bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity and Evolution of Highly Repetitive DNA Sequences Constituting Chromosome Site-Specific Heterochromatin in Two Gerbillinae Species
Authors: Uno Yoshinobu , Matsubara Kazumi , Inoue Jun , Inazawa Johji , Shinohara Akio , Koshimoto Chihiro , Ichiyanagi Kenji , Matsuda Yoichi
Published: October 2023

Constitutive heterochromatin, consisting of repetitive sequences, diverges very rapidly; therefore, its nucleotide sequences and chromosomal distributions are often largely different, even between closely related species. The chromosome C-banding patterns of two Gerbillinae species, Meriones unguiculatus and Gerbillus perpallidus, vary greatly, even though they belong to the same subfamily. To understand the evolution of C-positive heterochromatin in these species, we isolated highly repetitive sequences, determined their nucleotide sequences, and characterized them using chromosomal and filter hybridization. We obtained a centromeric repeat (MUN-HaeIII) and a chromosome 13-specific repeat (MUN-EcoRI) from M. unguiculatus. We also isolated a centromeric/pericentromeric repeat (GPE-MBD) and an interspersed-type repeat that was predominantly amplified in the X and Y chromosomes (GPE-EcoRI) from G. perpallidus. GPE-MBD was found to contain a 17-bp motif that is essential for binding to the centromere-associated protein CENP-B. This indicates that it may play a role in the formation of a specified structure and/or function of centromeres. The nucleotide sequences of the three sequence families, except GPE-EcoRI, were conserved only in Gerbillinae. GPE-EcoRI was derived from the long interspersed nuclear elements 1 retrotransposon and showed sequence homology throughout Muridae and Cricetidae species, indicating that the repeat sequence occurred at least in the common ancestor of Muridae and Cricetidae. Due to a lack of assembly data of highly repetitive sequences constituting heterochromatin in whole-genome sequences of vertebrate species published to date, the knowledge obtained in this study provides useful information for a deep understanding of the evolution of repetitive sequences in not only rodents but also in mammals.
Maintaining Renin-Angiotensin-Aldosterone System Inhibitor Treatment with Patiromer in Hyperkalaemic Chronic Kidney Disease Patients: Comparison of a Propensity-Matched Real-World Population with AMETHYST-DN
Authors: Chinnadurai Rajkumar , Rengarajan Sharmilee , Budden Jeffrey J. , Quinn Carol Moreno , Kalra Philip A.
Published: October 2023

Introduction: Guideline-directed renin-angiotensin-aldosterone system inhibitor (RAASi) therapy is rarely achieved in clinical settings, often due to hyperkalaemia. We assessed the potassium binder, patiromer, on continuation of RAASi therapy in hyperkalaemic patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) in the AMETHYST-DN trial, propensity score-matched to a real-world cohort not receiving patiromer (Salford Kidney Study). Methods: The phase 2, open-label AMETHYST-DN trial (NCT01371747) randomized 304 adults with CKD on RAASi, T2DM, hyperkalaemia (serum potassium [sK+] >5.0 mEq/L), and hypertension to receive patiromer, 8.4–33.6 g/day for 12 months. Patients underwent propensity score matching for systolic blood pressure (BP), heart failure status, and estimated glomerular filtration rate (eGFR), with 321 patients with CKD, T2DM, hyperkalaemia, and on RAASi from a prospective CKD cohort (Salford Kidney Study). Changes in RAASi utilization, sK+, BP, proteinuria, and eGFR during 12-month follow-up were assessed by Mann-Whitney U or χ2 tests. Results: Matching produced 135:135 patients with no significant differences in age, sex, systolic BP, sK+, eGFR, or heart failure status, although differences in diastolic BP remained (p < 0.001). After 12 months, 100% of AMETHYST-DN patients receiving patiromer remained on RAASi therapy, whereas 38.5% of the Salford Kidney Cohort discontinued RAASi (p < 0.001); hyperkalaemia contributed in 16% of patients (42% of RAASi discontinuations). Significantly greater reductions in sK+ and BP, but not proteinuria or eGFR, were observed in AMETHYST-DN, compared with Salford Kidney Study patients (p < 0.05). Conclusions: These results demonstrate the benefit of patiromer for sK+ management to enable RAASi use while revealing beneficial effects on BP.
Fat Intake and Fat Quality in Pregnant and Lactating Women, Infants, Children, and Adolescents and Related Health Outcomes: A Scoping Review of Systematic Reviews of Prospective Studies
Authors: Patro-Golab Bernadeta , Zalewski Bartlomiej M. , Kammermeier Michael , Schwingshackl Lukas , Koletzko Berthold ,   On behalf of International Union of Nutritional Sciences (IUNS) Task Force on Dietary Fat Quality
Published: October 2023

Introduction: Dietary fat intake during pregnancy and childhood is important for health. However, several health aspects are inconclusive. Methods: We systematically searched Medline, Cochrane Library, and Epistemonikos for systematic reviews (SRs) of randomized controlled trials (RCTs) and/or prospective cohort studies published from January 01, 2015, to December 31, 2019, assessing the association of dietary fat intake (including dietary supplements) during pregnancy and across childhood with pregnancy, perinatal, and child health outcomes. Results: Thirty-one SRs, mainly of RCTs, were included. Omega-3 fatty acids supplementation during pregnancy reduced the risk of early preterm birth, and in some SRs also any preterm birth, increased gestation length and birth weight, but mostly was not associated with other pregnancy/perinatal outcomes. Pre- and postnatal polyunsaturated fatty acids (PUFAs) intake was not consistently associated with growth, neurological, visual and cognitive outcomes, allergic diseases, cardiovascular, and metabolic health in childhood. Reduced saturated fatty acids (SFAs) intake and its replacement with PUFA/monounsaturated fatty acids had favourable effects on blood pressure and blood lipids in children. No apparent effects of total or trans fat on health outcomes across target groups were observed. Conclusion: Omega-3 PUFA supplementation during pregnancy and SFA intake reduction in childhood require further consideration in dietary recommendations targeting these populations.
Fluorodeoxyglucose-Positron Emission Tomography in Relapsed/Refractory Hodgkin Lymphoma: A Practical Approach
Authors: Tomarchio Valeria , Rigacci Luigi
Published: October 2023

