bluuebunny/crossref_metadata_2025 huggingface dataset:
A diving beetle’s dilemma: the impact of sexual conflict on Rensch’s rule
Authors: Polido Mariah , Lopez Vinicius M , Gonzaga da Silva Guilherme , Del Lama Marco A , Guillermo-Ferreira Rhainer
Published: October 2023

Sexual conflict is believed to be an important evolutionary force driving phenotypic diversification, especially sexual dimorphism. Males of diving beetles sometimes resort to coercive tactics to increase their chances of successful reproduction, which can impose costs on females. Sexual conflict can also drive sexual size dimorphism (SSD), particularly in species where males are larger than females. In this context, Rensch’s rule states that SSD tends to increase with body size in species with male-biased SSD and decrease with body size in species with female-biased SSD. The role of sexual conflict in driving the evolution of the allometric relationships between males and females remains unclear. We addressed whether sexual conflict in diving beetles might drive SSD. We found that dytiscids do not follow Rensch’s rule, whereby the SSD is isometric in relationship to species body size. Species with adhesive pads (Dytiscinae) showed a more pronounced SSD than other diving beetle species. These results suggest that the presence of adhesive pads might reduce the force necessary to control female movement during copulation and drive the evolution of smaller males. The findings of this study provide new insights into the role of sexual conflict in driving the evolution of SSD in animals.
Multimodal layer modelling reveals in vivo pathology in amyotrophic lateral sclerosis
Authors: Northall Alicia , Doehler Juliane , Weber Miriam , Tellez Igor , Petri Susanne , Prudlo Johannes , Vielhaber Stefan , Schreiber Stefanie , Kuehn Esther
Published: October 2023

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterized by the loss of motor control. Current understanding of ALS pathology is largely based on post-mortem investigations at advanced disease stages. A systematic in vivo description of the microstructural changes that characterize early stage ALS, and their subsequent development, is so far lacking.

Recent advances in ultra-high field (7 T) MRI data modelling allow us to investigate cortical layers in vivo. Given the layer-specific and topographic signature of ALS pathology, we combined submillimetre structural 7 T MRI data (qT1, QSM), functional localizers of body parts (upper limb, lower limb, face) and layer modelling to systematically describe pathology in the primary motor cortex (M1), in 12 living ALS patients with reference to 12 matched controls. Longitudinal sampling was performed for a subset of patients. We calculated multimodal pathology maps for each layer (superficial layer, layer 5a, layer 5b, layer 6) of M1 to identify hot spots of demyelination, iron and calcium accumulation in different cortical fields.

We show preserved mean cortical thickness and layer architecture of M1, despite significantly increased iron in layer 6 and significantly increased calcium in layer 5a and superficial layer, in patients compared to controls. The behaviourally first-affected cortical field shows significantly increased iron in L6 compared to other fields, while calcium accumulation is atopographic and significantly increased in the low myelin borders between cortical fields compared to the fields themselves. A subset of patients with longitudinal data shows that the low myelin borders are particularly disrupted and that calcium hot spots, but to a lesser extent iron hot spots, precede demyelination. Finally, we highlight that a very slow progressing patient (Patient P4) shows a distinct pathology profile compared to the other patients.

Our data show that layer-specific markers of in vivo pathology can be identified in ALS patients with a single 7 T MRI measurement after first diagnosis, and that such data provide critical insights into the individual disease state. Our data highlight the non-topographic architecture of ALS disease spread and the role of calcium, rather than iron accumulation, in predicting future demyelination. We also highlight a potentially important role of low myelin borders, that are known to connect to multiple areas within the M1 architecture, in disease spread. Finally, the distinct pathology profile of a very-slow progressing patient (Patient P4) highlights a distinction between disease duration and progression.

Our findings demonstrate the importance of in vivo histology imaging for the diagnosis and prognosis of neurodegenerative diseases such as ALS.
An Intelligent Air Monitoring System For Pollution Prediction: A Predictive Healthcare Perspective
Authors: Behal Veerawali , Singh Ramandeep
Published: October 2023

The extensive potential of Internet of Things (IoT) technology has enabled the widespread real-time perception and analysis of health conditions. Furthermore, the integration of IoT in the healthcare industry has resulted in the development of intelligent applications, including smartphone-based healthcare, wellness-aware recommendations and smart medical systems. Building upon these technological advancements, this research puts forth an enhanced framework designed for the real-time monitoring, detection and prediction of health vulnerabilities arising from air pollution. Specifically, a four-layered model is presented to categorize health-impacting particles associated with air pollution into distinct classes based on probabilistic parameters of Health Adversity (HA). Subsequently, the HA parameters are extracted and temporally analyzed using FogBus, a fog computing platform, to identify vulnerabilities in individual health. To facilitate accurate prediction, an assessment of the Air Impact on Health is conducted using a Differential Evolution-Recurrent Neural Network. Moreover, the temporal analysis of health vulnerability employs the Self-Organized Mapping technique for visualization. The proposed model’s validity is evaluated using a challenging dataset comprising nearly 60 212 data instances obtained from the online University of California, Irvine repository. Performance enhancement is assessed by comparing the proposed model with state-of-the-art decision-making techniques, considering statistical parameters such as temporal effectiveness, coefficient of determination, accuracy, specificity, sensitivity, reliability and stability.
ESOMIR: a curated database of biomarker genes and miRNAs associated with esophageal cancer
Authors: Sindhoo Asma , Sipy Saima , Khan Abbas , Selvaraj Gurudeeban , Alshammari Abdulrahman , Casida Mark Earl , Wei Dong-Qing
Published: October 2023

