bluuebunny/crossref_metadata_2025 huggingface dataset:
Oryza sativa ObgC1 Acts as a Key Regulator of DNA Replication and Ribosome Biogenesis in Chloroplast Nucleoids
Authors: Chen Ji , Wang Li , Jin Xiaowan , Wan Jian , Zhang Lang , Je Byoung Il , Zhao Ke , Kong Fanlei , Huang Jin , Tian Mengliang
Published: July 2021

Background

The Spo0B-associated GTP-binding protein (Obg) GTPase, has diverse and important functions in bacteria, including morphological development, DNA replication and ribosome maturation. Homologs of the Bacillus subtilis Obg have been also found in chloroplast of Oryza sativa, but their primary roles remain unknown.

Results

We clarify that OsObgC1 is a functional homolog of AtObgC. The mutant obgc1-d1 exhibited hypersensitivity to the DNA replication inhibitor hydroxyurea. Quantitative PCR results showed that the ratio of chloroplast DNA to nuclear DNA in the mutants was higher than that of the wild-type plants. After DAPI staining, OsObgC1 mutants showed abnormal nucleoid architectures. The specific punctate staining pattern of OsObgC1-GFP signal suggests that this protein localizes to the chloroplast nucleoids. Furthermore, loss-of-function mutation in OsObgC1 led to a severe suppression of protein biosynthesis by affecting plastid rRNA processing. It was also demonstrated through rRNA profiling that plastid rRNA processing was decreased in obgc1-d mutants, which resulted in impaired ribosome biogenesis. The sucrose density gradient profiles revealed a defective chloroplast ribosome maturation of obgc1-d1 mutants.

Conclusion

Our findings here indicate that the OsObgC1 retains the evolutionarily biological conserved roles of prokaryotic Obg, which acts as a signaling hub that regulates DNA replication and ribosome biogenesis in chloroplast nucleoids.
Recent progress of graphene oxide-based multifunctional nanomaterials for cancer treatment
Authors: Liu Lijun , Ma Qingming , Cao Jie , Gao Yang , Han Shangcong , Liang Yan , Zhang Tingting , Song Yang , Sun Yong
Published: July 2021

Background

In the last decade, graphene oxide-based nanomaterials, such as graphene oxide (GO) and reduced graphene oxide (rGO), have attracted more and more attention in the field of biomedicine. Due to the versatile surface functionalization, ultra-high surface area, and excellent biocompatibility of graphene oxide-based nanomaterials, which hold better promise for potential applications than among other nanomaterials in biomedical fields including drug/gene delivery, biomolecules detection, tissue engineering, especially in cancer treatment.

Results

Here, we review the recent progress of graphene oxide-based multifunctional nanomaterials for cancer treatment. A comprehensive and in-depth depiction of unique property of graphene oxide-based multifunctional nanomaterials is first interpreted, with particular descriptions about the suitability for applying in cancer therapy. Afterward, recently emerging representative applications of graphene oxide-based multifunctional nanomaterials in antitumor therapy, including as an ideal carrier for drugs/genes, phototherapy, and bioimaging, are systematically summarized. Then, the biosafety of the graphene oxide-based multifunctional nanomaterials is reviewed.

Conclusions

Finally, the conclusions and perspectives on further advancing the graphene oxide-based multifunctional nanomaterials toward potential and versatile development for fundamental researches and nanomedicine are proposed.

Graphic abstract
Genome-wide identification of cyclin-dependent kinase (CDK) genes affecting adipocyte differentiation in cattle
Authors: Pan Cuili , Lei Zhaoxiong , Wang Shuzhe , Wang Xingping , Wei Dawei , Cai Xiaoyan , Luoreng Zhuoma , Wang Lei , Ma Yun
Published: July 2021

Background

Cyclin-dependent kinases (CDKs) are protein kinases regulating important cellular processes such as cell cycle and transcription. Many CDK genes also play a critical role during adipogenic differentiation, but the role of CDK gene family in regulating bovine adipocyte differentiation has not been studied. Therefore, the present study aims to characterize the CDK gene family in bovine and study their expression pattern during adipocyte differentiation.

Results

We performed a genome-wide analysis and identified a number of CDK genes in several bovine species. The CDK genes were classified into 8 subfamilies through phylogenetic analysis. We found that 25 bovine CDK genes were distributed in 16 different chromosomes. Collinearity analysis revealed that the CDK gene family in Bos taurus is homologous with Bos indicus, Hybrid-Bos taurus, Hybrid Bos indicus, Bos grunniens and Bubalus bubalis. Several CDK genes had higher expression levels in preadipocytes than in differentiated adipocytes, as shown by RNA-seq analysis and qPCR, suggesting a role in the growth of emerging lipid droplets.

