bluuebunny/crossref_metadata_2025_split huggingface dataset:
Against Medical Advice for Induction of Labor Due to Post-term Pregnancies—The Impact on Pregnancy Outcome
Authors: Blecher Yair , Michaan Nadav , Baransi Saher , Baruch Yoav , Yogev Yariv 
Published: March 2023

ABSTRACT
Postterm pregnancies are associated with adverse perinatal outcomes, including meconium and meconium aspiration syndrome, Apgar score <4 at 5 minutes, oligohydramnios, fetal macrosomia, and stillbirth. To prevent or minimize these complications in pregnancies >41 weeks of gestation, routine antenatal surveillance is recommended. In comparison to expectant management, most evidence supports benefits from induction of labor in pregnancies at 41 and 42 weeks of gestation. Yet, individuals with postterm pregnancies may decide to decline the medical recommendation for induction. Evidence on the outcomes associated with choosing care that is against medical advice (AMA) is scant in this population. The aim of this study was to examine the effect of refusing medical advice for labor induction in postterm pregnancies on maternal and neonatal outcomes.
This was a retrospective cohort study of women with pregnancies >41 + 3 weeks' gestation who refused labor induction AMA. Included were healthy, adult women with low-risk, singleton pregnancies and cephalic presentation, who received care at a single tertiary hospital between 2017 and 2019. Excluded were those with a suspected small-for-gestational-age infant, as well as those in active labor or with premature rupture of membranes, nonreassuring fetal heart rate, hypertensive disorders, diabetes, or oligohydramnios. Women who refused induction AMA (study group) were compared with those who agreed to the medical recommendation (control group) in a 1:2 ratio.
The analysis included 249 postterm women—83 in the study group and 166 in the control group. There were significantly higher rates of cesarean delivery (21.7% vs 10.2%, P = 0.04), longer postdelivery hospitalizations (2.9 vs 2.4 days, P < 0.05), and more advanced gestational age at delivery (41 + 6 vs 41 + 4 weeks, P < 0.05) in the study group versus the control group. Cesarean delivery also was indicated most often for nonreassuring fetal heart rate (77% vs 47%), followed by arrest of dilation and arrest of descent (16% vs 17.6%) and failure of induction of labor (5.5% vs 35.2%) in the study group. Among those who refused induction AMA, 67% returned to the hospital at the onset of active delivery, 24% chose to continue surveillance twice a week, and 8% were admitted upon their request for daily nonstress test and biophysical scoring. They also experienced significantly higher rates of meconium stained amniotic fluid (44% vs 15.7%, P < 0.01), admission to the neonatal intensive care unit (9.6% vs 5%, P < 0.01), and mechanical ventilation (4.81% vs 0.6%, P < 0.01). The composite of adverse maternal and neonatal outcomes was higher in the study group than the control group (25.3% vs 17.46%, P < 0.001).
In conclusion, the risk of choosing to refuse induction AMA in postterm pregnancies is associated with increased risk of adverse maternal and neonatal outcomes, as well as cesarean delivery.
Case Report: Papilledema Secondary to Cerebral Venous Sinus Thrombosis after Severe COVID-19 Infection
Authors: Smith Levi J. , Khattar-Sullivan Alanna , Devore Eric , Blace Nancy 
Published: March 2023

SIGNIFICANCE
This case highlights ocular adverse effects of a rare, potentially life-threatening complication from coronavirus disease 2019 (COVID-19). Papilledema can occur because of increased intracranial pressure caused by cerebral venous sinus thrombosis, the incidence of which may be more likely in patients with a history of COVID-19 because of an induced hypercoagulable state.

PURPOSE
This case report presents a case of papilledema secondary to cerebral venous sinus thrombosis in a patient with a recent history of severe coronavirus disease (COVID-19).

CASE REPORT
A 29-year-old man hospitalized with a complicated course of coronavirus disease (COVID-19) was referred to the ophthalmology department for episodic blurry vision of both eyes and intermittent binocular diplopia. Clinical examination revealed diffuse bilateral optic disc edema. Magnetic resonance venography of the brain during his admission revealed subtotal occlusion of the right transverse sinus by thrombosis. At the time of diagnosis, the patient was already taking systemic anticoagulation therapy for treatment of a recent pulmonary embolism also thought to be induced by COVID-19. After additional treatment with acetazolamide, there was improvement in his optic nerve edema.

