bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal Dynamics of Functional Connectivity Density Associated With Chronic Neck Pain
Authors: Ni Xixiu , Zhang Jiabao , Sun Mingsheng , Wang Linjia , Xu Tao , Zeng Qian , Wang Xiao , Wang Ziwen , Liao Huaqiang , Hu Yimei , Gao Qing , Zhao Ling 
Published: June 2022

Background: Chronic neck pain (CNP) is highly prevalent and complicated, associated with limited movement, and accompanied by shoulder pain and other clinical manifestations such as dizziness, anxiety, and insomnia. Brain structural and functional abnormalities often occur in patients with CNP. However, knowledge of the brain’s functional organization and temporal dynamics in CNP patients is limited. Dynamic functional connectivity density (dFCD) can reflect the ability of brain areas or voxels to integrate information, and could become neuroimaging markers for objectively reflecting pain to a certain extent. Therefore, this study compared the dFCD between CNP patients and healthy controls (HCs) and investigated potential associations of the abnormal density variability in dynamic functional connectivity with pain characteristics in CNP patients.Methods: Resting functional magnetic resonance imaging was performed for 89 CNP patients and 57 HCs. After preprocessing resting-state fMRI images by the Data Processing and Analysis of Brain Imaging toolbox, the sliding window method was applied to investigate dFCD changes in CNP patients and HCs using the DynamicBC toolbox. Then we quantified dFCD variability using their standard deviation. Based on the pain-associated factors collected from the case report form of CNP patients, the mean dFCD variability values of each dFCD from region of interest were extracted to calculate Pearson’s correlation coefficient to study the potential correlation between dFCD abnormal variability and pain.Results: Compared with HCs, the dFCD values of the anterior cingulate cortex, occipital lobe, temporal lobe, and cerebellum were statistically different in patients with CNP. Subsequent correlation analysis showed that the variable dFCD in the related brain region was correlative with the course of the disease and clinical symptoms, such as pain and depression, in patients with CNP.Conclusion: Dynamic functional alterations were observed in the brain regions of CNP patients, and the dFCD of these brain regions could become neuroimaging markers for objectively reflecting pain to a certain extent. This suggests that chronic pain may cause changes in pain processing and emotional feedback and highlights the link between dynamic neural communication in brain regions and disease conditions, deepening our understanding of chronic pain diseases, and guiding clinical practice.
Silence in Conversations About Advancing Pediatric Cancer
Authors: Rockwell Sarah L. , Woods Cameka L. , Lemmon Monica E. , Baker Justin N. , Mack Jennifer W. , Andes Karen L. , Kaye Erica C. 
Published: June 2022

Background and ObjectivesSkillful use of silence by clinicians can support patient-centered communication. However, what makes a period of silence feel meaningful is not well understood. This study aimed to characterize profound, skillful silences during difficult conversations between pediatric oncologists, children with advancing cancer, and their families.MethodsWe audio-recorded serial disease reevaluation discussions between pediatric oncologists, patients with high-risk cancer, and their families across 24 months or until death, whichever occurred first. Using an inductive process, we performed content analysis across all dialogue recorded at timepoints of disease progression to examine types of silence.Results17 patient-parent dyads with disease progression yielded 141 recorded conversations. Inductive coding yielded a layered typology of silence, including “intentional silence” (≥5 seconds), “profound silence” (≥5 seconds following receipt of difficult information, juxtaposed with statements of shared understanding, emotion, or enlightenment), and “stacked silence” (series of silences juxtaposed within dialogue). Intentional silence lasting ≥5 seconds occurred 238 times in 35/49 “bad news” recordings; nearly half (103/238) of these silences were identified as profound silence, in which silences appeared to create space for processing, allowed for questions to emerge, and synergized with empathic and affirmational statements. In most cases, profound silences involved the juxtaposition, or stacking, of multiple silences close together.ConclusionsProfound silences occur often during conversations about advancing pediatric cancer and share distinct characteristics. Opportunities exist to teach clinicians to use profound and stacked silences with intention during difficult conversations as a fundamental aspect of communication.
Increased Severe Cases and New-Onset Type 1 Diabetes Among Children Presenting With Diabetic Ketoacidosis During First Year of COVID-19 Pandemic in Turkey
Authors: Kiral Eylem , Kirel Birgul , Havan Merve , Keskin Mehmet , Karaoglan Murat , Yildirim Ahmet , Kangin Murat , Talay Mehmet Nur , Urun Tuba , Altug Umit , Kesici Selman , Tufan Erennur , Kacmaz Ebru , Bozan Gurkan , Azapagasi Ebru , Uysal Yazici Mutlu , Ozturk Zeynelabidin , Yesilbas Osman , Karaguzel Gulay , Kaya Gulay , Barlas Ulkem , Duyu Muhterem , Boyraz Merve , Sevketoglu Esra , Akcay Nihal , Hancili Suna , Guven Ayla , Dursun Oǧuz , Ulgen Tekerek Nazan , Ozcifci Gokçen , Yazici Pinar , Turanli Eda , Kendirli Tanil , Kahveci Fevzi , Yetimakman Ayse Filiz , Citak Agop , Şik Guntulu , Bingol Ibrahim , Aygun Fatih , Durak Cansu , Yilmaz Resul , Bugrul Fuat , Sari Yusuf , Tekguç Hakan , Albayrak Hatice , Yener Nazik , Agin Hasan , Soydan Ekin , Yildizdas Dincer , Dilek Semine Ozdemir , Yalindag Nilufer , Incekoy-Girgin Feyza , Alacakir Nuri , Tutunculer Filiz , Arslanaoglu Mehmet Ozgur , Aydin Can , Bilgin Muzaffer , Simsek Enver , Dinleyici Ener Cagri 
Published: June 2022

