bluuebunny/crossref_metadata_2025 huggingface dataset:
Subtyping Schizophrenia Patients Based on Patterns of Structural Brain Alterations
Authors: Xiao Yuan , Liao Wei , Long Zhiliang , Tao Bo , Zhao Qiannan , Luo Chunyan , Tamminga Carol A , Keshavan Matcheri S , Pearlson Godfrey D , Clementz Brett A , Gershon Elliot S , Ivleva Elena I , Keedy Sarah K , Biswal Bharat B , Mechelli Andrea , Lencer Rebekka , Sweeney John A , Lui Su , Gong Qiyong
Published: August 2021

Schizophrenia is a complex and heterogeneous syndrome. Whether quantitative imaging biomarkers can identify discrete subgroups of patients as might be used to foster personalized medicine approaches for patient care remains unclear. Cross-sectional structural MR images of 163 never-treated first-episode schizophrenia patients (FES) and 133 chronically ill patients with midcourse schizophrenia from the Bipolar and Schizophrenia Network for Intermediate Phenotypes (B-SNIP) consortium and a total of 403 healthy controls were recruited. Morphometric measures (cortical thickness, surface area, and subcortical structures) were extracted for each subject and then the optimized subtyping results were obtained with nonsupervised cluster analysis. Three subgroups of patients defined by distinct patterns of regional cortical and subcortical morphometric features were identified in FES. A similar three subgroup pattern was identified in the independent dataset of patients from the multi-site B-SNIP consortium. Similarities of classification patterns across these two patient cohorts suggest that the 3-group typology is relatively stable over the course of illness. Cognitive functions were worse in subgroup 1 with midcourse schizophrenia than those in subgroup 3. These findings provide novel insight into distinct subgroups of patients with schizophrenia based on structural brain features. Findings of different cognitive functions among the subgroups support clinical differences in the MRI-defined illness subtypes. Regardless of clinical presentation and stage of illness, anatomic MR subgrouping biomarkers can separate neurobiologically distinct subgroups of schizophrenia patients, which represent an important and meaningful step forward in differentiating subtypes of patients for studies of illness neurobiology and potentially for clinical trials.
Quantifying Retinal Microvascular Morphology in Schizophrenia Using Swept-Source Optical Coherence Tomography Angiography
Authors: Bannai Deepthi , Adhan Iniya , Katz Raviv , Kim Leo A , Keshavan Matcheri , Miller John B , Lizano Paulo
Published: August 2021

Background

Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ.

Methods

This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 × 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI).

Results

Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores.

Conclusions and Relevance

These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.
Sensitivity of Colletotrichum nymphaeae to Six Fungicides and Characterization of Fludioxonil-Resistant Isolates in China
Authors: Usman Hafiz Muhammad , Tan Qin , Fan Fei , Karim Mohammad Mazharul , Yin Wei-Xiao , Zhu Fu-Xing , Luo Chao-Xi
Published: August 2021

Colletotrichum nymphaeae is the dominant species causing anthracnose disease of peach in China. In this study, 140 isolates of C. nymphaeae were assessed for their sensitivity to six fungicides. It was found that C. nymphaeae was highly resistant to carbendazim, procymidone, and boscalid but sensitive to pyraclostrobin and prochloraz. For fludioxonil, the fungus exhibited differential sensitivities (i.e., approximately 14% of isolates were resistant to fludioxonil and the resistance was stable). Fludioxonil-resistant isolates had a mean EC50 value of 2.2380 µg/ml, whereas the mean EC50 value was 0.0194 µg/ml in fludioxonil-sensitive isolates. The mean EC50 values of C. nymphaeae for pyraclostrobin and prochloraz were 0.0083 µg/ml and 0.002 µg/ml, respectively. No cross-resistance was observed between fungicides from different groups. Mycelial growth rate, control efficacy, and osmotic stress responses were significantly different (P < 0.05) between fludioxonil-sensitive (FluS) and -resistant (FluR) isolates, but no significant difference was observed (P > 0.05) in virulence and sporulation between FluS and FluR isolates. No mutation was detected in coding regions of the CnOs-1, Cal, Hk1, Hog1, TPI, and Mrr1 genes. Interestingly, with fludioxonil treatment, the expression of ABC transporter gene atrB was significantly overexpressed in some resistant isolates. However, overexpression of the atrB gene was not detected in one moderately and one highly resistant isolate, indicating that other unknown mechanisms may be involved. Current findings uncovered several effective chemicals and provided the foundation for designing management strategies to practically control peach anthracnose with the most effective demethylation inhibitor fungicides and quinone outside inhibitor fungicides.
New Approaches to an Old Problem: Dollar Spot of Turfgrass
Authors: Sapkota Suraj , Catching Katherine E. , Raymer Paul L. , Martinez-Espinoza Alfredo D. , Bahri Bochra A.
Published: August 2021

