bluuebunny/crossref_metadata_2025 huggingface dataset:
A direct test of competitive versus cooperative episodic–procedural network dynamics in human memory
Authors: Freedberg Michael V , Reeves Jack A , Fioriti Cynthia M , Murillo Jorge , Voss Joel L , Wassermann Eric M
Published: January 2022

Classical lesion studies led to a consensus that episodic and procedural memory arises from segregated networks identified with the hippocampus and the caudate nucleus, respectively. Neuroimaging studies, however, show that competitive and cooperative interactions occur between networks during memory tasks. Furthermore, causal experiments to manipulate connectivity between these networks have not been performed in humans. Although nodes common to both networks, such as the precuneus and ventrolateral thalamus, may mediate their interaction, there is no experimental evidence for this. We tested how network-targeted noninvasive brain stimulation affects episodic–procedural network interactions and how these network manipulations affect episodic and procedural memory in healthy young adults. Compared to control (vertex) stimulation, hippocampal network-targeted stimulation increased within-network functional connectivity and hippocampal connectivity with the caudate. It also increased episodic, relative to procedural, memory, and this persisted one week later. The differential effect on episodic versus procedural memory was associated with increased functional connectivity between the caudate, precuneus, and ventrolateral thalamus. These findings provide direct evidence of episodic–procedural network competition, mediated by regions common to both networks. Enhanced hippocampal network connectivity may boost episodic, but decrease procedural, memory by co-opting resources shared between networks.
Frontal eye fields in macaque monkeys: prefrontal and premotor contributions to visually guided saccades
Authors: Lowe Kaleb A , Zinke Wolf , Cosman Joshua D , Schall Jeffrey D
Published: January 2022

Neuronal spiking was sampled from the frontal eye field (FEF) and from the rostral part of area 6 that reaches to the superior limb of the arcuate sulcus, dorsal to the arcuate spur when present (F2vr) in macaque monkeys performing memory-guided saccades and visually guided saccades for visual search. Neuronal spiking modulation in F2vr resembled that in FEF in many but not all respects. A new consensus clustering algorithm of neuronal modulation patterns revealed that F2vr and FEF contain a greater variety of modulation patterns than previously reported. The areas differ in the proportions of visuomotor neuron types, the proportions of neurons discriminating a target from distractors during visual search, and the consistency of modulation patterns across tasks. However, between F2vr and FEF we found no difference in the magnitude of delay period activity, the timing of the peak discharge rate relative to saccades, or the time of search target selection. The observed similarities and differences between the 2 cortical regions contribute to other work establishing the organization of eye fields in the frontal lobe and may help explain why FEF in monkeys is identified within granular prefrontal area 8 but in humans is identified within agranular premotor area 6.
Individual resting-state alpha peak frequency and within-trial changes in alpha peak frequency both predict visual dual-pulse segregation performance
Authors: Drewes Jan , Muschter Evelyn , Zhu Weina , Melcher David
Published: January 2022

Although sensory input is continuous, information must be combined over time to guide action and cognition, leading to the proposal of temporal sampling windows. A number of studies have suggested that a 10-Hz sampling window might be involved in the “frame rate” of visual processing. To investigate this, we tested the ability of participants to localize and enumerate 1 or 2 visual flashes presented either at near-threshold or full-contrast intensities, while recording magnetoencephalography. The inter-stimulus interval (ISI) between the 2 flashes was varied across trials. Performance in distinguishing between 1 and 2 flashes was linked to the alpha frequency, both at the individual level and trial-by-trial. Participants with a higher resting-state alpha peak frequency showed the greatest improvement in performance as a function of ISI within a 100-ms time window, while those with slower alpha improved more when ISI exceeded 100 ms. On each trial, correct enumeration (1 vs. 2) performance was paired with faster pre-stimulus instantaneous alpha frequency. Our results suggest that visual sampling/processing speed, linked to peak alpha frequency, is both an individual trait and can vary in a state-dependent manner.
Naturalistic Audio-Movies reveal common spatial organization across “visual” cortices of different blind individuals
Authors: Musz Elizabeth , Loiotile Rita , Chen Janice , Bedny Marina
Published: January 2022

Occipital cortices of different sighted people contain analogous maps of visual information (e.g. foveal vs. peripheral). In congenital blindness, “visual” cortices respond to nonvisual stimuli. Do visual cortices of different blind people represent common informational maps? We leverage naturalistic stimuli and inter-subject pattern similarity analysis to address this question. Blindfolded sighted (n = 22) and congenitally blind (n = 22) participants listened to 6 sound clips (5–7 min each): 3 auditory excerpts from movies; a naturalistic spoken narrative; and matched degraded auditory stimuli (Backwards Speech, scrambled sentences), during functional magnetic resonance imaging scanning. We compared the spatial activity patterns evoked by each unique 10-s segment of the different auditory excerpts across blind and sighted people. Segments of meaningful naturalistic stimuli produced distinctive activity patterns in frontotemporal networks that were shared across blind and across sighted individuals. In the blind group only, segment-specific, cross-subject patterns emerged in visual cortex, but only for meaningful naturalistic stimuli and not Backwards Speech. Spatial patterns of activity within visual cortices are sensitive to time-varying information in meaningful naturalistic auditory stimuli in a broadly similar manner across blind individuals.
Stopping Hospital Infections With Environmental Services (SHINE): A Cluster-randomized Trial of Intensive Monitoring Methods for Terminal Room Cleaning on Rates of Multidrug-resistant Organisms in the Intensive Care Unit
Authors: Ziegler Matthew J , Babcock Hilary H , Welbel Sharon F , Warren David K , Trick William E , Tolomeo Pam , Omorogbe Jacqueline , Garcia Diana , Habrock-Bach Tracy , Donceras Onofre , Gaynes Steven , Cressman Leigh , Burnham Jason P , Bilker Warren , Reddy Sujan C , Pegues David , Lautenbach Ebbing , Kelly Brendan J , Fuchs Barry , Martin Niels D , Han Jennifer H
Published: January 2022

