bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioenergetics disruption, oxidative stress, and inflammation as underlying mechanisms of tramadol‐induced nephrotoxicity
Authors: Elmorsy Ekramy M. , Al Doghaither Huda A. , Al‐Ghafari Ayat B. 
Published: August 2024

AbstractTramadol (TR), a commonly prescribed pain reliever for moderate to severe pain, has been associated with kidney damage. This study investigates TR‐induced nephrotoxicity mechanisms, focusing on its effects on renal proximal tubular cells (PTCs). The study findings demonstrate that TR disrupts PTC bioenergetic processes, leading to oxidative stress and inflammation. Significant toxicity to PTCs was observed with estimated effective concentration 50 values of 9.8 and 11.5 µM based on 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and lactate dehydrogenase assays, respectively. TR also interferes with the function of PTC transporters, including organic cation uptake transporter 1, organic cation transporter 2, P‐glycoprotein, and multidrug resistance protein 2. Furthermore, bioenergetics assays showed that TR reduced the activities of mitochondrial complexes I and III, adenosine triphosphate production, mitochondrial membrane potential, and oxygen consumption rate while increasing lactate release. TR also increased the production of reactive oxygen species, lipid peroxidation thiobarbituric acid reactive substances end products, and the expression of the NRf2 gene while decreasing reduced glutathione (GSH‐R) stores and catalase and superoxide dismutase antioxidant activities. Additionally, TR increased the production of inflammatory cytokines (TNF‐α and IL‐6) and their coding genes expression. Interestingly, the study found that antioxidants like GSH‐R, inhibitors of IL‐6 and TNF‐α, and mitochondrial activating Co‐Q10 could protect cells against TR‐induced cytotoxicity. The study suggests that TR causes nephrotoxicity by disrupting bioenergetic processes, causing oxidative stress and inflammation, but antioxidants and agents targeting mitochondria may have protective and curative potential.
Isoliensinine activated the Nrf2/GPX4 pathway to inhibit glutamate‐induced ferroptosis in HT‐22 cells
Authors: Long Hui‐Zhi , Li Feng‐Jiao , Gao Li‐Chen , Zhou Zi‐Wei , Luo Hong‐Yu , Xu Shuo‐Guo , Dai Shang‐Ming , Hu Jing‐Da 
Published: August 2024

AbstractIsoliensinine (ISO), a natural compound, is a bibenzyl isoquinoline alkaloid monomer in lotus seed, which has strong antioxidant and free radical scavenging activities. The oxidative toxicity caused by glutamic acid overdose is one of the important mechanisms of nerve cell injury, and the oxidative toxicity caused by glutamic acid is related to ferroptosis. This study aims to establish a glutamate‐induced injury model of mouse hippocampal neurons HT‐22 cells, and investigate the protective effect of ISO on the neurotoxicity of glutamate‐induced HT‐22 cells. The results showed that ISO inhibited glutamate‐induced ferroptosis of neuronal cells through nuclear factor E2‐related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) signaling pathway. Pretreatment of HT‐22 cells with ISO significantly reduced glutamate‐induced cell death. Ferroptosis inhibitors have the same effect. ISO inhibited the decrease of mitochondrial membrane potential detection and the increase of iron content induced by glutamate, the increase of malondialdehyde and reactive oxygen species in cytoplasm and lipid, and protected the activities of GPx and superoxide dismutase enzymes. In addition, WB showed that glutamic acid could induce the upregulated expression of long‐chain esteryl coA synthase 4 (ACSL4) protein and the downregulated expression of SLC7A11 and GPX4 protein in HT‐22 cells, while ISO could prevent the abnormal expression of these proteins induced by glutamic acid. The nuclear translocation of Nrf2 in HT‐22 cells was increased, and the expression of downstream heme oxygenase‐1 protein was upregulated. In summary, ISO protects HT‐22 cells from glutamate‐induced ferroptosis through a novel mechanism of the Nrf2/GPX4 signaling pathway.
Management of the therapeutic relationship in a patient with Complex PTSD and Personality Disorder
Authors: Popolo Raffaele , Dimaggio Giancarlo , MacBeth Angus , Ottavi Paolo , Centonze Antonella 
Published: August 2024