Dollar spot, caused by fungal pathogens Clarireedia spp. (formerly Sclerotinia homoeocarpa), is the most common and widely distributed disease of turfgrass worldwide. It can drastically reduce the quality of turfgrass species and affect their aesthetic value and playability. Management of dollar spot typically includes a costly program of multiple application of fungicides within a growing season. Consequently, there have been reported cases of fungicide resistance in populations of Clarireedia spp. Host resistance could be an important component of dollar spot management; however, this approach has been hampered by the lack of sources of resistance because nearly all known warm- and cool-season turfgrass species are susceptible. With the recent advancement in genome sequencing technologies, studies on pathogen genomics and host–pathogen interactions are emerging with the hope of revealing candidate resistance genes in turfgrass and genes for virulence and pathogenicity in Clarireedia spp. Large-scale screening of turfgrass germplasm and quantitative trait locus (QTL) analysis for dollar spot resistance are important for resistance breeding, but only a handful of such studies have been conducted to date. This review summarizes currently available information on the dollar spot pathosystem, taxonomy, pathogen genomics, host–pathogen interaction, genetics of resistance, and QTL mapping and also provides some thoughts for future research prospects to better manage this disease.
An NF‐κB‐responsive long noncoding RNA, PINT, regulates TNF‐α gene transcription by scaffolding p65 and EZH2
Authors: Ye Mengling , Wang Cheng , Zhu Jie , Chen Mingkai , Wang Shuhong , Li Mingxuan , Lu Yajing , Xiao Pingping , Zhou Mengsi , Li Xiaoqing , Zhou Rui
Published: August 2021

Long noncoding RNAs (lncRNAs) are central regulators of the inflammatory response and play an important role in inflammatory diseases. PINT has been reported to be involved in embryonic development and tumorigenesis. However, the potential functions of PINT in the innate immune system are largely unknown. Here, we revealed the transcriptional regulation of inflammatory genes by PINT, whose expression is primarily dependent on the NF‐κB signaling pathway in human and mouse macrophage and intestinal epithelial cell lines. Functionally, PINT selectively regulates the expression of TNF‐α in basal and LPS‐stimulated cells. Mechanistically, PINT acts as a modular scaffold of p65 and EZH2 to coordinate their localization and specify their binding to the target genes. Further, a high expression level of PINT was detected in intestinal mucosal tissues from patients with ulcerative colitis (UC). Together, these findings demonstrate that PINT acts as an activator of inflammatory responses, highlighting the importance of this lncRNA as a potential therapeutic target in infectious diseases and inflammatory diseases.
Paternal high protein diet modulates body composition, insulin sensitivity, epigenetics, and gut microbiota intergenerationally in rats
Authors: Chleilat Faye , Schick Alana , Deleemans Julie M. , Ma Kyle , Alukic Erna , Wong Jolene , Noye Tuplin Erin W. , Nettleton Jodi E. , Reimer Raylene A.
Published: August 2021

Mounting evidence demonstrates that paternal diet programs offspring metabolism. However, the contribution of a pre‐conception paternal high protein (HP) diet to offspring metabolism, gut microbiota, and epigenetic changes remains unclear. Here we show that paternal HP intake in Sprague Dawley rats programs protective metabolic outcomes in offspring. Compared to paternal high fat/sucrose (HF/S), HP diet improved body composition and insulin sensitivity and improved circulating satiety hormones and cecal short‐chain fatty acids compared to HF/S and control diet (P < .05). Further, using 16S rRNA gene sequencing to assess gut microbial composition, we observed increased alpha diversity, distinct bacterial clustering, and increased abundance of Bifidobacterium, Akkermansia, Bacteroides, and Marvinbryantia in HP fathers and/or male and female adult offspring. At the epigenetic level, DNMT1and 3b expression was altered intergenerationally. Our study identifies paternal HP diet as a modulator of gut microbial composition, epigenetic markers, and metabolic function intergenerationally.
Teaching Culturally and Linguistically Diverse Students: Exploring the Challenges and Perceptions of Nursing Faculty
Authors: Guler Nilufer
Published: August 2021

AIM

The aim of this research was to analyze the challenges of nurse faculty when teaching culturally and linguistically diverse (CLD) students.

BACKGROUND

CLD students struggle academically and may need accommodations to be successful. There is a lack of research on challenges faced by faculty when teaching CLD students and faculty perceptions of those challenges.

METHOD

Data were collected via an online survey and in-person interviews.

RESULTS

Several challenges were uncovered. The most common challenges were related to language barriers and lack of support in teaching CLD students.

CONCLUSION

Nursing faculty members have several challenges in teaching CLD nursing students and should receive training to better understand, assess, and instruct their students.
Disability Attitudes of Nursing Students: A Curriculum Intervention
Authors: Edwards Allison P. , Hekel Barbara E. , Cron Stanley
Published: August 2021

People with disabilities (PWD) have reported that health care workers’ negative attitudes are among the most significant barriers to accessing health care services. PWD constitute one quarter of the population, yet the curriculum for PWD is inconsistent. This study describes a curriculum intervention allowing student interaction with a panel of PWD to change nursing student attitudes. Surveys were administered before and after the intervention. Our pilot study did not reveal a significant change in attitudes, which suggests that more exposure to PWD and education may be needed.
Benefits of a Pediatric Clinic Simulation Using Standardized Patients in Family Nurse Practitioner Education
Authors: Weston Cindy , Jones-Schubart Kara , Hare Martha , Gosselin Kevin , Cook Sharon
Published: August 2021

