bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of quantitative polymerase chain reaction for BCR–ABL1 transcripts in chronic myeloid leukaemia: Are improved outcomes in patients with e14a2 transcripts an artefact of technology?
Authors: Dominy Katherine M. , Claudiani Simone , O’Hare Matthew , Szydlo Richard , Gerrard Gareth , Foskett Pierre , Foroni Letizia , Milojkovic Dragana , Apperley Jane F. , Khorashad Jamshid
Published: January 2022

The clinical outcome of chronic myeloid leukaemia patients has vastly improved since the introduction of tyrosine kinase inhibitor treatment, with a significant proportion of patients able to achieve treatment‐free remission. However, studies have shown that patients with the e13a2 transcript were less likely to achieve major molecular response compared to those with e14a2 transcripts. Most quantitative polymerase chain reaction (PCR) assays for detection of the BCR–ABL1 fusion gene do not differentiate between the two transcripts and we therefore hypothesised that technical bias linked to the qPCR assay could partially explain the discrepancy in outcomes. We designed an e14a2‐specific assay and identified no difference in results compared to an e13a2 standard assay. We then demonstrated that the commercial e14a2 standards were causing a significant overestimation of the e13a2 transcripts. Finally, we reviewed patient management after the qPCR values were corrected, using our new evaluation. We concluded that despite statistically significant differences in qPCR results, there was no impact on patient management or outcome. We conclude that, at least in our institution, it would be inappropriate to perform separate assays for patients with e13a2 or e14a2.
5‐HT3A receptors maintain hippocampal LTP in a CB1 and GABAA receptor‐ dependent manner for spatial memory
Authors: Yu Yan , Li Jing‐Jing , He Xiao‐Qian , Lai Zi‐Ying , Hao Rui , Qi Yu , Cao Dong‐Qing , Fu Ming , Ma Hong , Xie Qiu‐Chen , Sun Mu , Huang Zhi‐Li , Jin Ling‐Jing , Sun Hui‐hui , Lu Ning , Wang Rui , Yung Wing‐Ho , Huang Ying
Published: January 2022

Background and Purpose

As the only ionotropic receptor in the 5‐HT receptor family, the 5‐HT3 receptor (5‐HT3R) is involved in psychiatric disorders and its modulators have potential therapeutic effects for cognitive impairment in these disorders. However, it remains unclear how 5‐HT3Rs shape synaptic plasticity for memory function.

Experimental Approach

Extracellular as well as whole‐cell electrophysiological recordings were used to monitor hippocampal LTP and synaptic transmission in hippocampal slices in 5‐HT3AR knockout or 5‐HT3AR‐GFP mice. Immunocytochemistry, qRT‐PCR and western blotting were used to measure receptor expression. We also assessed hippocampal dependent cognition and memory, using the Morris water maze (MWM) and novel object recognition.

Key Results

We found that 5‐HT3R dysfunction impaired hippocampal LTP in Schaffer collateral (SC)‐CA1 pathway in hippocampal slices, by facilitating GABAergic inputs in pyramidal cells. This effect was dependent on 5‐HT3Rs on axon terminals. It resulted from reduced expression and function of the cannabinoid receptor 1 (CB1R) co‐localized with 5‐HT3Rs on axon terminals, and then led to diminishment of tonic inhibition of GABA release by CB1Rs. Inhibition of CB1Rs mimicked the facilitation of GABAergic transmission by 5‐HT3R disruption. Consequently, mice with hippocampal 5‐HT3R disruption exhibited impaired spatial memory in MWM tasks.

Conclusion and Implications

These results suggest that 5‐HT3Rs are crucial in enabling hippocampal synaptic plasticity via a novel CB1R‐GABAA‐dependent pathway to regulate spatial memory.
Vaccination in pediatric solid organ transplant: A primer for the immunizing clinician
Authors: Chen Justin K. , Cheng Jennifer , Liverman Rochelle , Serluco Anastacia , Corbo Heather , Yildirim Inci
Published: January 2022

Pediatric solid organ transplant (SOT) recipients are at a uniquely elevated risk for vaccine preventable illness (VPI) secondary to a multitude of factors including incomplete immunization at the time of transplant, inadequate response to vaccines with immunosuppression, waning antibody titers observed post‐SOT, and uncertainty among providers on the correct immunization schedule to utilize post‐SOT. Multiple guidelines are in existence from the Infectious Diseases Society of America and the American Society of Transplantation, which require use in adjunct with additional published references. We summarize the present state of SOT vaccine recommendations from relevant resources in tandem with the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices guidance utilizing both routine and rapid catch‐up schedules. The purpose of this all‐inclusive review is to provide improved clarity on the most optimal pre‐ and post‐transplant vaccine management within a one‐stop‐shop for the immunizing clinician.
The type of SARS‐CoV‐2 vaccine influences serological response in kidney transplant recipients
Authors: Correia Ana Luísa , Leal Rita , Pimenta Ana Carolina , Fernandes Mariana , Guedes Marques Maria , Rodrigues Luís , Santos Lídia , Romãozinho Catarina , Sá Helena , Pratas Jorge , Araújo Lucília , Figueiredo Arnaldo , Alves Rui
Published: January 2022

Vaccination is a promising strategy to control the ongoing pandemic; however, solid organ recipients tend to develop a weaker immune response to vaccination. Anti‐spike SARS‐CoV‐2 antibodies titers were measured 2–4 weeks post‐vaccination completion in 131 KT patients without previous infection. Demographic, clinical, and laboratorial parameters were analyzed to identify which factors contributed to seroconversion. Factors that influenced seroconversion, that occurred in 76 patients (58%), were longer time post‐transplant, immunosuppression without an antiproliferative drug and vaccination with mRNA vaccines. Patients who received mRNA vaccines had significantly higher rates of seroconversion compared with adenovirus vector vaccines (67% vs 33%, P < .001) and higher anti‐spike IgG titers.

