bluuebunny/crossref_metadata_2025 huggingface dataset:
Dimensionality of genomic information and its impact on GWA and variant selection: a simulation study
Authors: Jang Sungbong , Tsuruta Shogo , Leite Natalia Galoro , Misztal Ignacy , Lourenco Daniela
Published: April 2022

Background

Identifying true-positive variants in genome-wide associations (GWA) depends on several factors, including the number of genotyped individuals. The limited dimensionality of the genomic information may give insights into the optimal number of individuals to use in GWA. This study investigated different discovery set sizes in GWA based on the number of largest eigenvalues explaining a certain proportion of variance in the genomic relationship matrix (G). An additional investigation included the change in accuracy by adding variants, selected based on different set sizes, to the regular SNP chips used for genomic prediction.

Methods

Sequence data were simulated containing 500k SNP with 200 or 2000 quantitative trait nucleotides (QTN). A regular 50k panel included one every ten simulated SNP. Effective population size (Ne) was 20 and 200. The GWA was performed with the number of genotyped animals equivalent to the number of largest eigenvalues ofG(EIG) explaining 50, 60, 70, 80, 90, 95, 98, and 99% of the variance. In addition, the largest discovery set consisted of 30k genotyped animals. Limited or extensive phenotypic information was mimicked by changing the trait heritability. Significant and high effect size SNP were added to the 50k panel and used for single-step GBLUP with and without weights.

Results

Using the number of genotyped animals corresponding to at least EIG98 enabled the identification of QTN with the largest effect sizes whenNewas large. Smaller populations required more than EIG98. Furthermore, using genotyped animals with higher reliability (i.e., higher trait heritability) helped better identify the most informative QTN. The greatest prediction accuracy was obtained when the significant or the high effect SNP representing twice the number of simulated QTN were added to the 50k panel. Weighting SNP differently did not increase prediction accuracy, mainly because of the size of the genotyped population.

Conclusions

Accurately identifying causative variants from sequence data depends on the effective population size and, therefore, the dimensionality of genomic information. This dimensionality can help identify the suitable sample size for GWA and could be considered for variant selection. Even when variants are accurately identified, their inclusion in prediction models has limited implications.
Synaptic wiring motifs in posterior parietal cortex support decision-making
Authors: Kuan Aaron T. , Bondanelli Giulio , Driscoll Laura N. , Han Julie , Kim Minsu , Hildebrand David G. C. , Graham Brett J. , Thomas Logan A. , Panzeri Stefano , Harvey Christopher D. , Lee Wei-Chung A.
Published: April 2022

The posterior parietal cortex (PPC) exhibits choice-selective activity during perceptual decision-making tasks. However, it is not known how this selective activity arises from the underlying synaptic connectivity. Here, we combined virtual reality behavior, two-photon calcium imaging, high throughput electron microscopy, and circuit modeling to analyze how synaptic connectivity between neurons in PPC relates to their selective activity. We found that excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity. In turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif. Using circuit models, we show that opponent inhibition amplifies selective inputs and induces competition between neural populations with opposite selectivity, thereby improving the encoding of trial-type information. These results provide evidence for how synaptic connectivity in cortical circuits supports a learned decision-making task.
A hybrid unsupervised approach for accurate short read clustering and barcoded sample demultiplexing in nanopore sequencing
Authors: Han Renmin , Qi Junhai , Xue Yang , Sun Xiujuan , Zhang Fa , Gao Xin , Li Guojun
Published: April 2022

Short nucleic acid sequences are usually attached as DNA barcodes for multiple sample sequencing and single cell protocols, which enables Oxford Nanopore sequencing to sequence multiple barcoded DNA samples on a single flow cell. However, due to the high base-calling error, short reads in Nanopore sequencing are difficult to be accurately identified by traditional tools. Here, we propose a hybrid unsupervised approach for the accurate clustering of short reads and demultiplexing of barcoded samples in Nanopore sequencing. In our approach, both the nucleic base information translated from base-calling and the raw current signal directly outputted by the flow cell are utilized. A GPU-supported parallelization strategy is proposed to ensure the runtime of our hybrid clustering. Comprehensive experiments demonstrate that our approach outperforms all the traditional unsupervised tools in short read clustering, and achieves comparable accuracy in barcoded sample demultiplexing compared with the learning-based methods.
The broad shell colour variation in common cockle (Cerastoderma edule) from Northeast Atlantic relies on a major QTL revealed by GWAS using a new high-density genetic map
Authors: Hermida Miguel , Robledo Diego , Díaz Seila , Costas Damián , Bruzos Alicia L. , Blanco Andrés ,   The Cockle’s Consortium, Martínez Paulino
Published: April 2022