Background

Multidrug-resistant organisms (MDROs) frequently contaminate hospital environments. We performed a multicenter, cluster-randomized, crossover trial of 2 methods for monitoring of terminal cleaning effectiveness.

Methods

Six intensive care units (ICUs) at 3 medical centers received both interventions sequentially, in randomized order. Ten surfaces were surveyed each in 5 rooms weekly, after terminal cleaning, with adenosine triphosphate (ATP) monitoring or an ultraviolet fluorescent marker (UV/F). Results were delivered to environmental services staff in real time with failing surfaces recleaned. We measured monthly rates of MDRO infection or colonization, including methicillin-resistant Staphylococcus aureus, Clostridioides difficile, vancomycin-resistant Enterococcus, and MDR gram-negative bacilli (MDR-GNB) during a 12-month baseline period and sequential 6-month intervention periods, separated by a 2-month washout. Primary analysis compared only the randomized intervention periods, whereas secondary analysis included the baseline.

Results

The ATP method was associated with a reduction in incidence rate of MDRO infection or colonization compared with the UV/F period (incidence rate ratio [IRR] 0.876; 95% confidence interval [CI], 0.807–0.951; P = .002). Including the baseline period, the ATP method was associated with reduced infection with MDROs (IRR 0.924; 95% CI, 0.855–0.998; P = .04), and MDR-GNB infection or colonization (IRR 0.856; 95% CI, 0.825–0.887; P < .001). The UV/F intervention was not associated with a statistically significant impact on these outcomes. Room turnaround time increased by a median of 1 minute with the ATP intervention and 4.5 minutes with UV/F compared with baseline.

Conclusions

Intensive monitoring of ICU terminal room cleaning with an ATP modality is associated with a reduction of MDRO infection and colonization.
Prolonged Shedding of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at High Viral Loads Among Hospitalized Immunocompromised Persons Living With Human Immunodeficiency Virus (HIV), South Africa
Authors: Meiring Susan , Tempia Stefano , Bhiman Jinal N , Buys Amelia , Kleynhans Jackie , Makhasi Mvuyo , McMorrow Meredith , Moyes Jocelyn , Quan Vanessa , Walaza Sibongile , du Plessis Mignon , Wolter Nicole , von Gottberg Anne , Cohen Cheryl ,   COVID-19 shedding study group, Black John , Goedhals Dominique , Maloba Bonnie , Potgieter Samantha , Black Marianne , Chibabhai Vindana , Mbenenge Nonhlanhla , Nana Trusha , Stacey Sarah , Treurnicht Florette , Moncho Masego , Nchabeleng Maphoshane , Shikwambane-Ntlemo Grace , Chomba Rispah , Nel Jeremy , Hoosen Anwar , Said Mohamed , Bayat Junaid , Sookan Lisha , Sirkar Surendra , Dawood Halima , Haffejee Sumayya , Pillay Somasundram , Ramjathan Praksha , Mvelase Nomonde , Mulla Javid , Lekalakala-Mokaba Ruth , Madua Matamela , Ntuli Sindile , Crede Thomas , Reddy Kessendri , Taljaard Jantjie , Whitelaw Andrew
Published: January 2022

Background

We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding duration and magnitude among persons living with human immunodeficiency virus (HIV, PLHIV).

Methods

From May through December 2020, we conducted a prospective cohort study at 20 hospitals in South Africa. Adults hospitalized with symptomatic coronavirus disease 2019 (COVID-19) were enrolled and followed every 2 days with nasopharyngeal/oropharyngeal (NP/OP) swabs until documentation of cessation of SARS-CoV-2 shedding (2 consecutive negative NP/OP swabs). Real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2 was performed, and cycle-threshold (Ct) values < 30 were considered a proxy for high SARS-CoV-2 viral load. Factors associated with prolonged shedding were assessed using accelerated time-failure Weibull regression models.

Results

Of 2175 COVID-19 patients screened, 300 were enrolled, and 257 individuals (155 HIV-uninfected and 102 PLHIV) had > 1 swabbing visit (median 5 visits [range 2–21]). Median time to cessation of shedding was 13 days (interquartile range [IQR] 6–25) and did not differ significantly by HIV infection. Among a subset of 94 patients (41 PLHIV and 53 HIV-uninfected) with initial respiratory sample Ct-value < 30, median time of shedding at high SARS-CoV-2 viral load was 8 days (IQR 4–17). This was significantly longer in PLHIV with CD4 count < 200 cells/µL, compared to HIV-uninfected persons (median 27 days [IQR 8–43] vs 7 days [IQR 4–13]; adjusted hazard ratio [aHR] 0.14, 95% confidence interval [CI] .07–.28, P < .001), as well as in unsuppressed-HIV versus HIV-uninfected persons.

