bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathionylation of a glycolytic enzyme promotes cell death and vigor loss during aging of elm seeds
Authors: Li Ying , Wang Yu , He Yu-Qi , Ye Tian-Tian , Huang Xu , Wu Hao , Ma Tian-Xiao , Pritchard Hugh W , Wang Xiao-Feng , Xue Hua 
Published: April 2024

Abstract
Seed deterioration during storage is a major problem in agricultural and forestry production and for germplasm conservation. Our previous studies have shown that a mitochondrial outer membrane protein VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) is involved in programmed cell death-like viability loss during the controlled deterioration treatment (CDT) of elm (Ulmus pumila L.) seeds, but its underlying mechanism remains unclear. In this study, we demonstrate that the oxidative modification of GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) is functioned in the gate regulation of VDAC during the CDT of elm seeds. Through biochemical and cytological methods and observations of transgenic material [Arabidopsis (Arabidopsis thaliana), Nicotiana benthamiana, and yeast (Saccharomyces cerevisiae)], we demonstrate that cysteine S-glutathionylated UpGAPDH1 interacts with UpVDAC3 during seed aging, which leads to a mitochondrial permeability transition and aggravation of cell death, as indicated by the leakage of the mitochondrial proapoptotic factor cytochrome c and the emergence of apoptotic nucleus. Physiological assays and inductively coupled plasma mass spectrometry analysis revealed that GAPDH glutathionylation is mediated by increased glutathione, which might be caused by increases in the concentrations of free metals, especially Zn. Introduction of the Zn-specific chelator TPEN [(N,N,N′,N′-Tetrakis (2-pyridylmethyl)ethylenediamine)] significantly delayed seed aging. We conclude that glutathionylated UpGAPDH1 interacts with UpVDAC3 and serves as a proapoptotic protein for VDAC-gating regulation and cell death initiation during seed aging.
Nano-hydroxyapatite promotes cell apoptosis by co-activating endoplasmic reticulum stress and mitochondria damage to inhibit glioma growth
Authors: Wang Yifu , Wu Hongfeng , Chen Zhu , Cao Jun , Zhu Xiangdong , Zhang Xingdong 
Published: April 2024

Abstract
Despite a growing body of studies demonstrating the specific anti-tumor effect of nano-hydroxyapatite (n-HA), the underlying mechanism remained unclear. Endoplasmic reticulum (ER) and mitochondria are two key players in intracellular Ca2+ homeostasis and both require Ca2+ to participate. Moreover, the ER–mitochondria interplay coordinates the maintenance of cellular Ca2+ homeostasis to prevent any negative consequences from excess of Ca2+, hence there needs in-depth study of n-HA effect on them. In this study, we fabricated needle-like n-HA to investigate the anti-tumor effectiveness as well as the underlying mechanisms from cellular and molecular perspectives. Data from in vitro experiments indicated that the growth and invasion of glioma cells were obviously reduced with the aid of n-HA. It is interesting to note that the expression of ER stress biomarkers (GRP78, p-IRE1, p-PERK, PERK, and ATF6) were all upregulated after n-HA treatment, along with the activation of the pro-apoptotic transcription factor CHOP, showing that ER stress produced by n-HA triggered cell apoptosis. Moreover, the increased expression level of intracellular reactive oxygen species and the mitochondrial membrane depolarization, as well as the downstream cell apoptotic signaling activation, further demonstrated the pro-apoptotic roles of n-HA induced Ca2+ overload through inducing mitochondria damage. The in vivo data provided additional evidence that n-HA caused ER stress and mitochondria damage in cells and effectively restrain the growth of glioma tumors. Collectively, the work showed that n-HA co-activated intracellular ER stress and mitochondria damage are critical triggers for cancer cells apoptosis, offering fresh perspectives on ER-mitochondria targeted anti-tumor therapy.
The clinical outcomes and healthcare resource utilization in IgG4-related disease: a claims-based analysis of commercially insured adults in the United States
Authors: Wallace Zachary S , Miles Gandarvaka , Smolkina Ekaterina , Petruski-Ivleva Natalia , Madziva Duane , Guzzo Krishan , Cook Claire , Fu Xiaoqing , Zhang Yuqing , Stone John H , Choi Hyon K 
Published: April 2024

Abstract

Objectives
IgG4-related disease (IgG4-RD) can affect nearly any organ and is often treated with glucocorticoids, which contribute to organ damage and toxicity. Comorbidities and healthcare utilization in IgG4-RD are poorly understood.

