bluuebunny/crossref_metadata_2025 huggingface dataset:
A First Insight Into the Heat-Induced Changes in Proteomic Profiles of the Coral Symbiotic Bacterium Endozoicomonas montiporae
Authors: Chan Ya-Fan , Chen Chia-Yu , Lu Chih-Ying , Tu Yung-Chi , Tandon Kshitij , Shikina Shinya , Tang Sen-Lin
Published: February 2022

Endozoicomonas, a core bacterial group in corals, may also be a coral symbiont. Endozoicomonas communities often decrease rapidly in corals under heat stress. However, how the bacteria respond to changes in temperature and coral host during heat stress is unknown. Here, we employed the cultivable, dominant species E. montiporae as a working organism to explore how Endozoicomonas responds to heat stress. We designed two experiments to clarify the extent to which E. montiporae is influenced by temperature and coral host. We detected differentially expressed protein (DEP) profiles in this bacterium at 31 and 33°C compared to 25°C by tandem mass tags-based quantitative proteome analysis. Fifty DEPs, including many heat shock proteins, were detected when the temperature changed. The expression of antioxidant defense proteins and key pyruvate synthase proteins decreased, suggesting that E. montiporae were in a physiology of stress at 33°C. Furthermore, some proteins were differentially expressed because of the heat-stress-treated coral lysate specifically, suggesting that not only heat but also heat-induced host factors can affect the protein expression of the bacterium. This study provides an in-depth analysis of how the molecular mechanisms of Endozoicomonas are affected by heat stress and coral host.
Combined Effect of Microneedling and Platelet-Rich Plasma for the Treatment of Acne Scars: A Meta-Analysis
Authors: Kang Cheng , Lu Dakai
Published: February 2022

Background

Microneedling is a promising method for the treatment of acne scars, while the effect of microneedling combined with platelet-rich plasma (PRP) remains unknown. We performed a meta-analysis of controlled studies to compare the efficacy and safety of microneedling treatment with and without additional PRP in patients with acne scars.

Methods

Randomized and non-randomized controlled studies were identified by search of Medline, Embase, and Cochrane's Library databases. Results were pooled with a random-effects model, incorporating the possible heterogeneity.

Results

Four randomized and 10 split-face non-randomized controlled studies with 472 patients were included. Compared to microneedling therapy without PRP, combined treatment with microneedling and PRP was associated with increased odds of clinical improvement of >50% in Goodman's qualitative scale [GQS: odds ratio (OR): 2.97, 95% confidence interval (CI): 1.96–4.51,p< 0.001;I2= 0%], and a significantly improved mean GQS score (mean difference: −0.32, 95% CI: −0.44 to −0.20,p< 0.001;I2= 0%). Combined treatment was associated with a higher patient satisfying rate (OR: 4.15, 95% CI: 2.13 to 8.09,p< 0.001;I2= 53%), while the incidence of severe adverse events such as severe erythema (OR: 1.59, 95% CI:.73 to 3.46,P= 0.24;I2= 0%) and severe edema (OR: 1.14, 95% CI: 0.47 to 2.76,P= 0.77;I2= 0%) were not significantly different.

Conclusions

Combined treatment with microneedling with PRP is more effective than microneedling without PRP for patients with acne scars.
Case Report: Multiple Retinal Astrocytic Hamartomas in Congenital Disorder of Glycosylation-Ia
Authors: Midena Giulia , Pilotto Elisabetta
Published: February 2022

Congenital disorder of glycosylation-Ia (CDG-Ia) is a rare autosomal recessive genetic disorder, characterized by systemic and ophthalmological abnormalities. Here, we report multiple retinal astrocytic hamartomas as a new retinal finding in an adolescent affected by congenital disorder of CDG-Ia. A 15-year-old boy affected by CDG-Ia underwent full ophthalmic examination, full field electroretinography (ERG) evaluation and retinal multimodal imaging, including: fundus photography, spectral domain optical coherence tomography (SD-OCT) and blue fundus autofluorescence (FAF). Blue FAF showed multiple papillary and iuxtapapillary bilateral hyper-FAF lesions, corresponding to hyperreflective thickening of the retinal nerve fiber layer, with internal optical empty spaces and posterior dense optical shadowing at SD-OCT. These imaging findings were consistent with retinal astrocytic hamartomas. Scotopic ERG response was significantly reduced in both eyes. Macular edema and absence of the retinal outer segments layer were also detectable. Retinal multi-modal imaging provides additional insights about retinal involvement of patients affected by CDG-Ia. In particular, this case shows the presence of multiple retinal astrocytic hamartomas.
The Positive Effects of Cancer Survivor Support Service on Distress in South Korea: A Nationwide Prospective Study
Authors: Lee Hyun Jeong , Kim Young Ae , Ryu Seong Yeob , Chun Mison , Yim Chang-Yeol , Kang Hee-Taik , Kang Jung Hun , Huh Jung-Sik , Kim Jong-Heun , Lim Kyu-Hyoung , Jung So-Youn , Kwon Hyoung-Cheol , Goh Eurah , Lee Yeon-Seung , Ju Hee Young , Yun E. Hwa , Chang Yoon Jung
Published: February 2022

Background and Aim

Cancer survivors are gradually increasing, however, they suffer from various difficulties. We aimed to investigate the characteristics of cancer survivors and the effects of the services of the Korean Cancer Survivorship Center Pilot Project launched by the South Korean government on distress.

Methods

A prospective observational cohort study was performed on cancer survivors who completed primary treatment. Cancer survivors' distress and symptoms such as fatigue, pain, depressive mood, anxiety, and insomnia were evaluated by well-trained nurses. Regarding their needs, medical and psychosocial support services were provided.