Background: Positron emission tomography (PET) with the use of 18F-fluorodeoxyglucose (FDG), implemented with low-dosage computer tomography, is to be considered as the most important evolution of imaging in the management and assessment of classical Hodgkin lymphoma patients. Summary: According to Lugano response criteria, FDG-PET is mandatory to define metabolic response to frontline therapy and moreover it is important in the definition of nonresponders or refractory disease patients. Refractory disease is reported in about 15% of patients, with some variations based on the choice of first-line chemotherapy, and particularly in advanced stages, up to 40% eventually relapse within 3 years. Key Messages: The aim of this review was to highlight a practical way to use FDG-PET in the subset of HL, with some notes of its use in first-line patients, and particularly centered on relapsed or refractory setting with a final focus of the evaluation of response by FDG-PET in the new treatment era of immunocheckpoint inhibitors.
Clinical Implication of CDH1 Mutations in Genetic Testing for Diffuse Gastric Cancer Patients
Authors: Corso Giovanni , Trovato Cristina Maria , Petitto Salvatore , Girardi Antonia , De Scalzi Alessandra Margherita , Bianchi Beatrice , Magnoni Francesca , Cioffi Antonio , Galimberti Viviana , Veronesi Paolo , Mazzarol Giovanni , Maisonneuve Patrick
Published: October 2023

Introduction: The objective of this study was to reclassify published germline CDH1 variants identified in gastric cancer (GC) in accordance with the latest ClinVar definition and to correlate their pathogenicity with the established international clinical criteria for genetic testing. Methods: The relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations in accord with PRISMA guidelines. The collected variants were classified according to the latest ClinVar definition into the following classes: benign (B), likely benign (LB), pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS). The McNemar test was used to compare the adequacy of current versus previous International GC Linkage Consortium (IGCLC) criteria. Results: We reclassified a total of 247 CDH1 variants, and we identified that about 70% of B/LB variant carriers were not fulfilling the defined clinical criteria. Instead, all P/LP variants (100%) were associated with the hereditary diffuse gastric cancer (HDGC) phenotype fulfilling the 2020 ILGCC criteria, with a significant improvement (p = 0.025) compared to previous version. Conclusions: We conclude that germline CDH1 genetic testing is indicated only in families meeting the clinical criteria for the HDGC syndrome. This observation suggests that clinical phenotypes that do not clearly fulfill these criteria should not be considered for CDH1 genetic testing.
Radiotherapy for Primary Pediatric Central Nervous System Malignancies: Current Treatment Paradigms and Future Directions
Authors: Liu Kevin X. , Haas-Kogan Daphne A. , Elhalawani Hesham
Published: October 2023

Background: Central nervous system tumors are the most common solid tumors in childhood. Treatment paradigms for pediatric central nervous system malignancies depend on elements including tumor histology, age of patient, and stage of disease. Radiotherapy is an important modality of treatment for many pediatric central nervous system malignancies. Summary: While radiation contributes to excellent overall survival rates for many patients, radiation also carries significant risks of long-term side effects including neurocognitive decline, hearing loss, growth impairment, neuroendocrine dysfunction, strokes, and secondary malignancies. In recent decades, clinical trials have demonstrated that with better imaging and staging along with more sophisticated radiation planning and treatment set-up verification, smaller treatment volumes can be utilized without decrement in survival. Furthermore, the development of intensity-modulated radiotherapy and proton-beam radiotherapy has greatly improved conformality of radiation. Key Messages: Recent changes in radiation treatment paradigms have decreased risks of short- and long-term toxicity for common histologies and in different age groups. Future studies will continue to develop novel radiation regimens to improve outcomes in aggressive central nervous system tumors, integrate molecular subtypes to tailor radiation treatment, and decrease radiation-associated toxicity for long-term survivors.
Combination of Osimertinib with Concurrent Chemotherapy and Hormonal Therapy for Synchronous NSCLC, Hormone Receptor-Positive Breast Cancer, and Triple-Negative Breast Cancer: Case Report
Authors: Park Changsu L. , Moria Feras , Saleh Ramy R.
Published: October 2023

Patients presenting with multiple primary malignancies remain a growing challenge for physicians due to a lack of data for generalizable guidelines. Identification of driver mutations in carcinogenesis leads to the development of targeted treatment of many different cancer types, but its combination with other anti-cancer therapy is not well understood. We report a case of a 66-year-old woman who presented with triple-negative breast cancer, multifocal hormone receptor-positive breast cancer, primary epidermal growth factor receptor-mutated lung adenocarcinoma, possible primary lung adenocarcinoma of unspecified mutational status in the contralateral lung, and a solitary metastatic lesion in the brain from one of her primary cancers. She was treated with stereotactic radiosurgery and osimertinib in combination with carboplatin/nab-paclitaxel, doxorubicin/cyclophosphamide, and letrozole, with excellent clinical and radiographical response. We did not observe synergistic toxicity or unexpected adverse events from the treatment. To the best of our knowledge, this is the first report of concurrent osimertinib with these chemotherapy and hormonal therapy agents. As large-scale studies are difficult to conduct for these rare cases requiring exceptional treatment, it is important for physicians to build on the community’s shared experience via case reports to better predict efficacy and safety of combining targeted agents with other conventional systemic treatments.
Clinicopathological Characteristics of Breast Cancer Patients with HER-2 Low Expression Receiving Neoadjuvant Therapy
Authors: Zhang Shiyuan , Yu Xiao , Xiu Yuting , Qiao Kun , Jiang Cong , Huang Yuanxi
Published: October 2023