The purpose of this study was to examine the effect of a pediatric clinic simulation with standardized patients on anxiety, self-efficacy, and performance in family nurse practitioner students. A pediatric clinic simulation was developed in which family nurse practitioner students encountered standardized patients presenting for a well-child visit or exhibiting a common chief complaint. Anxiety and self-efficacy were assessed pre/post the simulation intervention, along with faculty-observed student performance. The clinic simulation resulted in increased self-efficacy, lower anxiety, and improved performance (p < .01). High-fidelity simulation of a pediatric clinic was found to foster development of clinical competency, lower student anxiety, and improve self-efficacy.
Gender Differences in Cognitive and Personality Functioning in Patients With Substance Use Disorder
Authors: Höijer Irma , Ilonen Tuula , Löyttyniemi Eliisa , Salokangas Raimo K.R.
Published: August 2021

Objectives:

Substance abuse is associated with impairments in cognition and many serious physical and behavioral consequences both in men and women. Gender differences, however, are not clear. The aim of this study was to examine gender differences in specific neuropsychological measures and personality variables in a sample of single and polysubstance patients.

Methods:

A total of 164 hospitalized patients—97 men and 67 women—underwent neuropsychological tests of verbal capacity, attention, speed of processing, perceptual reasoning, memory and learning, executive functioning, and inhibitory capacity. Personality was measured using the Minnesota Multiphasic Personality Inventory. Associations between neuropsychological measures, personality variables, and gender differences were studied using multiway analysis of covariance controlled for regular substance use in years, onset age of regular substance use, polysubstance use, and education level.

Results:

After adjustment, all the differences between men and women disappeared in the neuropsychological tests. Men reported higher values of somatisation and emotions of depression and anxiety than women. Men were also more suspicious and elicited more disturbed thinking than women.

Conclusions:

Contrary to previous studies, women are not more vulnerable to the effects of substance use compared with men. Notably, men are more vulnerable to negative emotions than women.
Quantifying Urinary and Sexual Dysfunction After Pelvic Fracture
Authors: Lefaivre Kelly A. , Roffey Darren M. , Guy Pierre , O'Brien Peter J. , Broekhuyse Henry M.
Published: August 2021

Objectives:

To quantify the severity of urinary and sexual dysfunction and to evaluate the relationship between urinary and sexual dysfunction, injury, and treatment factors in patients with pelvic fracture.

Design:

Prospective cohort study.

Setting:

Level 1 trauma center.

Patients/Participants:

One hundred thirteen patients with surgically treated pelvic fracture (65.5% OTA/AO 61B fractures; 7 open fractures; 74 men).

Interventions:

Surgical pelvic stabilization.

Main Outcome Measures:

The 36-Item Short Form Health Survey and International Consultation Incontinence Questionnaire responses were collected at baseline, 6 months, and 1, 2, and 5 years. Patients were scored on symptoms of voiding and incontinence, and filling (for women), to derive urinary function. Sexual function was scored as a single domain. Both genders reported urinary and sexual bothersome symptoms. Regression analysis was used to isolate the importance of predictive factors on urinary and sexual function, urinary and sexual bother, and their impact on quality of life.

Results:

Patients with pelvic fracture have significant urinary and sexual dysfunction, which is sustained or worsens over time. Male urinary function was predicted by Injury Severity Score (P = 0.03) and 61C fracture (odds ratio: 3.23, P = 0.04). Female urinary function was predicted by urinary tract injury at admission (odds ratio: 7.57, P = 0.03). Neurologic injury and anterior fixation were identified as significant predictors for male sexual function and sexual bother, whereas urological injuries were important in predicting female urinary and sexual bother (P < 0.01). Sexual function (P = 0.02) and sexual bother (P < 0.001) were important predictors of overall mental well-being in men.

Conclusions:

Urinary and sexual dysfunction are prevalent and sustained in men and women and do not follow the prolonged slow recovery trajectory seen in physical function. Male urinary and sexual dysfunction was closely tied to neurologic injury, whereas female urinary and sexual dysfunction was predicted by the presence of a urinary tract injury. Urinary and sexual dysfunction were important to overall mental well-being in men.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Knee measurements among children with normal alignment, physiologic and pathologic bowing aged 0–3 years old: a systematic review
Authors: Jamil Kamal , Chew Woon Yee , Bohari Nur Eleyana , George Samuel , Isahak Nurul Husna , Boopalachandran Buvanisyaa , Hamizan Aneeza W , Ibrahim Sharaf
Published: August 2021

