bluuebunny/crossref_metadata_2025 huggingface dataset:
Case series of the inferior vena cava primary leiomyosarcoma treatment
Authors: Lazar Davidovic , Stefan Ducic , Marko Dragas , Zlatanovic Petar , Sladojevic Milos , Ilijas Cinara , Grubor Nikica , Andreja Dimic
Published: June 2024

Tumors of the inferior vena cava (IVC) are rare and usually malignant and they can be primary and secondary. The most common primary tumor of the IVC is primary leiomyosarcoma. The first case of primary IVC leiomyosarcoma has been described in 1871 [1].The total number of 218 cases has collected until 1996 [2]. After that, three large single center series of these tumors emerged [3–5]. Present a series of five cases of these tumors. All the patients underwent a wide complete resection of tumors and the reconstruction with Dacron grafts. One patient died 19 months after the surgery, while the remaining ones survived without a local and system disease relapse. Although a surgical resection combined with the chemotherapy is often not curative, it can achieve a significant long-term survival. For this reason, we recommend the aggressive surgical management using the modern vascular surgical and oncology techniques.
Arterial occlusion secondary to prior cardiac catheterization in a radial forearm flap—lessons learnt from an unusual case
Authors: Zhang Steven L , Chung Benjamin Z W , Ng Hui Wen
Published: June 2024

The radial forearm free flap (RFFF) is a workhorse flap for head and neck reconstruction. We present an unusual case of radial artery occlusion, likely from previous transradial cardiac catheterization, in a patient for whom an RFFF was raised for floor of mouth reconstruction following resection of squamous cell carcinoma. Pre-operative assessment with ultrasound Doppler and an Allen test was normal. The flap was raised uneventfully under tourniquet control. However, following flap elevation and tourniquet release, poor flap perfusion was noted, and cutback of the artery revealed a long segment of hard fibrous plaque within the lumen. Retrospective review of medical records showed a history of cardiac catheterization via the same radial artery. We discuss various measures that can prevent this occurrence, including careful pre-operative screening of previous procedures involving the radial artery, the reverse Allen test, Doppler ultrasound, and consideration of distal arterial exploration without a tourniquet.
Congenital cystohepatic duct found during laparoscopic cholecystectomy
Authors: Shumarova Svetlana , Koichev Anton , Sokolov Manol , Arabadzhiev Angel , Karamisheva Vesela
Published: June 2024

This case shows the need for in-depth knowledge also on congenital biliary anomalies that can become subject to iatrogenic damage. The patient is 44-years old with echographically proven cholelithiasis with complaints of intermittent pain in the right upper quadrant. During laparoscopic cholecystectomy, after identification of cystic duct and cystic artery, after their clipping and resection and subsequent mobilization of the gallbladder from the liver parenchyma, a bile duct was opened. Subsequent identification revealed a cystohepatic duct, which is a rare anatomic anomaly. Plastic surgery was performed on the tangential lesion of the right hepatic duct and placement of a transcistic drain, as well as a drain from the right hepatic duct through the Fateri papilla. Postoperative transdrainage cholangiography established the integrity of the bile ducts and the free passage of contrast to the duodenum.

Intraoperative identification of only two structures entering the gallbladder during cholecystectomy—cystic duct and cystic artery—is mandatory.
Family Physician’s Satisfaction Report: Military 2021 vs. Civilian 2020 and 2022
Authors: Burton Samue l , Fisher Daniel , Barrett John
Published: June 2024

Introduction

In the Medscape 2020 Compensation Report, family physicians ranked low for feeling fairly compensated, choosing their specialty again and choosing medicine again. However, the Medscape data may not represent military family physicians.

Methods

A large survey was emailed to 2,562 military family physicians via a military professional organization list-serve from February to April 2021. The inquiry included 6 statements pertaining to professional satisfaction. The main outcome measures were proportions of “agree” and “strongly agree.” The proportions were compared to the Medscape Compensation Report 2020 and 2022. Statistical analysis was completed with a two-tailed Z-score for 2 populations.

Results

Sixty-one percent of military family physicians feel fairly compensated compared to 54% of civilian family physicians in 2020 and 55% in 2022 (P = .065, .119). Eighty-six percent of military family physicians would reselect medicine compared to 74% of civilian family physicians in 2020 and 73% in 2022 (P < .001 for both). Eighty percent of military family physicians would reselect their specialty again compared to 70% of civilians in 2020 and 68% in 2022 (P = .004, P = .001, respectively).

Conclusions

Military family physicians were more likely to choose medicine generally and family medicine specifically again. Military family physicians and civilian family physicians do not statistically differ in feeling fairly compensated. A strong majority of military family physicians are satisfied with their military-sponsored medical education.
Precision Medicine Approach Using Triple Combination Antifungal Therapy for Fusarium Brain Abscesses and Endocarditis in an Adult Burn Patient
Authors: Barrios Evan L , Drabick Zachary , Rodriguez John , Fahy Brenda G , Cochran Amalia L , Driscoll Ian R , Munden Andrea M
Published: June 2024