Conclusion

In this research, 185 CDK genes were identified and grouped into eight distinct clades in Bovidae, showing extensively homology. Global expression analysis of different bovine tissues and specific expression analysis during adipocytes differentiation revealed CDK4, CDK7, CDK8, CDK9 and CDK14 may be involved in bovine adipocyte differentiation. The results provide a basis for further study to determine the roles of CDK gene family in regulating adipocyte differentiation, which is beneficial for beef quality improvement.
Factors influencing paramedics’ and emergency medical technicians’ level of knowledge about the 2015 basic life support guidelines
Authors: Kayadelen Celal Levent , Kayadelen Ayşe Nilgün , Durukan Polat
Published: July 2021

Background

This study aimed to determine the cardiopulmonary resuscitation (CPR) knowledge level and factors affecting the current CPR knowledge level among EMTs and paramedics working in the Kayseri 112 emergency health system.

Methods

This survey aimed to reach all paramedics and emergency medical technicians working in the 112 emergency health system in Kayseri province. The data collection consists of sociodemographic/occupational characteristics, CPR training and practice characteristics and 20 four-choice CPR knowledge questions. Multiple linear regression analysis was used to determine the independent variables that affect the number of correct answers given to the questionnaire.

Results

305 healthcare professionals were included in this study. 57.0% (n = 174) of the participants were female and 56.1% were under the age of 30. It was found that 65.6% (n = 200) of the healthcare professionals were EMTs, and 48.6% (n = 148) had been working for 6–10 years. The mean number of correct responses based on the 20 questions asked was 12.76 ± 3.11. In multivariable analysis, it was determined that having received training on CPR after 2015, having participated in a course or seminar on CPR in the last 3 months and having practiced defibrillation/cardioversion during CPR significantly increased the level of knowledge regarding CPR (respectively,p < 0.01,p = 0.025,p = 0.045).

Conclusion

CPR trainings, which have been received recently and based on the current guidelines, increase the level of CPR knowledge and the increasing knowledge level affects the use of defibrillation/cardioversion. Improving training increases knowledge and practice.
Describing people with cognitive impairment and their complex treatment needs during routine care in the hospital – cross-sectional results of the intersec-CM study
Authors: Kracht F. , Boekholt M. , Schumacher-Schönert F. , Nikelski A. , Chikhradze N. , Lücker P. , Vollmar H. C. , Hoffmann W. , Kreisel S. H. , Thyrian J. R.
Published: July 2021

Background

Cognitive impairment is an important determinant in health care. In the acute hospital setting cognition has a strong impact on treatment and care. Cognitive impairment can negatively affect diagnostics and treatment success. However, little is known about the individual situation and specific risks of people with cognitive impairments during hospital stays. The aim of the present research is to describe and analyze the treatment needs of people with cognitive impairments in acute hospital care.

Methods

The analyses use baseline data of the ongoing multisite, longitudinal, randomized controlled intervention trial intersec-CM (Supporting elderly people with cognitive impairment during and after hospital stays with Intersectoral Care Management), which recruited 402 participants at baseline. We assessed sociodemographic aspects, cognitive status, functional status, frailty, comorbidities, level of impairment, formal diagnosis of dementia, geriatric diagnoses, delirium, depression, pharmacological treatment, utilization of health care services and health care related needs.

Results

The sample under examination had been on average mildly cognitively impaired (MMSE M = 22.3) and had a mild to moderate functional impairment (Barthel Index M = 50.4; HABAM M = 19.1). The Edmonton Frail Scale showed a mean of 7.4 and half of the patients (52.3%) had been assigned a care level. About 46.9% had a geriatric diagnosis, 3.0% had a diagnosis of dementia. According to DSM-V 19.2% of the patients had at least one main symptom of depression. The mean number of regularly taken drugs per patient was 8.2. Utilization of health care services prior to the hospital stay was rather low. On average, the sample showed 4.38 care related needs in general, of which 0.60 needs were unaddressed at the time of assessment.

Conclusions

Descriptive analyses highlight an in-depth insight into impairments and different care needs of people with cognitive impairments. The results emphasize the need for gender-specific analyses as well as an increased attention to the heterogeneity of needs of people with cognitive impairments related to specific wards, settings and regions where they are admitted. Our results indicate also that people with cognitive impairments represent a high proportion of older patients in acute hospital care.

Trial registration

The intersec-CM trial is registered atClinicalTrials.gov(NCT03359408).
Factors associated with physical, psychological and social frailty among community-dwelling older persons in Europe: a cross-sectional study of Urban Health Centres Europe (UHCE)
Authors: Ye Lizhen , Elstgeest Liset E. M. , Zhang Xuxi , Alhambra-Borrás Tamara , Tan Siok Swan , Raat Hein
Published: July 2021

Background

Frailty is an age-related condition resulting in a state of increased vulnerability regarding functioning across multiple systems. It is a multidimensional concept referring to physical, psychological and social domains. The purpose of this study is to identify factors (demographic characteristics, lifestyle factors and health indicators) associated with overall frailty and physical, psychological and social frailty in community-dwelling older people from five European countries.