Introduction: Human epidermal growth factor receptor-2 (HER-2) low expression breast malignant tumors have become a research hotspot in recent years, but it is still unclear whether HER-2 low expression represents a special subtype of breast cancer. However, this molecular type requires more effective treatment regimens in the neoadjuvant therapy stage. Methods: This study enrolled breast cancer patients who were treated at Harbin Medical University Cancer Hospital with neoadjuvant treatment between October 2011 and May 2019 and was a single-center retrospective study. Results: A total of 1,053 breast cancer patients who received preoperative therapy, including 279 (26%) HER-2 low expression patients, were included in this retrospective study. The HER-2 low expression group had a higher proportion of patients under 50 years old than the other two molecular subtype groups (p = 0.047, 62.0% vs. 57.2% and 52.5%), and the percentage of patients with Ki67 index above 15% was lower than that in HER-2-negative and HER-2-positive patients (p < 0.001, 50.2% vs. 63.6% and 71.5%). Most of the patients with HER-2 low expression were hormone receptor (HR) positive (p < 0.001, 85.7% vs. 60.4% and 36.0%), and their pathologic complete response (pCR) rate after neoadjuvant therapy was significantly lower than that of HER-2-negative and HER-2-positive patients (p < 0.001, 5.7% vs. 11.8% and 20.5%). The results of the subgroup analysis showed HR-positive patients with HER-2 low expression had a lower pCR rate (p < 0.001, 4.6% vs. 14.6%) and objective response rate (p = 0.001, 77.8% vs. 91.0%) than HER-2-positive patients and had no significant difference in these rates compared to HER-2-negative patients. There were no significant differences in overall survival (OS) and disease-free survival (DFS) up to 67 months (the median follow-up time) among HER-2 low, HER-2-negative, and HER-2-positive patients. The results of Cox hazard proportional showed that the Ki67 index and T stage (T3) were independent influencing factors for DFS. In terms of OS, Ki67 index, P53, T stage, and objective response were independent influencing factors for OS in HER-2 low expression patients. Conclusions: In general, further studies are needed to confirm that HER-2 low expression is a special breast cancer molecular subtype. The efficacy of neoadjuvant therapy in patients with HER-2 low expression is relatively poor, and the efficacy of neoadjuvant therapy can predict the prognosis of patients with HER-2 low expression.
Sensitive Scalp and Trichodynia: Epidemiology, Etiopathogenesis, Diagnosis, and Management
Authors: Souza Emilly Neves , Anzai Alessandra , Fechine Carolina Oliveira Costa , Valente Neusa Yuriko Sakai , Romiti Ricardo
Published: October 2023

Sensitive scalp (SSc) is considered a sensitive skin on the scalp, with its particularities. Although it is not rare in the dermatological practice and the term is commonly present in personal care products, this entity is poorly investigated in the medical literature. The etiopathogenesis is still uncertain, and the sensitivity may be associated with hair loss. Clinical manifestations are subjective symptoms of pruritus, burning, pain, pricking, and/or trichodynia, often with scalp erythema. SSc can be triggered by several factors (endogenous or exogenous). The diagnosis is guided by the anamnesis, and there are still no specific trichoscopic features. Trigeminal trophic syndrome and postherpetic neuralgia are the main differential diagnosis to be considered. We organized the therapeutical approach in three steps: scalp care, topical and systemic treatment.
Lithium: An Old Drug for New Therapeutic Strategy for Alzheimer’s Disease and Related Dementia
Authors: Shim Seong Sool , Berglund Ken , Yu Shan Ping
Published: October 2023

Background: Although Alzheimer’s disease (AD) is the most common form of dementia, the effective treatment of AD is not available currently. Multiple trials of drugs, which were developed based on the amyloid hypothesis of AD, have not been highly successful to improve cognitive and other symptoms in AD patients, suggesting that it is necessary to explore additional and alternative approaches for the disease-modifying treatment of AD. The diverse lines of evidence have revealed that lithium reduces amyloid and tau pathology, attenuates neuronal loss, enhances synaptic plasticity, and improves cognitive function. Clinical studies have shown that lithium reduces the risk of AD and deters the progress of mild cognitive impairment and early AD. Summary: Our recent study has revealed that lithium stabilizes disruptive calcium homeostasis, and subsequently, attenuates the downstream neuropathogenic processes of AD. Through these therapeutic actions, lithium produces therapeutic effects on AD with potential to modify the disease process. This review critically analyzed the preclinical and clinical studies for the therapeutic effects of lithium on AD. We suggest that disruptive calcium homeostasis is likely to be the early neuropathological mechanism of AD, and the stabilization of disruptive calcium homeostasis by lithium would be associated with its therapeutic effects on neuropathology and cognitive deficits in AD. Key Messages: Lithium is likely to be efficacious for AD as a disease-modifying drug by acting on multiple neuropathological targets including disruptive calcium homeostasis.
Relation of Mechanical Ventilation to Acute Kidney Injury in Myocardial Infarction Patients
Authors: Frydman Shir , Freund Ophir , Zornitzki Lior , Banai Shmuel , Shacham Yacov
Published: October 2023