Shell colour pattern shows broad diversity in molluscs, and both genetic and environmental factors seem to interact to some extent on the final phenotype. Despite information on the genetic component and pathways involved in shell construction and colour has increased in the last decade, more data are needed particularly to understand colour variation and its putative role on adaptation. The European common cockle (Cerastoderma edule) is a valuable species from ecological and commercial perspectives with important variation in colour pattern, but this diversity has never been characterized and the underlying genetic architecture is unknown. In this study, we constructed a high-density genetic map, as an essential tool for genomic screening in common cockle, that was applied to ascertain the genetic basis of colour pattern variation in the species. The consensus map, including 13,874 2b-RAD SNPs, was constituted by the 19 linkage groups (LGs) corresponding to the n = 19 chromosomes of its karyotype and spanned 1,073 cM (730 markers per LG; inter-marker distance of 0.13 cM). Five full-sib families showing segregation for several colour-associated traits were used to perform a GWAS analysis. A major QTL on chromosome 13 explained most of the variation for shell colour patterns. Mining on this genomic region revealed the presence of several candidate genes enriched on Gene Ontology terms such as anatomical structure development, ion transport, membrane transport and cell periphery, closely related to shell architecture, including six chitin-related, one ependymin, several ion binding and transporters, and others related to transit across the cell membrane. Interestingly, this major QTL overlaps with a genomic region previously reported associated with divergent selection in the distribution range of the species, suggesting a putative role on local adaptation.
Heterogeneity in the gene regulatory landscape of leiomyosarcoma
Authors: Belova Tatiana , Biondi Nicola , Hsieh Ping-Han , Lutsik Pavlo , Chudasama Priya , Kuijjer Marieke L.
Published: April 2022

Soft-tissue sarcomas are group of rare, tremendously heterogeneous, and highly aggressive malignancies. Characterizing inter-tumor heterogeneity is crucial for selecting suitable sarcoma therapy, as the presence of diverse molecular subgroups of patients can be associated with disease outcome or response to treatment. While cancer subtypes are often characterized by differences in gene expression, the mechanisms that drive these differences are generally unknown. We therefore set out to model the regulatory mechanisms driving sarcoma heterogeneity. We subtyped soft-tissue sarcomas based on patient-specific, genome-wide gene regulatory networks and found pronounced regulatory heterogeneity in leiomyosarcoma—one of the most common soft-tissue sarcomas subtypes that arises in smooth muscle tissue. To characterize this regulatory heterogeneity, we developed a new computational framework. This method, PORCUPINE, combines knowledge on biological pathways with permutation-based network analysis to identify pathways that exhibit significant regulatory heterogeneity across a patient population. We applied PORCUPINE to patient-specific leiomyosarcoma networks modeled on data from The Cancer Genome Atlas and validated our results in an independent dataset from the German Cancer Research Center. PORCUPINE identified 37 heterogeneously regulated pathways, including pathways that represent potential targets for treatment of subgroups of leiomyosarcoma patients, such as FGFR and CTLA4 inhibitory signaling. We validated the detected regulatory heterogeneity through analysis of networks and chromatin states in leiomyosarcoma cell lines. In addition, we showed that the heterogeneity identified with PORCUPINE is not associated with methylation profiles or clinical features, thereby suggesting an independent mechanism of patient heterogeneity driven by the complex landscape of gene regulatory interactions.
Development of novel temporal beta-diversity indices for assessing community compositional shifts accounting for changes in the properties of individuals
Authors: Nakadai Ryosuke
Published: April 2022

Revealing the patterns of temporal biodiversity changes and deciphering the connection between individual life histories and large-scale ecological patterns is essential for improving the mechanistic understanding of macroecology. However, this is challenging because the relationship between individual life history and biodiversity remains unclear. In the present study, in order to link the individual life history and community-level phenomena, I developed novel indices that allow the evaluation of community compositional shifts over time by explicitly considering the contributions of the life histories of individuals (i.e. growth, mortality, and recruitment) in a community. These novel indices are quantitative extensions of the individual-based temporal beta-diversity indices which can include information on individual sizes. The indices were applied to a subset of data from the US Forest Inventory and Analysis database for the state of Rhode Island, USA, to identify changes in the contribution of individual life histories to biodiversity change. The results of this study represent methodological progress in community ecology and macroecology, as well as a conceptual advancement in bridging studies on biodiversity with those on individual life history and physiology. The individual-based diversity indices developed here pave the way for individual-based biodiversity science, which may facilitate the understanding of the effects of climate change across different hierarchies of biological organisation.
Anti-inflammatory therapy with nebulised dornase alfa for severe COVID-19 pneumonia
Authors: Porter Joanna C. , Inshaw Jamie , Solis Vincente Joel , Denneny Emma , Evans Rebecca , Temkin Mia I. , De Vasconcelos Nathalia , Aramburu Iker Valle , Hoving Dennis , Basire Donna , Crissell Tracey , Guinto Jesusa , Webb Alison , Esmail Hanif , Johnston Victoria , Last Anna , Rampling Thomas , Helbig Elisa Theresa , Lippert Lena , Kurth Florian , Williams Bryan , Flynn Aiden , Lukey Pauline T , Birault Veronique , Papayannopoulos Venizelos
Published: April 2022

Background

Cell-free (cf)-DNA, from cellular sources, including Neutrophil Extracellular Traps (NETs), is found in the circulation of COVID-19 patients and may contribute to immune dysregulation. This study determined whether pulmonary administration of the endonuclease, dornase alfa, reduced systemic inflammation by degrading local and systemic cf-DNA.

