bluuebunny/crossref_metadata_2025 huggingface dataset:
hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway
Authors: Shen Jing , Cai Wenpeng , Ma Yongfang , Xu Ruyue , Huo Zhen , Song Li , Qiu Xinyin , Zhang Yinci , Li Amin , Cao Weiya , Zhou Shuping , Tang Xiaolong
Published: November 2020

Delivery of tumor-specific inhibitors is a challenge in cancer treatment. Antibody-modified nanoparticles can deliver their loaded drugs to tumor cells that overexpress specific tumor-associated antigens. Here, we constructed sorafenib-loaded polyethylene glycol-b-PLGA polymer nanoparticles modified with antibody hGC33 to glypican-3 (GPC3 +), a membrane protein overexpressed in hepatocellular carcinoma. We found that hGC33-modified NPs (hGC33-SFB-NP) targeted GPC3+ hepatocellular carcinoma (HCC) cells by specifically binding to GPC3 on the surface of HCC cells, inhibited Wnt-induced signal transduction, and inhibited HCC cells in G0/1 by down-regulating cyclin D1 expression, thus attenuating HCC cell migration by inhibiting epithelial–mesenchymal transition. hGC33-SFB-NP inhibited the migration, cycle progression, and proliferation of HCC cells by inhibiting the Ras/Raf/MAPK pathway and the Wnt pathway in tandem with GPC3 molecules, respectively. hGC33-SFB-NP inhibited the growth of liver cancer in vivo and improved the survival rate of tumor-bearing mice. We conclude that hGC33 increases the targeting of SFB-NP to HCC cells. hGC33-SFB-NP synergistically inhibits the progression of HCC by blocking the Wnt pathway and the Ras/Raf/MAPK pathway.
Multitract percutaneous nephrolithotomy in the management of staghorn stones
Authors: Rashid Aso Omer , Mahmood Sarwar Noori , Amin Aram Karim , Bapir Rawa , Buchholz Noor
Published: November 2020

Background

Staghorn stones are difficult to manage with a risk of significant renal impairment and urosepsis. Percutaneous nephrolithotomy is the first-line treatment for staghorn stones. Often, multiple access tracts are needed to render the patient stone-free. PCNL has been combined with SWL, flexible URS (ECIRS), and mini-PCNL to access residual fragments without the need of additional tracts. However, in a country with limited access to technology and a restraint on resources, multitract PCNL still is the preferred option. The aim of this study was to assess the safety and efficacy of multitract PCNL in such an environment.

Methods

We analyzed data on sixty-five patients with staghorn calculus who underwent multitract PCNL for a staghorn calculus. Data included demographics, stone parameters, intraoperative parameters, complications and clinical outcomes. Hb-drop and creatinine changes were assessed pre- and post-OP. Complications were graded according to the modified Clavien-Dindo classification.

Results

In a total of 65 patients [47 males (72%)], 154 percutaneous access tracts were used in 66 renal units. The number of tracts varied between 2 and 4 in a single renal unit. The stone-free rate was 85%. 20% of patients developed grade I, 14% grade II, and 3% grade III b complications. There were no grade IV and V complications.

Conclusion

Multitract PCNL is safe and efficient, with a good stone-free rate and an acceptable complication rate. When auxiliary combination treatments are not available, multitract standard PCNL remains an option.
CGINet: graph convolutional network-based model for identifying chemical-gene interaction in an integrated multi-relational graph
Authors: Wang Wei , Yang Xi , Wu Chengkun , Yang Canqun
Published: November 2020

Background

Elucidation of interactive relation between chemicals and genes is of key relevance not only for discovering new drug leads in drug development but also for repositioning existing drugs to novel therapeutic targets. Recently, biological network-based approaches have been proven to be effective in predicting chemical-gene interactions.

Results

We present CGINet, a graph convolutional network-based method for identifying chemical-gene interactions in an integrated multi-relational graph containing three types of nodes: chemicals, genes, and pathways. We investigate two different perspectives on learning node embeddings. One is to view the graph as a whole, and the other is to adopt a subgraph view that initial node embeddings are learned from the binary association subgraphs and then transferred to the multi-interaction subgraph for more focused learning of higher-level target node representations. Besides, we reconstruct the topological structures of target nodes with the latent links captured by the designed substructures. CGINet adopts an end-to-end way that the encoder and the decoder are trained jointly with known chemical-gene interactions. We aim to predict unknown but potential associations between chemicals and genes as well as their interaction types.

Conclusions

We study three model implementations CGINet-1/2/3 with various components and compare them with baseline approaches. As the experimental results suggest, our models exhibit competitive performances on identifying chemical-gene interactions. Besides, the subgraph perspective and the latent link both play positive roles in learning much more informative node embeddings and can lead to improved prediction.
Visual adaptation of opsin genes to the aquatic environment in sea snakes
Authors: Seiko Takashi , Kishida Takushi , Toyama Mina , Hariyama Takahiko , Okitsu Takashi , Wada Akimori , Toda Mamoru , Satta Yoko , Terai Yohey
Published: November 2020

Background

Evolutionary transitions from terrestrial to aquatic life history cause drastic changes in sensory systems. Indeed, the drastic changes in vision have been reported in many aquatic amniotes, convergently. Recently, the opsin genes of the full-aquatic sea snakes have been reported. However, those of the amphibious sea snakes have not been examined in detail.