IntroductionThere have been some significant changes regarding healthcare utilization during the COVID-19 pandemic. Majority of the reports about the impact of the COVID-19 pandemic on diabetes care are from the first wave of the pandemic. We aim to evaluate the potential effects of the COVID-19 pandemic on the severity of diabetic ketoacidosis (DKA) and new onset Type 1 diabetes presenting with DKA, and also evaluate children with DKA and acute COVID-19 infection.MethodsThis is a retrospective multi-center study among 997 children and adolescents with type 1 diabetes who were admitted with DKA to 27 pediatric intensive care units in Turkey between the first year of pandemic and pre-pandemic year.ResultsThe percentage of children with new-onset Type 1 diabetes presenting with DKA was higher during the COVID-19 pandemic (p &lt; 0.0001). The incidence of severe DKA was also higher during the COVID-19 pandemic (p &lt; 0.0001) and also higher among children with new onset Type 1 diabetes (p &lt; 0.0001). HbA1c levels, duration of insulin infusion, and length of PICU stay were significantly higher/longer during the pandemic period. Eleven patients tested positive for SARS-CoV-2, eight were positive for new onset Type 1 diabetes, and nine tested positive for severe DKA at admission.DiscussionThe frequency of new onset of Type 1 diabetes and severe cases among children with DKA during the first year of the COVID-19 pandemic. Furthermore, the cause of the increased severe presentation might be related to restrictions related to the pandemic; however, need to evaluate the potential effects of SARS-CoV-2 on the increased percentage of new onset Type 1 diabetes.
Impact of the COVID-19 Pandemic on the Diagnosis of Tuberculosis in Brazil: Is the WHO End TB Strategy at Risk?
Authors: Souza Mariana do Rosário , Paz Wandklebson Silva da , Sales Vinícius Barbosa dos Santos , Jesus Gleidson Felipe Hilario de , Tavares Débora dos Santos , Lima Shirley V. M. Almeida , Sousa Álvaro Francisco Lopes , Melo Enaldo Vieira de , Carmo Rodrigo Feliciano do , Souza Carlos Dornels Freire de , Bezerra-Santos Márcio 
Published: June 2022