Methods

Eligible patients were randomized (3:1) to receive twice-daily nebulised dornase alfa in addition to best available care (BAC) or BAC alone for seven days or until discharge. A 2:1 ratio of matched contemporary controls (CC-BAC) provided additional comparators. The primary endpoint was improvement in C-reactive protein (CRP) over time, analysed using a repeated-measures mixed model, adjusted for baseline factors.

Results

Between June 2020-October 2021 we recruited 39 evaluable patients: 30 randomised to dornase alfa (R-BAC+DA); 9 randomised to BAC (R-BAC); with the addition of 60 CC-BAC participants. Dornase alfa was well tolerated and reduced CRP by 33% compared to combined BAC groups (T-BAC). Least squares (LS) mean post-dexamethasone CRP fell from 101.9mg/L to 23.23 mg/L in the BAC+ dornase alfa group versus a fall from 99.5mg/L to 34.82 mg/L in the T-BAC group at 7 days; P=0.01. This effect of dornase alfa on CRP was confirmed with subgroup and sensitivity analyses that mitigated potential biases associated with the use of the CC-BAC group. Dornase alfa increased the chance of live discharge by 63% (HR 1.63, 95% CI 1.01 to 2.61, P=0.03), increased lymphocyte counts (LS mean: 1.08 vs 0.87, P=0.02) and reduced circulating cf-DNA and the coagulopathy marker D-dimer (LS mean: 570.78 vs 1656.96 μg/mL, P=0.004).

Conclusion

We provide proof-of-concept evidence that dornase alfa reduces pathogenic inflammation in hospitalised patients with COVID-19 pneumonia, suggesting that best available care can be improved by the inclusion of anti-inflammatory treatments that target damage-associated molecules.
Social vulnerability and disasters: development and evaluation of a CONVERGE training module for researchers and practitioners
Authors: Adams Rachel Marie , Evans Candace , Wolkin Amy , Thomas Tracy , Peek Lori
Published: April 2022

Purpose

Social vulnerability in the context of disaster management refers to the sociodemographic characteristics of a population and the physical, social, economic, and environmental factors that increase their susceptibility to adverse disaster outcomes and capacity to anticipate, cope with, resist, and recover from disaster events. Because disasters do not impact people equally, researchers, public health practitioners, and emergency managers need training to meet the complex needs of vulnerable populations.

Design/methodology/approach

To address gaps in current education, the CONVERGE initiative, headquartered at the Natural Hazards Center at the University of Colorado Boulder, developed the Social Vulnerability and Disasters Training Module. This free online course draws on decades of research to examine the factors that influence social vulnerability to disasters. Examples of studies and evidence-based programs are included to illuminate common methods for studying social vulnerability and ways that research can guide practice. To evaluate the module, all trainees completed a pre- and post-training questionnaire.

Findings

Between July 2019 and September 2021, 1,089 people completed the module. Wilcoxon signed rank tests demonstrated a significant perceived increase in self-rated knowledge, skills, and attitudes (KSA). Students, members of historically underrepresented populations, and those new to or less experienced in the field, had the greatest perceived increase.

Practical implications

This training module can help participants understand the specific needs of socially vulnerable populations to help reduce human suffering from disasters.

Originality/value

This article describes a novel web-based training and offers evaluation data showing how it can help educate a broad hazards and disaster workforce on an important topic for disaster management.
Utility optimization-based multi-stakeholder personalized recommendation system
Authors: Shrivastava Rahul , Sisodia Dilip Singh , Nagwani Naresh Kumar
Published: April 2022

Purpose

In a multi-stakeholder recommender system (MSRS), stakeholders are the multiple entities (consumer, producer, system, etc.) benefited by the generated recommendations. Traditionally, the exclusive focus on only a single stakeholders' (for example, only consumer or end-user) preferences obscured the welfare of the others. Two major challenges are encountered while incorporating the multiple stakeholders' perspectives in MSRS: designing a dedicated utility function for each stakeholder and optimizing their utility without hurting others. This paper proposes multiple utility functions for different stakeholders and optimizes these functions for generating balanced, personalized recommendations for each stakeholder.

Design/methodology/approach

The proposed methodology considers four valid stakeholders user, producer, cast and recommender system from the multi-stakeholder recommender setting and builds dedicated utility functions. The utility function for users incorporates enhanced side-information-based similarity computation for utility count. Similarly, to improve the utility gain, the authors design new utility functions for producer, star-cast and system to incorporate long-tail and diverse items in the recommendation list. Next, to balance the utility gain and generate the trade-off recommendation solution, the authors perform the evolutionary optimization of the conflicting utility functions using NSGA-II. Experimental evaluation and comparison are conducted over three benchmark data sets.

Findings

The authors observed 19.70% of average enhancement in utility gain with improved mean precision, diversity and novelty. Exposure, hit, reach and target reach metrics are substantially improved.

Originality/value

A new approach considers four stakeholders simultaneously with their respective utility functions and establishes the trade-off recommendation solution between conflicting utilities of the stakeholders.
Whether, how and why home country environments influence emerging market firm acquisition behavior
Authors: Reddy Rama Krishna , Fabian Frances , Park Sung-Jin
Published: April 2022

Purpose

According to the 2019 World Investment Report, recent events in deglobalization have made many countries, especially developed markets, resist inward foreign direct investment (FDI) as ceding control to foreign countries. At the same time, many emerging market firms (EMFs) have been increasing their acquisitions in developed markets. The authors elaborate three unconventional motives that justify such acquisitions, and test whether conditions in home countries related to these motives predict the pursuit of greater or lesser equity control. Understanding how home country conditions may spur seeking greater equity control can help policymakers and business firm decision-makers improve these dynamics.