Distinguishing physiologic and pathologic genu varus is challenging among children below age 3. They can be assessed by measuring intercondylar distance (ICD), clinical tibiofemoral angle (cTFA) or radiologic TFA (rTFA). We aim to determine the knee measurement values among three groups of children. Medline (1946–) and EMBase (1947–) were searched until 31 July 2020 using a search strategy. Studies with original data which reported knee measurements among children with normal alignment, physiologic and pathologic bowing between the ages of 0–3 years were included. In total 1897 studies were identified, and 16 studies included after title and abstract screening. These studies involved 1335 patients with normal alignment, 286 with physiologic and 184 with pathologic bowing. Five studies provided data on ICD, seven on cTFA and eight on rTFA which were pooled for meta-analyses. Normal children had neither measurable ICD nor demonstrable varus on cTFA after 19 months old. The mean (95% confidence interval) ICD for children with pathologic genu varus at 18 months was 4.41 (4.19–4.63). The rTFA for children with pathologic compared to the physiologic bowing by age groups was; 11–20 months: 24.74°(23.22°–26.26°) vs. 19.44°(17.05°–21.84°), 21–30 months: 20.35°(18.13°–22.56°) vs. 14.72°(12.32°–17.12°) and 12–36 months: 32.60°(26.40°–38.80°) vs. 19.14°(17.78°–20.50°). Children above the age of 18 months with genu varus should be closely monitored clinically using ICD or cTFA. An ICD of more than 4 cm may warrant further investigation for pathologic cause. rTFA has limited use in the detection of pathologic varus.
Risk-tailored treatment of splenic marginal zone lymphoma
Authors: Castelli Roberto , Balzarotti Monica , Salvi Emanuele , Simona Rossi Roberta , Lambertenghi Deliliers Giorgio , Bergamaschini Luigi , Gidaro Antonio
Published: August 2021

Splenic marginal zone lymphoma (SMZL) is a rare lymphoproliferative disease involving B-cells and affecting elderly patients. SMZL plague peripheral blood and bone marrow, spleen. Lymph nodes are generally spared. SMZL is due to a protracted antigen stimulation of B lymphocytes and of microenvironment leading B-cell to polyclonal and then oligoclonal/monoclonal growth, promoting lymphoproliferation. Integration of the NOTCH2 and NFk-B signaling has been recently identified as the primary mechanism of neoplastic proliferation in SMZL. In total 20% of cases carry mutations in NOTCH2. Although SMZL has an indolent course, progression to diffuse large B-cell lymphoma occurs in about 10–15% of patients. Establishing the prognosis is a key step in disease management, depending on both individual risk and patients’ health status. This review discusses tailored treatment of SMZL patients. Progression risk factors include nodal and extra-nodal involvement, peripheral lymphocytosis, anemia and thrombocytopenia. Patients with two or more score points have a median survival of <5 years. Watch and wait strategy is appropriate in low-risk and asymptomatic patients, whereas treatment of symptomatic patients ranges from splenectomy to rituximab monotherapy or associated with chemotherapy.
CircASAP1 promotes the development of cervical cancer through sponging miR-338-3p to upregulate RPP25
Authors: Feng Lei , Zhao Manli , Wu Aihui
Published: August 2021

Circular RNAs have been identified as vital regulators to regulate the development of human cancers, including cervical cancer. Therefore, this study was designed to clarify the underlying mechanism of circASAP1 in cervical cancer. The real-time quantitative PCR assay was applied to quantify the expression levels of circASAP1, microRNA (miR)-338-3p, and ribonuclease P and MRP subunit p25 (RPP25) in cervical cancer tissues and cells. The cell proliferation ability was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide and colony-forming assays. The protein expression levels of cyclin D1, proliferating cell nuclear antigen, and RPP25 were assessed by western blot assay. Flow cytometry assays were used to determine the apoptosis and cell cycle distribution of cervical cancer cells. The transwell assay was employed to test the migration and invasion abilities of cervical cancer cells. The interaction relationship between miR-338-3p and circASAP1 or RPP25 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. The xenograft experiment was established to clarify the functional role of circASAP1 inhibition in vivo. CircASAP1 was overexpressed in cervical cancer tissues and cells compared with negative groups. Additionally, the loss-of-functional experiments implied that knockdown of circASAP1 impeded proliferation, migration, and invasion while induced apoptosis and cell cycle arrest in cervical cancer cells along with repressed tumor growth in vivo through regulation of miR-338-3p. In addition, RPP25 was a target mRNA of miR-338-3p, and overexpression of miR-338-3p suppressed proliferation, migration, and invasion while induced apoptosis and cell cycle arrest in cervical cancer cells by suppressing RPP25 expression. Mechanistically, circASAP1 could function as a sponge for miR-338-3p to increase the expression of RPP25, and further regulated proliferation, migration, invasion, apoptosis, and cell cycle program of cervical cancer cells, which might be potential markers for cervical cancer diagnosis.
Long-term extracranial metastatic relapse of an intraventricular solitary fibrous tumor: a case report
Authors: Assi Tarek , Samaha Elie , Nassereddine Hussein
Published: August 2021

Solitary fibrous tumors (SFTs), an uncommon subtype of soft tissue sarcomas mesenchymal, are frequently diagnosed in the intra-thoracic region. Distant metastasis is detected in 10–40% of SFT patients with a predilection site to the lungs; nevertheless, these can occur rarely in the liver, brain, and bones. This entity was also reported in the abdomen, trunk, head, and neck, extremities but also, in the central nervous system (CNS). In the latter form of SFTs, the meninges were mostly affected while only a few cases were reported in the intraventricular and intraparenchymal region with distinct clinical and behavioral characteristics. In this article, we report the rare case of a relapsing intraventricular SFT with secondary extra-cranial metastases to the bones and soft tissues after 11 years of initial diagnosis, with focus on the available data in the literature on CNS SFTs.
Pyrotinib treatment enhances the radiosensitivity in HER2-positive brain metastatic breast cancer patients
Authors: Tian Wuguo , Hao Shuai , Wang Lingli , Chen Yi , Li Zhirong , Luo Donglin
Published: August 2021

