bluuebunny/crossref_metadata_2025 huggingface dataset:
A bifurcated palea mutant infers functional differentiation of WOX3 genes in flower and leaf morphogenesis of barley
Authors: Yoshikawa Takanori , Hisano Hiroshi , Hibara Ken-Ichiro , Nie Jilu , Tanaka Yuki , Itoh Jun-Ichi , Taketa Shin
Published: May 2022

Barley (Hordeum vulgare) is the fourth most highly produced cereal in the world after wheat, rice and maize and is mainly utilized as malts and for animal feed. Barley, a model crop of the tribe Triticeae, is important in comparative analyses of Poaceae. However, molecular understanding about the developmental processes is limited in barley. Our previous work characterized one of two WUSCHEL-RELATED HOMEOBOX 3 (WOX3) genes present in the barley genome: NARROW LEAFED DWARF1 (NLD1). We demonstrated that NLD1 plays a pivotal role in the development of lateral organs. In the present study, we describe a bifurcated palea (bip) mutant of barley focusing on flower and leaf phenotypes. The palea in the bip mutant was split into two and develop towards inside the lemma surrounding the carpels and anthers. The bip mutant is devoid of lodicules, which develop in a pair at the base of the stamen within the lemma in normal barley. bip also exhibited malformations in leaves, such as narrow leaf due to underdeveloped leaf-blade width, and reduced trichome density. Map-based cloning and expression analysis indicated that BIP is identical to another barley WOX3 gene, named HvWOX3. The bip nld1 double mutant presented a more severe reduction in leaf-blade width and number of trichomes. By comparing the phenotypes and gene expression patterns of various WOX3 mutants, we concluded that leaf bilateral outgrowth and trichome development are promoted by both NLD1 and HvWOX3, but that HvWOX3 serves unique and pivotal functions in barley development that differ from those of NLD1.
ViBE: a hierarchical BERT model to identify eukaryotic viruses using metagenome sequencing data
Authors: Gwak Ho-Jin , Rho Mina
Published: May 2022

Viruses are ubiquitous in humans and various environments and continually mutate themselves. Identifying viruses in an environment without cultivation is challenging; however, promoting the screening of novel viruses and expanding the knowledge of viral space is essential. Homology-based methods that identify viruses using known viral genomes rely on sequence alignments, making it difficult to capture remote homologs of the known viruses. To accurately capture viral signals from metagenomic samples, models are needed to understand the patterns encoded in the viral genomes. In this study, we developed a hierarchical BERT model named ViBE to detect eukaryotic viruses from metagenome sequencing data and classify them at the order level. We pre-trained ViBE using read-like sequences generated from the virus reference genomes and derived three fine-tuned models that classify paired-end reads to orders for eukaryotic deoxyribonucleic acid viruses and eukaryotic ribonucleic acid viruses. ViBE achieved higher recall than state-of-the-art alignment-based methods while maintaining comparable precision. ViBE outperformed state-of-the-art alignment-free methods for all test cases. The performance of ViBE was also verified using real sequencing datasets, including the vaginal virome.
Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex
Authors: Lukacs Istvan P , Francavilla Ruggiero , Field Martin , Hunter Emily , Howarth Michael , Horie Sawa , Plaha Puneet , Stacey Richard , Livermore Laurent , Ansorge Olaf , Tamas Gabor , Somogyi Peter
Published: May 2022

Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in 2 distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBCs) had columnar “horsetail” axons descending through layers II–V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and nonpyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%), and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline) but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialized, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.
Graph-theoretical insights into the effects of aging on the speech production network
Authors: Schill Jana , Simonyan Kristina , Corsten Maximilian , Mathys Christian , Thiel Christiane , Witt Karsten
Published: May 2022

Speech production relies on the interplay of different brain regions. Healthy aging leads to complex changes in speech processing and production. Here, we investigated how the whole-brain functional connectivity of healthy elderly individuals differs from that of young individuals. In total, 23 young (aged 24.6 ± 2.2 years) and 23 elderly (aged 64.1 ± 6.5 years) individuals performed a picture naming task during functional magnetic resonance imaging. We determined whole-brain functional connectivity matrices and used them to compute group averaged speech production networks. By including an emotionally neutral and an emotionally charged condition in the task, we characterized the speech production network during normal and emotionally challenged processing. Our data suggest that the speech production network of elderly healthy individuals is as efficient as that of young participants, but that it is more functionally segregated and more modularized. By determining key network regions, we showed that although complex network changes take place during healthy aging, the most important network regions remain stable. Furthermore, emotional distraction had a larger influence on the young group’s network than on the elderly’s. We demonstrated that, from the neural network perspective, elderly individuals have a higher capacity for emotion regulation based on their age-related network re-organization.
Network-specific selectivity of functional connections in the neonatal brain
Authors: Sylvester Chad M , Kaplan Sydney , Myers Michael J , Gordon Evan M , Schwarzlose Rebecca F , Alexopoulos Dimitrios , Nielsen Ashley N , Kenley Jeanette K , Meyer Dominique , Yu Qiongru , Graham Alice M , Fair Damien A , Warner Barbara B , Barch Deanna M , Rogers Cynthia E , Luby Joan L , Petersen Steven E , Smyser Christopher D
Published: May 2022