Methods

This cross-sectional study used baseline data from 2289 participants of the Urban Health Center European project in five European countries. Multivariable logistic regression models were used to assess associations of the factors with overall frailty and the three frailty domains.

Results

The mean age was 79.7 (SD = 5.7). Participants who were older, were female, had secondary or equivalent education, lived alone, not at risk of alcohol use, were less physically active, had multi-morbidity, were malnourished or with a higher level of medication risk, had higher odds of overall frailty (all P < 0.05). Age was not associated with psychological and social frailty; sex was not associated with social frailty; smoking and migration background was not associated with overall frailty or any of its domains. There existed an interaction effect between sex and household composition regarding social frailty (P < 0.0003).

Conclusions

The present study contributed new insights into the risk factors for frailty and its three domains (physical, psychological and social frailty). Nurses, physicians, public health professionals and policymakers should be aware of the risk factors of each type of frailty. Furthermore, examine these risk factors more comprehensively and consider overall frailty as well as its three domains in order to further contribute to decision-making more precisely on the prevention and management of frailty.

Trial registration

The intervention of the UHCE project was registered in the ISRCTN registry as ISRCTN52788952. The date of registration is 13/03/2017.
Clinical features and outcome of Guillain–Barre syndrome in Saudi Arabia: a multicenter, retrospective study
Authors: Alanazy Mohammed H. , Bakry Sawsan S. , Alqahtani Afnan , AlAkeel Norah S. , Alazwary Naael , Osman Afag M. , Mustafa Rania A. , Al-Harbi Talal M. , Abdulmana Sameeh O. , Amper Aimee C. , Aldughaythir Yousef , Ali Abdulrahman S. , Makkawi Seraj , Maglan Alaa , Alamoudi Loujen , Alsulaiman Feras , Alabdali Majed , AlShareef Aysha A. , Abuzinadah Ahmad R. , Bamaga Ahmed K.
Published: July 2021

Background

Guillain–Barre syndrome (GBS) is an inflammatory polyradiculoneuropathy characterized by rapidly evolving weakness and areflexia, reaching nadir within 4 weeks. Data on the characteristic of GBS in Saudi Arabia are limited. This study aimed to describe the clinical, electrophysiological, and laboratory characteristics and outcome of a multicenter cohort of patients with GBS.

Methods

This is a retrospective multicenter nationwide study. Patients who had GBS, identified through Brighton Criteria, between January 2015 and December 2019 were included. Data collected included demographics, clinical features, cerebrospinal fluid profile, reported electrophysiological patterns, treatment, and outcome. Reported GBS subtypes were compared using chi-square, Fisher's exact, or Mann–Whitney U tests, as appropriate.

Results

A total of 156 patients with GBS were included (men, 61.5%), with a median age of 38 (interquartile range, 26.25–53.5) years. The most commonly reported antecedent illnesses were upper respiratory tract infection (39.1%) and diarrhea (27.8%). All but two patients (98.7%) had weakness, 64.1% had sensory symptoms, 43.1% had facial diplegia, 33.8% had oropharyngeal weakness, 12.4% had ophthalmoplegia, and 26.3% needed mechanical ventilation. Cytoalbuminological dissociation was observed in 69.1% of the patients. GBS-specific therapy was administered in 96.8% of the patients, of whom 88.1% had intravenous immunoglobulin, and 11.9% had plasmapheresis. Approximately half of the patients were able to walk independently within 9 months after discharge, and a third regained the ability to walk independently thereafter. Death of one patient was caused by septicemia. Acute inflammatory demyelinating polyradiculoneuropathy was the most commonly reported GBS subtype (37.7%), followed by acute motor axonal neuropathy (29.5%), and acute motor-sensory axonal neuropathy (19.2%).

Conclusion

The clinical and laboratory characteristics and outcome of GBS in the Arab population of Saudi Arabia are similar to the international cohorts. The overall prognosis is favorable.
An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations
Authors: Park Keunchil , Kim Jin-Soo , Kim Joo-Hang , Kim Young-Chul , Kim Hoon-Gu , Cho Eun Kyung , Jin Jong-Youl , Kim Miyoung , Märten Angela , Kang Jin-Hyoung
Published: July 2021

Background

Afatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its ‘real-world’ safety and efficacy.

Methods

EGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms.

Results

Eighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9–23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4–21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34–66%/36–66%/0–3% of patients over the first year.

