bluuebunny/crossref_metadata_2025 huggingface dataset:
AGAMA ISLAM DI MUNA PADA MASA PEMERINTAHAN RAJA TITAKONO:1600-1625
Authors: Rahman Marwan , Ali Basri La Ode , Hayari Hayari
Published: November 2020

Penelitian ini bertujuan untuk mengetahui: (1) Jalur-jalur apa yang digunakan dalam proses penyebaran agama Islam di Muna pada masa pemerintahan Raja Titakono: 1600-1625, (2) Bagaimana perkembangan agama Islam di Muna pada masa pemerintahan Raja Titakono: 1600-1625, (3) Faktor-faktor apa yang mendukung dan menghambat ajaran agama Islam di Muna pada masa pemerintahan Raja Titakono: 1600-1625. Metode  yang  digunakan dalam penelitian ini adalah metode sejarahyang dikemukakan oleh Kuntowijoyo yang terdiri dari lima tahapan yaitu: (1) PemilihanTopik (2) Heuristik  Sumber (3) Verifikasi Sumber (4) Interpretasi Sumber (5) Historiografi. Hasil penelitian menunjukkan bahwa: (1) Jalur-jalur yang digunakan dalam penyebaran dan pengembangan agama Islam di Muna pada masa pemerintahan Raja Titakono :1600-1625 melalui: (a) Jalur perdagangan, (b) Jalur tasawuf, (c) Jalur kesenian. (2) Agama Islam pada masa pemerintahan Raja Titakono:1600-1625 mulai berkembang secara perlahan setelah kedatangan Firus Muhammad. (3) Faktor pendukung dan penghambat penyebaran agama Islam di Muna pada masa pemerintahan Raja Titakono: 1600-1625 yaitu, pertama, faktor pendukung: (a) Kedatangan Mubaligh Firus Muhammad di Muna membuat agama Islam mengalami perkembangan secara perlahan, (b) Sikap toleransi Raja Titakono terhadap agama Islam, (c) Pengaruh penyebar Islam sebelumnya, membuat masyarakat Muna telah memiliki keyakinan agama Islam sebelum datangnya Firus Muhammad. Faktor penghambat penyebaran agama Islam pada masa pemerintahan Raja Titakono yakni masyarakat Muna masih memiliki kepercayaan animisme dan dinamisme.
FUNGSI DAN MAKNA SIMBOLIK RUMAH ADAT KAMALI DI DESA PAJAM KECAMATAN KALEDUPA KABUPATEN WAKATOBI
Authors: Yuliani Sri , Hasan Hasni , Burhan Faika
Published: November 2020

Pada masa kerajaan, Rumah Adat Kamali berfungsi sebagai tempat tinggal raja dan pusat pemerintahan. Pembangunannya dirancang dengan berbagai makna tersirat. Berkaitan dengan hal tersebut, adapun permasalahan dalam penelitian ini adalah (1) Bagaimana latar belakang sejarah rumah adat kamali di Dusun Palea Desa Pajam Kecamatan Kaledupa Kabupaten Wakatobi? (2)Bagaimana fungsi rumah adat kamali di Dusun Palea Desa Pajam Kecamatan Kaledupa Kabupaten Wakatobi ? (3) Apa makna simbolik rumah adat kamali  di Dusun Palea Desa Pajam Kecamatan Kaledupa Kabupaten Wakatobi?  Penelitian ini menggunakan metode sejarah menurut Kuntowijoyo dengan lima tahap yaitu: (1) Pemilihan topik (2) Heuristik  (3) Verifikasi (4) Interpretasi data, (5) Historiografi. Hasil penelitian menunjukkan bahwa (1) Pembangunan  rumah adat kamali berawal dari pemerintahan raja pertama Ndangi Tongka Allamu yang memutuskan untuk membangun Istana Kamali di Keraton  Palea dengan pertimbangan pemilihan tempatnya yang sangat strategis untuk menjalankan pusat aktivitas pemerintahan. (2) Fungsi rumah adat Kamali sangatlah beragam, di masa kerajaan difungsikan sebagai tempat kediaman raja dan tempat aktivitas pemerintahan. Rumah adat Kamali kemudian dialihfungsikan sebagai tempat ritual dan tempat wisata. (3) Makna simbolik rumah adat Kamali dipengaruhi oleh konsep tasawuf yang menganggap bahwa pemilik istana kamali, dalam hal ini Raja adalah replikasi dari “wajah Tuhan” (Allah) yang wujudnya dianalogikan dalam bentuk arsitektur rumahnya (istananya), baik yang bersifat konstruksi maupun dekorasi.
Rehabilitation Effects of Fatigue-Controlled Treadmill Training After Stroke: A Rat Model Study
Authors: Xu Yuchen , Yao Yuanfa , Lyu Hao , Ng Stephanie , Xu Yingke , Poon Wai Sang , Zheng Yongping , Zhang Shaomin , Hu Xiaoling
Published: November 2020

Background: Traditional rehabilitation with uniformed intensity would ignore individual tolerance and introduce the second injury to stroke survivors due to overloaded training. However, effective control of the training intensity of different stroke survivors is still lacking. The purpose of the study was to investigate the rehabilitative effects of electromyography (EMG)-based fatigue-controlled treadmill training on rat stroke model.

