bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Modulating Multivalent Ligand Binding Accessibility & Affinity on Liquid‐Liquid Phase Separation
Authors: Galagedera Sarasi K. , Dao Thuy P. , Castaneda Carlos A. 
Published: May 2022

Elucidating the molecular rules of ligand‐induced phase transitions is essential to determining the regulation of the formation and disassembly of biomolecular condensates. Ubiquitin‐binding shuttle protein Ubiquilin‐2 (UBQLN2) undergoes liquid‐liquid phase separation (LLPS) in vitro and colocalizes into stress‐induced cytoplasmic puncta in vivosuch as stress granules.[1] A recent study from our lab indicated that ubiquitin (Ub), and compact polyUb chains such as K48‐ & K11‐Ub4 can inhibit UBQLN2 LLPS by binding to phase separation‐driving UBQLN2 stickers whereas more extended chains such as K63‐ & M1‐Ub4 can promote UBQLN2 phase separation over a large Ub:UBQLN2 range by acting as a multivalent ligand scaffold.[2] Using a designed tetrameric ubiquitin construct (HOTag6‐Ub) that resembles a multi‐monoubiquitinated substrate, we further probed how alterations to the stickers and spacers of the HOTag6‐Ub ligand can modulate UBQLN2 phase behavior. Using turbidity and microscopy experiments, we obtained phase diagrams for LLPS driven by heterotypic interactions between UBQLN2 and HOTag6‐Ub. We discovered that, by changing the length and flexibility of the linker that tethers the Ub units to HOTag6, we can tune UBQLN2 LLPS. Single‐ and double‐point mutations to the Ub hydrophobic binding surface (I44 & V70 “stickers”) decreased the binding affinity between Ub and UBQLN2, thereby leading to changes in the shape of HOTag6‐Ub/UBQLN2 phase diagrams. Using nuclear magnetic resonance spectroscopy (NMR), microscopy and UV‐Vis spectroscopic methods we demonstrated that linker conformation, linker flexibility, and interactions with the Ub binding surface are driving factors of UBQLN2/HOTag6‐Ub co‐phase separation. Overall, our findings highlight how multivalent ligands can tune phase separation behavior of protein systems.[1] Dao, T. P., Kolaitis, R.‐M., Kim, H. J., O’Donovan, K., Martyniak, B., Colicino, E., Hehnly, H., Taylor, J. P., and Castañeda, C. A. (2018). Ubiquitin Modulates Liquid‐Liquid Phase Separation of UBQLN2 via Disruption of Multivalent Interactions. Mol. Cell 69, 965‐978.[2] Dao, T. P., Yang, Y., Cosgrove, M. S., Hopkins, J. B., Ma, W., Castaneda, C. A. (2021). Mechanistic insights into the enhancement or inhibition of phase separation by polyubiquitin chains of different lengths or linkages. bioRxiv 2021.11.12.467822; doi: https://doi.org/10.1101/2021.11.12.467822.
Effects of Metabolic Syndrome and SIRT1 Mutation on Store‐Operated Ca2+ Entry in Peripheral Blood Mononuclear Cells in Ossabaw Miniature Swine
Authors: Thamba Aish , Royer Chris , Collett Jason , Byrd James , Alloosh Mouhamad , Coutts Alex , Basile David , Sturek Michael 
Published: May 2022