Introduction: Acute kidney injury (AKI) is a common and serious complication in critically ill patients, particularly those with ST-elevation myocardial infarction (STEMI). Mechanical ventilation (MV) is often needed when respiratory deterioration occurs and is continuously associated with higher risk for AKI. Whether MV is an independent predictor for AKI in STEMI patients has not been evaluated before. We aimed to determine a potential association between MV and the occurrence of AKI in STEMI patients. Methods: A single-center retrospective cohort in a tertiary referral hospital. We evaluated consecutive patients that were admitted to the cardiac intensive care unit with acute STEMI between 2008 and 2019. Patients were divided into groups based on their need for MV upon admission. To minimize baseline differences between the two groups, propensity matching was performed. The primary outcome was the occurrence of AKI after intubation and secondary outcomes included severe AKI (>2 times the baseline creatinine) and renal recovery. Results: 2,929 patients were included and of them, 143 (5%) were intubated. After using the propensity matching, 138 pairs were available for analysis with similar demographic and clinical characteristics. MV was a predictor for AKI (Table 2, odds ratio [OR]: 3.3, 95% confidence interval [CI]: 1.9–5.6) and severe AKI (OR: 6.3, 95% CI: 2.5–16). These results remained significant after adjusting for the occurrence of a new heart failure and bleeding. Early or partial renal recovery was similar between the groups. Conclusion: MV is independently associated with the occurrence of AKI and severe AKI. The possible mechanism might be temporary, reflected by similar rates of renal recovery.
Long-Term Change in Flow Rates in Patients with Coronary Slow Flow
Authors: Ipek Gokturk , Kamber Tugay , Yilmaz Hale , Bolca Osman
Published: October 2023

Introduction: Coronary slow flow (CSF) is a condition characterized by impaired blood flow rates in the coronary arteries. It can result in severe cardiovascular outcomes. There is no sufficient evidence regarding the certain etiology and reversibility of slow flow patterns and changes in frame counts with long-term management. Methods: We retrospectively enrolled 48 patients with chronic coronary syndrome and CSF who underwent a second angiography. A corrected coronary frame rate (CFR) >27 was defined as CSF. We created 3 groups according to the change in CSF status as the improved, not changed, and worsened groups. We compared the CFR and CSF status of the patients between the first and second angiographies within a median of 2.6 years. Results: We determined a nonsignificant change in cCFR in left anterior descending (LAD) artery (34.4 [18.9] vs. 31.59 [10.3], p = 0.35), circumflex (Cx) artery (42.84 [12.56] vs. 40.66 [13.2], p = 0.35), and right coronary artery (RCA) (57.80 [30.13] vs. 50.32 [19.5], p = 0.11). In the comparison of CSF status of LAD (75% vs. 63%, p = 0.27), Cx (96% vs. 83%, p = 0.09), RCA (94% vs. 94%, p = 1.0) between first and second angiographies, there was no significant change. In the comparison of the 3 groups according to the improvement of CSF status, there was no significant difference in demographic features, change in laboratory parameters, and time between the groups. Conclusion: There was no significant change in the median CFR and CSF status in the overall group between the two angiographies after 3 years.
PLA2G12B Mediates Arachidonic Acid Metabolism through Activation of the NF-κB Pathway to Promote Membrane Nephropathy
Authors: Fu Linlin , Ping Jinliang , Guo Fei , Song Jiafeng , Luo Mingjun , Chen Lijing
Published: October 2023

Introduction: The disruption of podocyte structure and function are the main pathological mechanism of membranous nephropathy (MN). Phospholipases A2, Group XII B (PLA2G12B) was reported involved in the regulation of MN by interfering with arachidonic acid (AA) metabolism, but there is a lack of sufficient evidence. In this study, we investigated the role and molecular mechanism of PLA2G12B in MN. Methods: C57BL/6 mice were used to establish MN model to extract primary podocytes, then divided into control, model, si-phospholipases A2 receptor (PLA2R), PLA2G12B, PLA2G12B + si-PLA2R, PLA2G12B + nuclear factor kappa-B (NF-κB) inhibitor, PLA2G12B + NF-κB inhibitor + si-PLA2R groups. Hematoxylin-eosin staining and immunofluorescence were used to detect kidney histological arrangement, serum levels of cholesterol-related indices, and AA. Genes and proteins associated with metabolism and inflammatory factors were detected by quantitative real-time PCR and Western blot. Results: The results revealed that AA metabolites were activated in the MN model mice, and the expression of PLA2G12B and NF-κB pathway levels were elevated. Besides, cellular experiments demonstrated that prostaglandin I2 (PGI2), thromboxane A2 (TXA2), leukotriene B4 (LTB4), and NF-κB pathway were significantly increased in the PLA2G12B group. Also, PLA2G12B promotes apoptosis and suppresses cell activity in podocytes, and these effects could be antagonized by NF-κB inhibitors. Furthermore, with the inference of si-PLA2R, the NF-κB inhibitors’ effects were reversed. Conclusion: Promotional effects of PLA2G12B in primary MN are associated with the regulation of AA metabolism and NF-κB pathway.
Modulation of AMPK Significantly Alters Uveal Melanoma Tumor Cell Viability
Authors: Deliktas Ozge , Gedik M. Emre , Koc Irem , Gunaydin Gurcan , Kiratli Hayyam
Published: October 2023