Methods: Sprague–Dawley rats after intracerebral hemorrhage and EMG electrode implantation surgeries were randomly distributed into three groups: the control group (CTRL, n = 11), forced training group (FOR-T, n = 11), and fatigue-controlled training group (FAT-C, n = 11). The rehabilitation interventions were delivered every day from day 2 to day 14 post-stroke. No training was delivered to the CTRL group. The rats in the FOR-T group were forced to run on the treadmill without rest. The fatigue level was monitored in the FAT-C group through the drop rate of EMG mean power frequency, and rest was applied to the rats when the fatigue level exceeded the moderate fatigue threshold. The speed and accumulated running duration were comparable in the FAT-C and the FOR-T groups. Daily evaluation of the motor functions was performed using the modified Neurological Severity Score. Running symmetry was investigated by the symmetry index of EMG bursts collected from both hind limbs during training. The expression level of neurofilament-light in the striatum was measured to evaluate the neuroplasticity.

Results: The FAT-C group showed significantly lower modified Neurological Severity Score compared with the FOR-T (P ≤ 0.003) and CTRL (P ≤ 0.003) groups. The FAT-C group showed a significant increase in the symmetry of hind limbs since day 7 (P = 0.000), whereas the FOR-T group did not (P = 0.349). The FAT-C group showed a higher concentration of neurofilament-light compared to the CTRL group (P = 0.005) in the unaffected striatum and the FOR-T group (P = 0.021) in the affected striatum.

Conclusion: The treadmill training with moderate fatigue level controlled was more effective in motor restoration than forced training. The fatigue-controlled physical training also demonstrated positive effects in the striatum neuroplasticity. This study indicated that protocol with individual fatigue-controlled training should be considered in both animal and clinical studies for better stroke rehabilitation.
A Confidence-Based Assessment Method for Distinguishing Pyroclastic Density Current Deposits From Other Volcaniclastic Units
Authors: Cowlyn James , Kennedy Ben M. , Gravley Darren M. , Cronin Shane J.
Published: November 2020

Pyroclastic density currents (PDCs) are a destructive volcanic hazard. Quantifying the types, frequency and magnitudes of PDC events is essential for effective risk management, but since historical records at best extend a few hundred years this usually relies on identifying deposits in the geological record. However, small volume unconsolidated PDC deposits have low preservation potential and can be difficult to distinguish from other volcaniclastic units, especially in proximal locations. Consequently many small or poorly exposed deposits can be overlooked. Here, we introduce a structured field method for assessing volcaniclastic deposits of unknown origin with a particular focus on identifying deposits from concentrated PDCs (pyroclastic flows). The method differs from traditional identification schemes in that it does not uniquely attribute a deposit to a single depositional process, but instead assesses how confidently different volcaniclastic processes could explain the observed deposit features. Therefore, the underlying uncertainties in the assessment are explicitly addressed. The method allows consistent, rapid assessment of candidate pyroclastic flow deposits in the field, and the concept could easily be adapted for assessing other types of volcaniclastic deposit. The introduction of confidence levels in deposit interpretations should be useful for carrying though uncertainties into probabilistic assessments of volcanic hazards.
Risk Factors for Adverse Neurodevelopment in Transient or Persistent Congenital Hyperinsulinism
Authors: Roeper Marcia , Salimi Dafsari Roschan , Hoermann Henrike , Mayatepek Ertan , Kummer Sebastian , Meissner Thomas
Published: November 2020

Objective

Aim was to identify hypotheses why adverse neurodevelopment still occurs in children with transient or persistent hyperinsulinism despite improvements in long-term treatment options during the last decades.

Material and Methods

A retrospective review of 87 children with transient (n=37) or persistent congenital hyperinsulinism (CHI) (n=50) was conducted at the University Children’s Hospital Duesseldorf, Germany. Possible risk factors for neurodevelopmental sequelae due to hypoglycemia were analyzed with a focus on the first days after onset of disease.

Results

Median age at follow-up was 7 years (IQR 8). Adverse neurodevelopmental outcome was seen in 34.5% (n=30) of all CHI patients. Fifteen had mildly abnormal neurodevelopment and 15 had a severe hypoglycemic brain injury. In univariate analysis, mildly abnormal neurodevelopment was associated with the diagnosis of persistent CHI (odds ratio (OR) 8.3; p=0.004) and higher birth weight (mean difference 1049 g; p<0.001). Severe hypoglycemic brain injury was associated with the diagnosis of persistent CHI (OR 5.1; p=0.013), being born abroad (OR 18.3; p<0.001) or in a lower-level maternity hospital (OR 4.8; p=0.039), and of note history of hypoglycemic seizures (OR 13.0; p=<0.001), and a delay between first symptoms of hypoglycemia and first blood glucose measurement/initiation of treatment (OR 10.7; p<0.001). Children with severe hypoglycemic brain injury had lower recorded blood glucose (mean difference -8.34 mg/dl; p=0.022) and higher birth weight than children with normal development (mean difference 829 g; p=0.012). In multivariate binary logistic regression models, lowest blood glucose <20 mg/dl (OR 134.3; p=0.004), a delay between initial symptoms and first blood glucose measurement/initiation of treatment (OR 71.7; p=0.017) and hypoglycemic seizures (OR 12.9; p=0.008) were positively correlated with severe brain injury. Analysis showed that the odds for brain injury decreased by 15% (OR 0.85; p=0.035) if the blood glucose increased by one unit.