BackgroundMetabolic syndrome (MetS) impairs sarco‐endoplasmic reticulum Ca2+ ATPase (SERCA) activity that may decrease the ER Ca2+ store and increase store‐operated Ca2+ entry (SOCE) in a variety of cell types. Similar Ca2+ signaling via SOCE causes fibrosis, vascular disease, and may trigger immunogenic (type 1) diabetes by action on peripheral blood mononuclear cells (PBMCs). Sirtuin 1 (SIRT1) is a deacetylase that maintains healthy metabolism and generally attenuates vascular disease. SIRT1 impairment exacerbates MetS and vascular disease by hyper‐acetylation of SERCA, decreasing its activity and thereby potentially increasing SOCE.HypothesisThe SIRT1 mutation made in Ossabaw miniature swine would mimic the mutation found in humans and increase PBMC SOCE.MethodsUsing CRISPR/Cas9 methodology a point mutation (SIRT1L100P) was made in Ossabaw miniature swine to mimic the naturally occurring mutation in humans and decrease SIRT1 activity, thereby resulting in hyperacetylation of Ca2+transporters and impaired function. Four groups of pigs were used to analyze genotype and diet interactions: wild type lean, SIRT1 lean, wild type MetS, and SIRT1 MetS. Pigs were age 4 months at the start and fed normal chow (lean) or atherogenic diet (MetS) for 7 months. PBMCs were isolated and Ca2+ was measured with fura‐2. The ER Ca2+store was depleted by 10‐5M cyclopiazonic acid to inhibit SERCA in a Ca2+‐free extracellular solution to fully deplete the ER Ca2+store and then Ca2+ was returned to the solution to induce maximal SOCE. Cells were recovered in Ca2+‐free solution to partially re‐fill the ER Ca2+ store, then Ca2+ returned to the solution to observe submaximal SOCE.ResultsBoth MetS diet groups (wild type MetS, SIRT1 MetS) showed impaired glucose tolerance. Fasting glucose in SIRT1 mutants was not different from wild type pigs, thus SIRT1 does not cause immunogenic diabetes at this early stage. Robust coronary atherosclerosis was shown by angiography, intravascular ultrasound, and gross imaging in MetS groups, but there was no additive or synergistic effect of SIRT1 mutation. There was no effect of MetS or SIRT1 mutation on maximal SOCE. Two‐way ANOVA showed that MetS diet increased submaximal SOCE (p<0.009), but there was no effect of SIRT1 genotype on submaximal SOCE (p=0.266). The percentage of PBMCs that responded to partial ER Ca2+ depletion was 45% in lean pigs compared to 81% in wild type and 63% in SIRT1 pigs fed MetS diet.ConclusionSIRT1L100P mutation is likely to require longer duration to manifest robust effects on PBMC SOCE that were found with MetS diet. PBMC activation and can be easily studied longitudinally in the SIRT1L100P mutant swine model due to the ease of blood sampling.
Border zone repolarization duration as a predictor of early ischemic ventricular fibrillation
Authors: Tsvetkova Alena , Ovechkin Alexey , Azarov Jan , Bernikova Olesya 
Published: May 2022

Ventricular fibrillation (VF) is a dangerous complication of acute myocardial infarction. Within an episode of acute ischemia, VFs are clustered into early (1A) and delayed (1B) phases based on different mechanisms. Our previous work demonstrated that prolonged repolarization duration in the border zone predisposed to VF development. A prolongation of action potential duration in the affected area is a frequent though not inevitable change at the very beginning of ischemia. However, the role of this phenomenon in arrhythmogenesis is unclear. The objective of the present study was to evaluate an association between early (1A phase) VF with repolarization duration in the border zone in an experimental porcine myocardial infarction model.Myocardial ischemia was induced in 19 anesthetized domestic pigs by ligation of the left anterior descending (n=9) or left circumflex (n=10) coronary arteries. Epicardial mapping was done with a 64‐lead epicardial array placed on the affected area with adjacent regions. Recordings were done in the baseline state and during ischemia with a custom‐designed system (16 bits; bandwidth 0.05 to 1000 Hz; sampling rate 4000 Hz). Local activation time (AT) and end of repolarization time (RT) were measured in each epicardial lead as the instants of a dV/dt minimum during QRS‑complex and dV/dt maximum during T‑wave, respectively. Activation‐repolarization interval (ARI, a surrogate for action potential duration) was taken as a rate‐corrected difference between RT and AT. Dispersion of repolarization (DOR) was calculated as a difference between the latest and earliest RTs throughout all recorded epicardial leads.Ten early VF episodes developed during first minutes of ischemia (1‐8 min). In logistic regression analysis, VF incidence was associated with ARI duration in the border zone (regression coefficient 1.02, 95% CI 1.003‐1.037, p=0.023), but not DOR (regression coefficient 1.005, 95%CI 0.990‐1.021, p=0.508) during first ten minutes of ischemia. In multivariate logistic regression analysis (baseline ARI duration vs the fact of ARI prolongation), VF incidence was associated only with the baseline ARI duration (regression coefficient 1.025, 95%CI 1.007‐1.044, p=0.005).Our data demonstrated the role of the prolonged repolarization duration in the development of 1A phase VF, which was independent of DOR and related to its baseline duration. Since the border zone is by definition at least partly accessible for blood flow, it may present a target for VF prevention therapy in a setting of acute myocardial ischemia.
Estimates of Probabilities of Successful Development of Pain Medications: An Analysis of Pharmaceutical Clinical Development Programs from 2000 to 2020
Authors: Maher Dermot P. , Wong Chi Heem , Siah Kien Wei , Lo Andrew W. 
Published: May 2022

Background
The authors estimate the probability of successful development and duration of clinical trials for medications to treat neuropathic and nociceptive pain. The authors also consider the effect of the perceived abuse potential of the medication on these variables.

