bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reunification and Re-entry to Care: An Analysis of the National Datasets for Children Looked after in England
Authors: Goldacre Allie , Hood Rick , Jones Ed , King Adam , Wang Chao 
Published: April 2022

Abstract
This article reports on a quantitative study of the national datasets for children in state care in England. The aim of the study was to investigate the likelihood of re-entry to care for children who returned home to their parents or main carers after an episode of care. An anonymised extract of case-level information on all children who received an episode of care between 2014 and 2020 (n = 51,238) was assembled from local authority (LA) administrative data held by the UK government. Cox regression models were used to calculate the cumulative probability of re-entry to care over time and identify the factors associated with a higher or lower probability. The findings showed that one in five children re-entered care after one year and over a third of children re-entered care after six years. A number of factors affected the probability of re-entering care, including age, ethnicity, care history, placement type and whether provision was LA, voluntary or private sector. Implications are discussed for planning and design of services to support reunification from care, and for the broader goal of reducing the number of children looked after by the state.
TMEM63C mutations cause mitochondrial morphology defects and underlie hereditary spastic paraplegia
Authors: Tábara Luis Carlos , Al-Salmi Fatema , Maroofian Reza , Al-Futaisi Amna Mohammed , Al-Murshedi Fathiya , Kennedy Joanna , Day Jacob O , Courtin Thomas , Al-Khayat Aisha , Galedari Hamid , Mazaheri Neda , Protasoni Margherita , Johnson Mark , Leslie Joseph S , Salter Claire G , Rawlins Lettie E , Fasham James , Al-Maawali Almundher , Voutsina Nikol , Charles Perrine , Harrold Laura , Keren Boris , Kunji Edmund R S , Vona Barbara , Jelodar Gholamreza , Sedaghat Alireza , Shariati Gholamreza , Houlden Henry , Crosby Andrew H , Prudent Julien , Baple Emma L 
Published: April 2022

AbstractThe hereditary spastic paraplegias (HSP) are among the most genetically diverse of all Mendelian disorders. They comprise a large group of neurodegenerative diseases that may be divided into ‘pure HSP’ in forms of the disease primarily entailing progressive lower-limb weakness and spasticity, and ‘complex HSP’ when these features are accompanied by other neurological (or non-neurological) clinical signs. Here, we identified biallelic variants in the transmembrane protein 63C (TMEM63C) gene, encoding a predicted osmosensitive calcium-permeable cation channel, in individuals with hereditary spastic paraplegias associated with mild intellectual disability in some, but not all cases. Biochemical and microscopy analyses revealed that TMEM63C is an endoplasmic reticulum-localized protein, which is particularly enriched at mitochondria–endoplasmic reticulum contact sites. Functional in cellula studies indicate a role for TMEM63C in regulating both endoplasmic reticulum and mitochondrial morphologies. Together, these findings identify autosomal recessive TMEM63C variants as a cause of pure and complex HSP and add to the growing evidence of a fundamental pathomolecular role of perturbed mitochondrial-endoplasmic reticulum dynamics in motor neurone degenerative diseases.
Non-severe burn injury increases cancer incidence in mice and has long-term impacts on the activation and function of T cells
Authors: Barrett Lucy W , Fear Vanessa S , Foley Bree , Audsley Katherine , Barnes Samantha , Newnes Hannah , McDonnell Alison , Wood Fiona M , Fear Mark W , Waithman Jason 
Published: April 2022

Abstract

Background
Recent evidence suggests that burn patients are at increased risk of hospital admission for infection, mental health conditions, cardiovascular disease and cancer for many years after discharge for the burn injury itself. Burn injury has also been shown to induce sustained immune system dysfunction. This change to immune function may contribute to the increased risk of chronic disease observed. However, the mechanisms that disrupt long-term immune function in response to burn trauma, and their link to long-term morbidity, remain unknown. In this study we investigated changes to immune function after burn injury using a murine model of non-severe injury.

Methods
An established mouse model of non-severe burn injury (full thickness burn equivalent to 8% total body surface area) was used in combination with an orthotopic model of B16 melanoma to investigate the link between burns and cancer. Considering that CD8+ T cells are important drivers of effective tumour suppression in this model, we also investigated potential dysregulation of this immune population using mouse models of burn injury in combination with herpes simplex virus infection. Flow cytometry was used to detect and quantify cell populations of interest and changes in immune function.