CONCLUSIONS
Cerebral venous sinus thrombosis, a serious and potentially life-threatening condition, can occur as a rare complication of COVID-19. In such cases, patients may develop increased intracranial pressure, papilledema, and subsequent vision loss. Magnetic resonance venography should be ordered in patients with suspected papilledema to help rule out the presence of cerebral venous sinus thrombosis.
A Qualitative Assessment of the Experiences with Eye Health and Barriers to Eyeglasses among U.S. Youth
Authors: Killeen Olivia J. , Cho Juno , Raven Sarah A. , Wang Grace M. , Mubeen Amani , Kim Lydia , Claus Anne , Woodward Maria A. , Newman-Casey Paula Anne , Chang Tammy 
Published: March 2023

SIGNIFICANCE
Uncorrected refractive error is the main cause of visual impairment in U.S. youth and has profound impacts on individuals and society. Identifying and addressing barriers to eyeglasses in this population are critical to maximize youth academic performance, workplace productivity, and quality of life.

PURPOSE
We aimed to understand youth experiences with eye health, assess the value that youth place on vision, and identify barriers to refractive correction directly from a nationwide sample of youth to inform interventions to address uncorrected refractive error in this population.

METHODS
An open-ended poll was distributed to the MyVoice Text Message Cohort of U.S. youth eliciting youth experiences with eye health and barriers to wearing eyeglasses. Text message responses were coded using grounded theory.

RESULTS
Of 1204 recipients, 88.3% (n = 1063) responded. The mean age ± standard deviation was 20.3 ± 2.4 years, 58.8% (n = 625) were male, 74.0% (n = 787) were White, and 41.4% (n = 440) reported low socioeconomic status. Four major themes emerged from the open-ended responses: (1) many youth have experienced problems with their eyes or eyesight (n = 699 [65.8%]); (2) many youth value their eyesight highly (n = 905 [85.1%]; e.g., “Eyesight is one of the most important aspects of my health, particularly in our digital world…”); (3) common reasons youth might not wear glasses even if they need them include concerns over appearance (n = 553 [52.0%]; e.g., “I thought every pair made me look ugly…”), cost (n = 171 [16.1%]), inconvenience (n = 166 [15.6%]), and discomfort (n = 104 [9.8%]); and (4) youth are open to purchasing eyeglasses online (n = 539 [50.7%]).

CONCLUSIONS
Appearance, cost, inconvenience, and discomfort are critical barriers to wearing eyeglasses among U.S. youth. A multisectoral response is necessary to address these barriers.
Invertebrate herbivory damage of lowland plant species decreases after an experimental shift to higher altitudes
Authors: Hrubá Karolína , Hucková Dagmar , Klečka Jan 
Published: March 2023

AbstractMany species of plants and animals shift to higher altitudes in response to the ongoing climate warming. Such shifts of species distributions lead to the co-occurrence of species that have not previously lived in the same environment and allow the emergence of novel plant-animal interactions with potential implications for species diversity and community composition in mountain habitats. According to the enemy release hypothesis, the spread of plants in new geographic regions may be facilitated by the reduction of damage caused by natural enemies, such as herbivores. While the importance of this mechanism for the spread of invasive exotic species has been established, it is unclear whether the movement of plants uphill within their native region in response to increasing temperatures may be also facilitated by the reduction of herbivory at sites above their current upper altitudinal limit. In our study, we experimentally tested this hypothesis. We compared herbivory damage of six species of lowland plants grown in pots exposed to herbivores at their native sites in the lowland and at sites above their current upper altitudinal limit. As a control, we also measured herbivory damage of six plants growing naturally across the entire range of altitude. We found that lowland plants had reduced herbivory damage when they were moved to highland sites, while herbivory damage of species naturally growing at both altitudes did not differ. Changes of herbivory damage were modulated by leaf dry matter content and to a lesser degree also by specific leaf area and plant height. Our results provide support for the enemy release hypothesis in the novel context of altitudinal range shifts. We conclude that the reduction of herbivory damage may facilitate the spread of plants above their current upper altitudinal limit in response to increasing temperature.
Cholecalciferol improves cognitive impairment by amending impaired insulin signaling in sporadic Alzheimer’s Disease Rats
Authors: Das Tushar Kanti , Yong Estinnorell , Hamid Mas R.W. Abdul 
Published: March 2023