Results

Here, we investigated opsin genes and visual pigments of sea snakes. We determined the sequences ofSWS1,LWS, andRH1genes from one terrestrial, three amphibious and four fully-aquatic elapids. Amino acid replacements at four and one spectra-tuning positions were found in LWS and RH1, respectively. We measured or predicted absorption of LWS and RH1 pigments with A1-derived retinal. During their evolution, blue shifts of LWS pigments have occurred stepwise in amphibious sea snakes and convergently in both amphibious and fully-aquatic species.

Conclusions

Blue shifted LWS pigments may have adapted to deep water or open water environments dominated by blue light. The evolution of opsins differs between marine mammals (cetaceans and pinnipeds) and sea snakes in two fundamental ways: (1) pseudogenization of opsins in marine mammals; and (2) large blue shifts of LWS pigments in sea snakes. It may be possible to explain these two differences at the level of photoreceptor cell composition given that cone and rod cells both exist in mammals whereas only cone cells exist in fully-aquatic sea snakes. We hypothesize that the differences in photoreceptor cell compositions may have differentially affected the evolution of opsins in divergent amniote lineages.
Genetic analysis of rice seedling traits related to machine transplanting under different seeding densities
Authors: Zhu Dan , Zhang Yuping , Xiang Jing , Wang Yaliang , Zhu Defeng , Zhang Yikai , Chen Huizhe
Published: November 2020

Background

Due to the diversity of rice varieties and cropping systems in China, the limitation of seeding density and seedling quality makes it hard to improve machine-transplanted efficiency. Previous studies have shown that indica and japonica varieties varied in machine transplanting efficiency and optimal seeding density. In this study, a RIL population derived from ‘9311’ and ‘Nipponbare’ were performed to explore the seedling traits variations and the genetic mechanism under three seeding densities.

Results

The parents and RIL population exhibited similar trends as the seeding density increased, including seedling height and first leaf sheath length increases, shoot dry weight and root dry weight decreases. Among the 37 QTLs for six traits detected under the three seeding densities, 12 QTLs were detected in both three seeding densities. Five QTL hotspots identified clustered within genomic regions on chromosomes 1, 2, 4, 6 and 11. Specific QTLs such asqRDW1.1andqFLSL5.1were detected under low and high seeding densities, respectively. Detailed analysis the QTL regions identified under specific seeding densities revealed several candidate genes involved in phytohormones signals and abiotic stress responses. Whole-genome additive effects showed that ‘9311’ contributed more loci enhancing trait performances than ‘Nipponbare’, indicating ‘9311’ was more sensitive to the seeding density than ‘Nipponbare’. The prevalence of negative epistasis effects indicated that the complementary two-locus homozygotes may not have marginal advantages over the means of the two parental genotypes.

Conclusions

Our results revealed the differences between indica rice and japonica rice seedling traits in response to seeding density. Several QTL hotspots involved in different traits and specific QTLs (such asqRDW1.1andqFLSL5.1) in diverse seeding densities had been detected. Genome-wide additive and two-locus epistasis suggested a dynamic of the genetic control underlying different seeding densities. It was concluded that novel QTLs, additive and epistasis effects under specific seeding density would provide adequate information for rice seedling improvement during machine transplanting.
Genetic characterization of Addison’s disease in Bearded Collies
Authors: Gershony Liza C. , Belanger Janelle M. , Hytönen Marjo K. , Lohi Hannes , Famula Thomas R. , Oberbauer Anita M.
Published: November 2020

Background

Primary hypoadrenocorticism (or Addison’s disease, AD) is an autoimmune disease that results in destruction of the adrenal cortex and consequent adrenal insufficiency. The disease has been described in purebred and mixed breed dogs, although some breeds, including the Bearded Collie, are at increased risk for AD. Candidate gene approaches have yielded few associations that appear to be breed-specific. A single other genome-wide association study reported no significant regions of association for AD in Standard Poodles. The present study aimed to identify genomic regions of association for canine AD in Bearded Collies.

Results

Our study consists of the first genome-wide association analysis to identify a genome-wide significant region of association with canine AD (CFA18). Peaks of suggestive association were also noted on chromosomes 11, 16 and 29. Logistic regression analysis supported an additive effect of risk genotypes at these smaller effect loci on the probability of disease associated with carrying a risk genotype on CFA18. Potential candidate genes involved in adrenal steroidogenesis, regulation of immune responses and/or inflammation were identified within the associated regions of chromosomes 11 and 16. The gene-poor regions of chromosomes 18 and 29 may, however, harbor regulatory sequences that can modulate gene expression and contribute to disease susceptibility.