Methods
We conducted a cohort study using claims data from a US managed care organization. Incident IgG4-RD cases were identified using a validated algorithm; general population comparators were matched by age, sex, race/ethnicity and index date. The frequency of 21 expert-defined clinical outcomes associated with IgG4-RD or its treatment and healthcare-associated visits and costs were assessed 12 months before and 36 months after the index date (date of earliest IgG4-RD-related claim).

Results
There were 524 cases and 5240 comparators. Most cases received glucocorticoids prior to (64.0%) and after (85.1%) the index date. Nearly all outcomes, many being common glucocorticoid toxicities, occurred more frequently in cases vs comparators. During follow-up, the largest differences between cases and comparators were seen for gastroesophageal reflux disease (prevalence difference: +31.2%, P &lt; 0.001), infections (+17.3%, P &lt; 0.001), hypertension (+15.5%, P &lt; 0.01) and diabetes mellitus (+15.0%, P &lt; 0.001). The difference in malignancy increased during follow-up from +8.8% to +12.5% (P &lt; 0.001). Some 17.4% of cases used pancreatic enzyme replacement therapy during follow-up. Over follow-up, cases were more often hospitalized (57.3% vs 17.2%, P &lt; 0.01) and/or had an emergency room visit (72.0% vs 36.7%, P &lt; 0.01); all costs were greater in cases than comparators.

Conclusions
Patients with IgG4-RD are disproportionately affected by adverse outcomes, some of which may be preventable or modifiable with vigilant clinician monitoring. Glucocorticoid-sparing treatments may improve these outcomes.
Clinical Applications of Machine Learning
Authors: Mateussi Nadayca , Rogers Michael P. , Grimsley Emily A. , Read Meagan , Parikh Rajavi , Pietrobon Ricardo , Kuo Paul C. 
Published: April 2024

Objective:
This review introduces interpretable predictive machine learning approaches, natural language processing, image recognition, and reinforcement learning methodologies to familiarize end users.

Background:
As machine learning, artificial intelligence, and generative artificial intelligence become increasingly utilized in clinical medicine, it is imperative that end users understand the underlying methodologies.

Methods:
This review describes publicly available datasets that can be used with interpretable predictive approaches, natural language processing, image recognition, and reinforcement learning models, outlines result interpretation, and provides references for in-depth information about each analytical framework.

Results:
This review introduces interpretable predictive machine learning models, natural language processing, image recognition, and reinforcement learning methodologies.

Conclusions:
Interpretable predictive machine learning models, natural language processing, image recognition, and reinforcement learning are core machine learning methodologies that underlie many of the artificial intelligence methodologies that will drive the future of clinical medicine and surgery. End users must be well versed in the strengths and weaknesses of these tools as they are applied to patient care now and in the future.
Asymmetrical atrophy of the paraspinal muscles in patients undergoing unilateral lumbar medial branch radiofrequency neurotomy
Authors: Guven Ali E. , Evangelisti Gisberto , Burkhard Marco D. , Köhli Paul , Hambrecht Jan , Zhu Jiaqi , Chiapparelli Erika , Kelly Michael , Tsuchiya Koki , Amoroso Krizia , Zadeh Arman , Shue Jennifer , Tan Ek Tsoon , Sama Andrew A. , Girardi Federico P. , Cammisa Frank P. , Hughes Alexander P. 
Published: April 2024

