bluuebunny/crossref_metadata_2025_split huggingface dataset:
The miR-199a-5p/PD-L1 axis regulates cell proliferation, migration and invasion in follicular thyroid carcinoma
Authors: Lin Jianguang , Qiu Yanru , Zheng Xueqin , Dai Yijun , Xu Tianwen 
Published: July 2022

Abstract
Background
Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid and easily develops into distant metastasis. PD-L1 is known to be associated with the carcinogenesis and progression of thyroid carcinoma. Our study aimed to investigate the biological functions of PD-L1 and to identify miRNAs that were responsible for modulating the activity of PD-L1.

Methods
A total of 72 patients with FTC at The Second Affiliated Hospital of Fujian Medical University were enrolled in this retrospective study. Immunohistochemical (IHC) assay was used to measure PD-L1 expression in FTC. The association between PD-L1 expression and clinicopathologic characteristics was evaluated. Bioinformatics analysis, RT–qPCR and western blotting were used to examine the relationships between miR-199a-5p, PD-L1 and Claudin-1. Cell proliferation, migration and invasion were evaluated by using CCK8 and Transwell migration and invasion assays. Target prediction and luciferase reporter assays were performed to verify the binding between miR-199a-5p and PD-L1. Rescue assay was performed to confirm whether PD-L1 downregulation abolished the inhibitory effect of miR-199a-5p.

Results
Among 72 pairs of tumor and normal specimens, the proportion of PD-L1 positive samples was higher in FTC tissues than in normal tissues. The results of ESTIMATE and CIBERSORT illustrated that there was a positive correlation between PD-L1 expression and immune infiltration, especially regulatory T cells and M1 macrophages. Prediction of immunotherapy revealed that patients with high PD-L1 expression might benefit from immune checkpoint inhibitors. Transwell migration and invasion assays showed that PD-L1 downregulation in FTC cells could significantly inhibit cell migration and invasion. The bioinformatics analysis and luciferase activity results indicated that PD-L1 was a potential target of miR-199a-5p. Knockdown of PD-L1 reversed the miR-199a-5p inhibitor mediated promotion effect. In addition, we found that PD-L1 expression was positively correlated with Claudin-1 expression and that miR-199a-5p affected the progression of FTC cells through the negative regulation of PD-L1 and Claudin-1.

Conclusions
Our study revealed that PD-L1 expression was elevated in FTC and was closely associated with tumor aggressiveness and progression. MiR-199a-5p has a functional role in the progression and metastasis of FTC by regulating PD-L1 and Claudin-1 expression.
Factor structure, measurement invariance, and concurrent validity of the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder scale-7 in a Norwegian psychiatric outpatient sample
Authors: Brattmyr Martin , Lindberg Martin Schevik , Solem Stian , Hjemdal Odin , Havnen Audun 
Published: July 2022

Abstract
Objective
The aim of this study was to test factor structure, measurement invariance, and concurrent validity of the nine item Patient Health Questionnaire-9 (PHQ-9) and the seven item Generalized Anxiety Disorder scale-7 (GAD-7) in a heterogeneous outpatient sample.

Method
Outpatients completed the PHQ-9, GAD-7, and the Working Social Adjustment Scale (WSAS) before starting treatment. Study design was cross-sectional, with convenience sampling. The total sample consisted of 831 participants (61% women).

Results
Both PHQ-9 and GAD-7 demonstrated better fit statistics with two-factor and bifactor solutions consisting of a cognitive and somatic factor. Omega hierarchical was .78 for PHQ-9 and .81 for GAD-7. Both instruments achieved scalar invariance across gender, diagnosis, and comorbidity. However, the somatic factors demonstrated poor discriminant validity. These factors are not well separatable and risks being too similar if used together. The general factors of both instruments were most associated with functional impairment, although PHQ-9 demonstrated a stronger association with WSAS (γ = .74, r2 = .62) than GAD-7 (γ = .54, r2 = .32). Using latent mean difference, women and patients with comorbidity had significantly higher scores of both depression and anxiety.