Conclusions

Although SARS-CoV-2 shedding duration did not differ significantly by HIV infection, among a subset with high initial SARS-CoV-2 viral loads, immunocompromised PLHIV shed SARS-CoV-2 at high viral loads for longer than HIV-uninfected persons. Better HIV control may potentially decrease transmission time of SARS-CoV-2.
Dependent financialisation and its crisis: the case of Turkey
Authors: Akçay Ümit , Güngen Ali Rıza
Published: January 2022

Although the financialisation research agenda has developed rapidly, especially since the Great Recession, there are still some gaps in the literature regarding Emerging Capitalist Countries’ (ECCs) financialisation experiences. We argue that the concept of dependent financialisation applies more appropriately to ECCs, in line with a recently burgeoning heterodox literature on ECC financialisation. More specifically, we suggest that a critical rethinking of the Dependency School’s arguments in the light of the current uneven and combined financialisation experiences of ECCs will generate a better structured theoretical framework. To support this, we take Turkey’s financialisation experience and its 2018–19 crisis as a case study. We suggest that dependent financialisation in Turkey can be grasped in terms of the emergence of an economic structure with two specific characteristics: (i) it has structurally higher interest rates and a high dollarisation rate due to Turkey’s mode of integration into the hierarchical global financial system; (ii) economic activity increasingly depends on capital inflows, which make the country’s economy vulnerable to the negative effects of the monetary policy decisions of major central banks. Finally, we argue that recurrent crises are the manifestations of the limits of dependent financialisation, which generates an unsustainable mode of integration to the global economy.
Not in a Class of One’s Own: Social Origin Differentials in Applying to Gender-(A)Typical Fields of Study across the Educational Hierarchy
Authors: Prix Irene , Kilpi-Jakonen Elina
Published: January 2022

How and why does social origin matter for gender-segregated field of study choices? Analyses of gender-(a)typical educational interests have framed social origin differentials primarily through the lens of socialization, resting on the idea that children from socioeconomically advantaged families develop less gender-stereotypical interests via more egalitarian notions of gender roles. The social stratification literature, on the other hand, has discussed social gradients in field of study choice mainly from a perspective of social mobility and life chance risks, while remaining fairly detached from questions of gender segregation. Our aim in this article is to shed new light on how social inequality may be of consequence for gender-(a)typical interests in fields of study. Comparing register-based application patterns of a complete Finnish birth cohort (1989–1991) across three levels in the educational hierarchy, our results show that the same social origin may either lower or increase the probability of applying to gender-(a)typical fields, depending both on the educational level targeted and applicants’ gender. This context-dependency calls into question a strongly culturally framed interpretation of social origin gradients in gender-(a)typical interests. We conclude that social mobility prospects may align in a more nuanced and pragmatic way with gendered interests than previously suggested.
Endothelial cell-derived tetrahydrobiopterin prevents aortic valve calcification
Authors: Liu Zongtao , Dong Nianguo , Hui Haipeng , Wang Yixuan , Liu Fayun , Xu Li , Liu Ming , Rao Zhenqi , Yuan Zhen , Shang Yuqiang , Feng Jun , Cai Zhejun , Li Fei
Published: January 2022

Aims

Tetrahydrobiopterin (BH4) is a critical determinant of the biological function of endothelial nitric oxide synthase. The present study was to investigate the role of valvular endothelial cell (VEC)-derived BH4 in aortic valve calcification.

Methods and results

Plasma and aortic valve BH4 concentrations and the BH4:BH2 ratio were significantly lower in calcific aortic valve disease patients than in controls. There was a significant decrease of the two key enzymes of BH4 biosynthesis, guanosine 5′-triphosphate cyclohydrolase I (GCH1) and dihydrofolate reductase (DHFR), in calcified aortic valves compared with the normal ones. Endothelial cell-specific deficiency of Gch1 in Apoe  −/− (Apoe  −/−  Gch1  fl/fl  Tie2  Cre) mice showed a marked increase in transvalvular peak jet velocity, calcium deposition, runt-related transcription factor 2 (Runx2), dihydroethidium (DHE), and 3-nitrotyrosine (3-NT) levels in aortic valve leaflets compared with Apoe  −/−  Gch1  fl/fl mice after a 24-week western diet (WD) challenge. Oxidized LDL (ox-LDL) induced osteoblastic differentiation of valvular interstitial cells (VICs) co-cultured with either si-GCH1- or si-DHFR-transfected VECs, while the effects could be abolished by BH4 supplementation. Deficiency of BH4 in VECs caused peroxynitrite formation increase and 3-NT protein increase under ox-LDL stimulation in VICs. SIN-1, the peroxynitrite generator, significantly up-regulated alkaline phosphatase (ALP) and Runx2 expression in VICs via tyrosine nitration of dynamin-related protein 1 (DRP1) at Y628. Finally, folic acid (FA) significantly attenuated aortic valve calcification in WD-fed Apoe  −/− mice through increasing DHFR and salvaging BH4 biosynthesis.