Background: In 2014, the World Health Organization (WHO) launched the “post-2015 End TB strategy”, that aims to end the global tuberculosis (TB) epidemic by 2030. However, the COVID-19 pandemic has severely impacted global public health and the strict measures to control the coronavirus spread can affect the management of other diseases, such as TB. Herein, we aimed to assess the impact of the COVID-19 pandemic on the diagnosis of TB in Brazil, during 2020.Methods: We carried out an ecological and population-based study, using spatial analysis techniques. The variables used were the new cases of TB, pulmonary tuberculosis (PTB), and also baciloscopy-positive (BP) cases in Brazil between 2015 and 2020. The percentage of changes (% change) was calculated to verify if there was an increase or decrease of TB cases in 2020, along with time trend analyses given by Joinpoint regression model. Also, interrupted time series analyses were used to assess the trend of TB diagnosis before and after the onset of the COVID-19 in Brazil. Spatial distribution maps were elaborated, considering the % change of each Brazilian state.Findings: Data analyses showed a reduction in the diagnosis of TB (−8.3%) and PTB (−8.1%) in Brazil after the irruption of the COVID-19 pandemic. Likewise, 22 states depicted a reduction in TB diagnosis. An expressive reduction of BP cases (−17.1%) was also observed. Interestingly, interrupted time series analysis showed decline in TB and PTB diagnoses from March 2020. Spatial analyses revealed that all states had a progressive reduction of TB, PTB and PB cases, from March on, with the highest percentages of reduction in December (−100% to −75%).Interpretation: Taken together, our analyses demonstrated a reduction in TB diagnosis after the irruption of the COVID-19 pandemic in Brazil and its regions, signaling a serious impact on the WHO “End TB Strategy” global plan.
Astragalus–Scorpion Drug Pair Inhibits the Development of Prostate Cancer by Regulating GDPD4-2/PI3K/AKT/mTOR Pathway and Autophagy
Authors: You Xujun , Wu Yongrong , Li Qixin , Sheng Wen , Zhou Qing , Fu Wei 
Published: June 2022

Objective: Prostate cancer (PCa) is an epithelial malignancy of the prostate that currently lacks effective treatment. Traditional Chinese medicine (TCM) can play an anticancer role through regulating the immune system, anti-tumor angiogenesis, regulating tumor cell apoptosis, autophagy dysfunction, and other mechanisms. This study attempted to explore the active ingredients and potential mechanism of action of the Astragalus–Scorpion (A–S) drug pair in PCa, in order to provide new insights into the treatment of PCa.Methods: Network pharmacology was used to analyze the A–S drug pair and PCa targets. Bioinformatics analysis was used to analyze the LncRNAs with significant differences in PCa. The expression of LC3 protein was detected by immunofluorescence. CCK8 was used to detect cell proliferation. The expressions of GDPD4-2, AC144450.1, LINC01513, AC004009.2, AL096869.1, AP005210.1, and BX119924.1 were detected by RT-qPCR. The expression of the PI3K/AKT/mTOR pathway and autophagy-related proteins were detected by western blot. LC-MS/MS was used to identify the active components of Astragalus and Scorpion.Results: A–S drug pair and PCa have a total of 163 targets, which were mainly related to the prostate cancer and PI3K/AKT pathways. A–S drug pair inhibited the formation of PCa, promoted the expression of LC3Ⅱ and Beclin1 proteins, and inhibited the expression of P62 and PI3K–AKT pathway proteins in PCa mice. Astragaloside IV and polypeptide extract from scorpion venom (PESV) were identified as the main active components of the A–S drug pair. GDPD4-2 was involved in the treatment of PCa by Astragaloside IV-PESV. Silencing GDPD4-2 reversed the therapeutic effects of Astragaloside IV-PESV by regulating the PI3K/AKT/mTOR pathway.Conclusion: Astragaloside IV-PESV is the main active components of A–S drug pair treated PCa by regulating the GDPD4-2/PI3K–AKT/mTOR pathway and autophagy.
Bilberries: Curative and Miraculous – A Review on Bioactive Constituents and Clinical Research
Authors: Vaneková Zuzana , Rollinger Judith M. 
Published: June 2022

Bilberry (Vaccinium myrtillus L.) fruits are an important part of local diets in many countries and are used as a medicinal herb to treat various disorders. Extracts from fruits are often a part of eye health-promoting supplements, whereas extracts from leaves are advertised for type 2 diabetes mellitus and glycemic control. This review provides an overview of the current knowledge of the phytochemical contents of bilberry fruits and leaves and their bioactivities, critically summarizes origins of the health claims and the outcome of clinical trials, with special attention towards those published in the past 10 years. Overall, the three most referenced indications, which are type 2 diabetes mellitus, vision disorders and circulatory diseases, all include contradictory results with no clear conclusion as to the benefits and recommended dosages. Moreover, the indications for vision disorders and diabetes originate from unproven or false claims that have been repeated in research since the 20th century without consistent fact-checking. Beneficial clinical results have been attested for the treatment of dyslipidemia and chronic inflammatory disorders when applied as dietary supplementation of fresh bilberries or as anthocyanin-rich bilberry fruit extracts. However, there is a general lack of double-blinded controlled research with larger sample sizes.
Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss
Authors: Yang Zeyin , Zhang Yan , Yang Shuling , Ding Yongqing , Qu Yan 
Published: June 2022