These findings reinforce the need to discuss the vaccination strategy in this population, including a third dose with a mRNA vaccine.
Postreperfusion syndrome in liver transplantation: Outcomes, predictors, and application for recipient selection
Authors: Bekki Yuki , Myers Bryan , Wang Ryan , Smith Natalie , Zerillo Jeron , Rocha Chiara , Tabrizian Parissa , Moon Jang , Arvelakis Antonios , Facciuto Marcelo E. , DeMaria Samuel , Florman Sander
Published: January 2022

Background

This study aimed to identify risk factors for postreperfusion syndrome (PRS) and its impact on LT outcomes.

Methods

Data analysis was performed in 1021 adult patients undergoing donation after brain death (DBD) LT to identify PRS incidence, the risk factors for PRS development, and its impact on LT outcomes.

Results

The overall incidence of PRS was 16.1%. Independent risk factors for PRS included donor age (odds ratio (OR) 1.01, P = .02), donor body mass index (BMI) (OR 1.04, P = .003), moderate macrosteatosis (OR 2.48, P = .02), and cold ischemia time (CIT) (OR 1.06, P = .02). On multivariable analysis for 30‐day graft failure, PRS (hazard ratio (HR) 3.49; P < .001) and Model for End‐stage Liver Disease (MELD) score (HR 1.01; P = .05) were independent risk factors. Patients were categorized into four distinct groups based on PRS risk groups and MELD groups, which showed different 1‐year graft survival (P < .001). There were comparable outcomes between low PRS risk ‐ high MELD and high PRS risk ‐ low MELD group (P = .33).

Conclusions

Donor age, donor BMI, moderate macrosteatosis, and CIT were identified as risk factors for the development of PRS in LT using DBD grafts. PRS risk evaluation may improve donor‐to‐recipient matching based on their MELD scores.
Translational findings for odronextamab: From preclinical research to a first‐in‐human study in patients with CD20+ B‐cell malignancies
Authors: Zhu Min , Olson Kara , Kirshner Jessica R. , Khaksar Toroghi Masood , Yan Hong , Haber Lauric , Meagher Craig , Flink Dina M. , Ambati Srikanth R. , Davis John D. , DiCioccio A. Thomas , Smith Eric J. , Retter Marc W.
Published: January 2022

Odronextamab is a fully‐human IgG4‐based CD20xCD3 bispecific antibody that binds to CD3 on T cells and CD20 on B cells, triggering T‐cell‐mediated cytotoxicity independent of T‐cell‐receptor recognition. Adequate safety, tolerability, and encouraging durable complete responses have been observed in an ongoing first‐in‐human (FIH) study of odronextamab in patients with relapsed/refractory (R/R) B‐cell non‐Hodgkin lymphoma (B‐NHL; NCT02290951). We retrospectively evaluated the pharmacokinetic, pharmacodynamic, and antitumor characteristics of odronextamab in a series of in vitro/in vivo preclinical experiments, to assess their translational value to inform dose escalation for the FIH study. Half‐maximal effective concentration values from in vitro cytokine release assays (range: 0.05–0.08 mg/L) provided a reasonable estimate of odronextamab concentrations in patients associated with cytokine release at a 0.5 mg dose (maximum serum concentration: 0.081 mg/L) on week 1/day 1, which could therefore be used to determine the week 1 clinical dose. Odronextamab concentrations resulting in 100% inhibition of tumor growth in a Raji xenograft tumor mouse model (1–10 mg/L) were useful to predict efficacious concentrations in patients and inform dose‐escalation strategy. Although predicted human pharmacokinetic parameters derived from monkey data overestimated projected odronextamab exposure, they provided a conservative estimate for FIH starting doses. With step‐up dosing, the highest‐tested weekly odronextamab dose in patients (320 mg) exceeded the 1 mg/kg single dose in monkeys without step‐up dosing. In conclusion, combination of odronextamab in vitro cytokine data, efficacious concentration data from mouse tumor models, and pharmacokinetic evaluations in monkeys has translational value to inform odronextamab FIH study design in patients with R/R B‐NHL.
Evaluation of the knowledge of students concerning sexually transmitted infections in Bavaria/Germany (a cross‐sectional study)
Authors: Rummel Marcel , Clanner‐Engelshofen Benjamin M. , Nellessen Tobias , Zippel Stefan , Schuster Barbara , French Lars E. , Reinholz Markus
Published: January 2022

Background and objectives

Despite numerous information sources and campaigns on sexually transmitted infections (STIs), there has been an increase in STIs in Germany in recent years. The aim was to evaluate the awareness and knowledge level among young students in Bavaria/Germany for STIs with a focus on human papilloma viruses (HPV).

Methods

In a cross‐sectional survey rendered completely and irreversibly anonymous, a total of 4,100 students from Bavaria between the ages of 12 and 17 were interviewed using a multiple choice questionnaire about their knowledge and awareness of STI, on the basis of gender, school education and preventive youth health examinations that had taken place.