Results

This study included 1,921 cancer survivors, with a mean age of 57.3 years (68.7% females). Breast cancer was most common, followed by stomach and colorectal cancer. Psychosocial and medical support decreased the percentage of the high-distress group from 50.9 to 30.5% and decreased the percentage of cancer survivors with high scores in fatigue, pain, anxiety, depressive mood, and insomnia. The independent predictors of a low distress level after the use of the services were older age, the relief of fatigue, pain, and insomnia.

Conclusion

This study showed that psychosocial and medical support is associated with the lower distress and physical and mental symptoms of cancer survivors. Psychosocial and medical support could contribute to distress relief in cancer survivors. Further management strategies for fatigue, pain and insomnia are required.
Beyond the Lung: Geriatric Conditions Afflict Community-Dwelling Older Adults With Self-Reported Chronic Obstructive Pulmonary Disease
Authors: Witt Leah J. , Wroblewski Kristen E. , Pinto Jayant M. , Wang Esther , McClintock Martha K. , Dale William , White Steven R. , Press Valerie G. , Huisingh-Scheetz Megan
Published: February 2022

Rationale

Chronic obstructive pulmonary disease (COPD) predominantly affects older adults. However, the co-morbid occurrence of geriatric conditions has been understudied.

Objective

Characterize the prevalence of geriatric conditions among community-dwelling U.S. older adults with self-reported COPD.

Methods

We conducted a nationally representative, cross-sectional study of 3,005 U.S. community-dwelling older adults (ages 57–85 years) from the National Social Life, Health, and Aging Project (NSHAP). We evaluated the prevalence of select geriatric conditions (multimorbidity, functional disability, impaired physical function, low physical activity, modified frailty assessment, falls, polypharmacy, and urinary incontinence) and psychosocial measures (frequency of socializing, sexual activity in the last year, loneliness, cognitive impairment, and depressive symptoms) among individuals with self-reported COPD as compared to those without. Using multivariate logistic and linear regressions, we investigated the relationships between COPD and these geriatric physical and psychosocial conditions.

Main Results

Self-reported COPD prevalence was 10.7%, similar to previous epidemiological studies. Individuals with COPD had more multimorbidity [modified Charlson score 2.6 (SD 1.9) vs. 1.6 (SD 1.6)], more functional disability (58.1 vs. 29.6%; adjusted OR 3.1, 95% CI 2.3, 4.3), falls in the last year (28.4 vs. 20.8%; adjusted OR 1.4, 95% CI 1.01, 2.0), impaired physical function (75.8 vs. 56.6%; adjusted OR 2.1, 95% CI 1.1, 3.7), more frequently reported extreme low physical activity (18.7 vs. 8.1%; adjusted OR 2.3, 95% CI 1.5, 3.5) and higher frailty prevalence (16.0 vs. 2.7%; adjusted OR 6.3, 95% CI 3.0,13.0) than those without COPD. They experienced more severe polypharmacy (≥10 medications, 37.5 vs. 16.1%; adjusted OR 2.9, 95% CI 2.0, 4.2). They more frequently reported extreme social disengagement and were lonelier, but the association with social measures was eliminated when relationship status was accounted for, as those with COPD were less frequently partnered. They more frequently endorsed depressive symptoms (32.0 vs. 18.9%, adjusted OR 1.9, 95% CI 1.4, 2.7). There was no noted difference in cognitive impairment between the two populations.

Conclusions

Geriatric conditions are common among community-dwelling older adults with self-reported COPD. A “beyond the lung” approach to COPD care should center on active management of geriatric conditions, potentially leading to improved COPD management, and quality of life.
Case Report: Rowell Syndrome–Like Flare of Cutaneous Lupus Erythematosus Following COVID-19 Infection
Authors: Drenovska Kossara , Shahid Martin , Mateeva Valeria , Vassileva Snejina
Published: February 2022

The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had an important impact on dermatology practice, posing diagnostic and therapeutic challenges especially in patients with inflammatory and autoimmune skin disorders. Disease-specific and nonspecific cutaneous manifestations have been increasingly reported in the spectrum of COVID-19 but the influence of the infection on pre-existing dermatologic diseases has not been clearly defined. There has been a debate in the literature as to whether patients suffering from autoimmune dermatoses, including cutaneous lupus erythematosus (CLE), are at increased risk of SARS-CoV-2 infection, as well as if they experience worsening of their lupus erythematosus (LE)-related clinical symptoms. This article reports on a case of Rowell syndrome occurring after COVID-19 in a 67-year old woman with pre-existing chronic CLE manifesting with few discoid lesions on the face, scalp, and upper chest, successfully controlled with topical corticosteroids and photoprotection. Erythema multiforme (EM)-like eruption developed approximately two weeks after the SARS-CoV-2 infection, the latter being confirmed by positive nasopharyngeal swab and successfully treated with systemic antibiotics and antiaggregants. Diffuse hair loss and patches of cicatricial alopecia were also present upon scalp examination. Laboratory workup, including routine tests, histologic, immunofluorescent, and serologic investigations, was supportive to the diagnosis. Administration of topical and systemic corticosteroids along with peroral hydroxychloroquine resulted in the progressive improvement of the cutaneous lesions. Rowell syndrome is a rare entity in the spectrum of LE, characterized by EM-like lesions, photosensitivity, and positive antinuclear and anti-Ro antibodies, that is currently considered to be a variant of subacute CLE (SCLE). Several cases of SCLE have been described in association with medications, including anti-SARS-CoV-2 vaccines but only a few reports incriminate the infection itself as a potential exacerbating factor. Based on the clinical course of the disease, we suggest that the observed Rowell syndrome-like flare of CLE was related to the COVID-19 infection in this patient.
Differences in ICU Outcomes According to the Type of Anticancer Drug in Lung Cancer Patients
Authors: Hong Yoonki , Hong Ji Young , Park Jinkyeong
Published: February 2022

Purpose

We investigated the intensive care unit (ICU) outcomes of patients who used targeted therapy compared to those who received cytotoxic chemotherapy.