Results
We demonstrate that 4 weeks after a non-severe burn injury, mice were significantly more susceptible to tumour development than controls using an orthotopic model of B16 melanoma. In addition, our results reveal that CD8+ T cell expansion, differentiation and memory potential is significantly impaired at 1 month post-burn.

Conclusions
Our data suggests that CD8+ T cell-mediated immunity may be dysfunctional for a sustained period after even non-severe burn injury. Further studies in patients to validate these findings may support clinical intervention to restore or protect immunity in patients after burn injury and reduce the increased risk of secondary morbidities observed.
Organization and engagement of a prefrontal-olfactory network during olfactory selective attention
Authors: Cansler Hillary L , in ’t Zandt Estelle E , Carlson Kaitlin S , Khan Waseh T , Ma Minghong , Wesson Daniel W 
Published: April 2022

AbstractBackgroundSensory perception is profoundly shaped by attention. Attending to an odor strongly regulates if and how it is perceived – yet the brain systems involved in this process are unknown. Here we report integration of the medial prefrontal cortex (mPFC), a collection of brain regions integral to attention, with the olfactory system in the context of selective attention to odors.MethodsFirst, we used tracing methods to establish the tubular striatum (TuS, also known as the olfactory tubercle) as the primary olfactory region to receive direct mPFC input in rats. Next, we recorded (i) local field potentials from the olfactory bulb (OB), mPFC, and TuS, or (ii) sniffing, while rats completed an olfactory selective attention task.ResultsGamma power and coupling of gamma oscillations with theta phase were consistently high as rats flexibly switched their attention to odors. Beta and theta synchrony between mPFC and olfactory regions were elevated as rats switched their attention to odors. Finally, we found that sniffing was consistent despite shifting attentional demands, suggesting that the mPFC-OB theta coherence is independent of changes in active sampling.ConclusionsTogether, these findings begin to define an olfactory attention network wherein mPFC activity, as well as that within olfactory regions, are coordinated based upon attentional states.
Adolescent social isolation shifts the balance of decision-making strategy from goal-directed action to habitual response in adulthood via suppressing the excitatory neurotransmission onto the direct pathway of the dorsomedial striatum
Authors: Shan Qiang , Yu Xiaoxuan , Tian Yao 
Published: April 2022

AbstractAdverse experience, such as social isolation, during adolescence is one of the major causes of neuropsychiatric disorders that extend from adolescence into adulthood, such as substance addiction, obsessive–compulsive disorder, and eating disorders leading to obesity. A common behavioral feature of these neuropsychiatric disorders is a shift in the balance of decision-making strategy from goal-directed action to habitual response. This study has verified that adolescent social isolation directly shifts the balance of decision-making strategy from goal-directed action to habitual response, and that it cannot be reversed by simple regrouping. This study has further revealed that adolescent social isolation induces a suppression in the excitatory neurotransmission onto the direct-pathway medium spiny neurons of the dorsomedial striatum (DMS), and that chemogenetically compensating this suppression effect shifts the balance of decision-making strategy from habitual response back to goal-directed action. These findings suggest that the plasticity in the DMS causes the shift in the balance of decision-making strategy, which would potentially help to develop a general therapy to treat the various neuropsychiatric disorders caused by adolescent social isolation. Such a study is especially necessary under the circumstances that social distancing and lockdown have caused during times of world-wide, society-wide pandemic.
Resolving heterogeneity in obsessive–compulsive disorder through individualized differential structural covariance network analysis
Authors: Han Shaoqiang , Xu Yinhuan , Guo Hui-Rong , Fang Keke , Wei Yarui , Liu Liang , Cheng Junying , Zhang Yong , Cheng Jingliang 
Published: April 2022

