bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different modification pathways for m1A58 incorporation in yeast elongator and initiator tRNAs
Authors: Yared Marcel-Joseph , Yoluç Yasemin , Catala Marjorie , Tisné Carine , Kaiser Stefanie , Barraud Pierre 
Published: August 2023

AbstractAs essential components of the protein synthesis machinery, tRNAs undergo a tightly controlled biogenesis process, which include the incorporation of numerous posttranscriptional modifications. Defects in these tRNA maturation steps may lead to the degradation of hypomodified tRNAs by the rapid tRNA decay (RTD) and nuclear surveillance pathways. We previously identified m1A58 as a late modification introduced after modifications Ψ55 and T54 in yeast elongator tRNAPhe. However, previous reports suggested that m1A58 is introduced early during the tRNA modification process, in particular on primary transcripts of initiator tRNAiMet, which prevents its degradation by RNA decay pathways. Here, aiming to reconcile this apparent inconsistency on the temporality of m1A58 incorporation, we examined its introduction into yeast elongator and initiator tRNAs. We used specifically modified tRNAs to report on the molecular aspects controlling the Ψ55 → T54 → m1A58 modification circuit in elongator tRNAs. We also show that m1A58 is efficiently introduced on unmodified tRNAiMet, and does not depend on prior modifications. Finally, we show that m1A58 has major effects on the structural properties of initiator tRNAiMet, so that the tRNA elbow structure is only properly assembled when this modification is present. This observation provides a structural explanation for the degradation of hypomodified tRNAiMet lacking m1A58 by the nuclear surveillance and RTD pathways.
Health-related quality of life of pediatric brain tumor survivors after treatment in Jordan
Authors: Choi Han , Soliman Amr S , Al Mousa Randa , Yeh Jennifer , Khader Jamal , Sultan Iyad , Ibrahimi Ahmad Kh 
Published: August 2023

Abstract

Background
The number of cancer survivors and survivorship are increasing. Health-related quality of life (HRQOL) has not been widely studied in low-and-middle-income countries (LMICs). The aim of this study is to explore HRQOL of childhood brain tumor survivors and its determinants in Jordan.

Methods
Health-related quality of life information was collected from 80 patients treated at the King Hussein Cancer Center and their parents using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales questionnaire in Arabic. Multivariable linear OLS regression models were used to analyze correlates of HRQOL and compare differences between child- and parent-reported responses.

Results
Health-related quality of life scores reported by survivors and by parents were positively correlated on all subscales and total PedsQL scores (r = 0.59, P = .001). Survivors reported better HRQOL in cognitive subscale (β = 0.56, P = .03) and worse HRQOL in work subscale (β = 0.43, P = .04), but no significant differences in the physical, emotional, and social subscales and total PedsQL scores. Significant predictors of HRQOL reported by parents and by children were different. Supratentorial tumor location was associated with a 10.97-unit lower physical HRQOL score, and recurrence of tumors predicted a 17.5-unit lower total HRQOL score, indicating worse quality of life. Male gender (β = 14.9, P = .002) and diagnosis of hypopituitarism (β = 16.1, P = .03) were associated with better HRQOL. Furthermore, patients that only had radiotherapy treatment had better emotional HRQOL (β = 32.9, P = .006) compared to patients that had combined radiotherapy and chemotherapy.

Conclusion
This study provides evidence on determinants of HRQOL of pediatric brain tumor patients in Jordan. Future studies need to capitalize on the findings of this study to institute a system for regular assessment of quality of life of pediatric cancer patients in Jordan and other countries with similar health care systems and sociocultural backgrounds.
Ventriculoperitoneal shunting with an on–off valve for patients with leptomeningeal metastases and intracranial hypertension
Authors: Huntoon Kristin M , Gasco Jaime , Glitza Oliva Isabella C , Ferguson Sherise D , Majd Nazarin K , McCutcheon Ian E 
Published: August 2023

Abstract

Background
We report our experience with using a ventriculoperitoneal shunt (VPS) with an on–off valve and in-line Ommaya reservoir for the treatment of hydrocephalus or intracranial hypertension in patients with leptomeningeal disease (LMD). Our goal was to determine whether control of intracranial pressure elevation combined with intrathecal (IT) chemotherapy would extend patient survival.

Methods
In this IRB-approved retrospective study, we reviewed 58 cases of adult patients with LMD from solid cancers who received a VPS with a reservoir and an on–off valve at M D Anderson Cancer Center from November 1996 through December 2021. Primary tumors were most often melanoma (n = 19) or breast carcinoma (n = 20). Hydrocephalus was diagnosed by clinical symptoms and findings on magnetic resonance imaging (MRI), and LMD by MRI or cerebrospinal fluid analysis. Differences in overall survival (OS) were assessed with standard statistical techniques.

Results
Patients who received a VPS and more than 3 IT chemotherapy sessions survived longer (n = 26; OS time from implantation 11.7 ± 3.6 months) than those who received an occludable shunt but no IT chemotherapy (n = 24; OS time from implantation 2.8 ± 0.7 months, P &lt; .018). Peritoneal seeding appeared after shunt insertion in only two patients (3%).

Conclusions
This is the largest series reported to date of patients with LMD who had had shunts with on–off valves placed to relieve symptoms of intracranial hypertension. Use of IT chemotherapy and control of hydrocephalus via such shunts was associated with improved survival.
Evaluating chronic pain as a risk factor for COVID-19 complications among New York State Medicaid beneficiaries: a retrospective claims analysis
Authors: Perry Allison , Wheeler-Martin Katherine , Terlizzi Kelly , Krawczyk Noa , Jent Victoria , Hasin Deborah S , Neighbors Charles , Mannes Zachary L , Doan Lisa V , Pamplin II John R , Townsend Tarlise N , Crystal Stephen , Martins Silvia S , Cerdá Magdalena 
Published: August 2023

Abstract

Objective
To assess whether chronic pain increases the risk of COVID-19 complications and whether opioid use disorder (OUD) differentiates this risk among New York State Medicaid beneficiaries.

Design, Setting, and Subjects
This was a retrospective cohort study of New York State Medicaid claims data. We evaluated Medicaid claims from March 2019 through December 2020 to determine whether chronic pain increased the risk of COVID-19 emergency department (ED) visits, hospitalizations, and complications and whether this relationship differed by OUD status. We included beneficiaries 18–64 years of age with 10 months of prior enrollment. Patients with chronic pain were propensity score-matched to those without chronic pain on demographics, utilization, and comorbidities to control for confounders and were stratified by OUD. Complementary log–log regressions estimated hazard ratios (HRs) of COVID-19 ED visits and hospitalizations; logistic regressions estimated odds ratios (ORs) of hospital complications and readmissions within 0–30, 31–60, and 61–90 days.

Results
Among 773 880 adults, chronic pain was associated with greater hazards of COVID-related ED visits (HR = 1.22 [95% CI: 1.16–1.29]) and hospitalizations (HR = 1.19 [95% CI: 1.12–1.27]). Patients with chronic pain and OUD had even greater hazards of hospitalization (HR = 1.25 [95% CI: 1.07–1.47]) and increased odds of hepatic- and cardiac-related events (OR = 1.74 [95% CI: 1.10–2.74]).

Conclusions
Chronic pain increased the risk of COVID-19 ED visits and hospitalizations. Presence of OUD further increased the risk of COVID-19 hospitalizations and the odds of hepatic- and cardiac-related events. Results highlight intersecting risks among a vulnerable population and can inform tailored COVID-19 management.
Ultrasound-guided costovertebral joint injection—technique description and fluoroscopy and computerized tomography combined controlled cadaveric feasibility study
Authors: Ferreira-Silva Nuno , Worthy Lucy , Ribas Rita , Ferreira-Dos-Santos Guilherme , Bestic Joseph , Hurdle Mark Friedrich B 
Published: August 2023

Abstract

Objectives
To describe and assess the feasibility of an ultrasound-guided technique for intra-articular injection of the costovertebral joints, in an unembalmed cadaveric specimen, utilizing fluoroscopy and cone beam computerized tomography for confirmation of contrast spread and needle tip position, respectively.

Methodology
A single unembalmed cadaveric specimen was obtained. A single interventionist performed the placement of the needles under ultrasound guidance. Contrast dye was then injected through each of the needles under real-time fluoroscopy. Finally, the specimen was submitted to a cone beam computerized tomography with 3-dimensional acquisition and multiplanar reformatting to assess final needle tip position relative to the costovertebral joints.