Introduction: Uveal melanoma (UM) responds poorly to targeted therapies or immune checkpoint inhibitors. Adenosine monophosphate-activated protein kinase (AMPK) is a pivotal serine/threonine protein kinase that coordinates vital processes such as cell growth. Targeting AMPK pathway, which represents a critical mechanism mediating the survival of UM cells, may prove to be a novel treatment strategy for UM. We aimed to demonstrate the effects of AMPK modulation on UM cells. Methods: In silico analyses were performed to compare UM and normal melanocyte cells via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). The effects of AMPK modulation on cell viability and proliferation in UM cell lines with different molecular profiles (i.e., 92-1, MP46, OMM2.5, and Mel270) were investigated via XTT cell viability and proliferation assays after treating the cells with varying concentrations of A-769662 (AMPK activator) or dorsomorphin (AMPK inhibitor). Results: KEGG/GSEA studies demonstrated that genes implicated in the AMPK signaling pathway were differentially regulated in UM. Gene sets comprising genes involved in AMPK signaling and genes involved in energy-dependent regulation of mammalian target of rapamycin by liver kinase B1-AMPK were downregulated in UM. We observed gradual decreases in the numbers of viable UM cells as the concentration of A-769662 treatment increased. All UM cells demonstrated statistically significant decreases in cell viability when treated with 200 µm A-769662. Moreover, the effects of AMPK inhibition on UM cells were potent, since low doses of dorsomorphin treatment resulted in significant decreases in viabilities of UM cells. The half maximal inhibitory concentration (IC50) values confirmed the potency of dorsomorphin treatment against UM in vitro. Conclusion: AMPK may act like a friend or a foe in cancer depending on the context. As such, the current study contributes to the literature in determining the effects of therapeutic strategies targeting AMPK in several UM cells. We propose a new perspective in the treatment of UM. Targeting AMPK pathway may open up new avenues in developing novel therapeutic approaches to improve overall survival in UM.
Management of Implant Extrusion following Thyroplasty for Vocal Fold Paralysis: A Case Report
Authors: Konjević Barbara , Košec Andro , Peček Mirta , Stevanović Siniša
Published: October 2023

The most widely used laryngeal surgery technique for patients with vocal fold paralysis is medialization thyroplasty. Materials such as Gore-Tex, silastic, and hydroxyapatite are often used, and the most worrisome possible complication is extrusion of the implant. A 36-year-old female patient with a history of pediatric cardiac surgery was diagnosed with left vocal cord paralysis after an episode of upper respiratory infection with a working diagnosis of subclinical left vocal cord paralysis following cardiac surgery. She underwent medialization thyroplasty with a Gore-Tex implant under local anesthesia. On the 21st postoperative day, she presented with sudden-onset hoarseness and dysphagia due to Gore-Tex implant extrusion. The implant was removed and augmentation of the left vocal cord with adipose tissue was performed. Only 14 cases of Gore-Tex implant extrusion have been described in the literature so far. The aim of this case report was not only to show one possible complication when using a Gore-Tex implant but also to present fat augmentation as one of the solutions for revision medialization and salvage treatment, with sustained long-term results.
miR-26a Improves Microglial Activation and Neuronal Apoptosis in a Rat Model of Cerebral Infarction by Regulating the TREM1-TLR4/MyD88/NF-κB Axis
Authors: Xu Daxiong , Guo Qi'an
Published: October 2023

Emerging studies have indicated that abnormally expressed microRNAs (miRNAs) are related to the pathogenesis of cerebral ischemia. Nevertheless, the function of miR-26a in neuronal damage and microglial activation during cerebral infarction remains elusive. It was revealed that miR-26a was downregulated in oxygen-glucose deprivation (OGD)-treated microglia and neurons. Overexpressing miR-26a reduced the inflammatory reaction in BV2 cells and decreased neuronal apoptosis following OGD stimulation. miR-26a upregulation inactivated the TLR4/MyD88/NF-κB pathway and inhibited TREM1 expression. Repressing NF-κB phosphorylation inhibited the miR-26a level. As supported by the dual-luciferase reporter assay, TREM1 was directly targeted by miR-26a. Furthermore, a rat model of middle cerebral artery occlusion (MCAO) was built. We discovered that miR-26a improved cognitive, learning, and motor functions and reduced cerebral edema in MCAO rats. Mechanistically, upregulating miR-26a reduced inflammation and neuronal apoptosis by mitigating the TREM1-TLR4/MyD88/NF-κB pathway in the MCAO rat model. Collectively, this study verified that the miR-26a-TREM1-TLR4/MyD88/NF-κB axis contributes to modulating OGD-mediated microglial activation and neuronal injury.
Exclusion of Acute Myeloid Leukemia Patients with Central Nervous System Involvement from Clinical Trials: An Analysis of the National Institutes of Health Clinical Trials Registry from 2012 to 2022
Authors: Sastow Dahniel , Van Hyfte Grace , Feld Jonathan , Kremyanskaya Marina , Mascarenhas John , Tremblay Douglas
Published: October 2023