Conclusion

Our findings support the polygenic and complex nature of canine AD and identified a strongly associated locus on CFA18 that, when combined with three other smaller effect loci, was predictive of disease. The results offer progress in the identification of susceptibility loci for canine AD in the Bearded Collie. Further studies are needed to confirm association with the suggested candidate genes and identify actual causative mutations involved with AD susceptibility in this breed.
The elephant in the room: an exploratory study of hypertensive disorders of pregnancy (HDP) management in Indonesian primary care settings
Authors: Ekawati Fitriana Murriya , Emilia Ova , Gunn Jane , Licqurish Sharon , Lau Phyllis
Published: November 2020

Background

Indonesia has the highest maternal mortality rate in South East Asia, that a third of the mortality is caused by hypertensive disorders of pregnancy (HDP), including preeclampsia and eclampsia. Research suggests that maternal deaths from HDP are avoidable with appropriate initial management in primary care. However, little is known regarding the exact way HDP management is conducted in Indonesian primary care. This research aims to explore the way HDP management is provided, including its barriers and facilitators in Indonesian primary care settings.

Methods

This research applied a practical qualitative methodology using interviews with a topic guide. It is guided by the implementation science framework of the Medical Research Council (MRC) framework and Practical Robust Implementation and Sustainability Model (PRISM) to design and evaluate complex healthcare interventions. Primary care key stakeholders from Yogyakarta province were recruited from May–December 2018. The interviews were conducted in face-to-face, telephone, and teleconference interviews. Data from the interviews were analysed thematically using a mix of inductive and deductive approaches.

Results

A total of 24 participants were interviewed, consisting of four general practitioners, five midwives, three nurses, three obstetricians, a cardiologist, five policymakers and three women with a previous history of HDP. Referrals are the usual management performed for HDP women in primary care and the primary care providers’ practice is challenged by three identified themes: (i) providers’ limited confidence to perform HDP management, (ii) fragmented continuity of care, and (iii) community beliefs. Many participants also desired to have more focused guidance to improve HDP management in primary care practice.

Conclusion

Even though Indonesian antenatal care and referrals are generally accessible, there are many challenges and fragmentation of HDP management. The most prominent challenge is the primary care providers’ lack of confidence in performing the management and the ‘elephant’ of an urgent need of practice guidelines in primary care that has never been appropriately described in the literature. Further development of an evidence-based primary care-focused guidance will potentially improve primary care providers’ skills to perform optimal HDP management and provide appropriate education to their patients.
Age and pain score before gastrointestinal endoscopies in children are predictors for post procedure pain
Authors: Galai Tut , Yerushalmy-Feler Anat , Heller Nathan P. , Ben-Tov Amir , Weintraub Yael , Amir Achiya , Moran-Lev Hadar , Zac Lilach , Cohen Shlomi
Published: November 2020

Background

Gastrointestinal endoscopy may be associated with pain and anxiety. Predictors for high pain scores after endoscopies in children are not known. The aim of our study was to identify risk factors for prolonged recovery and higher pain scores after gastrointestinal endoscopy in children.

Methods

All the children that were electively admitted for gastrointestinal endoscopies were included. We retrospectively collected demographic, clinical and endoscopic data as well as information on the recovery process. A numerical rating scale and the Faces, Legs, Activity, Cry, and Consolability Scale were used for pain scoring.

Results

During the study period (01/2016–10/2016), 284 children (median age 10.7 years, interquartile range 6.7–14.8) were recruited. In a univariate analysis, older age, higher pre-procedure pain scores, longer procedure durations, higher number of biopsies and longer recovery duration were associated with higher post-procedure pain scores. In a multivariate analysis higher pain scores before the procedure (OR 12.42, 95% CI 3.67–42, P < 0.001) and older age (OR 1.016, 95% CI 1.007–1.025, P < 0.001) were associated with higher pain scores after the procedure. Children with a higher pain score before the procedure also had a longer recovery period (OR 5.28, 95% CI (1.93–14.49), P = 0.001).

Conclusion

Older age and higher pain score before the procedure were identified as predictors for higher pain score after pediatric gastrointestinal endoscopies. Children with these risk factors should be identified before the procedure in order to personalize their post-procedure management.
Recurrence of moderate to severe ulcerative colitis after fecal microbiota transplantation treatment and the efficacy of re-FMT: a case series
Authors: Dang Xiao-Fei , Qing-Xi Wang  , Yin Zhao , Sun Lin , Yang Wei-Hua
Published: November 2020

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), the pathogenesis of which is complicated, and it is difficult to treat. In recent years, the emerging fecal microbiota transplantation (FMT) has shown good effects in UC treatment and is therefore accepted by increasing numbers of patients. Our hospital has carried out FMT since 2017, and has achieved good results in UC treatment. We have found in our clinical work that the efficacy of re-FMT after recurrence decreased. This is difference from reported literatures. In order to attract clinical attention, here we selected typical cases for analysis.