‘Esophageal cancer’ (EC) is a highly aggressive and deadly complex disease. It comprises two types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with Barrett’s esophagus (BE) being the only known precursor. Recent research has revealed that microRNAs (miRNAs) play a crucial role in the development, prognosis and treatment of EC and are involved in various human diseases. Biological databases have become essential for cancer research as they provide information on genes, proteins, pathways and their interactions. These databases collect, store and manage large amounts of molecular data, which can be used to identify patterns, predict outcomes and generate hypotheses. However, no comprehensive database exists for EC and miRNA relationships. To address this gap, we developed a dynamic database named ‘ESOMIR (miRNA in esophageal cancer) (https://esomir.dqweilab-sjtu.com)’, which includes information about targeted genes and miRNAs associated with EC. The database uses analysis and prediction methods, including experimentally endorsed miRNA(s) information. ESOMIR is a user-friendly interface that allows easy access to EC-associated data by searching for miRNAs, target genes, sequences, chromosomal positions and associated signaling pathways. The search modules are designed to provide specific data access to users based on their requirements. Additionally, the database provides information about network interactions, signaling pathways and region information of chromosomes associated with the 3ʹuntranslated region (3ʹUTR) or 5ʹUTR and exon sites. Users can also access energy levels of specific miRNAs with targeted genes. A fuzzy term search is included in each module to enhance the ease of use for researchers. ESOMIR can be a valuable tool for researchers and clinicians to gain insight into EC, including identifying biomarkers and treatments for this aggressive tumor.

Database URL https://esomir.dqweilab-sjtu.com
Double robustness for complier parameters and a semi-parametric test for complier characteristics
Authors: Singh Rahul , Sun Liyang
Published: October 2023

We propose a semi-parametric test to evaluate (a) whether different instruments induce subpopulations of compliers with the same observable characteristics, on average; and (b) whether compliers have observable characteristics that are the same as the full population, treated subpopulation, or untreated subpopulation, on average. The test is a flexible robustness check for the external validity of instruments. To justify the test, we characterise the doubly robust moment for Abadie’s class of complier parameters, and we analyse a machine learning update to weighting that we call the automatic $\kappa$ weight. We use the test to reinterpret Angrist and Evans' different local average treatment effect estimates obtained using different instrumental variables.
Effective fitness under fluctuating selection with genetic drift
Authors: Song Siliang , Zhang Jianzhi
Published: October 2023

The natural environment fluctuates for virtually every population of organisms. As a result, the fitness of a mutant may vary temporally. While commonly used for summarizing the effect of fluctuating selection on the mutant, geometric mean fitness can be misleading under some circumstances due to the influence of genetic drift. Here, we show by mathematical proof and computer simulation that, with genetic drift, the geometric mean fitness does not accurately reflect the overall effect of fluctuating selection. We propose an alternative measure based on the average expected allele frequency change caused by selection and demonstrate that this measure—effective fitness—better captures the overall effect of fluctuating selection in the presence of drift.
Mutator transposon insertions within maize genes often provide a novel outward reading promoter
Authors: Ellison Erika L , Zhou Peng , Hermanson Peter , Chu Yi-Hsuan , Read Andrew , Hirsch Candice N , Grotewold Erich , Springer Nathan M
Published: October 2023

The highly active family of Mutator (Mu) DNA transposons has been widely used for forward and reverse genetics in maize. There are examples of Mu-suppressible alleles that result in conditional phenotypic effects based on the activity of Mu. Phenotypes from these Mu-suppressible mutations are observed in Mu-active genetic backgrounds, but absent when Mu activity is lost. For some Mu-suppressible alleles, phenotypic suppression likely results from an outward-reading promoter within Mu that is only active when the autonomous Mu element is silenced or lost. We isolated 35 Mu alleles from the UniformMu population that represent insertions in 24 different genes. Most of these mutant alleles are due to insertions within gene coding sequences, but several 5′ UTR and intron insertions were included. RNA-seq and de novo transcript assembly were utilized to document the transcripts produced from 33 of these Mu insertion alleles. For 20 of the 33 alleles, there was evidence of transcripts initiating within the Mu sequence reading through the gene. This outward-reading promoter activity was detected in multiple types of Mu elements and does not depend on the orientation of Mu. Expression analyses of Mu-initiated transcripts revealed the Mu promoter often provides gene expression levels and patterns that are similar to the wild-type gene. These results suggest the Mu promoter may represent a minimal promoter that can respond to gene cis-regulatory elements. Findings from this study have implications for maize researchers using the UniformMu population, and more broadly highlight a strategy for transposons to co-exist with their host.
Galectin-3 does not interact with RNA directly
Authors: Peltan Egan L , Riley Nicholas M , Flynn Ryan A , Roberts David S , Bertozzi Carolyn R
Published: October 2023