Conclusion

While some risk factors for adverse outcome in CHI are not influenceable, others like lowest recorded blood glucose values <20 mg/dl, hypoglycemic seizures, and insufficiently—or even untreated hypoglycemia can be avoided. Future guidelines for management of neonatal hypoglycemia should address this by ensuring early identification and immediate treatment with appropriate escalation steps.
Quantitative Genetics of Growth Rate and Filet Quality Traits in Atlantic Salmon Inferred From a Longitudinal Bayesian Model for the Left-Censored Gaussian Trait Growth Rate
Authors: Kristjánsson Ólafur H. , Gjerde Bjarne , Ødegård Jørgen , Lillehammer Marie
Published: November 2020

In selective breeding programs for Atlantic salmon, test fish are slaughtered at an average body weight where growth rate and carcass traits as filet fat (FF), filet pigment (FP) and visceral fat index (FF) are recorded. The objective of this study was to obtain estimates of genetic correlations between growth rate (GR), and the three carcass quality traits when fish from the same 206 families (offspring of 120 sires and 206 dams from 2 year-classes) were recorded both at the same age (SA) and about the same body weight (SW). In the SW group, the largest fish were slaughtered at five different slaughter events and the remaining fish at the sixth slaughter event over 6 months. Estimates of genetic parameters for the traits were obtained from a Bayesian multivariate model for (potentially) truncated Gaussian traits through a Gibbs sampler procedure in which phantom GR values were obtained for the unslaughtered, and thus censored SW group fish at each slaughter event. The heritability estimates for the same trait in each group was similar; about 0.2 for FF, 0.15 for FP and 0.35 for VF and GR. The genetic correlation between the same traits in the two groups was high for growth rate (0.91 ± 0.05) visceral index (0.86 ± 0.05), medium for filet fat (0.45 ± 0.17) and low for filet pigment (0.13 ± 0.27). Within the two groups, the genetic correlation between growth rate and filet fat changed from positive (0.59 ± 0.14) for the SA group to negative (−0.45 ± 0.17) for the SW group, while the genetic correlation between growth rate and filet pigment changed from negative (−0.33 ± 0.22) for the SA group to positive (0.62 ± 0.16) for the SW group. The genetic correlation of growth rate with FF and FP is sensitive to whether the latter traits are measured at the same age or the same body weight. The results indicate that selection for increased growth rate is not expected to have a detrimental effect on the quality traits if increased growth potential is realized through a reduced production time.
Controlling Cytokine Storm Is Vital in COVID-19
Authors: Tang Lu , Yin Zhinan , Hu Yu , Mei Heng
Published: November 2020

Corona virus disease 2019 (COVID-19) has caused a global outbreak and severely posed threat to people’s health and social stability. Mounting evidence suggests that immunopathological changes, including diminished lymphocytes and elevated cytokines, are important drivers of disease progression and death in coronavirus infections. Cytokine storm not only limits further spread of virus in the body but also induces secondary tissue damage through the secretion of large amounts of active mediators and inflammatory factors. It has been determined that cytokine storm is a major cause of deaths in COVID-19; therefore, in order to reverse the deterioration of severe and critically ill patients from this disease, the cytokine storm has become a key therapeutic target. Although specific mechanisms of the occurrences of cytokine storms in COVID-19 have not been fully illuminated, hyper-activated innate immune responses, and dysregulation of ACE2 (angiotensin converting enzyme 2) expression and its downstream pathways might provide possibilities. Tailored immunoregulatory therapies have been applied to counteract cytokine storms, such as inhibition of cytokines, corticosteroids, blood purification therapy, and mesenchymal stem cell therapy. This review will summarize advances in the research of cytokine storms induced by COVID-19, as well as potential intervention strategies to control cytokine storms.
Integrated Care for Older People Screening Tool for Measuring Intrinsic Capacity: Preliminary Findings From ICOPE Pilot in China
Authors: Ma Lina , Chhetri Jagadish K. , Zhang Yaxin , Liu Pan , Chen Yumeng , Li Yun , Chan Piu
Published: November 2020

Objectives: The World Health Organization (WHO) proposed the Integrated Care for Older People (ICOPE) screening tool to identify older people with priority conditions associated with declines in intrinsic capacity (IC). We aimed to determine the clinical utility of the WHO ICOPE screening tool in a Chinese population.

Method: A total of 376 adults aged 68.65 ± 11.41 years participated in the study. IC was assessed with the WHO ICOPE screening tool, covering five domains: cognitive, locomotor, sensory, vision, and psychological capacity. We assessed the activities of daily living (ADL); instrumental activities of daily living (IADL); the Fried frailty phenotype; FRAIL scale; Strength, Assistance With Walking, Rising From chair, Climbing Stairs, and Falls (SARC-F) scale; Mini-mental State Examination (MMSE); Geriatric Depression Scale (GDS); social frailty; and quality of life.

Results: There were 260 (69.1%) participants who showed declines in one or more IC dimensions. The percentages of decline in mobility, cognition, vitality, hearing, vision, and psychological capacity were 25.3, 46.8, 16.2, 15.4, 11.7, and 12.0%, respectively. IC decreased with increasing age. After adjusting for age, sex, and multimorbidity, participants with declines in IC were more likely to be older, frail, and disabled. They also had worse physical, mental, and overall health. There was a higher prevalence of declines in IC in participants with frailty. After adjusting for age, IC was positively correlated with walking speed, resilience score, and MMSE score and negatively correlated with frailty, SARC-F score, IADL score, GDS score, and physical and mental fatigue. The IC score was not associated with body composition variables such as fat-free mass, body fat percentage, or visceral fat area. Higher IC was associated with better quality of life. The area under the curve of the receiver operating characteristic (AUC-ROC) for the ICOPE screening tool vs. Fried phenotype, FRAIL, ADL disability, IADL disability, and SARC-F were 0.817, 0.843, 0.954, 0.912, and 0.909, respectively.