Introduction: Central nervous system (CNS) involvement in acute myeloid leukemia (AML) can be successfully treated with intrathecal chemotherapy and carries debatable prognostic impact. However, patients with CNS involvement are commonly excluded from clinical trials at an unknown rate. We systematically evaluated exclusion criteria of AML clinical trials based on CNS involvement and determined associations with clinical trial characteristics. Methods: The National Institutes of Health Clinical Trials Registry was searched for interventional adult AML trials between 2012 and 2022 that were phase 1, 2, or 3 and relevant trial characteristics were extracted. Results: 1,270 trials were included in the analysis with 790 trials (62.1%) explicitly excluding CNS involvement. There was no significant change in rates of CNS exclusion over the past decade. CNS exclusion was higher in trials that included the non-transplant population compared to trials exclusive to the transplant population (66.9% vs. 43.8%, p < 0.01). Non-transplant trials were also more likely to exclude patients with a history of or ambiguous timing of CNS involvement (p < 0.01). Phase 3 trials were associated with more liberal definitions of CNS exclusion (history or ambiguous timing) as compared to phase 1 and 2 trials that had higher rates of excluding patients with only active CNS involvement (p < 0.01). Conclusion: A majority of AML clinical trials, particularly in the non-transplant setting, exclude patients with CNS involvement. Many of these trials, most notably phase 3 trials, exclude patients not only with active but also with any history of CNS involvement. Further research is needed to determine optimal management of these patients in order to increase representation in large clinical trials.
In vitro Investigation of Platelet Dysfunction Induced by Osmotic Pressure Variations
Authors: Pantazi Despoina , Stratou Athina , Dounousi Evangelia , Petrou Anastasios , Tselepis Alexandros D.
Published: October 2023

Background: Severe variations in osmotic pressure are significant contributors to critical patient morbidity and mortality and might also affect platelet volume. We aimed to investigate possible osmotic-induced changes in mean platelet volume (MPV) and their possible effects on platelet aggregation activity (PLAG). Methods: We induced experimental variations of serum osmolality in blood samples from healthy volunteers (heparinized whole blood [WB]) and isolated platelets (platelet-rich plasma [PRP]) by adding isotonic, hypertonic, and hypotonic solutions of saline/water (pH = 7.2–7.4). PLAG was tested in WB samples with impedance aggregometry (IA) and in PRP samples with light transmission aggregometry (LTA) using three agonists: adenosine diphosphate (ADP, 10 μm), thrombin receptor activating peptide (TRAP-6, 10 μm), and arachidonic acid (500 μm). Osmolality was either calculated using a formula or measured directly. Results: We found almost identical osmolalities in WB and PRP preparations. Osmotic stress did not produce significant changes in MPV. In IA testing, the hypotonic challenge of WB preparations produced significant reductions at 50% (p = 0.056) (95% CI: 11.2–2.4, in Ohms) of ADP and at 31% (p = 0.017) (95% CI: 13.4–8.6, in Ohms) of TRAP-6-induced PLAG, respectively. In PRP, we did not observe any variations in PLAG with LTA. Conclusions: We conclude that in vitro hypotonic stress of WB samples has an inhibitory effect on the PAR-1 (TRAP-6-induced) pathway and on the P2Y12 (ADP-induced) pathway and reflects a distinct in vivo effect of hypoosmotic stress on WB human platelet preparations.
Clinical Application of Confocal Laser Endomircoscopy Combined with Cryobiopsy in the Diagnosis of Interstitial Lung Disease
Authors: Zuo Cuiyun , Xue Keying , Yang Hui , Huang Rui , Yong Zhiya , Zhang Meihua , Lin Yanli , Tian Xiaoqin , Gu Yingying , Ke Mingyao
Published: October 2023

Introduction: Confocal laser endomicroscopy (CLE) has the characteristics of high resolution, real-time imaging, and no radiation, which is helpful for the precise and effective implementation of transbronchial cryobiopsy (TBCB). The study aimed to compare the efficacy and safety of TBCB combined with CLE (CLE group) or fluoroscopy (fluoroscopy group) in the diagnosis of interstitial lung disease (ILD). Methods: From a prospective randomized controlled trial, 80 patients with undiagnosed ILD or ILD requiring biopsy between January 2022 and November 2022 were randomly assigned to CLE group and fluoroscopy group. The rate to reach an etiological diagnosis of ILD, maximum cross-sectional area of specimens, operation time, and complications were compared between the two groups. Results: The rate to reach an etiological diagnosis in the CLE group was significantly higher than that in the fluoroscopy group (95.0% vs. 80.0%, p < 0.05), but there was no difference in the maximum cross-sectional area of the specimens (42.1 ± 10.1 mm2 vs. 41.5 ± 10.3 mm2, p > 0.05). In terms of operation time, the CLE group was significantly shorter than the fluoroscopy group (37.6 ± 10.6 min vs. 54.8 ± 24.9 min, p < 0.05). The bleeding volume in the CLE group was significantly lower than that in the fluoroscopy group (4.9 ± 3.6 mL/case vs. 9.0 ± 9.2 mL/case, p < 0.05). Further analysis showed that the incidence of moderate bleeding was also lower in the CLE group (20.0% vs. 75.0%, p < 0.001). In addition, the incidence of pneumothorax in the CLE group was significantly lower than that in the fluoroscopy group (0 vs. 25.0%, p < 0.001). Conclusions: Compared with simple fluoroscopy, the combination of CLE significantly improves the rate of etiological diagnosis, shortens the operation time, and reduces complications such as bleeding and pneumothorax.
Effectiveness and Factors Associated with Response to Golimumab in Japanese Patients with Ulcerative Colitis in Real Clinical Practice: The Phoenix Study
Authors: Hirayama Daisuke , Motoya Satoshi , Ashida Toshifumi , Ando Katsuyoshi , Fujiya Mikihiro , Ito Takahiro , Furukawa Shigeru , Maemoto Atsuo , Katsurada Takehiko , Hinotsu Shiro , Sato Noriko , Mizuno Naomi , Ikawa Yoshiko , Nakase Hiroshi
Published: October 2023