Conclusion

The reduction in endothelial-dependent BH4 levels promoted peroxynitrite formation, which subsequently resulted in DRP1 tyrosine nitration and osteoblastic differentiation of VICs, thereby leading to aortic valve calcification. Supplementation of FA in diet attenuated hypercholesterolaemia-induced aortic valve calcification by salvaging BH4 bioavailability.
Long-term clinical impact of permanent pacemaker implantation in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis
Authors: Zito Andrea , Princi Giuseppe , Lombardi Marco , D’Amario Domenico , Vergallo Rocco , Aurigemma Cristina , Romagnoli Enrico , Pelargonio Gemma , Bruno Piergiorgio , Trani Carlo , Burzotta Francesco , Crea Filippo
Published: January 2022

Aims

The aims of this study is to assess by an updated meta-analysis the clinical outcomes related to permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) at long-term (≥12 months) follow-up (LTF).

Methods and results

A comprehensive literature research was performed on PubMed and EMBASE. The primary endpoint was all-cause death. Secondary endpoints were rehospitalization for heart failure, stroke, and myocardial infarction. A subgroup analysis was performed according to the Society of Thoracic Surgeon—Predicted Risk of Mortality (STS-PROM) score. This study is registered with PROSPERO (CRD42021243301). A total of 51 069 patients undergoing TAVI from 31 observational studies were included. The mean duration of follow-up was 22 months. At LTF, PPI post-TAVI was associated with a higher risk of all-cause death [risk ratio (RR) 1.18, 95% confidence interval (CI) 1.10–1.25; P < 0.001] and rehospitalization for heart failure (RR 1.32, 95% CI 1.13–1.52; P < 0.001). In contrast, the risks of stroke and myocardial infarction were not affected. Among the 20 studies that reported procedural risk, the association between PPI and all-cause death risk at LTF was statistically significant only in studies enrolling patients with high STS-PROM score (RR 1.25, 95% CI 1.12–1.40), although there was a similar tendency of the results in those at medium and low risk.

Conclusion

Patients necessitating PPI after TAVI have a higher long-term risk of all-cause death and rehospitalization for heart failure as compared to those who do not receive PPI.
Budget impact analysis of a machine learning algorithm to predict high risk of atrial fibrillation among primary care patients
Authors: Szymanski Tomasz , Ashton Rachel , Sekelj Sara , Petrungaro Bruno , Pollock Kevin G , Sandler Belinda , Lister Steven , Hill Nathan R , Farooqui Usman
Published: January 2022

Aims

We investigated whether the use of an atrial fibrillation (AF) risk prediction algorithm could improve AF detection compared with opportunistic screening in primary care and assessed the associated budget impact.

Methods and results

Eligible patients were registered with a general practice in UK, aged 65 years or older in 2018/19, and had complete data for weight, height, body mass index, and systolic and diastolic blood pressure recorded within 1 year. Three screening scenarios were assessed: (i) opportunistic screening and diagnosis (standard care); (ii) standard care replaced by the use of the algorithm; and (iii) combined use of standard care and the algorithm. The analysis considered a 3-year time horizon, and the budget impact for the National Health Service (NHS) costs alone or with personal social services (PSS) costs. Scenario 1 would identify 79 410 new AF cases (detection gap reduced by 22%). Scenario 2 would identify 70 916 (gap reduced by 19%) and Scenario 3 would identify 99 267 new cases (gap reduction 27%). These rates translate into 2639 strokes being prevented in Scenario 1, 2357 in Scenario 2, and 3299 in Scenario 3. The 3-year NHS budget impact of Scenario 1 would be £45.3 million, £3.6 million (difference ‒92.0%) with Scenario 2, and £46.3 million (difference 2.2%) in Scenario 3, but for NHS plus PSS would be ‒£48.8 million, ‒£80.4 million (64.8%), and ‒£71.3 million (46.1%), respectively.

Conclusion

Implementation of an AF risk prediction algorithm alongside standard opportunistic screening could close the AF detection gap and prevent strokes while substantially reducing NHS and PSS combined care costs.
LED color gradient as a new screening tool for rapid phenotyping of plant responses to light quality
Authors: Lejeune Pierre , Fratamico Anthony , Bouché Frédéric , Huerga-Fernández Samuel , Tocquin Pierre , Périlleux Claire
Published: January 2022

Background

The increasing demand for local food production is fueling high interest in the development of controlled environment agriculture. In particular, LED technology brings energy-saving advantages together with the possibility of manipulating plant phenotypes through light quality control. However, optimizing light quality is required for each cultivated plant and specific purpose.

Findings

This article shows that the combination of LED gradient set-ups with imaging-based non-destructive plant phenotyping constitutes an interesting new screening tool with the potential to improve speed, logistics, and information output. To validate this concept, an experiment was performed to evaluate the effects of a complete range of red:blue ratios on 7 plant species: Arabidopsis thaliana, Brachypodium distachyon, Euphorbia peplus, Ocimum basilicum, Oryza sativa, Solanum lycopersicum, and Setaria viridis. Plants were exposed during 30 days to the light gradient and showed significant, but species-dependent, responses in terms of dimension, shape, and color. A time-series analysis of phenotypic descriptors highlighted growth changes but also transient responses of plant shapes to the red:blue ratio.