The adult human brain is organized into functional brain networks, groups of functionally connected segregated brain regions. A key feature of adult functional networks is long-range selectivity, the property that spatially distant regions from the same network have higher functional connectivity than spatially distant regions from different networks. Although it is critical to establish the status of functional networks and long-range selectivity during the neonatal period as a foundation for typical and atypical brain development, prior work in this area has been mixed. Although some studies report distributed adult-like networks, other studies suggest that neonatal networks are immature and consist primarily of spatially isolated regions. Using a large sample of neonates (n = 262), we demonstrate that neonates have long-range selective functional connections for the default mode, fronto-parietal, and dorsal attention networks. An adult-like pattern of functional brain networks is evident in neonates when network-detection algorithms are tuned to these long-range connections, when using surface-based registration (versus volume-based registration), and as per-subject data quantity increases. These results help clarify factors that have led to prior mixed results, establish that key adult-like functional network features are evident in neonates, and provide a foundation for studies of typical and atypical brain development.
Impact of treatment adherence on the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation: a retrospective cohort study
Authors: Lee Won Kyung , Woo Seong Ill , Hyun Dong Keun , Jung Sun-Young , Kim Mi-sook , Lee Joongyub
Published: May 2022

Aims

The impact of adherence to oral anticoagulation has not been reported in terms of absolute risk, which would enhance patients’ understanding and treatment adherence.

Methods and results

This retrospective cohort study analysed data from the National Health Insurance Database of Korea, from January 2010 to December 2018, on 84 227 patients with non-valvular atrial fibrillation (NVAF). The participants were analysed according to their overall adherence to oral anticoagulants (OACs) and further divided into four groups: non-vitamin K antagonist oral anticoagulant (NOAC) adherent, vitamin K antagonist (VKA) adherent, NOAC non-adherent, and VKA non-adherent. The incidence of ischaemic stroke, major bleeding, and death was compared between the four groups using risk difference, number needed to treat and number needed to harm. Among the participants, 50 178 were adherent to (OACs), while 34 049 were non-adherent. The incidence of major bleeding was higher in the adherent group (4.49%; 95% confidence interval, 4.11–4.85%) than in the non-adherent group (3.61%; 3.16–4.06%), and the incidence of ischaemic stroke was higher in the non-adherent group (7.68%; 7.08–8.33%) than in the adherent group (5.61%; 5.17–6.07%). In terms of risk difference, adherence to OACs increased the risk of major bleeding by 0.87% and decreased the risk of ischaemic stroke by 2.08%. This finding suggests that one additional major bleeding event occurred for every 115 adherent patients, and one additional ischaemic stroke event was prevented for every 48 adherent patients.

Conclusion

The benefits of OAC adherence in NVAF patients for ischaemic stroke prevention exceeding the risk of bleeding are shown more clearly in terms of absolute risk.
The Grand Tour of Mercantilism: Lord Fauconberg’s Italian Mission (1669–1671)
Authors: Fusaro Maria , Addobbati Andrea
Published: May 2022

The extraordinary mission of Lord Fauconberg to some of the Italian states in 1669–1671 took place at a pivotal moment in early modern diplomatic relations, and is a most evocative case-study of the relationship between Restoration England and Europe in the last decades of the seventeenth century. This article will provide a close analysis of the mission and its protagonists, aiming to re-evaluate English diplomacy through cross-referencing English and Italian documentary evidence, but with a special attention to the Italian side of the story. By analysing how the Republic of Venice and the Grand Duchy of Tuscany—the major Italian trade partners of England––perceived and interpreted English trade policy, it provides an original analysis of Caroline diplomacy and trade in the early Restoration era.
The Uneasy Interplay between Digital Inequality and International Economic Law
Authors: Peng Shin-yi
Published: May 2022

This article addresses the questions of what role international economic law has played in the story of digital inequality’s emergence and evolution and how international economic law can reduce digital inequality instead of enhancing it. The first part of this study illustrates the uneasy interplay between digital inequality and international economic law. At the network layer, the economic benefit of the General Agreement on Trade in Services’ Mode 3 (foreign investment) market access commitments in the telecommunications sector has never been realized in many developing countries and least developed countries (LDCs). There is a missing link between the consequences of trade liberalization and broadband investment. At the application layer, today’s platformization of services was an ‘unforeseen development’ at the time the World Trade Organization (WTO) was established. Through the pro-liberalization of WTO jurisprudence, members’ decades-old Mode 1 (cross-border) market access commitments have played more than a marginal legal role in global datafication. The second part of this study discusses how international economic law can confront and potentially redress that inequality. In the context of trade and development, it remains to be seen how the WTO members can find the common ground needed to balance digital trade liberalization and development needs. Unless infrastructure concerns from developing countries and LDCs are addressed, the ongoing WTO e-commerce trade deal may end up being labelled the Digital ‘Haves’ Trade Agreement. In the context of trade and competition, the increasing inequality in digital platforms calls for a set of international competition rules to appropriately address market power in the data sector. By imposing cross-border disciplines for competition policy and thus curbing the power of big digital platforms, the proposed WTO Data Reference Paper may well be an effective instrument to address the second dimension of ‘digital inequality’ – data colonization.
Development of a ribosome profiling protocol to study translation in Kluyveromyces marxianus
Authors: Fenton Darren A , Kiniry Stephen J , Yordanova Martina M , Baranov Pavel V , Morrissey John P
Published: May 2022