Design/methodology/approach

Examining data covering the period 2006–2018, the authors test hypotheses using a sample of 4,130 acquisitions by EMFs into developed markets, and test hypotheses to investigate “How does the institutional and resource environment of an EMF's home country relate to the respective EMF acquisition behavior of seeking equity control?”

Findings

The authors found that higher institutional quality, poorer factor market development, and higher capital market quality in the home country are related to higher equity positions sought.

Practical implications

Acquiring and target firm managers, along with other stakeholders, can gain insights on how to respond to acquisition opportunities by recognizing how home country conditions influence emerging market internationalizing behaviors into developed markets.

Originality/value

The compilation of this data uniquely covers 48 different emerging markets and further concentrates on the relatively less understood pre-deal phase for EMNEs entering developed markets.
Personality effects on WoM and eWoM susceptibilty – a cross-country perspective
Authors: König Tatjana M. , Clarke Theresa B. , Hellenthal Maria , Clarke III Irvine
Published: April 2022

Purpose

This study utilizes social communication theory as the framework to examine the influence of personality on young word-of-mouth (WoM) and electronic word-of-mouth (eWoM) audiences across the US, France and Germany and explores relationships between personality traits and cultural dimensions.

Design/methodology/approach

An adaptation of the consumer susceptibility to interpersonal influence (CSII) scale measured WoM influence in an online review context. After pretesting and validating the consumer susceptibility to online review influence (CSRI) scale in Luxemburg, hypotheses were tested, and research questions were explored in a multi-group structural equation model based on French, German and US samples.

Findings

Personality traits are negatively linked to CSRI as well as to CSII across the three countries. Overall, the stronger the personality traits, the weaker the online and offline WoM influence seems. In contrast to France, results for the US and Germany show that young people are either more susceptible to WoM or to eWoM influence. Results imply tendencies for a potential interaction effect between power distance and openness to new experience on WoM and partially on eWoM.

Practical implications

Earned media is more effective among audiences with weaker personality structures. Stronger personalities may prefer to serve as senders of WoM and eWoM (influencers). The non-uniform results between WoM and eWoM susceptibility across the countries favor earned media strategies optimized on a country basis and psychological targeting when communicating online review results.

Originality/value

This study expands knowledge of individual (personality traits) and country similarities and differences across France, Germany and the US and how they affect earned media (WoM and eWoM) influence.
Establishing a blockchain online travel agency with a human–computer interaction perspective
Authors: Su Kuo-Wei , Chiu Po-Chih , Lin Tzu-Hsiang
Published: April 2022

Purpose

This study aims to incorporate innovative technology (i.e. blockchain) into the design of an online travel agency (B-OTA). The authors accelerated the design of the prototype system through expert interviews to understand the convenience of the blockchain travel and accommodation platform for users. The authors further validated the prototype system design and improved reference capability through usability testing.

Design/methodology/approach

Rapid prototyping of B-OTA was carried out through the Delphi method and literature compilation. Design validation of usability testing was conducted using modified systematic evaluation methodology. Prototype system suggestions and improvements were collected through feedback from test subjects.

Findings

This study will be helpful for the development of B-OTAs and related technologies. Through usability testing, the authors verified that creating a familiar operating environment for users can reduce users’ fear of unfamiliar technology. The results of this research provide future B-OTA researchers and practitioners with design guidelines.

Originality/value

Beyond the blockchain-related technologies used, few studies have reported experiences and interface design of B-OTAs. This study states that, as many human–computer interaction-related papers have pointed out, the basic prerequisite for successful interface design is a clearer definition of users’ needs during operation. User experience and user interface design should provide a good user experience.
Subsidiary strategic influence: the role of subsidiary attention-building activities
Authors: Gorgijevski Alexander N. , Holmström Lind Christine , Lagerström Katarina
Published: April 2022

Purpose

By the view of attention-building activities as “tools of power,” the authors investigate the impact of subsidiary involvement in attention-building activities on the strategic influence of subsidiaries within multinational corporations (MNCs).

Design/methodology/approach

The study is based on survey data from 110 international subsidiaries located in Sweden. Five hypotheses were tested using structural equation modeling with linear structural relations.

Findings

The study shows that organizational commitment and external scouting activities, as two attention-building activities, do not directly affect the ability of subsidiaries to gain a strategic influence in MNCs. Rather, the results provide support for the importance of headquarters’ positive attention as a mediator between such activities and subsidiary strategic influence. This implies that subsidiaries do not receive any strategic influence through these activities unless they receive explicit positive attention from the corporate headquarters.

Originality/value

This study contributes to the micro-political view of the MNC by offering insights into the impact of attention-building activities of subsidiaries as a potential source of strategic influence for MNC subsidiaries.
Flipped classroom goes sideways: reflections on active learning methodologies
Authors: Leão Pablo , Coelho Caio , Campana Carla , Viotto Marina Henriques
Published: April 2022

Purpose

The present study aims to investigate an unsuccessful implementation of an active learning methodology. Active learning methods have emerged in order to improve learning processes and increase students' roles in the classroom. Most studies on the subject focus on developing learning strategies based on successful implementations of such methods. Nevertheless, critical reflections on unsuccessful cases might also provide material for developing further contributions to this literature.