AbstractAlzheimer’s disease (AD) is the most common form of dementia and contributes to 50-70% of neurodegenerative brain diseases. AD has been associated with poor vitamin D nutrition, which is correlated with low mood and impaired cognitive performance in older people. The impact of vitamin D on the insulin signaling pathway in AD is not well known. Hence, this study was to explore the effects of cholecalciferol (Vitamin D3) on the expression of IRS-1, IRS-2, Akt, pAkt (Ser473), and GLUT3 in the sporadic AD rat model. The rats were induced to develop sporadic AD by intraperitoneal administration of Scopolamine. The downregulation expression of IRS-1, IRS-2, Akt, pAkt (Ser473) and GLUT3 may lead to impaired insulin signaling which is associated with the development of AD. All these data were compared to Saline-treated control rats. However, cholecalciferol treatment in AD rats may improve memory performance by increasing the expression of insulin signaling proteins and hence ameliorates impaired insulin signaling. All these data were compared to Scopolamine–induced AD rats and sunflower oil-treated rats. Therefore, cholecalciferol treatment may be an alternative approach for the treatment of AD.
Maternal age effects on offspring lifespan and reproduction vary within a species
Authors: Liguori Alyssa , Korm Sovannarith , Profetto Alex , Richters Emily , Gribble Kristin E. 
Published: March 2023

ABSTRACTAcross diverse taxa, offspring from older mothers have decreased lifespan and fitness. Little is known about whether such maternal age effects vary among genotypes for a given species, however. We compared maternal age effects among four strains of rotifers in theBrachionus plicatilisspecies complex. For each strain, we measured lifespan, reproductive schedule, and lifetime reproductive output of offspring produced by young, middle-aged, and old mothers. We found unexpected variability among strains in the magnitude and direction of maternal age effects on offspring life history traits. In one strain, offspring of young mothers lived 20% longer than offspring of old mothers, whereas there were no significant effects of maternal age on lifespan for the other strains. Across strains, advanced maternal age had positive effects, negative effects, or no effect on lifetime reproductive output. For all but one strain, older mothers produced offspring that had higher maximum daily reproduction early in life. Maternal age effects appear to be genetically determined traits, not features of life history strategy or due to accumulation of age-related damage in the germline. Investigating intraspecific variability is critical for understanding the ubiquity of maternal age effects and their role in the evolution of life history and aging.
Folding of Prestin’s Anion-Binding Site and the Mechanism of Outer Hair Cell Electromotility
Authors: Lin Xiaoxuan , Haller Patrick , Bavi Navid , Faruk Nabil , Perozo Eduardo , Sosnick Tobin R. 
Published: March 2023

AbstractPrestin responds to transmembrane voltage fluctuations by changing its cross-sectional area, a process underlying the electromotility of outer hair cells and cochlear amplification. Prestin belongs to the SLC26 family of anion transporters yet is the only member capable of displaying electromotility. Prestin’s voltage-dependent conformational changes are driven by the putative displacement of residue R399 and a set of sparse charged residues within the transmembrane domain, following the binding of a Cl-anion at a conserved binding site formed by amino termini of the TM3 and TM10 helices. However, a major conundrum arises as to how an anion that binds in proximity to a positive charge (R399), can promote the voltage sensitivity of prestin. Using hydrogen-deuterium exchange mass spectrometry, we find that prestin displays an unstable anion-binding site, where folding of the amino termini of TM3 and TM10 is coupled to Cl-binding. This event shortens the TM3-TM10 electrostatic gap, thereby connecting the two helices, resulting in reduced cross-sectional area. These folding events upon anion-binding are absent in SLC26A9, a non-electromotile transporter closely related to prestin. Dynamics of prestin embedded in a lipid bilayer closely match that in detergent micelle, except for a destabilized lipid-facing helix TM6 that is critical to prestin’s mechanical expansion. We observe helix fraying at prestin’s anion-binding site but cooperative unfolding of multiple lipid-facing helices, features that may promote prestin’s fast electromechanical rearrangements. These results highlight a novel role of the folding equilibrium of the anion-binding site, and helps define prestin’s unique voltage-sensing mechanism and electromotility.
Prolonging Genetic Circuit Stability through Adaptive Evolution of Overlapping Genes
Authors: Chlebek Jennifer L. , Leonard Sean P. , Kang-Yun Christina , Yung Mimi C. , Ricci Dante P. , Jiao Yongqin , Park Dan M. 
Published: March 2023