Materials and Methods

This study was based on Korean administrative health insurance claims from 2015 to 2019. We extracted data on lung cancer patients (>18 years old) who were admitted to the ICU after receiving chemotherapy.

Results

6,930 lung cancer patients who received chemotherapy within 30 days before ICU admission were identified; the patients received cytotoxic chemotherapy (85.4%, n = 5,919) and molecular targeted therapy (14.5%, n = 1,011). Grade 4 neutropenia was identified only in the cytotoxic chemotherapy group (0.6%). Respiratory failure requiring ventilator treatment was more common in the cytotoxic chemotherapy group than in the targeted therapy group (HR, 3.30; 95% CI, 2.99–3.63), and renal failure requiring renal replacement therapy was not significantly different between the two groups (HR, 1.57; 95% CI, 1.36–1.80). Patients who received targeted chemotherapy stayed longer in the ICU than the cytotoxic chemotherapy. The 28-day mortality was 23.4% (HR, 0.79; 95% CI, 0.67–0.90, p < 0.05) among patients who received targeted agents compared with 29.6% among patients who received cytotoxic chemotherapy.

Conclusion

Targeted chemotherapy for lung cancer may contribute to increasing access to critical care for lung cancer patients, which may play a role in improving critical care outcomes of lung cancer patients.
Epigenetic Activation of Silent Biosynthetic Gene Clusters in Endophytic Fungi Using Small Molecular Modifiers
Authors: Pillay Lynise C. , Nekati Lucpah , Makhwitine Phuti J. , Ndlovu Sizwe I.
Published: February 2022

The discovery of silent biosynthetic gene clusters (BGCs) in fungi provides unlimited prospects to harness the secondary metabolites encoded by gene clusters for various applications, including pharmaceuticals. Amplifying these prospects is the new interest in exploring fungi living in the extremes, such as those associated with plants (fungal endophytes). Fungal species in endosymbiosis relationship with plants are recognized as the future factories of clinically relevant agents since discovering that they can produce similar metabolites as their plant host. The endophytes produce these compounds in natural environments as a defense mechanism against pathogens that infect the plant host or as a strategy for mitigating competitors. The signaling cascades leading to the expression of silent biosynthetic gene clusters in the natural environment remain unknown. Lack of knowledge on regulatory circuits of biosynthetic gene clusters limits the ability to exploit them in the laboratory. They are often silent and require tailor-designed strategies for activation. Epigenetic modification using small molecular compounds that alter the chromatin network, leading to the changes in secondary metabolites profile, has achieved considerable success. This review aims to comprehensively analyze the secondary metabolite profiles expressed after treatment with various epigenetic modifiers. We first describe the regulatory circuits governing the expression of secondary metabolites in fungi. Following this, we provide a detailed review of the small molecular modifiers, their mechanism(s) of action, and the diverse chemistries resulting from epigenetic modification. We further show that genetic deletion or epigenetic inhibition of histone deacetylases does not always lead to the overexpression or induction of silent secondary metabolites. Instead, the response is more complex and often leads to differential expression of secondary metabolites. Finally, we propose using this strategy as an initial screening tool to dereplicate promising fungal species.
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase
Authors: Frey Kathleen M. , Bertoletti Nicole , Chan Albert H. , Ippolito Joseph A. , Bollini Mariela , Spasov Krasimir A. , Jorgensen William L. , Anderson Karen S.
Published: February 2022

Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT crystal structure complex that was solved with non-nucleoside reverse transcriptase inhibitor nevirapine. The release of this structure opened opportunities for designing many families of non-nucleoside reverse transcriptase inhibitors (NNRTIs). In paying tribute to the first RT-nevirapine structure, we have developed several compound classes targeting the non-nucleoside inhibitor binding pocket of HIV RT. Extensive analysis of crystal structures of RT in complex with the compounds informed iterations of structure-based drug design. Structures of seven additional complexes were determined and analyzed to summarize key interactions with residues in the non-nucleoside inhibitor binding pocket (NNIBP) of RT. Additional insights comparing structures with antiviral data and results from molecular dynamics simulations elucidate key interactions and dynamics between the nucleotide and non-nucleoside binding sites.
Gradual Not Sudden Change: Multiple Sites of Functional Transition Across the Microvascular Bed
Authors: Shaw Kira , Boyd Katie , Anderle Silvia , Hammond-Haley Matthew , Amin Davina , Bonnar Orla , Hall Catherine N.
Published: February 2022