Abstract
Lumbar medial branch radiofrequency neurotomy (RFN), a common treatment for chronic low back pain due to facet joint osteoarthritis (FJOA), may amplify paraspinal muscle atrophy due to denervation. This study aimed to investigate the asymmetry of paraspinal muscle morphology change in patients undergoing unilateral lumbar medial branch RFN. Data from patients who underwent RFN between March 2016 and October 2021 were retrospectively analyzed. Lumbar foramina stenosis (LFS), FJOA, and fatty infiltration (FI) functional cross-sectional area (fCSA) of the paraspinal muscles were assessed on preinterventional and minimum 2-year postinterventional MRI. Wilcoxon signed-rank tests compared measurements between sides. A total of 51 levels of 24 patients were included in the analysis, with 102 sides compared. Baseline MRI measurements did not differ significantly between the RFN side and the contralateral side. The RFN side had a higher increase in multifidus FI (+4.2% [0.3-7.8] vs +2.0% [−2.2 to 6.2], P = 0.005) and a higher decrease in multifidus fCSA (−60.9 mm2 [−116.0 to 10.8] vs −19.6 mm2 [−80.3 to 44.8], P = 0.003) compared with the contralateral side. The change in erector spinae FI and fCSA did not differ between sides. The RFN side had a higher increase in multifidus muscle atrophy compared with the contralateral side. The absence of significant preinterventional degenerative asymmetry and the specificity of the effect to the multifidus muscle suggest a link to RFN. These findings highlight the importance of considering the long-term effects of lumbar medial branch RFN on paraspinal muscle health.
Painful distortions: people with painful knee osteoarthritis have biased visuospatial perception of the environment
Authors: MacIntyre Erin , Braithwaite Felicity A. , Stanton Tasha R. 
Published: April 2024

Abstract
Visuospatial perception is thought to be adaptive—ie, hills are perceived as steeper when capacity is low, or threat is high—guiding appropriate interaction with the environment. Pain (bodily threat) may similarly modulate visuospatial perception, with the extent of modulation influenced by threat magnitude (pain intensity, fear) and associated with behaviour (physical activity). We compared visuospatial perception of the environment between 50 people with painful knee osteoarthritis and 50 age-/sex-matched pain-free control participants using 3 virtual reality tasks (uphill steepness estimation, downhill steepness estimation, and a distance-on-hill measure), exploring associations between visuospatial perception, clinical characteristics (pain intensity, state and trait fear), and behaviour (wrist-worn accelerometry) within a larger knee osteoarthritis group (n = 85). People with knee osteoarthritis overestimated uphill (F1,485 = 19.4, P < 0.001) and downhill (F1,480 = 32.3, P < 0.001) steepness more so than pain-free controls, but the groups did not differ for distance-on-hill measures (U = 1273, P = 0.61). There was also a significant group x steepness interaction for the downhill steepness task (F4,480 = 3.11, P = 0.02). Heightened overestimation in people with knee osteoarthritis relative to pain-free controls increased as downhill slopes became steeper. Results were unchanged in a replication analysis using all knee osteoarthritis participants (n = 85), except the downhill steepness interaction was no longer significant. In people with knee osteoarthritis, higher state fear was associated with greater over-estimation of downhill slope steepness (rho = 0.69, P < 0.001), and greater visuospatial overestimation (distance-on-hill) was associated with lower physical activity levels (rho = −0.22, P = 0.045). These findings suggest that chronic pain may shift perception of the environment in line with protection, with overestimation heightened when threat is greater (steeper hills, more fearful), although impact on real-world behaviour is uncertain.
Investigating the fluctuating nature of post-COVID pain symptoms in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP multicenter study
Authors: Fernández-de-las-Peñas César , Pellicer-Valero Oscar J. , Martín-Guerrero José D. , Hernández-Barrera Valentín , Arendt-Nielsen Lars 
Published: April 2024

Abstract

Objective:
This cohort study used Sankey plots and exponential bar plots for visualizing the fluctuating nature and trajectory of post-COVID pain in previously hospitalized COVID-19 survivors.

Methods:
A cohort of 1266 subjects hospitalised because of COVID-19 during the first wave of the pandemic were scheduled for a telephone interview at 8.4 (T1), 13.2 (T2), and 18.3 (T3) months in average after hospitalization for collecting data about post-COVID pain. Patients were asked for about pain symptomatology that was attributed to the infection. Hospitalization and clinical data were collected from medical records.

Results:
The prevalence of myalgia as COVID-19–associated symptom was 29.82% (n = 389) at hospitalization (T0). The prevalence of post-COVID pain was 41.07% (n = 520) at T1, 34.29% (n = 434) at T2, and 28.47% (n = 360) at T3. The recovery exponential curve revealed a decrease trend visualizing that post-COVID pain improved over the time span investigated. Pain in the lower extremity and widespread pain were the most prevalent locations. Female sex (OR 1.507, 95% CI 1.047–2.169), pre-existing pain symptoms (OR 1.724, 95% CI 1.237–2.403), headache as onset-symptom (OR 2.374, 95% CI 1.550–3.639), days at hospital (OR 1.012, 95% CI 1.000–1.025), and presence of post-COVID pain at T1 (OR 13.243, 95% CI 9.428–18.601) were associated with post-COVID pain at T2. Only the presence of post-COVID pain at T1 (OR 5.383, 95% CI 3.896–7.439) was associated with post-COVID pain at T3.