Methods
This study uses the Citeline database to compute the probabilities of success, duration, and survivorship of pain medication development programs between January 1, 2000, and June 30, 2020, conditioned on the phase, type of pain (nociceptive vs. neuropathic), and the abuse potential of the medication.

Results
The overall probability of successful development of all pain medications from phase 1 to approval is 10.4% (standard error, 1.5%). Medications to treat nociceptive and neuropathic pain have a probability of successful development of 13.3% (standard error, 2.3%) and 7.1% (standard error, 1.9%), respectively. The probability of successful development of medications with high abuse potential and low abuse potential are 27.8% (standard error, 4.6%) and 4.7% (standard error, 1.2%), respectively. The most common period for attrition is between phase 3 and approval.

Conclusions
The authors’ data suggest that the unique attributes of pain medications, such as their abuse potential and intended pathology, can influence the probability of successful development and duration of development.

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Melanocytic Nevus With Elastophilic Features
Authors: Tran Tien Anh N. 
Published: May 2022

Abstract:
In dermal melanocytoses such as blue nevus or nevus of Ota, an ultrastructural study has demonstrated an intimate relationship between the dendritic melanocytes and the dermal elastic fibers with elongated cytoplasmic processes of the melanocytes aligning lengthwise along the axis of the elastic fibers in longitudinal sections and encircling the elastic fibers in cross-sections. Such a close arrangement has not been reported in common melanocytic nevi. The current case described a similar arrangement between the melanocytes and the dermal elastic fibers in a usual intradermal melanocytic nevus. Of note, as the melanocytes matured with descent, the deep melanocytes were arranged in single cells embracing the elastic fibers, imparting a signet-ring cell/phagocytosis appearance. A Verhoeff—van Gieson stain showed hypertrophy of the melanocyte-associated elastic fibers compared with the elastic fibers in the dermal background, suggesting a paracrine or juxtracrine interaction between the melanocytes and the dermal cellular components. Because of the distinctive affinity of the melanocytes to the dermal elastic fibers in this melanocytic lesion, the term melanocytic nevus with elastophilic features is suggested for this peculiar melanocytic variant.
A Case of Tofacitinib-Induced Lymphomatoid Papulosis With Ocular Involvement
Authors: Knapp Calvin , Steele Eric , Mengden-Koon Stephanie , Williams Todd , Fett Nicole 
Published: May 2022

Abstract:
Janus kinase (JAK) inhibitors are being prescribed with increasing regularity in dermatology. We report on a patient who initiated treatment with tofacitinib for refractory erythema elevatum diutinum and subsequently developed a novel cutaneous outbreak characterized by firm violaceous papules on the trunk and extremities along with conjunctival injection and periorbital inflammation. Biopsy of affected tissue from both the cutaneous and ophthalmologic sources demonstrated increased numbers of CD30+ large atypical cells amid a mixed inflammatory cell infiltrate, consistent with lymphomatoid papulosis. A review of the literature reveals a plausible mechanism for the induction of persistent JAK signaling in the presence of a JAK inhibitor. We discuss this mechanism in depth because it pertains to this patient and recommend continued vigilance with the use of these immunologic agents.
Metastasis to the Oral Cavity: Report of 12 Cases
Authors: Lourenço Silvia V. , Florezi Giovanna P. , Smitter Anabel S. , Bologna Sheyla B. , Nico Marcello M. S. 
Published: May 2022

Abstract:
Oral cavity is not a common route for metastatic dissemination; metastasis to the oral region may affect soft tissues and jawbones, accounting for approximately 1% of all oral malignant neoplasms. The diagnosis of metastatic lesions to the oral cavity is usually challenging to clinicians and pathologists because of their complexity and rarity. We present a series of 12 metastatic neoplasms to the oral cavity that were detected previously or after the diagnosis of the primary tumor. All tumors were of epithelial origin with primary sites in the esophagus (2 cases), colon (2 cases), bladder, lungs, liver, larynx, skin, uterus, prostate, and adrenal gland, each with one case. The commonest site of the metastatic masses in the oral cavity was the gingiva, frequently presented as a vegetating, friable mass. The clinical examination and histopathologic analysis of the lesions were central to establishing the final diagnosis of the tumors. Metastatic masses to the oral cavity should always be considered as differential diagnosis of benign-looking lesions, especially in patients with previous history of a malignant disease. Biopsy is mandatory to establish an accurate diagnosis.
Associations Between Diaper Need and Child Sleep in Under-resourced Families
Authors: Shaffer Emma , Porter Sallie , Condon Eileen , Zha Peijia , Caldwell Barbara A. 
Published: May 2022

ABSTRACT:

Objective:
Sleep is critical for child health, but factors related to poverty create barriers to the achievement of healthful sleep. In this study, we examined the associations of insufficient diaper supply, a measure of material hardship, with child sleep.