In understanding the role of the neurovascular unit as both a biomarker and target for disease interventions, it is vital to appreciate how the function of different components of this unit change along the vascular tree. The cells of the neurovascular unit together perform an array of vital functions, protecting the brain from circulating toxins and infection, while providing nutrients and clearing away waste products. To do so, the brain’s microvasculature dilates to direct energy substrates to active neurons, regulates access to circulating immune cells, and promotes angiogenesis in response to decreased blood supply, as well as pulsating to help clear waste products and maintain the oxygen supply. Different parts of the cerebrovascular tree contribute differently to various aspects of these functions, and previously, it has been assumed that there are discrete types of vessel along the vascular network that mediate different functions. Another option, however, is that the multiple transitions in function that occur across the vascular network do so at many locations, such that vascular function changes gradually, rather than in sharp steps between clearly distinct vessel types. Here, by reference to new data as well as by reviewing historical and recent literature, we argue that this latter scenario is likely the case and that vascular function gradually changes across the network without clear transition points between arteriole, precapillary arteriole and capillary. This is because classically localized functions are in fact performed by wide swathes of the vasculature, and different functional markers start and stop being expressed at different points along the vascular tree. Furthermore, vascular branch points show alterations in their mural cell morphology that suggest functional specializations irrespective of their position within the network. Together this work emphasizes the need for studies to consider where transitions of different functions occur, and the importance of defining these locations, in order to better understand the vascular network and how to target it to treat disease.
Cerebral Microbleeds With Atrial Fibrillation After Ablation Therapy
Authors: Hirata Yoshinori , Kato Natsuko , Muraga Kanako , Shindo Akihiro , Nakamura Naoko , Matsuura Keita , Ii Yuichiro , Shiga Mariko , Tabei Ken-ichi , Satoh Masayuki , Fukuma Tomoyuki , Kagawa Yoshihiko , Fujita Satoshi , Kogue Ryota , Umino Maki , Maeda Masayuki , Sakuma Hajime , Dohi Kaoru , Tomimoto Hidekazu
Published: February 2022

Background

The prevalence of cerebral microbleeds (CMBs) is significantly higher in patients with atrial fibrillation (AF) than in those without AF. CMBs in patients with AF have been reported to be primarily of the lobar type, but the exact cause of this remains unknown. We investigated the possibility that hemorrhagic transformation of embolic microinfarction can account for de novo lobar CMBs.

Methods

A total of 101 patients who underwent ablation therapy for AF were prospectively registered, and 72 patients completed the assessment with MRI 6 months after catheter ablation. Brain MRI, including diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI), were examined at 1–3 days (baseline) and 6 months after catheter ablation. We quantitatively evaluated the spatial and temporal distribution of embolic microinfarctions and de novo CMBs.

Results

Of the 101 patients, 68 were enrolled in this study. Fifty-nine patients (86.8%) showed embolic microinfarctions on baseline DWI immediately after catheter ablation. There were 137 CMBs in SWI, and 96 CMBs were of the lobar type. Six months later, there were 208 CMBs, including 71 de novo CMBs, and 60 of 71 (84.5%) were of the lobar type. Of the 71 de novo CMBs, 56 (78.9%) corresponded to the location of previous embolic microinfarctions found on baseline DWI. The platelet count was significantly lower and hematocrit/hemoglobin and Fazekas score were higher in the group with de novo CMBs than in the group without de novo CMBs.

Conclusion

De novo CMBs frequently appeared after catheter ablation therapy. Our results suggest that embolic microinfarction can cause lobar CMBs.
Machine Learning Techniques in Blood Pressure Management During the Acute Phase of Ischemic Stroke
Authors: Mazza Orit , Shehory Onn , Lev Nirit
Published: February 2022

Background and Purpose

Elevated blood pressure (BP) in acute ischemic stroke is common. A raised BP is related to mortality and disability, yet excessive BP lowering can be detrimental. The optimal BP management in acute ischemic stroke remains insufficient and relies on expert consensus statements. Permissive hypertension is recommended during the first 24-h after stroke onset, yet there is ongoing uncertainty regarding the most appropriate blood BP management in the acute phase of ischemic stroke. This study aims to develop a decision support tool for improving the management of extremely high BP during the first 24 h after acute ischemic stroke by using machine learning (ML) tools.

Methods

This diagnostic accuracy study used retrospective data from MIMIC-III and eICU databases. Decision trees were constructed by a hierarchical binary recursive partitioning algorithm to predict the BP-lowering of 10–30% off the maximal value when antihypertensive treatment was given in patients with an extremely high BP (above 220/110 or 180/105 mmHg for patients receiving thrombolysis), according to the American Heart Association/American Stroke Association (AHA/ASA), the European Society of Cardiology, and the European Society of Hypertension (ESC/ESH) guidelines. Regression trees were used to predict the time-weighted average BP. Implementation of synthetic minority oversampling technique was used to balance the dataset according to different antihypertensive treatments. The model performance of the decision tree was compared to the performance of neural networks, random forest, and logistic regression models.

Results

In total, 7,265 acute ischemic stroke patients were identified. Diastolic BP (DBP) is the main variable for predicting BP reduction in the first 24 h after a stroke. For patients receiving thrombolysis with DBP <120 mmHg, Labetalol and Amlodipine are effective treatments. Above DBP of 120 mmHg, Amlodipine, Lisinopril, and Nicardipine are the most effective treatments. However, successful treatment depends on avoiding hyponatremia and on kidney functions.

Conclusion

This is the first study to address BP management in the acute phase of ischemic stroke using ML techniques. The results indicate that the treatment choice should be adjusted to different clinical and BP parameters, thus, providing a better decision-making approach.
Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray
Authors: Liu Lichun , Lai Yongxing , Zhan Zhidong , Fu Qingxian , Jiang Yuelian
Published: February 2022

Background

Friedreich's ataxia (FRDA) is a familial hereditary disorder that lacks available therapy. Therefore, the identification of novel biomarkers and key mechanisms related to FRDA progression is urgently required.