Conclusion

This approach, which generated a large reusable dataset, can be adapted for addressing specific needs in crop production or fundamental questions in photobiology.
Effects of mindfulness-based stress reduction and an organizational health intervention on Dutch teachers’ mental health
Authors: Janssen Math , Heerkens Yvonne , Van der Heijden Beatrice , Korzilius Hubert , Peters Pascale , Engels Josephine
Published: January 2022

This study aimed to test the effectiveness of mindfulness-based stress reduction (MBSR) combined with an organizational health intervention. A cluster randomized controlled trial was conducted in five Dutch secondary vocational schools. Teachers were assigned to Intervention Group 1 (IG1; MBSR) or 2 (IG2; MBSR and an organizational health intervention), or to the Waiting List Group. The primary outcome variable was mindfulness. Secondary outcomes included other mental health outcomes, work performance, personal competencies, and work-related perceptions. Data was collected before (T0), immediately after (T1), and three (T2) and nine months (T3) after the MBSR training and analyzed applying repeated measures between-subjects designs. As the additional intervention showed no effects, IG1 and IG2 were merged (IG). MBSR had positive short-term effects on the total mindfulness score, its dimensions ‘observing’ and ‘non-reactivity’, and the work engagement dimension ‘dedication’. Long-term effects were found for the total mindfulness score, its dimensions ‘observing’, ‘non-reactivity’, and ‘non-judging’, sleep quality complaints, negative emotions, and negative work–home interaction. IG displayed a larger short- and long-term decrease in organizational commitment. No significant differences were found for work performance, personal competencies, and work-related perceptions. Although teachers did not perceive a decrease in job demands after the training, they felt more mindful and lowered their organizational commitment. Their mental health improved and their dedication during work increased. These findings may suggest that enhanced mindfulness enabled them to mentally disengage from work during their leisure time, which allowed them to experience fewer symptoms of psychological strain. The trail is registered with the Dutch Trial Register (www.trialregister.nl): NL5581 (July 2016).
The prevalence, risk of premature births, mortality and causes of death of cleft lip with or without palate in South Korea: a nationwide population-based cohort study
Authors: Ryu Jeong Yeop , Park Tae Hyun , Cho Byung Chae , Choi Kang Young
Published: January 2022

Background

Very few recent nationwide studies have assessed the epidemiology of cleft lip with or without palate (CL/P). The purpose of this study was to identify the prevalence, risk of premature births, mortality and cause of death of CL/P.

Methods

This nationwide population-based cohort study evaluated all 5 747 830 live births in South Korea, including CL/P infants, from 2006 to 2018. The prevalence with trend analysis, risk of premature births, mortality and cause of death of CL/P with or without associated syndromes (non-syndromic, syndromic CL/P) and subgroups (cleft lip only, cleft palate only, cleft lip with palate) were evaluated.

Results

Among 5 747 830 live births, 11 284 children were identified as having CL/P during the study period. The annual prevalence was 1.96 per 1000 births. The prevalence ratio, which shows the trend during the period, was 1.021. Both non-syndromic and syndromic CL/P children had higher risk of premature births compared with children without CL/P (odds ratio: non-syndromic 1.43, syndromic 5.29). The mortality rates per 1000 person-years were 0.39 for children without CL/P, 0.98 for non-syndromic CL/P children and 12.20 for syndromic CL/P children. The causes of deaths were not different for children without CL/P in non-syndromic CL/P, but the most common cause of deaths was cardiovascular anomalies in syndromic CL/P.

Conclusion

The reported prevalence of 1.96 per 1000 births is one of the highest prevalences worldwide. CL/P children had high risks of premature births and risk of mortality. The most common cause of deaths was cardiovascular anomalies.
Inverse DEA-R models for merger analysis with negative data
Authors: Soltanifar Mehdi , Ghiyasi Mojtaba , Sharafi Hamid
Published: January 2022

Data envelopment analysis (DEA) is a mathematical programming technique for efficiency analysis. For dealing with the data in ratio form, the DEA model for ratio data known as DEA-R exists in the literature. However, some ratio data like financial risk may be negative naturally. In this paper, we contribute to the literature in two ways. In the first place, we deal with DEA-R models in the presence of negative ratio data by proposing an inverse DEA model for merger analysis. In the second place, we develop DEA-R models for merger analysis that can deal with negative data. We apply our models in a real-world application of efficiency and merger analysis of an Iranian bank with 66 branches. The proposed models maintain data confidentiality. This motivates managers to participate in the evaluation and merger process. Our models also provide a reasonable endogenous weight restriction framework without restricting weights exogenously.
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes
Authors: Tatovic D , McAteer M A , Barry J , Barrientos A , Rodríguez Terradillos K , Perera I , Kochba E , Levin Y , Dul M , Coulman S A , Birchall J C , von Ruhland C , Howell A , Stenson R , Alhadj Ali M , Luzio S D , Dunseath G , Cheung W Y , Holland G , May K , Ingram J R , Chowdhury M M U , Wong F S , Casas R , Dayan C , Ludvigsson J
Published: January 2022

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies
Association of Hyperferritinemia With Distinct Host Response Aberrations in Patients With Community-Acquired Pneumonia
Authors: Brands Xanthe , van Engelen Tjitske S R , de Vries Floris M C , Haak Bastiaan W , Klarenbeek Augustijn M , Kanglie Maadrika M N P , van den Berk Inge A H , Schuurman Alex R , Peters-Sengers Hessel , Otto Natasja A , Faber Daniël R , Lutter René , Scicluna Brendon P , Stoker Jaap , Prins Jan M , Joost Wiersinga W , van der Poll Tom
Published: January 2022

Background

Strongly elevated ferritin levels have been proposed to reflect systemic hyperinflammation in patients admitted to the intensive care unit. Knowledge of the incidence and pathophysiological implications of hyperferritinemia in patients with acute infection admitted to a non–intensive care setting is limited.