We report a management strategy for disseminated Fusarium solani fungal infection in an adult 35% total body surface area burn patient with brain abscesses and concomitant pulmonic valve endocarditis resulting in the longest survival reported in a burn patient. Early in his hospital course, the patient was diagnosed with a Fusarium burn wound infection with concomitant fungemia and was treated with a prolonged course of intravenous (IV) antifungal monotherapy. Shortly thereafter, he developed focal neurologic deficits and was found to have brain abscesses on MRI. He underwent emergent craniotomy with debridement, and triple antifungal therapy was initiated. Transesophageal echocardiography demonstrated pulmonic valve vegetations, which resolved with triple antifungal therapy. Disseminated Fusarium solani infection is quite rare with mortality approaching 100%. Given the rarity of this disease process, there are no established antifungal treatment guidelines. However, this patient survived for approximately 1 year after diagnosis with treatment including source control via craniotomy and debridement coupled with prolonged courses of combination antifungal therapy (given the near pan-resistance of his fungal infection). Pharmacogenomic testing was utilized to establish the patient’s metabolism of voriconazole and dosing adjusted accordingly to improve the efficacy of the combination therapy. To our knowledge, an adult burn patient surviving this length of time after Fusarium brain abscesses with disseminated infection has not been previously described.
The impact of incorrect dissociation energies on inferred photospheric abundances
Authors: Aquilina Sarah E , Casey Andrew R , Wheeler Adam J
Published: June 2024

Spectral synthesis codes are essential for inferring stellar parameters and detailed chemical abundances. These codes require many physical inputs to predict an emergent spectrum. Developers adopt the best measurements of those inputs at the time they release their code, but those measurements usually improve over time faster than the software is updated. In general, the impact of using incorrect or uncertain dissociation energies is largely unknown. Here, we evaluate how incorrect dissociation energies impact abundances measured from C2, CN, CH, TiO, and MgO features. For each molecule, we synthesized optical spectra of FGKM-type main-sequence and giant stars using the literature dissociation energy and an incorrect (perturbed) dissociation energy. We find that the uncertainties in the dissociation energies adopted by spectral synthesis codes for CN, CH, TiO, and MgO lead to negligible differences in flux or abundance. C2 is the only diatomic molecule where the uncertainty of the inputted dissociation energy translates to a significant difference in flux and carbon abundance differences of up to 0.2 dex. For solar-like stars, the impact on carbon abundance is up to 0.09 dex. These large abundance differences demonstrate the importance of updating the inputs adopted by spectral synthesis codes, as well as a consensus on appropriate values between different codes.
The kinematics of Polycyclic Aromatic Hydrocarbons (PAHs) in Galaxies revealed by Principal Component Analysis (PCA) tomography with JWST/NIRSpec
Authors: Donnan Fergus R , Rigopoulou Dimitra , García-Bernete Ismael
Published: June 2024

Polycyclic Aromatic Hydrocarbons (PAHs) are organic molecules which comprise the smallest particles of dust in the interstellar medium (ISM). Due to their broad/complex emission profiles, obtaining kinematics is a challenge with traditional methods, especially before the advent of the JWST. In this work, we employ Principal Component Analysis (PCA) tomography to analyse JWST/NIRSpec IFU data of three nearby luminous infrared galaxies (LIRGs), namely, NGC 3256 N, NGC 3256 S, and NGC 7469. We detect the signature of rotation in the second principal component of the 3.3 $\mu$m PAH feature in all three targets. We construct velocity maps from the principal components for the 3.3 $\mu$m PAH feature, Br β (2.625 $\mu$m) and molecular hydrogen, H2 1–0 S(1) (2.12 $\mu$m). We find that in each target, the PAHs qualitatively follow the rotation of the galaxy, consistent with the rotational signature derived from Br β and H2. There are however some differences, with the PAH rotation in NGC 3256 N appearing at a different position angle, which suggest differences in the motion of the dust as compared to the gas. This kind of analysis opens a new window into this key component of the ISM.
ChemFREE: a one-stop comprehensive platform for ecological and environmental risk evaluation of chemicals in one health world
Authors: Chen Dongyu , Liu Yingwei , Liu Yang , Zhao Kejun , Zhang Tianhan , Gao Yangyang , Wang Qi , Song Baoan , Hao Gefei
Published: June 2024

Addressing health and safety crises stemming from various environmental and ecological issues is a core focus of One Health (OH), which aims to balance and optimize the health of humans, animals, and the environment. While many chemicals contribute significantly to our quality of life when properly used, others pose environmental and ecological health risks. Recently, assessing the ecological and environmental risks associated with chemicals has gained increasing significance in the OH world. In silico models may address time-consuming and costly challenges, and fill gaps in situations where no experimental data is available. However, despite their significant contributions, these assessment models are not web-integrated, leading to user inconvenience. In this study, we developed a one-stop comprehensive web platform for freely evaluating the eco-environmental risk of chemicals, named ChemFREE (Chemical Formula Risk Evaluation of Eco-environment, available in http://chemfree.agroda.cn/chemfree/). Inputting SMILES string of chemicals, users will obtain the assessment outputs of ecological and environmental risk, etc. A performance evaluation of 2935 external chemicals revealed that most classification models achieved an accuracy rate above 0.816. Additionally, the $Q_{F1}^2$ metric for regression models ranges from 0.618 to 0.898. Therefore, it will facilitate the eco-environmental risk evaluation of chemicals in the OH world.
Structure of the E. coli nucleoid-associated protein YejK reveals a novel DNA binding clamp
Authors: Schumacher Maria A , Singh Rajiv R , Salinas Raul
Published: June 2024