Conclusion
This study shows that the PHQ-9 and GAD-7 may be used as one-dimensional instruments in clinical settings. Tests for measurement invariance supported that both measures are understood and interpreted comparably across gender and diagnostic subgroups.
Implementation of buprenorphine services in NYC syringe services programs: a qualitative process evaluation
Authors: Jakubowski Andrea , Rath Caroline , Harocopos Alex , Wright Monique , Welch Alice , Kattan Jessica , Navos Behrends Czarina , Lopez-Castro Teresa , Fox Aaron D. 
Published: July 2022

Abstract
Background
Syringe services programs (SSPs) hold promise for providing buprenorphine treatment access to people with opioid use disorder (OUD) who are reluctant to seek care elsewhere. In 2017, the New York City Department of Health and Mental Hygiene (DOHMH) provided funding and technical assistance to nine SSPs to develop “low-threshold” buprenorphine services as part of a multipronged initiative to lower opioid-related overdose rates. The aim of this study was to identify barriers to and facilitators of implementing SSP-based buprenorphine services.

Methods
We conducted 26 semi-structured qualitative interviews from April 2019 to November 2019 at eight SSPs in NYC that received funding and technical assistance from DOHMH. Interviews were conducted with three categories of staff: leadership (i.e., buprenorphine program management or leadership, eight interviews), staff (i.e., buprenorphine coordinators or other staff, eleven interviews), and buprenorphine providers (six interviews). We identified themes related to barriers and facilitators to program implementation using thematic analysis. We make recommendations for implementation based on our findings.

Results
Programs differed in their stage of development, location of services provided, and provider type, availability, and practices. Barriers to providing buprenorphine services at SSPs included gaps in staff knowledge and comfort communicating with participants about buprenorphine, difficulty hiring buprenorphine providers, managing tension between harm reduction and traditional OUD treatment philosophies, and financial constraints. Challenges also arose from serving a population with unmet psychosocial needs. Implementation facilitators included technical assistance from DOHMH, designated buprenorphine coordinators, offering other supportive services to participants, and telehealth to bridge gaps in provider availability. Key recommendations include: (1) health departments should provide support for SSPs in training staff, building health service infrastructure and developing policies and procedures, (2) SSPs should designate a buprenorphine coordinator and ensure regular training on buprenorphine for frontline staff, and (3) buprenorphine providers should be selected or supported to use a harm reduction approach to buprenorphine treatment.

Conclusions
Despite encountering challenges, SSPs implemented buprenorphine services outside of conventional OUD treatment settings. Our findings have implications for health departments, SSPs, and other community organizations implementing buprenorphine services. Expansion of low-threshold buprenorphine services is a promising strategy to address the opioid overdose epidemic.
Pyrokinin receptor silencing in females of the southern cattle tick Rhipicephalus (Boophilus) microplus is associated with a reproductive fitness cost
Authors: Wulff Juan P. , Temeyer Kevin B. , Tidwell Jason P. , Schlechte Kristie G. , Xiong Caixing , Lohmeyer Kimberly H. , Pietrantonio Patricia V. 
Published: July 2022

Abstract
Background
Rhipicephalusmicroplus is the vector of deadly cattle pathogens, especially Babesia spp., for which a recombinant vaccine is not available. Therefore, disease control depends on tick vector control. However, R.microplus populations worldwide have developed resistance to available acaricides, prompting the search for novel acaricide targets. G protein-coupled receptors (GPCRs) are involved in the regulation of many physiological processes and have been suggested as druggable targets for the control of arthropod vectors. Arthropod-specific signaling systems of small neuropeptides are being investigated for this purpose. The pyrokinin receptor (PKR) is a GPCR previously characterized in ticks. Myotropic activity of pyrokinins in feeding-related tissues of Rhipicephalussanguineus and Ixodesscapularis was recently reported.

Methods
The R.microplus pyrokinin receptor (Rhimi-PKR) was silenced through RNA interference (RNAi) in female ticks. To optimize RNAi, a dual-luciferase assay was applied to determine the silencing efficiency of two Rhimi-PKR double-stranded RNAs (dsRNA) prior to injecting dsRNA in ticks to be placed on cattle. Phenotypic variables of female ticks obtained at the endpoint of the RNAi experiment were compared to those of control female ticks (non-injected and beta-lactamase dsRNA-injected). Rhimi-PKR silencing was verified by quantitative reverse-transcriptase PCR in whole females and dissected tissues.