Methods

We identified the up-regulated and down-regulated differentially expressed genes (DEGs) in children and adult FRDA from the GSE11204 dataset and intersected them to determine the co-expressed DEGs (co-DEGs). Enrichment analysis was conducted and a protein-protein interaction (PPI) network was constructed to identify key pathways and hub genes. The potential diagnostic biomarkers were validated using the GSE30933 dataset. Cytoscape was applied to construct interaction and competitive endogenous RNA (ceRNA) networks.

Results

Gene Set Enrichment Analysis (GSEA) indicated that the genes in both the child and adult samples were primarily enriched in their immune-related functions. We identified 88 co-DEGs between child and adult FRDA samples. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment analysis suggested that these co-DEGs were primarily enriched in immune response, inflammatory reaction, and necroptosis. Immune infiltration analysis showed remarkable differences in the proportions of immune cell subtype between FRDA and healthy samples. In addition, ten core genes and one gene cluster module were screened out based on the PPI network. We verified eight immune-specific core genes using a validation dataset and found CD28, FAS, and ITIF5 have high diagnostic significance in FRDA. Finally, NEAT1-hsa-miR-24-3p-CD28 was identified as a key regulatory pathway of child and adult FRDA.

Conclusions

Downregulation of three immune-specific hub genes, CD28, FAS, and IFIT5, may be associated with the progression of child and adult FRDA. Furthermore, NEAT1-hsa-miR-24-3p-CD28 may be the potential RNA regulatory pathway related to the pathogenesis of child and adult FRDA.
Triglyceride-Glucose Index and Intravenous Thrombolysis Outcomes for Acute Ischemic Stroke: A Multicenter Prospective–Cohort Study
Authors: Lin Sheng-Feng , Hu Han-Hwa , Chao Hai-Lun , Ho Bo-Lin , Chen Chih-Hung , Chan Lung , Lin Huey-Juan , Sun Yu , Lin Yung-Yang , Chen Po-Lin , Lin Shinn-Kuang , Wei Cheng-Yu , Lin Yu-Te , Lee Jiunn-Tay , Chao A-Ching
Published: February 2022

Background

The triglyceride-glucose (TyG) index has recently been proposed as a reliable marker of insulin resistance. There is insufficient evidence to verify that the TyG index is correlated with functional outcomes and hemorrhagic transformation and in patients with stroke treated with intravenous thrombolysis (IVT).

Methods

We designed a multicenter cohort study, which enrolled patients with acute ischemic stroke treated with IVT between December 2004 and December 2016. The TyG index was divided into tertiles and calculated on a continuous scale. Unfavorable functional outcomes were defined by the modified Rankin Scale of 3–6 at 90 days and the incident rates of symptomatic intracranial hemorrhage (SICH) within 36 h of IVT onset were surveyed. Stroke severity was defined as mild (4–8), moderate (9–15), or high (≥16) based on the National Institutes of Health Stroke Scale (NIHSS) scores.

Results

Among 914 enrolled patients, the tertiles of the TyG index were 8.48 for T1, 8.48–9.04 for T2, and 9.04 for T3. T3 showed an increased risk of unfavorable functional outcomes at 90 days [odds ratio (OR): 1.76; P = 0.0132]. The TyG index was significantly associated with unfavorable functional outcomes at 90 days (OR: 1.32; P = 0.0431 per unit increase). No association was found between the TyG index and SICH. These findings were applicable for T3 with stroke of moderate (OR, 2.35; P = 0.0465) and high severity (OR: 2.57, P = 0.0440) patients with stroke.

Conclusion

This study supports the strong association between the increased TyG index and increased unfavorable functional outcomes at 90 days in patients with acute ischemic stroke treated with IVT. These findings were found to be robust in patients with moderate and high stroke severity.
Effect of Training on Visual Identification of High Frequency Oscillations—A Delphi-Style Intervention
Authors: Spring Aaron M. , Pittman Daniel J. , Rizwan Arsalan , Aghakhani Yahya , Jirsch Jeffrey , Connolly Mary , Wiebe Samuel , Appendino Juan Pablo , Datta Anita , Steve Trevor , Pillay Neelan , Javidan Manouchehr , Scantlebury Morris , Hrazdil Chantelle , Josephson Colin Bruce , Boelman Cyrus , Gross Donald , Singh Shaily , Bello-Espinosa Luis , Huh Linda , Jetté Nathalie , Federico Paolo
Published: February 2022

Objective

We examined the effect of a simple Delphi-method feedback on visual identification of high frequency oscillations (HFOs) in the ripple (80–250 Hz) band, and assessed the impact of this training intervention on the interrater reliability and generalizability of HFO evaluations.

Methods

We employed a morphology detector to identify potential HFOs at two thresholds and presented them to visual reviewers to assess the probability of each epoch containing an HFO. We recruited 19 board-certified epileptologists with various levels of experience to complete a series of HFO evaluations during three sessions. A Delphi-style intervention was used to provide feedback on the performance of each reviewer relative to their peers. A delayed-intervention paradigm was used, in which reviewers received feedback either before or after the second session. ANOVAs were used to assess the effect of the intervention on the reviewers' evaluations. Generalizability theory was used to assess the interrater reliability before and after the intervention.

Results

The intervention, regardless of when it occurred, resulted in a significant reduction in the variability between reviewers in both groups (pGroupDI = 0.037, pGroupEI = 0.003). Prior to the delayed-intervention, the group receiving the early intervention showed a significant reduction in variability (pGroupEI = 0.041), but the delayed-intervention group did not (pGroupDI = 0.414). Following the intervention, the projected number of reviewers required to achieve strong generalizability decreased from 35 to 16.