Conclusion: Our research affirms that the ICOPE screening tool is useful to identify adults with poor physical and mental function in a Chinese sample. This tool may assist in identifying declines in IC in an integrative care model and help slow down function decline and onset of care dependence.
Clinical Evaluation of Li Brush Endometrial Samplers for Diagnosing Endometrial Lesions in Women With Intrauterine Devices
Authors: Han Lu , Ma Sijia , Zhao Lanbo , Liu Yu , Wang Yiran , Feng Xue , Zhang Kailu , Wang Lei , Wang Li , Yin Panyue , Liang Dongxin , Hou Huilian , Shi Guizhi , Li Qiling
Published: November 2020

Background: For women with intrauterine devices (IUDs), it is difficult to sample the endometrium when abnormal uterine bleeding occurs or when regular screening of endometrial cancer is proposed. The purpose of this study is to evaluate the validity of endometrial sampling using Li Brush in IUD users.

Methods: This study was a prospective cohort study and conducted in two parts. Part I was to assess the impact of Li Brush on the position of IUDs. Transvaginal ultrasound was used to locate IUDs before and after sampling. Part II was to explore the diagnostic accuracy of Li Brush in detecting endometrial lesions. IUD users with irregular uterine bleeding were recruited in the IUD group and IUD non-users who arranged for dilatation and curettage (D&C) were recruited in the control group. The endometrium was sampled by Li Brush for cells and by D&C for tissues in both groups. The satisfactoriness of sampling and validity of Li Brush were evaluated.

Results: Seventeen cases in part I confirmed no significant difference in the position of IUDs before and after sampling (p = 0.20). 112 IUD users and 139 IUD non-users were recruited in part II. Li Brush achieved 94.64 and 92.09% satisfactory sampling rates in the IUD group and control group, respectively, without statistically significant difference between the two groups (p = 0.42). The Sensitivity and specificity of Li Brush for detection of endometrial lesions in IUD group were 95.35 and 87.76% respectively.

Conclusions: Li Brush used for endometrial biopsy did not affect the position of IUDs and had high yield of satisfactory samples and good validity for endometrial diagnoses. It was feasible to screen endometrial lesions by Li Brush for women with IUDs.
What Role Does Trabecular Bone Score Play in Chronic Inflammatory Rheumatic Diseases?
Authors: Ruaro Barbara , Casabella Andrea , Molfetta Luigi , Salton Francesco , Confalonieri Paola , Confalonieri Marco , Baratella Elisa , De Tanti Antonio , Bruni Cosimo
Published: November 2020

Patients suffering from rheumatic inflammatory diseases, e.g., systemic sclerosis, rheumatoid arthritis, and ankylosing spondylitis, are at risk of low bone mass. Dual-energy X-ray Absorptiometry (DXA) is the traditional radiological measurement technique for bone mineral density (BMD). The recently developed trabecular bone score (TBS) enhances the skeletal information provided by standard BMD. It re-analyzes the spatial dynamics of pixel intensity changes in lumbar spine DXA images, defining a quantitative index, characterizing trabecular bone microarchitecture. It has been demonstrated that low TBS values are associated with an increased incidence of fractures in patients with rheumatic diseases. These methods used together for bone damage evaluation can be of value to identify individuals who will potentially fracture. The main scientific literature on the clinical aspects of osteoporosis, including the use of TBS in evaluating this pathology, are herein reported aimed at shedding light on the role trabecular bone score plays in chronic inflammatory rheumatic diseases.
Case Report: Rosai-Dorfman Disease Involving Sellar Region in a Pediatric Patient: A Case Report and Systematic Review of Literature
Authors: Zhang Yi , Liu Jie , Zhu Jianyu , Zhou Xiang , Zhang Kun , Wang Shirui , Ma Wenbin , Pan Hui , Wang Renzhi , Zhu Huijuan , Yao Yong
Published: November 2020

Rosai-Dorfman disease (RDD) is an extremely rare histiocytic disorder characterized by cervical lymphadenopathy, while the involvement of sellar region is less observed. Here we report a pediatric patient who was initially suspected as sellar germinoma but later identified as RDD. We also conducted a systematic review about RDD involving sellar region. A total of only 14 cases were included and analyzed in our study in terms of clinical presentation, endocrine abnormality, radiological features, pathology, treatment, and follow up. The most common neurological manifestations of sellar RDD is diabetes insipidus and visual changes. Two typical kinds of MRI manifestations were presented in sellar RDD; one is like meningioma-like mass lesions, another showing infiltrative pattern that demonstrates hyperintense areas on T2WI. Currently, the treatment of RDD is tailored to the individual clinical circumstances. For sellar RDD, surgical treatment can be considered to completely remove or debulk the tumor.
The Perspective on Bio-Nano Interface Technology for Covid-19
Authors: Kamaraj Sathish-Kumar
Published: November 2020

The field of bio-nano interfaces paves the way for a better understanding, development, and implementation of the advanced biotechnological process. Interfacing biomolecules with the nanomaterials will result in the development of new tools and techniques that, in turn, will enable to explore the fundamental process at the nano level and fabricate cost-effective portable devices. Fascinating biomolecules like DNA, RNA and proteins in the regime of nanoscale are intelligent materials that are capable of storing the information and controlling the basic structure and function of the complex biological systems. Following this concept, the current pandemic situation would be a natural selection process, where the selective pressure is on the ssRNA of Covid-19 to choose the suitable progeny for survival. Consequently, the interaction of human DNA invoking response with Covid-19 happens at the nanoscale and it could be a better candidate to provoke combat against the virus. The extent of this interaction would give us the insights at the nanotechnological level to tackle the prevention, diagnosis and treatment for Covid-19. Herein, the possible features and obstacles in Covid-19 and a probable solution from the advent of nanotechnology are discussed to address the current necessity. Moreover, the perspective sustainable green graph mask that can be prepared using green plant extract/graphene (Bio-Nano composite mask) is suggested for the possible protection of virus-like Covid-19. The composite material will not only effectively trap the virus but also inactivate the virus due to the presence of antiviral compounds in the plant extracts.
Dynamic Change in Mean Platelet Volume and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
Authors: Chen Liuwei , Zhang Quanbin
Published: November 2020

Background: The mean platelet volume (MPV) has been shown to predict short-term outcomes in patients who have experienced aneurysmal subarachnoid hemorrhage (aSAH). The purpose of this study was to explore the temporal variation of MPV in patients with aSAH and its relationship to the development of delayed cerebral ischemia (DCI).

