bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standardizing Fetal Movement Monitoring using Count the Kicks
Authors: Burgess Adriane , Aucutt Megan , Coleman Sarah L. 
Published: July 2024

Abstract
Stillbirth affects 1 in 175 pregnancies in the United States. There are significant racial and ethnic disparities in rates of stillbirth. Rates of stillbirth are highest among non-Hispanic Native Hawaiian or Other Pacific Islander and non-Hispanic Black women, more than twice the rate of non-Hispanic White women. Stillbirth is a public health crisis that warrants attention as it has significant physical, psychosocial, and economic effects on women and their family. Many stillbirths occur due to placental insufficiency, causing a lack of oxygenation of the fetus, which can result in decreased movement. Pregnant patients who experience stillbirth often observe decreased fetal movement days before birth. Daily fetal movement monitoring has the potential to identify pregnancies at risk so providers can intervene. Count the Kicks is a fetal movement monitoring program that provides standardized education and resources for expectant parents. Increased awareness of providers and childbearing families about the importance of fetal movement monitoring, standardized provision of education on fetal movement counting, and what to do if a baby's normal movement patterns change can be helpful in promoting healthy pregnancy outcomes.
Emotional Awareness Is Correlated With Ambulatory Heart Rate Variability: A Replication and Extension
Authors: Spangler Derek P. , Reis Harry T. , Hsu Chiu-Hsieh , Zareba Wojciech , Lane Richard D. 
Published: July 2024

ABSTRACT

Objective
In healthy volunteers, a positive association has previously been observed between emotional awareness (EA), the ability to identify and describe emotional experiences in oneself and others, and resting heart rate variability (HRV), which is dominated by vagus nerve activity. The current study aimed to investigate the EA-HRV association across multiple assessments in a “real-world” ambulatory context in patients with long QT syndrome (LQTS) who are at genetic risk for sudden cardiac death.

Methods
Participants (157 LQTS patients; MeanAge = 35.1, SDAge = 10.4; 115 women) completed the levels of emotional awareness scale (LEAS) on one occasion, which served as our measure of EA. In an ecological momentary assessment study involving 10 assessments per day over 3 days, multiple 5-minute ECG assessments (mean = 24.6, SD = 5.1) were obtained in each patient using a Holter monitor, from which high-frequency HRV (HF-HRV) was computed on each occasion.

Results
There was a significant positive association between LEAS scores and HF-HRV controlling for biobehavioral covariates. We also detected a similar inverse relation between EA and mean heart rate.

Conclusion
These findings suggest that, in patients with a well-defined genetic risk for ventricular arrhythmia and sudden death, the ability to experience emotions in a complex and differentiated way covaries with greater parasympathetic influences on the heart. These findings are consistent with the overlapping neural substrates of EA and HRV and their common contribution to adaptive emotional responding, consistent with the Neurovisceral Integration Model.
Pediatric Anatomy of the Sternocleidomastoid Muscle on Magnetic Resonance Imaging Views
Authors: Beger Burhan , Yalinkiliç Abdulaziz , Erdem Mehmet Zeki , Mengi Sevinç , Beger Orhan 
Published: July 2024

Objective:
This study aimed to investigate morphologic features of the sternocleidomastoid muscle (SCM) in children for pediatric head-neck surgeries.

Methods:
Magnetic resonance imaging images of 84 (46 males/38 females) pediatric patients aged ages 1 to 18 years (mean age: 9.38 ± 4.46 y) constituted the study universe. The size of SCM (including its height, width, and angulation) was measured, and the origin types of SCM were noted.

Results:
All patients had SCM bilaterally. The origin variation of SCM was observed in 22 sides (13.10%). The authors observed type 1 in 146 sides (86.90%), type 2a in 15 sides (8.90%), type 3 in 2 sides (1.20%), type 4 in 1 side (0.60%), and type 5 in 4 sides (2.40%). The absence and presence of SCM variation were not affected by sex (P = 0.370) and side (P = 0.360). All measured parameters were similar in right and left sides, and also in males and females, except from the angle between the junction of the sternal and clavicular heads of SCM. The angle was greater in males than females (P = 0.004). All measured parameters increased with advancing age (between 1 and 18 y; P < 0.05).