Significance

This study shows a robust effect of a Delphi-style intervention on the interrater variability, reliability, and generalizability of HFO evaluations. The observed decreases in HFO marking discrepancies across 14 of the 15 reviewers are encouraging: they are necessarily associated with an increase in interrater reliability, and therefore with a corresponding decrease in the number of reviewers required to achieve strong generalizability. Indeed, the reliability of all reviewers following the intervention was similar to that of experienced reviewers prior to intervention. Therefore, a Delphi-style intervention could be implemented either to sufficiently train any reviewer, or to further refine the interrater reliability of experienced reviewers. In either case, a Delphi-style intervention would help facilitate the standardization of HFO evaluations and its implementation in clinical care.
A Novel Endovascular Therapy Strategy for Acute Ischemic Stroke Due to Intracranial Atherosclerosis-Related Large Vessel Occlusion: Stent-Pass-Aspiration-resCuE-Micowire-Angioplasty (SPACEMAN) Technique
Authors: Wu Yingchun , Wang Junmei , Sun Rui , Feng Guanqing , Li Wenzhao , Gui Yuejiang , Zheng Yanan
Published: February 2022

Background

There is no clear consensus on the optimal endovascular treatment strategy for patients with ischemic stroke caused by ICAS-related large vessel occlusion (LVO). SPACEMAN, a novel thrombectomy technique that entails passing an aspiration catheter over the stent retriever and then retaining the microwire for angioplasty, has not been described. The aim of this prospective study was to evaluate our initial application of SPACEMAN and compare this technique with the Solumbra technique.

Methods

Forty-four consecutive patients with acute ischemic stroke resulting from ICAS-related LVO were randomly divided into two groups: Solumbra group (n = 22) and SPACEMAN group (n = 22). Demographic and clinical data were prospectively collected. Modified Rankin Scale (mRS) score of ≤ 2 of anterior circulation and mRS score ≤ 3 of posterior circulation at 3 months post-discharge was regarded as good prognosis.

Results

The SPACEMAN group showed reduced mean time from femoral access to recanalization compared with the Solumbra group (39.55 ± 10.63 min vs. 50.73 ± 9.89 min, P = 0.001). The overall recanalization rate in the entire cohort was 93.18% (41/44). At 3-month follow-up, the overall good prognosis rate was 47.73%; 13 patients (59.09%) in the SPACEMAN group and 8 (36.36%) in the Solumbra group showed good prognosis. One patient in the SPACEMAN group (4.55%) and two patients in the Solumbra group (9.09%) developed symptomatic intracranial hemorrhage. The overall mortality rate was 4.55% (2/44).

Conclusions

This study suggests that SPACEMAN exhibits a shorter operation revascularization time than the standard thrombectomy. Complications and prognosis were comparable between the two groups. The safety and efficacy of this novel technique need to be studied in larger patient series.
Estimation of the Internal Dose Imparted by 18F-Fluorodeoxyglucose to Tissues by Using Fricke Dosimetry in a Phantom and Positron Emission Tomography
Authors: Tippayamontri Thititip , Betancourt-Santander Esteban , Guérin Brigitte , Lecomte Roger , Paquette Benoit , Sanche Léon
Published: February 2022

Purpose

Assessment of the radiation dose delivered to a tumor and different organs is a major issue when using radiolabelled compounds for diagnostic imaging or endoradiotherapy. The present article reports on a study to correlate the mean 18F-fluorodeoxyglucose (18F-FDG) activity in different tissues measured in a mouse model by positron emission tomography (PET) imaging, with the dose assessed in vitro by Fricke dosimetry.

Methods

The dose-response relationship of the Fricke dosimeter and PET data was determined at different times after adding 18F-FDG (0–80 MBq) to a Fricke solution (1 mM ferrous ammonium sulfate in 0.4 M sulfuric acid). The total dose was assessed at 24 h (~13 half-lives of 18F-FDG). The number of coincident events produced in 3 mL of Fricke solution or 3 mL of deionized water that contained 60 MBq of 18F-FDG was measured using the Triumph/LabPET8TM preclinical PET/CT scanner. The total activity concentration measured by PET was correlated with the calculated dose from the Fricke dosimeter, at any exposure activity of 18F-FDG.

Results

The radiation dose measured with the Fricke dosimeter increased rapidly during the first 4 h after adding 18F-FDG and then gradually reached a plateau. Presence of non-radioactive-FDG did not alter the Fricke dosimetry. The characteristic responses of the dosimeter and PET imaging clearly exhibit linearity with injected activity of 18F-FDG. The dose (Gy) to time-integrated activity (MBq.h) relationship was measured, yielding a conversion factor of 0.064 ± 0.06 Gy/MBq.h in the present mouse model. This correlation provides an efficient alternative method to measure, three-dimensionally, the total and regional dose absorbed from 18F-radiotracers.

Conclusions

The Fricke dosimeter can be used to calibrate a PET scanner, thus enabling the determination of dose from the measured radioactivity emitted by 18F-FDG in tissues. The method should be applicable to radiotracers with other positron-emitting radionuclides.
Associations Between Gestational Weight Gain and Adverse Birth Outcomes: A Population-Based Retrospective Cohort Study of 9 Million Mother-Infant Pairs
Authors: Liu Xue , Wang Huan , Yang Liu , Zhao Min , Magnussen Costan G. , Xi Bo
Published: February 2022

Background

Gestational weight gain (GWG) reflects maternal nutrition during pregnancy. However, the associations between maternal GWG and adverse birth outcomes are inconclusive.