ABSTRACTThe development of synthetic biological circuits that maintain functionality over application relevant timescales remains a significant challenge. Here, we employed synthetic overlapping sequences in which one gene is encoded or “entangled” entirely within an alternative reading frame of another gene. In this design, the toxin-encodingrelEwas entangled withinilvA, which encodes threonine deaminase, an enzyme essential for isoleucine biosynthesis. A functional entanglement construct was obtained upon modification of the ribosome binding site of the internalrelEgene. Using this optimized design, we found that the selection pressure to maintain functional IlvA stabilized the production of burdensome RelE for over 130 generations, which compares favorably with the most stable kill-switch circuits developed to date. This stabilizing effect was achieved through a complete alteration of the mutational landscape such that mutations inactivating the entangled genes were disfavored. Instead, the majority of lineages accumulated mutations within the regulatory region ofilvA. By reducing baselinerelEexpression, these more ‘benign’ mutations lowered circuit burden, which suppressed the accumulation ofrelEinactivating mutations, thereby prolonging kill-switch function. Overall, this work demonstrates the utility of sequence entanglement paired with an adaptive laboratory evolution campaign to increase the evolutionary stability of burdensome synthetic circuits.
Live-cell Fluorescence Microscopy of HSV-1 Cellular Egress by Exocytosis
Authors: Bergeman Melissa H. , Hernandez Michaella Q. , Diefenderfer Jenna , Drewes Jake A. , Velarde Kimberly , Tierney Wesley M. , Enow Junior A. , Glenn Honor L. , Rahman Masmudur M. , Hogue Ian B. 
Published: March 2023

1.1AbstractThe human pathogen Herpes Simplex Virus 1 (HSV-1) produces a lifelong infection in the majority of the world’s population. While the generalities of alpha herpesvirus assembly and egress pathways are known, the precise molecular and spatiotemporal details remain unclear. In order to study this aspect of HSV-1 infection, we engineered a recombinant HSV-1 strain expressing a pH-sensitive reporter, gM-pHluorin. Using a variety of fluorescent microscopy modalities, we can detect individual virus particles undergoing intracellular transport and exocytosis at the plasma membrane. We show that particles exit from epithelial cells individually, not bulk release of many particles at once, as has been reported for other viruses. In multiple cell types, HSV-1 particles accumulate over time at the cell periphery and cell-cell contacts. We show that this accumulation effect is the result of individual particles undergoing exocytosis at preferential sites and that these egress sites can contribute to cell-cell spread. We also show that the viral membrane proteins gE, gI, and US9, which have important functions in intracellular transport in neurons, are not required for preferential egress and clustering in non-neuronal cells. Importantly, by comparing HSV-1 to a related alpha herpesvirus, pseudorabies virus, we show that this preferential exocytosis and clustering effect is cell type-dependent, not virus dependent. This preferential egress and clustering appears to be the result of the arrangement of the microtubule cytoskeleton, as virus particles co-accumulate at the same cell protrusions as an exogenous plus end-directed kinesin motor.ImportanceAlpha herpesviruses produce lifelong infections of their human and animal hosts. The majority of people in the world are infected with Herpes Simplex Virus 1 (HSV-1), which typically causes recurrent oral or genital lesions. However, HSV-1 can also spread to the central nervous system, causing severe encephalitis, and might also contribute to the development of neurodegenerative diseases. Many of the steps of how these viruses infect and replicate inside host cells are known in depth, but the final step, exiting from the infected cell, is not fully understood. In this study, we engineered a novel variant of HSV-1 that allows us to visualize how individual virus particles exit from infected cells. With this imaging assay, we investigated preferential egress site formation in certain cell types and their contribution to cell-cell spread of HSV-1.
Candida aurisevades innate immunity by using metabolic strategies to escape and kill macrophages while avoiding antimicrobial inflammation
Authors: Weerasinghe Harshini , Simm Claudia , Djajawi Tirta , Tedja Irma , Lo Tricia L , Shasha David , Mizrahi Naama , Olivier Françios AB , Speir Mary , Lawlor Kate E. , Ben-Ami Ronen , Traven Ana 
Published: March 2023