Results

A total of 3,834 questionnaires were included in the data analysis. Interestingly, the awareness level for HPV is remarkably lower compared to other STIs. Girls and adolescents who had already taken preventive youth health examinations showed a higher knowledge of STIs on average. Additionally, we could show that adolescents of lower educational levels, such as secondary school students, had the least knowledge.

Conclusions

The cross‐sectional study shows that many young people are still insufficiently informed about STIs. The gaps in information and lack of knowledge underline the necessity of intensive and long‐term educational work.
Global sharing of COVID‐19 vaccines: A duty of justice, not charity
Authors: Jecker Nancy S.
Published: January 2022

Global scarcity of COVID‐19 vaccines raises ethical questions about their fair allocation between nations. Section I introduces the question and proposes that wealthy nations have a duty of justice to share globally scarce COVID‐19 vaccines. Section II distinguishes justice from charity and argues that beneficiaries of unjust structures incur duties of justice when they are systematically advantaged at others expense. Section III gives a case‐based argument describing three upstream structural injustices that systematically advantaged wealthy countries and disadvantaged poorer countries, contributing to global disparities of COVID‐19 vaccines. Section IV examines more closely the duties of justice owed, including a duty to relinquish holdings, restitute victims, and restore relationships. Section V concludes that wealthy nations have a duty of justice to share COVID‐19 vaccines with poor nations and to restore relationships damaged by injustice. All nations should take steps to transform unjust structures.
Echocardiography for extracorporeal membrane oxygenation
Authors: Hussey Patrick T. , von Mering Gregory , Nanda Navin C. , Ahmed Mustafa I. , Addis Dylan R.
Published: January 2022

Extracorporeal membrane oxygenation (ECMO) provides advanced cardiopulmonary life support for patients in cardiac and/or respiratory failure. Echocardiography provides essential diagnostic and anatomic information prior to ECMO initiation, allows for safe and efficient ECMO cannula positioning, guides optimization of flow, provides a modality for rapid troubleshooting and patient evaluation, and facilitates decision‐making for eventual weaning of ECMO support. Currently, guidelines for echocardiographic assessment in this clinical context are lacking. In this review, we provide an overview of echocardiographic considerations for advanced imagers involved in the care of these complex patients. We focus predominately on new cannulas and complex cannulation techniques, including a special focus on double lumen cannulas and a section discussing indirect left ventricular venting. Echocardiography is tremendously valuable in providing optimal care in these challenging clinical situations. It is imperative for imaging physicians to understand the pertinent anatomic considerations, the often complicated physiological and hemodynamic context, and the limitations of the imaging modality.
Systolic and diastolic functional reserve of the subpulmonary and systemic right ventricles as assessed by pharmacologic and exercise stress: A systematic review
Authors: Cheng Sabine , Li Vivian Wing‐Yi , Cheung Yiu‐Fai
Published: January 2022

We performed a systematic review of the literature on the assessment of subpulmonary and systemic right ventricular (RV) functional reserve during pharmacological and exercise stress in congenital heart patients and patients with pulmonary arterial hypertension (PAH). Literature search was conducted using PubMed, EMBASE, and MEDLINE from their inception up to August 2020. Of 913 records identified, 56 studies with a total of 1730 patients were included. Of the 56 studies, 23 assessed subpulmonary RV functional reserve in repaired tetralogy of Fallot patients, 19 assessed systemic RV reserve in patients with transposition of the great arteries (TGA) after atrial switch and those with congenitally corrected TGA, and 14 assessed subpulmonary RV research in patients with PAH. Pharmacological and exercise stress was used, respectively, in 22 and 34 studies. The main findings were (1) impairment of RV systolic and diastolic functional reserve, (2) associations between impaired functional reserve and worse baseline functional parameters, and (3) prognostic implications of RV systolic functional reserve on clinical outcomes in patients with volume and/or pressure‐loaded subpulmonary and systemic right ventricles. Further studies are required to establish the incremental value of incorporating stress studies of RV systolic and diastolic function in the clinical management algorithm of congenital heart patients and patients with PAH.
Three‐dimensional right ventriculo‐arterial coupling as an independent determinant of severe heart failure symptoms in patients with dilated cardiomyopathy
Authors: Vîjîiac Aura , Onciul Sebastian , Deaconu Silvia , Vătășescu Radu , Guzu Claudia , Verinceanu Violeta , Scărlătescu Alina , Zamfir Diana , Petre Ioana , Scafa‐Udriște Alexandru , Dorobanţu Maria
Published: January 2022

Background

Right ventricular‐pulmonary artery coupling (RVPAC) is a predictor of outcome in pulmonary hypertension. However, the role of this parameter in dilated cardiomyopathy (DCM) remains to be established. The aim of this study was to assess the contribution of RVPAC to the occurrence of severe heart failure (HF) symptoms in patients with DCM using three‐dimensional (3D) echocardiography.

Methods

We prospectively screened 139 outpatients with DCM, 105 of whom were enrolled and underwent 3D echocardiographic assessment. RVPAC was estimated non‐invasively as the 3D right ventricular stroke volume (SV) to end‐systolic volume (ESV) ratio. Severe HF symptoms were defined by New York Heart Association (NYHA) class III or IV. We evaluated differences in RVPAC across NYHA classes and the ability of RVPAC to predict severe symptoms.

Results

Mean left ventricular (LV) ejection fraction was 28±7%. Mean RVPAC was 0.77±0.30 and it was significantly more impaired with increasing symptom severity (p = 0.001). RVPAC was the only independent determinant of severe HF symptoms, after adjusting for age, diuretic use, LV systolic function, LV diastolic function, and pulmonary artery systolic pressure (OR 0.035 [95% CI, 0.004–0.312], p = 0.003). By receiver‐operating characteristic analysis, the RVPAC cut‐off value for predicting severely symptomatic status was 0.54 (area under the curve = 0.712, p < 0.001).

Conclusion

3D echocardiographic SV/ESV ratio is an independent correlate of severe HF symptoms in patients with DCM. 3D RVPAC might prove to be a useful risk stratification tool for these patients, should it be further validated in larger studies.
Phoretic specialization on insect herbivores facilitates mite transportation to host plants
Authors: Bizzarri Laura , Kuprewicz Erin K. , Varma Megana , García‐Robledo Carlos
Published: January 2022

Phoresy, the use of another organism for dispersal, is one of the most intriguing commensalistic interactions. The selection of a correct host is fundamental for phoretic organisms to ensure arrival to suitable habitats and to encounter potential mates. This study focuses on a group of phoretic mites in the genus Lasioseius (Acari: Blattisociidae). In La Selva Biological Station, a tropical wet forest in Costa Rica, Lasioseius mites feed on nematodes inside the scrolls formed by the young leaves of their hosts, plants in the order Zingiberales. When leaves expand and unfurl, mites disperse to another rolled leaf by clinging onto ‘rolled‐leaf beetles’, a group of insect herbivores specialized on Zingiberales (genera Cephaloleia and Chelobasis; Coleoptera: Chrysomelidae). In this study, we determined whether Lasioseius mites associated with Cephaloleia belti Baly are specialized on this beetle species as a phoretic host. Mites may also be attracted to Chelobasis perplexa Baly, sharing the same host plant. Another possibility is that Lasioseius mites are opportunistic generalists and attach to rolled‐leaf beetle species (e.g., Cephaloleia dorsalis Baly) that never share host plants with either C. belti or Ch. perplexa. In a laboratory setting, we tested whether mites preferred scents from and/or attached to particular beetle species. Scent attraction experiments showed that Lasioseius mites collected from C. belti were attracted to scents from C. belti and Ch. perplexa, but were not attracted to scents from C. dorsalis. Mites collected from C. belti attached to both C. belti and Ch. perplexa, but never to C. dorsalis. In conclusion, Lasioseius mites are not strict specialists, but are able to detect and attach to beetle species that inhabit their host plant.
Effects of NeemAzal‐T/S on different developmental stages of rose aphid, Macrosiphum rosae
Authors: Bartelsmeier Imke , Kilian Michael , Dicke Marcel
Published: January 2022

Natural insecticides often do not provide a strong knock‐down effect and have a lower efficacy than synthetic pesticides. For an effective application of natural insecticides, it is essential to know the product’s mode of action in detail. The efficacy of the commercial neem [Azadirachta indica A. Juss (Meliaceae)] product NeemAzal‐T/S and its influence on stage‐specific mortality, development, and reproduction of rose aphids, Macrosiphum rosae L. (Hemiptera: Aphididae), were determined in greenhouse trials. NeemAzal‐T/S had an efficacy of 40% against M. rosae in standard efficacy trials with initial infestations between 100 and 270 aphids per plant. However, it has a significant impact on the survival of nymphs in the first to third instar as well as on juvenile development. Nymphs treated with NeemAzal‐T/S exhibit a significant delay in molting to the second instar and most of them die before the first molt. Furthermore, reproduction of adult M. rosae females is reduced when aphids are exposed to sub‐lethal concentrations of neem as first instars. Population growth is inhibited or delayed on rose plants treated with NeemAzal‐T/S. The results indicate that applications of NeemAzal‐T/S can be used to control rose aphids in integrated pest management (IPM) systems. Because this insecticide has no rapid knock‐down effect and no effect on adult aphids, combinations with natural enemies of pest insects as well as with other insecticides are possibilities to enhance the efficacy.
Mutation profiling of circulating tumor DNA identifies distinct mutation patterns in non‐Hodgkin lymphoma
Authors: Fu Haiying , Shen Jianzhen , Zhou Huarong , Zhang Feng , Li Hongping , Ma Zhiming , Huang Wanling , Chen Lushan , Chen Yi , Liu Tingbo
Published: January 2022

Objective

Circulating tumor DNA (ctDNA) is emerging as a versatile biomarker for noninvasive genotyping and response monitoring in specific B‐cell lymphomas; however, few studies have been conducted to explore ctDNA‐based mutation profiling across non‐Hodgkin lymphomas (NHLs) and genomic changes after initiation of chemotherapy.

Methods

A targeted sequencing of 362 genes was performed to detect the mutation profiles in paired blood and tissue samples from 42 NHL patients. Genomic alterations were explored in 11 diffuse large B‐cell lymphoma (DLBCL) patients using paired blood samples collected pre‐ and post‐R‐CHOP chemotherapy.

Results

The frequencies of PIM1, MYD88, MYC, ZNF292, JAK, and MAF mutations were higher in aggressive than in indolent B‐cell lymphoma and NK/T subtypes. Tumor mutation burden in blood samples was higher in aggressive than in indolent B‐cell lymphomas and higher in patients who progressed than in those who responded to treatments. Our data also revealed significant enhance of concordance index through integrating mutated genes that were significantly associated with prognosis into International Prognostic Index‐based prognostic model. Moreover, acquisition of mutations such as PCLO_p.L1220Tfs*3 was associated with resistance to R‐CHOP in DLBCL patients.

Conclusions

Our findings illustrated distinct mutation patterns across various NHL subtypes and suggested the association of genomic alterations in ctDNA with treatment outcomes.
Ecological validity in exercise neuroscience research: A systematic investigation
Authors: Chang Melissa , Büchel Daniel , Reinecke Kirsten , Lehmann Tim , Baumeister Jochen
Published: January 2022

The contribution of cortical processes to adaptive motor behaviour is of great interest in the field of exercise neuroscience. Next to established criteria of objectivity, reliability and validity, ecological validity refers to the concerns of whether measurements and behaviour in research settings are representative of the real world. Because exercise neuroscience investigations using mobile electroencephalography are oftentimes conducted in laboratory settings under controlled environments, methodological approaches may interfere with the idea of ecological validity. This review utilizes an original ecological validity tool to assess the degree of ecological validity in current exercise neuroscience research. A systematic literature search was conducted to identify articles investigating cortical dynamics during goal‐directed sports movement. To assess ecological validity, five elements (environment, stimulus, response, body and mind) were assessed on a continuum of artificiality–naturality and simplicity–complexity. Forty‐seven studies were included in the present review. Results indicate lowest average ratings for the element of environment. The elements stimulus, body and mind had mediocre ratings, and the element of response had the highest overall ratings. In terms of the type of sport, studies that assessed closed‐skill indoor sports had the highest ratings, whereas closed‐skill outdoor sports had the lowest overall rating. Our findings identify specific elements that are lacking in ecological validity and areas of improvement in current exercise neuroscience literature. Future studies may potentially increase ecological validity by moving from reductionist, artificial environments towards complex, natural environments and incorporating real‐world sport elements such as adaptive responses and competition.
Establishment and evaluation of a quantitative analysis model for potentially toxic metals in wet soil samples by LIBS
Authors: Xu Yuxing , Han Bing , Tan Xin , Jiao Qingbin , Ma Zhenyu , Lv Baolin , Li Yuhang , Li Hui , Zou Yubo , Yang Lin
Published: January 2022

Fast on‐site detection of potentially toxic metals in soils is crucial for soil remediation and contamination monitoring. The moisture in soils is a challenge for quantitative analysis of potentially toxic metals. Here, we used laser‐induced breakdown spectroscopy (LIBS) and partial least squares regression (PLSR) for fast on‐site quantitative analysis of potentially toxic metals in wet soil samples. The model offered direct measurement of the moisture content in soil samples: the coefficient of determination (R2) value and the root‐mean‐square error of prediction (RMSEP) of predicted moisture content were 0.98% and 1.3%, respectively. The correlation between laser ablation factor and moisture content of the samples was determined by analysing the influence of sample moisture content on laser ablation. Quantitative analysis of wet soil samples based on ablation factor was established with an R2 of 0.97. Potentially toxic elemental Cu and Cr in sample 4# were verified by the quantitative analysis model through weighing and direct measurement. The relative error of concentration was within 10%, and the accuracy was improved by over 80%. The preliminary results show that the quantitative analysis model of potentially toxic metals in wet soil samples based on LIBS technology can detect potentially toxic metals in wet soil samples quickly and accurately on‐site. This has important guiding significance for real‐time and on‐site monitoring of contaminated soils.

Highlights

Fast on‐site quantitative analysis of potentially toxic metals in wet soil samples

Quantitative analysis of wet soil samples based on ablation factor was established

The relative error of concentration was within 10%, and the accuracy was improved by over 80%

The model can detect potentially toxic metals in wet soil samples quickly and accurately on‐site
Proposal for an updated seizure classification framework in clinical trials
Authors: Steriade Claude , Sperling Michael R. , DiVentura Bree , Lozano Meryl , Shellhaas Renée A. , Kessler Sudha Kilaru , Dlugos Dennis , French Jacqueline
Published: January 2022

The International League Against Epilepsy (ILAE) seizure classification scheme has been periodically updated to improve its reliability and applicability to clinicians and researchers alike. Here, members of the Epilepsy Study Consortium propose a pragmatic seizure classification, based on the ILAE scheme, designed for use in clinical trials with a focus on outcome measures that have high reliability, broad interpretability across stakeholders, and clinical relevance in the context of the development of novel antiseizure medications. Controversies around the current ILAE classification scheme are discussed in the context of clinical trials, and pragmatic simplifications to the existing scheme are proposed, for intended use by investigators, industry sponsors, and regulatory agencies.
Intracranial electroencephalographic biomarker predicts effective responsive neurostimulation for epilepsy prior to treatment
Authors: Scheid Brittany H. , Bernabei John M. , Khambhati Ankit N. , Mouchtaris Sofia , Jeschke Jay , Bassett Dani S. , Becker Danielle , Davis Kathryn A. , Lucas Timothy , Doyle Werner , Chang Edward F. , Friedman Daniel , Rao Vikram R. , Litt Brian
Published: January 2022

Objective

Despite the overall success of responsive neurostimulation (RNS) therapy for drug‐resistant focal epilepsy, clinical outcomes in individuals vary significantly and are hard to predict. Biomarkers that indicate the clinical efficacy of RNS—ideally before device implantation—are critically needed, but challenges include the intrinsic heterogeneity of the RNS patient population and variability in clinical management across epilepsy centers. The aim of this study is to use a multicenter dataset to evaluate a candidate biomarker from intracranial electroencephalographic (iEEG) recordings that predicts clinical outcome with subsequent RNS therapy.