Objective

We aimed to examine the associations between maternal GWG and adverse birth outcomes according to maternal pre-pregnancy body mass index (BMI) categories in a large, multiethnic and diverse population in the U.S.

Study Design

We used nationwide birth certificate data from the National Vital Statistics System to examine the association of GWG (below, within and above the Institute of Medicine [IOM] guidelines) with six adverse birth outcomes (preterm birth, low birthweight, macrosomia, small for gestational age [SGA], large for gestational age [LGA], and low Apgar score) according to the pre-pregnancy BMI categories (underweight to obesity grade 3). Multivariable logistic regression analyses were performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).

Results

A total of 9,191,842 women aged 18–49 years at delivery with live singleton births were included. Among them, 24.5% of women had GWG below IOM guidelines, 27.6% within the guidelines, and 47.9% above the guidelines. Compared with maternal GWG within guidelines, GWG below guidelines was associated with higher odds of preterm birth (OR = 1.52, 95%CI = 1.51–1.53), low birthweight (OR = 1.46, 95%CI = 1.45–1.47) and SGA (OR = 1.44, 95%CI = 1.43–1.45). In contrast, maternal GWG above guidelines was associated with higher odds of macrosomia (OR = 2.12, 95%CI = 2.11–2.14) and LGA (OR = 2.12, 95%CI = 2.11–2.14). In addition, maternal GWG below or above guidelines had slightly higher odds of low Apgar score (below guidelines: OR = 1.04, 95%CI = 1.03–1.06, above guidelines: OR = 1.17, 95%CI = 1.15–1.18). The results were largely similar among women with GWG below or above guidelines across pre-pregnancy BMI categories of underweight, overweight, and obesity grade 1 to grade 3.

Conclusion

Pregnant women with GWG below or above the IOM guidelines have increased odds of selected adverse infant birth outcomes. Monitoring maternal GWG could enable physicians to provide tailored nutrition and exercise advice as well as prenatal care to pregnant women to reduce the likelihood of adverse birth outcomes.
Case Report: Pancreatic Neuroendocrine Tumor With Liver Metastasis and Portal Vein Thrombosis
Authors: Tian Yulong , Qi Xingshun , Aljbri Afaf , Xu Ke , Zhong Hongshan
Published: February 2022

Introduction

Pancreatic neuroendocrine neoplasms (PNENs) are rare pancreatic tumors originating from pancreatic neuroendocrine cells. There is no consensus on the treatment for PNENs with unresectable liver metastases. Transcatheter arterial chemoembolization (TACE) is the preferred treatment for unresectable primary liver cancer. But the efficacy of TACE and anticoagulation in PNENs with unresectable liver metastases and portal vein thrombosis has never been reported.

Methods and Results

We present the case of a 50-year-old male patient with hepatitis C who was found to have a single liver mass during a regular physical examination in 2016. The liver mass was surgically removed. Postoperative pathology suggested a neuroendocrine tumor of the liver, and it was suggested to look for the primary tumor. The patient was followed up until 2020, and the primary pancreatic tumor was found, along with multiple liver metastases and portal vein thrombosis. After transcatheter arterial embolization, anticoagulation, and endocrine therapy, the patient’s tumor load was relieved, and the portal vein was recanalized.

Conclusion

The article reports the disease course in a case of a functional pancreatic neuroendocrine tumor with liver metastasis and portal vein thrombosis and reviews previous literature. To our knowledge, we reported for the first time the efficacy of TACE and anticoagulation in PNENs with unresectable liver metastases and portal vein thrombosis.
Integrated Genomic and Transcriptomic Analyses of Diffuse Large B-Cell Lymphoma With Multiple Abnormal Immunologic Markers
Authors: Sheng Lingshuang , Fu Di , Cao Yiwen , Huo Yujia , Wang Shuo , Shen Rong , Xu Pengpeng , Cheng Shu , Wang Li , Zhao Weili
Published: February 2022

Background

Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma and related to autoimmune diseases (AIDs). Primary B-cell receptor-mediated AIDs are associated with poor clinical outcome of DLBCL. To further determine the role of immunological alterations on disease progression, our study integrated genomic and transcriptomic analyses on DLBCL with multiple abnormal immunologic markers.

Methods

The clinical data of 1,792 patients with newly diagnosed DLBCL were collected, with DNA- and RNA-sequencing conducted for 164 and 127 patients, respectively. Frequent gene mutations and the involved dysregulated pathways, along with gene expression pattern and tumor microenvironment alternations, were analyzed and compared based on the immune status of the patients.

Results

DLBCL with multiple abnormal immunologic markers demonstrated a variety of characteristics including elevated serum lactic dehydrogenase level, inferior prognosis, and dysregulated cell cycle and immune response, as well as activated oxidative phosphorylation pathway and increased Th1/Th2 and Th17/Treg ratios, which were highly similar as those that occur in AIDs.

Conclusions

We piloted the description of the clinical and genetic features of DLBCL with multiple abnormal immunologic markers, illustrated possible mechanisms of disease progression, and provided a clinical rationale of mechanism-based targeted therapy in this subset of DLBCL.
Case Report: Complete Response to Antiangiogenesis and Immune Checkpoint Blockade in an Unresectable MMR-Deficient Leiomyosarcoma Harboring Biallelic Loss of PTEN
Authors: Guo Xi , Li Suyao , Tong Hanxing , Zhang Yong , Ji Yuan , Zhuang Rongyuan , Zhang Chenlu , You Yang , Lu Weiqi , Zhou Yuhong
Published: February 2022

Background

Leiomyosarcoma (LMS) is a malignant smooth muscle neoplasm, in which the efficacy of immune checkpoint blockade (ICB) is very limited. What is worse, loss of PTEN, known as a negative factor for ICB, frequently occurred in LMS. Seeking new strategies for LMS patients harboring loss of PTEN is important and challenging.