ABSTRACTCandida auriscauses life-threatening, drug-resistant infections. In addition to drug resistance, therapeutic innovation is hindered by our limited knowledge of the mechanisms used byC. auristo evade immunity and establish infection. Here we show thatC. aurisescapes phagocytic containment and kills macrophages, and demonstrate that the mechanisms rely on metabolic regulation. We found thatC. auris-infected macrophages undergo immunometabolic reprogramming and increase glycolysis but this does not lead to the expected antimicrobial responses, as macrophages fail to activate IL-1β cytokine and curbC. aurisgrowth. Further analysis showed thatC. aurisrelies on its own metabolic capacity to egress from macrophages, cause macrophage metabolic stress and cell death, and establish infectionin vivo. We identified a transcriptional regulator ofC. aurismetabolism and macrophage evasion, and further show that, contrary to several other pathogens,C. auris-induced macrophage metabolic dysfunction and death fail to activate the NLRP3 inflammasome. Consequently, inflammasome-dependent antimicrobial responses remain inhibited throughout infection. Our findings establish a pivotal role for metabolic regulation in enablingC. auristo eliminate macrophages while remaining immunologically silent to ensure its own survival.
Systematic characterization ofUstilago maydissirtuins shows Sir2 as a modulator of pathogenic gene expression
Authors: Navarrete Blanca , Ibeas José I. , Barrales Ramón R. 
Published: March 2023

AbstractPhytopathogenic fungi must adapt to the different environmental conditions found during infection and avoid the immune response of the plant. For these adaptations, fungi must tightly control gene expression, allowing sequential changes in transcriptional programs. In addition to transcription factors, chromatin modification is used by eukaryotic cells as a different layer of transcriptional control. Specifically, the acetylation of histones is one of the chromatin modifications with a strong impact on gene expression. Hyperacetylated regions usually correlate with high transcription and hypoacetylated areas with low transcription. Thus, histone deacetylases (HDACs) commonly act as repressors of transcription. One member of the family of HDACs is represented by sirtuins, which are deacetylases dependent on NAD+, and, thus, their activity is considered to be related to the physiological stage of the cells. This property makes sirtuins good regulators during environmental changes. However, only a few examples exist, and with differences in the extent of the implication of the role of sirtuins during fungal phytopathogenesis. In this work, we have performed a systematic study of sirtuins in the maize pathogenUstilago maydis, finding Sir2 to be involved in the dimorphic switch from yeast cell to filament and pathogenic development. Specifically, the deletion ofsir2promotes filamentation, whereas its overexpression highly reduces tumor formation in the plant. Moreover, transcriptomic analysis revealed that Sir2 represses genes that are expressed during biotrophism development. Interestingly, our results suggest that this repressive effect is not through histone deacetylation, indicating a different target of Sir2 in this fungus.
Structural basis for DARC binding in reticulocyte invasion byPlasmodium vivax
Authors: Moskovitz Re’em , Pholcharee Tossapol , DonVito Sophia M. , Guloglu Bora , Lowe Edward , Mohring Franziska , Moon Robert W. , Higgins Matthew K. 
Published: March 2023

AbstractThe symptoms of malaria occur during the blood stage of infection, when the parasite replicates within human red blood cells. The human malaria parasite,Plasmodium vivax, selectively invades reticulocytes in a process which requires an interaction between the ectodomain of the human DARC receptor and thePlasmodium vivaxDuffy-binding protein, PvDBP. Previous studies have revealed that a small helical peptide from DARC binds to region II of PvDBP (PvDBP-RII). However, it is also known that sulphation of tyrosine residues on DARC affects its binding to PvDBP and these residues were not observed in previous structures. We have therefore determined the structure of PvDBP-RII bound to sulphated DARC peptide, showing that a sulphate on tyrosine 41 binds to a charged pocket on PvDBP-RII. We use molecular dynamics simulations, affinity measurements and growth-inhibition experiments in parasites to confirm the importance of this interaction. We also reveal the epitope for vaccine-elicited growth-inhibitory antibody, DB1. This provides a complete understanding of the binding of PvDBP-RII to DARC and will guide the design of vaccines and therapeutics to target this essential interaction.