bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyroidectomy via unilateral axillo-breast approach (UABA) with gas insufflation: prospective multicentre European study
Authors: Saavedra-Perez David , Manyalich Marti , Dominguez Paula , Vilaça Jaime , Jordan Julio , Lopez-Boado Miguel A , Rull Ramon , Vidal Oscar
Published: July 2022

Background

Extracervical approaches for thyroidectomy are seldom explored in the western population. The objective of this study was to evaluate the outcomes of hemithyroidectomy via endoscopic unilateral axillo-breast approach (UABA) with gas insufflation.

Method

Consecutive patients undergoing UABA hemithyroidectomy for symptomatic benign or cytologically indeterminate nodules (Bethesda III lesions) of less than 5 cm from July 2015 to December 2020 at three European institutions were included. Patients were excluded if presenting with a BMI more than 25 kg/m2, had previous neck surgery and/or radiation, had bilateral thyroid lesions, retrosternal goitre, Hashimoto thyroiditis or Graves’ disease. Follow-up was carried out at 2 weeks, 3 months and 1 year. Outcomes of interest were surgical (including operating time, mean duration of hospital stay and complications) and self-assessed cosmetic outcomes.

Results

Out of 984 patients treated with hemithyroidectomy during the study interval, 253 were selected, including 214 women and 39 men. Patients’ mean age was of 46.6 years with a mean BMI of 22.57. Mean operating time was 72.9 minutes. A transient recurrent laryngeal nerve injury was reported in 3.6 per cent of the patients, but none was persistent. Transient pectoral/cervical hypoesthesia was noted in 24.1 per cent of patients, with no permanent hypoesthesia. Skin burns and subcutaneous hematoma developed in 2.4 per cent and 2 per cent of patients but resolved within the third month after surgery. There was no tracheal/oesophageal perforation, conversion to open surgery or reoperation. The final pathology revealed 241 benign nodules, nine underlying papillary thyroid carcinomas, and three cases of follicular carcinoma. Hospital discharge was achieved on the first in 68.8 per cent of the patients and on the second postoperative day in 31.2 per cent of the cases. All patients were satisfied with the cosmetic aspect.

Conclusion

In selected patients, UABA with gas insufflation for hemithyroidectomy could be performed for the treatment of unilateral thyroid pathologies.
bell hooks’s Legacy and Social Work: A Distillation of Her Key Ideas about Love and Some Implications for Social Work Practice
Authors: Ross Dyann
Published: July 2022

bell hooks is regarded as one of the most influential cultural critics, writers and speakers of the last fifty years. She has published more than forty books which collectively articulate a feminist critique of white supremacy, capitalism and patriarchy. At the same time, she offers a loving, non-violent and just vision for attaining collective and personal well-being. Hooks makes feminist theory meaningful as a guide not only for Black American women but also for anyone seeking to resist inequality and discrimination due to race, class and gender. Her main thesis is that where there is love there can be no oppression. hooks’s contribution is traced through some of the key themes of her books which explicitly refer to love to develop a rich understanding of love and its transformative power. These contributions are then considered for the relevance they have for social work. Social workers can practice love by fostering their own and others’: self-love; willingness to learn; and cultural responsiveness. Two loving practices with other people are dadirri (deep listening) and narrative resistance. Love provides the power to do the justice and healing work.
Group B Streptococcus (GBS) colonization is dynamic over time, whilst GBS capsular polysaccharides-specific antibody remains stable
Authors: Haeusler I L , Daniel O , Isitt C , Watts R , Cantrell L , Feng S , Cochet M , Salloum M , Ikram S , Hayter E , Lim S , Hall T , Athaide S , Cosgrove C A , Tregoning J S , Le Doare K
Published: July 2022

Group B Streptococcus (GBS) is a leading cause of adverse pregnancy outcomes due to invasive infection. This study investigated longitudinal variation in GBS rectovaginal colonization, serum and vaginal GBS capsular polysaccharide (CPS)-specific antibody levels. Non-pregnant women were recruited in the UK and were sampled every 2 weeks over a 12-week period. GBS isolates were taken from recto-vaginal swabs and serotyped by polymerase chain reaction. Serum and vaginal immunoglobulin G (IgG) and nasal immunoglobulin A (IgA) specific to CPS were measured by Luminex, and total IgG/A by ELISA. Seventy women were enrolled, of median age 26. Out of the 66 participants who completed at least three visits: 14/47 (29.8%) women that were GBS negative at screening became positive in follow-up visits and 16/19 (84.2%) women who were GBS positive at screening became negative. There was 50% probability of becoming negative 36 days after the first positive swab. The rate of detectable GBS carriage fluctuated over time, although serum, vaginal, and nasal CPS-specific antibody levels remained constant. Levels of CPS-specific antibodies were higher in the serum of individuals colonized with GBS than in non-colonized, but similar in the vaginal and nasal mucosa. We found correlations between antibody levels in serum and the vaginal and nasal mucosa. Our study demonstrates the feasibility of elution methods to retrieve vaginal and nasal antibodies, and the optimization of immunoassays to measure GBS-CPS-specific antibodies. The difference between the dynamics of colonization and antibody response is interesting and further investigation is required for vaccine development.
Hippocampal and motor regions contribute to memory benefits after enacted encoding: cross-sectional and longitudinal evidence
Authors: Noroozian Maryam , Kormi-Nouri Reza , Nyberg Lars , Persson Jonas
Published: July 2022