Conclusion:
The authors’ SCM-related data may be useful for clinicians to estimate the size origin variations of SCM in children.
Association of Hospital System Affiliation with Spending and Postoperative Outcomes
Authors: Diaz Adrian , Nuliyalu Usha , Ryan Andrew M , Dimick Justin B , Ibrahim Andrew M , Nathan Hari 
Published: July 2024

Objective:
To determine whether hospital system affiliation was associated with changes in surgical episode spending or postoperative outcomes.

Background:
Over 70% of US hospitals are now part of a hospital system. The presumed benefits of hospital consolidation include concentrating volume and expertise, care integration, and investment in quality improvement. However, there is conflicting evidence as to whether expanding hospital systems are actually reducing health spending or improving quality. These observations call into question whether systems are leveraging their collective volume and experience to standardize care and maximize efficiencies.

Methods:
The American Hospital Association Annual Survey was used to identify whether a hospital was part of a system and in which year a hospital joined the respective system. Using 100% Medicare claims data, we identified fee-for-service Medicare patients undergoing elective inpatient coronary artery bypass graft colon resection, lung resection, hip replacement, or knee replacement from 2010 to 2018. We used a difference-in-differences framework to evaluate hospital spending and outcomes before and after joining a system. The primary outcome was Medicare 30-day episode spending, with specific attention to the total episode payment, index hospitalization, and post-acute care components. Secondary outcomes included serious complications, 30-day mortality, and 30-day readmission.

Results:
The cohort included 3,395,565 Medicare beneficiaries who underwent surgery between 2010 and 2018. Patients were treated at 3961 hospitals, of which 1097 (27.7%) were never in a system, 2262 (57.1%) were always in a system, and 602 (15.2%) joined a system during the study period. By 1 year after system affiliation, 30-day episode spending had decreased by $303 (95% CI: 63, 454, P=0.01), and after 5 years, 30-day episode spending decreased by $429 (95% CI: 5, 853, P=0.04). One year after system association, index hospitalization spending was not statistically different from before system affiliation ($−30, 95% CI: −160, 100, P=0.65). Conversely, 1 year after system association, postacute care spending decreased by $268 (95% CI: 107, 429, P<0.01) and remained lower for ≥5 years. There was no significant change in hospitals serious complications (−0.14, 95% CI: −0.40, 0.11, P=0.27), 30-day readmission (−0.14, 95% CI:−0.52, 0.25, P=0.48), or 30-day mortality (−0.08, 95% CI: −0.18, 0.03, P=0.17), 1 year after joining a system; similar patterns were observed at three and ≥5 years.

Conclusions:
system affiliation was associated with a small decrease in 30-day episode spending, driven by decreased spending in postacute care services. Notably, there was no difference in postoperative outcomes after system affiliation.
Codon-Optimized and de novo–Synthesized E-Selectin/AAV2 Dose–Response Study for Vascular Regeneration Gene Therapy
Authors: Voza Francesca A. , Byrne Barry J. , Ortiz Yulexi Y. , Li Yan , Le Nga , Osafo Lucy , Ribieras Antoine C. , Shao Hongwei , Huerta Carlos Theodore , Wei Yuntao , Falero-Diaz Gustavo , Franco-Bravo Andres , Lassance-Soares Roberta M. , Vazquez-Padron Roberto I. , Liu Zhao-Jun , Velazquez Omaida C. 
Published: July 2024

Objective:
This study focuses on dose–response investigation using a codon-optimized and de novo–synthesized E-Selectin/AAV2 (E-Sel/AAV2) vector in preparation for Investigational New Drug enabling of subsequent clinical studies.

Background:
Gene therapy is a potential solution for patients suffering from chronic limb-threatening ischemia. Understanding the dose for effective gene delivery is crucial for future Investigational New Drug–enabling studies.