Brain metastasis is a common cause of death in HER2-positive breast cancer patients. Currently, it is mainly treated by whole-brain radiotherapy. Pyrotinib is an irreversible pan-ErbB inhibitor, which has demonstrated promising tumor-suppressing activity and acceptable tolerance in previous phase trials. In the present study, we evaluated the efficacy of pyrotinib on HER2-positive brain metastatic breast cancer patients treated with whole-brain radiotherapy. A total of 20 such patients were separated into pyrotinib plus capecitabine and capecitabine-only groups in a 1:1 ratio. All patients met either the primary or secondary endpoints. Oral admission of pyrotinib together with radiotherapy can significantly increase the overall response rate, progression-free survival, time to progression and duration of response of HER2+ brain metastatic breast cancer patients, without causing extra adverse events. In addition, pyrotinib can enhance the radiosensitivity of in-vitro cultured HER2+ breast cancer cell lines. The outcome of our study suggests that pyrotinib might be an effective medication to enhance the tumor radiosensitivity of HER2-positive brain metastatic breast cancer patients.
Circ_0005875 sponges miR-502-5p to promote renal cell carcinoma progression through upregulating E26 transformation specific-1
Authors: Luo Sheng , Deng Fang , Yao Nana , Zheng Fu
Published: August 2021

Increasing evidence has shown that circular RNAs (circRNAs) play critical roles in various cancers, including renal cell carcinoma (RCC). We aimed to explore the role and underlying mechanism of circ_0005875 in RCC. The expression levels of circ_0005875, microRNA-502-5p (miR-502-5p) and E26 transformation specific-1 (ETS1) mRNA were determined by quantitative real-time PCR. Cell proliferation was assessed by Cell Counting Kit-8, colony formation, and 5-Ethynyl-2′-deoxyuridine (EdU) assays. Cell migration and invasion were monitored by wound healing assay and transwell assay, respectively. Flow cytometry analysis was applied to determine cell apoptosis and cell cycle distribution. Western blot assay was performed to measure the protein expression of CyclinD1 and ETS1. The interaction between miR-502-5p and circ_0005875 or ETS1 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft tumor model was established to confirm the role of circ_0005875 in vivo. Circ_0005875 and ETS1 were upregulated and miR-502-5p was downregulated in RCC tissues and cells. Knockdown of circ_0005875 suppressed RCC cell proliferation, migration and invasion, and induced apoptosis and cell cycle arrest. MiR-502-5p was a target of circ_0005875, and miR-502-5p inhibition reversed the inhibitory effects of circ_0005875 knockdown on the malignant behaviors of RCC cells. ETS1 was a direct target of miR-502-5p, and miR-502-5p exerted its anti-tumor role in RCC cells by targeting ETS1. Moreover, circ_0005875 knockdown decreased ETS1 expression by sponging miR-502-5p. Additionally, circ_0005875 depletion suppressed tumor growth in vivo. Circ_0005875 knockdown suppressed RCC progression by regulating miR-502-5p/ETS1 axis, which might provide a promising therapeutic target for RCC.
The prolonged clinical benefit with metronomic chemotherapy (VEX regimen) in metastatic breast cancer patients
Authors: Montagna Emilia , Pagan Eleonora , Cancello Giuseppe , Sangalli Claudia , Bagnardi Vincenzo , Munzone Elisabetta , Salè Emanuela Omodeo , Malengo Daniela , Cazzaniga Marina Elena , Negri Mara , Peruzzotti Giulia , Veronesi Paolo , Viale Giuseppe , Colleoni Marco
Published: August 2021

Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data available on the efficacy and tolerability of prolonged usage of metronomic therapy are limited. We analyzed patients with MBC, enrolled in a clinical trial, who obtained a prolonged clinical benefit for a duration of at least 12 months with vinorelbine 30 or 40 mg orally three times a week, cyclophosphamide 50 mg daily and capecitabine 500 mg three times a day (VEX regimen). The patients were treated at the European Institute of Oncology, Milan. We identified 67 MBC patients. The median age before starting the VEX regimen was 53 years. There were 59 patients (88%) who had hormone-receptors positive and HER2 negative BC. We had 37 patients who received VEX as the first-line treatment for MBC, while 30 patients were pretreated. The objective response rate was 49% (95% CI, 37–62). The median duration of VEX treatment after the first year was 14 months (min–max range 0.3–81.3 months). The progression-free survival at 3 years was 25.4% (95% CI, 15.7–36.2) and at 4 years was 18.5% (95% CI, 10.1–28.8 time 0 corresponds to 1 year after starting VEX). A total of 25 patients required a dose reduction, 7% of patients experienced G3 hand and foot syndrome. Metronomic VEX regimen can induce prolonged clinical benefit in MBC. On the basis of this long-term safety evaluation, there is no evidence of specific cumulative or delayed toxicities with metronomic chemotherapy.
Combination of radiotherapy and targeted therapy for melanoma brain metastases: a systematic review
Authors: Ge Yi , Che Xuanlin , Gao Xin , Zhao Shuang , Su Juan
Published: August 2021