Methods:
This cross-sectional study included 129 parents of very young children. Each participant responded to an online material hardship assessment and the Brief Infant Sleep Questionnaire–Revised. Multiple linear regression was used to analyze the relationship between diaper need and sleep.

Results:
Controlling for family and socioeconomic variables, diaper need was associated with disrupted, shorter sleep periods (β = −11.95, p < 0.001) and lower total sleep scores (β = −6.49, p = 0.004). High diaper need was associated with parent perception of poor sleep (β = −7.28, p = 0.017).

Conclusion:
The findings suggest that an inadequate supply of diapers adversely affects children's sleep. Further research should evaluate how screening and connecting families to resources may improve pediatric sleep.
The Modified Sternoplasty: A Novel Surgical Technique for Treating Mediastinitis
Authors: Kachel Erez , Arazi Mattan , Grosman-Rimon Liza , Yehezkeel Shachar , Rimon Jordan , Gohari Jacob , Shinfeld Amihay , Sternik Leonid , Raanani Ehud , Moshkovitz Yaron 
Published: May 2022

Summary:
Deep sternal wound infection (DSWI) is one of the most complex and devastating complications post cardiac surgery. We present here the modified sternoplasty, a novel surgical technique for treating DSWI post cardiac surgery. The modified sternoplasty includes debridement and sternal refixation via bilateral longitudinal stainless-steel wires that are placed parasternally along the ribs at the midclavicular or anterior axillary line, followed by six to eight horizontal stainless-steel wires that are anchored laterally and directly into the ribs. On top of that solid structure, wound reconstruction is performed by the use of bilateral pectoralis muscle flaps followed by subcutaneous tissue and skin closure. We reported mortality rates and length of hospitalization of patients who underwent the modified sternoplasty. In total, 68 patients underwent the modified sternoplasty. Two of these critically ill patients died (2.9%). The average length of hospitalization from the diagnosis of DSWI was 24.63 ± 22.09 days. The modified sternoplasty for treating DSWI is a more complex surgery compared with other conventional sternoplasty techniques. However, this technique was demonstrated to be more effective, having a lower rate of mortality, and having a length of hospitalization lower than or comparable to other techniques previously reported in the literature.
Primary Monocanalicular Stent Intubation for Children With Congenital Nasolacrimal Duct Obstruction: Surgical Outcome and Risk Factors
Authors: Katowitz William R. , Prat Daphna Landau , Munroe Christiana E. , Revere Karen , Khatib Lama , Hua Peiying , Ying Gui-Shuang , Binenbaum Gil 
Published: May 2022

Purpose:
To determine the risk factors impacting the surgical success of primary monocanalicular stent intubation for congenital nasolacrimal duct obstruction (CNLDO).

Methods:
This is a retrospective interventional case series of patients 18 years and younger treated more than a 12-year period with monocanalicular stent intubation with inferior turbinate fracture for CNLDO by a single surgeon. Patients with dacryocystoceles, dacryocystitis, Down syndrome and previous tear duct surgery were excluded. An intraoperative grading scale of tear duct stenosis, date of stent removal, stent length, and postoperative symptoms were recorded. Surgical success was defined as the complete resolution of symptoms.

Results:
One thousand four hundred sixty-nine stents were placed in 1,001 pediatric participants (533 unilateral, 468 bilateral). The mean age at surgery was 1.86 years (0.1–18.07). The mean follow up was 34.99 months (0.43–134.3) with mean in-office stent removal at 3.41 months (0.63–36.9). Early stent loss occurred in 14.8% intubations (217/1,469). The overall success rate was 92.4% (1,357/1,469 eyes). Subjects less than the age of 4 years had a success rate of 92.8% (1,296/1,397) compared with 84.7% (61/72) in children more than 4. In multivariable analysis, bilateral surgery, severe tear duct stenosis, and early stent loss were significantly associated with higher risk of surgical failure.