Results
In total, 18 spinal needles were placed under ultrasound guidance. Fluoroscopy showed 4 distinct patterns of contrast spread: intra-articular in the costovertebral joint (13 levels in total), epidural (1 level), intra-articular in the facet joint of the target level (3 levels), and undetermined (1 level). Cone-beam computerized tomography confirmed 13 out of 18 needles to be adequately placed in the costovertebral joints (72% of the total) and 5 out of the 18 needles to be misplaced: 3 needles were placed in the facet joint of the target level, and 2 needles were placed in the epidural space.

Conclusions
This study suggests that, when performed by experienced interventionists, this technique has an accuracy rate of 72%. Further studies are warranted before these results can be extrapolated to daily clinical practice.
Albumin-based nanosystem for dual-modality imaging-guided chem-phototherapy against immune-cold triple-negative breast cancer
Authors: Peng Chen , Zeng Xiaodie , Cai Jiali , Huang Hanyu , Yang Fan , Jin Shaowen , Guan Xiuhong , Wang Zhiyong 
Published: August 2023

Abstract
Triple-negative breast cancer is a highly aggressive and metastatic tumor; diagnosing it in the early stages is still difficult, and the prognosis for conventional radio-chemotherapy and immunotreatment is not promising due to cancer’s immunosuppressive microenvironment. The utilization of protein-based nanosystem has proven to be effective in delivering agents with limited adverse effects, yet the combination of diagnosis and treatment remains a difficult challenge. This research took advantage of natural albumin and organic molecules to construct a self-assemble core-shell nanostructure combining with superparamagnetic iron oxide nanocrystals and heptamethine cyanine dye IR780 through non-covalent interactions. This nanocomposite successfully decreased the transverse relaxation time of the magnetic resonance hydrogen nucleus, resulting in outstanding T2 imaging, as well as emitting near-infrared II fluorescence, thereby the resulting dual-modality imaging tool was applied to improve diagnostic competency. It is noteworthy that the nanocomposites exhibited impressive enzyme-like catalytic and photothermal capabilities, resulting in a successful activation of the immune system to efficiently suppress distant metastatic lesions in vivo. Consequently, this nano-drug-based therapy could be an advantageous asset in reinforcing the immune system and hindering the growth and reappearance of the immune-cold breast cancer.
Impaired Lactate Release in Dorsal CA1 Astrocytes Contributed to Nociceptive Sensitization and Comorbid Memory Deficits in Rodents
Authors: Han Shuang , Jiang Bin , Ren Jiale , Gao Feng , Wen Junjian , Zhou Taihe , Wang Laijian , Wei Xuhong 
Published: August 2023

Background
Memory deficits are a common comorbid disorder in patients suffering from neuropathic pain. The mechanisms underlying the comorbidities remain elusive. The hypothesis of this study was that impaired lactate release from dysfunctional astrocytes in dorsal hippocampal CA1 contributed to memory deficits.

Methods
A spared nerve injury model was established to induce both pain and memory deficits in rats and mice of both sexes. von Frey tests, novel object recognition, and conditioned place preference tests were applied to evaluate the behaviors. Whole-cell recording, fiber photometry, Western blotting, and immunohistochemistry combined with intracranial injections were used to explore the underlying mechanisms.

Results
Animals with spared sciatic nerve injury that had displayed nociception sensitization or memory deficit comorbidities demonstrated a reduction in the intrinsic excitability of pyramidal neurons, accompanied by reduced Ca2+ activation in astrocytes (ΔF/F, sham: 6 ± 2%; comorbidity: 2 ± 0.4%) and a decrease in the expression of glial fibrillary acidic protein and lactate levels in the dorsal CA1. Exogenous lactate supply or increasing endogenous lactate release by chemogenetic activation of astrocytes alleviated this comorbidity by enhancing the cell excitability (129 ± 4 vs. 88 ± 10 for 3.5 mM lactate) and potentiating N-methyl-d-aspartate receptor–mediated excitatory postsynaptic potentials of pyramidal neurons. In contrast, inhibition of lactate synthesis, blocking lactate transporters, or chemogenetic inhibition of astrocytes resulted in comorbidity-like behaviors in naive animals. Notably, β2-adrenergic receptors in astrocytes but not neurons were downregulated in dorsal CA1 after spared nerve injury. Microinjection of a β2 receptor agonist into dorsal CA1 or activation of the noradrenergic projections onto the hippocampus from the locus coeruleus alleviated the comorbidity, possibly by increasing lactate release.