Background: To investigate the pathophysiology of age-related hearing loss (ARHL) and the mechanism of resveratrol (RSV) in prevention and treatment of ARHL.Methods: C57BL/6 mice of different ages were used in this study. Auditory brainstem response (ABR) was performed to assess hearing and identify abnormalities. Surface preparation and hair cell-specific marker Myo VIIa were employed to evaluated cochlear hair cell losses. Scanning electron microscopy (SEM) was to observe the microstructure of the organ of Corti (OC). The expression of related proteins in the RIPK1/RIPK3/MLKL pathway in cochlear tissue was detected by immunofluorescence.Results: In old mice (15 months), the ABR threshold increased significantly compared with the young mice. After 50 mg/kg RSV intervention, the hearing threshold of the old mice was significantly reduced at 8 kHz and 12 kHz as well as click. 100 mg/kg RSV led to a statistically significant reduction in hearing threshold only at clicks, whereas 300 mg/kg RSV showed no difference at all frequencies tested. In terms of cochlear hair cell loss, the damage of OHC and IHC was severe in old mice, but the damage was evidently reduced in RSV 50 mg/kg group. Notably, in the RSV 300 mg/kg group, the loss and disorientation of both the OHCs and IHCs were aggravated. Under SEM, a large number of OHCs were lost in the old group, but increased significantly in the RSV 50 mg/kg group, and even the OHCs were more seriously damaged in the RSV 300 mg/kg group. Furthermore, immunofluorescence showed that 50 mg/kg RSV significantly reduced the expression of RIPK3, RIPK1, and MLKL in the cochlea during aging, especially in necroptosis-sensitive regions OCs and SGN.Conclusion: Low-dose RSV inhibited RIPK3-mediated necroptosis in aging cochlea and delayed the onset of ARHL, which was a promising therapeutic strategy for ARHL.
Irisin is an Effector Molecule in Exercise Rehabilitation Following Myocardial Infarction (Review)
Authors: Qin Shuguang , Tian Zhenjun , Boidin Maxime , Buckley Benjamin J. R. , Thijssen Dick H. J. , Lip Gregory Y. H. 
Published: June 2022

Background: Regular exercise is an effective non-pharmacological therapy for treatment and prevention of cardiovascular disease (CVD). The therapeutic benefits of exercise are mediated partly through improved vascular and increase in metabolic health. Release of exercise-responsive myokines, including irisin, is associated with beneficial effects of exercise in CVD patients.Observations: The present review provides an overview of the role of exercise in cardiac rehabilitation of patients with myocardial infarction (MI). Further, the role of irisin as a motion-responsive molecule in improving vascular and metabolic health is explored. Possible mechanism of cardioprotective effect of irisin-mediated exercise on myocardial infarction are also summarized in this review.Conclusion and significance of the review: Irisin is associated with reduced inflammation, antioxidant properties, and anti-apoptotic effect, implying that it is a potential key mediator of the beneficial effects of exercise on vascular and metabolic health. The findings show that irisin is a promising therapeutic target for treatment of patients with cardiovascular disease, particularly post-MI. Further research should be conducted to elucidate the potential mechanisms of cardioprotective effects of irisin and explored whether irisin induced by exercise exerts rehabilitation effects post-MI.
Development of CRISPR/Cas9-Mediated Gene-Drive Construct Targeting the Phenotypic Gene in Plutella xylostella
Authors: Asad Muhammad , Liu Dan , Li Jianwen , Chen Jing , Yang Guang 
Published: June 2022