Kluyveromyces marxianus is an interesting and important yeast because of particular traits such as thermotolerance and rapid growth, and for applications in food and industrial biotechnology. For both understanding its biology and developing bioprocesses, it is important to understand how K. marxianus responds and adapts to changing environments. For this, a full suite of omics tools to measure and compare global patterns of gene expression and protein synthesis is needed. We report here the development of a ribosome profiling method for K. marxianus, which allows codon resolution of translation on a genome-wide scale by deep sequencing of ribosome locations on mRNAs. To aid in the analysis and sharing of ribosome profiling data, we added the K. marxianus genome as well as transcriptome and ribosome profiling data to the publicly accessible GWIPS-viz and Trips-Viz browsers. Users are able to upload custom ribosome profiling and RNA-Seq data to both browsers, therefore allowing easy analysis and sharing of data. We also provide a set of step-by-step protocols for the experimental and bioinformatic methods that we developed.
An analytical solution simulating growth of Lewy bodies
Authors: Kuznetsov Ivan A , Kuznetsov Andrey V
Published: May 2022

This paper reports a minimal model simulating the growth of a Lewy body (LB). To the best of our knowledge, this is the first model simulating LB growth. The LB is assumed to consist of a central spherical core, which is composed of membrane fragments and various dysfunctional intracellular organelles, and a halo, which is composed of alpha-synuclein (α-syn) fibrils. Membrane fragments and α-syn monomers are assumed to be produced in the soma at constant rates. The growth of the core and the halo are simulated by the Finke–Watzky model. Analytical (closed-form) solutions describing the growth of the core and the halo are obtained. A sensitivity analysis in terms of model parameters is performed.
Distress vocalizations in five species of armadillos (Xenarthra, Cingulata)
Authors: Amaya Juan P , Abba Agustín M , Pardo Victor M , Zufiaurre Emmanuel , Bustillos Cayoja Huascar , Superina Mariella , Areta Juan I
Published: May 2022

Distress vocalizations are emitted by animals experiencing extreme physical distress, such as when caught by a predator. These signals are emitted by numerous and phylogenetically distant vertebrate species and are composed of sequences of broadband and high-amplitude notes. In this study, we provide the first acoustic characterization of distress vocalizations in four armadillo species: pink fairy armadillo (Chlamyphorus truncatus), greater fairy armadillo (Calyptophractus retusus), Southern three-banded armadillo (Tolypeutes matacus), and Chacoan naked-tailed armadillo (Cabassous chacoensis). We also recharacterized the weeping call of the screaming hairy armadillo (Chaetophractus vellerosus) to compare vocalizations, discuss potential homologies, and examine possible causes of structural and acoustic similarities among these species. In three species the vocalizations were sequences of exhaled notes that differed in their fine spectral structure (exhaled harmonic notes in C. retusus, and exhaled harsh notes in C. truncatus and T. matacus). The vocalization of C. chacoensis was composed of exhaled harsh and inhaled harsh notes that occurred alternately and continuously in a quick sequence. Based on the mode of production and acoustic similarity, we propose that the notes of C. retusus and C. truncatus would be homologous to the conspicuous crying notes of C. vellerosus. The exhaled harsh notes of T. matacus and C. chacoensis may also be homologous to the crying notes of C. vellerosus, but the notes of T. matacus are quite different in various acoustic parameters. Furthermore, the inhaled and exhaled harsh notes of C. chacoensis are similar to the inhaled and exhaled sobbing notes of C. vellerosus, making assessments of homologies uncertain in these species. Because a common motivational state (physical distress) underlies these vocalizations, we propose that the notable differences in body size and habitat preferences of the armadillos could represent potential drivers of the acoustic divergence among their vocalizations.
Is There Life After Death?: The Persuasive Value of Annulled Investment Awards
Authors: Csernus Máté
Published: May 2022

In investment arbitral jurisprudence, previous decisions of arbitral tribunals are held in high regard. But what happens to an award’s persuasive value when it is annulled? The article seeks to examine the legal status, legitimacy, and, through these factors, the persuasiveness of annulled investment awards. The article finds that since the quasi-precedential system of investment arbitration is largely governed by meta-legal considerations, the status of annulled awards is also governed by these considerations, that is, considerations of legitimacy. The author compares the persuasive value of annulled investment awards with that of dissenting opinions of arbitrators and with overturned World Trade Organization (WTO)Panel Reports with the aim of shedding some additional light on questions of legitimacy and persuasiveness. Finally, the article offers a typology of investment arbitral tribunals’ possible reasons for referring to annulled awards and illustrates the relevant categories with some of the more influential annulled investment awards of recent years.
Constraining parameter uncertainty for predicting oxygen and hydrogen isotope values in fruit
Authors: Cueni Florian , Nelson Daniel B , Lehmann Marco M , Boner Markus , Kahmen Ansgar
Published: May 2022