AbstractIndividuals diagnosed with Complex PTSD (C‐PTSD) have experienced repeated and often prolonged traumatic events. From a therapeutic perspective this can lead to difficulties in emotion regulation within‐session, challenges with patient‐therapist attunement, and impaired coregulation of emotions during therapeutic interactions. As a result, frequent therapeutic alliance ruptures can emerge, which in turn pose challenges for symptom‐focused work. We describe a case study involving a 38‐year‐old woman presenting with C‐PTSD, dissociation, anxiety and borderline and dependent personality disorder traits. We explore how difficulties in attunement and emotion regulation during therapy were mostly attributable to (i) maladaptive ideas regarding the self and others; and (ii) difficulties in recognizing both her own mental states and those of her therapist. For instance, the patient believed that the therapist was distant and critical; which she held to be fact rather than reflective of a mental state. We show how the therapist addressed these difficulties, incorporating repair of the therapeutic alliance, which enabled a return to symptom focused work. The case description offers guidance on how to maintain a dual focus on therapeutic alliance alongside symptoms when treating C‐PTSD (with or without comorbidity).
Co‐morbid sarcopenia and low bone mineral density in young paediatric cancer survivors
Authors: Marmol‐Perez Andres , Ubago‐Guisado Esther , Gil‐Cosano Jose J. , Llorente‐Cantarero Francisco J. , Pascual‐Gázquez Juan Francisco , Muñoz‐Torres Manuel , Martinez‐Vizcaino Vicente , Ness Kirsten K. , Ruiz Jonatan R. , Gracia‐Marco Luis 
Published: August 2024

AbstractBackgroundSarcopenia and low areal bone mineral density (aBMD) are prevalent musculoskeletal complications after paediatric cancer treatment. However, their relationship has not been examined in young paediatric cancers survivors. This study aimed to evaluate aBMD differences according to sarcopenia status and the risk of low aBMD Z‐score in young paediatric cancer survivors with sarcopenia confirmed/probable.MethodsThis cross‐sectional study included 116 paediatric cancer survivors (12.1 ± 3.3 years old; 42.2% female). Handgrip strength was used to assessed muscle strength. Dual‐energy X‐ray absorptiometry estimated aBMD (g/cm2) and appendicular lean mass index (ALMI, kg/m2). ‘No sarcopenia’ was defined when muscle strength was >decile 2. ‘Sarcopenia probable’ was defined when muscle strength was ≤ decile 2 and ALMI Z‐score was > −1.5 standard deviation (SD). ‘Sarcopenia confirmed’ was defined when muscle strength was ≤ decile 2 and ALMI Z‐score ≤ −1.5 SD. Analysis of covariance and logistic regression, adjusted for time from treatment completion, radiotherapy exposure, calcium intake, and physical activity, was used to evaluate aBMD and estimate the odds ratios (ORs) of low aBMD (aBMD Z‐score < −1.0).ResultsSurvivors with sarcopenia confirmed had significantly lower aBMD than those without sarcopenia at total body (−1.2 [95% CI: −1.5 to −0.8] vs. 0.2 [−0.2 to 0.6], P < 0.001), lumbar spine (−0.7 [−1.1 to −0.3] vs. 0.4 [0.0 to 0.8], P < 0.001), total hip (−0.5 [−0.9 to −0.2] vs. 0.4 [0.1 to 0.8], P < 0.001), and femoral neck (−1.0 [−1.4 to −0.6] vs. 0.1 [−0.3 to 0.4], P = 0.001). Compared with survivors with sarcopenia probable, survivors with sarcopenia confirmed had significantly lower aBMD Z‐score at total body (−1.2 [−1.5 to −0.8] vs. −0.2 [−0.7 to 0.4], P = 0.009), total hip (−0.5 [−0.9 to −0.2] vs. 0.5 [−0.1 to 1.0], P = 0.010), and femoral neck (−1.0 [−1.4 to −0.6] vs. 0.1 [−0.5 to 0.7], P = 0.014). Survivors with sarcopenia confirmed were at higher risk of low aBMD Z‐score at the total body (OR: 6.91, 95% CI: 2.31–24.15), total hip (OR: 2.98, 1.02–9.54), and femoral neck (OR: 4.72, 1.72–14.19), than those without sarcopenia. Survivors with sarcopenia probable were at higher risk of low aBMD Z‐score at the total body (OR: 4.13, 1.04–17.60) than those without sarcopenia.ConclusionsYoung paediatric cancer survivors with sarcopenia present higher risk of low aBMD. Resistance training‐based interventions designed to mitigate osteosarcopenia in this population should be implemented at early stages.
A rapid realist review of literature examining Co‐production in mental health services for youth
Authors: Jones Verity Rose , Waring Justin , Wright Nicola , Fenton Sarah‐Jane 
Published: August 2024