Conclusions

No unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations.

Trials registration

ClinicalTrials.gov NCT01931306; 29/08/2013.
End-organ saturations correlate with aortic blood flow estimates by echocardiography in the extremely premature newborn – an observational cohort study
Authors: Altit Gabriel , Bhombal Shazia , Chock Valerie Y.
Published: July 2021

Background

Near-infrared spectroscopy (NIRS) measures of cerebral saturation (Csat) and renal saturation (Rsat) in extreme premature newborns may be affected by systemic blood flow fluctuations. Despite increasing clinical use of NIRS to monitor tissue saturation in the premature infant, validation of NIRS measures as a correlate of blood flow is still needed. We compared echocardiography (ECHO) derived markers of ascending aorta (AscAo) and descending aorta (DesAo) blood flow with NIRS measurements obtained during the ECHO.

Methods

Newborns < 29 weeks’ gestation (2013–2017) underwent routine NIRS monitoring. Csat, Rsat and systemic saturation at the time of ECHO were retrospectively analyzed and compared with Doppler markers of aortic flow. Renal and cerebral fractional tissue oxygen extraction (rFTOE and cFTOE, respectively) were calculated. Mixed effects models evaluated the association between NIRS and Doppler markers.

Results

Forty-nine neonates with 75 Csat-ECHO and 62 Rsat-ECHO observations were studied. Mean post-menstrual age was 28.3 ± 3.8 weeks during the ECHO. Preductal measures including AscAo velocity time integral (VTI) and AscAo output were correlated with Csat or cFTOE, while postductal measures including DesAo VTI, DesAo peak systolic velocity, and estimated DesAo output were more closely correlated with Rsat or rFTOE.

Conclusions

NIRS measures are associated with aortic blood flow measurements by ECHO in the extremely premature population. NIRS is a tool to consider when following end organ perfusion in the preterm infant.
Impacts of multimorbidity on medication treatment, primary healthcare and hospitalization among middle-aged and older adults in China: evidence from a nationwide longitudinal study
Authors: Zhao Yang , Zhao Siqi , Zhang Lin , Haregu Tilahun Nigatu , Wang Haipeng
Published: July 2021

Background

Multimorbidity is a significant contributor to inequalities in healthcare and has become a major unaddressed challenge for the health system in China. The aim of this study is to assess the socio-demographic distribution of multimorbidity and the relationships between multimorbidity, primary healthcare, hospitalization and healthcare spending.

Methods

We conducted this nationwide population-based panel data study in China. Study participants included 12,306 residents aged ≥45 years from the China Health and Retirement Longitudinal Study in 2011, 2013 and 2015. Random-effects logistic regression models were applied to estimate the association between multimorbidity and primary healthcare as well as admission to the hospital. We used log-linear regression models to investigate the association between multimorbidity and health spending.

Results

Overall, 46.2% of total interviewees reported multimorbidity. Random-effects logistic regression analyses showed that multimorbidity was associated with a higher likelihood of medication use (Adjusted odds ratio (AOR) =19.19, 95% CI = 17.60, 20.93), health check (AOR = 1.51, 95% CI = 1.43, 1.59), outpatient care (AOR = 2.39, 95% CI = 2.23, 2.56) and admission to hospital (AOR = 2.94, 95% CI = 2.68, 3.21). Log-linear regression models showed that multimorbidity was also positively associated with spending for outpatient care (coefficient = 0.64, 95% CI = 0.59, 0.68) and hospitalization (coefficient = 0.65, 95% CI = 0.60, 0.71).

Conclusions

Multimorbidity is associated with higher levels of primary care, hospitalization and greater financial burden to individuals in China. Health systems need to shift from single-disease models to new financing and service delivery models to more effectively manage multimorbidity.
A rare case of ciliated muconodular papillary tumor accompanied with adenocarcinoma in situ
Authors: Zhao Lei , Willson Conner M. , Givens Nathan T. , Zhu Ziwen , Wakefield Mark R. , Wang Yongsheng , Yang Wanchun , Fang Yujiang
Published: July 2021

Background

Ciliated muconodular papillary tumor (CMPT) is an incredibly rare pulmonary tumor. Currently, little is known about CMPT, and it has not yet been classified by the World Health Organization. The clinical manifestation of CMPT is nonspecific and the diagnosis is only based on pathology. CMPT has been documented in limited reports as a benign tumor, thus the treatment is typically with surgical excision if a solid tumor is identifiable. The prognosis of CMPT is very positive, as no recurrence has been reported in the limited literature available. However, CMPT accompanied with adenocarcinoma in situ has not been reported previously in the literature.