Understanding δ18O and δ2H values of agricultural products like fruit is of particular scientific interest in plant physiology, ecology, and forensic studies. Applications of mechanistic stable isotope models to predict δ18O and δ2H values of water and organic compounds in fruit, however, are hindered by a lack of empirical parameterizations and validations. We addressed this lack of data by experimentally evaluating model parameter values required to model δ18O and δ2H values of water and organic compounds in berries and leaves from strawberry and raspberry plants grown at different relative humidities. Our study revealed substantial differences between leaf and berry isotope values, consistent across the different relative humidity treatments. We demonstrated that existing isotope models can reproduce water and organic δ18O and δ2H values for leaves and berries. Yet, these simulations require organ-specific model parameterization to accurately predict δ18O and δ2H values of leaf and berry tissue and water pools. We quantified these organ-specific model parameters for both species and relative humidity conditions. Depending on the required model accuracy, species- and environment-specific model parameters may be justified. The parameter values determined in this study thus facilitate applications of stable isotope models where understanding δ18O and δ2H values of fruit is of scientific interest.
A low-energy-dense dietary pattern: a narrative review
Authors: Burns Kaelyn F , Robson Shannon M , Raynor Hollie A
Published: May 2022

Background

Dietary recommendations have promoted the consumption of a low-energy-dense dietary pattern; however, guidelines to implement this dietary pattern are lacking.

Objectives

The objectives of this narrative review are to discuss approaches used to implement a low-energy-dense dietary pattern within dietary interventions and to understand if these approaches achieve a lower energy-dense diet.

Methods

Interventions that modified the diet for the purpose of altering energy density were referenced. Articles were chosen on the basis of the authors’ knowledge of the energy density literature, reviewing relevant articles’ reference lists, and discussion among coauthors.

Results

Eight articles were chosen for this review. Two approaches have been used to alter energy density: 1) modification to the consumption of dietary components that influence energy density (eg, reducing fat, increasing fruits and vegetables) or 2) use of an energy density classification method based on the numeric energy density value of foods. Although both approaches were used successfully to lower energy density, only the approach that used an energy density classification method allowed for the establishment of specific behavioral goals for participants to achieve regarding energy density.

Conclusion

The use of an energy density classification method to develop specific intake goals may aid in the behavioral implementation of a low-energy-dense dietary pattern, but more high-quality studies are needed to draw stronger conclusions. Furthermore, barriers to consuming a low-energy-dense dietary pattern, such as dietary costs, need to be considered.
Osa-miR1320targets the ERF transcription factor OsERF096 to regulate cold tolerance via JA-mediated signaling
Authors: Sun Mingzhe , Shen Yang , Chen Yue , Wang Yan , Cai Xiaoxi , Yang Junkai , Jia Bowei , Dong Weifeng , Chen Xi , Sun Xiaoli
Published: May 2022

MicroRNAs play key roles in abiotic stress response. Rice (Oryza sativa L.) miR1320 is a species-specific miRNA that contributes to miR168-regulated immunity. However, it is still unknown whether miR1320 is involved in rice response to abiotic stress. In this study, we illustrated that the miR1320 precursor generated two mature miR1320s, miR1320-3p, and miR1320-5p, and they both displayed decreased expression under cold stress. Genetic evidence showed that miR1320 overexpression resulted in increased cold tolerance, while miR1320 knock down (KD) reduced cold tolerance. Furthermore, an APETALA2/ethylene-responsive factor (ERF) transcription factor OsERF096 was identified as a target of miR1320 via 5′-RACE and dual luciferase assays. OsERF096 expression was altered by miR1320 overexpression and KD and exhibited an opposite pattern to that of miR1320 in different tissues and under cold stress. Consistently, OsERF096 negatively regulated cold stress tolerance. Furthermore, we suggested that OsERF096 could bind to the GCC and DRE cis-elements and act as a transcriptional activator in the nucleus. Based on RNA-sequencing and targeted metabolomics assays, we found that OsERF096 modified hormone content and signaling pathways. Finally, phenotypic and reverse transcription-quantitative PCR assays showed that jasmonic acid (JA) methyl ester application recovered the cold-sensitive phenotype and JA-activated expression of three Dehydration Responsive Element Binding genes in the OsERF096-OE line. Taken together, our results strongly suggest that the miR1320–OsERF096 module regulates cold tolerance by repressing the JA-mediated cold signaling pathway.
Use of science in public policy: Lessons from the COVID-19 pandemic efforts to ‘Follow the Science’
Authors: Bozeman Barry
Published: May 2022