AbstractBackgroundAn overview of internationally published literature on what works for co‐production in youth mental health services is missing, despite a practice and policy context strongly recommending this approach. This rapid realist review develops a theory about how and why co‐production methods in youth mental health services work, for whom and in which circumstances.MethodsRelevant evidence was synthesised to develop Context–Mechanism–Outcome configurations (CMOs) that can inform policy and practice. Stakeholders were iteratively involved by engaging an expert panel including young people and a separate youth advisory group. Searches across eight databases and expert panel suggestions identified 5716 documents which were screened at abstract level, 532 at full‐text and 57 documents were included in the review.ResultsData extracted from 57 papers contributed to five CMO configurations to describe the generative mechanisms by which co‐production in youth mental health services are linked to outcomes and influenced by context. The final programme theory is: Youth experts by experience (YEBE), particularly those from minoritised communities, provided with a supportive organisational culture can experience authentic engagement where their knowledge is perceived as credible by wider stakeholders. This leads to personal development for participating YEBE as well as service improvements from their input.ConclusionsRich data from a heterogenous sample of papers along with stakeholder consultation enabled this review to refine a clear programme theory for co‐production in mental health services for young people. Nevertheless, further information is needed to identify what constitutes a supportive organisational culture and to explore rival theories or under‐evidenced areas.
Joint line convergence angle is the most associated alignment factor with the severity of medial knee osteoarthritis
Authors: Tsushima Takahiro , Sasaki Eiji , Sakamoto Yukiko , Kimura Yuka , Tsuda Eiichi , Ishibashi Yasuyuki 
Published: August 2024

AbstractPurposeThe purpose of this study was to evaluate the relationship between the joint line convergence angle (JLCA) and the severity of medial knee osteoarthritis (OA). We hypothesise that JLCA is the most associated factor with the severity of medial knee OA.MethodsThis retrospective study included a total of 202 knees that underwent either high tibial osteotomy or medial meniscus repair/partial resection. Kellgren–Lawrence grade and hip–knee–ankle angle (HKAA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA) and JLCA were assessed from preoperative radiographs. Medial meniscus extrusion (MME) was measured using preoperative magnetic resonance imaging. The International Cartilage Research Society (ICRS) grade on the medial femoral condyle and medial tibial plateau were also assessed. The relationships between JLCA and Kellgren–Lawrence grades and MME and ICRS grades were analysed using Spearman's correlation test and regression analysis.ResultsThe JLCA was correlated with the Kellgren–Lawrence grade (R = 0.765, p < 0.001), MME (R = 0.638, p < 0.001), ICRS grade on the MFC (R = 0.586, p < 0.001) and the MTP (R = 0.586, p < 0.001). Regression analysis showed that age (p = 0.002) and JLCA (p < 0.001) were associated with Kellgren–Lawrence grade. Furthermore, JLCA was related to ICRS grade on the MFC (p < 0.001) and MTP (p < 0.001).ConclusionThe JLCA, reflecting radiological severity, meniscus status, and cartilage lesion, was the most associated alignment parameter in the severity of medial knee OA. The JLCA may be beneficial for quantitative assessment of medial knee OA.Level of EvidenceLevel III, retrospective cohort study.
A mouldable fibreglass backslab device as a novel approach to offload chronic plantar foot ulcers: A retrospective observational audit
Authors: Ting Melissa , Ferreira Ivana , Hiew Jonathan , McEvoy Mahalia , Tan Gabrielle , Shah Priyal , Nicolandis Eugenie , Hamilton Emma J. , Ritter Jens Carsten , Nicolaou Michael , Manning Laurens 
Published: August 2024