Methods

Among all UC patients who received FMT in our hospital, 12 patients with moderate to severe UC were selected. They all received multiple FMT and were followed up for 52 weeks. Besides, none of them had other underlying diseases. Colonoscopy images of patients were presentated, SCCAI and UCDAI were used assess the effect of FMT.

Results

On the whole, FMT has a significant effect on moderate to severe UC. Of the 12 patients, 11 (91.7%) achieved a clinical response, 9 (75.0%) achieved clinical remission, and only one patient did not respond to FMT treatment. However, 6 patients relapsed within 52 weeks after remission, with a recurrence rate of 54.5%. Four of the six relapsed patients received FMT again, but the efficacy of FMT after relapse was significantly lower than that of the initial FMT. Fortunately, compared to before the initial FMT treatment, the severity of the disease after relapse was significantly reduced.

Conclusion

FMT has a good effect on the relief of moderate to severe UC. However, the effect of FMT treatment after relapse is reduced. For patients who relapse after remission, the efficacy of FMT reapplication requires more experiments to verify.
Hearing aids to support cognitive functions of older adults at risk of dementia: the HearCog trial- clinical protocols
Authors: Jayakody Dona M. P. , Almeida Osvaldo P. , Ford Andrew H. , Atlas Marcus D. , Lautenschlager Nicola T. , Friedland Peter L. , Robinson Suzanne , Makate Marshall , Coetzee Lize , Liew Angela S. P. , Flicker Leon
Published: November 2020

Background

Globally, about 50 million people were living with dementia in 2015, with this number projected to triple by 2050. With no cure or effective treatment currently insight, it is vital that factors are identified which will help prevent or delay both age-related and pathological cognitive decline and dementia. Observational data have suggested that hearing loss is a potentially modifiable risk factor for dementia, but no conclusive evidence from randomised controlled trials is currently available.

Methods

The HearCog trial is a 24-month, randomised, controlled clinical trial aimed at determining whether a hearing loss intervention can delay or arrest the cognitive decline. We will randomise 180 older adults with hearing loss and mild cognitive impairment to a hearing aid or control group to determine if the fitting of hearing aids decreases the 12-month rate of cognitive decline compared with the control group. In addition, we will also determine if the expected clinical gains achieved after 12 months can be sustained over an additional 12 months and if losses experienced through the non-correction of hearing loss can be reversed with the fitting of hearing aids after 12 months.

Discussion

The trial will also explore the cost-effectiveness of the intervention compared to the control arm and the impact of hearing aids on anxiety, depression, physical health and quality of life. The results of this trial will clarify whether the systematic correction of hearing loss benefits cognition in older adults at risk of cognitive decline. We anticipate that our findings will have implications for clinical practice and health policy development.

Trial registration

Australian and New Zealand Clinical Trials Registry (ANZCTR: 12618001278224), registered on 30.07.2018.
Pneumatocele formation in a fatal adult pneumonia patient coinfected with Streptococcus pyogenes emm-type 3 and influenza A: a case report
Authors: Sano Masahiro , Shimamoto Aya , Ueki Nozomi , Sekino Motohiro , Nakaoka Hiroshi , Takaki Masahiro , Yamashita Yoshiro , Tanaka Takeshi , Morimoto Konosuke , Yanagihara Katsunori , Nakashima Masahiro , Ashizawa Kazuto , Ariyoshi Koya
Published: November 2020

Background

A pneumatocele is a transient thin-walled lesion and rare complication in adult pneumonia.

A variety of infectious pathogens have been reported in children with pneumatoceles. We report the first case of adult pneumonia with pneumatocele formation that is likely caused by Streptococcus pyogenes and coinfection with influenza A virus.

Case presentation

A 64-year-old Japanese man presented with a one-week history of fever, sore throat, and arthralgia. He was referred to our university hospital for respiratory distress. He required mechanical ventilation in the intensive care unit (ICU). Bacterial culture detected S. pyogenes in the bronchoscopic aspirates, which was not detected in blood. Although a rapid influenza antigen test was negative, an influenza A polymerase chain reaction (PCR) test was positive. Therefore, he was diagnosed with coinfection of influenza A and group A streptococcus (GAS) pneumonia complicated by probable streptococcal toxic shock syndrome. A chest radiograph on admission showed diffuse patchy opacification and consolidation in the bilateral lung fields.

Multiple thin-walled cysts appeared in both middle lung fields on computed tomography (CT). On the following day, the bilateral cysts had turned into a mass-like opacity. The patient died despite intensive care. An autopsy was performed. The pathology investigation revealed multiple hematomas formed by bleeding in pneumatoceles.

Conclusions

There have been no previous reports of a pneumatocele complicated by S. pyogenes in an adult patient coinfected with influenza A. Further molecular investigation revealed that the S. pyogenes isolate had the sequence type of emm3.
First case report of cerebral folate deficiency caused by a novel mutation of FOLR1 gene in a Chinese patient
Authors: Zhang Ciliu , Deng Xiaolu , Wen Yafei , He Fang , Yin Fei , Peng Jing
Published: November 2020

Background

Cerebral folate deficiency (CFD) is a neurological disease, hallmarked by remarkable low concentrations of 5-methyltetrahydrofolic acid (5-MTHF) in cerebrospinal fluid (CSF). The primary causes of CFD include the presence of folate receptor (FR) autoantibodies, defects of FR encoding gene FOLR1, mitochondrial diseases and congenital abnormalities in folate metabolism.