The paper asks: ‘What can we learn from COVID-19 pandemic about effective use of scientific and technical information (STI) in policymaking and how might the lessons be put to use?’ The paper employs the political rhetoric of ‘follow the science’ as a lens for examining contemporary concerns in the use of STI, including (1) ‘Breadth of Science Products’, the necessity of a broader concept of STI that includes by-products science, (2) ‘Science Dynamism’, emphasizing the uncertainty and impeachability of science, (3) ‘STI Urgency’ suggesting that STI use during widespread calamities differs from more routine applications, and (4) ‘Hyper-politicization of Science’, arguing that a step-change in the contentiousness of politics affects uses and misuses of STI. The paper concludes with a discussion, STI Curation, as a possible ingredient to improving effective use. With more attention to credibility and trust of STI and to the institutional legitimacy of curators, it should prove possible to improve the effective use of STI in public policy.
Are Newborn Outcomes Different for Term Babies Who Were Exposed to Antenatal Corticosteroids?
Authors: McKinzie Alexandra H. , Yang Ziyi , Teal Evgenia , Daggy Joanne K. , Tepper Robert S. , Quinney Sara K. , Rhoads Eli , Haneline Laura S. , Haas David M.
Published: May 2022

(Abstracted from Am J Obstet Gynecol 2021;225:536.e1–536.e7)

The administration of antenatal corticosteroids can improve newborn lung function following antenatal treatment of pregnant women who are between 24 and 36 + 6/7 weeks' gestation and at risk of preterm delivery within 7 days. Antenatal corticosteroids, such as betamethasone (BMZ), reduce the risks of respiratory distress syndrome, the need for respiratory support, and admission to the neonatal intensive care unit (NICU).
Association Between Income and Perinatal Mortality in the Netherlands Across Gestational Age
Authors: Vidiella-Martin Joaquim , Been Jasper V. , Van Doorslaer Eddy , García-Gómez Pilar , Van Ourti Tom
Published: May 2022

(Abstracted from JAMA Network Open 2021;4(11):e2132124)

While the contribution of socioeconomic status to disparities in neonatal death and stillbirth has received considerable attention, several key aspects remain understudied. These include the specificity of the association between household income and perinatal outcomes and the contribution of gestational age and birth weight to income-related disparities in perinatal mortality.
Toward Trauma-Informed Pedagogy: An Intersectional Analysis of Pimping in Medical Education
Authors: Kherani Imaan Zera , Sharma Malika
Published: May 2022

Increased awareness of the role of power and privilege in medical education demands reevaluation and critical reflection on the role of pimping, both in name and practice. The authors use an intersectional approach to explore the ways in which the term pimping is rooted in sexist, racist, and classist stereotypes. In using this term to describe a pedagogical approach rooted in hierarchical power and stark knowledge differentials, the medical community intentionally or unintentionally reinforces racist stereotypes, acts of carceral violence, gender-based violence, and harmful ways of referring to sex work. The authors suggest drawing on principles of trauma-informed care, often considered solely in the context of clinical care, as a means of engaging in transformative pedagogy. Embracing such a trauma-informed, transformative pedagogical approach can help dismantle entrenched hierarchies and create a liberatory learning environment grounded in knowledge cocreation and reimagination of teacher–learner binaries. Decentralization of power in teaching relationships can further empower trainees to become active knowledge partners alongside educators, encouraging shared responsibility, trust, and empathy in learning spaces.
Medical Student Identity Construction Within Longitudinal Integrated Clerkships: An International, Longitudinal Qualitative Study
Authors: Brown Megan E.L. , Ard Catherine , Adams Jennifer , O’Regan Andrew , Finn Gabrielle M.
Published: May 2022

Purpose

Longitudinal integrated clerkships (LICs) have been implemented worldwide to increase authentic student participation in patient care over time. Studies have shown benefits of the model include the ability of LICs to attract future practitioners to underserved areas, student engagement in advocacy, and development of an “ethic of caring.” Less is known, however, about how LICs impart their benefits, although LICs may strengthen professional identity. As such, this study aimed to explore medical student professional identity construction through time within LICs internationally.

Method

This was a longitudinal qualitative study from 2019 to 2020, involving 33 students across 4 medical schools in the United Kingdom, Ireland, and the United States. The authors explored participating students’ identity construction during LICs. Data collection involved 3 stages: individual, semistructured interviews at entry (n = 33) and exit of the LIC (n = 29), and audio diaries throughout. Data were analyzed inductively using a reflexive thematic approach.

Results

Three themes were identified. Longitudinal relationships with patients and preceptors encouraged patient care ownership and responsibility; LIC students identified as patient advocates; and longitudinal relationships shaped students’ social consciences. Themes were underpinned by continuity of relationships between students and patients, and students and tutors.