Design/methodology/approach

The authors conducted an intrinsic case study of an unsuccessful application of the flipped classroom method to an undergraduate basic statistics course at a Brazilian business school. The data collected comprised the course's syllabus, evaluation forms and two rounds of interviews with students and the professor.

Findings

The findings indicate that, apart from that which had been mapped by past literature, three additional aspects may limit the chances of successfully implementing a flipped classroom methodology: students' educational backgrounds, the course's structural issues and methodological and relational issues.

Originality/value

The present study contributes to the literature on active learning methodologies mainly by mapping additional aspects that should be considered in the implementation of the flipped classroom methodology. Additionally, the authors investigate an unsuccessful case of such an implementation, an investigation that is still scant within this literature.
De‐migration‐based supervised learning for interpolation and regularization of 3D offset classes
Authors: Hlebnikov Volodya , Greiner Thomas Andre Larsen , Vinje Vetle , Lie Jan Erik , Poole Gordon
Published: April 2022

Regularization and interpolation of 3D offset classes prior to imaging are an important and challenging step in the marine seismic data processing flow. Here we describe how to perform this task using a deep neural network, and we explain how to overcome the challenge of creating a suitable training data set. The training data set is generated by de‐migrating stacked pre‐stack depth migration images. For each offset class volume, we de‐migrate the pre‐stack depth migrated stacked image into two configurations: (i) the original survey configuration consisting of the recorded source/receiver positions and (ii) an ‘Ideal’ survey configuration with constant offset and azimuth for each 3D offset class. The training creates a 3D convolutional encoder–decoder model that will regularize and interpolate seismic data. The convolutional encoder–decoder is trained on 3D sliding windows in each 3D offset cube to map from (i) to (ii), i.e. to map the original survey configuration with irregular and sparse sampling into the fully sampled regular offset cubes suitable for offset‐based migration, such as Kirchhoff migration. Such migration algorithms rely on regular and sufficiently dense sampling to achieve constructive interference to image the structures and destructive interference to suppress migration noise. We test the new method on one synthetic and one field data example and show that it performs better than a standard regularization/interpolation method based on anti‐leakage Fourier transform, especially for the smallest offset classes. On the synthetic data, we also demonstrate that the convolutional encoder–decoder method preserves the amplitude versus offset as well as the standard method.
Does preventive dental care reduce nonpreventive dental visits and expenditures among Medicaid‐enrolled adults?
Authors: Taylor Heather L. , Sen Bisakha , Holmes Ann M. , Schleyer Titus , Menachemi Nir , Blackburn Justin
Published: April 2022

Objective

To determine whether preventive dental visits are associated with fewer subsequent nonpreventive dental visits and lower dental expenditures.

Data Sources

Indiana Medicaid enrollment and claims data (2015–2018) and the Area Health Resource File.

Study Design

A repeated measures design with individual and year fixed effects examining the relationship between preventive dental visits (PDVs) and nonpreventive dental visits (NPVs) and dental expenditures.

Data Collection/Extraction Methods

Not applicable.

Principal Findings

Of 28,152 adults (108,349 observation‐years) meeting inclusion criteria, 36.0% had a dental visit, 27.8% a PDV, and 22.1% a NPV. Compared to no PDV in the prior year, at least one was associated with fewer NPVs (β = −0.13; 95% CI –0.12, −0.11), lower NPV expenditures (β = −$29.12.53; 95% CI –28.07, −21.05), and lower total dental expenditures (−$70.12; 95% –74.92, −65.31), as well as fewer PDVs (β = −0.24; 95% CI –0.26, −0.23).

Conclusions

Our findings suggest that prior year PDVs are associated with fewer subsequent NPVs and lower dental expenditures among Medicaid‐enrolled adults. Thus, from a public insurance program standpoint, supporting preventive dental care use may translate into improved population oral health outcomes and lower dental costs among certain low‐income adult populations, but barriers to consistent utilization of PDV prohibit definitive findings.
‘It Takes Two to Tango’: South–South Cooperation Measurement Politics in a Multiplex World
Authors: Trajber Waisbich Laura
Published: April 2022

This paper examines whether and how the imperatives of measuring Official Development Assistance (ODA; or development aid) are being translated to the policy world of South–South cooperation (SSC). Through a historical and political ethnographic account of a decade of global policy debates on Southern‐led development cooperation between 2009 and 2019, the paper argues that growing conversations on ‘SSC effectiveness’, and how to measure it, reflect both prevalent ‘measurementalities’ in the field as well as ‘traditional/Northern donor countries’ continuous will to socialise and integrate ‘(re)‐emerging Southern providers’ into existing aid norms and practices. The paper also demonstrates Southern powerhouses'—such as Brazil, China, and India—agency in these accountability‐related debates and their will to integrate differently into the ‘aid system’ by proposing alternative tools to measure SSC flows and initiatives in their own terms. Finally, the paper argues that unfolding negotiations over quantifying, reporting, and evaluating Southern‐led development cooperation reflect the politicised consolidation of SSC in the second decade of the 21st century. Current impasses at the multilateral level, moreover, reveal unsolved North–South disputes over power, status, and responsibility in international development and international affairs, more broadly.
Ex‐gay activism and the reification of sexual identity in law
Authors: McIvor Méadhbh
Published: April 2022