AbstractBackgroundThe high heterogeneity of obsessive–compulsive disorder (OCD) denies attempts of traditional case–control studies to derive neuroimaging biomarkers indicative of precision diagnosis and treatment.MethodsTo handle the heterogeneity, we uncovered subject-level altered structural covariance by adopting individualized differential structural covariance network (IDSCN) analysis. The IDSCN measures how structural covariance edges in a patient deviated from those in matched healthy controls (HCs) yielding subject-level differential edges. One hundred patients with OCD and 106 HCs were recruited and whose T1-weighted anatomical images were acquired. We obtained individualized differential edges and then clustered patients into subtypes based on these edges.ResultsPatients presented tremendously low overlapped altered edges while frequently shared altered edges within subcortical–cerebellum network. Two robust neuroanatomical subtypes were identified. Subtype 1 presented distributed altered edges while subtype 2 presented decreased edges between default mode network and motor network compared with HCs. Altered edges in subtype 1 predicted the total Yale-Brown Obsessive Compulsive Scale score while that in subtype 2 could not.ConclusionsWe depict individualized structural covariance aberrance and identify that altered connections within subcortical–cerebellum network are shared by most patients with OCD. These 2 subtypes provide new insights into taxonomy and facilitate potential clues to precision diagnosis and treatment of OCD.
Activity-dependent feedback regulation of thalamocortical axon development by Lhx2 in cortical layer 4 neurons
Authors: Wang Chia-Fang , Yang Jenq-Wei , Zhuang Zi-Hui , Hsing Hsiang-Wei , Luhmann Heiko J , Chou Shen-Ju 
Published: April 2022

AbstractEstablishing neuronal circuits requires interactions between pre- and postsynaptic neurons. While presynaptic neurons were shown to play instructive roles for the postsynaptic neurons, how postsynaptic neurons provide feedback to regulate the presynaptic neuronal development remains elusive. To elucidate the mechanisms for circuit formation, we study the development of barrel cortex (the primary sensory cortex, S1), whose development is instructed by presynaptic thalamocortical axons (TCAs). In the first postnatal weeks, TCA terminals arborize in layer (L) 4 to fill in the barrel center, but it is unclear how TCA development is regulated. Here, we reported that the deletion of Lhx2 specifically in the cortical neurons in the conditional knockout (cKO) leads to TCA arborization defects, which is accompanied with deficits in sensory-evoked and spontaneous cortical activities and impaired lesion-induced plasticity following early whisker follicle ablation. Reintroducing Lhx2 back in L4 neurons in cKO ameliorated TCA arborization and plasticity defects. By manipulating L4 neuronal activity, we further demonstrated that Lhx2 induces TCA arborization via an activity-dependent mechanism. Additionally, we identified the extracellular signaling protein Sema7a as an activity-dependent downstream target of Lhx2 in regulating TCA branching. Thus, we discovered a bottom-up feedback mechanism for the L4 neurons to regulate TCA development.
Effectiveness of Messenger RNA Coronavirus Disease 2019 Vaccines Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Delta Variant Epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS)
Authors: Maeda Haruka , Saito Nobuo , Igarashi Ataru , Ishida Masayuki , Suami Kazuya , Yagiuchi Ai , Kimura Yuya , Komino Masaru , Arai Hiromi , Morikawa Toru , Motohashi Iori , Miyazawa Rei , Moriyama Tetsu , Kamura Hiroshi , Terada Mayumi , Kuwamitsu Osamu , Hayakawa Tomoichiro , Sando Eiichiro , Ohara Yasuji , Teshigahara Osamu , Suzuki Motoi , Morimoto Konosuke 
Published: April 2022

Abstract

Background
Although high vaccine effectiveness of messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines has been reported in studies in several countries, data are limited from Asian countries, especially against the Delta (B.1.617.2) variant.

Methods
We conducted a multicenter test-negative case-control study in patients aged ≥16 years visiting hospitals or clinics with signs or symptoms consistent with COVID-19 from 1 July to 30 September 2021, when the Delta variant was dominant (≥90% of SARS-CoV-2 infections) nationwide in Japan. Vaccine effectiveness of BNT162b2 or mRNA-1273 against symptomatic SARS-CoV-2 infections was evaluated. Waning immunity among patients aged 16–64 years was also assessed.