Conclusions
Impaired lactate release from dysfunctional astrocytes, which could be rescued by activation of the locus coeruleus, led to nociception and memory deficits after peripheral nerve injury.

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Composite measures to assess disease damage, disease severity and treatment response in systemic sclerosis clinical trials
Authors: Ross Laura , Nikpour Mandana 
Published: August 2023

Purpose of review
The aim of this study was to summarize the composite outcome measures available to assess disease damage, severity and treatment response in systemic sclerosis (SSc).

Recent findings
There have been many recent efforts to rigorously develop and validate composite outcome measures to assess the totality of the impact of SSc on patients. All initiatives have used both consensus and data-driven methods. Recently developed are a SSc-specific damage index, a patient-reported disease impact questionnaire (ScleroID) and a treatment response index (ACR-CRISS).

Summary
Multiorgan, composite measures are being increasingly applied to assess treatment efficacy in clinical trials. Although a fully validated, disease-specific composite measure is not yet available, there has been significant recent progress towards developing measures of treatment response, damage and overall impact of SSc for application in randomized controlled trials.
SCLERAL SUTURED TORIC INTRAOCULAR LENS WITH PARS PLANA VITRECTOMY FOR THE CORRECTION OF CORNEAL ASTIGMATISM WITHOUT CAPSULAR SUPPORT
Authors: Starr Matthew R. , Ferenchak Kevin , Mogil Rachel 
Published: August 2023

Purpose:
To describe the repair of a patient with bilateral subluxed cataract and corneal astigmatism in the setting of a coloboma of the iris, zonules, lens, and retina. Preoperatively, his best-corrected acuity was 20/500 in the right eye and 20/200 in the left eye. His preoperative refraction was −7.25 +1.00 at 080 in the right eye and −7.75 +3.00 at 040 in the left eye. On corneal topography, he had 1.95D and 1.45D of regular astigmatism in the right and left eye, respectively.

Methods:
This technique involves pars plana vitrectomy in combination with the placement of a MX60 toric intraocular lens fixated to the sclera using 8-0 Gore-Tex in line with the axis of steep corneal astigmatism. The lens is affixed through two pairs of nasal and temporal sclerotomies, with each pair located 3 mm posterior to the limbus and 5 mm apart, centered along the axis of steep astigmatism.

Results:
Postoperatively, uncorrected visual acuity in this patient was 20/25 in the right eye and 20/20 in the left eye with a refraction of −0.75 +0.50 at 180 in the right eye and −0.75 +1.00 at 180 in the left eye.

Conclusion:
Scleral sutured toric intraocular lens placement and pars plana vitrectomy is a viable solution for patients with regular corneal astigmatism and cataract repair in the absence of zonular support.
Management of low astigmatism in implantable collamer lens surgery: opposite clear corneal incisions vs toric implantable collamer lens
Authors: González-Cruces Timoteo , Sánchez-Ventosa Álvaro , Villarrubia Alberto , Sánchez-González José-María , Cano-Ortiz Antonio 
Published: August 2023

Purpose:To compare 2 techniques to correct low astigmatism during implantable collamer lens (ICL) surgery: astigmatic opposite clear corneal incisions (OCCIs) and toric ICL (T-ICL).Setting:Arruzafa Ophthalmological Hospital, Cordoba, Spain.Design:Randomized prospective comparative study.Methods:The study comprised 152 myopic eyes undergoing ICL surgery. Patients were separated into 2 groups: Group 1 (57 patients; 76 eyes) received a spherical ICL with OCCIs and Group 2 (53 patients; 76 eyes) received a T-ICL. The inclusion criteria were refractive astigmatism up to 1.50 diopters (D), regular corneal astigmatism up to 2.00 D (Sim K, Pentacam), and agreement between the refractive and topographic corneal cylinders (discrepancies less than 30 degrees axis or 0.50 D). The outcomes were evaluated after a 1-month follow-up.Results:The T-ICL group achieved a mean postoperative spherical equivalent refraction and refractive astigmatism of −0.04 ± 0.17 D and −0.03 ± 0.12 D, respectively, vs −0.14 ± 0.33 D and −0.20 ± 0.36 D, in the OCCI group (P< .001). Postoperative refractive astigmatism of less than 0.25 D was achieved in 94.74% of cases in the T-ICL group vs 73.68% in the OCCI group. Undercorrection of corneal astigmatism occurred in the OCCI group with a surgically induced astigmatism of 0.48 ± 0.24 D and correction index = 0.46.Conclusions:Both the T-ICL and OCCI techniques provided excellent results in terms of safety and efficacy. T-ICL surgery was shown to be more predictable and accurate for correcting low astigmatism with a lower postoperative spherical equivalent and less residual astigmatism compared to incisional management.
A novel formulation enabled transformation of 3 HIV drugs tenofovir-lamivudine-dolutegravir (TLD) from short-acting to long-acting all-in-one injectable
Authors: Perazzolo Simone , Stephen Zachary , Eguchi Masa , Xu Xiaolin , Fratte Rachele Delle , Collier Ann C. , Melvin Ann J. , Ho Rodney J.Y. 
Published: August 2023