Introduction: There have been limited reports on the clinical efficacy of golimumab (GLM) in Japanese patients with ulcerative colitis (UC) in real clinical practice. This study aimed to explore the real-life effectiveness and factors associated with response to GLM in Japanese patients with UC. Methods: This observational, retrospective, multicenter study was conducted in hospitals with expertise in inflammatory bowel disease treatment. Sixty-three patients treated with GLM and active UC were included in the analysis. Clinical remission (CR) (partial Mayo (pMayo) score ≤2) in the induction and maintenance phases after GLM treatment and associated factors were evaluated. Results: The proportion of patients achieving CR in the induction and maintenance phases was 41.3% (26/63) and 46.0% (29/63, the last observation carried forward method was used for patients who discontinued treatment for reasons other than inadequate response), respectively. The median pMayo score was 5 (interquartile range (IQR): 4–6) at baseline, 3 (IQR: 1–5) in the induction phase, and 1 (IQR: 0–3) in the maintenance phase. Hemoglobin, platelet, and C-reactive protein levels changed, consistent with the pMayo score. Multivariate logistic analysis revealed that biologic-naive status was an independent factor associated with CR in the induction (p = 0.0200) and maintenance (p = 0.0459) phases, and a disease duration of >60 months until GLM initiation was associated with CR in the induction phase (p = 0.0427). Conclusions: The effectiveness of GLM in daily clinical practice has been confirmed in Japanese patients with active UC. Biologic-naive patients responded more to GLM in the induction and maintenance phases, and patients with disease duration of >60 months until initiation of GLM were more responsive in the induction phase.
Changes of Optic Disc and Macular Vessel Perfusion Density in Primary Angle Closure Glaucoma: A Quantitative Study Using Optical Coherence Tomography Angiograph
Authors: Li Chao , Tan Li , Xu Xing , Chen Shirong , Huang Chukai
Published: October 2023

Introduction: This study aims to investigate the changes of retinal vascular system in primary angle closure glaucoma (PACG) and acute primary angle closure (APAC) by optical coherence tomography (OCT) angiograph (OCTA) and to evaluate the diagnostic ability of changes of vessel density (VD) in different sectors and layers of optic disc and macular area in APAC and PACG. Methods: In this cross-sectional, observational study, 21 APAC patients (22 eyes) and 21 PACG patients (27 eyes) along with 17 healthy people were enrolled from August 2018 to March 2019. Optic disc region and macular region were imaged using swept-source OCTA system. VD of the macular region was quantified by Image J (1.52a, USA) and Matlab 2018a. The circumpapillary retinal nerve fiber layer (cpRNFL) thickness and ganglion cell complex thickness were obtained by spectral-domain OCT. Results: Compared with the healthy group, the cpRNFL thickness in superior sector was thicker in the APAC group, and this area had the most diffuse microvascular dropout as well. The difference in the macular superficial capillary plexus (SCP) VD between APAC and the control group was not statistically significant. The area under the ROC curves (AUC) of the total optic disc VD in the radial peripapillary capillary (RPC) layer was higher than the AUC of the papillary VD in the optic nerve head (ONH) layer. Compared to the control group, the total optic disc VD, peripapillary VD, and each quadrant of peripapillary VD were decreased in PACG (p < 0.01). In PACG macular region, SCP VD, and deep capillary plexus (DCP) VD, parafovea VD (except temporal sectors) decreased (p < 0.01). The PACG eyes had a greater decrease percentage of VD in total ONH than total macula. The diagnostic value of the VD in the ONH layer and the RPC layer was similar. The diagnostic value of the SCP VD in the macula was greater than the DCP VD in the macula. The AUC was no significant difference between cpRNFL thickness and the total optic disc VD AUC. Conclusion: Elevated intraocular pressure preferentially affects vascular perfusion in the optic disc region more than the macular region in APAC and PACG. In the APAC eyes, there was a perfusion defect in the optic disc region and an increase in RNFL thickness. In this study, the OCTA vascular parameters have similar performance to the OCT structural parameters for glaucoma diagnosis in PACG.
Ungual Scabies: A Case Report and Review of Literature
Authors: Gaurav Vishal , Tyagi Mehul , Grover Chander , Das Shukla
Published: October 2023

Introduction: Nail unit infestation by scabies mites (ungual scabies) is uncommon. It usually presents with distal subungual lesions, leading to recurrent and persistent disease by acting as a reservoir of infection. Periungual involvement in scabies with nail loss is rare and may lead to severe nail damage. Case Presentation: We report a 14-year-old boy on chemotherapy for acute lymphocytic leukemia (ALL) who presented with extensive scaling and crusted plaques of scabies. Nail unit revealed periungual crusted plaques with paronychia and onychomadesis involving five digits. It was associated with partial to complete nail loss. Dermoscopy of periungual crusted plaques showed greyish-white scales with brown dots and globules. A sinuous burrow with a brown-triangular structure was visualized in the web space. KOH mount from skin scrapings showed the scabies mites. Treatment of scabies led to a marked improvement. Conclusion: Though ungual scabies is generally a benign disease, proximal periungual involvement with damage to nail matrix is possible, leading to nail loss. We review manifestations of nail unit scabies reported in literature. Treatment options used and outcomes are also analyzed. The importance of nail-directed therapy in preventing relapses of scabies cannot be undermined.
Concurrent and Predictive Validity of the Mann Assessment of Swallowing Ability in Belgian Acute Stroke Patients Based on a 1-Year Follow-Up Study
Authors: Simpelaere Ingeborg Sylvia , Hansen Tina , Roelant Ella , Vanderwegen Jan , De Bodt Marc , Van Nuffelen Gwen
Published: October 2023