Case presentation

In this report, we presented a case of a 53-year-old male smoker with CMPT associated with adenocarcinoma in situ. This diagnosis was confirmed by pathological examination, including immunohistostaining. No solid resectable lesion was identified on CT scan; therefore, no surgery was performed. The patient’s adenocarcinoma in situ was disseminated in both lungs, thus chemotherapeutic treatment with cisplatin and pemetrexed was given. The patient will be continually followed up closely on a wait-and-watch basis.

Conclusions

In summary, our report reveals a unique case of CMPT in conjunction with adenocarcinoma in situ, potentially revealing an association between CMPT and malignancy which has not been previously reported. More similar case studies will be beneficial to determine the authentic relationship between CMPT and adenocarcinoma in situ.
Contrast-enhanced ultrasound guided pleural biopsy improves diagnostic confidence for pleural based lesions: a 3-year prospective study
Authors: Sun Wenwen , Zhou Yiming , Yang Cong , Dong Zhengwei , Zhang ZheMin , Wang Yin , Fan Lin
Published: July 2021

Objective

To evaluate the accuracy and safety of contrast-enhanced ultrasound (CEUS) guided biopsy in the diagnosis of radiologically determined pleural based lesions.

Method

A prospective study was conducted on patients with radiologically determined pleural based lesions. Patients who met the inclusion criteria received pleural biopsy guided by CEUS to obtain specimens, followed by histomathological and microbiological examinations. After treatment and follow-up, surgical thoracoscopy was performed on cases with undefinite diagnosis.

Result

A total of 460 patients were finally included. CEUS showed internal necrosis in 72.17% cases and obvious peripheral vessels in 55.43% cases, both of which were significantly higher than the conventional ultrasound imaged (p < 0.05). The diagnostic accuracy through CEUS guided biopsy sampling was 98.91% (455/460). The microbiological diagnostic yield achieved 71.88% (225/313) in infectious lesions. In 330 cases combined pleural effusion, CEUS guided biopsy increased the diagnostic yield from 60.30% (199 /330) to 98.36% (325 /330) in all cases (p < 0.05), from 15.56% (14/90) to 94.44% (85/90) in malignant lesions (p < 0.01) and from 77.08% (185/240) to 100% (240/240) in infectious lesions (p < 0.05). No serious adverse events occurred.

Conclusion

CEUS guided biopsy provides a minimally invasive, effective and safe diagnostic biopsy method for pleural lesions.

Clinical Trials Registration: Chinese Clinical Trial Registry ChiCTR2000029749 (ChiCTR, www.chictr.org.cn).
An update of the long-term outcome of patients with nonspecific pleurisy at medical thoracoscopy
Authors: Yu Yan-Xia , Yang Yuan , Wu Yan-Bing , Wang Xiao-Juan , Xu Li-Li , Wang Zhen , Wang Feng , Tong Zhao-Hui , Shi Huan-Zhong
Published: July 2021

Background

Medical thoracoscopy (MT) is recommended in patients with undiagnosed exudative pleural effusion and offers a degree of diagnostic sensitivity for pleural malignancy. However, not all patients who undergo MT receive an exact diagnosis. Our previous investigation from 2014 summarized the long-term outcomes of these patients with nonspecific pleurisy (NSP); now, we offer updated data with the goal of refining our conclusions.

Methods

Between July 2005 and August 2018, MT with pleural biopsies were performed in a total of 1,254 patients with undiagnosed pleural effusions. One hundred fifty-four patients diagnosed with NSP with available follow-up data were included in the present study, and their medical records were reviewed.

Results

A total of 154 patients were included in this study with a mean follow-up duration of 61.5 ± 43.7 months (range: 1–180 months). No specific diagnosis was established in 67 (43.5%) of the patients. Nineteen patients (12.3%) were subsequently diagnosed with pleural malignancies. Sixty-eight patients (44.2%) were diagnosed with benign diseases. Findings of pleural nodules or plaques during MT and the recurrence of pleural effusion were associated with malignant disease.

Conclusions

Although most NSP patients received a diagnosis of a benign disease, malignant disease was still a possibility, especially in those patients with nodules or plaques as noted on the MT and a recurrence of pleural effusion. One year of clinical follow-up for NSP patients is likely sufficient. These updated results further confirm our previous study’s conclusions.
HIFU for the treatment of gastric cancer with liver metastases with unsuitable indications for hepatectomy and radiofrequency ablation: a prospective and propensity score-matched study
Authors: Zhou Bin , He Ning , Hong Jiaze , Yang Tong , Ng Derry Minyao , Gao Xudong , Yan Kun , Fan Xiaoxiang , Zheng Zhi , Chen Ping , Zheng Jianjun , Zheng Qi
Published: July 2021

Background

The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA).

Methods

This is a prospective, observational study on GCLM patients with 1–3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS).

Results

Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group.