Methods:
Expression of the codon-optimized E-Selectin gene was assessed by flow cytometry following in vitro cell transfection assay and RT-qPCR for murine limbs injected in vivo with AAV-m-E-Selectin (E-Sel/AAV2). Dose–response studies involved 3 cohorts of FVB/NJ mice (n=6/group) with escalating log doses of E-Selectin/AAV2 injected intramuscularly in divided aliquots, ranging from 2 × 109 VG to 2 × 1011 VG, into ischemic limbs created by left femoral artery/vein ligation/excision and administration of nitric oxide synthase inhibitor, L-NAME. Limb perfusion, extent of gangrene free limb, functional limb recovery, and therapeutic angiogenesis were assessed.

Results:
Codon-optimized E-Sel/AAV2 gene therapy exhibits a superior expression level than WT E-Sel/AAV2 gene therapy both in vitro and in vivo. Mice treated with a high dose (2 × 1011 VG) of E-Sel/AAV2 showed significantly improved perfusion indices, lower Faber scores, increased running stamina, and neovascularization compared with lower doses tested with control groups, indicating a distinct dose-dependent response. No toxicity was detected in any of the animal groups studied.

Conclusions:
E-Sel/AAV2 Vascular Regeneration Gene Therapy holds promise for enhancing the recovery of ischemic hindlimb perfusion and function, with the effective dose identified in this study as 2 × 1011 VG aliquots injected intramuscularly.
Preliminary Guidelines for Resuming Electroconvulsive Therapy After a Complication of Status Epilepticus
Authors: Hazimeh Maya , Arnoudse Nicholas , Wilson Saydra , Walczak Thaddeus , Nahas Ziad 
Published: July 2024

Abstract
Electroconvulsive therapy (ECT) is an effective and safe treatment for severe major depressive disorder. However, status epilepticus is a rare yet serious complication that can occur following treatment. We present a case of a patient with severe major depression who experienced convulsive status epilepticus during the first treatment of her fourth ECT course. Electroconvulsive therapy treatment was then discontinued, and the patient underwent unsuccessful medication trials. Due to deterioration of depressive symptoms, ECT resumption was considered 3 months later after the patient had been maintained on an antiepileptic drug and no further seizures had occurred. Electroconvulsive therapy was resumed with a detailed safety protocol that included electroencephalographic monitoring before and after ECT treatment, remaining on an antiepileptic drug during the course of treatment, performing ECT in the operating room, and preparing seizure-terminating drugs before each treatment. The patient completed her ECT course with no tardive seizures or other neurological complications. We present the safety measures taken for resumption of ECT in our patient, and we offer preliminary clinical guidelines for resuming ECT after a complication of status epilepticus.
Hormonal dynamics reveal a stimulatory role for secretoneurin in zebrafish ovulation
Authors: Peng Di , Lu Chunyu , Spadacini Victoria , Mitchell Kimberly , Tan Yongjun , Zhang Dapeng , Levavi-Sivan Berta , Hu Wei , Trudeau Vance L. 
Published: July 2024

AbstractSurge release of luteinizing hormone (Lh) from the pituitary is essential for fertility as it triggers ovulation. While secretoneurin (SN) is a phylogenetically conserved secretogranin-2 derived peptide that stimulates Lh, its role in ovulation has not been established. To directly compare periovulatory changes in the classical hormones to the emerging reproductive neuropeptides SNa and SNb, simultaneous mass spectrometry measurement of 9 peptides and 5 steroids was conducted in female zebrafish. Regression analysis indicated that levels of SNa1-34 in the brain peaked when type 3 gonadotropin-releasing hormone (Gnrh3) increased (R2=0.71) at the time of the Lh surge, 3.5 h before ovulation. In contrast, levels of the naturally occurring derivative SNa1-14 were highest at ovulation, while SNb1-31 was invariable. The bioactivities of SNa1-34 and SNa1-14 were investigated. After injection of SNa1-34 in females that had been isolated from males, 61% (11/18) ovulated within 6 h, which was like the effects of the Lh analog human chorionic gonadotropin (hCG) (72%; 13/18 females). SNa1-34 could induce ovulation by stimulating time-dependent expression ofgnrh3in the brain,chorionic gonadotropin alpha (cga), luteinizing hormone b (lhb)subunit in pituitary, and thenuclear progesterone receptor (npr)in ovaries. In contrast, SNa1-14 exhibited far fewer effects on gene expression and did not induce ovulation. Our results support the proposal that SN is a reproductive hormone.Significance statementSecretogranin-2 is a secretory granule protein that is enzymatically processed to the bioactive neuropeptide secretoneurin. It is produced in hypothalamic neurons and anterior pituitary cells, and we providein vivoevidence that secretoneurin plays an important role to induce ovulation. Secretoneurin levels in the brain increase concomitantly with gonadotropin-releasing hormone prior to ovulation in normal zebrafish. Injection of a synthetic secretoneurin peptide increased expression of reproduction-related genes at all levels of the hypothalamic-pituitary-ovarian axis. Secretoneurin stimulates ovulation in otherwise anovulatory females. Together these data place the evolutionarily conserved secretoneurin amongst other critical neuroendocrine regulators. Secretoneurin or synthetic agonists could be used to improve breeding in fish species, or to potentially help with infertility treatments
Drugging Disordered Proteins by Conformational Selection to Inform Therapeutic Intervention
Authors: Bogin Bryan A. , Levine Zachary A. 
Published: July 2024

ABSTRACTDrugging intrinsically disordered proteins (IDPs) has historically been a major challenge due to their lack of stable binding sites, conformational heterogeneity, and rapid ability to self-associate or bind non-specific neighbors. Furthermore, it is unclear whether binders of disordered proteins i) induce entirely new conformations or ii) target transient pre-structured conformations via stabilizing existing states. To distinguish between these two mechanisms, we utilize molecular dynamics simulations to induce structured conformations in islet amyloid polypeptide (IAPP), a disordered endocrine peptide implicated in Type II Diabetes. Using umbrella sampling, we measureconformation-specificaffinities of molecules previously shown to bind IAPP to determine if they can discriminate between two distinct IAPP conformations (fixed in either ⍺-helix or β-sheet). We show our two-state model of IAPP faithfully predicts the experimentally observed selectivity of two classes of IAPP binders while revealing differences in their molecular mechanisms of binding. Specifically, the binding preferences of foldamers designed for human IAPP was not fully accounted for by conformational selection, unlike β-breaking peptides designed to mimic IAPP self-assembly sequences. Furthermore, the binding of these foldamers, but not β-breaking peptides, was disrupted by changes in the rat IAPP sequence. Taken together, our data quantifies the sequence and conformational specificity for IAPP binders and reveals conformational selection sometimes overrides sequence-level specificity. This work highlights the important role of conformational selection in stabilizing IDPs, and it reveals how fixed conformations can provide a tractable target for developing disordered protein binders.
PEPCy: Photostable fluoromodules for live cell, super-resolution microscopy of surface proteins
Authors: Sasazawa Moeka , Chimthanawala Afroze , Zeng Rui , Kim Danah , Buchan Katherine , Zhang Ming , Saurabh Saumya 
Published: July 2024

AbstractWe report the evolution and application of two genetically encoded tags that bind the cyanine dyes Cy3 or Cy5 with high specificity and selectivity, in addition to enhancing their photostability. These tags, which we call PEPCy, can be used to target membrane proteins such as G-protein coupled receptors. Due to their orthogonality and high binding-affinity for cognate cyanine dyes, the PEPCy tags can be used for wash-free labeling of cell surface receptors to observe their dynamics at a single molecule level. Together with self-labeling tags, these photostability enhancing proteins against cyanine dyes present a novel, complementary and powerful approach to explore protein dynamics with high spatiotemporal resolution.
An ornithological survey of Fergusson Island, D’Entrecasteaux Archipelago, Papua New Guinea, reveals new island records and noteworthy natural history observations
Authors: Boersma Jordan , Gregg Jason , Nason Doka , Malesa Eli , Le Breton Cosmo , Ketaloya Serena , Iova Bulisa , Mittermeier John C. 
Published: July 2024

AbstractFergusson Island lies off the southeastern end of New Guinea and is the largest landmass in the D’Entrecasteaux and Trobriand Island Endemic Bird Area. We conducted audiovisual and camera trapping surveys in eastern Fergusson in September 2022 and recorded 97 bird species, documenting breeding and vocalizations for several of the EBA’s endemic taxa. Notably, we provide the first confirmed documentation of the “lost”insularissubspecies of Pheasant PigeonOtidiphaps nobilis(often recognized as a distinct species, Black-naped Pheasant-pigeon), in 126 years, observations of eight bird species not previously recorded from Fergusson, and nesting of Goldie’s Bird-of-ParadiseParadisea decoraand the endemiccrookshankitaxon of Capped White-eyeZosterops fuscicapilla(or Oya Tabu White-eye). Our new distributional records were mostly either migratory species or species found in open habitats, highlighting the value of surveying across seasons and habitats. We summarise our results and provide comments on distributional records, breeding behaviour, and vocalizations.
Deciphering thecis-regulatory landscape of natural yeast Transcript Leaders
Authors: Akirtava Christina , May Gemma , McManus C. Joel 
Published: July 2024

ABSTRACTProtein synthesis is a vital process that is highly regulated at the initiation step of translation. Eukaryotic 5’ transcript leaders (TLs) contain a variety ofcis-regulatory features that influence translation and mRNA stability. However, the relative influences of these features in natural TLs are poorly characterized. To address this, we used massively parallel reporter assays (MPRAs) to quantify RNA levels, ribosome loading, and protein levels from 11,027 natural yeast TLsin vivoand systematically compared the relative impacts of their sequence features on gene expression. We found that yeast TLs influence gene expression over two orders of magnitude. While a leaky scanning model using Kozak contexts and uAUGs explained half of the variance in expression across transcript leaders, the addition of other features explained ∼70% of gene expression variation. Our analyses detected keycis-acting sequence features, quantified their effects in vivo, and compared their roles to motifs reported from anin vitrostudy of ribosome recruitment. In addition, our work quantitated the effects of alternative transcription start site usage on gene expression in yeast. Thus, our study provides new quantitative insights into the roles of TL cis-acting sequences in regulating gene expression.
The role of ER exit sites in maintaining P-body organization and transmitting ER stress response duringDrosophila melanogasteroogenesis
Authors: Milano Samantha N. , Bayer Livia V. , Ko Julie J. , Casella Caroline E. , Bratu Diana P. 
Published: July 2024

ABSTRACTProcessing bodies (P-bodies) are cytoplasmic membrane-less organelles which host multiple mRNA processing events. While the fundamental principles of P-body organization are beginning to be elucidatedin vitro, a nuanced understanding of how their assembly is regulatedin vivoremains elusive. Here, we investigate the potential link between ER exit sites and P-bodies inDrosophila melanogasteregg chambers. Employing a combination of live and super-resolution imaging, we found that P-bodies associated with ER exit sites are larger and less mobile than cytoplasmic P-bodies, indicating that they constitute a distinct class of P-bodies which are more mature than their cytoplasmic counterparts. Moreover, we demonstrate that altering the composition of ER exit sites has differential effects on core P-body proteins (Me31B, Cup, and Trailer Hitch) suggesting a potential role for ER exit sites in P-body organization. We further show that in the absence of ER exit sites, P-body integrity is compromised and the stability and translational repression efficiency of the maternal mRNA,oskar, are reduced. Finally, we show that ER stress is communicated to P-bodies via ER exit sites, highlighting the pivotal role of ER exit sites as a bridge between membrane-bound and membrane-less organelles in ER stress response. Together, our data unveils the significance of ER exit sites not only in governing P-body organization, but also in facilitating inter-organellar communication during stress, potentially bearing implications for a variety of disease pathologies.