Galectin-3, well characterized as a glycan binding protein, has been identified as a putative RNA binding protein, possibly through participation in pre-mRNA maturation through interactions with splicosomes. Given recent developments with cell surface RNA biology, the putative dual-function nature of galectin-3 evokes a possible non-classical connection between glycobiology and RNA biology. However, with limited functional evidence of a direct RNA interaction, many molecular-level observations rely on affinity reagents and lack appropriate genetic controls. Thus, evidence of a direct interaction remains elusive. We demonstrate that antibodies raised to endogenous human galectin-3 can isolate RNA-protein crosslinks, but this activity remains insensitive to LGALS3 knock-out. Proteomic characterization of anti-galectin-3 IPs revealed enrichment of galectin-3, but high abundance of hnRNPA2B1, an abundant, well-characterized RNA-binding protein with weak homology to the N-terminal domain of galectin-3, in the isolate. Genetic ablation of HNRNPA2B1, but not LGALS3, eliminates the ability of the anti-galectin-3 antibodies to isolate RNA-protein crosslinks, implying either an indirect interaction or cross-reactivity. To address this, we introduced an epitope tag to the endogenous C-terminal locus of LGALS3. Isolation of the tagged galectin-3 failed to reveal any RNA-protein crosslinks. This result suggests that the galectin-3 does not directly interact with RNA and may be misidentified as an RNA-binding protein, at least in HeLa where the putative RNA associations were first identified. We encourage further investigation of this phenomenon employ gene deletions and, when possible, endogenous epitope tags to achieve the specificity required to evaluate potential interactions.
Functional analysis of germline VANGL2 variants using rescue assays of vangl2 knockout zebrafish
Authors: Derrick Christopher J , Szenker-Ravi Emmanuelle , Santos-Ledo Adrian , Alqahtani Ahlam , Yusof Amirah , Eley Lorraine , Coleman Alistair H L , Tohari Sumanty , Ng Alvin Yu-Jin , Venkatesh Byrappa , Alharby Essa , Mansard Luke , Bonnet-Dupeyron Marie-Noelle , Roux Anne-Francoise , Vaché Christel , Roume Joëlle , Bouvagnet Patrice , Almontashiri Naif A M , Henderson Deborah J , Reversade Bruno , Chaudhry Bill
Published: October 2023

Developmental studies have shown that the evolutionarily conserved Wnt Planar Cell Polarity (PCP) pathway is essential for the development of a diverse range of tissues and organs including the brain, spinal cord, heart and sensory organs, as well as establishment of the left-right body axis. Germline mutations in the highly conserved PCP gene VANGL2 in humans have only been associated with central nervous system malformations, and functional testing to understand variant impact has not been performed. Here we report three new families with missense variants in VANGL2 associated with heterotaxy and congenital heart disease p.(Arg169His), non-syndromic hearing loss p.(Glu465Ala) and congenital heart disease with brain defects p.(Arg135Trp). To test the in vivo impact of these and previously described variants, we have established clinically-relevant assays using mRNA rescue of the vangl2 mutant zebrafish. We show that all variants disrupt Vangl2 function, although to different extents and depending on the developmental process. We also begin to identify that different VANGL2 missense variants may be haploinsufficient and discuss evidence in support of pathogenicity. Together, this study demonstrates that zebrafish present a suitable pipeline to investigate variants of unknown significance and suggests new avenues for investigation of the different developmental contexts of VANGL2 function that are clinically meaningful.
MdAIL5 overexpression promotes apple adventitious shoot regeneration by regulating hormone signaling and activating the expression of shoot development-related genes
Authors: Liu Kai , Yang An , Yan Jiadi , Liang Zhaolin , Yuan Gaopeng , Cong Peihua , Zhang Liyi , Han Xiaolei , Zhang Caixia
Published: October 2023

Adventitious shoot (AS) regeneration is a significant factor in the genetic transformation of horticultural plants. It is also a noteworthy approach to their vegetative propagation. AS regeneration remains highly dependent on the genotype or maturity of explants. We here found that the AS regeneration abilities of apple leaves were positively correlated with MdAIL5 expression. MdAIL5 overexpression dramatically increased AS regeneration efficiency. Notably, MdAIL5 overexpression could restore the AS formation ability of explants to a certain extent, which was lost with an increase in maturity. Endogenous hormone detection revealed that MdAIL5 overexpression changed the contents of auxin, cytokinin (CK), and other hormones in apple leaves. Transcriptome analysis revealed that many genes related to auxin, CK, and brassinolide signaling pathways were significantly and differentially expressed between MdAIL5-overexpressing transgenic apple and wild-type apple plants. Yeast one-hybrid assays, the electrophoretic mobility shift assay, and the dual-luciferase reporter assay revealed that MdAIL5 directly binds to MdARF9 and MdHB14 promoters and positively affects their expression. We here established a model of MdAIL5 regulating AS formation, which acts as a theoretical basis for facilitating genotype- or explant maturity-independent AS regeneration in the future.
Naked Civil Servant: Queer Sex, Catholicism and Conformism in the Post-War London Diaries of George Lucas
Authors: Janes Dominic
Published: October 2023