Conclusion:
Current results show a fluctuating evolution with a decreasing tendency of post-COVID pain during the first years after hospitalization. The development of post-COVID pain soon after SARS-CoV-2 infection predispose for long-lasting chronic pain.
Thin Free Perforator Flap as a Viable Option for Forefoot Reconstruction: Comprehensive Evaluation of Outcomes
Authors: Lee Eun Song , Kim Da Eun , Lee Kyeong-Tae 
Published: April 2024

Background:
Reconstruction of forefoot defects often necessitates free tissue transfer due to the limited availability of local tissue. Microsurgical reconstruction of the forefoot remains challenging, as it requires durable yet thin soft-tissue coverage for functional restoration. This study aimed to evaluate the efficacy of free thin perforator flaps for forefoot reconstruction, with a focus on functional outcomes.

Methods:
Records of patients who underwent microsurgical forefoot reconstruction between March of 2020 and September of 2023 were reviewed. Development of postoperative complications and functional outcomes were evaluated.

Results:
In total, 53 patients (mean age, 62.7 years) were analyzed. The most common cause of defects was oncologic surgery, followed by chronic wound, with a majority involving the plantar side. The superthin anterolateral thigh flap and superficial circumflex iliac artery perforator flap were predominantly used. The median flap thickness was 4.0 mm. Digital vessels were the most frequently used as recipients. All but one flap survived, resulting in a success rate of 98.1%. Postoperative flap site complications developed in 20 patients, the majority of which resolved with conservative treatment. The median hospital stay was 8.0 days, and the mean time for initiating weight-bearing ambulation was 12.4 days. In the postoperative Foot Function Index questionnaire survey, the overall score was 9.41, showing minimal impairment, and it did not differ according to defect size or location. A secondary debulking operation was needed in 7 patients.

Conclusion:
Use of thin free perforator flaps might provide reliable outcomes with rapid recovery and excellent postoperative function in forefoot reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Medial Femoral Condyle Periosteal Free Flap for Bone Coverage Following Debridement of Intermediate-Stage Osteoradionecrosis of the Jaw
Authors: Hurrell Michael J.L. , Leinkram David , Stokan Murray J. , Clark Jonathan R. 
Published: April 2024

Study design: Case report. Osteoradionecrosis (ORN) of the jaw is a potentially devastating consequence of head and neck irradiation. The progression of ORN can lead to loss of bone, teeth, soft tissue necrosis, pathologic fracture, and oro-cutaneous fistula. Reconstructive surgery has mostly been reserved for late-stage disease where segmental resections are frequently necessary. Evidence is emerging to support earlier treatment in the form of debridement in combination with soft tissue free flaps for intermediate-stage ORN. The authors present a case of a 76-year-old male with persistent Notani 2 ORN of the mandible, treated with surgical removal of all remaining mandibular teeth, transoral debridement of all necrotic mandibular bone, and bone coverage with a left medial femoral condyle (MFC) periosteal free flap based on the descending genicular artery. Treatment was uneventful both intraoperatively and postoperatively. Since surgery (15 mo) the patient has remained free from clinical and radiologic signs of ORN. The MFP periosteal free flap provided an excellent result with minimal surgical complexity and morbidity in this case. Such treatment at an intermediate stage likely results in a reduction in segmental resections, less donor site morbidity, less operative time, less overall treatment time, and possibly fewer postoperative complications compared with the status quo.
Identification of Differentially Expressed Genes in Cold Storage–associated Kidney Transplantation
Authors: Zhu Jiefu , Xiang Xiaohong , Shi Lang , Song Zhixia , Dong Zheng 
Published: April 2024

Background.
Although it is acknowledged that ischemia–reperfusion injury is the primary pathology of cold storage–associated kidney transplantation, its underlying mechanism is not well elucidated.