Methods: Data from 197 consecutive aSAH patients who were treated at our institution between January 2017 and December 2019 were collected and analyzed. Blood samples to assess MPV were obtained at 1–3, 3–5, 5–7, and 7–9 d after the initial hemorrhage. Univariate and multivariate analyses were performed to investigate whether MPV was an independent predictor of DCI and the receiver operating characteristic (ROC) curve and area under the curve (AUC) were determined.

Results: The MPV values in patients with DCI were significantly higher compared to those without DCI at 1–3, 3–5, 5–7, and 7–9 d after hemorrhage (P < 0.001). The trend for MPV in patients with DCI was increased at first and then decreased. The transition from increases to decreases occurred at 3–5 d after hemorrhage. The optimal cutoff value for MPV to accurately predict DCI was 10.35 fL at 3–5 d after aSAH in our cohort. Furthermore, the MPV observed at 3–5 d was an independent risk factor for DCI [odds ratio (OR) = 4.508, 95% confidence interval (CI): 2.665–7.626, P < 0.001].

Conclusions: MPV is a dynamic variable that occurs during aSAH, and a high MPV at 3–5 days after hemorrhage is associated with the development of DCI.
Early Supported Discharge for Neurorehabilitation Following Acquired Brain Injury
Authors: King Regan , Seeger Trevor , Wang Meng , Li Pi Shan Rodney , McGovern Christine , Knox Jason , Patel Lisa , Fung Tak , Sajobi Tolulope , Debert Chantel
Published: November 2020

Introduction: Early Supported Discharge (ESD) is a clinical flow management service offering interdisciplinary rehabilitation, wherein patients are provided supported in-home rehabilitation treatment; in comparison to conventional hospital-based rehabilitation model of service delivery. There has been little research into the functional outcomes for other types of acquired brain injury (ABI).

Methods: In this prospective cohort study, ABI patients presenting at a level I trauma center in Calgary, Canada were placed in either an ESD program or conventional inpatient rehabilitation (IPR) program based on their medical history and presentation. A small number of patients completed both programs (ESD+IPR group). ESD therapies were designed to emulate IPR. Participants completed professionally-rated Mayo-Portland Adaptability Index-4 (MPAI), Quality of Life after Brain Injury (QOLIBRI), Generalized Anxiety Questionnaire-7 (GAD7), Montreal Cognitive Assessment (MoCA), and Patient Health Questionnaire-9 (PHQ9) surveys at 1, 3, and 6 months following initial assessment pre-rehabilitation. Caregivers completed the Zarit Burden Interview (ZBI) at the same time points. The Supervision Rating Scale (SRS) and Disability Rating Scale (DRS) were completed at admission to rehabilitation and all follow-ups. Generalized estimate equations models were used to describe the three groups over time, including age as a covariate.

Results: Significant effects of time were reported in the MPAI participant sub-score in the ESD and IPR groups (χ(2)2 = 42.429, p < 0.000; χ(2)2 = 9.773, p = 0.008), showing significantly higher scores between 1 and 3 month timepoints for both groups. ZBI scores were significantly lower in the ESD group at 1 month compared to 3 and 6 months (χ(2)2 = 31.252, p < 0.001). The proportion of patients with medical complications during rehabilitation was 25.3% in ESD compared to 74.7% patients in IPR.

Conclusions: Improvements in functional outcomes were evident in patients participating in ESD and IPR, with more medical complications reported in the IPR group. Caregiver burden lessened over time in the ESD group but not in the IPR group. Both ESD and ESD+IPR groups can be considered viable alternatives to traditional inpatient rehabilitation. A randomized control trial would be required to properly compare rehabilitation streams. Further investigation into affective and lifestyle elements of ABI recovery would also improve our understanding of targeted neurorehabilitation in this population.
Transcranial Direct Current Stimulation to Enhance Cognitive Impairment in Parkinson's Disease: A Systematic Review and Meta-Analysis
Authors: Suarez-García Diana M. A. , Grisales-Cárdenas Johan S. , Zimerman Máximo , Cardona Juan F.
Published: November 2020

Cognitive deficits are increasingly being recognized as a common trait in Parkinson's disease (PD). Recently, transcranial direct current stimulation (tDCS) has been shown to exert positive effects as an adjunctive therapy on motor and non-motor symptoms in PD. This systematic review and meta-analysis aims to provide an overview of reported evidence on the efficacy of tDCS interventions in the treatment of cognitive impairments in PD. A systematic literature review was conducted to examine articles that were published in the past 10 years and that study the effects of tDCS on cognitive deficits in PD patients. The PubMed, Scopus and Scielo databases were searched. Eight tDCS studies involving 168 participants were included for the analysis. Our meta-analysis results showed that anodal tDCS (atDCS) had various levels or no evidence of effectiveness. In the pre-post stimulation analysis, a strong effect was reported for executive functions (pre-post: g = 1.51, Z = 2.41, p = 0.016); non-significant effects were reported for visuospatial skills (pre-post: g = 0.27, Z = 0.69, p = 0.490); attention (pre-post: g = 0.02, Z = 0.08, p = 0.934), memory (pre-post: g = 0.01, Z = 0.03, p = 0.972) and language (pre-post: g = 0.07, Z = 0.21, p = 0.832). However, in the pre-follow-up stimulation analysis, the duration of the effect was not clear. This study highlights the potential effectiveness of atDCS to improve cognitive performance in PD patients but failed to establish a cause-effect relationship between tDCS intervention and cognitive improvement in PD. Future directions and recommendations for methodological improvements are outlined.
Levodopa Improves Cognitive Function and the Deficits of Structural Synaptic Plasticity in Hippocampus Induced by Global Cerebral Ischemia/Reperfusion Injury in Rats
Authors: Wang Wenzhu , Liu Xu , Yang Zhengyi , Shen Hui , Liu Lixu , Yu Yan , Zhang Tong
Published: November 2020