The neurobiological underpinnings of action-related episodic memory and how enactment contributes to efficient memory encoding are not well understood. We examine whether individual differences in level (n = 338) and 5-year change (n = 248) in the ability to benefit from motor involvement during memory encoding are related to gray matter (GM) volume, white matter (WM) integrity, and dopamine-regulating genes in a population-based cohort (age range = 25–80 years). A latent profile analysis identified 2 groups with similar performance on verbal encoding but with marked differences in the ability to benefit from motor involvement during memory encoding. Impaired ability to benefit from enactment was paired with smaller HC, parahippocampal, and putamen volume along with lower WM microstructure in the fornix. Individuals with reduced ability to benefit from encoding enactment over 5 years were characterized by reduced HC and motor cortex GM volume along with reduced WM microstructure in several WM tracts. Moreover, the proportion of catechol-O-methyltransferase-Val-carriers differed significantly between classes identified from the latent-profile analysis. These results provide converging evidence that individuals with low or declining ability to benefit from motor involvement during memory encoding are characterized by low and reduced GM volume in regions critical for memory and motor functions along with altered WM microstructure.
Trade Defence Instruments: A New Tool for the European Union’s Extractivism
Authors: Crochet Victor
Published: July 2022

The European Union (EU) is regularly criticized for using its trade policies to arm-twist other countries into agreeing to supply European factories with raw materials. One area of its trade policy, however, has thus far escaped attention in this regard: trade defence. This should change as the EU increasingly uses trade defence instruments not only to address unfair trade practices but also to seek access to raw materials from other countries. It does so by imposing higher trade defence tariffs on countries that employ policies that ensure raw materials extracted within their territories are processed domestically. This approach is worrisome since, due to the EU’s market size, it may discourage resource-rich countries from developing downstream industries of their own. Furthermore, these countries’ policies are often in line with their international obligations so that the EU is unilaterally infringing on these countries’ sovereignty over their natural resources when targeting these policies. These countries and their exporting producers should thus seize the means at their disposal to put a stop to the EU’s practices.
Strategic Litigation before the International Court of Justice: Evaluating Impact in the Campaign for Rohingya Rights
Authors: Ramsden Michael
Published: July 2022

Strategic litigation, a form of litigation brought with the goal to stimulate structural change, is a growing practice in international courts. Although there has been increased scholarly attention on these trends, it has yet to consider the impact arising from strategic litigation before the International Court of Justice (ICJ). This article outlines a basic structure to evaluate the impact of ICJ strategic litigation. It does so generally and through a case study into the campaign by the Organisation of Islamic Cooperation (OIC) to restore Rohingya rights and secure accountability for crimes committed against this population through the claim that Myanmar has violated the Genocide Convention. This article identifies the OIC’s campaign goals and how the ICJ case initiated by The Gambia furthered that campaign and evaluates the impact of this case in advancing Rohingya rights.
Removing the surface waves scattered by steep topography from receiver functions
Authors: Lu Yifan , Tian Xiaobo , Liu Youshan
Published: July 2022

Higher frequency receiver function (RF) analysis based on dense nodal arrays has been widely used for imaging crustal structures. However, the scattered Rayleigh waves generated by the steep topography including mountain ranges and basin-range junction zones, have become a significant interference that can lead to false structures in RF images. In this study, we propose a novel method to remove scattered Rayleigh waves from RF profiles by using a high-resolution linear Radon transform. Based on the difference in the apparent velocity of Rayleigh and converted waves at interfaces, we construct a scheme to design an optimal filter mask. Synthetic and observed data show that this method can be an effective tool to remove high-amplitude Rayleigh waves and preserve low-amplitude converted waves almost harmlessly. Modelling tests also show that it is suitable for non-uniform station spacing, white noise and models that include dipping interfaces.
The gendered drivers of absenteeism in the Nigerian health system
Authors: Ogbozor Pamela , Onwujekwe Obinna , Balabanova Dina , Odii Aloysius , Agwu Prince , McKee Martin , Obi Uche , Orjiakor Charles Tochukwu , Hutchinson Eleanor
Published: July 2022

The ability to deliver primary care in Nigeria is undermined by chronic absenteeism, but an understanding of its drivers is needed if effective responses are to be developed. While there is a small but growing body of relevant research, the gendered dynamics of absenteeism remains largely unexplored. We apply a gendered perspective to understanding absenteeism and propose targeted strategies that appear likely to reduce it. We did so by means of a qualitative study that was part of a larger project examining corruption within the health system in six primary healthcare facilities across rural and urban regions in Enugu State, south-east Nigeria. We conducted 30 in-depth interviews with frontline health workers, healthcare managers and community members of the health facility committee. Six focus group discussions were held with male and female service users. Data were analysed using thematic analysis. Participants described markedly gendered differences in the factors contributing to health worker absenteeism that were related to gender norms. Absence by female health workers was attributed to domestic and caregiving responsibilities, including housekeeping, childcare, cooking, washing and non-commercial farming used to support their families. Male health workers were most often absent to fulfil expectations related to their role as breadwinners, with dual practice and work in other sectors to generate additional income generation as their formal salaries were considered irregular and poor. Demands arising from socio-cultural and religious events affected the attendance of both male and female health workers. Both men and women were subject to sanctions, but managers and facility chairs were more lenient with women when absence was due to caregiving and other domestic responsibilities. In summary, gender roles influence absenteeism amongst primary healthcare workers in Nigeria and thus should be taken into account in developing nuanced responses that take account of the social, economic and cultural factors that underpin these roles.
Selection and performance evaluation of waste and by-product materials for thermal storage applications
Authors: Erregueragui Zineb , Tizliouine Abdeslam , Ouhsaine Lahoucine , Chafi Mohammed , Omari Lhaj El Hachemi
Published: July 2022