Introduction: The Mann Assessment of Swallowing Ability (MASA) is a standardized clinical swallowing examination, specifically developed as a diagnostic test for the presence of oropharyngeal dysphagia and aspiration in the early period after stroke onset. In the original validation study, cutoff scores of <178 and <170 points, respectively, for the identification of dysphagia and aspiration risk are reported. However, a literature search revealed that alternative cutoff scores for dysphagia and/or aspiration provide better diagnostic accuracy. The aim of this secondary data analysis study was to evaluate the concurrent and predictive validity of the MASA. Methods: Data were derived from a Belgian cohort study of an acute stroke population (n = 151). The MASA total score (MASA-TS), which is the sum of weighted scores on the 24 items, was evaluated against the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) to assess concurrent validity. To assess predictive validity of the MASA-TS, pneumonia during hospitalization and over 1 year and mortality acted as a future criterion. Analyses included receiver operating characteristic curves and area under the curve (AUC). Results: Diagnostic accuracy of the MASA-TS was good for dysphagia (AUC = 0.85) and for the presence of relevant aspiration risk (AUC = 0.84). Using the original cutoff scores, the MASA-TS showed perfect sensitivity (Se = 1.00) for the identification of dysphagia and aspiration but inadequate specificity (Sp) for dysphagia (Sp = 0.16) and aspiration (Sp = 0.43). After determining new MASA cutoff scores, the optimal MASA cutoff scores were ≤146 for both dysphagia and aspiration with adequate thresholds (Se = 0.71 and Sp = 0.81 for dysphagia; Se = 0.73 and Sp = 0.80 for aspiration). The MASA-TS was a significant predictor of pneumonia during hospitalization (AUC = 0.85) and 1-year follow-up (AUC = 0.86), and of mortality (AUC = 0.79). Conclusion: The MASA-TS showed good concurrent validity with the FEDSS. Furthermore, using new cutoff scores (≤146 for the identification of dysphagia and aspiration) lead in general to more accurate diagnostic indexes. The MASA-TS is a good predictor of aspiration pneumonia during hospitalization and 1-year follow-up and of mortality.
Fibrosis quística: Facilitar urgentemente el acceso al diagnóstico temprano también en los países emergentes
Authors: Figueroa-Hurtado Esperanza , Ortiz-Farías Diana Lizbeth , Cortés-Telles Arturo
Published: October 2023

Background: The Cystic Fibrosis Foundation Patient Registry (CFFPR) reports a high prevalence of asthma (34.6%) in people with Cystic Fibrosis (PwCF). While our current understanding of this relationship is limited, a type 2 inflammatory (T2) phenotype has often been identified in CF patients. Research question: This study aimed to evaluate the relationship between the eosinophilic CF T2 inflammatory phenotype and CF-related pulmonary outcomes and microbiological data. Study design: and methods: We conducted a retrospective chart review of adult patients with CF (18 and older; n = 93) receiving their care at University of Virginia Medical Center adult program from January, 2013 through December, 2018. Data collected included demographic data, CFTR (CF transmembrane conductance regulator) mutation, CF comorbidities, medications, Absolute Eosinophil Counts (AEC) in cells/µL and Immunoglobulin E (IgE) levels in IU/mL. Results: Of 93 patients screened for study eligibility, 74 were included in the final analysis; 19 patients were excluded due to lack of longitudinal data across the study timeline. Lung function decline correlated with increased AEC (p < 0.001) and IgE (p < 0.001) even when adjusting for covariates: age, gender, presence of Pseudomonas spp., MRSA, other bacterial spp., Aspergillus spp., and other fungi (p < 0.001). Univariate analysis demonstrated that people with CF who experienced more than 2 exacerbations requiring hospitalizations and/or intravenous antibiotics a year were more likely to have high AEC (p = 0.018). Logistic regression showed that as AEC increases, the probability that the measurement was taken during a CF exacerbation increases (p = 0.0039). A linear mixed model showed that each additional annual exacerbation event increased on average the log IgE by 0.04. (p = 0.015). This finding remained stable in a multivariate model (p = 0.0145). When adjusted for atopy, log IgE increases as the number of exacerbation events increases (p = 0.022). There was no association between AEC and IgE and microbiological colonization.
Endobronchial Metastasis of Renal Cancer Presented as Atelectasis
Authors: You Jae Hyung , Jeong Young Beom
Published: October 2023

The most common primary tumors associated with endobronchial metastasis (EBM) are colorectal, breast, and renal. When EBM is present, respiratory symptoms such as shortness of breath or hemoptysis accompanied by coughing usually appear. Herein, we report a case of atelectasis caused by EBM of renal cell carcinoma (RCC) in a 53-year-old man who underwent laparoscopic radical nephrectomy for RCC 5 years ago. The patient’s primary RCC stage was pT1b, and the histological cell type was clear cell RCC with Fuhrman nuclear grade 3/4. At the time of EBM diagnosis, the patient was classified as “favorable” according to IMDC (International mRCC Database Consortium) risk calculator. The patient refused surgical treatment and received targeted therapy with sunitinib. A tumor mass spontaneously detached and came out through the airway during targeted therapy. Subsequently, the patient’s respiratory symptoms were alleviated, and his atelectasis disappeared. This case shows that when there is atelectasis due to EBM of RCC, the obstructed bronchus may be reopened with targeted therapy without any interventional treatment.