Methods

We assembled a federated dataset of iEEG recordings, collected prior to RNS implantation, from a retrospective cohort of 30 patients across three major epilepsy centers. Using ictal iEEG recordings, each center independently calculated network synchronizability, a candidate biomarker indicating the susceptibility of epileptic brain networks to RNS therapy.

Results

Ictal measures of synchronizability in the high‐γ band (95–105 Hz) significantly distinguish between good and poor RNS responders after at least 3 years of therapy under the current RNS therapy guidelines (area under the curve = .83). Additionally, ictal high‐γ synchronizability is inversely associated with the degree of therapeutic response.

Significance

This study provides a proof‐of‐concept roadmap for collaborative biomarker evaluation in federated data, where practical considerations impede full data sharing across centers. Our results suggest that network synchronizability can help predict therapeutic response to RNS therapy. With further validation, this biomarker could facilitate patient selection and help avert a costly, invasive intervention in patients who are unlikely to benefit.
A Mind of Winter: The Transformative Experience of Estrangement by a Stateless Kurd in Exile in Denmark
Authors: Bregnbæk Susanne
Published: January 2022

This article explores the transformative experience of estrangement by a Kurdish Iranian refugee named Hiwa in exile in Denmark. Through a person‐centered approach, I focus on what was at stake for stateless people, such as Hiwa, at a time when right‐wing populist asylum politics made achieving permanent citizenship an uphill battle and leaving Denmark impossible due to the Dublin Regulation. Drawing on psychoanalytic theories of “the multiple self,” I describe Hiwa's changing self‐states as involving a triple reorientation in the form of an estranged relationship to his past, present, and envisioned future. I analyze this transformative experience as linked to an existential quest to find a space between the struggle for freedom and submission to a sense of powerlessness—experiences that sometimes elude conventional language. Finally, I suggest that reading poetry and writing about exile constituted a transitional experience enabling an inner world of emotions to be expressed. The article provides a window to the human consequences of the “Paradigm Shift” in Danish asylum politics, which entailed making all residence permits temporary—and more broadly to the growing problem of statelessness in Europe.
Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise
Authors: Yin Fei
Published: January 2022

Alzheimer’s disease (AD) is an age‐associated neurodegenerative disorder with multifactorial etiology, intersecting genetic and environmental risk factors, and a lack of disease‐modifying therapeutics. While the abnormal accumulation of lipids was described in the very first report of AD neuropathology, it was not until recent decades that lipid dyshomeostasis became a focus of AD research. Clinically, lipidomic and metabolomic studies have consistently shown alterations in the levels of various lipid classes emerging in early stages of AD brains. Mechanistically, decades of discovery research have revealed multifaceted interactions between lipid metabolism and key AD pathogenic mechanisms including amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, and myelin degeneration. In the present review, converging evidence defining lipid dyshomeostasis in AD is summarized, followed by discussions on mechanisms by which lipid metabolism contributes to pathogenesis and modifies disease risk. Furthermore, lipid‐targeting therapeutic strategies, and the modification of their efficacy by disease stage, ApoE status, and metabolic and vascular profiles, are reviewed.
Incorporating thermal niche to benefit understanding climate‐induced biological variability in small pelagic fishes in the Kuroshio ecosystem
Authors: Ma Shuyang , Tian Yongjun , Li Jianchao , Ju Peilong , Sun Peng , Ye Zhenjiang , Liu Yang , Watanabe Yoshiro
Published: January 2022

Climate‐induced fluctuations in marine fish populations have been raising great scientific concerns. Previous studies generally dedicate to parameterization of climatic, environmental, and biological variability patterns with focuses on their empirical or incompletely mechanistic relationships. Little consideration on physiological characteristics of organisms prevents from exploring mechanisms behind the apparent relationships. Therefore, incorporating physiological information into investigation on climate–environment–biology relationships is essential to understand climate‐induced biological variability. Small pelagic fishes play unparalleled roles in the Kuroshio ecosystem and show dramatic fluctuations in response to environmental changes, serving as ideal research targets in studies on climate‐induced biological variability. This study focuses on Japanese sardine, chub mackerel, and Japanese anchovy, three key small pelagic fishes in the Kuroshio ecosystem with distinct physiological characteristics, with attempts to incorporate thermal niches into investigations on their responses to climate variability. The recruitment suitable index (RSI) is developed considering both sea surface temperature (SST) and species thermal niche. Results show that the RSI significantly increase explanations on variations in resource abundance indices of the three key small pelagic fishes. Responses of small pelagic fishes to climate variability show differences by species and stocks. In addition, variations in the Siberian High pressure system and Atlantic Multidecadal Oscillation contribute highly to variations in resource abundance indices through affecting the SST and further the RSI. This study demonstrates importance of physiological information for understanding climate‐induced biological variability and effectiveness of combining thermal niches with the investigation on mechanistic climate–environment–biology relationships, which should be extensively considered in the future studies.
Microclimate‐based species distribution models in complex forested terrain indicate widespread cryptic refugia under climate change
Authors: Stark Jordan R. , Fridley Jason D.
Published: January 2022

Aim

Species’ climatic niches may be poorly predicted by regional climate estimates used in species distribution models (SDMs) due to microclimatic buffering of local conditions. Here, we compare SDMs generated using a locally validated below‐canopy microclimate model to those based on interpolated weather station data at two spatial scales to determine the effects of scale and topography on potential future below‐canopy warming and species distributions.

Location

Great Smoky Mountains National Park (2,090 km2; NC, TN, USA).

Time period

1970–2006, late‐century warming.