The minutely documented diaries of an ‘everyman’ such as George Lucas enable us to view the complex pleasures and challenging realities of the post-war queer quotidian in remarkable detail. A sample of the years after 1957, when Lucas was aged in his thirties, suggests that more attention needs to be paid to age-differential relationships and to the problematic aspects of the sexual idolization of young men. Lucas’s respectably boring career and Catholic faith can, however, be understood as having provided the stability on which his emotional survival depended, helping us to view other such unglamorous queer lives with greater empathy.
Prospects of battery assembly for electric vehicles based on patent analysis
Authors: Yang Chen , Shi Hong-Juan
Published: October 2023

The ceiling of energy density of batteries in materials level motivates the innovation of cell, module and pack that constitute the battery assembly for electric vehicles (EVs). Patent analysis is a powerful means to inform technology life cycle and forecast upcoming innovations. To date, only a handful of research have quantitatively analysed and compared battery assembly in the EV field, resulting in a lack of information to discern the battery layout. Herein, battery patents are categorized into cell, module and pack levels, and are recorded with a function of timeline and technology life cycle to identify their development status. It indicates the maturity stage of the cell level while noting the growth stage of module and pack levels, which probably results from the intensive demand of large-size and high-quality batteries for EVs. Moreover, the global patent distribution reveals that China and Japan possess most patents among cell, module and pack levels, and that patent assignees are scattered in China, whereas concentrated in Japan and Korea. This work is expected to figure out the battery technology trends to construct energy-dense batteries in the EV field, as well as provide instructive information for decision-makers to lay out battery technologies in the future.
Causal Analysis of Tactics in Soccer: The Case of Throw-ins
Authors: Epasinghege Dona Nirodha , Swartz Tim B
Published: October 2023

Accepted by: Phil Scarf

This paper investigates optimal target locations for throw-ins in soccer. The investigation is facilitated by the use of tracking data which provide the positioning of players measured at frequent intervals (i.e. 10 times per second). The methods for the investigation are necessarily causal since there are confounding variables that impact both the throw-in location and the result of the throw-in. A simple causal analysis indicates that on average, backwards throw-ins are beneficial and lead to an extra two shots per 100 throw-ins. We also observe that there is a benefit to long throw-ins where on average, they result in roughly four more shots per 100 throw-ins. These results are corroborated by a more complex causal analysis that relies on the spatial structure of throw-ins.
Syphilis Prevalence, Incidence, and Demographic Differences in a Longitudinal Study of Young Sexual and Gender Minority Adults Assigned Male at Birth
Authors: Xavier Hall Casey D , Ryan Daniel , Hayford Christina , Morgan Ethan , Tabidze Irina , D’Aquila Richard , Mustanski Brian
Published: October 2023

Background

Syphilis rates in the United States have increased. Few studies have examined syphilis incidence and prevalence prospectively among young sexual and gender minorities (YSGM).

Methods

This study of YSGM assigned male at birth comes from a Chicago-based prospective cohort at 2 visits 6 months apart (N = 882). Syphilis cases were identified through serologic test results and self-reported history.

Results

In this sample, 25.1% had a lifetime prevalence, and 3.3% were incident cases with a crude incidence rate of 6.76 per 100 person-years.

Conclusions

Lifetime syphilis and incidence are high in this sample of YSGM relative to general population samples.
Economic status as the predictor of dengue awareness among local residents of Sabah, Malaysia
Authors: Elia-Amira Nur Mohd Roslin , Chen Chee Dhang , Low Van Lun , Lau Koon Weng , Haziqah-Rashid Amirah , Amelia-Yap Zheng Hua , Chew Fong Peng , Sofian-Azirun Mohd
Published: October 2023

We investigated the knowledge, attitudes, and practices (KAPs) regarding dengue and its prevention among local residents in all five divisions of Sabah, Malaysia. A cross-sectional questionnaire survey was conducted with 1,000 residents aged 18 years and above. The results revealed that less than one-tenth of the respondents scored high in knowledge (9.6%), while more than half scored high in attitude (64.6%), and less than one-fifth (15.6%) scored high in dengue prevention practices. Economic factors (monthly salary and occupation) were the final independent predictors in all KAP domains. KAP parameters were correlated with each other, but wide gaps between the scores implied that a positive attitude was not translated into either high knowledge or practice scores. Therefore, it is imperative for the authorities to employ multifaceted approaches in future dengue awareness campaigns to increase all KAP domains, especially among those with lower economic status.
Use of clinical variables for preoperative prediction of lymph node metastasis in endometrial cancer
Authors: Ueno Yuta , Yoshida Emiko , Nojiri Shuko , Kato Tomoyasu , Ohtsu Takashi , Takeshita Toshiyuki , Suzuki Shunji , Yoshida Hiroshi , Kato Ken , Itoh Masayoshi , Notomi Tsuguto , Usui Kengo , Sozu Takashi , Terao Yasuhisa , Kawaji Hideya , Kato Hisamori
Published: October 2023

Objective

Endometrial cancer is the most common gynaecological cancer, and most patients are identified during early disease stages. Noninvasive evaluation of lymph node metastasis likely will improve the quality of clinical treatment, for example, by omitting unnecessary lymphadenectomy.

