bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Subset of Intracanalicular Vestibular Schwannomas Demonstrates Minimal Growth Over a 10-Year Period
Authors: Wu Matthew J. , Knoll Renata M. , Chen Jenny X. , Reinshagen Katherine , Roychowdhury Prithwijit , McKenna Michael J. , Kozin Elliott D. , Remenschneider Aaron K. , Jung David H. 
Published: January 2022

Objective:
Vestibular schwannomas (VS) commonly undergo magnetic resonance imaging (MRI) surveillance, but long-term data to support the ideal frequency is limited. Herein, we aim to investigate intracanalicular VS growth predictors and long-term growth rates (GR).

Study Design:
Retrospective chart review.

Setting:
Two tertiary care centers.

Patients:
Sporadic intracanalicular VS with initial conservative management and at least two sequential MRIs.

Intervention:
Serial MRI.

Main Outcome Measure(s):
VS were categorized by baseline internal auditory canal tertile sublocalization (fundus, midpoint, porus) and size (≤100, 100–200, >200 mm3). Throughout follow-up, volumetric GR (mm3/yr) were determined (baseline–3 yrs, 3–5 yrs, 5–10 yrs) and treatment rates were assessed.

Results:
Ninety-nine intracanalicular VS were identified (mean follow-up of 6.1 ± 4.5 yrs). Mean GR before 5-year follow-up were comparable for baseline tertile involvement and size. After 5-year follow-up, mean GR of VS involving the fundus at baseline were lower than those involving the midpoint and fundus (6.17 ± 21.16 and 119.74 ± 117.57 mm3/yr, respectively; p = 0.034). Mean GR of VS with less than or equal to 100 mm3 at baseline (–7.29 ± 25.44 mm3/yr) were lower than those with 100 to 200 mm3 (86.55 ± 103.99 mm3/yr; p = 0.011) and more than 200 mm3 (45.70 ± 35.71 mm3/yr; p = 0.031). Vestibular schwannomas involving the midpoint and fundus had greater treatment rates compared with VS involving only the fundus (p < 0.001).

Conclusions:
Baseline tertile involvement and size may predict long-term intracanalicular VS growth where fundal tumors or those less than or equal to 100 mm3 exhibit little long-term growth. Extending surveillance after 5-year follow-up may be reasonable for fundal VS.
Psychopathology and Poor Clinical Insight in Psychotic Patients
Authors: Habibi Asgarabad Mojtaba , Ruhollah Hosseini Seyed , Salehi Yegaei Pardis , Moradi Shahram , Lysaker Paul H. 
Published: January 2022

Abstract
Poor clinical insight is one of the most common features of schizophrenia spectrum disorders and plays a critical role in prognosis and treatment. Considering the biological and phenomenological overlap between schizophrenia and bipolar I disorder with psychotic features (BID) and increasing incidents of methamphetamine-induced psychotic disorder (MIPD) patients in Iran, it is necessary to have a clear picture of insight among these three groups. The aim of the present study was to compare clinical insight and other aspects of illness among three different disorders: schizophrenia, BID, and MIPD. In addition, we sought to examine the relationship of the severity of psychotic symptoms with clinical insight in each group. A total of 115 male inpatients, including 48 persons diagnosed with schizophrenia, 35 persons diagnosed with BID, and 32 persons diagnosed with MIPD, were selected. All participants completed the Scale to Assess Unawareness of Mental Disorder and the Positive and Negative Syndrome Scale. The results of analysis of variance indicated that schizophrenia patients reported higher rates of illness duration and number of hospital admissions in comparison to the MIPD and BID groups. In addition, persons diagnosed with BID reported more of these outcomes than MIPD groups. However, the three groups showed similar patterns in terms of age of onset and educational, marital, and occupational statuses. The results also revealed that awareness of the disorder was more impaired in schizophrenia patients compared with BID and MIPD patients and in MIPD compared with BID groups. However, the level of awareness of the effect of medication, the awareness of social consequences, and the total score of clinical insight were similar across the three diagnostic groups. As expected, poor clinical insight was correlated with high levels of positive, negative, and cognitive symptoms in the schizophrenia group; with high levels of positive, cognitive, and depressive symptoms in the BID group; and with high levels of positive and excitement symptoms in MIPD. In addition, hierarchical linear regression analyses revealed that only cognitive symptoms in the schizophrenia group and excitement symptoms in the MIPD group significantly predicted the overall score of clinical insight. In the BID group, both cognitive and depressive symptoms significantly predicted clinical insight. These findings suggest that there are differing levels of poor clinical insight in schizophrenia, MIPD, and BID and that poor clinical insight found within each group may have different antecedents.
Relationship of Psychiatric Disorders and Sleep Quality to Physical Symptoms in Coronary Artery Disease
Authors: Peng Anshu , Lin Ze , Zhu Chunying 
Published: January 2022