Case Presentation

A 42-year-old Chinese male was diagnosed as having unresectable LMS of the iliopsoas. After the failure of two prior chemotherapy regimens, whole-exome sequencing revealed that tumor tissue had high tumor mutation burden (689 Muts), high microsatellite instability, and some somatic mutations, including PTEN (copy number loss and p.N323fs), MSH6 (p.F1088fs), TP53 p.R273C, ASXL1 p.G645fs, ATR p.S1843P, and CDKN2A p.A118P. Then, antiangiogenic agent (pazopanib or anlotinib) plus pembrolizumab was administered from January 2 to August 6, 2018. However, pazopanib was stopped on June 18 due to the grade 2/3 adverse effect of hand–foot skin reaction, and anlotinib was administered. Considering that the tumor shrunk after immunotherapy, he underwent radical resection on September 6, 2018. The final pathological diagnosis confirmed pathologic complete response (CR). Until the latest follow-up (September 15, 2021), no progressive disease was observed and total disease-free survival has exceeded 36 months.

Conclusion

We presented a patient with an unresectable mismatch repair (MMR)-deficient LMS harboring biallelic loss of PTEN who achieved CR from a combination strategy of antiangiogenesis plus pembrolizumab. Such a strategy might be a promising strategy to overcome the ICB resistance caused by the loss of PTEN. Such conclusions need to be further confirmed in further investigations.
Network Pharmacology Study and Experimental Validation of Yiqi Huayu Decoction Inducing Ferroptosis in Gastric Cancer
Authors: Song Siyuan , Wen Fang , Gu Suping , Gu Peixin , Huang Wenjie , Ruan Shuai , Chen Xiaoxue , Zhou Jiayu , Li Ye , Liu Jiatong , Shu Peng
Published: February 2022

Objective

This study aimed to identify the mechanism of Yiqi Huayu Decoction (YQHY) induced ferroptosis in gastric cancer (GC) by using network pharmacology and experimental validation.

Methods

The targets of YQHY, ferroptosis-related targets, and targets related to GC were derived from databases. Following the protein–protein interaction (PPI) network, the hub targets for YQHY induced ferroptosis in GC were identified. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the hub targets from a macro perspective. We verified the hub targets by molecular docking, GEPIA, HPA, and the cBioPortal database. Finally, we performed cell viability assays, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, lipid peroxidation, and GSH assays to explore the mechanism of YQHY induced ferroptosis in GC.

Results

We identified the main active compounds and hub targets: Quercetin, DIBP, DBP, Mipax, Phaseol and TP53, ATM, SMAD4, PTGS2, and ACSL4. KEGG enrichment analyses indicated that the JAK2-STAT3 signaling pathway may be a significant pathway. Molecular docking results showed that the main active compounds had a good binding activity with the hub targets. The experimental results proved that YQHY could induce ferroptosis in AGS by increasing the MDA content and reducing the GSH content. qRT–PCR and Western blot results showed that YQHY can induce ferroptosis in GC by affecting the JAK2-STAT3 pathway and the expression of ACSL4.

Conclusions

This study indicated that YQHY can induce ferroptosis in GC by affecting the JAK2–STAT3 pathway and the expression of ACSL4, and induction of ferroptosis may be one of the possible mechanisms of YQHY’s anti-recurrence and metastasis of GC.
Comparison of Immunotherapy, Chemotherapy, and Chemoimmunotherapy in Advanced Pulmonary Lymphoepithelioma-Like Carcinoma： A Retrospective Study
Authors: Xiao Yi , He Jinyuan , Luo Shaoning , Dong Min , Li Wei , Liu Gaijiao , Chen Hongjie , Yang Xiongwen , Huang Shaohong
Published: February 2022

Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare subtype of lung cancer that is associated with the Epstein-Barr virus in Asia. Due to the lack of prospective studies, the best first-line treatment and survival outcomes remain unclear. Herein, This study investigated the efficacy and safety of different treatment regimens for advanced pLELC. This retrospective study included 68 patients with advanced pLELC from two centers in China. Patients were divided into three groups according to different first-line treatments: chemotherapy (n=49, 72.1%), immunotherapy (n=7, 10.3%), and chemoimmunotherapy (n=12,17.6%). The primary endpoint of this study was the 2-year progression-free survival (PFS) of each group. The results show that the median PFS was 6.9 months (range, 2.3–not estimable) in the chemotherapy group, 11.0 months (range, 2–not estimable) in the immunotherapy group, and 11.8 months (range, 6–not estimable) in the chemoimmunotherapy group. There was a significant difference in 2-year PFS between the chemoimmunotherapy group and the chemotherapy group (hazard ratio, 0.38, 95% confidence interval: 0.18-0.78, log-rank P=0.007). The most frequent grade 3-4 adverse event in the chemotherapy and chemoimmunotherapy groups was myelosuppression (10/49 [22.4%] and 4/12 [33.3%], respectively). The most frequent grade 3-4 adverse events in the immunotherapy group were diarrhea (1/7, 14.8%) and hepatotoxicity (1/7, 14.8%). Chemoimmunotherapy had the highest 2-year PFS as a first-line treatment for advanced pLELC compared to chemotherapy and immunotherapy. This study suggests that chemoimmunotherapy may be the best first-line treatment for patients with advanced pLELC.