The increasing visibility of sexualities beyond heterosexual, gay/lesbian, and bisexual is often associated with progressive politics and the questioning of heteronormativity. Yet non‐majoritarian sexualities can also include self‐identifications premised upon an opposition to LGBTQ+ equality and inclusion, including those who identify as “ex‐gay.” Drawing on fieldwork with evangelical Christian activists in London, UK, this paper uses a court case in which the “legality” of ex‐gay sexuality was contested to discuss the law's simultaneous desire and inability to render contested identities legally legible. In seeking recognition as a sexual minority, self‐described ex‐gay evangelicals reveal the inadequacy of modern law's efforts to regulate difference as either “innate” or “chosen,” thus upsetting the terms of the hetero‐secular legal gaze even as they embrace heterosexual supremacy. As such, this activism, which is typically analyzed in terms of evangelicalism's commitment to heteronormativity, works to denaturalize the concept of sexual orientation(s)—including, I argue, the heterosexuality ex‐gay Christians pursue.
Acetyl‐L‐carnitine improves erectile function in bilateral cavernous nerve injury rats via promoting cavernous nerve regeneration
Authors: Wang Jiaxin , Song Jingyu , Song Guoda , Feng Yuhong , Pan Jiancheng , Yang Xiaoqing , Xin Zhongcheng , Hu Peng , Sun Taotao , Liu Kang , Xu Wenchao , Wang Tao , Wang Shaogang , Liu Jihong , Ruan Yajun
Published: April 2022

Background

Neurogenic erectile dysfunction (NED) caused by cavernous nerve (CN) injury is a typical complication after pelvic surgery, which lacks efficient treatments. Acetyl‐L‐carnitine (ALCAR) has been proven to promote nerve repair.

Objectives

To investigate the effect and potential mechanism of ALCAR in the treatment of NED.

Materials and methods

Thirty‐two rats were randomly divided into bilateral CN injury (BCNI) group, BCNI + lower‐dose ALCAR (50 mg/kg/day) group, BCNI + higher‐dose (100 mg/kg/day) group, and sham‐operated group. Erectile function was assessed 14 days after daily intraperitoneal injection of ALCAR or placebo. The penile tissues were gathered for subsequent histological and molecular biological analysis. Rat Schwann cell (SC) line S16 was used to verify the mechanism of ALCAR in vitro.

Results

We found that the erectile function of the rats in the BCNI group was severely impaired, which was improved considerably in both BCNI+ALCAR‐LD and BCNI+ALCAR‐HD groups. Also, we observed decreased smooth muscle and increased collagen content in the corpus cavernosum in the BCNI group. The expressions of fibrosis markers transforming growth factor‐beta (TGF‐β), connective tissue growth factor (CTGF), and Smad 2/3 were significantly up‐regulated in the BCNI group. The above changes were alleviated after the administration of lower and higher‐dose ALCAR. Meanwhile, the nitric oxide (NO)/cyclic guanosine monophosphate pathway (cGMP) was promoted and the Ras homolog gene family member A (RhoA)/Rho‐associated protein kinase (ROCK) pathway was inhibited in the corpus cavernosum of BCNI rats after ALCAR treatment, accompanied by increased neuronal nitric oxide synthase (nNOS) and down‐regulated tyrosine hydroxylase (TH). In vitro, ALCAR promoted the migration and proliferation of SC and increased the expression of 22‐kD peripheral myelin protein and nerve growth factor (NGF). Further, rats treated with ALCAR had high expression of ATF3 and S100 in the distal nerve tissues of the CN extrusion site.

Discussion and conclusion

ALCAR could promote nerve repair and regeneration, inhibit penile fibrosis, and improve penile erection by promoting the proliferation and migration of SC and the secretion of NGF. Our study confirms that ALCAR may be a potential treatment strategy for NED.
Impact of pre‐emptive rapid testing for glucose‐6‐phosphate dehydrogenase deficiency prior to rasburicase administration at a tertiary care centre: A retrospective study
Authors: Ganapathi Mythily , Campbell Peter , Ofori Kenneth , Aggarwal Vimla , Francis Richard O. , Kratz Alexander
Published: April 2022

Aims

Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy in humans, can cause acute haemolysis resulting from exposure to certain medications, chemicals, infections and fava beans. Rasburicase, used to manage elevated uric acid levels in the oncologic emergency of tumour lysis syndrome, is one such drug. The US Food and Drug Administration (FDA) recommends testing of G6PD status prior to rasburicase administration for patients at higher risk for G6PD deficiency.

Methods

We performed a retrospective chart review of all oncology patients for whom a semi‐quantitative biochemical test for detecting G6PD deficiency was performed prior to rasburicase administration over a 2.5‐year period, in a large academic metropolitan hospital.