Objective:
To develop an injectable dosage form of the daily oral HIV drugs, tenofovir (T), lamivudine (L), and dolutegravir (D), creating a single, complete, all-in-one TLD 3-drug-combination that demonstrates long-acting pharmacokinetics.

Design:
Using drug-combination-nanoparticle (DcNP) technology to stabilize multiple HIV drugs, the 3 HIV drugs TLD, with disparate physical-chemical properties, are stabilized and assembled with lipid-excipients to form TLD-in-DcNP. TLD-in-DcNP is verified to be stable and suitable for subcutaneous administration. To characterize the plasma time-courses and PBMC concentrations for all 3 drugs, single subcutaneous injections of TLD-in-DcNP were given to nonhuman primates (NHP, M. nemestrina).

Results:
Following single-dose TLD-in-DcNP, all drugs exhibited long-acting profiles in NHP plasma with levels that persisted for 4 weeks above predicted viral-effective concentrations for TLD in combination. Times-to-peak were within 24 hr in all NHP for all drugs. Compared to a free-soluble TLD, TLD-in-DcNP provided exposure enhancement and extended duration 7.0-, 2.1-, and 20-fold as AUC boost and 10-, 8.3-, and 5.9-fold as half-life extension. Additionally, DcNP may provide more drug exposure in cells than plasma with PBMC-to-plasma drug ratios exceeding one, suggesting cell-targeted drug-combination delivery.

Conclusions:
This study confirms that TLD with disparate properties can be made stable by DcNP to enable TLD concentrations of 4 weeks in NHP. Study results highlighted the potential of TLD-in-DcNP as a convenient all-in-one, complete HIV long-acting product for clinical development.
A New Minimally Invasive Procedure for Treating Plantar Heel Pain
Authors: Wu Bihua , Xiao Shune , Yang Sanhong , Wei Zairong , Deng Chengliang 
Published: August 2023

Atrophy of the fat pad is considered to be one of the main causes of plantar heel pain. Recent studies showed fat grafting increased fat pad volume and was beneficial for treating pedal fat pad atrophy. However, traditional fat grafting has a high absorption rate because of lower concentration of adipose-derived stem cells. Stromal vascular fraction gel (SVF-gel), as a novel fat grafting and rich in adipose-derived stem cells, is prepared by a simple mechanical process. This study aimed to assess the efficacy of SVF-gel in the treatment of plantar heel pain.

Methods
Fourteen patients who experienced plantar heel pain and underwent plantar heel SVF-gel grafting between January 2019 and June 2020 were included in this retrospective study. Foot pain and disability were measured at the screening visit and at the 3-, 6-, and 12-month follow-up visits. The volume of the heel fat pad was measured by magnetic resonance imaging.

Results
Four of the patients had bilateral plantar heel pain, and 10 patients had unilateral plantar heel pain. All patients showed significant improvements in pain and foot function at 3 months after SVF-gel grafting compared with the baseline, with the greatest improvement at 6 months and the effect lasting 1 year or more. In addition, the thickness of the heel fat pad was significantly greater than at baseline at 3 months, and the effect lasted for 1 year or more.

Conclusion
Stromal vascular fraction gel grafting is a safe, minimally invasive, and effective approach to treat plantar heel pain.