Radiotherapy is a mainstay of efficient treatment of brain metastases from solid tumors. Immunotherapy has improved the survival of metastatic cancer patients across many tumor types. However, targeted therapy is a feasible alternative for patients unable to continue immunotherapy or with poor outcomes of immunotherapy. The combination of radiotherapy and targeted therapy for the treatment of brain metastases has a strong theoretical underpinning, but data on the efficacy and safety of this combination is still limited. A systematic search of PubMed, Embase, Web of Science and the Cochrane library database was conducted. Eleven studies were included for a total of 316 patients. Median OS was about 6.2–17.8 months from radiotherapy. Weighted survival and local control at 1 and 2 years were correlated (50.1 and 17.8%, 90.7 and 14.7% at 1 and 2 year, respectively). Radiotherapy given before or concurrently to targeted therapy provided the best effect on the outcome. For patients with brain metastases from cutaneous melanoma, the addition of concurrent targeted therapy to brain radiotherapy can increase survival and provide long-term control.
The Role of Beliefs and Psychological Factors in Caring of Patients With Cancer
Authors: Eghtedar Samereh , Jasemi Madineh , Habibzadeh Hossein
Published: August 2021

Cancer affects not only the patient but also family members as informal caregivers. In order for family caregivers to achieve balance and improve their caregiving roles, it is essential to identify the beliefs and psychological aspects affecting them. The present study was carried out qualitatively with a descriptive phenomenological design in 2020. The main participants in this study were selected from one of the major referral centers for cancer patients in West Azerbaijan Province, located in northwestern, Iran. Twenty-two family caregivers were selected through a purposive sampling method. Data analysis showed that the 3 main themes of “emotional and religious preconceptions,” “feeling committed to caring for beloveds,” and “resilience” played a prominent role in family caregivers. These factors led to caregivers' commitment to and responsibility for care. Holistic care necessitates consideration of all aspects of human life. The results of this study led to an understanding of the complex tendencies and feelings of family caregivers. Based on the results, it was found that care is influenced by beliefs, religious preconceptions, sociocultural, and psychological factors. Identifying these variables helps medical staff share planning, interventions, and counseling with family caregivers and address issues that affect them.
A Randomized Controlled Trial on the Efficacy of Integrated Yoga on Pregnancy Outcome
Authors: Pais Maria , Pai Muralidhar V. , Kamath Asha , Bhat Ramesh , Bhat Parvathy , Joisa Ganapathi H.
Published: August 2021

Physiological and biochemical changes occur in pregnancy to nurture the developing fetus. Pregnancy-related experience is unique to every woman. Pregnancy symptoms and complications can range from mild to severe. Many women can lower their risk by performing different therapies. In this context, the present study targets to evaluate the efficacy of integrated yoga consisting of (asanas and pranayama) on pregnancy to reduce the risk of complications. This study is a prospective randomized controlled single-blinded trial with parallel arms: the intervention arm received specific integrated yoga therapy; the control arm received routine standard care from 18 to 22 weeks of gestation until delivery. The incidence of preeclampsia and preterm delivery was lower in the intervention arm. Women in the intervention arm delivered at higher gestational age. Apgar scores and birth weights of neonates were significantly higher in the intervention arm. The findings suggest that yoga is a safe and effective intervention during pregnancy to reduce or prevent pregnancy-related complications. However, further randomized controlled trials are needed to provide firmer evidence regarding the utility and validity of yoga intervention during pregnancy.
Granular Cell Tumor of the Orbit: Review of the Literature and a Proposed Treatment Modality
Authors: Barrantes Paula Cortes , Zhou Paul , MacDonald Shannon M. , Ioakeim-Ioannidou Myrsini , Lee Nahyoung Grace
Published: August 2021

Purpose:

To document a unique case of granular cell tumor of the orbit, located lateral to and abutting the optic nerve, that benefited from treatment with proton beam irradiation, with a comprehensive review of the literature on granular cell tumor of the orbit.

Methods:

Clinicopathologic case report with detailed imaging features and histopathologic and immunohistochemical evaluation for cytoplasmic tumor biomarkers differentiating granular cell tumor (GCT) from it mimicking lesions with relevant literature citations. The authors reviewed 20 cases of orbital GCT from 2011 to 2020 in addition to 40 cases from 1948 to 2011 and included a summary of imaging and clinical features, outcomes, and recommended treatment modalities.

Results:

A 32-year-old man with 1-year history of left retrobulbar pain and diplopia on lateral gaze, intermittent left eyelid swelling, and a tonic left pupil was found to have a fusiform intraconal mass extending toward the orbital apex and abutting the optic nerve. Histopathologic and immunohistochemical investigations collectively supplied data diagnostic of a GCT with an initial low proliferation rate. GCT is a soft tissue neoplasm that originates in the nervous system and can occur anywhere in the body. This enhancing tumor is isointense to gray matter on T1-weighted MRI, hypointense on T2. After an incisional biopsy, the patient’s symptoms persisted, and follow-up imaging several months later revealed further growth of the mass. The impossibility of complete surgical removal prompted the decision to treat with proton beam radiation therapy, which resulted in substantial regression in the size of the residual tumor. Most frequently involving the inferior rectus muscle (42%), orbital GCT is usually benign with only 4 reported cases of malignant orbital GCT (7%). Wide surgical resection with complete removal is usually curative for benign orbital GCT, and proton beam radiation therapy can aid in tumor shrinkage.