Case presentation

Here we first present a Chinese male CFD patient whose seizure onset at 2 years old with convulsive status epilepticus. Magnetic Resonance Imaging (MRI) revealed the development of encephalomalacia, laminar necrosis in multiple lobes of the brain and cerebellar atrophy. Whole Exome Sequencing (WES) uncovered a homozygous missense variant of c.524G > T (p.C175F) in FOLR1 gene. Further laboratory tests demonstrated the extremely low level of 5-MTHF in the CSF from this patient, which was attributed to cerebral folate transport deficiency. Following the intravenous and oral treatment of calcium folinate, the concentrations of 5-MTHF in CSF were recovered to the normal range and seizure symptoms were relieved as well.

Conclusions

One novel variation of FOLR1 was firstly identified from a Chinese male patient with tonic-clonic seizures, developmental delay, and ataxia. The WES and laboratory results elucidated the etiology of the symptoms. Clinical outcomes were improved by early diagnosis and proper treatment.
Two novel mutations in the DNAH11 gene in primary ciliary dyskinesia (CILD7) with considerable variety in the clinical and beating cilia phenotype
Authors: Schultz Rüdiger , Elenius Varpu , Lukkarinen Heikki , Saarela Tanja
Published: November 2020

Background

Diagnosis of primary ciliary dyskinesia (PCD) still remains a challenge, especially with mutations in the Dynein Arm Heavy Chain 11 (DNAH11) gene. Classical diagnostic measures like Transmission Electron Microscopy (TEM) are not applicable for mutations in the DNAH11 gene since ultrastructural defects of the ciliary apparatus are absent. Novel mutations encoding for PCD appear all the time with considerable variation in the clinical picture, making it necessary to update data bases and guidelines for PCD diagnostics.

Methods

In this study we examined two unrelated, Finnish families with symptoms of PCD applying the clinical scoring system: Primary ciliary dyskinesia Rule (PICADAR), high speed video microscopy analysis (HSVMA) for ciliary movement, a commercially available gene panel analysis and nasal Nitric Oxide (nNO) measurements if applicable.

Results

Two, likely pathogenic variants in the DNAH11 gene (c.2341G > A, p. (Glu781Lys) ja c.7645 + 5G > A) were detected. In the first family, compound heterozygous mutations led to disease manifestation in two of 4 children, which showed a similar phenotype of cilia beating pattern but marked differences in disease severity. In the second family, all three children were homozygotes for the c.2341G > A p.(Glu781Lys) mutation and showed a similar degree of disease severity. However, the phenotype of cilia beating pattern was different ranging from stiff, static cilia to a hyperkinetic movement in one of these children.

Conclusions

In this study we describe two Finnish families with PCD, revealing two novel mutations in the DNAH11 gene which show considerable variety in the clinical and beating cilia phenotype. The results of this study show the clinician that PCD can be much milder than generally expected and diagnosis demands a combination of measures which are only successful in experienced hands. Chronic and repeatedly treated wet cough should raise suspicion of PCD, referring the patient for further diagnostics to a specialised PCD centre.
Changes to bone mineral density, the trabecular bone score and hip structural analysis following parathyroidectomy: a case report
Authors: Lin Raymond , Vucak-Dzumhur Mirna , Elder Grahame J.
Published: November 2020

Background

Reduction in bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) occurs in secondary hyperparathyroidism associated with chronic kidney disease. BMD generally increases following parathyroidectomy, however longitudinal changes to other DXA-derived parameters, the trabecular bone score (TBS) and hip structural analysis (HSA), have not been described. Postoperative calcium requirements and positive calcium balance raise concerns for an increased risk of vascular calcification. This case illustrates the dramatic increase in BMD that can follow parathyroidectomy in a patient on dialysis, and for the first time demonstrates improvements to HSA parameters and to the TBS.

Case presentation

A 30-year old woman on haemodialysis underwent subtotal parathyroidectomy for secondary hyperparathyroidism. She developed a post-operative ‘hungry bone syndrome’ requiring substantial calcium and calcitriol supplementation. Six months post-parathyroidectomy, BMD increased by 42% at the lumbar spine, 30% at the femoral neck and 25% at the total proximal femur, with increases sustained over the following 18 months. The TBS increased by 8%. HSA showed a 63% increase in femoral neck cortical thickness and 38% reduction in the buckling ratio, consistent with increased femoral neck stability. The abdominal aortic vascular calcification score (0–24) increased from zero 8-years pre-parathyroidectomy to 2/24 at 18-months post-parathyroidectomy.