Recycled materials and by-products could help solve the waste crisis and support the circular economy. The aim of this study was to compare the performance of potentially available wastes and by-products in Morocco to the local rock Gneiss, for use in sensible heat thermal energy storage. A heat transfer model was developed to undertake the benchmark, a control volume approach and an implicit scheme have been used to solve the modelling equations. The study concludes that Gneiss followed by asbestos-containing waste ceramics presented the fastest charging rates and elevated energy and exergy efficiencies, while the demolition wastes showed the highest amount of recovered energy during longer periods of charge and discharge.
Techniques and applications of lignocellulose biomass sources as transport fuels and other bioproducts
Authors: Inyang Victoria , Laseinde O T , Kanakana Grace M
Published: July 2022

Lignocellulosic materials are important, cheap and abundantly available biomass feedstock, which include agricultural waste or residues, micro algae, forestry and urban solid wastes for the production of fuels and platform chemicals. These renewable energy supplies assist in decreasing dependence on fossil fuels, greenhouse gas emissions and thus environmental pollution. The various stages necessary for the conversion of lignocellulosic biomass to biofuels and bio products include pre-treatment, hydrolysis, fermentation and product recovery. However, there are many challenges that need to be overcome for successful conversion into useful commercial products while minimizing the formation of by-products at the same time. Each technology involved in the bioconversion has its own characteristics and limitations. A general overview of the different technologies involved in the conversion of lignocellulosic materials is explored, assessed and analysed in this study. Lignocellulosic biomass is most likely to be an indispensable renewable source for the economic biofuels and bioproducts production because of its availability and sustainability. The biofuels and bioproducts have potentials to decrease the use of imported fossil resources thus providing economic benefits. The development of clean, green and renewable technologies will pave the way for commercialization.
Outcomes of Mayo Clinic reBoot camps for postimplementation training in the electronic health record
Authors: Gordon Joel E , Belford Sylvia M , Aranguren Dawn L , Blair David , Fleming Richard , Gajarawala Nikunj M , Heiderscheit Jon , Laabs Susan B , Looft Kathryn A , Rosedahl Jordan K , O’Horo John C
Published: July 2022

Objective

After a new electronic health record (EHR) was implemented at Mayo Clinic, a training program called reBoot Camp was created to enhance ongoing education in response to needs identified by physician leaders.

Materials and Methods

A reBoot camp focused on EHR topics pertinent to ambulatory care was offered from April 2018 through June 2020. There were 37 2-day sessions and 43 1-day sessions, with 673 unique participants. To evaluate outcomes of the reBoot camp, we used survey data to study baseline, immediate, and long-term perceptions of program satisfaction and self-assessed skills with the EHR. The study was conducted among practitioners at a large ambulatory practice network based in several states. Data were collected from April 2018 through January 2021. We analyzed automatically collected metadata and scores that evaluated the amount of personalization and proficiency of use.

Results

Confidence in skills increased by 13.5 points for general EHR use and was significant in 5 subdomains of use (13–18 point improvement). This degree of user confidence was maintained at the 6-month reassessment. The outcomes of configuration and proficiency scores also improved significantly.

Discussion

Ongoing education regarding EHR tools is necessary to support continued use of technology. This study was novel because of the amount and breadth of data collected, diversity of user participation, and validation that improvements were maintained over time.

Conclusions

Participating in a reBoot camp significantly improved user confidence in each domain of the EHR and demonstrated use of best-practice tools. Users maintained gains at the 6-month evaluation phase.
Automated growth monitoring app (GROWIN): a mobile Health (mHealth) tool to improve the diagnosis and early management of growth and nutritional disorders in childhood
Authors: de Arriba Muñoz Antonio , García Castellanos María Teresa , Cajal Mercedes Domínguez , Beisti Ortego Anunciación , Ruiz Ignacio Martínez , Labarta Aizpún José Ignacio
Published: July 2022

Objective

To assess the functionality and feasibility of the GROWIN app for promoting early detection of growth disorders in childhood, supporting early interventions, and improving children’s lifestyle by analyzing data collected over 3 years (2018–2020).

Methods

We retrospectively assessed the growth parameters (height, weight, body mass index [BMI], abdominal circumference) entered by users (caregivers/parents) in the GROWIN app. We also analyzed the potential health problems detected and the messages/recommendations the app showed. Finally, we assessed the possible impact/benefit of the app on the growth of the children.