AbstractBackgroundPressure offloading is a critical component of plantar foot ulcer management, including diabetes‐related foot ulcers (DFU). Conventional offloading options such as total contact casting and removable knee‐high walkers may be unsuitable or unsuccessful in patients with morbid obesity, intermittent lower limb oedema, high exudative wounds or poor mobility. A mouldable fibreglass backslab device (BSD) may be a practical alternative to be considered in these situations.MethodsData were retrospectively collected on 28 patients (29 foot ulcers) with non‐healing ulcers who received a BSD to offload their foot ulcer as an extension to standard offloading care. Baseline data included: patient demographics, type of offloading prior to BSD application, date of ulcer onset, days ulcer present prior to BSD application and ulcer size at BSD initiation. Measures of success included ulcer size reduction 12 weeks post‐BSD application, time to complete ulcer healing in BSD, time to 50% reduction in ulcer size post‐BSD application and total number of days ulcer present.ResultsThe median (IQR) ulcer area and ulcer duration at baseline for 19 patients (20 ulcers) who used the BSD was 1.65 (0.4–3.8) cm2 and 531 (101–635) days. At 12 weeks, the median (IQR) ulcer area was 0.3 (0–0.55) cm2 with a median (IQR) reduction of 97 (80–100) %. Nine (45%) ulcers achieved complete wound healing (100% reduction in wound size) at 12 weeks post‐BSD application, and the remaining 11 (55%) ulcers achieved at least 50% reduction in wound size. The median (IQR) time to complete wound healing and 50% reduction in wound size was 71 (35–134) days and 24 (15–44) days, respectively. Nine patients ceased use of the BSD and reverted to conventional offloading before their wounds had healed. Of these, four patients achieved a 50% reduction in wound size at the 12‐week mark with conventional offloading.ConclusionOur preliminary data suggests that a mouldable fibreglass BSD may be a practical offloading option in the management of DFUs, especially when conventional offloading methods are unsuccessful, unsuitable or unacceptable to patients. Higher level evidence is required to demonstrate suitability or efficacy of the BSD compared to current evidence‐based recommended offloading methods.
Routine hemostasis profile in steady state sickle cell disease adult patients compared to laboratory values, between phenotypes and during pregnancy: A retrospective, descriptive study
Authors: Affo Comlan , Schmidt Carine , Bosquet Antoine , Dumont Bénédicte , Mahé Isabelle 
Published: August 2024

AbstractSickle cell disease is a rare genetic disease resulting from an abnormality in hemoglobin. Hemostasis in the steady state, defined as ≥2 months without vaso‐occlusive crises, is poorly described in the literature. We report the routine hemostasis profile in steady state patients with sickle cell disease (SCD), including during pregnancy and according to phenotype. This retrospective study collected data over the period 2010 to 2021. Data on routine hemostasis parameters (prothrombin time [PT] activated partial thromboplastin time [aPTT], and platelets) were collected from medical records and were compared with laboratory norms including during pregnancy; the HbSS phenotype was compared with the HbSC, HbSB°thalassemia, and HbSB+thalassemia phenotypes. we included 119 adults (representing 190 day‐hospitals) with SCD who had attended at least one checkup in the steady state. Seven patients (15 day‐hospitals) on anticoagulants were excluded. Eleven (17 day‐hospitals) were pregnant. Mean routine hemostasis parameters were within normal values regardless of pregnancy. Mean PT was lower during pregnancy (12.3 ± 0.6 s vs. 13.2 ± 1.0 s; P = .01). PT and platelet counts were higher (P = .01) and aPTT was lower (P = .03) in men and nonpregnant women in the HbSS group compared with those in the HbSC group. routinely collected hemostasis parameters in steady state patients were within normal laboratory values, including in pregnant women. PT values differed significantly between pregnant women and nonpregnant women, and PT, aPTT, and platelet counts differed between HbSS, HbSC, and HbSB+thalassemia phenotypes.
Gastrotheca Fitzinger, 1843 tadpole morphology: Larval cranium description and its evolutionary implications (Amphibia: Anura: Hemiphractidae)
Authors: Folly Manuella , Amaral Lucas C. , da Silveira Luiz F. L. , de Carvalho‐e‐Silva Sergio P. , Dias Pedro Henrique dos Santos 
Published: August 2024