Conclusion

BMD losses incurred by secondary hyperparathyroidism recover rapidly after parathyroidectomy, particularly at sites of trabecular bone. Bone architectural parameters, measured as the TBS and by HSA, also improve. Greater BMD gains may be associated with higher post-operative calcium requirements. While bone is the major reservoir for post-parathyroidectomy calcium supplementation, positive calcium balance may contribute to vascular calcification risk.
Elevation of erythrocyte sedimentation rate and C-reactive protein levels reflects renal interstitial inflammation in drug-induced acute tubulointerstitial nephritis
Authors: Zheng Xi-zi , Gu Yang-hui , Su Tao , Zhou Xu-jie , Huang Jun-wen , Sun Ping-ping , Jia Yan , Xu Da-min , Wang Su-xia , Liu Gang , Yang Li
Published: November 2020

Background

A renal biopsy is needed to define active inflammatory infiltration and guide therapeutic management in drug-induced acute tubulointerstitial nephritis (D-ATIN). However, factors such as various contraindications, refusal of informed consent and limited technical support may stop the biopsy process. It is thus of great importance to explore approaches that could deduce probable pathologic changes.

Methods

A total of 81 biopsy-proven D-ATIN patients were enrolled from a prospective cohort of ATIN patients at Peking University First Hospital. The systemic inflammation score (SIS) was developed based on the CRP and ESR levels at biopsy, and patients were divided into high-SIS, median-SIS, and low-SIS groups. The demographic data, clinicopathologic features, and renal outcomes were compared.

Results

The SIS was positively correlated with inflammatory cell infiltration and was inversely correlated with interstitial fibrosis. The number of interstitial inflammatory cells increased significantly with increasing SISs. The proportions of neutrophils and plasma cells were the highest in the high-SIS group compared with the other two groups. Prednisone (30–40 mg/day) was prescribed in all patients. The high-SIS group tended to have more favorable renal restoration than the other two groups. By 12 months postbiopsy, a decreased eGFR (< 60 mL/min/1.73 m2) was observed in 66.7% of medium-SIS patients, 32.4% of high-SIS patients, and 30.4% of low-SIS patients.

Conclusion

The SIS was positively correlated with active tubulointerstitial inflammation and therefore could help to aid therapeutic decisions in D-ATIN.
The effects of 16-weeks of prebiotic supplementation and aerobic exercise training on inflammatory markers, oxidative stress, uremic toxins, and the microbiota in pre-dialysis kidney patients: a randomized controlled trial-protocol paper
Authors: Headley Samuel A. , Chapman Donna J. , Germain Michael J. , Evans Elizabeth E. , Hutchinson Jasmin , Madsen Karen L. , Ikizler Talat Alp , Miele Emily M. , Kirton Kristyn , O’Neill Elizabeth , Cornelius Allen , Martin Brian , Nindl Bradley , Vaziri Nosratola D.
Published: November 2020

Background

Chronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated.

Methods

The study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3–4 CKD patients (ages of 30–75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55–65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks.

Discussion

This study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables.

Trial registration

Clinicaltrials.gov

Trial registration#NCT03689569.

9/28/2018, retrospectively registered.
Nocardiosis in glomerular disease patients with immunosuppressive therapy
Authors: Han Yuzhang , Huang Zineng , Zhang Huifang , He Liyu , Sun Lin , Liu Yu , Liu Fuyou , Xiao Li
Published: November 2020

Background

Glomerular disease patients have a high risk of infection, which contributes to the progression of disease per se and mortality, especially in those with long-term use of glucocorticoids and (or) immunosuppressive agents. Cases of sporadic nocardiosis have been reported in glomerular disease patients, and this observation was conducted to comprehensively understand the manifestations of and treatments for nocardiosis, which is commonly misdiagnosed as pneumonia or tuberculosis or even as lung cancer or metastatic tumors in glomerular disease patients.

Methods

We reviewed the demographic characteristics, laboratory abnormalities, radiological features, and treatments of 7 patients with nocardiosis and glomerular disease receiving steroids and immunosuppression therapy at the nephrology department of the Second Xiangya Hospital between 2012 and 2019.

Results

It was found that all 7 patients had been receiving methylprednisolone for renal disease at a median dose of 20 mg per day and a median duration of 4 months before developing nocardiosis. There were 4 males and 3 females, and the median age was 52.14 years. All 7 patients had hypoalbuminemia at the time of admission. In addition, various cystic abscesses in the subcutaneous tissue, with or without lung and brain involvement, were observed in these patients. Encouragingly, body temperatures returned to normal, and subcutaneous abscesses diminished or disappeared with compound sulfamethoxazole treatment alone or in combination with linezolid, imipenem and mezlocillin/sulbactam.