Nucleoid-associated proteins (NAPs) play central roles in bacterial chromosome organization and DNA processes. The Escherichia coli YejK protein is a highly abundant, yet poorly understood NAP. YejK proteins are conserved among Gram-negative bacteria but show no homology to any previously characterized DNA-binding protein. Hence, how YejK binds DNA is unknown. To gain insight into YejK structure and its DNA binding mechanism we performed biochemical and structural analyses on the E. coli YejK protein. Biochemical assays demonstrate that, unlike many NAPs, YejK does not show a preference for AT-rich DNA and binds non-sequence specifically. A crystal structure revealed YejK adopts a novel fold comprised of two domains. Strikingly, each of the domains harbors an extended arm that mediates dimerization, creating an asymmetric clamp with a 30 Å diameter pore. The lining of the pore is electropositive and mutagenesis combined with fluorescence polarization assays support DNA binding within the pore. Finally, our biochemical analyses on truncated YejK proteins suggest a mechanism for YejK clamp loading. Thus, these data reveal YejK contains a newly described DNA-binding motif that functions as a novel clamp.
Longitudinal assessment of quality of life, neurocognition, and psychopathology in patients with low-grade glioma on first-line temozolomide: A feasibility study
Authors: Darlix Amélie , Monnier Maëva , Castan Florence , Coutant Louise , Fabbro Michel , Denis-Chammas Ève , Carrière Mathilde , Menjot-de-Champfleur Nicolas , Rigau Valérie , Duffau Hugues , Guerdoux Estelle
Published: June 2024

Background

The treatment timing and choice after neurosurgical resection in patients with newly diagnosed diffuse low-grade glioma (DLGG) remain controversial. Indeed, the effect of such treatments must be balanced with the possible side effects. This study evaluated the feasibility of longitudinal exhaustive quality of life (QoL) and neuropsychological assessments in patients with DLGG receiving first-line temozolomide.

Methods

QoL, neurocognition, and psychological disorders were assessed prospectively until disease progression, using testing, clinician-reported, and self-reported questionnaires. The primary endpoint was the participation and adherence to this complete assessment at Baseline (before temozolomide initiation), months 6 and 12 of treatment, and month 6 post-treatment. The QoL and neuropsychological changes over time also were described.

Results

Twenty-six of the twenty-nine eligible patients were enrolled (participation rate: 89.7%, 95% CI: 72.6–97.8). The adherence rate was 95.7% (95% CI: 78.1–99.9; n = 23 because 3 patients progressed in the first 12 months of treatment). Up to month 6 post-treatment, QoL and fatigue remained stable (EORTC QLQC30 and BN20, MFI-20); some specific symptoms were transitory. Both subjective (FACT-Cog) and objective (Z-scores of neurocognitive tests) neurocognitive outcomes remained stable or tended to improve. The percentage of patients with severe depression (BDI-II), anxiety (STAI-Y), or anger (STAXI-II) was stable over time.

Conclusions

This prospective study demonstrated the feasibility of an exhaustive and longitudinal evaluation of QoL, neurocognition, and psychological disorders, with high acceptability by patients with DLGG undergoing chemotherapy. First-line temozolomide seems to have limited short-term effects on QoL and neurocognition. These findings must be confirmed in the long term and in a larger cohort.
Impact of intensity-modulated proton therapy in reducing radiation-induced lymphopenia in glioma patients
Authors: Das Anindita , Sylvia Jacinthlyn , Krishnan Ganapathy , Panda Pankaj Kumar , Subramanyam Preethi , Kumar Roopesh , Adhithyan Rajendran , Patil Sushama , Sharma Dayananda , Jalali Rakesh
Published: June 2024

Background

Current standard management in adult grades 2–4 gliomas includes maximal safe resection followed by adjuvant radiotherapy (RT) and chemotherapy. Radiation-induced lymphopenia (RIL) has been shown to possibly affect treatment outcomes adversely. Proton beam therapy (PBT) may reduce the volume of the normal brain receiving moderate radiation doses, and consequently RIL. Our aim was to evaluate the incidence and severity of RIL during proton beam therapy (PBT).

Methods

We identified patients with grades 2–4 glioma treated with PBT at our center between January 2019 and December 2021. We evaluated the incidence and severity of RIL from weekly complete blood count (CBC) data collected during PBT and compared it to the patients who were treated with photon-based RT (XRT) at our center during the same time.

Results

The incidence of any degree of lymphopenia (48% in PBT, vs. 81.2% in XRT, P value = .001) and severe lymphopenia (8% in PBT, vs. 24.6% in XRT, P value = .093) were both significantly lesser in patients who received PBT. Severe RIL in patients receiving PBT was seen in only CNS WHO Gr-4 tumors. Mean whole brain V20GyE and V25GyE inversely correlated to nadir ALC and were both significantly lower with PBT. Patients with lymphopenia during PBT showed a trend toward poorer progression-free survival (P = .053) compared to those with maintained lymphocyte counts.