Methods

We determined the association between hyperferritinemia, defined by 2 cutoff values (500 and 250 ng/mL), and aberrations in key host response mechanisms among patients with community-acquired pneumonia (CAP) on admission to a general hospital ward (clinicaltrials.gov NCT02928367; trialregister.nl NTR6163).

Results

Plasma ferritin levels were higher in patients with CAP (n = 174; median [interquartile ranges], 259.5 [123.1–518.3] ng/mL) than in age- and sex-matched controls without infection (n = 50; 102.8 [53.5–185.7] ng/mL); P < .001); they were ≥500 ng/mL in 46 patients (26%) and ≥250 ng/mL in 90 (52%). Measurements of 26 biomarkers reflective of distinct pathophysiological domains showed that hyperferritinemia was associated with enhanced systemic inflammation, neutrophil activation, cytokine release, endothelial cell activation and dysfunction, and activation of the coagulation system. Results were robust across different cutoff values.

Conclusions

Hyperferritinemia identifies patients with CAP with a broad deregulation of various host response mechanisms implicated in the pathogenesis of sepsis. This could inform future therapeutic strategies targeting subgroups within the CAP population.
Dengue Virus Ribonucleic Acid Detection Rates in Blood Donors Correlate With Local Infection Incidences During a Dengue Outbreak in Taiwan
Authors: Chen Yun-Yuan , Lu Chi-Te , Tsai Mei-Hua , Yang Cheng-Fen , Shu Pei-Yun , Wu Chia-Wen , Chen Jen-Wei , Hung Chi-Ming , Wei Sheng-Tang , Hou Sheng-Mou , Chen Pei-Jer
Published: January 2022

Background

Evidence for mitigation of transfusion-transmitted dengue informed by surveillance data is lacking. In this study, we evaluated the risk of positive dengue viral (DENV) ribonucleic acid (RNA) from blood transfusions during a large outbreak in Taiwan.

Methods

Serum collected from blood donors living in districts experiencing the dengue epidemic were tested for DENV RNA using a qualitative transcription-mediated nucleic acid amplification assay (TMA). The TMA-reactive specimens were further tested for immunoglobulin (Ig)M and IgG antibodies, nonstructural protein 1 (NS1) antigen, and viral RNA by reverse-transcription polymerase chain reaction. We estimated DENV RNA prevalence and the number of DENV infections among blood donors.

Results

A total of 4976 specimens were tested for DENV RNA, and 21 were TMA-reactive. The detection rate was 0.84 (95% confidence interval [CI], 0.15–4.73), 3.36 (95% CI, 1.31–8.60), and 6.19 (95% CI, 3.14–12.17) per 1000 donors in districts where the weekly dengue incidence was 5–50, 50–200, and 200 or more per 100 000 residents, respectively. Alanine aminotransferase screening only detected 4.4% of TMA-reactive donations. A total of 143 transfusion-transmitted DENV infections probably occurred during this outbreak, accounting for 9.2 in 10 000 dengue infections.

Conclusions

Approximately 0.5%–1% of blood donations were DENV RNA positive in epidemic districts. The correlation of DENV RNA rates with dengue incidence may inform the design of effective control measures.
Can Urbanisation Improve Household Welfare? Evidence From Ethiopia
Authors: Abay Kibrom A , Tiberti Luca , Woldemichael Andinet , Mezgebo Tsega G , Endale Meron
Published: January 2022

Despite evolving evidence that Africa is experiencing urbanisation in a different way, empirical evaluations of the welfare implications of urban-development programs in Africa remain scant. We investigate the welfare implications of recent urbanisation processes in Ethiopia using household-level longitudinal data and satellite-based nightlight intensity. We also examine the impact of urban growth on the composition of household consumption and welfare. We employ temporal and spatial variations in nightlight intensity to capture urban expansion and growth. Controlling for time-invariant unobserved heterogeneity across individuals and localities, we find that urbanisation, as measured by nightlight intensity, is associated with significant welfare improvement. We find that tripling existing average nightlight intensity in a village is associated with a 42–46% improvement in household welfare. Urbanisation is also associated with a significant increase in the share of non-food consumption, which is a good measure of overall welfare and poverty. In addition, we find significant heterogeneity in urban expansion across major towns and small towns. Urban expansion in rural areas and small towns appears more impactful than similar expansion in major cities. Finally, quantile regression results suggest that better-off households are likely to benefit more from urban expansion, which may translate into higher inequality across households or communities. Our results can inform public policy debates on the consequences and implications of urban expansion in Africa.
Abusive pricing practices by online platforms: a framework review of Article 102 TFEU for future cases
Authors: Mandrescu Daniel
Published: January 2022