Results

We identified 16 out of 260 tested individuals as G6PD‐deficient (6.1%), including six females. On average, test results were electronically available to health care providers within 4 hours of sample collection, with most results available within 2–3 hours. Four G6PD‐deficient patients developed elevated uric acid levels. Two of the G6PD‐deficient patients were treated with rasburicase, and subsequently developed haemolysis, which was appropriately managed.

Conclusion

In summary, by providing information about G6PD status with a rapid turnaround time, we have taken a significant step towards personalized medicine in our institution. In spite of the test implementation, two out of four G6PD‐deficient patients, who were no longer candidates for rasburicase use, still received the drug, highlighting the need for improved provider education.
Identification of clinical factors related to antibody‐mediated immune response to the subfornical organ
Authors: Nakamura‐Utsunomiya Akari , Goda Satoshi , Hayakawa Seiichi , Sonoko Sakata , Hoorn Ewout J. , Blanchard Anne , Saito‐Hakoda Akiko , Kakimoto Haruna , Hachiya Rumi , Kamimura Miki , Kawakita Rie , Higuchi Shinji , Fujimaru Rika , Shirai Yoko , Miyaoka Daichi , Nagata Yuki , Kishi Yutaro , Wada Aya , Mitsuboshi Akari , Ozaki Kayo , Komatsu Nagisa , Niizuma Hidetaka , Kanno Junko , Fujiwara Ikuma , Hasegawa Yukihiro , Yorifuji Tohru , Brickman Wendy , Vantyghem Marie‐Christine , Yamaguchi Kei , Goshima Naoki , Hiyama Takeshi Y.
Published: April 2022

Objective

We recently reported cases of adipsic hypernatremia caused by autoantibodies against the subfornical organ in patients with hypothalamic‐pituitary lesions. This study aimed to clarify the clinical features of newly identified patients with adipsic hypernatremia whose sera displayed immunoreactivity to the mouse subfornical organ.

Design

Observational cohort study of patients diagnosed with adipsic hypernatremia in Japan, United States, and Europe.

Methods

The study included 22 patients with adipsic hypernatremia but without overt structural changes in the hypothalamic‐pituitary region and congenital disease. Antibody response to the mouse subfornical organ was determined using immunohistochemistry. The clinical characteristics were compared between the patients with positive and negative antibody responses.

Results

Antibody response to the mouse subfornical organ was detected in the sera of 16 patients (72.7%, female/male ratio, 1:1, 12 pediatric and 4 adult patients). The prolactin levels at the time of diagnosis were significantly higher in patients with positive subfornical organ (SFO) immunoreactivity than in those with negative SFO immunoreactivity (58.9 ± 33.5 vs. 22.9 ± 13.9 ng/ml, p < .05). Hypothalamic disorders were found in 37.5% of the patients with positive SFO immunoreactivity. Moreover, six patients were diagnosed with rapid‐onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation/neural tumor syndrome after the diagnosis of adipsic hypernatremia. Plasma renin activity levels were significantly higher in patients with serum immunoreactivity to the Nax channel.

Conclusions

The patients with serum immunoreactivity to the SFO had higher prolactin levels and hypothalamic disorders compared to those without the immunoreactivity. The clinical characteristics of patients with serum immunoreactivity to the subfornical organ included higher prolactin levels and hypothalamic disorders, which were frequently associated with central hypothyroidism and the presence of retroperitoneal tumors.
Different FT3/TSH correlation in acquired and congenital hypothyroid patients reveals a different hypothalamic set‐point
Authors: Russo Marco , Gullo Damiano , Tumino Dario , Leonardi Daniela , Malandrino Pasqualino , Frasca Francesco
Published: April 2022

Objective

To understand differences in thyroid hormone replacement therapy with levo‐thyroxine (l‐T4) between acquired and congenital hypothyroid (CH) patients.

Design

We compared biochemical thyroid parameters between euthyroid subjects (EU) and both CH adult patients and thyroidectomized patients (TP) under replacement therapy.

Patients and Measurements

A retrospective analysis was performed on a series of 98 consecutive adult CH patients (27 males and 71 females) with a median age of 24 years (range 18−58). Serum TSH, FT3, FT4, l‐T4 dose and body weight were assessed. For comparison purposes, large series of 461 TP for thyroid cancer and 1852 EU followed at our Thyroid Clinic were used as control groups.

Results

The daily weight‐based l‐T4 dose was significantly higher in CH than TP group (1.9 vs. 1.7 mcg/kg, p = .03). FT3/FT4 ratio was significantly higher in the EU group, intermediate in CH and lower in TP groups (0.32, 0.28 and 0.24, respectively). Linear regression analysis displayed an inverse correlation between FT4 and TSH in all the groups. An inverse correlation between FT3 and TSH was observed in the TP group, but not in the EU and CH group suggesting that CH patients, under replacement therapy, display biochemical thyroid parameters similar to EU subjects.