Abstract
Psychiatric disorders (depression/anxiety) and sleep quality are linked to coronary artery disease (CAD). CAD patients often complain of various physical symptoms (PSs), which are not only organic changes of biological origin, but also somatization of mental illness. PSs also affect CAD progression. However, the relationship between psychiatric disorders/sleep quality and PS in CAD is less studied, which this study aims to clarify. This cross-sectional observational study was conducted on the first 305 CAD patients diagnosed with PS by Patient Health Questionnaire-15. They were compared with 521 other CAD patients showing no PS. On multivariate analysis, sex, age, family history, psychiatric disorders, and sleep quality were the significant independent predictors of PS. A significant correlation was found between PS severity and the severity of both psychiatric disorders and sleep quality. Further studies are warranted to explore the impact of psychological and sleep intervention on PS and long-term outcomes.
Assessment of Iron Status in Adolescents Presenting to the Emergency Department With Heavy Menstrual Bleeding
Authors: Stoffers Victoria L. , Weyand Angela C. , Quint Elisabeth H. , Rosen Monica W. 
Published: January 2022

Objective
Iron deficiency is extremely common in adolescents with heavy menstrual bleeding (HMB) presenting to the emergency department; however, patients are rarely screened for this. The objective of this study was to evaluate screening for iron deficiency in adolescents presenting to the emergency department for HMB.

Methods
This is a secondary analysis of a single-center, cross-sectional observational study using retrospective chart review. The study subjects are adolescents ages 11 to 19 years with International Classification of Diseases, Ninth Revision, Clinical Modification/International Classification of Diseases, Tenth Revision, Clinical Modification, codes for HMB who presented to the emergency department at a national tertiary care hospital from 2006 to 2018. Pregnant adolescents with HMB were excluded. Chart abstraction for demographic data, symptoms, laboratory tests, treatments, and outcomes was performed. The main outcome measure was the number of adolescents who had an iron evaluation in the emergency department and were discharged on oral iron.

Results
Of the 258 nonpregnant adolescents who sought care for HMB in the emergency department, 225 (87.2%) were evaluated with serum hemoglobin testing. Ninety-four (41.7%) of those tested were anemic. Only 23 of the 258 patients (8.9%) had iron studies (serum ferritin) performed; 18 of 23 (78.3%) had iron deficiency and 21 of 23 (92.3%) were anemic. Subjects presenting with fatigue, headache, or palpitations were more likely to have iron studies performed than those without these symptoms (all P < 0.01). Thirty-two of the 258 subjects (12.4%) were discharged on oral iron therapy, which included only 15 of the 18 subjects (83.3%) with iron deficiency determined by ferritin testing.

Conclusions
Adolescents presenting to the emergency department with HMB are at significant risk of iron deficiency but are not being screened or treated, which may have significant consequences.
Variations in 2-Minute Walk Test outcomes for people with lower limb amputation in the outpatient clinic and research settings
Authors: Shank Christopher , Kristal Anat , Van Veld Renee , Applegate Brooks , Gaunaurd Ignacio , Gailey Robert 
Published: January 2022

Background:
This study determined the differences in 2-Minute Walk Test (2MWT) distances between people with lower limb amputations in clinical and research settings and described variations in test administration in various clinical settings.

Study Design:
Retrospective Cross-sectional design.

Methods:
The 2MWT for 290 patients with lower limb amputations were obtained from a medium-sized prosthetic company with locations within the central United States. Data on 12 prosthetists’ 2MWT administration decisions were obtained from the results of an administrative questionnaire. Patient 2MWT distances were compared with published distances. Multiple regression was used to examine the impact of test settings on 2MWT outcomes. Descriptive statistics were used to present prosthetists’ variations in test administration.