The challenges involved in the application of Article 102 TFEU to online platforms have become the main topic of debate in the context of EU competition policy in digital markets. This debate has recently also extended to the topic of platform pricing with the complaints about the pricing strategies of Apple with respect to its App Store and it is a matter of time before similar complaints will follow with respect to other prominent platforms. Applying the current framework of price related abuses under Article 102 TFEU to the pricing practices of online platforms will, however, require adapting the respective legal tests of abuse to the commercial reality of these actors. Doing so will inevitably entail accounting for their multisided nature which would sometimes require that the assessments of abuse extend to more than one side of the platform. Furthermore, such legal assessments would also have to consider the special role played by platform pricing as a coordination tool for getting multiple types of customer groups on board with the aim of facilitating profitable interactions between them. Therefore, this article seeks to explore how the current frameworks for price-related abuses could be applied and, if needed, adapted so as to fit the commercial reality of online platforms. The aim of this effort is to provide guidance for ongoing and future cases so as to prevent legitimate pricing practices from being erroneously scrutinized as well as to prevent anti-competitive pricing practices from escaping legal scrutiny due to the intricacies of platform pricing schemes.
Evaluation of MALDI-TOF MS for Identification of Species in the Candida parapsilosis Complex from Candidiasis Cases
Authors: Samantaray Subhashree , Singh Rakesh
Published: January 2022

Background

Phenotypically identified Candida parapsilosis is actually a complex of 3 member species named Candida parapsilosis sensu stricto (CPSS), Candida orthopsilosis (CO), and Candida metapsilosis (CM), which can be identified only by molecular methods and automated methods such as MALDI-TOF mass spectrometry (MS). This study was undertaken to evaluate the VITEK MS, which uses the principle of MALDI-TOF MS for the identification of member species of C. parapsilosis complex (CPC).

Methods

In this cross-sectional study, 126 presumptively identified and stocked isolates of CPC were included. Definite identification to species level was done by VITEK MS and PCR as the gold standard method. Clinico-demographic characters and risk factors were analyzed. Antifungal susceptibility testing was performed for fluconazole and voriconazole.

Results

Twelve isolates were not identified as CPC either by VITEK MS or PCR and hence were excluded from the analysis. Out of 114 CPC isolates, 89 (78.1%), 18 (15.8%), and 7 (6.1%) isolates were identified as CPSS, CO, and CM, respectively, by VITEK MS. PCR identified 84 (79.2%), 15 (14.2%), and 7 (6.6%) isolates as CPSS, CO, and CM, respectively. However, PCR did not detect 8 isolates of CPSS detected by VITEK MS. VITEK MS showed 95.3% agreement in species identification and showed a kappa coefficient of 0.87, which is almost perfect agreement. Predominant isolations of all 3 species were from blood. Resistance was observed more in CPSS for both the azoles.

Conclusion

MALDI-TOF MS can be used as a rapid, reliable, cost-effective method to identify the species of CPC.
A framework for employing longitudinally collected multicenter electronic health records to stratify heterogeneous patient populations on disease history
Authors: Maurits Marc P , Korsunsky Ilya , Raychaudhuri Soumya , Murphy Shawn N , Smoller Jordan W , Weiss Scott T , Petukhova Lynn M , Weng Chunhua , Wei Wei-Qi , Huizinga Thomas W J , Reinders Marcel J T , Karlson Elizabeth W , van den Akker Erik B , Knevel Rachel
Published: January 2022

Objective

To facilitate patient disease subset and risk factor identification by constructing a pipeline which is generalizable, provides easily interpretable results, and allows replication by overcoming electronic health records (EHRs) batch effects.

Material and Methods

We used 1872 billing codes in EHRs of 102 880 patients from 12 healthcare systems. Using tools borrowed from single-cell omics, we mitigated center-specific batch effects and performed clustering to identify patients with highly similar medical history patterns across the various centers. Our visualization method (PheSpec) depicts the phenotypic profile of clusters, applies a novel filtering of noninformative codes (Ranked Scope Pervasion), and indicates the most distinguishing features.

Results

We observed 114 clinically meaningful profiles, for example, linking prostate hyperplasia with cancer and diabetes with cardiovascular problems and grouping pediatric developmental disorders. Our framework identified disease subsets, exemplified by 6 “other headache” clusters, where phenotypic profiles suggested different underlying mechanisms: migraine, convulsion, injury, eye problems, joint pain, and pituitary gland disorders. Phenotypic patterns replicated well, with high correlations of ≥0.75 to an average of 6 (2–8) of the 12 different cohorts, demonstrating the consistency with which our method discovers disease history profiles.

Discussion

Costly clinical research ventures should be based on solid hypotheses. We repurpose methods from single-cell omics to build these hypotheses from observational EHR data, distilling useful information from complex data.

Conclusion

We establish a generalizable pipeline for the identification and replication of clinically meaningful (sub)phenotypes from widely available high-dimensional billing codes. This approach overcomes datatype problems and produces comprehensive visualizations of validation-ready phenotypes.
Will Apple devices’ passive atrial fibrillation detection prevent strokes? Estimating the proportion of high-risk actionable patients with real-world user data
Authors: Feldman Keith , Duncan Ray G , Nguyen An , Cook-Wiens Galen , Elad Yaron , Nuckols Teryl , Pevnick Joshua M
Published: January 2022

Objective

Utilizing integrated electronic health record (EHR) and consumer-grade wearable device data, we sought to provide real-world estimates for the proportion of wearers that would likely benefit from anticoagulation if an atrial fibrillation (AFib) diagnosis was made based on wearable device data.