Results

A total of 21 633 users (Spanish [65%], Latin American [30%], and others [5%]) entered 10.5 ± 8.3 measurements (0–15 y old). 1200 recommendations were for low height and 550 for low weight. 1250 improved their measurements. A specialist review was recommended in 500 patients due to low height. 2567 nutrition tests were run. All children with obesity (n = 855, BMI: 27.8 kg/m2 [2.25 SD]) completed the initial test with a follow-up of ≥1 year. Initial results (score: 8.1) showed poor eating habits (fast food, commercially baked goods, candy, etc.), with >90% not having breakfast. After 3–6 months, BMI decreased ≥1 point, and test scores increased ≥2 points. This benefit was maintained beyond 1 year and was correlated with an improvement in BMI (r = −.65, P = .01).

Discussion/Conclusions

The GROWIN app represents an innovative automated solution for families to monitor growth. It allows the early detection of abnormal growth indicators during childhood and adolescence, promoting early interventions. Additionally, in children with obesity, an improvement in healthy nutritional habits and a decrease in BMI were observed.
Markets, Sovereignty, and Racialization
Authors: Fakhri Michael
Published: July 2022

The 2009 European Union (EU) Seal Regime banning the importation of seal products on moral grounds and the series of cases before the EU courts and World Trade Organization provide an opportunity to understand how capitalism relies on racial categories. The EU Seal Regime is racist since it constructs an Indigenous identity based on abstract European definitions of subsistence hunting. It also has a unique racializing dynamic that proports to protect Indigenous identity from afar but in effect decimates Indigenous communities in their homeland. In this struggle over seals and the trade laws that constitute the global seal market, the concept of sovereignty in this instance helps clarify what is at stake. What is at stake is a contest over who has jurisdiction over seal bodies: whoever has the power to create the market rules that determine the taking and selling of seals in effect determines the sovereign power in the Arctic. Ultimately, what is problematic with the Seal Regime is that the definition of European morals used to justify the ban of seal products relied on a relationship that simultaneously ignored and threatened Indigenous existence.
Causes of Inappropriate Laboratory Test Ordering from the Perspective of Medical Laboratory Technical Professionals: Implications for Research and Education
Authors: VanSpronsen Amanda D , Zychla Laura , Turley Elona , Villatoro Valentin , Yuan Yan , Ohinmaa Arto
Published: July 2022

Objective

Inappropriate laboratory test ordering is a significant and persistent problem. Many causes have been identified and studied. Medical laboratory professionals (MLPs) are technical staff within clinical laboratories who are uniquely positioned to comment on why inappropriate ordering occurs. We aimed to characterize existing MLP perceptions in this domain to reveal new or underemphasized interventional targets.

Methods

We developed and disseminated a self-administered survey to MLPs in Canada, including open-ended responses to questions about the causes of inappropriate laboratory test ordering.

Results

Four primary themes were identified from qualitative analysis: ordering-provider factors, communication factors, existing test-ordering processes, and patient factors. Although these factors can largely be found in previous literature, some are under-studied.

Conclusion

MLP insights into nonphysician triage ordering and poor result communication provide targets for further investigation. A heavy focus on individual clinician factors suggests that current understandings and interprofessional skills in the MLP population can be improved.
Knowledge and Attitudes Regarding Human Papillomavirus Among Active Duty Service Members at a Large Military Base
Authors: Ward Marion , Beltran Thomas , Corbo Allyson , Sevilla Maureen , Bedno Sheryl , Penick Emily
Published: July 2022

Objective

To assess gaps in human papillomavirus (HPV) knowledge and current attitudes toward HPV vaccination among active duty soldiers at Fort Bragg, NC, and to evaluate the impact of the instruction intervention on knowledge and attitudes regarding HPV vaccination.

Methods

A six-question assessment was administered to soldiers presenting for appointments through the Epidemiology and Disease Control (EDC) Clinic at Fort Bragg in January 2020. Questions included five multiple choice knowledge assessments and a Likert scale attitude question regarding HPV vaccination. The assessment was administered before and after a one-on-one educational intervention conducted by the EDC Clinic nursing staff. Pre- and post-assessments were matched using unique encounter numbers.

Results

A total of 139 matched pre- and post-education assessments were completed. Statistically significant changes in HPV knowledge were observed in test score and percent correct (P < .001). Additionally, for individuals reporting no prior HPV vaccination, attitudes toward receiving it increased from 4 (interquartile range 3-5) to 5 (4-5) following instructions (P < .001). This indicates a shift from moderately interested to very interested.

Conclusions

Results among soldiers demonstrated a lack of knowledge regarding HPV infection, its long-term effects, and preventive measures available among this population of active duty members. Assessment results also illustrated education about HPV infection and vaccination positively impacts soldiers’ knowledge and attitudes toward HPV vaccination.
Ground-based observability of Dimorphos DART impact ejecta: photometric predictions
Authors: Moreno Fernando , Campo Bagatin Adriano , Tancredi Gonzalo , Liu Po-Yen , Domínguez Bruno
Published: July 2022