Results
The Rhimi-PKR transcript was expressed in all developmental stages. Rhimi-PKR silencing was confirmed in whole ticks 4 days after injection, and in the tick carcass, ovary and synganglion 6 days after injection. Rhimi-PKR silencing was associated with an increased mortality and decreased weight of both surviving females and egg masses (P < 0.05). Delays in repletion, pre-oviposition and incubation periods were observed (P < 0.05).

Conclusions
Rhimi-PKR silencing negatively affected female reproductive fitness. The PKR appears to be directly or indirectly associated with the regulation of female feeding and/or reproductive output in R.microplus. Antagonists of the pyrokinin signaling system could be explored for tick control.

Graphical abstract
Effectiveness and safety of allergen immunotherapy in patients with allergic rhinitis complicated by rheumatic autoimmune diseases: a case series study
Authors: Fujioka Kazuki , Kasahara Akiko , Kida Takashi , Fujii Wataru , Seno Takahiro , Wada Makoto , Kohno Masataka , Kawahito Yutaka 
Published: July 2022

Abstract
Background
Allergen immunotherapy (AIT) is the only treatment that has modified the natural history of allergic diseases. However, since its overall effect on the immune system has not been elucidated, AIT is either absolutely or relatively contraindicated in patients with rheumatic autoimmune diseases (RADs). Therefore, there have been no long-term observations of patients with RADs receiving AIT; thus, the effectiveness and safety of AIT in these patients remain unclear.

Methods
This was a single-center retrospective observational study. RAD patients receiving AIT for allergic rhinitis at our institution were selected. Changes in the activity of RAD patients were investigated for 2 years from baseline, including those who discontinued AIT. The effectiveness of AIT was also investigated using the Japan Allergic Rhinitis Standard Quality of Life Questionnaire.

Results
Thirteen patients with RADs were enrolled in the study. All patients received sublingual immunotherapy, of which four discontinued AIT owing to adverse events. Among all patients, the symptoms of RADs in three patients worsened during the observation period; however, none of them were causally related to AIT. Most of the adverse events associated with AIT were mild, in which only one patient required drug intervention due to worsening rhinitis symptoms. In the nine patients who were able to continue AIT, their eye and nasal symptom scores showed a significant improvement from 1.67 (1.5–2.0) at baseline to 0.67 (0–1.17) in the 2nd year of treatment (p = 0.0141).

Conclusions
AIT is a safe and effective treatment modality for patients with allergic rhinitis complicated by RADs.
Gross hematuria can be an impact of severe acute respiratory syndrome coronavirus 2 vaccination on immunoglobulin A nephropathy: a case report
Authors: Kanamori Hiroshi 
Published: July 2022

Abstract
Background
Immunoglobulin A nephropathy is typically accelerated by upper respiratory tract infections and can relapse following vaccination. There have been reports of patients who presented with immunoglobulin A nephropathy flares with or without gross hematuria following coronavirus disease 2019 vaccination. However, this relationship remains to be elucidated.

Case presentation
Herein, we present the case of a patient with newly diagnosed immunoglobulin A nephropathy who presented with gross hematuria following the second dose of coronavirus disease 2019 vaccine. A 21-year-old Japanese woman presented with fever and new-onset gross hematuria 1 day after receiving the second dose of the coronavirus disease 2019 vaccine (Pfizer). She had microhematuria without proteinuria for 2 years at the time of her medical check-up. Gross hematuria resolved 6 days after the second dose of the coronavirus disease 2019 vaccine; however, microhematuria (> 100 per high-power field) and mild proteinuria were observed. She was admitted to our hospital 4 weeks after the second vaccination because of persistent urinary abnormalities. She was well before the vaccination and did not have any pulmonary involvement on chest radiography or any symptoms suggestive of coronavirus disease 2019. Renal biopsy revealed an immunoglobulin A nephropathy. The Oxford MEST-C score was M0E0S0T0C0. Our patient’s urinary abnormalities implied exacerbation of immunoglobulin A nephropathy after coronavirus disease 2019 vaccination.