Results
We enrolled 1936 patients, including 396 test-positive cases and 1540 test-negative controls for SARS-CoV-2. The median age was 49 years, 53.4% were male, and 34.0% had underlying medical conditions. Full vaccination (receiving 2 doses ≥14 days before symptom onset) was received by 6.6% of cases and 38.8% of controls. Vaccine effectiveness of full vaccination against symptomatic SARS-CoV-2 infections was 88.7% (95% confidence interval [CI], 78.8%–93.9%) among patients aged 16–64 years and 90.3% (95% CI, 73.6%–96.4%) among patients aged ≥65 years. Among patients aged 16–64 years, vaccine effectiveness was 91.8% (95% CI, 80.3%–96.6%) within 1–3 months after full vaccination, and 86.4% (95% CI, 56.9%–95.7%) within 4–6 months.

Conclusions
mRNA COVID-19 vaccines had high effectiveness against symptomatic SARS-CoV-2 infections in Japan during July–September 2021, when the Delta variant was dominant nationwide.
Financialisation of monetary policy in a dollarised economy: the case of Georgia
Authors: Eradze Ia 
Published: April 2022

Abstract
This paper examines the financialisation of monetary policy—articulated as inflation targeting—and provides insight on the implications this phenomenon has on dollarised economies. The analysis provided has been developed via a thorough investigation into these dynamics in the country of Georgia: a neoliberal and foreign direct investment (FDI)-led accumulation regime with an open capital account, where the inflow of foreign capital led to enhanced lending by foreign-owned banks in foreign currency and encouraged persistent dollarisation. This paper contributes to the literature on the role of foreign capital in developing economies, and the volatilities of these economies in terms of overvalued exchange rates, capital flight and rise of public debt. This paper concludes that the financialisation of monetary policy has encouraged the process of dollarisation in Georgia. The use of inflation targeting was an ineffective strategy for Georgia’s dollarised economy due to the primacy of price stability over currency stability, the reduction of the capacity of Georgia’s central bank as well as increased economic influence of foreign-owned commercial banks.
Is the China Effect Real? Ideational Change and the Political Contestation of Chinese State-Led Investment in Europe
Authors: Babić Milan , Dixon Adam D 
Published: April 2022

Abstract
Chinese outward investment is increasing in its relevance for the global economy, and its effects on host states are increasingly being scrutinized globally. While European policy-making was ambiguous about the question of hosting Chinese state-led investment (CSLI) in the early 2010s, we can observe a recent surge of protectionist legal measures across Europe. What explains this trend among different European countries? Through the lens of incremental ideational change, we hypothesize that the rise of China as a global investor shifts the perceptions of policy-makers away from being a source of investment toward a potential threat to national security. We argue that this China effect affects advanced European economies similarly. We provide evidence by studying the shift in perceptions among policy-makers in a coordinated and a liberal market economy, Germany and the UK. By drawing on document analysis and expert interviews, we unpack the policy processes in both countries in the last decade. Despite being two dissimilar cases, both show a similar outcome in increasingly curbing CSLI on the grounds of national security reasons. Our results add important insights to recent International Political Economy discussions on the “geopoliticization” of European trade and investment rules in the face of a rising China.
Diagnostic Performance of Metagenomic Next-Generation Sequencing in Pediatric Patients: A Retrospective Study in a Large Children’s Medical Center
Authors: Tao Yue , Yan Hui , Liu Yujie , Zhang Fang , Luo Lijuan , Zhou Yajuan , An Kang , Yang Ruwen , Yang Bin , Xu Teng , Xie Li , Ren Hong , Xu Zhuoming , Cao Qing , Mo Xi 
Published: April 2022

Abstract

Background
Metagenomic next-generation sequencing (mNGS) has the potential to become a complementary, if not essential, test in some clinical settings. However, the clinical application of mNGS in a large population of children with various types of infectious diseases (IDs) has not been previously evaluated.

Methods
From April 2019 to April 2021, 640 samples were collected at a single pediatric hospital and classified as ID [479 (74.8%)], non-ID [NID; 156 (24.4%)], and unknown cases [5 (0.8%)], according to the final clinical diagnosis. We compared the diagnostic performance in pathogen detection between mNGS and standard reference tests.