Methods

The study population comprised 611 patients with endometrial cancer who underwent lymphadenectomy at four types of institutions, comprising seven hospitals in total. We systematically assessed the association of 18 preoperative clinical variables with postoperative lymph node metastasis. We then constructed statistical models for preoperative lymph node metastasis prediction and assessed their performance with a previously proposed system, in which the score was determined by counting the number of high-risk variables among the four predefined ones.

Results

Of the preoperative 18 variables evaluated, 10 were significantly associated with postoperative lymph node metastasis. A logistic regression model achieved an area under the curve of 0.85 in predicting lymph node metastasis; this value is significantly higher than that from the previous system (area under the curve, 0.74). When we set the false-negative rate to ~1%, the new predictive model increased the rate of true negatives to 21%, compared with 6.8% from the previous one. We also provide a spreadsheet-based tool for further evaluation of its ability to predict lymph node metastasis in endometrial cancer.

Conclusions

Our new lymph node metastasis prediction method, which was based solely on preoperative clinical variables, performed significantly better than the previous method. Although additional evaluation is necessary for its clinical use, our noninvasive system may help improve the clinical treatment of endometrial cancer, complementing minimally invasive sentinel lymph node biopsy.
End-of-life walking ability in cancer patients with spinal metastases
Authors: Sawada Ryoko , Shinoda Yusuke , Ohki Takahiro , Ishibashi Yuki , Kobayashi Hiroshi , Matsubayashi Yoshitaka , Tanaka Sakae , Haga Nobuhiko
Published: October 2023

Background

Even terminal cancer patients desire to walk to the toilet by themselves until the very last day. This study aimed to describe the walking ability of patients with spinal metastases at the end-of-life stage and identify the factors affecting this ability.

Methods

Among 527 patients who first visited our multidisciplinary team for bone metastasis between 2013 and 2016, 56 patients who had spinal metastases with a Spinal Instability Neoplastic Score ≥7 and died during follow-up were included. We collected general clinical data, performance status, Frankel classification, epidural spinal cord compression scale and Spinal Instability Neoplastic Score at the first consultation. Patients’ last day of walking and date of death were also examined. Univariate analyses (chi-squared tests) were performed to identify the factors that impacted walking ability 30 and 14 days before patients’ death.

Results

A total of 56 patients were extracted, and 57.1% (32/56) and 32.7% (16/49) of patients were ambulatory 30 and 14 days before death, respectively. Their performance status (P = 0.0007), Frankel grade (P = 0.012) and epidural spinal cord compression grade (P = 0.006) at the first examination, and administration of bone modifying agents during follow-up period (P = 0.029) were significantly related to walking ability 30 days before death. Among ambulatory patients 30 days before death, those with Spinal Instability Neoplastic Score ≥10 (P = 0.005), especially with high scores of collapse (P = 0.002) and alignment (P = 0.002), were less likely to walk 14 days before death. The walking period in the last month of their life was significantly longer in patients with total Spinal Instability Neoplastic Score 7–9 (P = 0.009) and in patients without collapse (P = 0.040) by the Wilcoxon test.

Conclusion

The progression of spinal metastasis, especially neurological deficit, at the initial consultation were associated with walking ability 30 days before death, and spinal stability might be crucial for preserving walking ability during the last month. Early diagnosis and implementation of appropriate bone management might be important for the end-of-life walking ability.
Climate change and cancer: the Environmental Justice perspective
Authors: Nogueira Leticia M , Yabroff K Robin
Published: October 2023

Despite advances in cancer control—prevention, screening, diagnosis, treatment, and survivorship—racial disparities in cancer incidence and survival persist and, in some cases, are widening in the United States. Since 2020, there’s been growing recognition of the role of structural racism, including structurally racist policies and practices, as the main factor contributing to historical and contemporary disparities. Structurally racist policies and practices have been present since the genesis of the United States and are also at the root of environmental injustices, which result in disproportionately high exposure to environmental hazards among communities targeted for marginalization, increased cancer risk, disruptions in access to care, and worsening health outcomes. In addition to widening cancer disparities, environmental injustices enable the development of polluting infrastructure, which contribute to detrimental health outcomes in the entire population, and to climate change, the most pressing public health challenge of our time. In this commentary, we describe the connections between climate change and cancer through an Environmental Justice perspective (defined as the fair treatment and meaningful involvement of people of all racialized groups, nationalities, or income, in all aspects, including development, implementation, and enforcement, of policies and practices that affect the environment and public health), highlighting how the expertise developed in communities targeted for marginalization is crucial for addressing health disparities, tackling climate change, and advancing cancer control efforts for the entire population.
Trickle-Down Burdens: The Effect of Provider Burdens on Clients’ Experience
Authors: Zuber Katie , Strach Patricia , Pérez-Chiqués Elizabeth
Published: October 2023