Conclusions:
Severe tear duct stenosis, early stent loss, and bilateral surgery were significant risk factors for surgical failure. While the success rate stratified by age at surgery suggested a lower success after the age of 4. Primary monocanalicular stent intubation is an effective and safe treatment for CNLDO sparing a child the need for multiple staged surgeries.
Nursing Students' Home Care Learning Delivered in an Innovative 360-Degree Immersion Experience
Authors: Woodworth Julie A. 
Published: May 2022

Background:
Health care is delivered to patients in the community, frequently in their own homes. New graduates need to be prepared for this unique nursing role to care for patients in the home health setting.

Purpose:
The purpose of this study was to assess student satisfaction with an innovative pedagogy to teach home health nursing using an immersion experience. The immersion experience delivered the home health nursing activity using 360-degree footage and zoom in pictures presented via a web platform.

Methods:
This study used a descriptive cross-sectional design with convenience sampling of 81 nursing students enrolled in the third semester of an associate degree program. Data were collected through an online survey eliciting anonymous feedback.

Results:
Participant feedback revealed this new pedagogy engaged nursing students and received overwhelmingly positive responses. A review of student feedback through written comments provided further support that this immersion experience exceeded expectations.

Conclusion:
The 360-degree immersion home care experience provided problem-based learning that positively impacted student self-reported satisfaction and perceived learning.
Identification of Initial and Subsequent Injury in Young Infants
Authors: Thackeray Jonathan D. , Crichton Kristin G. , McPherson Paul , Izsak Eugene , Vavul-Roediger Lori , Kim Grace , Spencer Sandra , Baker Carrie , Eismann Emily A. , Shapiro Robert A. ,   on behalf of the TRAIN Collaborative
Published: May 2022

Objectives
The objective of this study was to identify opportunities to improve identification and evaluation of child abuse by (1) describing rates of initial and recurrent injury in young infants, (2) describing the frequency of a history of prior injury in young children evaluated by a child abuse pediatrician, and (3) identifying practice variation, including use of skeletal surveys as an example, in the identification and evaluation of injury across a network of 6 children’s hospitals.

Methods
Six children's hospitals identified infants with an initial injury and recurrent injury over a 1-year period using 2 methods: (1) diagnostic code method — infants 6 months or younger presenting with at least 1 diagnostic code for injury were tracked for 12 months to determine the frequency of recurrent injury, and (2) consult method — all available medical records of children 18 months or younger seen for an inpatient consultation for suspected child abuse were reviewed to identify history of a first injury at 6 months or younger.

Results
Using the diagnostic code method, 682 unique infants were identified with initial injuries, most commonly fractures (37.0%), bruising/ecchymosis (35.9%), and superficial injuries (28.3%). Forty-two infants (6.2%) returned with a second injury, and no demographic factors were significantly associated with the likelihood of a second injury. Using the consult method, 37 of 342 consults (10.8%) were identified as having a history of at least 1 initial injury. Of the initial injuries identified, the most common was bruising/ecchymosis (64.9%). The number of injuries identified with either method varied significantly across hospitals, as did completion of skeletal surveys for infants with bruising (range, 4.5%–71.1%; P < 0.001) and any injury (range, 4.4%–62.7%; P < 0.001).

Conclusions
Our study demonstrates that young infants who experience 1 injury often experience a second injury. There exists significant variability in the identification of injury and the completion of skeletal surveys across a network of 6 children's hospitals. A standardized quality improvement approach may improve identification of injury and reduce the variability in practice observed.
A Comprehensive Review on the Supraclavicular Flap for Head and Neck Reconstruction
Authors: Hamidian Jahromi Alireza , Horen Sydney R. , Miller Emily J. , Konofaos Petros 
Published: May 2022

Abstract
The supraclavicular artery flap (SCF) is a highly vascularized fasciocutaneous flap overlying the shoulder. The flap was first described in 1979 by Lamberty but did not gain popularity until much later due to lack of a reliable technique. The main advantages of using the SCF include avoiding microsurgical techniques, requiring only a single-stage operation, shorter operative time compared with alternative options, and a wider patient population including those with comorbidities who may be excluded from more extensive operations including free flaps surgeries. The SCF has been successfully performed on individuals with advanced age, poor nutrition, cachexia, obesity, diabetes, tobacco use, severe chronic obstructive pulmonary disease, hypertension, coronary artery disease, peripheral vascular disease, supraventricular tachycardia, atrial fibrillation, heart failure, asthma, and steroid use. The largest disadvantages of the SCF include the possibility of distal tip necrosis, size limitation without pre-expansion, and a moderately visible donor site scar. The following review and meta-analysis of the SCF details its use historically as both an island and a pedicle flap, and its application in head and neck reconstruction.