Conclusions

Proton therapy seems to have a superior sparing of normal brain to moderate dose radiation than photon-based RT and reduces the incidence of lymphopenia. Glioma patients with lymphopenia possibly have worse outcomes than the ones with maintained lymphocyte counts.
Simulated Target Attainment of Multidose Regimens of Dalbavancin for Prolonged Durations of Therapy
Authors: Volk Cecilia F , Hutson Paul R , Rose Warren E
Published: June 2024

Background

Dalbavancin is a long-acting lipoglycopeptide antibiotic that is increasingly utilized for infections that require prolonged treatment durations despite the lack of Food and Drug Administration approval for these indications. There is no consensus regarding optimal dosing of dalbavancin for these infections and no available pharmacokinetic studies to identify optimal dosing for long-term use.

Methods

An in silico pharmacokinetic simulation was performed to assess the predicted dalbavancin concentration resulting from commonly utilized dosing regimens, in addition to modified regimens. The primary endpoint evaluated was days of median 24-hour free area under the curve over the minimum inhibitory concentration (AUC/MIC) >27.1, the established PK target.

Results

A dosing regimen of 1500 mg on day 0 and day 7 resulted in median AUC/breakpoint value above the target for 57 days (lower 95% confidence interval [CI], 37 days). A modified regimen of 1500 mg on day 0 and day 21 resulted in an additional 11 days of median AUC/breakpoint target attainment. The other standard dosing regimen modeled was 1000 mg on day 0, then 500 mg weekly for 5 doses. This regimen achieved the AUC/breakpoint target for 76 days (lower 95% CI, 59 days). This regimen was modified to 1000 mg on day 0, then 500 mg on days 14 and 28, which shortened the median effective treatment duration by 14 days but required 3 fewer doses.

Conclusions

These simulated results, when combined with the favorable observational data, support the use of commonly reported dalbavancin regimens for prolonged therapy durations. In addition, these pharmacokinetic/pharmacodynamic data support extending the dosing interval beyond the frequently reported weekly regimens, which should be investigated further with a clinical trial.
Oncofusions – shaping cancer care
Authors: Dashi Giovanna , Varjosalo Markku
Published: June 2024

Cancer manifests through a spectrum of mutations, including gene fusions termed oncofusions. These structural alterations influence tumorigenesis across various cancer types. Oncofusions arise primarily from genomic rearrangements and operate through deregulation or hybrid gene formation mechanisms. Notable examples such as BCR::ABL and EWS::FLI1 underscore their clinical significance. Several case studies exemplify the role of identifying and targeting oncofusions in guiding treatment decisions and improving patient outcomes. However, challenges persist in discerning drivers from passenger mutations and addressing acquired resistance. Despite advancements, the complexity of oncofusions warrants further exploration of their full potential as therapeutic targets, requiring a multidisciplinary approach integrating genomics, functional studies, and innovative drug discovery strategies to achieve precision in medicine.
You are unmuted: The impact of virtual arrangements on women and old age legislators’ participation during the COVID-19 pandemic
Authors: Ting Wang Leung
Published: June 2024

During the COVID-19 pandemic, parliaments around the world implemented virtual arrangements to facilitate participation by legislators who were negatively affected. This article explores if the pandemic had a differential impact on MP participation in parliamentary proceedings by age or gender and whether virtual arrangements have mitigated these adverse effects. Using the adoption of hybrid proceedings in the United Kingdom House of Commons as its case study, and exploiting the change in its form and application during the pandemic period as treatment, this article demonstrates that the pandemic has had an especially adverse impact on women MPs’ participation in parliamentary proceedings and that virtual arrangements had a substantive role in mitigating the gendered effect of the pandemic when its application was more extensive. These results suggest that maintaining virtual arrangements for parliamentary proceedings post-pandemic is potentially beneficial for the descriptive representation of women.
Mineral Textures and Chemistry Trace the Origin and Transcrustal Evolution of the Sanyuangou Syenite in Southern North China Craton
Authors: Ma Jian-Feng , Zhao Tai-Ping , Hou Tong , Qu Chuan-Hao
Published: June 2024

Alkaline rocks are widely distributed in various geological environments and are important carriers for exploring the formation and compositional diversity of continental crust. Extensive studies have investigated the processes of mantle melting and crustal differentiation that produced such rocks. However, the potential interaction processes between mantle-derived magma and crust during their formation are poorly constrained. In this study, we focus on a Paleoproterozoic garnet-bearing syenite in the Xiong'er large igneous province (LIP) on the southern margin of the North China Craton through detailed whole-rock and mineral analyses. The high K2O (7.4–8.8 wt %) syenite emplaced at ~1772 Ma with ancient inherited zircon (1800–2800 Ma). The dominant mineral assemblage is composed of clinopyroxene, garnet, and K-feldspar with a small amount of titanite. Complex compositional oscillatory zoning of clinopyroxene and garnet indicates that magma mixing played a significant role in the formation of the syenite. We estimated the major elements composition for melts in equilibrium with clinopyroxene and calculated the clinopyroxene/melt partition coefficients by crystal lattice strain model, thus calculating the trace elements of the equilibrated melts. The equilibrium melts of high Mg# (>85) clinopyroxene have high CaO/Al2O3 (>0.6) and low Hf/Sm (<0.4), which suggests a role for carbonatitic metasomatism of the mantle. The variables La/Yb (24.4–56.1), Dy/Yb (0.8–5.9), and Yb (0.6–10.3 μg/g) indicate that the initial melts were formed by 1% to 2% partial melting of spinel-garnet phlogopite lherzolite. An REE-based model for melts in equilibrium with low Mg# (<85) clinopyroxene indicates that 10% to 30% felsic magma from ancient crust participated in hybridization. In addition to well-documented magma mixing, the oscillatory zoning of garnet is also related to competition with titanite. The initial alkaline magmas have a high water content (~4 wt %), which delays the crystallization of K-feldspar, leading to the enrichment of K2O, until the K-feldspar accumulates in the shallow crust to form the syenite. Magma mixing under an open system further leads to alkalinity enrichment. Magma source and crustal evolution jointly determine the potassium-rich characteristics of syenite. Multiple episodes of magma mixing and fractional crystallization occur in the crust (700–300 MPa), suggesting complex and vertically extensive magma chambers. This study represents the first identification of carbonatitic metasomatism as a mantle source in the Xiong'er LIP. Furthermore, it offers a new perspective on magma mixing between the mantle and crust in transcrustal magmatic systems, contributing to the formation of alkaline rocks.
Effects of motor imagery using virtual reality on pain sensitivity and affect in healthy individuals: a prospective randomized crossover study
Authors: Niwa Yuto , Shimo Kazuhiro , Ohga Satoshi , Hattori Takafumi , Dokita Ayaka , Matsubara Takako
Published: June 2024

Objective

Exercise induces a hypoalgesic response and improves affect. However, some individuals are unable to exercise for various reasons. Motor imagery, involving kinesthetic and visual imagery without physical movement, activates brain regions associated with these benefits and could be an alternative for those unable to exercise. Virtual reality also enhances motor imagery performance because of its illusion and embodiment. Therefore, we examined the effects of motor imagery combined with virtual reality on pain sensitivity and affect in healthy individuals.

Design

Randomized crossover study.

Setting

Laboratory.

Subjects

Thirty-six participants (women: 18) were included.

Methods

Each participant completed three 10-min experimental sessions, comprising actual exercise, motor imagery only, and motor imagery combined with virtual reality. Hypoalgesic responses and affective improvement were assessed using the pressure-pain threshold and the Positive and Negative Affect Schedule, respectively.

Results

All interventions significantly increased the pressure-pain threshold at the thigh (P < .001). Motor imagery combined with virtual reality increased the pressure-pain threshold more than motor imagery alone, but the threshold was similar to that of actual exercise (both P ≥ .05). All interventions significantly decreased the negative affect of the Positive and Negative Affect Schedule (all P < .05).

Conclusions

Motor imagery combined with virtual reality exerted hypoalgesic and affective-improvement effects similar to those of actual exercise.

Clinical trials registration

The study was enrolled in the UMIN Clinical Trials Registry (registration number: UMIN000046095). The website for registration information is https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000052614
Regulating neuronal excitability: The role of S-palmitoylation in NaV1.7 activity and voltage sensitivity
Authors: Tang Cheng , Duran Paz , Calderon-Rivera Aida , Loya-Lopez Santiago , Gomez Kimberly , Perez-Miller Samantha , Khanna Rajesh
Published: June 2024

S-palmitoylation, a reversible lipid post-translational modification, regulates the functions of numerous proteins. Voltage-gated sodium channels (NaVs), pivotal in action potential generation and propagation within cardiac cells and sensory neurons, can be directly or indirectly modulated by S-palmitoylation, impacting channel trafficking and function. However, the role of S-palmitoylation in modulating NaV1.7, a significant contributor to pain pathophysiology, has remained unexplored. Here, we addressed this knowledge gap by investigating if S-palmitoylation influences NaV1.7 channel function. Acyl-biotin exchange assays demonstrated that heterologously expressed NaV1.7 channels are modified by S-palmitoylation. Blocking S-palmitoylation with 2-bromopalmitate resulted in reduced NaV1.7 current density and hyperpolarized steady-state inactivation. We identified two S-palmitoylation sites within NaV1.7, both located in the second intracellular loop, which regulated different properties of the channel. Specifically, S-palmitoylation of cysteine 1126 enhanced NaV1.7 current density, while S-palmitoylation of cysteine 1152 modulated voltage-dependent inactivation. Blocking S-palmitoylation altered excitability of rat dorsal root ganglion neurons. Lastly, in human sensory neurons, NaV1.7 undergoes S-palmitoylation, and the attenuation of this post-translational modification results in alterations in the voltage-dependence of activation, leading to decreased neuronal excitability. Our data show, for the first time, that S-palmitoylation affects NaV1.7 channels, exerting regulatory control over their activity and, consequently, impacting rodent and human sensory neuron excitability. These findings provide a foundation for future pharmacological studies, potentially uncovering novel therapeutic avenues in the modulation of S-palmitoylation for NaV1.7 channels.
Power law of path multiplicity in complex networks
Authors: Deng Ye , Wu Jun
Published: June 2024

Complex networks describe a wide range of systems in nature and society. As a fundamental concept of graph theory, the path connecting nodes and edges plays a vital role in network science. Rather than focusing on the path length or path centrality, here we draw attention to the path multiplicity related to decision-making efficiency, which is defined as the number of shortest paths between node pairs and thus characterizes the routing choice diversity. Notably, through extensive empirical investigations from this new perspective, we surprisingly observe a “hesitant-world” feature along with the “small-world” feature and find a universal power-law of the path multiplicity, meaning that a small number of node pairs possess high path multiplicity. We demonstrate that the power-law of path multiplicity is much stronger than the power-law of node degree, which is known as the scale-free property. Then, we show that these phenomena cannot be captured by existing classical network models. Furthermore, we explore the relationship between the path multiplicity and existing typical network metrics, such as average shortest path length, clustering coefficient, assortativity coefficient, and node centralities. We demonstrate that the path multiplicity is a distinctive network metric. These results expand our knowledge of network structure and provide a novel viewpoint for network design and optimization with significant potential applications in biological, social, and man-made networks.
Sequence-developability mapping of affibody and fibronectin paratopes via library-scale variant characterization
Authors: Nielsen Gregory H , Schmitz Zachary D , Hackel Benjamin J
Published: June 2024

Protein developability is requisite for use in therapeutic, diagnostic, or industrial applications. Many developability assays are low throughput, which limits their utility to the later stages of protein discovery and evolution. Recent approaches enable experimental or computational assessment of many more variants, yet the breadth of applicability across protein families and developability metrics is uncertain. Here, three library-scale assays—on-yeast protease, split green fluorescent protein (GFP), and non-specific binding—were evaluated for their ability to predict two key developability outcomes (thermal stability and recombinant expression) for the small protein scaffolds affibody and fibronectin. The assays’ predictive capabilities were assessed via both linear correlation and machine learning models trained on the library-scale assay data. The on-yeast protease assay is highly predictive of thermal stability for both scaffolds, and the split-GFP assay is informative of affibody thermal stability and expression. The library-scale data was used to map sequence-developability landscapes for affibody and fibronectin binding paratopes, which guides future design of variants and libraries.
RPA3-UMAD1 rs12702634 and rheumatoid arthritis–associated interstitial lung disease in European ancestry
Authors: Juge Pierre-Antoine , Sparks Jeffrey A , Gazal Steven , Ebstein Esther , Borie Raphaël , Debray Marie-Pierre , Kannengiesser Caroline , McDermott Gregory C , Cui Jing , Hayashi Keigo , Doyle Tracy J , van Moorsel Coline H M , van der Vis Joanne J , Grutters Jan C , Knevel Rachel , Heckert Sascha L , Vasarmidi Eirini , Antoniou Katerina M , van der Helm van Mil Annette H M , Boileau Catherine , Crestani Bruno , Dieudé Philippe
Published: June 2024

Objective

Recently, a genome-wide association study identified an association between RA-associated interstitial lung disease (ILD) and RPA3-UMAD1 rs12702634 in the Japanese population, especially for patients with a usual interstitial pneumonia (UIP) pattern. We aimed to replicate this association in a European population and test for interaction with MUC5B rs35705950.

Methods

In this genetic case–control association study, patients with RA and ILD and controls with RA and no ILD were included from France, the USA and the Netherlands. Only cases and controls from European genetic ancestries determined by principal components analysis were included in the analyses. RA was defined by the 1987 ACR or 2010 ACR/EULAR criteria and ILD by chest high-resolution CT scan, except in the control dataset from the Netherlands, where the absence of ILD was determined by chart review. Patients were genotyped for RPA3-UMAD1 rs12702634 and MUC5B rs35705950. Associations were tested using logistic regression adjusted for sex, age at RA onset, age at ILD onset or at certified absence of ILD, tobacco smoking status and country of origin.

Results

Among the 883 patients included, 322 were RA-ILD cases (36.5%). MUC5B rs35705950 was strongly associated with RA-ILD in all datasets {combined adjusted odds ratio [OR] 2.9 [95% CI 2.1, 3.9], P = 1.1 × 10−11. No association between RPA3-UMAD1 rs12702634 and RA-ILD was observed [combined OR 1.2 (95% CI 0.8, 1.6), P = 0.31. No interaction was found between RPA3-UMAD1 rs12702634 and MUC5B rs35705950 (P = 0.70).

Conclusion

Our findings did not support a contribution of RPA3-UMAD1 rs12702634 to the overall RA-ILD susceptibility in the European population.
Caught in the Act: Incipient Speciation at the Southern Limit of Viburnum in the Central Andes
Authors: Maya-Lastra Carlos A , Sweeney Patrick W , Eaton Deren A R , Torrez Vania , Maldonado Carla , Ore-Rengifo Malu I , Arakaki Mónica , Donoghue Michael J , Edwards Erika J
Published: June 2024

A fundamental objective of evolutionary biology is to understand the origin of independently evolving species. Phylogenetic studies of species radiations rarely are able to document ongoing speciation; instead, modes of speciation, entailing geographic separation and/or ecological differentiation, are posited retrospectively. The Oreinotinus clade of Viburnum has radiated recently from north to south through the cloud forests of Mexico and Central America to the Central Andes. Our analyses support a hypothesis of incipient speciation in Oreinotinus at the southern edge of its geographic range, from central Peru to northern Argentina. Although several species and infraspecific taxa have been recognized in this area, multiple lines of evidence and analytical approaches (including analyses of phylogenetic relationships, genetic structure, leaf morphology, and climatic envelopes) favor the recognition of just a single species, V. seemenii. We show that what has previously been recognized as V. seemenii f. minor has recently occupied the drier Tucuman-Bolivian forest region from Samaipata in Bolivia to Salta in northern Argentina. Plants in these populations form a well-supported clade with a distinctive genetic signature and they have evolved smaller, narrower leaves. We interpret this as the beginning of a within-species divergence process that has elsewhere in the neotropics resulted repeatedly in Viburnum species with a particular set of leaf ecomorphs. Specifically, the southern populations are in the process of evolving the small, glabrous, and entire leaf ecomorph that has evolved in four other montane areas of endemism. As predicted based on our studies of leaf ecomorphs in Chiapas, Mexico, these southern populations experience generally drier conditions, with large diurnal temperature fluctuations. In a central portion of the range of V. seemenii, characterized by wetter climatic conditions, we also document what may be the initial differentiation of the leaf ecomorph with larger, pubescent, and toothy leaves. The emergence of these ecomorphs thus appears to be driven by adaptation to subtly different climatic conditions in separate geographic regions, as opposed to parapatric differentiation along elevational gradients as suggested by Viburnum species distributions in other parts of the neotropics.
Influence of proportion of Brahman genetics on productivity of Brahman–Angus cows at weaning
Authors: Martins Thiago , Rocha Cecília Constantino , Driver Joseph Danny , Rae Owen , Elzo Mauricio Aguirre , Mateescu Raluca G , Santos José Eduardo Portela , Binelli Mario
Published: June 2024

This study evaluated the association between the proportion of Brahman genetics and productivity of Brahman–Angus cows at weaning using a 31-yr dataset containing 6,312 cows and 5,405 pregnancies. Cows were contemporaneously reared and enrolled in yearly breeding seasons under subtropical conditions of North-Central Florida. They were evenly distributed in six-breed groups (G) according to the proportion of Brahman genetics: G0% to 19%, G21% to 34%, G38% (Brangus), G41% to 59%, G63% to 78%, and G81% to 100%. The proportion of cows calving (84.9%) did not differ across the six-breed groups. However, cows in the G81% to 100% weaned fewer calves (90.8%) than cows in the G0% to 19% and G21% to 34% (95.7%, each). The weaning rate of cows in the G38% (94.3%), G41% to 59% (94.2%), and G63% to 78% (93.0%) was intermediate between these three breed groups. The preweaning calf mortality was greater for cows in the G81% to 100% (9.2%) than cows in the G0% to 19% and G21% to 34% (4.3%, each), but intermediate for cows in the G38% (5.7%), G41% to 59% (5.8%), and G63% to 78% (7.0%). Cows in the G81% to 100% also weaned lighter calves (220.6 kg) than cows in the G0% to 19% (245.2 kg), G21% to 34% (250.2 kg), G38% (247.9 kg), G41% to 59% (252.5 kg), and G63% to 78% (245.2 kg). Cows in the G0% to 19% weaned lighter calves than cows with 21% to 78% of Brahman genetics. The 205-d adjusted weaning weight evidenced the less productive results of cows in G0% to 19% and G81% to 100% compared with other genetic groups, as they calved at the fastest and slowest rate, respectively. Thus, the 205-d adjusted weaning weight eliminated this bias. Additionally, younger cows weaned lighter calves; and male calves were heavier at weaning than female calves. Both parity order of cow and calf sex altered the magnitude of the described association between breed group of cows and calf weaning weights. Overall, after adjusting for weaning rate and age of calves at weaning, the number of kilograms produced per cow submitted to reproduction was less for cows in the G0% to 19% (191.1 kg) and G81% to 100 (181.8 kg) compared with cows in the G21% to 34 (197.0 kg), G38 (195.9 kg), G41% to 59 (199.7), and G63% to 78 (196.2). Cows in the G81% to 100% were the least productive. Thus, a proportion of Brahman genetics between 21% and 78% ensured superior productivity of Brahman–Angus cows subjected to subtropical conditions.
Effects of developmental exposure to arsenic species on behavioral stress responses in larval zebrafish and implications for stress-related disorders
Authors: McAtee Demetrius , Abdelmoneim Ahmed
Published: June 2024

Arsenic (As) is globally detected in drinking water and food products at levels repeatedly surpassing regulatory thresholds. Several neurological and mental health risks linked to arsenic exposure are proposed; however, the nature of these effects and their association with the chemical forms of arsenic are not fully understood. Gaining a clear understanding of the etiologies and characteristics of these effects is crucial, particularly in association with developmental exposures where the nervous system is most vulnerable. In this study, we investigated the effects of early developmental exposure (6- to 120-h postfertilization [hpf]) of larval zebrafish to environmentally relevant concentrations of arsenic species—trivalent/pentavalent, inorganic/organic forms—on developmental, behavioral, and molecular endpoints to determine their effect on stress response and their potential association with stress-related disorders. At 120 hpf, the developing larvae were assessed for a battery of endpoints including survival, developmental malformities, background activity, and behavioral responses to acute visual and acoustic stimuli. Pooled larval samples were analyzed for alterations in the transcript levels of genes associated with developmental neurotoxicity and stress-related disorders. Developmental exposures at target concentrations did not significantly alter survival, overall development, or background activity, and had minor effects on developmental morphology. Sodium arsenate and monomethylarsonic acid exaggerated the behavioral responses of larval zebrafish, whereas sodium arsenite depressed them. Sodium arsenate induced significant effects on molecular biomarkers. This study highlights the effects of developmental exposure to arsenicals on the behavioral stress response, the role chemical formulation plays in exerting toxicological effects, and the possible association with stress-related disorders.
Incidence of complications among operative pediatric supracondylar humerus fractures using medial and lateral pins: a safe technique for percutaneous medial pin placement
Authors: Minifee Christopher D. , DeFilippo Christine G. , Carmichael Kelly D.
Published: June 2024