Results
According to final clinical diagnosis, the sensitivity and specificity of mNGS were 75.0% (95% CI: 70.8%–79.2%) and 59.0% (95% CI: 51.3%–66.7%), respectively. For distinguishing ID from NID, the sensitivity of mNGS was approximately 45.0% higher than that of standard tests (75.0% vs 30.0%; P &lt; 0.001). For fungal detection, mNGS showed positive results in 93.0% of cases, compared to 43.7% for standard tests (P &lt; 0.001). Diagnostic information was increased in respiratory system samples through the addition of meta-transcriptomic sequencing. Further analysis also showed that the read counts in sequencing data were highly correlated with clinical diagnosis, regardless of whether infection was by single or multiple pathogens (Kendall’s tau b = 0.484, P &lt; 0.001).

Conclusions
For pediatric patients in critical condition with suspected infection, mNGS tests can provide valuable diagnostic information to resolve negative or inconclusive routine test results, differentiate ID from NID cases, and facilitate accurate and effective clinical therapeutic decision-making.
Dutch National Round Robin Trial on Plasma-Derived Circulating Cell-Free DNA Extraction Methods Routinely Used in Clinical Pathology for Molecular Tumor Profiling
Authors: van der Leest Paul , Ketelaar Emma M , van Noesel Carel J M , van den Broek Daan , van Boerdonk Robert A A , Deiman Birgit , Rifaela Naomi , van der Geize Robert , Huijsmans Cornelis J J , Speel Ernst Jan M , Geerlings Maartje J , van Schaik Ron H N , Jansen Maurice P H M , Dane-Vogelaar Ria , Driehuis Else , Leers Mathie P G , Sidorenkov Grigory , Tamminga Menno , van Kempen Léon C , Schuuring Ed 
Published: April 2022

Abstract

Background
Efficient recovery of circulating tumor DNA (ctDNA) depends on the quantity and quality of circulating cell-free DNA (ccfDNA). Here, we evaluated whether various ccfDNA extraction methods routinely applied in Dutch laboratories affect ccfDNA yield, ccfDNA integrity, and mutant ctDNA detection, using identical lung cancer patient–derived plasma samples.

Methods
Aliquots of 4 high-volume diagnostic leukapheresis plasma samples and one artificial reference plasma sample with predetermined tumor-derived mutations were distributed among 14 Dutch laboratories. Extractions of ccfDNA were performed according to local routine standard operating procedures and were analyzed at a central reference laboratory for mutant detection and assessment of ccfDNA quantity and integrity.

Results
Mutant molecule levels in extracted ccfDNA samples varied considerably between laboratories, but there was no indication of consistent above or below average performance. Compared to silica membrane–based methods, samples extracted with magnetic beads–based kits revealed an overall lower total ccfDNA yield (−29%; P &lt; 0.0001) and recovered fewer mutant molecules (−41%; P &lt; 0.01). The variant allelic frequency and sample integrity were similar. In samples with a higher-than-average total ccfDNA yield, an augmented recovery of mutant molecules was observed.

Conclusions
In the Netherlands, we encountered diversity in preanalytical workflows with potential consequences on mutant ctDNA detection in clinical practice. Silica membrane–based methodologies resulted in the highest total ccfDNA yield and are therefore preferred to detect low copy numbers of relevant mutations. Harmonization of the extraction workflow for accurate quantification and sensitive detection is required to prevent introduction of technical divergence in the preanalytical phase and reduce interlaboratory discrepancies.
Improvement of MADRL Equilibrium Based on Pareto Optimization
Authors: Zhao Zhiruo , Cao Lei , Chen Xiliang , Lai Jun , Zhang Legui 
Published: April 2022

Abstract
In order to solve the incalculability caused by the issue of inconsistent objective functions in multi-agent deep reinforcement learning, the concept of Nash equilibrium is introduced. However, a Marko game may have multiple equilibriums, how to filter out a stable and optimal one is worth studying. Besides solution concept, how to keep the balance between exploration and exploitation is another key issue in reinforcement learning. On basis of the methods, which can converge to Nash equilibrium, this paper makes improvement through Pareto optimization. In order to alleviate the problem of over fitting caused by Pareto optimization and non-convergence caused by strategy change, we use stratified sampling in place of random sampling as assistance. What’s more, our methods are trained through fictitious self-play to make full of self-learning experiences. By analyzing the experiment carried out on MAgent platform, the proposed methods are not only far better than traditional methods, but also reaching or even surpassing the state of art MADRL methods.