Administrative burden research disproportionately examines micro-level burdens on clients claiming benefits from public agencies. Yet we know little about meso-level burdens on third-party providers making up the submerged state—private actors working on behalf of a public purpose—and what effect these burdens have on services. We draw on interviews, participant observation, and focus groups with substance-use disorder service providers to map provider burdens and how they affect services that third parties offer. We supplement the provider perspective with data from clients and their families about their experience with services. We find that providers face significant administrative burdens resulting from federal and state policy; that these burdens affect the quality of the services they are able to offer; and, ultimately, that burdens on providers can trickle down to become burdens on clients. Our research has implications for how we understand administrative burdens, the solutions best suited to reducing them, and the role of burdens as a form of hidden politics in the submerged state.
Efficacy, Safety, and Tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Results Through Week 96 from IMPAACT 2014
Authors: Rungmaitree Supattra , Aurpibul Linda , Best Brookie M , Li Xiang , Warshaw Meredith G , Wan Hong , Tobin Nicole H , Jumes Patricia , Leavitt Randi , McCarthy Katie , Scheckter Rachel , Ounchanum Pradthana , Violari Avy , Teppler Hedy , Campbell Havilland , Krotje Chelsea , Townley Ellen , Moye Jack , Melvin Ann J ,   IMPAACT 2014 study team, Beck Justine , Sise Thucuma , Kapogiannis Bill G , George Kathleen , Morgan Patricia , Woolwine-Cunningham Yvonne , Leblanc Rebecca , Trabert Kathleen , Mendell Jeanne , Alvero Carmelita , Farhad Mona , Pasyar Sarah , Muresan Petronella , Patel Nehali , English Adrienne , Heince Ryan , Jones Sandra , Cooper Ellen , McLaud Debra , McFarland Elizabeth , Hays Shane Curran , Dunn Jennifer , Navarro Kacey , Robson Amanda , Ndiwani Hilda , Mathiba Ruth , Violari Avy , Ramsagar Nastassja , Chotirosniramit Nuntisa , Khamrong Chintana , Chantong Jiraporn , Srita Angkana , Cressey Tim R , Sukrakanchana Praornsuda , Kaewmamuang Kanyanee , Thaweesombat Yupawan , Vanprapar Nirun , Chokephaibulkit Kulkanya , Kongstan Nantaka , Lermankul Watcharee
Published: October 2023

Background

IMPAACT 2014 study is a phase I/II, multicenter, open-label, nonrandomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed-dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks.

Methods

Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF. The efficacy endpoint was the proportion of participants with HIV-1 RNA <40 copies/mL assessed at weeks 48 and 96 using the observed failure approach. Safety and tolerability outcomes were incidence of adverse events (AEs) and treatment discontinuations.

Results

A total of 45 adolescents, median age 15 (range, 12–17) years, 58% females, were enrolled and 2 (4.4%) participants were ARV naïve. Of the 45 participants, 42 (93.3%) completed the study and 41 (91.1%) completed the study treatment. At week 48, 41/42 (97.6%; 95% confidence interval [CI], 87.4–99.9) and week 96, 37/40 (92.5%; 95% CI, 79.6–98.4) participants had achieved or maintained HIV-1 RNA <40 copies/mL. There were no treatment-related discontinuations due to AEs and no drug-related AEs ≥grade 3 or deaths.

Conclusions

We found once-daily dosing of DOR FDC to be safe and well tolerated for maintaining viral suppression through 96 weeks in adolescents living with HIV-1.
The strength of correlation between female genital self-image and sexual function: a systematic review and meta-analysis
Authors: Alavi-Arjas Fatemeh , Goodman Michael P , Simbar Masoumeh , Alavi Majd Hamid , Nahidi Fatemeh
Published: October 2023

Background

Mounting evidence indicates that female genital aesthetic complaints impact sexual relationships.

Aim

The study sought to determine the strength of the correlation between genital self-image and sexual function.

Methods

Electronic databases were comprehensively searched including PubMed, Web of Science, Scopus, PsycINFO, Embase, and the Cochrane Library from January 2000 to December 2022. After duplicate removal, 146 articles were retrieved by searching keywords in titles and abstracts.

Outcomes

A positive correlation is noted between genital self-image and sexual function; the strength of this correlation was 0.375.

Results

By omitting irrelevant articles according to the eligibility criteria, 16 articles remained for a total of 13 505 participants. All but 1 of them indicated a statistically significant positive correlation between genital self-image and sexual function. For a more accurate result, a meta-analysis was conducted noting a considerable heterogeneity.

Clinical Implications

The results of this study may be used in counseling women with sexual dysfunction who are dissatisfied with their genital appearance.

Strengths and Limitations

This study is the first systematic review to reveal the strength of the correlation between genital self-image and sexual function. The most important limitation of this study is the heterogeneity of the studies reported.

Conclusion

This systematic review indicates a positive correlation between genital self-image and sexual function. The results are restricted by inconsistency of the articles considered. Using different tools in different cultural contexts without considering confounding factors leads to a wide range of correlation sizes and significant heterogeneity is evident.
Flavonols affect the interrelated glucosinolate and camalexin biosynthetic pathways in Arabidopsis thaliana
Authors: Naik Jogindra , Tyagi Shivi , Rajput Ruchika , Kumar Pawan , Pucker Boas , Bisht Naveen C , Misra Prashant , Stracke Ralf , Pandey Ashutosh
Published: October 2023