Conclusions

Though continuity is lauded as the cornerstone of LICs, these findings suggest that this is too broad a way of understanding the benefits of LICs. Instead, continuity should be seen as facilitating the development of important relationships within diverse communities of practice, which leads medical students to construct professional identities as responsible, compassionate advocates for underserved populations. This was the case across the institutions, nations, and LIC types in this study. By highlighting the ways in which LICs influence identity, these findings offer important insight relating to the future development and delivery of LICs.
ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy
Authors: Love Charito , Desai Neil B. , Abraham Tony , Banks Kevin P. , Bodei Lisa , Boike Thomas , Brown Richard K.J. , Bushnell David L. , DeBlanche Lorraine E. , Dominello Michael M. , Francis Tony , Grady Erin C. , Hobbs Robert F. , Hope Thomas A. , Kempf Jeffrey S. , Pryma Daniel A. , Rule William , Savir-Baruch Bital , Sethi Ila , Subramaniam Rathan M. , Xiao Ying , Schechter Naomi R.
Published: May 2022

Objectives:

This practice parameter (PP) for Lutetium-177 (Lu-177) DOTATATE peptide receptor radionuclide therapy (PRRT) aims to guide authorized users in selection of appropriate adult candidates with gastroeneropancreatic neuroendocrine tumors (GEP-NETs) from foregut, midgut, and hindgut. The essential selection criteria include somatostatin receptor-positive GEP-NETs, which are usually inoperable and progressed despite standard therapy. Lu-177 DOTATATE is a radiopharmaceutical with high avidity for somatostatin receptors that are overexpressed by these tumors. This document ensures safe handling of Lu-177 DOTATATE by the authorized users and safe management of affected patients.

Methods:

The document was developed according to the systematic process developed by the American College of Radiology (ACR) and described on the ACR Web site (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards). The PP development was led by 2 ACR Committees on Practice Parameters (Nuclear Medicine and Molecular Imaging and Radiation Oncology) collaboratively with the American College of Nuclear Medicine, American Society of Radiation Oncology, and Society of Nuclear Medicine and Molecular Imaging.

Results:

The Lu-177 DOTATATE PP reviewed pharmacology, indications, adverse effects, personnel qualifications, and required clinical evaluation before starting the treatment, as well as the recommended posttherapy monitoring, quality assurance, documentation, and appropriate radiation safety instructions provided in written form and explained to the patients.

Conclusions:

Lu-177 DOTATATE is available for therapy of inoperable and/or advanced GEP-NETs when conventional therapy had failed. It can reduce tumor size, improve symptoms, and increase the progression free survival. The PP document provides clinical guidance for authorized users to assure an appropriate, consistent, and safe practice of Lu-177 DOTATATE.
Per- and polyfluoroalkyl substances in drinking water and hypertensive disorders of pregnancy in the United States during 2013–2015
Authors: Zhu Yachen , Bartell Scott M.
Published: May 2022

Background:

Per- and polyfluoroalkyl substances (PFAS) widely exist in the environment and human bodies. Contaminated drinking water is one of the major exposure pathways for humans. Previous studies found weak or moderate associations between PFAS and hypertensive disorders of pregnancy (HDP).

Methods:

We obtained the number of births and counts of HDP cases for singleton births multiply stratified by county, maternal age, race, education, smoking status, and parity from CDC WONDER, and PFAS water concentrations from EPA UCMR3 data in the United States during 2013–2015. We used binomial regression on the multiply stratified HDP data to produce equal effect estimates and standard errors to those that would be derived from using individual-level data on binary HDP status and demographic covariates in logistic regression.

Results:

After adjusting for demographic covariates, we found small but statistically significant positive associations between HDP and population-weighted average water concentrations (ng/L) of all four PFAS: Odds ratio (OR) = 1.009, 95% CI = (1.001, 1.016) per IQR increase in perfluorooctanoic acid (PFOA); 1.030, 95% CI = (1.021, 1.040) per IQR increase in perfluorooctane sulfonate (PFOS); 1.008, 95% CI = (1.005, 1.011) per IQR increase in perfluoroheptanoic acid (PFHpA); 1.007, 95% CI = (1.004, 1.010) per IQR increase in perfluorohexane sulfonic acid (PFHxS), and 1.032, 95% CI = (1.022, 1.042) per IQR increase in the sum of four PFAS. Further adjustment for coexposures reversed the effect of PFOA from positive to inverse, and attenuated the effects of PFOS and PFHxS toward the null. After drinking water to serum concentration conversions, our effect estimates for PFOA, PFOS, and PFHxS are similar to previous studies.