The gene-drive system can ensure that desirable traits are transmitted to the progeny more than the normal Mendelian segregation. The clustered regularly interspersed palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) mediated gene-drive system has been demonstrated in dipteran insect species, including Drosophila and Anopheles, not yet in other insect species. Here, we have developed a single CRISPR/Cas9-mediated gene-drive construct for Plutella xylostella, a highly-destructive lepidopteran pest of cruciferous crops. The gene-drive construct was developed containing a Cas9 gene, a marker gene (EGFP) and a gRNA sequence targeting the phenotypic marker gene (Pxyellow) and site-specifically inserted into the P. xylostella genome. This homing-based gene-drive copied ∼12 kb of a fragment containing Cas9 gene, gRNA, and EGFP gene along with their promoters to the target site. Overall, 6.67%–12.59% gene-drive efficiency due to homology-directed repair (HDR), and 80.93%–86.77% resistant-allele formation due to non-homologous-end joining (NHEJ) were observed. Furthermore, the transgenic progeny derived from male parents showed a higher gene-drive efficiency compared with transgenic progeny derived from female parents. This study demonstrates the feasibility of the CRISPR/Cas9-mediated gene-drive construct in P. xylostella that inherits the desired traits to the progeny. The finding of this study provides a foundation to develop an effective CRISPR/Cas9-mediated gene-drive system for pest control.
A Mixed Comparison of Interventions for Kinesiophobia in Individuals With Musculoskeletal Pain: Systematic Review and Network Meta-Analysis
Authors: Huang Jialu , Xu Yining , Xuan Rongrong , Baker Julien S. , Gu Yaodong 
Published: June 2022

ObjectiveThis systematic review aims to make a mixed comparison of interventions for kinesiophobia and individuals with musculoskeletal pain.MethodsA comprehensive search strategy was conducted in the database of PubMed, MEDLINE, and Web of Science with the inclusion criteria: (1) randomized controlled design; (2) patients with musculoskeletal pain as participants; (3) treatments protocols of kinesiophobia as interventions or comparisons; (4) the score of Tampa Scale Kinesiophobia (TSK) as outcome measures. A network meta-analysis was used to synthesize the data after checking the model consistency. The risk of bias was assessed by the Cochrane Collaboration Risk of Bias Assessment Tool.ResultsThirty-one studies were included in this review after a comprehensive search strategy with a low risk of bias and good consistency. According to the results of the network meta-analysis, a multi-modal treatment protocol had the highest probability to become the best choice in dealing with kinesiophobia caused by musculoskeletal pain, whereas psychological treatment protocols also showed a potentially positive effect on musculoskeletal pain-induced kinesiophobia.ConclusionMulti-modal protocols could be recommended as the preferred option when dealing with kinesiophobia caused by musculoskeletal pain. However, it is still worth mentioning that there are also potentially positive therapeutic effects of psychological interventions. Since the concept of kinesiophobia is based on the fear-avoidance model, the psychological mechanism should be paid enough attention to during treatment.Registration NumberCRD42021286450.
Depression and Insomnia of Front-Line Medical Staff During the COVID-19 Outbreak in China: An On-Line Cross-Sectional Study
Authors: Zhang Donglin , Luo Hailong , Xiao Litian , Zhang Zhun , Huang Jianqing , Li Xiaoqin , Zhu Hongke , Lai Cuiwei 
Published: June 2022

PurposeDuring the COVID-19 outbreak, medical staff working in high-risk workplaces had a higher rate of epidemic infection. They also faced heavy workloads and pressure, which means they are more likely to suffer from psychological problems than others. To understand the mental health of medical staff during the epidemic, we explore the characteristics of medical staff susceptible to negative psychological emotions during the outbreak of public safety and health events. At the same time, we provide corresponding prevention and intervention measures to help them relieve negative emotions, this study compared the psychological symptoms of front-line and non-front-line medical staff, then explored its influencing factors.MethodsThis research investigated 5,924 medical staff in Guangdong, Beijing, Hubei, Hainan, Jiangxi, and Henan in China. The questionnaires were released online by Questionnaire Star, and levels of depression, anxiety, insomnia, and social support were measured by Patients' Health Questionnaire Depression Scale-9 item (PHQ-9), Generalized Anxiety Disorder 7-item Scale (GAD-7), Insomnia Severity Index (ISI) and Social Support Rating Scale (SSRS).ResultsThe depressive, anxious, and insomniac scores of front-line medical staff during the COVID-19 epidemic period were higher than those of non-front-line with significant differences (P &lt; 0.001). In addition, front-line nurses went through the most serious psychological problems. Age, education, and anxiety level were the influencing factors of depression and insomnia in front-line medical staff. Among them, age was a protective factor for depression (OR = 0.71 &lt;1, P = 0.001 &lt;0.05, Beta = −0.34), while educational level was a risk factor for insomnia (OR = 1.27, P = 0.02 &lt;0.05, Beta = 0.24).ConclusionsDuring the epidemic, front-line medical staff would experience more serious psychological problems, especially those who were younger, less experienced, and insufficiently educated. Attention should be paid to giving them psychological assistance and psychological interventions in the future.