Conclusions
In our case, gross hematuria served as a trigger for immunoglobulin A nephropathy diagnosis, suggesting that nephrologists should pay close attention to gross hematuria and urinalysis after coronavirus disease 2019 vaccination.
Clinical status of patients 1 year after hospital discharge following recovery from COVID-19: a prospective cohort study
Authors: Li Dapeng , Liao Xuejiao , Ma Zhenghua , Zhang Lina , Dong Jingke , Zheng Guoqin , Zi Mei , Peng Wujian , Wei Lanlan , Li Zhiyan , Kong Yingjun , Wang Lifei , Liu Dongjing , Wang Fang , He Qing , Li Guobao , Zhang Zheng , Liu Lei 
Published: July 2022

Abstract
Background
The long-term clinical status of coronavirus disease 2019 (COVID-19) in recovered patients remains largely unknown. This prospective cohort study evaluated clinical status of COVID-19 and explored the associated risk factors.

Methods
At the outpatient visit, patients underwent routine blood tests, physical examinations, pulmonary function tests, 6-min walk test, high-resolution computed tomography (CT) of the chest, and extrapulmonary organ function tests.

Results
230 patients were analyzed. Half (52.7%) reported at least one symptom, most commonly fatigue (20.3%) and sleep difficulties (15.8%). Anxiety (8.2%), depression (11.3%), post-traumatic symptoms (10.3%), and sleep disorders (26.3%) were also reported. Diffusion impairments were found in 35.4% of the patients. Abnormal chest CT scans were present in 63.5% of the patients, mainly reticulation and ground-glass opacities. Further, a persistent decline in kidney function was observed after discharge. SARS-CoV-2-specific antibodies of IgA, IgG, and IgM were positive in 56.4%, 96.3%, and 15.2% of patients, respectively. Multivariable logistic regression showed that disease severity, age, and sex were closely related to patient recovery.

Conclusions
One year after hospital discharge, patients recovered from COVID-19 continued to experience both pulmonary and extrapulmonary dysfunction. While paying attention to pulmonary manifestations of COVID-19, follow-up studies on extrapulmonary manifestations should be strengthened.
Burden of female breast cancer in the Middle East and North Africa region, 1990–2019
Authors: Safiri Saeid , Noori Maryam , Nejadghaderi Seyed Aria , Sullman Mark J. M. , Bragazzi Nicola Luigi , Almasi-Hashiani Amir , Mansournia Mohammad Ali , Kolahi Ali-Asghar 
Published: July 2022

Abstract
Background
There is no region-specific publication investigating the attributable burden of breast cancer, particularly among females. This article reported the burden of female breast cancer in the Middle East and North Africa (MENA) region, and its attributable risk factors between 1990 and 2019, by age, sex, and socio-demographic index (SDI).

Methods
Publicly available data on the incidence, death and disability-adjusted life years (DALY) were retrieved from the Global Burden of Disease (GBD) 2019 study for the 21 countries and territories in MENA, between 1990 and 2019, along with 95% uncertainty intervals (UIs). The relationship between the burden of female breast cancer, in terms of DALYs, and the SDI were also assessed using Smoothing Spline models.

Results
In 2019, the regional age-standardised incidence and death rates of female breast cancer were 37.5 and 15.2 per 100,000, which represent a 90.9 and 24.0% increase since 1990, respectively. In addition, in 2019 the regional age-standardised DALY rate was 472.7 per 100,000, which was 19.5% higher than in 1990. In 2019, the death rate increased steadily with advancing age, while the DALY rate increased steeply with age and reached its peak in the 70–74 age group. There was a positive association between SDI and the burden of breast cancer over the period 1990 to 2019. Moreover, in 2019 high fasting plasma glucose (6.9%) contributed to the largest proportion of attributable DALYs for female breast cancer in the MENA region.

Conclusions
There was a significant increase in the incidence rate of female breast cancer in MENA over the past three decades, although the death and DALY rates were both largely unchanged. Preventive programs targeting the major risk factors should be implemented in the region.
Evidence based recommendations for an optimal prenatal supplement for women in the US: vitamins and related nutrients
Authors: Adams James B. , Kirby Jasmine K. , Sorensen Jacob C. , Pollard Elena L. , Audhya Tapan 
Published: July 2022