The Double Asteroid Redirection Test (DART) is a NASA mission intended to crash a projectile on Dimorphos, the secondary component of the binary (65803) Didymos system, to study its orbit deflection. As a consequence of the impact, a dust cloud will be be ejected from the body, potentially forming a transient coma- or comet-like tail on the hours or days following the impact, which might be observed using ground-based instrumentation. Based on the mass and speed of the impactor, and using known scaling laws, the total mass ejected can be roughly estimated. Then, with the aim to provide approximate expected brightness levels of the coma and tail extent and morphology, we have propagated the orbits of the particles ejected by integrating their equation of motion, and have used a Monte Carlo approach to study the evolution of the coma and tail brightness. For typical power-law particle size distribution of index –3.5, with radii rrmin = 1 μm and rmax = 1 cm, and ejection speeds near 10 times the escape velocity of Dimorphos, we predict an increase of brightness of ∼3 magnitudes right after the impact, and a decay to pre-impact levels some 10 d after. That would be the case if the prevailing ejection mechanism comes from the impact-induced seismic wave. However, if most of the ejecta is released at speeds of the order of ≳100 m s−1, the observability of the event would reduce to a very short time span, of the order of 1 d or shorter.
A truncated inner disc in the Seyfert 1 galaxy WKK 4438
Authors: Gallo L C , Buhariwalla M Z , Jiang J , D’Ammando F , Walton D J
Published: July 2022

Understanding whether and when the accretion disc extends down to the innermost stable circular orbit is important since it is the fundamental assumption behind measuring black hole spin. Here, we examine the 2013 and 2018 NuSTAR and Swift data ($0.5\!-\!50{\rm \, keV}$) of the narrow-line Seyfert 1 galaxy, WKK 4438. The X-ray emission can be fitted well with models depicting a corona and blurred reflection originating from a disc around a low-spin (a* ≈ 0) black hole. However, such models result in unconventional values for some of the parameters (e.g. inverted emissivity profile and high coronal height). Alternatively, equally good fits can be achieved if the disc is truncated at $\sim 10{\, r_{\rm g}}$ and the black hole is spinning at the Thorne limit (a* = 0.998). In these cases, the model parameters are consistent with the interpretation that the corona is centrally located close to the black hole and illuminating the disc at a larger distance.
Activating natural product synthesis using CRISPR interference and activation systems in Streptomyces
Authors: Ameruoso Andrea , Villegas Kcam Maria Claudia , Cohen Katherine Piper , Chappell James
Published: July 2022

The rise of antibiotic-resistant bacteria represents a major threat to global health, creating an urgent need to discover new antibiotics. Natural products derived from the genus Streptomyces represent a rich and diverse repertoire of chemical molecules from which new antibiotics are likely to be found. However, a major challenge is that the biosynthetic gene clusters (BGCs) responsible for natural product synthesis are often poorly expressed under laboratory culturing conditions, thus preventing the isolation and screening of novel chemicals. To address this, we describe a novel approach to activate silent BGCs through rewiring endogenous regulation using synthetic gene regulators based upon CRISPR-Cas. First, we refine CRISPR interference (CRISPRi) and create CRISPR activation (CRISPRa) systems that allow for highly programmable and effective gene repression and activation in Streptomyces. We then harness these tools to activate a silent BGC by perturbing its endogenous regulatory network. Together, this work advances the synthetic regulatory toolbox for Streptomyces and facilitates the programmable activation of silent BGCs for novel chemical discovery.
Structural analysis of the basal state of the Artemis:DNA-PKcs complex
Authors: Watanabe Go , Lieber Michael R , Williams Dewight R
Published: July 2022

Artemis nuclease and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are key components in nonhomologous DNA end joining (NHEJ), the major repair mechanism for double-strand DNA breaks. Artemis activation by DNA-PKcs resolves hairpin DNA ends formed during V(D)J recombination. Artemis deficiency disrupts development of adaptive immunity and leads to radiosensitive T- B- severe combined immunodeficiency (RS-SCID). An activated state of Artemis in complex with DNA-PK was solved by cryo-EM recently, which showed Artemis bound to the DNA. Here, we report that the pre-activated form (basal state) of the Artemis:DNA-PKcs complex is stable on an agarose-acrylamide gel system, and suitable for cryo-EM structural analysis. Structures show that the Artemis catalytic domain is dynamically positioned externally to DNA-PKcs prior to ABCDE autophosphorylation and show how both the catalytic and regulatory domains of Artemis interact with the N-HEAT and FAT domains of DNA-PKcs. We define a mutually exclusive binding site for Artemis and XRCC4 on DNA-PKcs and show that an XRCC4 peptide disrupts the Artemis:DNA-PKcs complex. All of the findings are useful in explaining how a hypomorphic L3062R missense mutation of DNA-PKcs could lead to insufficient Artemis activation, hence RS-SCID. Our results provide various target site candidates to design disruptors for Artemis:DNA-PKcs complex formation.
Regulated dicing of pre-mir-144 via reshaping of its terminal loop
Authors: Shang Renfu , Kretov Dmitry A , Adamson Scott I , Treiber Thomas , Treiber Nora , Vedanayagam Jeffrey , Chuang Jeffrey H , Meister Gunter , Cifuentes Daniel , Lai Eric C
Published: July 2022