Major taxa studied

Vascular plant species of Southern Appalachian forests.

Methods

We compared the fit and spatio‐temporal predictions of SDMs generated using occurrence records of 154 plant species and three climate models: macroclimate (1 km, WorldClim), downscaled climate (based on a 30‐m digital elevation model), and fine‐scale microclimate (30 m) from a below‐canopy sensor network.

Results

We found that, although SDM fit was similar across models, microclimate‐derived SDMs predicted substantially greater species persistence with 4°C of regional warming, with a difference of 50% of the species pool in some areas. Microclimate models predicted that warming trends will be buffered in high‐elevation and near‐stream habitats. Microclimate SDMs predicted higher stability of mid‐elevation species, particularly in thermally buffered areas near streams, and critically, less change in species composition at high elevation. In contrast, predictions of macroclimate and downscaled climate models were similar despite improved resolution.

Main conclusions

Our results demonstrate that careful selection of climate drivers, including local near‐ground validation rather than downscaling solely with elevation, is critical for projecting distributions. They also suggest that some species at risk from climate change might persist, even with 4°C of macroclimate warming, in cryptic refugia buffered by microclimate, pointing to the roles of forest cover and topography in explaining slower‐than‐expected changes in understorey communities. However, certain species, such as those currently occurring on low‐elevation ridges that are sensitive to atmospheric changes, may be at more risk than macroclimate or downscaled climate SDMs suggest.
Global development, diasporic communities, and civic space
Authors: Peck Sarah
Published: January 2022

Over the last twenty years increasing attention has been paid to the ways in which diasporic communities can shape global development processes, thorough a variety of intersecting scales and spatialities. This promotion of diasporic‐centred development has occurred in parallel to a narrowing of civic space and it is these juxtaposing narratives that this paper interrogates. This paper firstly considers diasporic‐centred development before moving on to think about how the contemporary narrowing of civic space may be (re)shaping diasporic civic life and participation in global development processes. The paper concludes that the spaces for diasporic civic participation in development are vulnerable to being squeezed in multiple intersecting ways, including through the racialised marginalisation of diasporic communities in everyday life, restrictions on diasporic associational life, the delegitimising of diasporic organisations in the (formal) development sphere and the extra‐territorial narrowing of diasporic civic space by state (and non‐state) actors. It is imperative that we explore the intersections in the diasporic‐civic space‐development nexus, with further research needed to understand how diasporic communities are responding to these changes, how diasporic civic spaces are reconfiguring and reconstituting themselves in this context, and what this means for global development.
Indignação and declaração corporal: Luta and artivism in Brazil during the times of the pandemic
Authors: Shymko Yuliya , Quental Camilla , Navarro Mena Madeleine
Published: January 2022

In this article, we interrogate vergonha alheia (shame on behalf of others; or “vicarious embarrassment”), which is experienced when viewing an embarrassing action from the outside. We question if shame—associated with the worst of human behavior brought about and made visible by the COVID‐19 pandemic—can ignite a new kind of cultural sensitivity to the pain of others. Turning to the work of several feminist scholars, we reveal the generative power of shame in artistic and political mobilization. We study examples of artistic activism (i.e., artivism) during the COVID‐19 pandemic, as presented by two Brazilian women—Adriana Calcanhotto and Debora Diniz. By intimately engaging with their work and situating it in the context of the popular feminist struggle in Brazil—that is, a luta (the struggle), we discern two performative patterns articulated through distinct symbolic utterances: indignação and declaração corporal (indignation and bodily declaration). We contend that these utterances help overcome individual apathy, summon radically different forms of sensitivity and meaning making that may initiate potentially transformative shifts in public perceptions of social justice. We conclude with our reflections on how feminist artivism in Latin America not only questions the validity of the abstract, universal, and modern human being but also reveals new frames of progress.
Association between Helicobacter pylori infection and growth outcomes in children: A meta‐analysis
Authors: Xu Chenjing , Wu Yao , Xu Shunfu
Published: January 2022

Background

Multiple studies have reported the association between Helicobacter pylori (H. pylori) infection and children's growth. The results of these studies are controversial. Our meta‐analysis aimed to evaluate the association between H. pylori infection and growth outcomes in children.

Methods

We searched PubMed, Embase, Web of Science, and Cochrane Library, as well as two Chinese databases, Wanfang, and CNKI from inception to September 2019. Odds ratios (ORs) and standardized mean differences (SMDs) with their 95% confidence interval (95% CI) were selected as the effect size. We assessed pooled data using a random‐effects model. Subgroup and sensitivity analyses were conducted.

Results

In total, 29 studies provided data from 9384 subjects. The meta‐analysis results indicated a significant association of H. pylori infection with ponderal growth disorders (OR: 2.47; 95% CI: 1.13, 5.37; p = 0.02) and linear growth disorders (OR =1.76; 95% CI: 1.15, 2.69, p = 0.01). H. pylori infection has an adverse impact on children's height‐for‐age Z (HAZ) scores (SMD = −0.41; 95% CI: −0.69, −0.13; p < 0.01). Pooling SMDs by other outcomes (height, weight, BMI, weight‐for‐age and BMI‐for‐age Z scores, weight‐for‐age percentile scores, and linear and ponderal growth velocity with/without infection and eradication/non‐eradication) all indicated no significant association.