Conclusion

The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.
Phytochemical, acute toxicity and renal protective appraisal of Ajuga parviflora hydromethanolic leaf extract against CCl4 induced renal injury in rats
Authors: Burki Samiullah , Burki Zeba Gul , Asghar Muhammad Arif , Ali Imdad , Zafar Saba
Published: July 2021

Background

Degenerative kidney diseases are mostly associated with oxidative stress. Natural products are considered as the antioxidants enrich food that can restrict the progress of oxidative stress induced disorders. Therefore, the present study was aimed to evaluate the renal protective effect of Ajuga parviflora leaf extract in carbon tetrachloride intoxicated rats.

Methods

The hydromethanolic extract of A. parviflora leaves was obtained by extracting twice in 60% methanol. The principal bioactive constituents were detected by LC/MS analysis. Toxicity of plant extract was assessed using brine shrimp lethal toxicity test and acute toxicity model on healthy Sprague-Dawley male rats. Nephroprotective effects of plant extract were also evaluated on rats by inducing CCl4 renal toxicity in comparison with positive control and naïve groups. The dose of A. parviflora administered to animal was 100, 200 and 300 mg/kg. All administrations were given orally on an alternate day basis for 30 days. Urine and serum biomarkers were analyzed, along with antioxidant enzymes. Finally, the DNA damages, lipid peroxides, hydrogen peroxides and nitrites were assessed in rat’s renal tissue. The histopathology alterations in renal tissues were further studied for kidney damages.

Results

The LC/MS analysis confirmed the presence of different important pharmacological compounds in A. parviflora methanolic leaf extract. The key bioactive compounds include pyocyanin, zonisamide, D Saccharic acid, altretamine, carbocyclic thromboxane A2, Sinapyl alcohol, and vitamin C. The important polypeptides identified include Lys-Tyr-Lys, His-His-Lys, Met-Asp-Arg, Phe-Val-Arg, and PyroGlu-Val-Arg. The LD50 of A. parviflora was found to be > 1000 μg/mL. A. parviflora administration significantly subsides CCl4 toxicity in rats, reduced the elevated level of RBCs, pus and epithelial cells. The abnormal elevated level of specific gravity, creatinine, urobilinogen, urea and albumin were also reduced to normal physiological level. The reduced urinary protein and pH were also normalized. The serum urobilinogen, urea and total bilirubin levels were also reversed to normal levels while the diminished albumin and total protein levels also came to normal. The important phase I and II enzyme levels were also reversed in A. parviflora administered rats. The H2O2, thiobarbituric acid reactive substance (TBARS) and nitrite levels were significantly decreased. Furthermore, the damaged DNA and histopathological changes in CCl4 exposed rats were also highly significantly reversed after the administration of A. parviflora. All effects were significant (P < 0.05) and highly significant (P < 0.005) at 100 and 300 mg/kg respectively.

Conclusion

The restored urine and serum profile of various parameters to normal physiological levels suggests that the A. parviflora has potential antioxidant and repairing potential in renal disorders.
Creation of clinical algorithms for decision-making in oncology: an example with dose prescription in radiation oncology
Authors: Dennstädt Fabio , Treffers Theresa , Iseli Thomas , Panje Cédric , Putora Paul Martin
Published: July 2021

In oncology, decision-making in individual situations is often very complex. To deal with such complexity, people tend to reduce it by relying on their initial intuition. The downside of this intuitive, subjective way of decision-making is that it is prone to cognitive and emotional biases such as overestimating the quality of its judgements or being influenced by one’s current mood. Hence, clinical predictions based on intuition often turn out to be wrong and to be outperformed by statistical predictions. Structuring and objectivizing oncological decision-making may thus overcome some of these issues and have advantages such as avoidance of unwarranted clinical practice variance or error-prevention. Even for uncertain situations with limited medical evidence available or controversies about the best treatment option, structured decision-making approaches like clinical algorithms could outperform intuitive decision-making. However, the idea of such algorithms is not to prescribe the clinician which decision to make nor to abolish medical judgement, but to support physicians in making decisions in a systematic and structured manner. An example for a use-case scenario where such an approach may be feasible is the selection of treatment dose in radiation oncology. In this paper, we will describe how a clinical algorithm for selection of a fractionation scheme for palliative irradiation of bone metastases can be created. We explain which steps in the creation process of a clinical algorithm for supporting decision-making need to be  performed and which challenges and limitations have to be considered.
The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells
Authors: Zhang Huilin , He Ping , Zhou Qing , Lu Yan , Lu Bingjian
Published: July 2021

Background

CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet.

Methods

Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression.

Results

We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells.