The cognitive impairment caused by cerebral ischemia/reperfusion is an unsolved problem in the field of international neural rehabilitation. Not only ameliorates the consciousness level of certain patients who suffered from ischemia-reperfusion injury and were comatose for a long time period after cerebral resuscitation treatment, but levodopa also improves the symptoms of neurological deficits in rats with global cerebral ischemia-reperfusion injury. However, Levodopa has not been widely used as a brain protection drug after cardiopulmonary resuscitation, because of its unclear repair mechanism. Levodopa was used to study the neuroplasticity in the hippocampus of global cerebral ischemia/reperfusion injury rat model, established by Pulsinelli's four-vessel occlusion method. Levodopa was injected intraperitoneally at 50 mg/kg/d for 7 consecutive days after 1st day of surgery. The modified neurological function score, Morris water maze, magnetic resonance imaging, Nissl and TH staining, electron microscopy and western blot were used in the present study. The results showed that levodopa improved the neurological function and learning and memory of rats after global cerebral ischemia/reperfusion injury, improved the integrity of white matter, and density of gray matter in the hippocampus, increased the number of synapses, reduced the delayed neuronal death, and increased the expression of synaptic plasticity-related proteins (BDNF, TrkB, PSD95, and Drebrin) in the hippocampus. In conclusion, levodopa can improve cognitive function after global cerebral ischemia/reperfusion injury by enhancing the synaptic plasticity in the hippocampus.
Influence of Autapses on Synchronization in Neural Networks With Chemical Synapses
Authors: Protachevicz Paulo R. , Iarosz Kelly C. , Caldas Iberê L. , Antonopoulos Chris G. , Batista Antonio M. , Kurths Jurgen
Published: November 2020

A great deal of research has been devoted on the investigation of neural dynamics in various network topologies. However, only a few studies have focused on the influence of autapses, synapses from a neuron onto itself via closed loops, on neural synchronization. Here, we build a random network with adaptive exponential integrate-and-fire neurons coupled with chemical synapses, equipped with autapses, to study the effect of the latter on synchronous behavior. We consider time delay in the conductance of the pre-synaptic neuron for excitatory and inhibitory connections. Interestingly, in neural networks consisting of both excitatory and inhibitory neurons, we uncover that synchronous behavior depends on their synapse type. Our results provide evidence on the synchronous and desynchronous activities that emerge in random neural networks with chemical, inhibitory and excitatory synapses where neurons are equipped with autapses.
Combination of T-Cell Bispecific Antibodies With PD-L1 Checkpoint Inhibition Elicits Superior Anti-Tumor Activity
Authors: Sam Johannes , Colombetti Sara , Fauti Tanja , Roller Andreas , Biehl Marlene , Fahrni Linda , Nicolini Valeria , Perro Mario , Nayak Tapan , Bommer Esther , Schoenle Anne , Karagianni Maria , Le Clech Marine , Steinhoff Nathalie , Klein Christian , Umaña Pablo , Bacac Marina
Published: November 2020

T-cell Bispecific Antibodies (TCBs) elicit anti-tumor responses by cross-linking T-cells to tumor cells and mediate polyclonal T-cell expansion that is independent of T-cell receptor specificity. TCBs thus offer great promise for patients who lack antigen-specific T-cells or have non-inflamed tumors, which are parameters known to limit the response of checkpoint inhibitors. The current study deepens the understanding of TCB mode of action and elaborates on one of the adaptive resistance mechanisms following its treatment in vivo in humanized mice and syngeneic pre-clinical tumor models. Single-agent TCB treatment reduced tumor growth compared with controls and led to a 2–10-fold increase in tumor-infiltrating T-cells, regardless of the baseline tumor immune cell infiltration. TCB treatment strongly induced the secretion of CXCL10 and increased the frequency of intra-tumor CXCR3+ T-cells pointing to the potential role of the CXCL10-CXCR3 pathway as one of the mechanisms for T-cell recruitment to tumors upon TCB treatment. Tumor-infiltrating T-cells displayed a highly activated and proliferating phenotype, resulting in the generation of a highly inflamed tumor microenvironment. A molecular signature of TCB treatment was determined (CD8, PD-1, MIP-a, CXCL10, CXCL13) to identify parameters that most robustly characterize TCB activity. Parallel to T-cell activation, TCB treatment also led to a clear upregulation of PD-1 on T-cells and PD-L1 on tumor cells and T-cells. Combining TCB treatment with anti-PD-L1 blocking antibody improved anti-tumor efficacy compared to either agent given as monotherapy, increasing the frequency of intra-tumoral T-cells. Together, the data of the current study expand our knowledge of the molecular and cellular features associated with TCB activity and provide evidence that the PD-1/PD-L1 axis is one of the adaptive resistance mechanisms associated with TCB activity. This mechanism can be managed by the combination of TCB with anti-PD-L1 blocking antibody translating into more efficacious anti-tumor activity and prolonged control of the tumor outgrowth. The elucidation of additional resistance mechanisms beyond the PD-1/PD-L1 axis will constitute an important milestone for our understanding of factors determining tumor escape and deepening of TCB anti-tumor responses in both solid tumors and hematological disorders.
The Role of Non-Coding RNAs in Controlling Cell Cycle Related Proteins in Cancer Cells
Authors: Ghafouri-Fard Soudeh , Shoorei Hamed , Anamag Farhad Tondro , Taheri Mohammad
Published: November 2020