Results:
Clinical 2MWT distances were significantly less than distances obtained in a research setting. Clinical facilities reported inconsistent path dimensions and potential obstacles in proximity to the test area. Variations in test administration by prosthetists with respect to path length, instructions, turn marker, and overage measurement may contribute to the differences.

Conclusions:
Prosthetists should be aware that comparisons of patients’ 2MWT distance in a clinical environment may differ from published results. Although variations in clinical environments are usually nonmodifiable characteristics of the clinical facility, test administration and scoring could be modified.
IgA Nephropathy in a Patient With Metastatic Carcinoma of Unknown Primary
Authors: Huang Shuhui , Qi Zhibing , Huang Rui , Su Minggang 
Published: January 2022

Abstract
A 35-year-old man with mesenteric metastases of unknown primary was referred for 18F-FDG PET/MRI. The images demonstrated that FDG accumulated in the chest, abdomen, bilateral kidneys, and external genitalia. Renal and testicular metastases were suspected. The primary tumor was still not found. In addition, kidney biopsy findings indicated a diagnosis of IgA nephropathy.
68Ga-Pentixafor PET/CT Improves the Detection of Recurrent Myeloma in the Temporal Bone Masked by the Physiological 18F-FDG Uptake of the Brain and Extraocular Muscles
Authors: Pan Qingqing , Luo Yaping , Cao Xinxin , Li Jian 
Published: January 2022

Abstract
A 71-year-old woman was recently diagnosed with multiple myeloma. Baseline 18F-FDG and 68Ga-pentixafor PET/CT showed diffusely increased uptake in bone marrow, consistent with infiltrated myeloma. She had very good partial response after 9 cycles of chemotherapy. However, during the maintenance with ixazomib, she experienced progressed disease. In the follow-up PET/CT, except for diffusely infiltrated disease in bone marrow, 68Ga-pentixafor PET/CT additionally detected a new emerging lesion in the right temporal bone with lytic bone destruction, which was initially missed in 18F-FDG PET/CT due to the intense physiological uptake of the brain and extraocular muscles.
Anastomosing Hemangioma on 68Ga-DOTATATE PET/CT
Authors: Chua Wei Ming , Hoe Kian Ming Jeremy , Dalan Rinkoo , Too Chow Wei , Ong Simon Yew Kuang , Tay Timothy Kwang Yong , Loke Kelvin Siu Hoong 
Published: January 2022

Abstract
Anastomosing hemangioma (AH) is a rare benign vascular lesion that primarily involves the genitourinary tract. Cases have also rarely been reported in other organs. AH is often discovered incidentally and resembles angiosarcoma histologically. On imaging, it may mimic other vascular lesions such as renal cell carcinoma and neuroendocrine tumors. We present a case of a 32-year-old woman with incidentally detected AH involving the kidneys, adrenal glands, liver, and retroperitoneum, initially presumed to be neuroendocrine tumors based on imaging findings on CT and 68Ga-DOTATATE PET scans.
Incidental Intrahepatic Hepatocellular Cholangiocarcinoma Detected on 68Ga-PSMA PET/CT
Authors: Kang Christine , Jiang James Yuheng , Lee Marco Enoch , Shen Lily , Mansberg Robert 
Published: January 2022

Abstract
A 69-year-old man with intermediate-risk prostate cancer and a mildly elevated prostate-specific antigen of 8.2 μg/L was referred for 68Ga–prostate-specific membrane antigen (68Ga-PSMA) PET/CT for primary staging. An incidental intensely 68Ga-PSMA–avid hepatic focus was seen on PSMA PET and subsequent FDG PET/CT and MRI cholangiogram. This was confirmed to be hepatocellular cholangiocarcinoma on subsequent histopathological examination.
Low and high frequency intracranial neural signals match in the human associative cortex
Authors: Jacques Corentin , Jonas Jacques , Colnat-Coulbois Sophie , Maillard Louis , Rossion Bruno 
Published: January 2022