Conclusion

The current evidence supports the hypothesis that H. pylori infection is associated with growth outcomes in children, mainly HAZ scores. Clinicians might consider H. pylori infection in investigating linear growth disorders in children.
Pepsinogen II in gastritis and Helicobacter pylori infection
Authors: Di Mario Francesco , Crafa Pellegrino , Barchi Alberto , Franzoni Lorella , Franceschi Marilisa , Russo Michele , Bricca Ludovica , Brozzi Lorenzo , Rodriguez Castro Kryssia , Rugge Massimo
Published: January 2022

Background and Aim

In the gastric mucosa, pepsinogen II (PgII) is produced/secreted by glands in the mucus‐secreting antral and cardia compartments, but also by the chief cells and the oxyntic glands. Increasing PgII serum levels are associated with the whole spectrum of gastric inflammatory diseases, including gastritis induced by Helicobacter pylori (H. pylori). This review critically addresses the clinical value of PgII serology for assessing gastric mucosal inflammation, and as a marker of H. pylori status, in both H. pylori‐positive patients and after eradication therapy.

Results

A search in PubMed/Scopus records yielded 39 out of 1190 published scientific studies meeting the selection criteria for this study. In the studies considered, PgII levels were significantly associated with non‐atrophic gastric inflammatory lesions (p‐values: 0.025–0.0001). H. pylori‐positive patients had significantly higher PgII levels than H. pylori‐negative individuals (p‐values: 0.o5–0.0001). While a significant drop in serum PgII levels is consistently reported in H. pylori‐eradicated patients (p‐values: from 0.05 to 0.0001), inconsistencies in the related negative and positive predictive values significantly lower the clinical reliability of PgII testing by comparison with other available non‐invasive tests.

Conclusions

PgII serology may provide clinically useful information on gastric inflammatory diseases, particularly if they are non‐atrophic. PgII serology is inconsistent, however, for the purposes of distinguishing patients whose H. pylori eradication therapy is successful from those who remain infected.
A broadband near‐infrared Sc1−x(PO3)3:XCr3+ phosphor with enhanced thermal stability and quantum yield by Yb3+ codoping
Authors: Yu Ting , Sheng Haoyang , Chen Shenghai , Yuan Jian , Deng Tingting , Wu Ming , Guo Yue , Zeng Qingguang
Published: January 2022

Broadband near‐infrared (NIR) phosphors converted light‐emitting diodes (pc‐LEDs) have attracted tremendous attention for their great potential in NIR spectroscopy applications. Herein, we report on the photoluminescence (PL) properties of Cr3+‐doped Sc(PO3)3, which exhibits a broadband NIR emission centered at 900 nm with a full width at half‐maximum (FWHM) of 161 nm upon excitation at 480 nm. In terms of the examination of spectroscopic parameters, we find that Cr3+ ions occupy a weak crystal field site (Dq/B = 1.94) in the Sc(PO3)3 host with a stronger electron–phonon coupling (Huang‐Rhys factor, S = 5.5), which results in a serious thermal quenching and a low internal quantum efficiency (IQE). Thermal stability and IQE of phosphors can be substantially enhanced by the introduction of Yb3+ ions. In the light of the analysis of excited‐state dynamics, we demonstrate that the enhancement mechanism is ascribed to the efficient Cr3+→Yb3+ energy transfer from the thermal sensitive Cr3+ centers to the thermal stable Yb3+ emitters. An NIR pc‐LED device has been finally fabricated by the combination of a blue‐emitting chip and a Cr3+/Yb3+ codoped Sc(PO3)3 phosphor whose potential application for broadband NIR pc‐LEDs is also discussed.
Organization capital effect in stock returns—The role of R&D
Authors: Chan Konan , Li Mei‐Xuan , Lin Chu‐Bin , Wang Yanzhi
Published: January 2022

Previous studies document a strong organization capital effect in stock returns. We investigate whether and how research and development (R&D) activities affect this organization capital effect. We find that the organization capital effect is stronger in firms with R&D activities. The annual abnormal return of the hedge portfolio sorted by organization capital is 2.41% for R&D firms but only 0.41% for non‐R&D firms. Further analyses show that the organization capital effect can be attributed to R&D characteristics rather than R&D risk factors.
LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer
Authors: Nie Xiaobo , Liu Huiyang , Ye Wenling , Wei Xiaoyun , Fan Lili , Ma Han , Li Lanqing , Xue Wanting , Qi Wenting , Wang Yan‐Dong , Chen Wei‐Dong
Published: January 2022

The overactivation of canonical Wnt/β‐catenin pathway and the maintenance of cancer stem cells (CSCs) are essential for the onset and malignant progression of most human cancers. However, their regulatory mechanism in colorectal cancer (CRC) has not yet been well demonstrated. Low‐density lipoprotein receptor‐related protein 5 (LRP5) has been identified as an indispensable co‐receptor with frizzled family members for the canonical Wnt/β‐catenin signal transduction. Herein, we show that activation of LRP5 gene promotes CSCs‐like phenotypes, including tumorigenicity and drug resistance in CRC cells, through activating the canonical Wnt/β‐catenin and IL‐6/STAT3 signalling pathways. Clinically, the expression of LRP5 is upregulated in human CRC tissues and closely associated with clinical stages of patients with CRC. Further analysis showed silencing of endogenous LRP5 gene is sufficient to suppress the CSCs‐like phenotypes of CRC through inhibiting these two pathways. In conclusion, our findings not only reveal a regulatory cross‐talk between canonical Wnt/β‐catenin signalling pathway, IL‐6/STAT3 signalling pathway and CD133‐related stemness that promote the malignant behaviour of CRC, but also provide a valuable target for the diagnosis and treatment of CRC.