Cross-pinning of displaced pediatric supracondylar elbow fractures offers a superior stability construct. However, there is a reluctance to use this construct by closed means because of the risk of iatrogenic ulnar nerve injuries associated with percutaneous medial pin placement. This study describes a safe technique for closed reduction percutaneous with medial pin placement. This study reviewed the clinical charts of 232 pediatric patients who underwent closed reduction with cross-pinning of Gartland type II and III supracondylar fractures from 2000 to 2022 at a single institution. All surgeries were performed by the same attending surgeon at the same institution, with the same technique of medial pin placement. The inpatient and outpatient notes were used to record patient demographic information, fracture classification, and postoperative complications. A total of 232 pediatric patients [114 boys, 118 girls; mean age: 5.8 (range: 1–14) years] with Gartland type II (n = 97) and III (n = 135) supracondylar fractures were included in the study. There were a total of seven (3.02%) postoperative complications: four (1.7%) ulnar neuropathies, two (0.86%) pin site infections, and one (0.43%) anterior interosseous nerve palsy. All documented postoperative complications were resolved by the 3-month follow-up visit. There were no complications of deep infection, malunion, or nonunion. With the proper technique, closed reduction with percutaneous medial pin fixation of pediatric supracondylar fractures is safe and produces excellent postoperative outcomes.

Level of Evidence: Level IV, case series.
Surgeon Recommendations for Physical Activity in Patients With Pediatric Hip Conditions
Authors: Li Jacqueline , Schaeffer Emily K. , Miller Stacey , Schreiber Verena M. , Hailer Yasmin D. , Clohisy John C. , Kim Harry K.W. , Mulpuri Kishore
Published: June 2024

Background:

While physical activity (PA) is important during youth, it is unclear if children and adolescents with developmental dysplasia of the hip (DDH), Legg-Calvé-Perthes disease (LCPD), or slipped capital femoral epiphysis (SCFE) are expected or encouraged to return to PA once they have healed. This study examines the orthopaedic surgeons’ role in advising pediatric hip patients on the PA they should engage in, assessing their practice, opinions, and consensus when making recommendations.

Methods:

Orthopaedic surgeons were invited from member lists of 4 hip study groups. The survey included demographics, opinions regarding PA, and 10 case scenarios that queried respondents on the duration and intensity of PA as well as the restrictions on activity type that they would recommend for DDH, LCPD, or SCFE patients. Consensus was evaluated on a scale ranging from 0 to 1, with a value of 0 indicating no agreement among respondents and a value of 1 indicating complete agreement.

Results:

A total of 51 orthopaedic surgeons responded. While 94% agreed that it is important for school-aged hip patients to return to PA after they have healed, 53% believed that PA may compromise the hip and contribute to the development of osteoarthritis. Average standardized consensus was 0.92 for suggesting the patient engage in some amount of PA, 0.44 for suggesting the recommended daily minimum of 60 minutes of moderate-to-vigorous physical activity (MVPA), and 0.33 for suggesting restrictions on activity type. The most frequently selected restrictions included avoiding impact activities (93%, 235/254) and contact activities (58%, 147/254), followed by weight-bearing activities (24%, 62/254). Respondents were not aware of existing PA guidelines, although 57% expressed interest in following guidelines and 39% were uncertain.

Conclusions:

While there is consensus among orthopaedic surgeons that children with chronic hip conditions should engage in PA, there is considerable variation when recommending the recommended daily MVPA minimum and placing restrictions on activity type. This study suggests interest among orthopaedic surgeons in developing PA guidelines that optimize outcomes for pediatric hip patients.

Level of Evidence:

Level II—Survey study.
Intraoperative O-arm Use for Physeal Bar Excision
Authors: Richard Brian , Abbas Mohammed , Odeneye Oluwatobi , Türker Tolga
Published: June 2024

Introduction:

Growth arrest caused by physeal bar formation in pediatric patients has posed a longstanding challenge in orthopedics. While growth arrest in pediatric distal radius fractures is relatively uncommon, its downstream consequences impact function, pain, and cosmesis. Physeal bar excision can be used to correct and prevent further growth arrest. The results of bar excision have been unreliable due to the difficulty of balancing complete bar resection while minimizing iatrogenic insult to the physis.

Materials and Methods:

In this article, we present a method utilizing intraoperative computed tomography O-arm for physeal bar excision.

Results:

A 10-year-old boy sustained an open distal radius fracture that was initially stabilized with plates and screws. Two of these screws were transphyseal and resulted in physeal bars and growth arrest. Due to age and the central location of his bars, bar excision was performed with the addition of intraoperative computed tomography. This resulted in a successful outcome with restoration of longitudinal growth of his distal radius.

Discussion:

This method offers improved localization of physeal bars intraoperatively and, subsequently, more precise bar excision while minimizing the risk of complications.