ABSTRACTIn vivo intracranial recordings of neural activity offer a unique opportunity to understand human brain function. Intracranial electrophysiological (iEEG) activity related to sensory, cognitive or motor events manifests mostly in two types of signals: event-related local field potentials in lower frequency bands (<30 Hz, LF) and broadband activity in the higher end of the frequency spectrum (>30 Hz, High frequency, HF). While most current studies rely exclusively on HF, thought to be more focal and closely related to spiking activity, the relationship between HF and LF signals is unclear, especially in human associative cortex. Here we provide a large-scale in-depth investigation of the spatial and functional relationship between these 2 signals based on intracranial recordings from 121 individual brains (8000 recording sites). We measure selective responses to complex ecologically salient visual stimuli – human faces - across a wide cortical territory in the ventral occipito-temporal cortex (VOTC), with a frequency-tagging method providing high signal-to-noise ratio (SNR) and the same objective quantification of signal and noise for the two frequency ranges. While LF face-selective activity has higher SNR across the VOTC, leading to a larger number of significant electrode contacts especially in the anterior temporal lobe, LF and HF display highly similar spatial, functional, and timing properties. Specifically, and contrary to a widespread assumption, our results point to nearly identical spatial distribution and local spatial extent of LF and HF activity at equal SNR. These observations go a long way towards clarifying the relationship between the two main iEEG signals and reestablish the informative value of LF iEEG to understand human brain function.
Collagen XVIII promotes breast cancer through EGFR/ErbB signaling and its ablation improves the efficacy of ErbB-targeting inhibitors
Authors: Devarajan Raman , Peltoketo Hellevi , Izzi Valerio , Ruotsalainen Heli , Kauppila Saila , Väisänen Marja-Riitta , Rask Gunilla , Martínez-Nieto Guillermo , Karppinen Sanna-Maria , Väisänen Timo , Kaur Inderjeet , Koivunen Jussi , Sasaki Takako , Winqvist Robert , Wärnberg Fredrik , Sund Malin , Pihlajaniemi Taina , Heljasvaara Ritva 
Published: January 2022

AbstractThe tumor extracellular matrix (ECM) is a critical regulator of cancer progression and metastasis, significantly affecting the treatment response. Expression of collagen XVIII (ColXVIII), a ubiquitous component of basement membranes, is induced in many solid tumors, but its involvement in tumorigenesis has remained elusive. We show here that ColXVIII is markedly upregulated in human breast cancer (BC) cells and is closely associated with a poor prognosis in high-grade BC, especially in human epidermal growth factor receptor 2 (HER2)-positive and basal/triple-negative cases. We identified a novel mechanism of action for ColXVIII as a modulator of epidermal growth factor receptor (EGFR/ErbB) signaling and show that it forms a complex with EGFR, HER2 and α6 integrin to promote cancer cell proliferation in a pathway involving its N-terminal portion and the MAPK/ERK1/2 and PI3K/Akt cascades. In vivo studies with Col18a1 mouse models crossed with the MMTV-PyMT mammary carcinogenesis model showed that the short ColXVIII isoform promotes BC growth and metastasis in a tumor cell-autonomous manner. Moreover, the number of mammary cancer stem cells was significantly reduced in both mouse and human cell models upon ColXVIII inhibition. Finally, ablation of ColXVIII in human BC cells and the MMTV-PyMT model substantially improved the efficacy of certain EGFR/ERbB-targeting therapies, even abolishing resistance to EGFR/ErbB inhibitors in some cell lines. In summary, a new function is revealed for ColXVIII in sustaining the stemness properties of BC cells, and tumor progression and metastasis through EGFR/ErbB signaling, suggesting that targeting ColXVIII in the tumor milieu may have significant therapeutic potential.One Sentence SummaryCollagen XVIII is upregulated in breast cancer and promotes mammary carcinogenesis through EGFR/ErbB signaling and by sustaining cancer stem cells, so that its targeting improves the efficacy of ErbB-targeted therapies.
Prenatal stress programs behavioral pattern separation in adult mice
Authors: Rajendran S , Kaci ML , Ladeveze E , Abrous DN , Koehl M 
Published: January 2022