Although the route to generate microRNAs (miRNAs) is often depicted as a linear series of sequential and constitutive cleavages, we now appreciate multiple alternative pathways as well as diverse strategies to modulate their processing and function. Here, we identify an unusually profound regulatory role of conserved loop sequences in vertebrate pre-mir-144, which are essential for its cleavage by the Dicer RNase III enzyme in human and zebrafish models. Our data indicate that pre-mir-144 dicing is positively regulated via its terminal loop, and involves the ILF3 complex (NF90 and its partner NF45/ILF2). We provide further evidence that this regulatory switch involves reshaping of the pre-mir-144 apical loop into a structure that is appropriate for Dicer cleavage. In light of our recent findings that mir-144 promotes the nuclear biogenesis of its neighbor mir-451, these data extend the complex hierarchy of nuclear and cytoplasmic regulatory events that can control the maturation of clustered miRNAs.
The molecular mechanism of microRNA duplex selectivity of Arabidopsis ARGONAUTE10
Authors: Xiao Yao , MacRae Ian J
Published: July 2022

Small RNAs (sRNAs), including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are essential gene regulators for plant and animal development. The loading of sRNA duplexes into the proper ARGONAUTE (AGO) protein is a key step to forming a functional silencing complex. In Arabidopsis thaliana, the specific loading of miR166/165 into AGO10 (AtAGO10) is critical for the maintenance of the shoot apical meristem, the source of all shoot organs, but the mechanism by which AtAGO10 distinguishes miR166/165 from other cellular miRNAs is not known. Here, we show purified AtAGO10 alone lacks loading selectivity towards miR166/165 duplexes. However, phosphate and HSP chaperone systems reshape the selectivity of AtAGO10 to its physiological substrates. A loop in the AtAGO10 central cleft is essential for recognizing specific mismatches opposite the guide strand 3′ region in miR166/165 duplexes. Replacing this loop with the equivalent loop from Homo sapiens AGO2 (HsAGO2) changes AtAGO10 miRNA loading behavior such that 3′ region mismatches are ignored and mismatches opposite the guide 5′ end instead drive loading, as in HsAGO2. Thus, this study uncovers the molecular mechanism underlying the miR166/165 selectivity of AtAGO10, essential for plant development, and provides new insights into how miRNA duplex structures are recognized for sRNA sorting.
Strand annealing and motor driven activities of SMARCAL1 and ZRANB3 are stimulated by RAD51 and the paralog complex
Authors: Halder Swagata , Ranjha Lepakshi , Taglialatela Angelo , Ciccia Alberto , Cejka Petr
Published: July 2022

SMARCAL1, ZRANB3 and HLTF are required for the remodeling of replication forks upon stress to promote genome stability. RAD51, along with the RAD51 paralog complex, were also found to have recombination-independent functions in fork reversal, yet the underlying mechanisms remained unclear. Using reconstituted reactions, we build upon previous data to show that SMARCAL1, ZRANB3 and HLTF have unequal biochemical capacities, explaining why they have non-redundant functions. SMARCAL1 uniquely anneals RPA-coated ssDNA, which depends on its direct interaction with RPA, but not on ATP. SMARCAL1, along with ZRANB3, but not HLTF efficiently employ ATPase driven translocase activity to rezip RPA-covered bubbled DNA, which was proposed to mimic elements of fork reversal. In contrast, ZRANB3 and HLTF but not SMARCAL1 are efficient in branch migration that occurs downstream in fork remodeling. We also show that low concentrations of RAD51 and the RAD51 paralog complex, RAD51B–RAD51C–RAD51D–XRCC2 (BCDX2), directly stimulate the motor-driven activities of SMARCAL1 and ZRANB3 but not HLTF, and the interplay is underpinned by physical interactions. Our data provide a possible mechanism explaining previous cellular experiments implicating RAD51 and BCDX2 in fork reversal.
Systemic approaches using single cell transcriptome reveal that C/EBPγ regulates autophagy under amino acid starved condition
Authors: Kim Dongha , Kim Junil , Yu Young Suk , Kim Yong Ryoul , Baek Sung Hee , Won Kyoung-Jae
Published: July 2022

Autophagy, a catabolic process to remove unnecessary or dysfunctional organelles, is triggered by various signals including nutrient starvation. Depending on the types of the nutrient deficiency, diverse sensing mechanisms and signaling pathways orchestrate for transcriptional and epigenetic regulation of autophagy. However, our knowledge about nutrient type-specific transcriptional regulation during autophagy is limited. To understand nutrient type-dependent transcriptional mechanisms during autophagy, we performed single cell RNA sequencing (scRNAseq) in the mouse embryonic fibroblasts (MEFs) with or without glucose starvation (GS) as well as amino acid starvation (AAS). Trajectory analysis using scRNAseq identified sequential induction of potential transcriptional regulators for each condition. Gene regulatory rules inferred using TENET newly identified CCAAT/enhancer binding protein γ (C/EBPγ) as a regulator of autophagy in AAS, but not GS, condition, and knockdown experiment confirmed the TENET result. Cell biological and biochemical studies validated that activating transcription factor 4 (ATF4) is responsible for conferring specificity to C/EBPγ for the activation of autophagy genes under AAS, but not under GS condition. Together, our data identified C/EBPγ as a previously unidentified key regulator under AAS-induced autophagy.
Exploiting Genomic Features to Improve the Prediction of Transcription Factor-Binding Sites in Plants
Authors: Rivière Quentin , Corso Massimiliano , Ciortan Madalina , Noël Grégoire , Verbruggen Nathalie , Defrance Matthieu
Published: July 2022