Conclusions:

GCT should be considered in the differential diagnosis when encountering patients with mass lesions involving the extraocular muscles, peripheral nerves, or less frequently, the optic nerve or orbital apex. Immunohistochemical analysis of biopsied tissue is required for the definitive diagnosis of GCT. Consideration of adjuvant therapies such as proton beam radiation therapy may be appropriate in cases of incomplete surgical resection of benign GCT. Proton beam radiation therapy can be an excellent therapeutic option for symptomatic relief and residual tumor size reduction with an acceptable toxicity profile.
Serum levels of alpha1-antitrypsin isoforms in patients with ovarian clear cell carcinoma: An exploratory study
Authors: Chen Sung-Yao , Chang Ting-Chang , Lin Chiao-Yun , Lai Chyong-Huey , Wu Ren-Chin , Yang Lan-Yang , Chang Wei-Yang , Lee Yun-Shien , Yang Wei-Chung Vivian , Chao Angel
Published: August 2021

Background:

Ovarian clear cell carcinoma (OCCC) is frequently associated with endometriosis. Since serum levels of cancer antigen 125 (CA125) have limited diagnostic and prognostic value in this malignancy, there is an unmet need for reliable and specific biomarkers. Previous findings indicated that alpha 1-antitrypsin isoforms (isoAAT) are significantly increased in the peritoneal fluid of patients with endometriosis. This study was undertaken to examine whether serum isoAAT levels in patients with OCCC differ from those measured in women with endometriosis or benign ovarian tumors. We also investigated whether this biomarker may be useful for predicting survival in OCCC.

Methods:

Paired serum samples before and after debulking surgery were collected from 27 patients with OCCC. All sera from patients with endometriosis (n = 44) and benign ovarian tumors (n = 32) were obtained in the pretreatment phase. Serum isoAAT levels were assayed using a proprietary ELISA kit.

Results:

The highest levels of serum isoAAT (median, range) were identified in patients with OCCC (preoperative values: 160.9 ng/mL, range, 101.4−1098.8 ng/mL), followed by patients with endometriosis (125.0 and 83.4−473.2 ng/mL), and those with benign tumors (125.2 and 60.5−191.3 ng/mL). The differences in serum isoAAT levels between patients with OCCC and benign tumors were significant (p = 0.041). Debulking surgery of OCCC resulted in a significant decrease in serum isoAAT levels compared with the preoperative period (median, 160.9 versus 113.0 ng/mL, respectively, p = 0.012). As for prognostic prediction, we found that none of the nine patients with OCCC and serum isoAAT levels ≤130 ng/mL died of disease.

Conclusion:

Serum isoAAT levels may be diagnostically useful to distinguish OCCC from benign ovarian tumors and could also serve as a potential prognostic marker.
Hepatitis D virus dual infection increased the risk of hepatocellular carcinoma compared with hepatitis B virus mono infection: A meta-analysis
Authors: Chang Tien-En , Su Chien-Wei , Huang Yi-Shin , Huang Yi-Hsiang , Hou Ming-Chih , Wu Jaw-Ching
Published: August 2021

Background:

Hepatitis delta virus (HDV) is a defective virus that relies on the supply of hepatitis B surface antigen (HBsAg) from hepatitis B virus (HBV) to assemble HDV virions and infect hepatocytes. However, controversy remains in whether the presence of HDV increases the risk of hepatocellular carcinoma (HCC). Our aim is to evaluate the influence of HDV on the risk of HCC through a systematic review and meta-analysis.

Methods:

A review of all English-language literature was conducted in the major medical databases using the subject search terms “hepatocellular carcinoma,” “liver cancer,” “hepatic tumor,” and “hepatitis delta.” A meta-analysis of the qualifying publications was then performed.

Results:

The meta-analysis included 21 studies, which revealed a significantly higher risk of HCC among patients with HDV/HBV dual infection (odds ratio [OR] = 2.08, 95% confidence interval [CI], 1.37-3.14, p < 0.01) compared with those with HBV monoinfection. Those with HDV/HBV dual infection remained at higher risk of HCC in the subgroup analysis, irrespective of the status of hepatitis C virus (HCV) or human immunodeficiency virus (HIV) coinfection and in different ethnicities. The HCC risk remained higher in patients with HDV/HBV dual infection with heterogeneous fibrosis stage (OR = 2.04, 95% CI, 1.31-3.17, p < 0.01). The difference in the risk of HCC between HDV/HBV dual infection and HBV monoinfection was not statistically significant in patients with cirrhosis or advanced fibrosis (OR = 1.84, 95% CI, 0.48-7.02, p = 0.37). However, this subgroup comprised only two studies.