Cell cycle is regulated by a number of proteins namely cyclin-dependent kinases (CDKs) and their associated cyclins which bind with and activate CDKs in a phase specific manner. Additionally, several transcription factors (TFs) such as E2F and p53 and numerous signaling pathways regulate cell cycle progression. Recent studies have accentuated the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of cell cycle. Both lncRNAs and miRNAs interact with TFs participating in the regulation of cell cycle transition. Dysregulation of cell cycle regulatory miRNAs and lncRNAs results in human disorders particularly cancers. Understanding the role of lncRNAs, miRNAs, and TFs in the regulation of cell cycle would pave the way for design of anticancer therapies which intervene with the cell cycle progression. In the current review, we describe the role of lncRNAs and miRNAs in the regulation of cell cycle and their association with human malignancies.
Hyperinflammation in Two Severe Acute Respiratory Syndrome Coronavirus 2-Infected Adolescents Successfully Treated With the Interleukin-1 Inhibitor Anakinra and Glucocorticoids
Authors: Calò Carducci Francesca I. , De Ioris Maria Antonietta , Agrati Chiara , Carsetti Rita , Perrotta Daniela , D'Argenio Patrizia , De Benedetti Fabrizio , Notari Stefania , Rossi Paolo , Campana Andrea
Published: November 2020

Background:In severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) critically ill adults, hyperinflammation plays a key role in disease progression. The clinical manifestations of SARS-CoV-2 infection among children are much less severe compared with adult patients and usually associated with a good prognosis. However, hyperinflammation in SARS-CoV-2-infected pediatric patients has been described as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 or as Kawasaki-like disease but is still little known, and optimal management has to be defined. The World Health Organization (WHO) on the 15th of May 2020 has developed a preliminary case definition for multisystem inflammatory disorder in children and adolescents with coronavirus disease 2019 (COVID-19) and stated for an urgent need to collect data on this condition. Here, we report two adolescent patients affected by COVID-19 presenting with multisystem inflammatory disorder, 3–4 weeks after the first symptoms of SARS-CoV-2 infection, treated with the interleukin-1 receptor antagonist anakinra and glucocorticoids with good clinical response.

Cases:We report two patients chronically ill appearing, with high fever, severe gastrointestinal involvement, and increased biomarkers of inflammation onset 3–4 weeks after paucisymptomatic SARS-CoV-2 infection. They had no lung involvement, but abdominal ultrasound and CT scan showed thickening of the bowel wall. SARS-CoV-2 PCR was positive on ileum biopsy in both patients, whereas it was negative on other common sampled sites. They have been admitted to the pediatric intensive care unit and have been treated with a combination of anakinra 6–8 mg/kg/day i.v. and a standard dose of methylprednisolone 2 mg/kg/day in addition to lopinavir/ritonavir 400 mg q12h and low molecular weight heparin 100 UI/kg q12h with good clinical response.
Modeling Long-Term Erythropoietic Recovery After Allogeneic Stem Cell Transplants in Pediatric Patients
Authors: von Asmuth Erik G. J. , Mohseny Alexander B. , Putter Hein , Schilham Marco W. , Lankester Arjan C.
Published: November 2020

Long term erythropoietic reconstitution after allogeneic hematopoietic stem cell transplantation (alloHSCT) has not been extensively studied. We aimed to describe erythropoietic reconstitution as an indicator of long-term graft function by modeling hemoglobin levels during the first 3 years post HSCT in pediatric patients. We retrospectively included 414 patients and 11,957 measurements. The largest hemoglobin increase was at day 45 and levels reached a steady state at day 648 with a level of 7.48 mmol/L. In patients transplanted for hematological malignancies hemoglobin levels normalized faster (p < 0.0001). Increasing patient age correlated with faster recovery (p < 0.0001), while donor age had no influence. Conditioning, donor type and graft source did not influence recovery significantly. In the ABO mismatched group there was a transient negative effect on hemoglobin levels, and a delay in reticulocyte recovery (21 vs. 19 days; p = 0.012). In contrast, hemoglobin levels reached a higher plateau beyond 9 months in these patients (p < 0.0001). After alloHSCT, experiencing a CMV reactivation negatively affected reconstitution (p = 0.034), while EBV reactivations and acute graft vs. host disease did not. In summary, erythropoietic recovery was mainly influenced by patient factors and primary disease, and less influenced by donor factors.
A Retrospective Study on the Use of Chinese Patent Medicine in 24 Medical Institutions for COVID-19 in China
Authors: Zhang Nan , Shi Nannan , Li Siyu , Liu Guoxiu , Han Yonglong , Liu Li , Zhang Xin , Kong Xiangwen , Zhang Bihua , Yuan Wenpeng , Liu Yi , Deng Deqiang , Zheng Minxia , Zhang Ying , Li Lihua , Wang Xiaoping , Wu Jiankun , Lin Xiaolan , Nian Hua , Wu Xiaohong , Wang Hua , Liu Fang , Wang Hongli , Wang Hongshun , Liu Ying , Liu Li , Zeng Weixin , Yang Manqin , Wang Yanping , Zhai Huaqiang , Wang Yongyan
Published: November 2020

Objective: This research aims to analyze the application regularity of Chinese patent medicine during the COVID-19 epidemic by collecting the names of the top three Chinese patent medicines used by 24 hospitals in 14 provinces of China in four time periods (January 20–22, February 16–18, March 01–03, April 01–03, 2020), and explore its contribution to combating the disease.

