagatomo Yuji , Hosoda Toru , Kohsaka Shun , Yamamoto Takeshi , Nagao Ken , Takayama Morimasa
Published: August 2020

Background

Many patients with emergent heart failure (HF) readmission have a delay between symptom onset and hospitalization. The present study aimed to characterize the interval between symptom onset and hospitalization in patients being readmitted for HF and to compare the clinical phenotypes of patients with delay before emergent readmission with those who presented to the hospital earlier.

Methods

Data for a total of 2073 consecutive patients was collected from the Tokyo CCU Network database; the patients were divided into delayed (those who sought medical help > 2 days after symptom onset; n = 271) and early groups (remaining patients; n = 1802), and their clinical characteristics and mode of presentation were compared.

Results

Age, sex, and laboratory findings including brain natriuretic peptide and serum creatinine levels were not significantly different between the two groups. Patients in the delayed group had greater chronic fluid retention and symptoms not associated with respiratory failure, whereas those in the early group were more likely to have acute respiratory distress, faster heart and respiration rates, and higher systolic blood pressure.

Conclusions

More than one in ten patients with HF readmission delay seeking treatment > 2 days after symptom onset. Patients who delayed seeking treatment showed the phenotype of chronic fluid retention, whereas those who presented to the hospital earlier had the phenotype of acute respiratory failure.