Flavonols are structurally and functionally diverse biomolecules involved in plant biotic and abiotic stress tolerance, pollen development, and inhibition of auxin transport. However, their effects on global gene expression and signaling pathways are unclear. To explore the roles of flavonol metabolites in signaling, we performed comparative transcriptome and targeted metabolite profiling of seedlings from the flavonol-deficient Arabidopsis loss-of-function mutant flavonol synthase1 (fls1) with and without exogenous supplementation of flavonol derivatives (kaempferol, quercetin, and rutin). RNA-seq results indicated that flavonols modulate various biological and metabolic pathways, with significant alterations in camalexin and aliphatic glucosinolate synthesis. Flavonols negatively regulated camalexin biosynthesis but appeared to promote the accumulation of aliphatic glucosinolates via transcription factor-mediated up-regulation of biosynthesis genes. Interestingly, upstream amino acid biosynthesis genes involved in methionine and tryptophan synthesis were altered under flavonol deficiency and exogenous supplementation. Quercetin treatment significantly up-regulated aliphatic glucosinolate biosynthesis genes compared with kaempferol and rutin. In addition, expression and metabolite analysis of the transparent testa7 mutant, which lacks hydroxylated flavonol derivatives, clarified the role of quercetin in the glucosinolate biosynthesis pathway. This study elucidates the molecular mechanisms by which flavonols interfere with signaling pathways, their molecular targets, and the multiple biological activities of flavonols in plants.
High-redshift metallicity calibrations for JWST spectra: insights from line emission in cosmological simulations
Authors: Hirschmann Michaela , Charlot Stephane , Somerville Rachel S
Published: October 2023

Optical emission-line ratios are traditionally used to estimate gas metallicities from observed galaxy spectra. While such estimators have been calibrated primarily at low redshift, they are commonly used to interpret observations of high-redshift galaxies, where their applicability may be questioned. We use comprehensive emission-line catalogues of galaxies from the IllustrisTNG simulation including ionization by stars, active galactic nuclei, and shocks to reassess the calibrations of both optical and ultraviolet metallicity estimators at redshifts $0\lesssim z \lesssim 8$. For present-day galaxies, the predicted optical-line calibrations are consistent with previously published ones, while we find different ultraviolet-line ratios, such as He ii λ1640/C iii] λ1908, can provide powerful metallicity diagnostics. At fixed metallicity, most emission-line ratios are predicted to strongly increase or decrease with redshift (with the notable exception of N2O2 = [N ii]λ6584/[O ii] λ3727), primarily because of a change in ionization parameter. The predicted dependence of R3 = [O iii]λ5007/H β and R23 = ([O ii] λ3727 + [O iii]λ5007)/H β, and to a slightly lesser extent R2 = [O ii] λ3727/H β and O32 = [O iii]λ5007/[O ii] λ3727, on O abundance for galaxies at z = 4–8 agrees remarkably well with Te-based measurements in 14 galaxies observed with JWST. This success motivates us to provide new calibrations of optical and ultraviolet metallicity estimators specifically designed for galaxies at z > 4, to guide interpretations of future, high-redshift spectroscopic surveys. We further demonstrate that applying classical z = 0 calibrations to high-redshift galaxies can bias oxygen abundance estimates downward by up to 1 dex, leading to the inference of stronger evolution of the mass–metallicity relation than is actually occurring.
Much ado about no offset – characterizing the anomalous multiple-image configuration and the model-driven displacement between light and mass in the multiplane strong lens Abell 3827
Authors: Lin Joyce , Wagner Jenny , Griffiths Richard E
Published: October 2023

Abell 3827 is a unique galaxy cluster with a dry merger in its core causing a highly resolved multiple-image configuration of a blue spiral galaxy at zs = 1.24. The surface brightness profiles of four merging galaxies around zd = 0.099 complicate a clear identification of the number of images and finding corresponding small-scale features across them. The entailed controversies about offsets between luminous and dark matter have never been settled and dark matter characteristics in tension with bounds from complementary probes and simulations seemed necessary to explain this multiple-image configuration. We resolve these issues with a systematic study of possible feature matchings across all images and their impact on the reconstructed mass density distribution. From the local lens properties directly constrained by these feature matchings without imposing any global lens model, we conclude that none of them are consistent with expected local characteristics from standard single-lens-plane lensing, nor can they be motivated by the light distribution in the cluster. Inspecting complementary spectroscopic data, we show that all these results originate from an insufficient constraining power of the data and seem to hint at a thick lens and not at exotic forms of dark matter or modified gravity. If the thick-lens hypothesis can be corroborated with follow-up multiplane lens modelling, A3827 suffers from a full three-dimensional degeneracy in the distribution of dark matter because combinations of shearings and scalings in a single lens plane can also be represented by an effective shearing and a rotation caused by multiple lens planes.
TOI-5126: a hot super-Neptune and warm Neptune pair discovered by TESS and CHEOPS
Authors: Fairnington Tyler R , Nabbie Emma , Huang Chelsea X , Zhou George , Foo Orion , Millholland Sarah , Wright Duncan , Belinski Alexandre A , Bieryla Allyson , Ciardi David R , Collins Karen A , Collins Kevin I , Everett Mark , Howell Steve B , Lissauer Jack J , Lund Michael B , Murgas Felipe , Palle Enric , Quinn Samuel N , Relles Howard M , Safonov Boris S , Schwarz Richard P , Scott Nicholas J , Srdoc Gregor , Ricker George , Vanderspek Roland , Seager Sara , Latham David W , Winn Joshua W , Jenkins Jon M , Bouma Luke G , Shporer Avi , Ting Eric B , Dragomir Diana , Kunimoto Michelle , Eisner Nora L
Published: October 2023