Conclusions

Adult CH patients require a higher daily l‐T4 dose than adult TP. However, the different correlation of TSH and FT3 values between CH and TP patients suggests an adaptive and different hypothalamic−pituitary−thyroid axis regulation that may depend on the early timing of the onset of hypothyroidism in CH.
Suboptimal accuracy of ultrasound and ultrasound‐based risk stratification systems in detecting medullary thyroid carcinoma should not be overlooked. Findings from a systematic review with meta‐analysis
Authors: Ferrarazzo Giulia , Camponovo Chiara , Deandrea Maurilio , Piccardo Arnoldo , Scappaticcio Lorenzo , Trimboli Pierpaolo
Published: April 2022

Objective

Ultrasound (US) is the pivotal procedure during the diagnostic work‐up of thyroid nodule and several US‐based risk stratification systems (RSSs) have been recently developed. Since the performance of RSSs in detecting medullary thyroid carcinoma (MTC) has been rarely investigated, the present systematic review aimed to achieve high evidence about (1) how MTC is classified according to RSSs; (2) if RSSs correctly classify MTC at high risk/suspicion, and (3) if MTC is classified as suspicious at US when RSSs are not used.

Design

The review was performed according to MOOSE. The online search was performed by specific algorithm on January 2022. A random‐effects model was used for statistical analysis.

Results

Twenty‐five papers were initially included and their risk of bias was generally low. According to ATA system, 65% of MTCs was assessed at high suspicion and 25% at intermediate suspicion. Considering all RSSs, a 54.8% of MTCs was put in a high‐risk/suspicion category. Pooling data from studies without data of RSS the prevalence of ultrasonographically suspicious MTCs was 60%.

Conclusions

As conclusion, MTC presentation according to RSSs is partially known and it is classified in a high‐risk/suspicion category of RSSs in just over a half of cases. This advises for further studies, ideally supported by international societies, to better define the US presentation of MTC.
Development and regulation of stem cell‐based therapies in China
Authors: Gao Jianchao , Gao Chenyan
Published: April 2022

Background

Clinical researches of stem cell‐based therapies are highly active in China, while it was arduous to determine the most effective way of clinical translation of those advanced therapies.

Methods

This article briefly introduced the regulatory framework development, the progress in stem cell clinical researches and clinical trials of commercially developed stem cell‐based products, as well as the clinical review concerns of stem cell‐based products in China.

Main findings

The current regulatory framework of stem cell clinical researches in China was launched in 2015, when regulatory authorities issued “Administrative Measures on Stem Cell Clinical Research” (AMSCCR) detailing the rules of stem cell clinical research. Thereafter, the rapidly growing stem cell clinical researches were rigorously managed and clinical use of stem cell therapy was halted. Meanwhile, commercially developed stem cell‐based products are supervised by Drug Administration Law (DAL).

Conclusion

The regulatory framework of stem cell‐based therapy in China has progressed in the last few decades, which is currently regulated according to AMSCCR and DAL. Well‐designed and patient‐focused clinical trial is required for commercially developed stem cell‐based products, and definite clinical benefit evidence is crucial to obtain marketing authorization.
MORAL HAZARD IN REMOTE TEAMS
Authors: Bisetti Emilio , Tengelsen Benjamin , Zetlin‐Jones Ariel
Published: April 2022

We reexamine the ability of teams to credibly self‐impose group punishments and prevent free riding when individual inputs are unobservable. We formulate self‐imposed group punishments as performance underreporting by the team. Although underreporting is not credible in a static game, we show that simple strategies can sustain underreporting in a repeated game, and that the threat of underreporting improves welfare only if team members' preferences between shirking and team output consumption are nonseparable. Our results suggest that self‐assessments can replace increased managerial monitoring in remote work environments.
Overexpression of FOXD2‐AS1 enhances proliferation and impairs differentiation of glioma stem cells by activating the NOTCH pathway via TAF‐1
Authors: Wang Yang , Cheng Yanli , Yang Qi , Kuang Lei , Liu Guolei
Published: April 2022

Emerging data have highlighted the importance of long noncoding RNAs (lncRNAs) in exerting critical biological functions and roles in different forms of brain cancer, including gliomas. In this study, we sought to investigate the role of lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2‐AS1) in glioma cells. First, we used sphere formation assay and flow cytometry to select U251 glioma stem cells (GSCs). Then, we quantified the expression of lncRNA FOXD2‐AS1, TATA‐box binding protein associated factor 1 (TAF‐1) and NOTCH1 in glioma tissues and GSCs, as well as the expression of GSC stem markers, OCT4, SOX2, Nanog, Nestin and CD133 in GSCs. Colony formation assay, sphere formation assay, and flow cytometry were used to evaluate GSC stemness. Next, the correlations among lncRNA FOXD2‐AS1, TAF‐1 and NOTCH1 were investigated. LncRNA FOXD2‐AS1, TAF‐1 and NOTCH1 were found to be elevated in glioma tissues and GSCs, and silencing lncRNA FOXD2‐AS1 inhibited stemness and proliferation, while promoting apoptosis and differentiation of GSCs. LncRNA FOXD2‐AS1 overexpression also led to increased NOTCH1 by recruiting TAF‐1 to the NOTCH1 promoter region, thereby promoting stemness and proliferation, while impairing cell apoptosis and differentiation. Mechanistically, lncRNA FOXD2‐AS1 elevation promoted glioma in vivo by activating the NOTCH signalling pathway via TAF‐1 upregulation. Taken together, the key findings of our investigation support the proposition that downregulation of lncRNA FOXD2‐AS1 presents a viable and novel molecular candidate for improving glioma treatment.