Conclusions:

We found a weak positive association between the PFAS mixture and HDP, although the generalizability is subject to inherent limitations of the public-available datasets.
E74-like factor 1 contributes to nerve trauma-induced nociceptive hypersensitivity through transcriptionally activating matrix metalloprotein-9 in dorsal root ganglion neurons
Authors: Zhang Luyao , Li Xiang , Feng Xiaozhou , Berkman Tolga , Ma Ruining , Du Shibin , Wu Shaogen , Huang Congcong , Amponsah Akwasi , Bekker Alex , Tao Yuan-Xiang
Published: May 2022

Nerve trauma-induced alternations of gene expression in the neurons of dorsal root ganglion (DRG) participate in nerve trauma-caused nociceptive hypersensitivity. Transcription factors regulate gene expression. Whether the transcription factor E74-like factor 1 (ELF1) in the DRG contributes to neuropathic pain is unknown. We report here that peripheral nerve trauma caused by chronic constriction injury (CCI) of unilateral sciatic nerve or unilateral fourth lumbar spinal nerve ligation led to the time-dependent increases in the levels of Elf1 mRNA and ELF1 protein in injured DRG, but not in the spinal cord. Preventing this increase through DRG microinjection of adeno-associated virus 5 expressing Elf1 shRNA attenuated the CCI-induced upregulation of matrix metallopeptidase 9 (MMP9) in injured DRG and induction and maintenance of nociceptive hypersensitivities, without changing locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking this increase through DRG microinjection of AAV5 expressing full-length Elf1 upregulated DRG MMP9 and produced enhanced responses to mechanical, heat, and cold stimuli in naive mice. Mechanistically, more ELF1 directly bond to and activated Mmp9 promoter in injured DRG neurons after CCI. Our data indicate that ELF1 participates in nerve trauma-caused nociceptive hypersensitivity likely through upregulating MMP9 in injured DRG. E74-like factor 1 may be a new target for management of neuropathic pain.
Perception and Utilization of Standardized Outcome Measures in Acute Care Physical Therapy
Authors: Smith Darby , Furtado Michael , Brusola Gregory
Published: May 2022

Purpose:

To assess the relationship between characteristics of acute care physical therapists (PTs) and use of standardized outcome measures (OMs); also describe the perceived barriers, facilitators, and resources to the use of OMs by PTs in the acute care setting.

Methods:

An electronic survey was distributed to PTs who currently work, or have worked, in the adult acute care setting in the past 5 years. Separate quantitative and qualitative analyses were performed followed by triangulation of findings.

Results:

A convenience sample included 227 respondents. Most respondents (n = 159, 70%) reported using OMs. PTs with a clinical specialty used OMs significantly more (P = .041) than those without. No significant difference was found in the frequency of OM use between years of experience, entry-level degree, and primary patient population. The top barrier was lack of time (60%). The top facilitator was support from administration (81%). Themes generated for barriers, facilitators, and resources included lack of resources, setting specificity, patient population and acuity, objective data, facility support, and continuing education.

Conclusions:

Most acute care PTs reported using OMs, although a higher frequency was observed in those with a clinical specialty. This study presents opportunities to provide knowledge translation and resources to combat barriers to OM use in the acute care setting.
Improved symptoms and signs of refractory interstitial cystitis in women after intravesical Nanofat plus platelet-rich plasma grafting: A pilot study
Authors: Hung Man-Jung , Tsai Ching-Pei , Ying Tsung-Ho , Chen Gin-Den , Su Hong-Lin , Tseng Chih-Jen
Published: May 2022

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder pain accompanied by irritative urinary symptoms, and typical cystoscopic and histological features. In this pilot study, we assessed the impact of lesion-targeted bladder injection therapy using a biocellular regenerative medicine on patients with refractory IC/BPS. The medicine, which was an autologous emulsified fat (Nanofat) and platelet-rich plasma (PRP) combination, was prepared intraoperatively. Six patients (aged 40-54 years), who completed a standard protocol of four consecutive treatments at 3-month intervals, were followed up at 6 months postoperatively. All patients (100%) reported marked (+3; +3 ~ −3) improvement of their overall bladder conditions. Mean bladder pain (from 8.2 to 1.7; range: 0 ~ 10), IC-related symptoms (from 18.5 to 5.7; range: 0 ~ 20), and bother (from 14.8 to 3.8; range: 0 ~ 16) improved significantly (p < 0.01). The normalization of bladder mucosal morphology with treatments was remarkable under cystoscopic examination, and no significant adverse events were found. The cultured mesenchymal stem cells from Nanofat samples of the six patients were verified in vitro. Our preliminary results suggest novel intravesical therapy with autologous Nanofat plus PRP grafting is safe and effective for refractory IC/BPS. Surgical efficacy might be attributed to an in vivo tissue engineering process.
Comparison of single platelet-rich plasma injection with hyaluronic acid injection for partial-thickness rotator cuff tears
Authors: Huang Shou-Hsien , Hsu Po-Cheng , Wang Kevin A. , Chou Chen-Liang , Wang Jia-Chi
Published: May 2022

Background:

Partial-thickness rotator cuff tears (PTRCTs) is not uncommon, and various nonsurgical injection therapy for PTRCTs emerged. Platelet-rich plasma (PRP) and hyaluronic acid (HA) injection were proposed for treating PTRCTs; however, the relation of dose among injectates was still lacking.