Conclusions

Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.
Sustained zinc release in cooperation with CaP scaffold promoted bone regeneration via directing stem cell fate and triggering a pro-healing immune stimuli
Authors: Huang Xin , Huang Donghua , Zhu Ting , Yu Xiaohua , Xu Kaicheng , Li Hengyuan , Qu Hao , Zhou Zhiyuan , Cheng Kui , Wen Wenjian , Ye Zhaoming
Published: July 2021

Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into β-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M$$\varphi $$
φ
s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.
The appearance and increase in the quantity and proportion of the clinical research coordinator’s service fee in drug clinical trial research fund and its impact on trial quality
Authors: Chen Liran , Chen Zhimin , Chen Huafang
Published: July 2021

Objective

The changes of absolute value and relative value of clinical research coordinator service fee and its influence on the quality of drug clinical trial were analyzed.

Methods

This study compared the amount and structural changes of drug clinical trial costs in before 3 years and after 3 years of self-examination and inspection initiated by the China Food and Drug Administration, identified the increase number and composition of each individual cost of a clinical trial research funds which including clinical research coordinator service fee, investigator labor fee, subjects examination fee, subjects traffic subsidy, documents management fee, drug management fee, etc.

Result

The most significant appearance of increase in volume and proportion was the clinical research coordinator service fee. From the initial few to the global multicenter tumor drug clinical trials RMB31,624 or 34.92% of the proportion and domestic multicenter tumor drug clinical trials RMB16,500, accounted for 33.74%.

Discussion

It has become common for more money to be spent on clinical trials to be accompanied by improved quality, but the occurrence and continuous increase of clinical research coordinator service fee were divided into two aspects, On the one hand, the quality of clinical trials was promoted by the large amount of low-skill trivial work undertaken by clinical research coordinator; on the other hand, the quality of clinical trials was undermined by the fact that clinical research coordinator did too much treatment evaluation work that should have been done by the investigator.

Conclusion

The clinical research coordinators’ access standards, pre-employment training and examination, job and performance evaluation, in addition to the SMO specification management and avoiding malicious competition between the industry, are important factors in the quality assurance of drug clinical trials.
Association between high mobility group box 1 protein and juvenile idiopathic arthritis: a prospective longitudinal study
Authors: Xu Dan , Zhang Yu , Zhang Zhi-Yong , Tang Xue-Mei
Published: July 2021

Objective

To analyze the levels of high mobility group box 1 (HMGB1) protein on different courses of juvenile idiopathic arthritis (JIA).

Methods

In our prospective longitudinal study, children with JIA were included with their blood samples collected at the first visit, 1-month, 3-month, and 6-month follow-up, respectively. Samples were also collected from healthy controls and children with reactive arthritis at the first visit. Levels of HMGB1 were determined using enzyme-linked immunosorbent assays. Clinical disease characteristics and routine laboratory findings were analyzed as well.

Results

A total of 64 children were enrolled, of whom 31 (48.4%) were female. The median age at the first visit for participants with JIA was 9.25 years (range, 1.42–15.42) and the median duration of disease was 2.38 months (range, 1.53–49.31). Serum HMGB1 levels at the first visit were significantly elevated in children with systemic JIA compared with other groups, and so were in enthesitis-related arthritis versus healthy controls. Significant correlations were established at the first visit between HMGB1 levels and duration of disease, C-reactive protein, percentage of neutrophils, and ferritin. Data from all samples revealed that serum HMGB1 levels in JIA were significantly associated with erythrocyte sedimentation rates, C-reactive protein, percentage of neutrophils, and disease activity scores.

Conclusions

Serum HMGB1 may be associated with clinical disease activity of JIA and specifically increased at the first visit in children with systemic JIA, suggesting its function as a sensitive inflammatory marker. Further large-scale studies are warranted to explore its spectrum in JIA.
Examining supports and barriers to breastfeeding through a socio-ecological lens: a qualitative study
Authors: Snyder Kailey , Hulse Emily , Dingman Holly , Cantrell Angie , Hanson Corrine , Dinkel Danae
Published: July 2021

Background

Early breastfeeding cessation is a societal concern given its importance to the health of mother and child. More effective interventions are needed to increase breastfeeding duration. Prior to developing such interventions more research is needed to examine breastfeeding supports and barriers from the perspective of breastfeeding stakeholders. One such framework that can be utilized is the Socio-Ecological Model which stems from Urie Broffenbrenner’s early theoretical frameworks (1973–1979). The purpose of this study was to examine supports and barriers to breastfeeding across environmental systems.

Methods

A total of 49 representatives participated in a telephone interview in Nebraska, USA in 2019. Interviewees represented various levels of the model, based on their current breastfeeding experience (i.e., mother or significant other) or occupation. A direct content analysis was performed as well as a constant comparative analysis to determine differences between level representatives.