The identification of transcription factor (TF) target genes is central in biology. A popular approach is based on the location by pattern matching of potential cis-regulatory elements (CREs). During the last few years, tools integrating next-generation sequencing data have been developed to improve the performance of pattern matching. However, such tools have not yet been comprehensively evaluated in plants. Hence, we developed a new streamlined method aiming at predicting CREs and target genes of plant TFs in specific organs or conditions. Our approach implements a supervised machine learning strategy, which allows decision rule models to be learnt using TF ChIP-chip/seq experimental data. Different layers of genomic features were integrated in predictive models: the position on the gene, the DNA sequence conservation, the chromatin state and various CRE footprints. Among the tested features, the chromatin features were crucial for improving the accuracy of the method. Furthermore, we evaluated the transferability of predictive models across TFs, organs and species. Finally, we validated our method by correctly inferring the target genes of key TFs controlling metabolite biosynthesis at the organ level in Arabidopsis. We developed a tool—Wimtrap—to reproduce our approach in plant species and conditions/organs for which ChIP-chip/seq data are available. Wimtrap is a user-friendly R package that supports an R Shiny web interface and is provided with pre-built models that can be used to quickly get predictions of CREs and TF gene targets in different organs or conditions in Arabidopsis thaliana, Solanum lycopersicum, Oryza sativa and Zea mays.
Class and culture in the making of an assisted living market
Authors: Altomonte Guillermina
Published: July 2022

This article examines the growing industry of elite assisted living in Chile, which represents a break with a longstanding culture of care provided at home by family members and domestic workers. How does this market, locally associated with deprivation, abandonment and standardization, become a legitimate option for the rich clientele it caters to? Drawing on 40 interviews with consumers and providers of institutional care, I show that the market for assisted living is moralized through material and symbolic continuities with forms of class privilege that residents feel slipping away. Respondents interpret assisted living as an extension of the domestic work previously consumed in clients’ homes, they reframe care as an exclusive commodity and they highlight residents’ entitlement to bend organizational structures and retain authority over space and labor. These findings shed light on the relationship of class to processes of cultural legitimation by revealing the extent to which not only the affective meanings of ‘home’, but its social hierarchies, play a role in moralizing markets of care.
XIThe Eighteenth Century
Authors: Lyons-Mcfarland Michelle , Milne Fiona , Carver Dylan , Distel Kristin M
Published: July 2022

This chapter has four sections: 1. General and Prose; 2. The Novel; 3. Poetry; 4. Drama. Section 1 is by Michelle Lyons-McFarland; section 2 is by Fiona Milne; section 3 is by Dylan Carver; section 4 is by Kristin M. Distel.
Novel Resistances Provide New Avenues to Manage Alternaria Leaf Spot (Alternaria brassicae) in Canola (Brassica napus), Mustard (B. juncea), and Other Brassicaceae Crops
Authors: Al-lami Hebba F. D. , You Ming Pei , Banga Surinder S. , Barbetti Martin J.
Published: July 2022

Alternaria leaf spot (Alternaria brassicae) can be a devastating disease in canola (Brassica napus) and mustard (B. juncea), but there are no highly effective host resistances available. Screening of 150 diverse Brassicaceae varieties under glasshouse conditions highlighted important novel resistances. In particular, Camelina sativa ‘4076’ and Diplotaxis erucoides ‘Wasabi Rocket’ had complete resistance across disease assessment parameters (leaf incidence [%LDI]; severity [%LAD]; consequent defoliation [%LCI]). The next most resistant varieties were C. sativa ‘CSA’ (%LDI 0.6; %LAD 0.4), ‘4144’ (%LDI 1.2; %LAD 0.5), ‘405’ (%LDI 1.7; %LAD 0.7), C. sativa ‘3274’ (%LDI 2.5; %LAD 0.8), Carrichtera annua ‘CAN3’ (%LDI 7.7; %LAD 4.0), and Sisymbrium irio ‘London Rocket’ (%LDI 2.1; %LAD 0.8), all with %LCI values of 0. Other genotypes showing high-level resistance included S. erysimoides ‘SER 4’ (%LDI 11.8; %LAD 5.6; %LCI 0) and D. cardaminoides ‘Wild Rocket’ (%LDI 15.5; %LAD 7.2; %LCI 0), and those showing moderate resistance were Brassica carinata ‘ML-EM-1’ (Rungwe), B. insularis ‘Moris’, B. napus ‘ZY006’, B. oxyrrhina ‘BOX1’, B. oleracea var. capitata ‘Sugarloaf’, B. tournefortii ‘CN01-104-2’, and Sinapis alba ‘Concerta’ with %LDI 21.6 to 29.8, %LAD 12.8 to 21.0, and %LCI 0 to 5.7. In particular, B. napus ‘ZY006’ for canola and B. oleracea var. capitata ‘Sugarloaf’ can now be directly utilized (i.e., without crossing impairment) for Brassica species and vegetable breeding programs, respectively. While all B. juncea genotypes were susceptible, there were some less susceptible varieties from India in comparison with genotypes from Australia or China. The most susceptible test genotype was Rapistrum sativus (%LDI 89.4; %LAD 83.9; %LCI 71.0), highlighting the value of the resistances identified. These findings not only highlight a range of novel resistances against A. brassicae for canola, mustard, and other diverse Brassicaceae breeding programs to develop resistant commercial varieties, but also emphasize highly susceptible varieties to avoid in both breeding programs and commercial situations conducive to Alternaria leaf spot.
Responsiveness and Minimally Important Differences of the Traditional Chinese Version of PROMIS Paediatric-25 Profile in Chinese Children With Cancer
Authors: Chan Stephen W. W. , Wong Arnold Y. L. , Chien C. W. , Pang Marco Y. C.
Published: July 2022

Background:

Although the Patient-Reported Outcomes Measurement Information System Paediatric-25 Profile version 2.0 (PROMIS-25) has shown good reliability and validity in assessing HRQOL in Chinese children with cancer, its responsiveness (ie, the ability of the instrument to identify temporal changes in the construct to be measured) in detecting clinically meaningful changes in these children remains unclear.