Conclusions

It was shown that multisite abscesses, including subcutaneous, pulmonary and cerebral abscesses, were the common manifestations of nocardiosis in glomerular disease patients. Sulfonamide was the first-line antibiotic therapy for nocardiosis, and combinations of other antibiotics were also needed in some serious cases.
Agreement between self-reported pre-pregnancy weight and measured first-trimester weight in Brazilian women
Authors:   Brazilian Maternal and Child Nutrition Consortium, Rangel Bousquet Carrilho Thaís , M. Rasmussen Kathleen , Rodrigues Farias Dayana , Freitas Costa Nathalia Cristina , Araújo Batalha Mônica , E. Reichenheim Michael , O. Ohuma Eric , Hutcheon Jennifer A. , Kac Gilberto
Published: November 2020

Background

Self-reported pre-pregnancy weight and weight measured in the first trimester are both used to estimate pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) but there is limited information on how they compare, especially in low- and middle-income countries, where access to a weight scale can be limited. Thus, the main goal of this study was to evaluate the agreement between self-reported pre-pregnancy weight and weight measured during the first trimester of pregnancy among Brazilian women so as to assess whether self-reported pre-pregnancy weight is reliable and can be used for calculation of BMI and GWG.

Methods

Data from the Brazilian Maternal and Child Nutrition Consortium (BMCNC, n = 5563) and the National Food and Nutritional Surveillance System (SISVAN, n = 393,095) were used to evaluate the agreement between self-reported pre-pregnancy weight and weights measured in three overlapping intervals (30–94, 30–60 and 30–45 days of pregnancy) and their impact in BMI classification. We calculated intraclass correlation and Lin’s concordance coefficients, constructed Bland and Altman plots, and determined Kappa coefficient for the categories of BMI.

Results

The mean of the differences between self-reported and measured weights was < 2 kg during the three intervals examined for BMCNC (1.42, 1.39 and 1.56 kg) and about 1 kg for SISVAN (1.0, 1.1 and 1.2 kg). Intraclass correlation and Lin’s coefficient were > 0.90 for both datasets in all time intervals. Bland and Altman plots showed that the majority of the difference laid in the ±2 kg interval and that the differences did not vary according to measured first-trimester BMI. Kappa coefficient values were > 0.80 for both datasets at all intervals. Using self-reported pre-pregnancy or measured weight would change, in total, the classification of BMI in 15.9, 13.5, and 12.2% of women in the BMCNC and 12.1, 10.7, and 10.2% in the SISVAN, at 30–94, 30–60 and 30–45 days, respectively.

Conclusion

In Brazil, self-reported pre-pregnancy weight can be used for calculation of BMI and GWG when an early measurement of weight during pregnancy is not available. These results are especially important in a country where the majority of woman do not initiate prenatal care early in pregnancy.
Linguistic validation of the simplified Chinese version of the US National Cancer Institute’s patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE™)
Authors: KKF Cheng , Mitchell S. A. , Chan N. , Ang E. , Tam W. , Kanesvaran R.
Published: November 2020

Background

The aim of this study was to translate and linguistically validate the U.S. National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) into Simplified Chinese for use in Singapore.

Methods

All 124 items of the English source PRO-CTCAE item library were translated into Simplified Chinese using internationally established translation procedures. Two rounds of cognitive interviews were conducted with 96 cancer patients undergoing adjuvant treatment to determine if the translations adequately captured the PRO-CTCAE source concepts, and to evaluate comprehension, clarity and ease of judgement. Interview probes addressed the 78 PRO-CTCAE symptom terms (e.g. fatigue), as well as the attributes (e.g. severity), response choices, and phrasing of ‘at its worst’. Items that met the a priori threshold of ≥20% of participants with comprehension difficulties were considered for rephrasing and retesting. Items where < 20% of the sample experienced comprehension difficulties were also considered for rephrasing if better phrasing options were available.

Results

A majority of PRO-CTCAE-Simplified Chinese items were well comprehended by participants in Round 1. One item posed difficulties in ≥20% and was revised. Two items presented difficulties in < 20% but were revised as there were preferred alternative phrasings. Twenty-four items presented difficulties in < 10% of respondents. Of these, eleven items were revised to an alternative preferred phrasing, four items were revised to include synonyms. Revised items were tested in Round 2 and demonstrated satisfactory comprehension.

Conclusions

PRO-CTCAE-Simplified Chinese has been successfully developed and linguistically validated in a sample of cancer patients residing in Singapore.
Human CD133-positive hematopoietic progenitor cells enhance the malignancy of breast cancer cells
Authors: Zhang Zhe , Zheng Qinglian , Liu Yonghui , Sun Lianqing , Han Pingping , Wang Rui , Zhao Jiao , Hu Shan , Zhao Xinhan
Published: November 2020

Background

Human CD133+ hematopoietic progenitor cells (HPCs) are a specific subset of cells that can regulate tumor malignancy. However, the mechanism by which CD133+ HPCs affect the malignancy of human breast cancer has not been reported.

Methods

CD133+ HPCs were isolated and purified from human umbilical cord blood (UCB). We used in vitro culture of MCF-7 and MDA-MB-231 cell lines, and MCF-7 and MDA-MB-231 cells in nude mice to evaluate whether CD133+ HPCs affected the apoptosis, proliferation, invasion and epithelial mesenchymal transition EMT of breast cancer cells.