We present the confirmation of a hot super-Neptune with an exterior Neptune companion orbiting a bright (V  = 10.1 mag) F-dwarf identified by the Transiting Exoplanet Survey Satellite (TESS). The two planets, observed in sectors 45, 46, and 48 of the TESS extended mission, are $4.74_{-0.14}^{+0.16}$ and $3.86_{-0.16}^{+0.17}$ R⊕ with $5.4588385_{-0.0000072}^{+0.0000070}$ and $17.8999_{-0.0013}^{+0.0018}$ d orbital periods, respectively. We also obtained precise space-based photometric follow-up of the system with ESA’s CHaracterising ExOplanets Satellite to constrain the radius and ephemeris of TOI-5126 b. TOI-5126 b is located in the ‘hot Neptune Desert’ and is an ideal candidate for follow-up transmission spectroscopy due to its high-predicted equilibrium temperature (Teq = ${1442}_{-40}^{+46}$ K) implying a cloud-free atmosphere. TOI-5126 c is a warm Neptune (Teq = $971_{-27}^{+31}$ K) also suitable for follow-up. Tentative transit timing variations have also been identified in analysis, suggesting the presence of at least one additional planet, however this signal may be caused by spot-crossing events, necessitating further precise photometric follow-up to confirm these signals.
The orbital period, black hole mass, and distance to the X-ray transient GRS 1716-249 ( =N Oph 93)
Authors: Casares J , Yanes-Rizo I V , Torres M A P , Abbott T M C , Armas Padilla M , Charles P A , Cúneo V A , Muñoz-Darias T , Jonker P G , Maguire K
Published: October 2023

We present evidence for a 0.278(8) d ( =6.7 h) orbital period in the X-ray transient GRS 1716-249 (=N Oph 93), based on a superhump modulation detected during the 1995 mini-outburst plus ellipsoidal variability in quiescence. With a quiescent magnitude of r = 23.19 ± 0.15 N Oph 93 is too faint to warrant a full dynamical study through dedicated time-resolved spectroscopy. Instead, we apply the FWHM–K2 correlation to the disc H α emission line detected in Gran Telescopio Canarias spectra and obtain K2 = 521 ± 52 km s−1. This leads to a mass function f(M) = 4.1 ± 1.2 M⊙, thus indicating the presence of a black hole in this historic X-ray transient. Furthermore, from the depth of the H α trough and the quiescent light curve we constrain the binary inclination to i = 61 ± 15°, while the detection of superhumps sets an upper limit to the donor to compact star mass ratio q = M2/M1 ≲ 0.25. Our de-reddened (r − i) colour is consistent with a ≈ K6 main sequence star that fills its Roche lobe in a 0.278 d orbit. Using all this information we derive a compact object mass $M_{1}=6.4^{+3.2}_{-2.0}$ M⊙ at 68 per cent confidence. We also constrain the distance to GRS 1716-249 to 6.9 ± 1.1 kpc, placing the binary ∼0.8 kpc above the Galactic Plane, in support of a large natal kick.
Not-so-fast Kepler-1513: a perturbing planetary interloper in the exomoon corridor
Authors: Yahalomi Daniel A , Kipping David , Nesvorný David , Dalba Paul A , Benni Paul , Cacho-Negrete Ceiligh , Collins Karen , Earwicker Joel T , Lewis John Arban , McLeod Kim K , Schwarz Richard P , Wang Gavin
Published: October 2023

Transit timing variations (TTVs) can be induced by a range of physical phenomena, including planet–planet interactions, planet–moon interactions, and stellar activity. Recent work has shown that roughly half of moons would induce fast TTVs with a short period in the range of 2–4 orbits of its host planet around the star. An investigation of the Kepler TTV data in this period range identified one primary target of interest, Kepler-1513 b. Kepler-1513 b is a $8.05^{+0.58}_{-0.40}$ R⊕ planet orbiting a late G-type dwarf at $0.53^{+0.04}_{-0.03}$ au. Using Kepler photometry, this initial analysis showed that Kepler-1513 b’s TTVs were consistent with a moon. Here, we report photometric observations of two additional transits nearly a decade after the last Kepler transit using both ground-based observations and space-based photometry with TESS. These new transit observations introduce a previously undetected long period TTV, in addition to the original short period TTV signal. Using the complete transit data set, we investigate whether a non-transiting planet, a moon, or stellar activity could induce the observed TTVs. We find that only a non-transiting perturbing planet can reproduce the observed TTVs. We additionally perform transit origami on the Kepler photometry, which independently applies pressure against a moon hypothesis. Specifically, we find that Kepler-1513 b’s TTVs are consistent with an exterior non-transiting ∼Saturn mass planet, Kepler-1513 c, on a wide orbit, $\sim 5~{{\ \rm per \, cent}}$ outside a 5:1 period ratio with Kepler-1513 b. This example introduces a previously unidentified cause for planetary interlopers in the exomoon corridor, namely an insufficient baseline of observations.