Conclusion:

HDV and HBV dual infection significantly increase the risk of HCC development compared with HBV monoinfection.
Acute Traumatic Stress Screening Can Identify Patients and Their Partners at Risk for Posttraumatic Stress Disorder Symptoms After a Cardiac Arrest
Authors: Armand Sophia , Wagner Mette K. , Ozenne Brice , Verbunt Jeanine , Sep Simone J.S. , Berg Selina K. , Knudsen Gitte M. , Stenbæk Dea S.
Published: August 2021

Background

Posttraumatic stress disorder (PTSD) is prevalent in patients who have had a cardiac arrest and their partners. Accordingly, acute traumatic stress screening is recommended, but its association with later PTSD symptoms has never been addressed in postresuscitation settings.

Objective

The aim of this study was to examine whether acute traumatic stress is associated with PTSD symptoms in patients who have had a cardiac arrest and their partners.

Methods

This multicenter longitudinal study of 141 patients and 97 partners measures acute traumatic stress at 3 weeks and PTSD symptoms at 3 months and 1 year after resuscitation, using the Impact of Event Scale. Linear regression models were used to evaluate the association between severity of acute traumatic stress and PTSD symptoms and post hoc to explore effects of group (patients/partners), age, and sex on acute traumatic stress severity. We categorized Impact of Event Scale scores higher than 26 at 3 months and 1 year as clinical severe PTSD symptoms.

Results

Higher acute traumatic stress severity is significantly positively associated with higher PTSD symptom severity at 3 months (patients and partners: P < .001) and 1 year (patients and partners: P < .001) postresuscitation, with the strongest association for women compared with men (P = .03). Acute traumatic stress was higher in women compared with men across groups (P = .02). Clinical severe PTSD symptoms were present in 26% to 28% of patients and 45% to 48% of partners.

Conclusion

Experiencing a cardiac arrest may elicit clinical severe PTSD symptoms in patients, but particularly in their partners. Screening patients and partners for acute traumatic stress postresuscitation is warranted to identify those at increased risk of long-term PTSD symptoms.
The Effects of Nonconventional Exercise on Functional Capacity and Quality of Life in Patients With Heart Failure
Authors: Hong Kevin , Esquivel Jill Howie
Published: August 2021

Background

Patients with heart failure (HF) experience decreased functional capacity (FC) and poor quality of life (QOL). Exercise and cardiac rehabilitation programs are an integral part of managing HF because they have been shown to provide a multitude of benefits including improved FC and QOL. In recent years, nonconventional exercise interventions have offered a promising approach for promoting physical activity in patients with HF, thus leading to improved FC and QOL.

Purpose

This review aimed to assess the effects of either supervised or unsupervised, nonconventional exercise interventions on FC and QOL in patients with HF.

Methods

A literature search using PubMed, Web of Science, Cochrane Library, and Science Direct for relevant studies was conducted. Experimental studies that examined nonconventional exercise interventions in adults with HF were eligible for inclusion. Two reviewers independently selected the studies, assessed the quality of the studies, and then narratively synthesized each study.

Results

The authors identified 14 studies that included 879 patients with HF. Most studies were ranked moderate to high quality where 13 studies found significantly improved FC and 10 found significantly improved QOL after nonconventional exercises.

Conclusions

This review provides preliminary evidence that patients with HF may benefit from alternative forms of exercise to improve FC and QOL. Walking was the most frequent exercise, but other nonconventional exercises such as aquatic exercise, dance, resistance training, stretching, Tai Chi, and yoga are also promising interventions that may improve FC and QOL in patients with HF.

Clinical Implications

Nonconventional exercise can be a convenient and alternative method of exercise versus traditional cardiac rehabilitation, thereby providing new opportunities that can lead to improved FC and QOL.
Hemorheological Approach to Improve Perfusion of Red Blood Cells with Reduced Deformability Using Drag-Reducing Polymer (In Vitro Study)
Authors: Crompton Dan , Gudla Shushma , Waters Jonathan H. , Sundd Prithu , Kameneva Marina V.
Published: August 2021

Drag-reducing polymers (DRPs) are nontoxic water-soluble blood additives that have been shown to beneficially alter hemodynamics when delivered intravenously in nanomolar concentrations. This study examines the ability of DRPs to alter the traffic of mixtures of normal and less-deformable red blood cells (RBCs) through branched microchannels and is intended to support and expand upon previous experiments within straight capillary tubes to promote DRPs for future clinical use. Branched polydimethylsiloxane microchannels were perfused with a mixture of normal bovine RBCs also containing heat-treated less-deformable RBCs at a hematocrit of 30% with 10 ppm of the DRP poly(ethylene oxide) (MW 4M Da). Suspensions were driven by syringe pump, collected at outlets, and RBC dimensions measured while subject to shear stress to determine the proportion of healthy RBCs in each sample. DRPs eliminated evidence of the plasma skimming phenomena and significantly increased the pressure drop across microchannels. Further, DRPs were found to cause an increase in the proportion of healthy RBCs exiting the branch outlet from –8.5 ± 2.5% (control groups) to +12.1 ± 5.4% (n = 6, p = 0.02). These results suggest DRP additives may be used to improve the perfusion of less-deformable RBCs in vivo and indicates their potential for future clinical use.