Methods.
To extend the understanding of molecular events and mine hub genes posttransplantation, we performed bulk RNA sequencing at different time points (24 h, day 7, and day 14) on a murine kidney transplantation model with prolonged cold storage (10 h).

Results.
In the present study, we showed that genes related to the regulation of apoptotic process, DNA damage response, cell cycle/proliferation, and inflammatory response were steadily elevated at 24 h and day 7. The upregulated gene profiling delicately transformed to extracellular matrix organization and fibrosis at day 14. It is prominent that metabolism-associated genes persistently took the first place among downregulated genes. The gene ontology terms of particular note to enrich are fatty acid oxidation and mitochondria energy metabolism. Correspondingly, the key enzymes of the above processes were the products of hub genes as recognized. Moreover, we highlighted the proximal tubular cell-specific increased genes at 24 h by combining the data with public RNA-Seq performed on proximal tubules. We also focused on ferroptosis-related genes and fatty acid oxidation genes to show profound gene dysregulation in kidney transplantation.

Conclusions.
The comprehensive characterization of transcriptomic analysis may help provide diagnostic biomarkers and therapeutic targets in kidney transplantation.
Generation of human iPSC-derived phrenic-like motor neurons to model respiratory motor neuron degeneration in ALS
Authors: Thiry Louise , Sirois Julien , Durcan Thomas M. , Stifani Stefano 
Published: April 2024

AbstractThe fatal motor neuron (MN) disease Amyotrophic Lateral Sclerosis (ALS) is characterized by progressive MN degeneration. Phrenic MNs (phMNs) controlling the activity of the diaphragm are prone to degeneration in ALS, leading to death by respiratory failure. Understanding of the mechanisms of phMN degeneration in ALS is limited, mainly because human experimental models to study phMNs are lacking. Here we describe a method enabling the derivation of phrenic-like MNs from human iPSCs (hiPSC-phMNs) within 30 days. This protocol uses an optimized combination of small molecules followed by cell-sorting based on a cell-surface protein enriched in hiPSC-phMNs, and is highly reproducible using several hiPSC lines. We show further that hiPSC-phMNs harbouring ALS-associated amplification of theC9orf72gene progressively lose their activity and undergo increased death compared to isogenic controls. These studies establish a previously unavailable protocol to generate human phMNs, offering a disease-relevant system to study mechanisms of respiratory MN dysfunction.
“Holy cow, where do I sign up?” Attitudes of Military Veterans toward Epigenomic Biomarker Toxic Exposure Testing
Authors: Pereira Stacey , Apodaca Calvin , Slominski Kyle , Lipsky Rachele K. , Coarfa Cristian , Walker Cheryl L. , McGuire Amy L. , Steele Lea , Helmer Drew A. 
Published: April 2024

AbstractBackgroundWith the signing of the PACT Act in 2022, there is great interest and investment in studying toxic exposures encountered during military service. One way to address this is through the identification of epigenomic biomarkers associated with exposures. There is increasing evidence suggesting that exposure to toxic substances may result in alterations to DNA methylation and resultant gene expression. These epigenomic changes may lead to adverse health effects for exposed individuals and their offspring. While the development of epigenomic biomarkers for exposures could facilitate understanding of these exposure-related health effects, such testing could also provide unwanted information.ObjectivesExplore Veterans’ attitudes toward epigenomic biomarker research and the potential to test for past exposures that could pose intergenerational risk.MethodsSemi-structured interviews with Veterans (n=22) who experienced potentially harmful exposures during their military service.ResultsTwenty Veterans said they would hypothetically want to receive epigenomic information related to their toxic exposures and potential health impacts as part of a research study. Veterans identified nine potential benefits of this research, including promoting insights concerning intergenerational health, identification of early health interventions to mitigate the impact of exposures, and additional knowledge or explanation for their experiences. At the same time, 16 participants noted potential risks, including psychological distress in response to results, concerns about receiving non-actionable, uncertain, or inaccurate results, and issues related to privacy and discrimination. Ten participants also identified at least one condition in their children that they thought could be related to their exposure and most said they would be interested in receiving research results related to their children’s and grandchildren’s risk of developing a health condition associated with their exposure.DiscussionResults suggest that Veterans might welcome benefits of epigenomic research related to military exposures yet have some concerns about potential negative impacts.