Results

At the Individual level, breastfeeding is a valued behavior, however, women are hindered by exhaustion, isolation, and the time commitment of breastfeeding. At the Interpersonal level, social media, peer-to-peer, and family were identified as supports for breastfeeding, however lack of familial support was also identified as a barrier. At the community level, participants were split between identifying cultural acceptance of breastfeeding as support or barrier. At the organizational level, hospitals had supportive breastfeeding friendly policies in place however lacked enough personnel with breastfeeding expertise. At the policy level, breastfeeding legislation is supportive, however, more specific breastfeeding legislation is needed to ensure workplace breastfeeding protections.

Conclusion

Future efforts should target hospital-community partnerships, family-centered education, evidence-based social media strategies and improved breastfeeding legislation to ensure breastfeeding women receive effective support throughout their breastfeeding journey.
Resequencing and transcriptomic analysis reveal differences in nitrite reductase in jujube fruit (Ziziphus jujuba Mill.)
Authors: Li Na , Song Yuqin , Li Jie , Hao Ruijie , Feng Xinxin , Li Liulin
Published: July 2021

Background

Jujube is a typical fruit tree species from China. ‘Muzao’, a cracking-susceptible cultivar, and ‘Linhuang No. 1’, a cracking-resistant cultivar, were selected in a previous study as contrasting research materials. Whole-genome resequencing and transcriptomic analysis of ‘Linhuang No. 1’ and ‘Muzao’ allowed the identification of differentially expressed genes with different gene structures between the two cultivars and could be helpful in explaining the differences and similarities between the two cultivars.

Results

Resequencing identified 664,129 polymorphic variable sites between ‘Linhuang No. 1’ and ‘Muzao’. To determine the genetic relationship among ‘Linhuang No. 1’, ‘Muzao’ and the jujube genome reference cultivar ‘Dongzao’, the characteristic polymorphic variable sites were analysed by principal component analysis. The genetic relationship between ‘Linhuang No. 1’ and ‘Muzao’ was closer than that of either variety and ‘Dongzao’. Nineteen differentially expressed genes were identified by combining transcriptomic analysis with resequencing analysis. LOC107427052 (encoding a nitrite reductase) was identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for further study. The identified insertion was not in the domain region of the LOC107427052 gene coding sequence (CDS) region and was verified by the finding that the insertion did not affect translation of the protein. The LOC107427052 gene expression levels, nitrite reductase activities and nitrite contents of ‘Muzao’ were significantly higher than the corresponding values of ‘Linhuang No. 1’ at the young fruit stage. There was no significant difference in the quantity of the product of nitrite reductase, namely, ammonia, between the two cultivars.

Conclusions

The present study was the first to explore the differences between different jujube cultivars (‘Linhuang No. 1’ and ‘Muzao’) by combining genome resequencing and transcriptomics. LOC107427052 (encoding a nitrite reductase) was characterized by KEGG enrichment analysis. The insertion in the CDS region of the LOC107427052 gene provides a new direction for the study of nitrogen metabolism in jujube. Our study has laid a foundation for the comparative analysis of nitrite metabolism between the jujube cultivars ‘Linhuang No. 1’ and ‘Muzao’.
Risk factors for screw loosening in patients with adult degenerative scoliosis: the importance of paraspinal muscle degeneration
Authors: Wang Wei , Li Weishi , Chen Zhongqiang
Published: July 2021

Background

Paraspinal muscle is an important component to maintain spinal stability. But the relationship between the degeneration of paraspinal muscle and postoperative screw loosening in patients with adult degenerative scoliosis has not been studied. The objective of this study was to investigate risk factors for screw loosening in patients with adult degenerative scoliosis, including paraspinal muscle degeneration.

Methods

We investigated 93 patients with adult degenerative scoliosis who underwent spinal interbody fusion and pedicle screw fixation surgery. The lateral curvature was located in the lumbar spine and the follow-up time was ≥ 2 years. The patients were divided into loosening and non-loosening groups. Screw loosening was defined as a 1-mm or wider circumferential radiolucent line around the pedicle screw. We checked the cross-sectional area of paraspinal muscles, spinopelvic parameters, bone mineral density, number of fusion segment, and other factors. The potential risk factors for screw loosening were investigated by using binary logistical regression analysis.

Results

Fifty-seven patients showed screw loosening, which is 63.4% of total. Compared with patients in the non-loosening group, the cross-sectional area of erector spinae and psoas major muscle at L5 level were significantly smaller in patients with screw loosening (P < 0.05). Among these factors, the number of fused segments and relative erector spinae total cross-sectional area were independent risk factors for screw loosening.

Conclusions

The degeneration of paraspinal muscle and the increase of fusion segment were independent factors for screw loosening in patients with adult degenerative scoliosis.