AbstractThe blood levels of most vitamins decrease during pregnancy if un-supplemented, including vitamins A, C, D, K, B1, B3, B5, B6, folate, biotin, and B12. Sub-optimal intake of vitamins from preconception through pregnancy increases the risk of many pregnancy complications and infant health problems. In the U.S., dietary intake of vitamins is often below recommended intakes, especially for vitamin D, choline and DHA. Many studies suggest that insufficient vitamin intake is associated with a wide range of pregnancy complications (anemia, Cesarean section, depression, gestational diabetes, hypertension, infertility, preeclampsia, and premature rupture of membranes) and infant health problems (asthma/wheeze, autism, low birth weight, congenital heart defects, intellectual development, intrauterine growth restriction, miscarriage, neural tube defects, orofacial defects, and preterm birth). The primary goal of this paper is to review the research literature and propose evidence-based recommendations for the optimal level of prenatal supplementation for each vitamin for most women in the United States. A secondary goal was to compare these new recommendations with the levels of vitamins in over 180 commercial prenatal supplements. The analysis found that prenatal supplements vary widely in content, often contained only a subset of essential vitamins, and the levels were often below our recommendations. This suggests that increasing prenatal vitamin supplementation to the levels recommended here may reduce the incidence of many pregnancy complications and infant health problems which currently occur.
Calculation and management of ketogenic diet parenteral nutrition in super-refractory status epilepticus
Authors: Zeng Ya , Mu Jie , Zhou Dong 
Published: July 2022

AbstractSuper-refractory status epilepticus (SRSE) is an important neurological emergency associated with high mortality and morbidity and poses a heavy economic burden on patients. Ketogenic diet parenteral nutrition (KD-PN) is ketogenic diet therapy provided through parenteral administration and may be an adjuvant treatment for these who cannot accept enteral diet. However, the calculation and management of KD-PN presents a challenge for clinicians. This review focuses on the practical aspects of KD-PN therapy for treatment of SRSE, including the dietary composition, potential drug-diet interactions, and monitoring during KD-PN treatment. As with all SRSE treatments, KD-PN has many adverse effects, like hyperlipemia, hepatotoxicity, metabolic acidosis, insufficient ketosis or hyper-ketosis, and propofol infusion syndrome. We summarize monitoring and treatment methods in our review. This review provides some practical aspects for treatment of SRSE.
Neurophysiological evaluation of juvenile systemic lupus erythematosus
Authors: Thabet Alaa M. , Elnwam Sara A. , Mekky Jaidaa F. , Abdelghany Hayam M. , Fathy Hanan M. 
Published: July 2022

Abstract
Background
Peripheral nervous system and the central nervous system involvement in systemic lupus erythematosus (SLE) patients are one of the major causes of morbidity and mortality. The aim of this work was to study the nervous system clinically and electrophysiologically in children with systemic lupus erythematosus.

Results
The study was carried out on thirty-eight children with SLE. Their age ranged from 5 to 16 years. The most encountered neurologic manifestations were tremors. It was observed in 47.4% of children, followed by headache in 39.5%, sensory manifestation as numbness in 23.7%, cerebrovascular stroke in 5.3%, and chorea in 2.6%, which was unilateral mostly in the upper limb, tics, and convulsion had the same percentage. Around 16% of children had positive findings in MRI, such as cerebrovascular disease, minimal hematoma, pseudotumorcerebri, vasculitis, and ectatic ventricles. Subclinical peripheral neuropathy was reported in nearly 52.6% of children, and clinical peripheral neuropathy was reported in 23.6%. Pure sensory subclinical peripheral neuropathy was detected in 13.1% of children, but mixed subclinical peripheral neuropathy was detected in 39.4%. Nearly 53% of studied children had an abnormal somatosensory-evoked potential study of posterior tibial and median nerves.

Conclusion
The current study reported that the clinical neurological manifestations in juvenile SLE is common. Peripheral neuropathy is commonly detected, which could be either clinical or sub-clinical. Somatosensory evoked potential study is of value for early detection of central affection.
So, we recommend more studies to determine the guidelines when to order these informative investigations for children with JSLE.
Attachment behaviour in autism versus attachment disorders
Authors: Biswas Asit B. , Beardsworth Peter 
Published: July 2022

SUMMARYDifferentiating between autism spectrum disorder and attachment disorders such as reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) can be difficult. We comment on Davidson et al's article on this problem, note the dearth of validated assessment tools for RAD and DSED, and point to the utility of the Early Trauma-Related Disorders Questionnaire.