Results

Co-culture with CD133+ HPCs, but not UCB CD133- cells, promoted the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells, accompanied by reducing in vitro spontaneous apoptosis. Co-administration of these two lines with CD133+ HPCs significantly enhanced the growth of implanted breast cancer in vivo. Furthermore, co-culture with CD133+ HPCs, enhanced the invasion of breast cancer cells, N-cadherin and Vimentin expression, but reduced E-cadherin expression in breast cancer cells.

Conclusions

Our study demonstrated that CD133+ HPCs enhance the malignancy of breast cancer cells by attenuating spontaneous apoptosis and promoting the process of epithelial mesenchymal transition. These findings may provide new insights into the role of human CD133+ HPCs in breast cancer pathogenesis. Therefore, CD133+ HPCs may be a new therapeutic target for inhibiting the progression of breast cancer.
Radiotherapy plays an important role in improving the survival outcome in patients with T1–2N1M0 breast cancer – a joint analysis of 4262 real world cases from two institutions
Authors: Sun Guang-Yi , Wen Ge , Zhang Yu-Jing , Tang Yu , Jing Hao , Wang Jian-Yang , Zhang Jiang-Hu , Yang Yong , Zhao Xu-Ran , Chen Si-Ye , Jin Jing , Song Yong-Wen , Liu Yue-Ping , Fang Hui , Ren Hua , Tang Yuan , Qi Shu-Nan , Li Ning , Chen Bo , Lu Ning-Ning , Wang Shu-Lian , Li Ye-Xiong
Published: November 2020

Background

To compare the survival outcomes between breast-conserving surgery (BCS) and modified radical mastectomy (MRM), and to investigate the role of radiotherapy (RT) in patients with pT1–2N1M0 breast cancer.

Methods

A total of 4262 women with T1–2N1M0 breast cancer treated at two institutions were retrospectively reviewed. A total of 3858 patients underwent MRM, and 832 (21.6%) of them received postoperative RT (MRM + RT). A total of 404 patients received BCS plus postoperative RT (BCS + RT). All patients received axillary lymph node dissection, while 3.8% of them had upfront sentinel node biopsy. The association of survival outcomes with different surgical modalities (BCS vs. MRM) and the role of RT were evaluated using multivariable proportional hazards regression and confirmed by the propensity score-matching (PSM) method.

Results

At a median follow-up of 71 months (range of 6–230 months), the 5-year overall survival (OS) rates of the BCS and MRM groups were 96.5 and 92.7%, respectively (P = .001), and the corresponding 5-year disease-free-survival (DFS) and locoregional recurrence (LRR) rates were 92.9 and 84.0%, and 2.0 and 7.0% (P = .001), respectively (P < .001). Multivariate analysis revealed that RT was an independent prognostic factor for improved OS (P = .001) and DFS (P = .009), and decreased LRR (P < .001). However, surgery procedure was not independently associated with either OS (P = .495), DFS (P = .204), or LRR (P = .996), which was confirmed by PSM analysis.

Conclusion

Postoperative radiotherapy rather than the surgery procedures was associated with superior survival outcomes in patients with T1–2N1M0 breast cancer.
Long non-coding RNA SNHG15 in various cancers: a meta and bioinformatic analysis
Authors: Chen Caizhi , Feng Yeqian , Wang Jingjing , Liang Ye , Zou Wen
Published: November 2020

Background

The snoRNA host gene SNHG15 produces a long non-coding RNA (lncRNA) with a short half-life and has been reported to be dysregulated in multiple cancers and has recently been found to be correlated with tumour progression. Therefore, this meta-analysis was performed to evaluate the generalised prognostic role of small nucleolar RNA host gene 15 (SNHG15) in malignancies, based on variable data from different studies.

Methods

Four public databases were used to identify eligible studies. The association between prognostic indicators and clinical features was extracted and pooled to estimate the hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was measured using Begg’s test and Egger’s test, and the stability of pooled results were measured using sensitivity analysis. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was screened to further validate our results. Ultimately, we predicted the molecular regulation of SNHG15 based on the public databases.

Results

In total, 11 studies including 1087 patients were ultimately enrolled in our meta-analysis. We found that SNHG15 overexpression was associated with worse overall survival (OS) and disease-free survival (DFS), and this was validated in the Gene Expression Profiling Interactive Analysis (GEPIA) cohort. Moreover, increased SNHG15 expression suggested advanced TNM stage and LNM, but was not associated with age, gender, or tumour size. No publication bias or instability of the results was observed. SNHG15 was significantly upregulated in seven cancers and elevated expression of SNHG15 indicated shorter OS and DFS in five malignancies based on the validation using the GEPIA cohort. Further functional prediction indicated that SNHG15 may participate in some cancer-related pathways.

Conclusions

Upregulation of lncRNA SNHG15 was notably associated with worse prognosis and clinical features, suggesting that SNHG15 might serve as a novel prognostic factor in various cancers.