Objective:

To evaluate the responsiveness and minimally important difference (MID) of the traditional Chinese PROMIS-25 for Chinese children with cancer.

Design:

Prospective study.

Methods:

The responsiveness of traditional Chinese PROMIS-25 domains before and after cancer treatment was evaluated by testing 24 a priori hypotheses of the correlations between changes in the domain scores and the corresponding changes in domain/total scores of the traditional Chinese Patient Health Questionnaire-9, traditional Chinese Paediatric Quality of Life Inventory 4.0, and 11-point numeric pain rating scale. The MID for each domain was determined by anchored-based method (MID-A), receiver operating characteristic curve analysis method, and distribution-based method (MID-D).

Results:

A total of 103 children with cancer (13.1 ± 1.8 years) were recruited. The traditional Chinese PROMIS-25 demonstrated moderate to high responsiveness. As all MID-As were higher than the MID-Ds, MID-As were recommended to determine domain changes. The MID-As were Physical Function = 12.3; Anxiety = 17.2; Depression = 15.4; Fatigue = 13.6; Peer Relationships = 6.5; and Pain Interference = 13.0.

Limitations:

This study excluded children with cognitive or visual impairments, as well as those requiring end-of-life care.

Conclusions:

The traditional Chinese PROMIS-25 is a responsive instrument to detect health-related quality of life changes among Chinese children with cancer. Our results provided important references for using PROMIS-25 in clinical practice and research.
Redefining Child Protection
Authors: Wakeman Sarah E. , Bryant Allison , Harrison Nzinga
Published: July 2022

There has been growing attention on the effect of substance use, including opioid use disorder, on pregnant and birthing people and their infants. Although effective medication treatment for opioid use disorder is the standard of care, racial disparities are evident in access during pregnancy. Structural racism affects treatment access and approaches to reporting to child welfare services. Black people and their newborns are more likely to be drug tested in medical settings, and Black newborns are more likely to be reported to child welfare services. Child welfare models often focus on substance use as being the dominant issue that drives risk for abuse or neglect of a child, and current reporting practices, which vary by state, contribute to these disparities. This commentary proposes an alternate way of thinking about family-based support. We suggest changes to law, institutional policy, clinical care, and ideology. Specifically, we propose realigning around shared goals of supporting the birthing person–infant dyad and recognizing that substance use is not synonymous with abuse or neglect; creating an anonymous notification process outside of the child welfare system to meet federal data-collection requirements; limiting perinatal drug testing and requiring written, informed consent for parental and neonatal testing; and developing integrated care teams and hospital settings and policies that support dyadic care.
Transcutaneous Electrical Nerve Stimulation for Post–Cesarean Birth Pain Control
Authors: Kurata Nicole B. , Ghatnekar Reema J. , Mercer Elizabeth , Chin Jennifer M. , Kaneshiro Bliss , Yamasato Kelly S.
Published: July 2022

OBJECTIVE:

To evaluate whether transcutaneous electrical nerve stimulation (TENS) reduces opioid use after cesarean birth.

METHODS:

We conducted a randomized, double-blind, placebo-controlled trial of TENS after cesarean birth, with the primary outcome of opioid use during the first 60 hours postoperatively. Secondary outcomes included pain scores and satisfaction with pain control on each postoperative day, duration of postoperative hospitalization, and adverse effects of TENS. We estimated 60 patients in each arm for 80% power to detect a 25% decrease in opioid use, assuming 10% attrition. To assess for a placebo effect, an additional 60 patients were randomized to no TENS during recruitment for secondary analyses comparing opioid use, pain scores, and pain control satisfaction between no TENS and placebo TENS. Analysis was by intention-to-treat.

RESULTS:

From January 2020 through March 2021, we enrolled 180 participants—60 per group. Baseline characteristics were similar across groups. Median (interquartile range) opioid consumption in the first 60 hours postoperatively, in morphine milligram equivalents, was 7.5 (0–30) with active TENS and 0 (0–22.5) with placebo TENS (P=.31). There were no significant differences in pain scores, satisfaction with pain control, or postoperative length of stay. In the no TENS group, median (interquartile range) opioid consumption in the first 60 hours postoperatively was 7.5 (0–21.9), similar to that in the placebo group (P=.57). There were also no significant differences in pain scores or pain control satisfaction between participants allocated to no TENS and those allocated to placebo TENS.

CONCLUSION:

Use of TENS after cesarean birth did not change hospital opioid consumption, pain scores, or length of postoperative stay. There was no evidence for a placebo effect of TENS on opioid use or pain scores.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov: NCT04399707.

FUNDING SOURCE:

Cardinal Health.