Materials and Methods

This study utilized EHR and Apple Watch data from an observational cohort of 1802 patients at Cedars-Sinai Medical Center who linked devices to the EHR between April 25, 2015 and November 16, 2018. Using these data, we estimated the number of high-risk patients who would be actionable for anticoagulation based on (1) medical history, (2) Apple Watch wear patterns, and (3) AFib risk, as determined by an existing validated model.

Results

Based on the characteristics of this cohort, a mean of 0.25% (n = 4.58, 95% CI, 2.0–8.0) of patients would be candidates for new anticoagulation based on AFib identified by their Apple Watch. Using EHR data alone, we find that only approximately 36% of the 1802 patients (n = 665.93, 95% CI, 626.0–706.0) would have anticoagulation recommended even after a new AFib diagnosis.

Discussion and Conclusion

These data suggest that there is limited benefit to detect and treat AFib with anticoagulation among this cohort, but that accessing clinical and demographic data from the EHR could help target devices to the patients with the highest potential for benefit. Future research may analyze this relationship at other sites and among other wearable users, including among those who have not linked devices to their EHR.
Chatbot use cases in the Covid-19 public health response
Authors: Amiri Parham , Karahanna Elena
Published: January 2022

Objective

To identify chatbot use cases deployed for public health response activities during the Covid-19 pandemic.

Material and Methods

We searched PubMed/MEDLINE, Web of Knowledge, and Google Scholar in October 2020 and performed a follow-up search in July 2021. We screened articles based on their abstracts and keywords in their text, reviewed potentially relevant articles, and screened their references to (a) assess whether the article met inclusion criteria and (b) identify additional articles. Chatbots, their use cases, and chatbot design characteristics were extracted from the articles and information from other sources and by accessing those chatbots that were publicly accessible.

Results

Our search returned 3334 articles, 61 articles met our inclusion criteria, and 61 chatbots deployed in 30 countries were identified. We categorized chatbots based on their public health response use case(s) and design. Six categories of public health response use cases emerged comprising 15 distinct use cases: risk assessment, information dissemination, surveillance, post-Covid eligibility screening, distributed coordination, and vaccine scheduler. Design-wise, chatbots were relatively simple, implemented using decision-tree structures and predetermined response options, and focused on a narrow set of simple tasks, presumably due to need for quick deployment.

Conclusion

Chatbots’ scalability, wide accessibility, ease of use, and fast information dissemination provide complementary functionality that augments public health workers in public health response activities, addressing capacity constraints, social distancing requirements, and misinformation. Additional use cases, more sophisticated chatbot designs, and opportunities for synergies in chatbot development should be explored.
Nomos and Narrative in International Criminal Justice
Authors: Gissel Line Engbo
Published: January 2022

This article grounds contemporary contestations over the International Criminal Court (ICC) in the constitutive moment of the 1990s, when the Court was a global idea that took shape around a set of key concepts and related understandings of world order. It studies the positions communicated by 129 states during the negotiations of ICC establishment, applying Robert Cover’s narrative law and its pluralist notion of legal meaning to a systematic content analysis. Contrary to the founding ‘epic’ of ICC creation, which centres on the Like-Minded Group and its Others, the analysis identifies two competing and fairly coherent visions for the ICC: A compulsory and a consensual vision. Both aim to build an effective and independent Court, but understand these terms differently and consequently envisage different ICC regimes. The consensual vision has rarely been analysed, but is typically portrayed as the scattered ideas of an undecided majority. Given the Court’s profound lack of universality, however, it is useful to revisit the ideas that animated a large share of international society.
Advanced Visualization of Intrusions in Flows by Means of Beta-Hebbian Learning
Authors: Quintián Héctor , Jove Esteban , Casteleiro-Roca José-Luis , Urda Daniel , Arroyo Ángel , Luis Calvo-Rolle José , Herrero Álvaro , Corchado Emilio
Published: January 2022

Detecting intrusions in large networks is a highly demanding task. In order to reduce the computation demand of analysing every single packet travelling along one of such networks, some years ago flows were proposed as a way of summarizing traffic information. Very few research works have addressed intrusion detection in flows from a visualizations perspective. In order to bridge this gap, the present paper proposes the application of a novel projection method (Beta Hebbian Learning) under this framework. With the aim to validate this method, 8 traffic segments, containing many flows, have been analysed by means of this projection method. The promising results obtained for these segments, extracted from the University of Twente dataset, validate the proposed application.
Investigating growth models with linearization domain analysis and residual analysis
Authors: Marek Jaroslav , Pozdílková Alena , Kupka Libor
Published: January 2022

Growth modelling is of interest to scientists in various disciplines. In our article, we will collect 17 models designed for growth modelling, appraise these models and contribute to the discussion of their applicability. The merit of the paper lies in studying the convergence properties of nonlinear regression in selected models. Our studies will be performed mainly concerning the quality of the obtained estimates, which are closely related to the intrinsic curvature of the model according to Bates and Watts. This curvature determines the size of the linearization domains. Only if the initial solution is in this domain, then the convergence of the estimate in nonlinear regression is guaranteed. The primary goal is to design a methodology for selecting a growth model. We will demonstrate fruitfulness of our methodology on the weight measurements of 10 calves under 25 months of age from cowsheds in the village Záluží in the Czech Republic. Estimated parameters of growth curves, sizes of linearization domain, calculated residues and coefficients of determination indices will be the subject of discussion.