Methods: 1) We built a database of the top three Chinese patent medicines used by 24 hospitals. 2) The frequency and efficacy distribution of Chinese patent medicine were analyzed with risk areas, regions, and hospitals of different properties as three factors. 3) Finally, we analyzed the differences in the use of heat-clearing and non-heat-clearing medicines among the three factors (χ2 test) and the correlation between the Chinese patent medicine and COVID-19 epidemic (correlation analysis) with SPSS 23.0 statistical software.

Results: 1) The heat-clearing medicine was the main use category nationwide during January 20–22, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas (p < 0.01). 2) The variety of Chinese patent medicine was increased nationwide during February 16–18, 2020, mainly including tonics, blood-activating and resolving-stasis, and heat-clearing medicines. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in the southern and northern regions (p < 0.05). 3) Tonics, and blood-activating and resolving-stasis medicines became the primary use categories nationwide during March 01–03, 2020. 4) The tonics class, and blood-activating and resolving-stasis medicine were still the primary categories nationwide during April 01–03, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas (p < 0.01).

Conclusion: Chinese patent medicine has a certain degree of participation in fighting against the COVID-19. The efficacy distribution is related to the risk area, region, and hospital of different properties, among which the risk area is the main influencing factor. It is hoped that future research can further collect the application amount of Chinese patent medicine used in hospitals all over the country, so as to perfectly reflect the relationship between Chinese patent medicine and the epidemic situation.
Galangin Attenuates Isoproterenol-Induced Inflammation and Fibrosis in the Cardiac Tissue of Albino Wistar Rats
Authors: Thangaiyan Radhiga , Arjunan Sundaresan , Govindasamy Kanimozhi , Khan Haseeb A. , Alhomida Abdullah S. , Prasad Nagarajan Rajendra
Published: November 2020

Galangin (GA) is an active flavonoid of the rhizome ofAlpinia galangathat belongs to the ginger family. GA exhibit potent anti-inflammatory properties. Therefore, we evaluated the preventive effects of GA against isoproterenol (ISO)-induced inflammation and myocardial fibrosis in male albino Wistar rats. We found that GA (1 mg/kg b.wt.) pretreatment attenuated the ISO-mediated (5 mg/kg b.wt. for 14 consecutive days) elevation of heart rate, activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-MB (CKMB) in the rat serum. We also noticed that GA prevented the ISO-mediated cardiac markers i.e. cardiac troponin T and I (cTnT and cTnI) expression in the serum of rats. Further, GA pretreatment prevented ISO-mediated lipid peroxidation and diminished blood pressure and loss of antioxidants status in the heart tissue of ISO treated rats. In addition, GA treatment modulates ISO-induced alterations the expressions of tissue inhibitor of metalloproteinases-1 (TIMP-1), p-AKT, glycogen synthase kinase-3β (p-GSK-3β) and peroxisome proliferators-activated receptor-γ (PPAR-γ) in the heart tissue. Furthermore, molecular analysis (PCR array and western blot) revealed that GA pretreatment prevented inflammation and fibrosis related gene expression pattern in ISO-induced rats. Taken together, the results indicate the cardioprotective effect of GA against ISO-induced inflammation and fibrosis. The antioxidant and anti-inflammatory potential of GA could be considered for its cardioprotective effect in the ISO-treated rats.
A Prognostic Model Based on Immune-Related Long Non-Coding RNAs for Patients With Cervical Cancer
Authors: Chen Peijie , Gao Yuting , Ouyang Si , Wei Li , Zhou Min , You Hua , Wang Yao
Published: November 2020

Objectives: The study is performed to analyze the relationship between immune-related long non-coding RNAs (lncRNAs) and the prognosis of cervical cancer patients. We constructed a prognostic model and explored the immune characteristics of different risk groups.

Methods: We downloaded the gene expression profiles and clinical data of 227 patients from The Cancer Genome Atlas database and extracted immune-related lncRNAs. Cox regression analysis was used to pick out the predictive lncRNAs. The risk score of each patient was calculated based on the expression level of lncRNAs and regression coefficient (β), and a prognostic model was constructed. The overall survival (OS) of different risk groups was analyzed and compared by the Kaplan–Meier method. To analyze the distribution of immune-related genes in each group, principal component analysis and Gene set enrichment analysis were carried out. Estimation of STromal and Immune cells in MAlignant Tumors using Expression data was performed to explore the immune microenvironment.

Results: Patients were divided into training set and validation set. Five immune-related lncRNAs (H1FX-AS1, AL441992.1, USP30-AS1, AP001527.2, and AL031123.2) were selected for the construction of the prognostic model. Patients in the training set were divided into high-risk group with shorter OS and low-risk group with longer OS (p = 0.004); meanwhile, similar result were found in validation set (p = 0.013), combination set (p < 0.001) and patients with different tumor stages. This model was further confirmed in 56 cervical cancer tissues by Q-PCR. The distribution of immune-related genes was significantly different in each group. In addition, the immune score and the programmed death-ligand 1 expression of the low-risk group was higher.

Conclusions: The prognostic model based on immune-related lncRNAs could predict the prognosis and immune status of cervical cancer patients which is conducive to clinical prognosis judgment and individual treatment.