AbstractStress is an unavoidable condition in human life. Stressful events experienced during development, including in utero, have been suggested as one major pathophysiological mechanism for developing vulnerability towards neuropsychiatric and neurodevelopmental disorders in adulthood. One cardinal feature of such disorders is impaired cognitive ability, which may in part rely on abnormal structure and function of the hippocampus. In the hippocampus, the dentate gyrus is a site of continuous neurogenesis, a process that has been recently implicated in spatial pattern separation, a cognitive phenomenon that serves to reduce the degree of overlap in the incoming information to facilitate its storage with minimal interference. We previously reported that adult neurogenesis is altered by prenatal stress allowing us to hypothesize that prenatal stress may possibly lead to impairment in pattern separation. To test this hypothesis, both control (C) and prenatally stressed (PS) adult mice were tested for metric and contextual discrimination abilities. We report for the first time that prenatal stress impairs pattern separation process, a deficit that may underlie their cognitive alterations and that may result in defective behaviors reminiscent of psychiatric illness such as post‐traumatic stress disorder.
Amniotic fluid stem cell extracellular vesicles promote fetal lung branching and cell differentiation in experimental congenital diaphragmatic hernia
Authors: Khalaj Kasra , Figueira Rebeca Lopes , Antounians Lina , Gandhi Sree , Wales Matthew , Montalva Louise , Biouss George , Zani Augusto 
Published: January 2022

ABSTRACTPulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, β-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages, and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.Graphical abstractBabies with congenital diaphragmatic hernia have hypoplastic lungs characterized by impaired branching morphogenesis and undifferentiated epithelium and mesenchyme. The authors demonstrate that amniotic fluid stem cell extracellular vesicles (AFSC-EVs) administered to rat hypoplastic fetal lungs restore branching and exert regenerative effects on epithelial and mesenchymal cells, partly through miRNA cargo transfer. AFSC-EV beneficial effects were obtained at translationally relevant timepoints.
Highly efficient multiplex genome editing in dicots using improved CRISPR/Cas systems
Authors: Li Bingjie , shang Yun , Wang Lixianqiu , Lv Jing , Wang Fengjiao , Chao Jiangtao , Mao Jingjing , Ding Anming , Wu Xinru , Cui Mengmeng , Sun Yuhe , Dai Changbo 
Published: January 2022

AbstractCRISPR/Cas9-mediated gene editing provides a powerful tool for dissecting gene function and improving important traits in crops. However, there are still persisting challenges to obtain high homozygous/bi-allelic (ho/bi) mutations in dicot plants. Here, we develop an improved CRISPR/Cas9 system harboring a calreticulin-like gene promoter, which can boost targeted mutations in dicots. Additionally, the pDC45_dsg construct, combining a 35Spro-tRNA_sgRNA-EU unit and PCE8pro-controlled Cas9, can achieve more than 80.0% ho/bi mutations at target sites in allotetraploid tobacco. We construct pDC45_Fast system that can simultaneously fulfill gene editing and shorten the life span of T0 generation tobacco and tomato. This study provides new tools for improving targeted gene mutagenesis in dicots, and makes manipulations of genes in Solanum more feasible.
36-year study reveals stability of a wild wheat population across microhabitats
Authors: Dahan-Meir Tal , Ellis Thomas James , Mafessoni Fabrizio , Sela Hanan , Rudich Ori , Manisterski Jacob , Avivi-Ragolsky Naomi , Raz Amir , Feldman Moshe , Anikster Yehoshua , Nordborg Magnus , Levy Avraham A. 
Published: January 2022

AbstractLong-term genetic studies of wild populations are very scarce, but are essential for connecting ecological and population genetics models, and for understanding the dynamics of biodiversity. We present a study of a wild wheat population sampled over a 36-year period at high spatial resolution. We genotyped 832 individuals from regular sampling along transects during the course of the experiment. Genotypes were clustered into ecological microhabitats over scales of tens of metres, and this clustering was remarkably stable over the 36 generations of the study. Simulations show that it is difficult to explain this spatial and temporal stability using only limited dispersal, suggesting a role for fine-scale local adaptation to ecological parameters. Using a common-garden experiment, we showed that the genotypes found in distinct microhabitats differ phenotypically, further supporting the hypothesis of local adaptation. Our results provide a rare insight into the population genetics of a natural population over a long monitoring period.