Methods:

This was a prospective, nonrandomized, comparative study. The aim of the study was to compare the effects of ultrasound-guided single PRP injection with three doses of HA injection, combination of postinjection rehabilitation, for treating PTRCTs. Subjects received either ultrasound-guided PRP injection and rehabilitation exercise, or ultrasound-guided subacromial HA injection and rehabilitation exercise. Shoulder Pain and Disability Index (SPADI), range of motion (ROM), pain visual analog scale (VAS), and Constant-Murley Shoulder Score (CMSS) were recorded before injection, and at 1 and 3 months after injection.

Results:

Forty-eight patients were enrolled. They received either ultrasound-guided single PRP (n = 24) intralesional and peritendinous injection or three doses of HA (n = 24) subacromial injection plus rehabilitation exercise. In the PRP group, SPADI scores, VAS scores, CMSS significantly improved at 1-month and 3-month follow up; flexion and abduction ROM significantly increased at 3-month follow up. In the HA group, SPADI scores, VAS during overhead activities, VAS night pain, and CMSS significantly improved in the first and third months; flexion and active abduction ROM significantly increased in the third month. The PRP group revealed significantly better passive abduction ROM and CMSS at third month than HA group.

Conclusion:

Ultrasound-guided single PRP injection exhibited comparable benefit to three doses of HA injection in patients with PTRCTs short-termly, with an extended effect regarding passive shoulder abduction ROM and CMSS.
Holistic care for obstructive sleep apnea (OSA) with an emphasis on restoring nasal breathing: A review and perspective
Authors: Tsai Ming-Shao , Chen Hung-Chin , Liu Stanley Yung-Chuan , Lee Li-Ang , Lin Cheng-Yu , Chang Geng-He , Tsai Yao-Te , Lee Yi-Chan , Hsu Cheng-Ming , Li Hsueh-Yu
Published: May 2022

Obstructive sleep apnea (OSA) is characterized by partial or complete airway blockage during sleep. Nocturnal nasal obstruction usually leads to mouth breathing while sleeping, which worsens sleep apnea by aggravating tongue base and lateral pharyngeal wall collapse. The pathogenesis of OSA is multifactorial, and the precipitating factors vary significantly among individuals. Although continuous positive airway pressure (CPAP) is considered the first-line therapy for OSA, its adherence rate remains a challenge. Oral appliances are more suitable for simple snorers or patients with mild OSA. Maxillomandibular advancement (MMA) is highly effective for treating those with mandibular retrognathia and moderate-to-severe OSA. Intrapharyngeal surgeries yield favorable outcomes in patients with large tonsils and low tongue resting position (Friedman Stage I); however, their efficacy declines with time. Each therapy has its own strength and weakness; thus, the principle of multimodality treatment should be adopted. Nasal surgery plays an indispensable role in the holistic care for OSA. In addition to alleviating nasal congestion, nasal surgery significantly reduces snoring intensity and daytime sleepiness, which improves the quality of life of patients with OSA. Although it significantly reduces the respiratory disturbance index, its effect on the apnea–hypopnea index remains controversial. A combination of nasal surgery and multilevel pharyngeal surgery may result in better prognosis. Nasal surgery can significantly reduce the therapeutic pressure and improve the CPAP compliance of patients undergoing CPAP therapy. In conclusion, multimodality treatment and holistic care for OSA should involve nasal surgery for optimizing treatment outcomes.
The impact of hepatotoxic drugs on the outcome of patients with acute deterioration of hepatitis B virus-related chronic disease
Authors: Sun Jian , Yu Xueping , Weng Zhangyan , Jin Lei , Yang Jian , Zhang Huatang , Gu Jun , Wang Ni , Yang Jianghua
Published: May 2022

Background and aims

Hepatotoxic drugs can worsen outcomes in patients with chronic liver disease (CLD), whereas this negative effect in acute deterioration of hepatitis B virus (HBV)-related CLD (HBV-CLD) is rarely reported. We aimed to assess the impact of hepatotoxic drugs on the outcome of patients with acute deterioration of HBV-CLD.

Methods

This retrospective study included consecutive patients admitted to three medical centers in eastern China from 2015 to 2020 for HBV-related severe liver injury (HBV-SLI) or acute decompensation of cirrhosis (HBV-AD). The prevalence of hepatotoxic drugs and their impact on organ failure, the development of acute-on-chronic liver failure (ACLF), and 90-day survival were evaluated.

Results:

A total of 335 patients with HBV flare (median age, 44 years; 85.7% male; 38.2% HBV-SLI and 61.8% HBV-AD) were included. Of them, 72 (21.5%) received hepatotoxic drugs, with herbs (44.4%) being the most common form. Patients in the drugs group had a significantly higher prevalence of all types of organ failure except respiratory failure. The multivariate logistic model showed that hepatotoxic drugs raised the risk of developing ACLF by 7.66-fold. ACLF occurrence was the strongest risk factor for 90-day mortality with a hazard ratio of 5.54 in the Cox regression analysis. In contrast, the hepatitis B envelope antigen status and HBV DNA levels had weak associations with the development of organ failure and ACLF.

Conclusions:

Hepatotoxic drugs are closely associated with the development of organ failure and ACLF, and contribute to reduced 90-day survival rates among patients with acute deterioration of HBV-CLD.