AbstractHemiphractids have a singular mode of reproduction that involves maternal care. The Andean‐endemic Gastrotheca marsupiata species group includes direct‐developing and tadpole‐bearing species, the latter trait being unique among Gastrotheca. Larval morphology has proven to be a valuable source of evidence to understand the taxonomy and evolution of frogs but remains understudied in Hemiphractids. Herein, we redescribe the larval cranium of G. espeletia, G. gracilis, G. marsupiata, G. peruana, G. pseustes, and G. riobambae, and describe those of G. aureomaculata, G. chrysosticta, G. litonedis, G. monticola and G. psychrophila. Additionally, based on the data gathered, we explore their phylogenetic significance, expanding the knowledge regarding Gastrotheca larval internal morphology. We suggest that the presence of the posterolateral process of crista parotica, the concave palatoquadrate, the quadratoorbital commissure, and the proximal commissures II and III are putative synapomorphies for Gastrotheca. Furthermore, we suggest the long pseudopterygoid process as a putative synapomorphy for Hemiphractyidae.
Epstein–Barr virus noncoding RNA EBER1 promotes the expression of a ribosomal protein paralog to boost oxidative phosphorylation
Authors: Paudel Sita , Lee Nara 
Published: August 2024

AbstractEpstein–Barr virus (EBV) is a highly successful pathogen that infects ~95% of the adult population and is associated with diverse cancers and autoimmune diseases. The most abundant viral factor in latently infected cells is not a protein but a noncoding RNA called EBV‐encoded RNA 1 (EBER1). Even though EBER1 is highly abundant and was discovered over forty years ago, the function of EBER1 has remained elusive. EBER1 interacts with the ribosomal protein L22, which normally suppresses the expression of its paralog L22‐like 1 (L22L1). Here we show that when L22 binds EBER1, it cannot suppress L22L1, resulting in L22L1 being expressed and incorporated into ribosomes. We further show that L22L1‐containing ribosomes preferentially translate mRNAs involved in the oxidative phosphorylation pathway. Moreover, upregulation of L22L1 is indispensable for growth transformation and immortalization of resting B cells upon EBV infection. Taken together, our results suggest that the function of EBER1 is to modulate host gene expression at the translational level, thus bypassing the need for dysregulating host gene transcription.
Technologies and techniques to improve precision in breast conserving surgery
Authors: Leff Daniel R. 
Published: August 2024

AbstractImprecision in breast conserving surgery results in high rates of take back to theatre for reexcision of margins. This paper reviews the various approaches to improving the precision of oncological margin control in breast conserving surgery. The review describes the rationale for improved tissue characterization over tumor localization and explores technology‐free approaches, as well as progress being made to develop and test innovative technological solutions.
Lymph node metrics following neoadjuvant therapy to refine patient selection for adjuvant chemotherapy in resected pancreatic cancer: A multi‐institutional analysis
Authors: Amirian Haleh , Dickey Erin , Ogobuiro Ifeanyichukwu , Box Edmond W. , Shah Ankit , Martos Mary P. , Patel Manan , Wilson Gregory C. , Snyder Rebecca A. , Parikh Alexander A. , Hammill Chet , Kim Hong J. , Abbott Daniel , Maithel Shishir K. , Zafar Syed Nabeel , LeCompte Michael T. , Kooby David A. , Ahmad Syed A. , Merchant Nipun B. , Hester Caitlin A. , Datta Jashodeep 
Published: August 2024

AbstractBackgroundIn patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high‐risk features on histopathologic examination. We evaluated the interaction between post‐NAT lymph node metrics and AC receipt on survival.MethodsPatients who received NAT followed by pancreatectomy (2010–2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS.ResultsOf 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien–Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post‐NAT LNP rates were not different, and median LNR was 0.1, in AC and non‐AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non‐AC (24 vs. 20 months, respectively; p = 0.04).ConclusionsLNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC.