bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of GeBP-like α factor by MiR827 suggests their involvement in senescence and phosphate homeostasis
Authors: Ma Chao , Chen Qiuju , Wang Shiping , Lers Amnon
Published: May 2021

Background

Leaf senescence is a genetically controlled degenerative process intimately linked to phosphate homeostasis during plant development and responses to environmental conditions. Senescence is accelerated by phosphate deficiency, with recycling and mobilization of phosphate from senescing leaves serving as a major phosphate source for sink tissues. Previously, miR827 was shown to play a significant role in regulating phosphate homeostasis, and induction of its expression was also observed during Arabidopsis leaf senescence. However, whether shared mechanisms underlie potentially common regulatory roles of miR827 in both processes is not understood. Here, we dissect the regulatory machinery downstream of miR827.

Results

Overexpression or inhibited expression of miR827 led to an acceleration or delay in the progress of senescence, respectively. The transcriptional regulator GLABRA1 enhancer-binding protein (GeBP)-like (GPLα) gene was identified as a possible target of miR827. GPLα expression was elevated in miR827-suppressed lines and reduced in miR827-overexpressing lines. Furthermore, heterologous co-expression of pre-miR827 in tobacco leaves reduced GPLα transcript levels, but this effect was eliminated when pre-miR827 recognition sites in GPLα were mutated. GPLα expression is induced during senescence and its inhibition or overexpression resulted in senescence acceleration and inhibition, accordingly. Furthermore, GPLα expression was induced by phosphate deficiency, and overexpression of GPLα led to reduced expression of phosphate transporter 1 genes, lower leaf phosphate content, and related root morphology. The encoded GPLα protein was localized to the nucleus.

Conclusions

We suggest that MiR827 and the transcription factor GPLα may be functionally involved in senescence and phosphate homeostasis, revealing a potential new role for miR827 and the function of the previously unstudied GPLα. The close interactions between senescence and phosphate homeostasis are further emphasized by the functional involvement of the two regulatory components, miR827 and GPLα, in both processes and the interactions between them.
Viscoelasticity measured by shear wave elastography in a rat model of nonalcoholic fatty liver disease: comparison with dynamic mechanical analysis
Authors: Pi Zhaoke , Wang Mengke , Lin Haoming , Guo Yanrong , Chen Siping , Diao Xianfen , Xia Hui , Liu Guoqiang , Zeng Jie , Zhang Xinyu , Chen Xin
Published: May 2021

Background

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common liver diseases. Ultrasound elastography has been used for the diagnosis of NAFLD. However, clinical research on steatosis by elastography technology has mainly focused on steatosis with fibrosis or non-alcoholic steatohepatitis (NASH), while steatosis without fibrosis has been poorly studied. Moreover, the relationship between liver viscoelasticity and steatosis grade is not clear. In this study, we evaluated the degree of liver steatosis in a simple steatosis rat model using shear wave elastography (SWE).

Results

The viscoelasticity values of 69 rats with hepatic steatosis were measured quantitatively by SWE in vivo and validated by a dynamic mechanical analysis (DMA) test. Pathological sections were used to determine the steatosis grade for each rat. The results showed that the elasticity values µ obtained by the two methods followed the same trend, and µ is significantly correlated with liver steatosis. The Pearson’s correlation coefficients indicate that $$\mu$$
μ
obtained by SWE is positively linear correlated with DMA (r = 0.628, p = 7.85 × 10–9). However, the viscosity values $$\eta$$
η
obtained by SWE were relatively independent of those obtained by DMA with a correlation coefficient of − 0.01. The combined Voigt elasticity measurements have high validity in the prediction of steatosis (S0 vs. S1–S4), with an AUROC of 0.755 (95% CI 0.6175–0.8925, p < 0.01) and the optimal cutoff value was 2.08 kPa with a sensitivity of 78% and specificity of 63%.

Conclusion

SWE might have the feasibility to be introduced as an auxiliary technique for NAFLD patients in clinical settings. However, the viscosity results measured by SWE and DMA are significantly different, because the two methods work in different frequency bands.
High-resolution age-specific mapping of the two-week illness prevalence rate based on the National Health Services Survey and geostatistical analysis: a case study in Guangdong province, China
Authors: Wen Chuchun , Huang Xiaoliang , Feng Lifen , Chen Long , Hu Wei , Lai Yingsi , Hao Yuantao
Published: May 2021

Background

The two-week illness prevalence rate is an important and comparable indicator of health service needs. High-spatial-resolution, age-specific risk mapping of this indicator can provide valuable information for health resource allocation. The age-prevalence relationships may be different among areas of the study region, but previous geostatistical models usually ignored the spatial-age interaction.

Methods

We took Guangdong province, the province with the largest population and economy in China, as a study case. We collected two-week illness data and other potential influencing predictors from the fifth National Health Services Survey in 2013 and other open-access databases. Bayesian geostatistical binary regression models were developed with spatial-age structured random effect, based on which, high-resolution, age-specific two-week illness prevalence rates, as well as number of people reporting two-week illness, were estimated. The equality of health resource distribution was further evaluated based on the two-week illness mapping results and the health supply data.

Results

The map across all age groups revealed that the highest risk was concentrated in the central (i.e., Pearl River Delta) and northern regions of the province. These areas had a two-week illness prevalence > 25.0%, compared with 10.0–20.0% in other areas. Age-specific maps revealed significant differences in prevalence between age groups, and the age-prevalence relationships also differed across locations. In most areas, the prevalence rates decrease from age 0 to age 20, and then increase gradually. Overall, the estimated age- and population-adjusted prevalence was 16.5% [95% Bayesian credible interval (BCI): 14.5–18.6%], and the estimated total number of people reporting illness within the two-week period was 17.5 million (95% BCI: 15.5–19.8 million) in Guangdong Province. The Lorenz curve and the Gini coefficient (resulted in 0.3526) showed a moderate level of inequality in health resource distribution.

Conclusions

We developed a Bayesian geostatistical modeling framework with spatial-age structured effect to produce age-specific, high-resolution maps of the two-week illness prevalence rate and the numbers of people reporting two-week illness in Guangdong province. The methodology developed in this study can be generalized to other global regions with available relevant survey data. The mapping results will support plans for health resource allocation.
Unclassified mesenchymal sarcoma with NTRK1-KHDRBS1 gene fusion: a case report of long-term tumor-free survival with crizotinib treatment
Authors: Chen Weijie , Wang Huimei , Jiang Dongxian , Luan Lijuan , Zhou Yuhong , Hou Yingyong
Published: May 2021

Background

Mesenchymal sarcomas are tumors that originate from mesenchymal tissue. Most mesenchymal sarcomas can be accurately classified, but some are unclassifiable in clinical practice. Molecular detection methods enable patients to benefit from molecular-targeted therapies for many cancers, including lung, breast, and bowel cancers. Further, even unclassified tumors can have therapeutic targets. NTRK gene fusions are sporadic genetic alterations that occur across tumor entities. If NTRK gene fusions are detected, TRK inhibitors can be used regardless of the tumor entity.

Case presentation

This report describes a case with an unclassifiable mesenchymal sarcoma carrying a neurotrophic tyrosine receptor kinase NTRK1-KHDRBS1 gene fusion that was diagnosed and treated at multiple hospitals. Diagnostic work-up included pathological and immunohistochemical analysis, which excluded angiosarcoma, dendritic cell sarcoma, and pseudomyogenic hemangioendothelioma. The patient achieved a long-term survival without tumor relapse after treatment with crizotinib.

Conclusions

This case will be of significant interest to pathologists because, despite the tumor being unclassified, a molecular target was identified. Although the FDA does not currently approve crizotinib for treatment of patients harboring NTRK gene fusions, this case provides new insights for diagnosis and treatment of mesenchymal sarcomas with NTRK1 gene translocations. Similar to ALKomas, which can be successfully treated using NTRK molecular-targeted therapy, tumors with NTRK gene translocations can be classified as NTRKomas, even when they occur at different organ sites, and with varying histological morphologies, and immunophenotypes.
Risk factors for central lymph node metastasis in the cervical region in papillary thyroid carcinoma: a retrospective study
Authors: Li Xiang , Zhang Hanwen , Zhou Yu , Cheng Ruochuan
Published: May 2021

Background

To investigate the influence of different risk factors on central lymph node metastasis (CLNM) in the cervical region in patients with papillary thyroid carcinoma (PTC).

Methods

This retrospective study included 2586 PTC patients. Potential risk factors were identified by univariate analysis, and the relationships between these factors and CLNM were ascertained by multivariable analysis. A scoring system was constructed, and the optimal cut-off value was determined.

Results

On univariate analysis, sex, age, tumor diameter, multifocality, capsule invasion, vascular invasion, total number of lymph nodes in the central region, and serum thyroid peroxidase antibody (TPOAb) concentration were identified as potential risk factors for CLNM in the cervical region, whereas nerve invasion, thyroid-stimulating hormone concentration, and thyroglobulin antibody (TgAb) concentration were not. Multivariable analysis indicated that male sex, young age, large tumor diameter, multifocality, vascular invasion, a large number of central lymph nodes, and a low TPOAb concentration were significant risk factors. From these factors, a preoperative CLNM risk assessment scale was constructed for predicting CLNM in the cervical region for PTC patients.

Conclusion

Male sex, young age, large tumor diameter, multifocality, vascular invasion, a large number of central lymph nodes, and a low TPOAb concentration were positively correlated with CLNM in the cervical region in PTC patients. The preoperative CLNM risk assessment scale based on these risk factors is expected to offer accurate preoperative assessment of central lymph node status in PTC patients.
Assessing preparation for care transition among adolescents with rheumatologic disease: a single-center assessment with patient survey
Authors: Roberts Jordan E. , Halyabar Olha , Petty Carter R. , Son Mary Beth
Published: May 2021

Background

Despite the risk for poor outcomes and gaps in care in the transfer from pediatric to adult care, most pediatric rheumatology centers lack formal transition pathways. As a first step in designing a pathway, we evaluated preparation for transition in a single-center cohort of adolescents and young adults (AYA) with rheumatologic conditions using the ADolescent Assessment of Preparation for Transition (ADAPT) survey.

Findings

AYA most frequently endorsed receiving counseling on taking charge of their health and remembering to take medications. Less than half reported receiving specific counseling about transferring to an adult provider.

AYA with lower education attainment compared with those who had attended some college or higher had lower scores in self-management (1.51 vs 2.52, p = 0.0002), prescription medication counseling (1.96 vs 2.41, p = 0.029), and transfer planning (0.27 vs 1.62, p < 0.001). AYA with a diagnosis of MCTD, Sjögren’s or SLE had higher self-management scores than those with other diagnoses (2.6 vs 1.9; p = 0.048). Non-white youth indicated receiving more thorough medication counseling than white youth (2.71 vs 2.07, p = 0.027).

When adjusting for age, educational attainment remained an independent predictor of transfer planning (p = 0.037). AYA with longer duration of seeing their physician had higher transition preparation scores (p = 0.021).

Conclusion

Few AYA endorsed receiving comprehensive transition counseling, including discussion of transfer planning. Those who were younger and with lower levels of education had lower preparation scores. A long-term relationship with providers was associated with higher scores. Further research, including longitudinal assessment of transition preparation, is needed to evaluate effective processes to assist vulnerable populations.
Factors associated with reduced infliximab exposure in the treatment of pediatric autoimmune disorders: a cross-sectional prospective convenience sampling study
Authors: Funk Ryan S. , Shakhnovich Valentina , Cho Yu Kyoung , Polireddy Kishore , Jausurawong Taina , Gress Kyle , Becker Mara L.
Published: May 2021

Background

Inadequate systemic exposure to infliximab (IFX) is associated with treatment failure. This work evaluated factors associated with reduced IFX exposure in children with autoimmune disorders requiring IFX therapy.

Methods

In this single-center cross-sectional prospective study IFX trough concentrations and anti-drug antibodies (ADAs) were measured in serum from children diagnosed with inflammatory bowel disease (IBD) (n = 73), juvenile idiopathic arthritis (JIA) (n = 16), or uveitis (n = 8) receiving maintenance IFX infusions at an outpatient infusion clinic in a tertiary academic pediatric hospital. IFX concentrations in combination with population pharmacokinetic modeling were used to estimate IFX clearance. Patient demographic and clinical data were collected by chart review and evaluated for their relationship with IFX clearance.

Results

IFX trough concentrations ranged from 0 to > 40 μg/mL and were 3-fold lower in children with IBD compared to children with JIA (p = 0.0002) or uveitis (p = 0.001). Children with IBD were found to receive lower IFX doses with longer dosing intervals, resulting in dose intensities (mg/kg/day) that were 2-fold lower compared to children with JIA (p = 0.0002) or uveitis (p = 0.02). Use of population pharmacokinetic analysis to normalize for variation in dosing practices demonstrated that increased IFX clearance was associated with ADA positivity (p = 0.004), male gender (p = 0.02), elevated erythrocyte sedimentation rate (ESR) (p = 0.02), elevated c-reactive protein (CRP) (p = 0.001), reduced serum albumin concentrations (p = 0.0005), and increased disease activity in JIA (p = 0.009) and IBD (p ≤ 0.08). No significant relationship between diagnosis and underlying differences in IFX clearance was observed. Multivariable analysis by covariate population pharmacokinetic modeling confirmed increased IFX clearance to be associated with anti-IFX antibody positivity, increased ESR, and reduced serum albumin concentrations.

Conclusions

Enhanced IFX clearance is associated with immunogenicity and inflammatory burden across autoimmune disorders. Higher systemic IFX exposures observed in children with rheumatologic disorders are driven primarily by provider drug dose and interval selection, rather than differences in IFX pharmacokinetics across diagnoses. Despite maintenance IFX dosing at or above the standard recommended range for IBD (i.e., 5 mg/kg every 8 weeks), the dosing intensity used in the treatment of IBD is notably lower than dosing intensities used to treat JIA and uveitis, and may place some children with IBD at risk for suboptimal maintenance IFX exposures necessary for treatment response.
Integrase inhibitors versus efavirenz combination antiretroviral therapies for TB/HIV coinfection: a meta-analysis of randomized controlled trials
Authors: Shu Yuanlu , Deng Ziwei , Wang Hongqiang , Chen Yi , Yuan Lijialong , Deng Ye , Tu Xiaojun , Zhao Xiang , Shi Zhihua , Huang Minjiang , Qiu Chengfeng
Published: May 2021

Background

Integrase inhibitors (INIs)-based antiretroviral therapies (ART) are more recommended than efavirenz (EFV)-based ART for people living with HIV/AIDS (PLWHA). Yet, the advantage of integrase inhibitors in treating TB/HIV coinfection is uncertain. Therefore, the objective of this systematic review is to evaluate the effects and safety of INIs- versus EFV-based ART in TB/HIV coinfection, and demonstrate the feasibility of the regimens.

Methods

Four electronic databases were systematically searched through September 2020. Fixed-effects models were used to calculate pooled effect size for all outcomes. The primary outcomes were virologic suppression and bacteriology suppression for INIs- versus EFV-based ART. Secondary outcomes included CD4+ cell counts change from baseline, adherence and safety.

Results

Three trials (including 672 TB/HIV patients) were eligible. ART combining INIs and EFV had similar effects for all outcomes, with none of the point estimates argued against the INIs-based ART on TB/HIV patients. Compared to EFV-based ART as the reference group, the RR was 0.94 (95% CI 0.85 to 1.05) for virologic suppression, 1.00 (95% CI 0.95 to 1.05) for bacteriology suppression, 0.98 (95% CI 0.95 to 1.01) for adherence. The mean difference in CD4+ cell counts increase between the two groups was 14.23 cells/μl (95% CI 0− 6.40 to 34.86). With regard to safety (adverse events, drug-related adverse events, discontinuation for drugs, grade 3–4 adverse events, IRIS (grade 3–4), and death), INIs-based regimen was broadly similar to EFV-based regimens. The analytical results in all sub-analyses of raltegravir- (RAL) and dolutegravir (DTG) -based ART were valid.

Conclusion

This meta-analysis demonstrates similar efficacy and safety of INIs-based ART compared with EFV-based ART. This finding supports INIs-based ART as a first-line treatment in TB/HIV patients. The conclusions presented here still await further validation owing to insufficient data.
The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China
Authors: Song Zhilin , Cui Yanru , Li Qiufu , Deng Junhang , Ding Xianping , He Jiaoyu , Liu Yiran , Ju Zhuang , Fang Liyuan
Published: May 2021

Background

Variations in human papillomavirus (HPV) E6 and E7 have been shown to be closely related to the persistence of the virus and the occurrence and development of cervical cancer. Long control region (LCR) of HPV has been shown multiple functions on regulating viral transcription. In recent years, there have been reports on E6/E7/LCR of HPV-16 and HPV-58, but there are few studies on HPV-52, especially for LCR. In this study, we focused on gene polymorphism of the HPV-52 E6/E7/LCR sequences, assessed the effects of variations on the immune recognition of viral E6 and E7 antigens, predicted the effect of LCR variations on transcription factor binding sites and provided more basic date for further study of E6/E7/LCR in Chengdu, China.

Methods

LCR/E6/E7 of the HPV-52 were amplified and sequenced to do polymorphic and phylogenetic analysis. Sequences were aligned with the reference sequence by MEGA 7.0 to identify SNP. A neighbor-joining phylogenetic tree was constructed by MEGA 7.0, followed by the secondary structure prediction of the related proteins using PSIPRED 4.0. The selection pressure of E6 and E7 coding regions were estimated by Bayes empirical Bayes analysis of PAML 4.9. The HLA class-I and II binding peptides were predicted by the Immune Epitope Database server. The B cell epitopes were predicted by ABCpred server. Transcription factor binding sites in LCR were predicted by JASPAR database.

Results

50 SNP sites (6 in E6, 10 in E7, 34 in LCR) were found. From the most variable to the least variable, the nucleotide variations were LCR > E7 > E6. Two deletions were found between the nucleotide sites 7387–7391 (TTATG) and 7698–7700 (CTT) in all samples. A deletion was found between the nucleotide sites 7287–7288 (TG) in 97.56% (40/41) of the samples. The combinations of all the SNP sites and deletions resulted in 12 unique sequences. As shown in the neighbor-joining phylogenetic tree, except for one belonging to sub-lineage C2, others sequences clustered into sub-lineage B2. No positive selection was observed in E6 and E7. 8 non-synonymous amino acid substitutions (including E3Q and K93R in the E6, and T37I, S52D, Y59D, H61Y, D64N and L99R in the E7) were potential affecting multiple putative epitopes for both CD4+ and CD8+ T-cells and B-cells. A7168G was the most variable site (100%) and the binding sites for transcription factor VAX1 in LCR. In addition, the prediction results showed that LCR had the high probability binding sites for transcription factors SOX9, FOS, RAX, HOXA5, VAX1 and SRY.

Conclusion

This study provides basic data for understanding the relation among E6/E7/LCR mutations, lineages and carcinogenesis. Furthermore, it provides an insight into the intrinsic geographical relatedness and biological differences of the HPV-52 variants, and contributes to further research on the HPV-52 therapeutic vaccine development.
The relationship of different levels of high iodine and goiter in school children: a meta-analysis
Authors: Xu Tingting , Ren Zhiyuan , Li Shaohan , Tan Long , Zhang Wanqi
Published: May 2021

Background

Over the past decade, the phenomenon of high urine iodine (HUI) and high water iodine (HWI) has become more common. But the risk of goiter caused by different levels of HUI and HWI remains unclear.

Objectives

To explore the risk of goiter development caused by HUI and HWI, and compare the risk of goiter development from different levels of high iodine.

Methods

The Medline, Cochrane library, Embase, China National Knowledge Infrastructure and Wan fang databases were searched for relevant population-based studies investigating the link between high iodine levels and goiter development in mainland China. Three reviewers extracted data from the included studies independently, assessing the prevalence of goiter development due to high iodine.

Results

Taking 100 μg/L ≤ UIC < 300 μg/L (UIC = urinary iodine concentration) as the reference group, the odds ratio (OR) regarding high iodine levels and goiter formation was 1.74 (95% CI 1.50, 2.01,P < 0.001), if the water iodine concentration (WIC) was greater than 100 μg/L, the OR between goiter development and WIC was 4.74 (95% CI 1.15, 19.46,P = 0.001). The Linear trend analysis of HUI and goiter showed that the prevalence of goiter increased with the increase of UIC (χ2 = 734.605, P < 0.001).

Conclusions

When the UIC ≥ 300 μg/L or the WIC ≥ 100 μg/L, the risk of goiter will increase. The higher the UIC, the greater the risk of goiter development. In order to improve the public thyroid health, we should adhere to the monitoring of urinary iodine and water iodine, and keep them at an appropriate level.

Trial registration

PROSPEROCR, CRD42020197620. Registered 8 August 2020,https://www.crd.york.ac.uk/PROSPERO/.
Subjective symptoms and serum methadone concentrations: what should guide dose adjustments in methadone maintenance treatment? A naturalistic cohort study from Norway
Authors: Chalabianloo Fatemeh , Fadnes Lars Thore , Høiseth Gudrun , Ohldieck Christian , Vold Jørn Henrik , Aas Christer , Løberg Else-Marie , Johansson Kjell Arne , Bramness Jørgen G.
Published: May 2021

Background

There is little evidence-based guidance on how to optimize methadone dosages among patients with opioid addiction undergoing methadone maintenance treatment (MMT). This study aims to investigate whether self-perceived opioid withdrawal symptoms, adverse effects, and self-reported substance use in patients on MMT are related to serum methadone concentrations and the role that these variables could play in clinical decisions on dose adjustments.

Methods

This naturalistic prospective cohort study included clinical and laboratory measurements from 83 patients undergoing MMT in outpatient clinics in Bergen, Norway, from May 2017 to January 2020. Information on age, gender, methadone daily doses and serum concentrations, subjective opioid withdrawal symptoms using 16 items Subjective Opioid Withdrawal Scale (SOWS) questionnaire, self-reported adverse effects, and substance use was obtained. Linear mixed modelling was used for analyzing the data.

Results

The mean age of the participants was 45 years, and 33% were women. Almost half reported mild to moderate subjective opioid withdrawal symptoms, and all had experienced at least one subjective adverse effect. The use of at least one substance was reported by 88% of the participants. Serum concentration-to-dose ratios were lower among those who had reported subjective opioid withdrawal symptoms (p) = 0.039). The total SOWS score (p < 0.001); the specific subjective withdrawal symptoms of anxiety (p = 0.004), bone and muscle aches (p = 0.003), restlessness (p = 0.017), and (slightly) shaking (p = 0.046), also use of heroin (p = 0.015) and alcohol (p = 0.011) were associated with lower methadone concentrations. Cannabis use was slightly related to higher methadone concentrations (p = 0.049).

Conclusions

The findings suggest that the patient’s self-perceived symptoms and current clinical condition are related to the serum concentrations of methadone. This interpretation supports dose adjustments based on patient-reported symptoms. In some aberrant cases, measurement of serum concentrations together with other individual assessments may be considered to support the clinical decision.
An ionising radiation-induced specific transcriptional signature of inflammation-associated genes in whole blood from radiotherapy patients: a pilot study
Authors: Cruz-Garcia Lourdes , Badie Christophe , Anbalagan Selvakumar , Moquet Jayne , Gothard Lone , O’Brien Grainne , Somaiah Navita , Ainsbury Elizabeth A.
Published: May 2021

Background

This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients.

Methods

Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumours. Nanostring nCounter analysis of transcriptional changes was carried out in samples prior and 24 h post-delivery of the 1st radiotherapy fraction, just prior to the 5th or 6th fraction, and just before the last fraction.

Results

Statistical analysis with BRB-ArrayTools, GLM MANOVA and nSolver, revealed a radiation responsive panel of genes which varied by patient group (type of cancer) and with time since exposure (as an analogue for dose received), which may be useful as a biomarker of radiation response.

Conclusion

Further validation in a wider group of patients is ongoing, together with work towards a full understanding of patient specific responses in support of personalised approaches to radiation medicine.
A survey among German-speaking radiation oncologists on PET-based radiotherapy of prostate cancer
Authors: Vogel Marco M. E. , Dewes Sabrina , Sage Eva K. , Devecka Michal , Gschwend Jürgen E. , Eiber Matthias , Combs Stephanie E. , Schiller Kilian
Published: May 2021

Background

Positron emission tomography-(PET) has evolved as a powerful tool to guide treatment for prostate cancer (PC). The aim of this survey was to evaluate the acceptance and use of PET—especially with prostate-specific membrane antigen (PSMA) targeting tracers—in clinical routine for radiotherapy (RT) and the impact on target volume definition and dose prescription.

Methods

We developed an online survey, which we distributed via e-mail to members of the German Society of Radiation Oncology (DEGRO). The survey included questions on patterns of care of RT for PC with/without PET. For evaluation of doses we used the equivalent dose at fractionation of 2 Gy with α/β = 1.5 Gy [EQD2(1.5 Gy)].

Results

From 109 participants, 78.9% have the possibility to use PET for RT planning. Most centers use PSMA-targeting tracers (98.8%). In 39.5%, PSMA-PET for biochemical relapse after prior surgery is initiated at PSA ≥ 0.5 ng/mL, while 30.2% will perform PET at ≥ 0.2 ng/mL (≥ 1.0 ng/mL: 16.3%, ≥ 2.0 ng/mL: 2.3%, regardless of PSA: 11.7%). In case of PET-positive local recurrence (LR) and pelvic lymph nodes (LNs), 97.7% and 96.5% of the participants will apply an escalated dose. The median total dose in EQD2(1.5 Gy) was 70.00 Gy (range: 56.89–85.71) for LR and 62.00 Gy (range: 52.61–80.00) for LNs. A total number of ≤ 3 (22.0%) or ≤ 5 (20.2%) distant lesions was most often described as applicable for the definition as oligometastatic PC.

Conclusion

PSMA-PET is widely used among German radiation oncologists. However, specific implications on treatment planning differ among physicians. Therefore, further trials and guidelines for PET-based RT are warranted.
Comparison of outcomes of ORIF versus bidirectional tractor and arthroscopically assisted CRIF in the treatment of lateral tibial plateau fractures: a retrospective cohort study
Authors: Deng Xiangtian , Hu Hongzhi , Zhang Yiran , Liu Weijian , Song Qingcheng , Cheng Xiaodong , Zhu Jian , Yang Sifan , Ye Zhipeng , Guan Haitao , Zhang Boyu , Zheng Zhanle , Zhang Yingze
Published: May 2021

Background

Lateral tibial plateau fractures (TPFs) are often treated with conventional open reduction and internal fixation (ORIF) through standard anterolateral sub-meniscal arthrotomy. There has been increasing support for “bidirectional rapid redactor” device-assisted closed reduction and internal fixation (CRIF) for treating TPFs. The aim of the present study is to compare the clinical and radiological outcomes between CRIF and ORIF procedures.

Methods

We performed a retrospective cohort study of 55 lateral TPF patients (Schatzker types I–III) who accepted surgical treatment at our trauma level 1 center between January 2016 and January 2018. They were divided into the CRIF group (32 patients) and the ORIF group (23 patients) based upon the different surgical protocols. The patients’ clinical outcome analysis was evaluated by using the Knee Society Score (KSS) and Rasmussen’s clinical score. For radiological assessment, changes in tibial plateau width (TPW), articular depression depth (ADD), medial proximal tibial angle (MPTA), and posterior tibial slope angle (PTSA) were evaluated using radiographs and computed tomography (CT) scan.

Results

The CRIF group had a mean follow-up of 28.9 months, and the ORIF group had a mean follow-up of 30.7 months (p>0.05). Furthermore, there was no statistically significant difference in terms of age, gender, injury mechanism, follow-up time, time interval from injury to surgery, and Schatzker classification in the two groups. With respect to the clinical outcomes including the KSS score and Rasmussen’s clinical score, there was also no significant difference (p>0.05). Nevertheless, the CRIF group had lower intra-operative blood loss, shorter hospitalization days, and better range of movement of the knee joint than the ORIF group (p<0.05). Furthermore, CRIF had better radiological results when compared to the ORIF group using Rasmussen’s radiological score (p<0.05), although no significant difference was observed in TPW, ADD, MPTA, and PTSA between the two groups (p>0.05).

Conclusion

The present study showed that CRIF could achieve comparable clinical outcomes and better radiological results for treating lateral TPFs as compared with conventional ORIF.
A technique for repairing rotator cuff transtendinous tears with a remnant attached to the footprint
Authors: Choi Hyung-Suk , Lee Byung-Ill , Kim Jae-Hyung , Cho Hyung-Ki , Seo Gi-Won
Published: May 2021

Background

Some unusual rotator cuff (RC) tears are located in more proximal tendinous portions, with substantial remnant tissue attached to the footprint. The two options for surgical repair are sacrificing or preserving the remnant tissue. We introduce a surgical repair technique that preserves as much of the remnant footprint as possible.

Surgical technique

A double-loaded suture anchor is inserted into the subchondral bone at the medial portion of the RC footprint; the lateral remnant tissue is preserved. Each strand is shuttled and repassed through the medial portion of the tendon in a mattress fashion using a suture hook device. Then, multiple no. 1 PDS sutures are passed through the medial and lateral stumps and left untied. Strands from the suture anchor are first tied in a double mattress fashion. Then, the repair is completed by tying the remaining no. 1 PDS sutures.

Conclusions

We propose a remnant-preserving RC repair technique for transtendinous RC tears with sufficient tissue remaining within the RC footprint. This technique appears advantageous in terms of re-establishing an environment that promotes tendon healing after repair.
Multiple arterial conduits for multi-vessel coronary artery bypass grafting in patients with mild to moderate left ventricular systolic dysfunction: a multicenter retrospective study
Authors: Zhang Hang , Chen Wen , Zhao Yang , Guan Lichun , Yu Min , Wang Rui , Chen Xin
Published: May 2021

Background

Advantages of multiple arterial conduits for coronary artery bypass grafting (CABG) have been reported previously. We aimed to evaluate the mid-term outcomes of multiple arterial CABG (MABG) among patients with mild to moderate left ventricular systolic dysfunction (LVSD).

Methods

This multicenter study using propensity score matching took place from January 2013 to June 2019 in Jiangsu Province and Shanghai, China, with a mean and maximum follow-up of 3.3 and 6.8 years, respectively. We included patients with mild to moderate LVSD, undergoing primary, isolated multi-vessel CABG with left internal thoracic artery. The in-hospital and mid-term outcomes of MABG versus conventional left internal thoracic artery supplemented by saphenous vein grafts (single arterial CABG) were compared. The primary end points were death from all causes and death from cardiovascular causes. The secondary end points were stroke, myocardial infarction, repeat revascularization, and a composite of all mentioned outcomes, including death from all causes (major adverse events). Sternal wound infection was included with 6 months of follow-up after surgery.

Results

243 and 676 patients were formed in MABG and single arterial CABG cohorts after matching in a 1:3 ratio. In-hospital death was not significantly different (MABG 1.6% versus single arterial CABG 2.2%, p = 0.78). After a mean (±SD) follow-up time of 3.3 ± 1.8 years, MABG was associated with lower rates of major adverse events (HR, 0.64; 95% CI, 0.44–0.94; p = 0.019), myocardial infarction (HR, 0.39; 95% CI, 0.16–0.99; p = 0.045) and repeat revascularization (HR, 0.42; 95% CI, 0.18–0.97; p = 0.034). There was no difference in the rates of death, stroke, and sternal wound infection.

Conclusions

MABG was associated with reduced mid-term rates of major adverse events and cardiovascular events and may be the procedure of choice for patients with mild to moderate LVSD requiring CABG.
Prognostic impact of lymph node metastasis along the left gastric artery in esophageal squamous cell carcinoma
Authors: Liu Xuan , Wu Leilei , Zhang Dongkun , Lin Peng , Long Hao , Zhang Lanjun , Ma Guowei
Published: May 2021

Background

Although the incidence of lymph node (LN) metastasis (LNM) along the left gastric artery is high, its relationship with the prognosis in postoperative patients with esophageal squamous cell carcinoma (ESCC) is rarely reported. This study clarified the prognostic impact of LNM along the left gastric artery in postoperative patients with ESCC.

Methods

This study assessed data of 1521 patients with ESCC who underwent esophagectomy at the Sun Yat-sen University Cancer Center between March 1992 and March 2012. A chi-squared test and Mann-Whitney U test were used to explore the preliminary correlation between clinical factors and LNM along the left gastric artery. Univariate and multivariate Cox regression analyses were used to assess whether LNM along the left gastric artery was an independent predictor of overall survival. Kaplan–Meier analysis and the log-rank test were used to present a classifying effect based on LN status.

Results

LNM was observed in 598 patients (39.3%) and was found along the branches of the left gastric artery in 256 patients (16.8%). The patients were classified into two groups based on the presence of LNM along the left gastric artery. Patients without LNM along the left gastric artery had better cancer-specific survival than those with positive LNs (P <  0.001).

Conclusions

This study indicated that LNM along the left gastric artery was an important independent prognostic factor for long-term survival among ESCC patients (P = 0.011).
Comparative analysis of postoperative sexual dysfunction and quality of life in type a aortic dissection patients of different ages
Authors: Luo Zeng-Rong , Liao Dong-Shan , Chen Liang-Wan
Published: May 2021

Background

To compare postoperative sexual dysfunction (SD) and quality of life (QOL) in Type A Aortic Dissection (AAD) Patients of Different Ages.

Methods

From January 2018 to December 2019, 204 AAD postoperative survivors in Union Hospital of Fujian Medical University were selected and were divided into young group (less than 50 years old) and elderly group (more than 50 years old). We evaluated SD according to the male International Erectile Dysfunction Index (IIEF-5) and female sexual function index (FSFI). The Short Form 12 Health Survey Questionnaire (SF-12) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were used to investigate the QOL, Quick Inventory Depressive Symptomatology-Self Report (QIDS-SR) and the Beck Depression Inventory-II (BDI-II) to investigate depressive symptoms.

Results

One hundred seventy-five patients completed all the questionnaire (85.8%). The total SD prevalence rate was 38.9% (68 cases), with 27.4% of the young (20 cases) and 47.1% of the elderly (48 cases). The age of non-SD and SD patients was 49.0 ± 11.5 and 56.9 ± 10.8 years, respectively (P = 0.03). Compared with non-SD patients, the total physical health of SD patients was significantly worse (P = 0.04), however, the mental health was not significantly worse (P = 0.77); the depressive symptoms did not expressed a significant difference between the SD and non-SD groups (QIDS-SR P = 0.15, BDI-II P = 0.06). Total physical health scores in the young SD group did not show significant better than elderly SD group (P = 0.24), however, total mental health scores showed significantly worse (P = 0.04), depressive symptoms scores were significantly higher (QIDS-SR P = 0.03, BDI-II P = 0.04).

Conclusion

The postoperative AAD SD prevalence of elderly is higher than that of young, and the total physical health of SD patients is poorer than those without SD patients. The young SD patients did not show a significant higher physical health scores than the elderly SD patients, instead, the young SD patients were more psychologically affected than the elderly SD patients, whose mental health was worse, and depression symptoms were more obvious, suggesting that the factors affecting the QOL of postoperative SD patients are related to physical factors, but the young postoperative SD patients mainly affected by psychological factors.
Survival risk prediction model for patients with pT1–3 N0M0 esophageal squamous cell carcinoma after R0 esophagectomy with two-field lymphadenectomy for therapeutic purposes
Authors: Qi Zhan , Hu Yuanping , Qiu Rong , Li Juan , Li Yuekao , He Ming , Wang Yuxiang
Published: May 2021

Background

The overall survival (OS) remains unsatisfactory in patients with esophageal squamous cell carcinoma (ESCC) after extended esophagectomy with two-field lymphadenectomy. Therefore, this retrospective study aimed to identify the risk factors that contribute to the low survival of patients with pT1–3N0M0 ESCC.

Methods

Patients with pT1–3N0M0 ESCC who only underwent R0 esophagectomy with two-field lymphadenectomy in our department from January 2008 to December 2012 were retrospectively enrolled in this study and medical records were reviewed. Postoperative OS, disease-free survival (DFS), recurrence-free survival (RFS), and locoregional recurrence-free survival (LRFS) were analyzed sequentially.

Results

This study recruited a total of 488 patients, whose follow-up visits were completed at the end of December 2019. The five-year OS, DFS, RFS and LRFS rates were 62.1, 53.1, 58.3 and 65.6%, respectively. Multivariate Cox analysis identified patient age, site of the lesion, small mediastinal lymph nodes in CT imaging (SLNs in CT), dissected lymph nodes (LNs), and stage of esophageal malignancy as independent risk factors for OS of the patients. Of these factors, the site of the lesion, SLNs in CT and stage of the cancer were determined to be independent factors for DFS, RFS and LRFS. Based on all five factors, the recursive partitioning analysis (RPA) score system was developed to stratify the patients into low-, medium- and high-risk groups, which were found to possess significantly different rates of OS, DFS, RFS and LRFS (p < 0.001).

Conclusions

Several factors were associated with the survival of patients with pT1–3 N0M0 ESCC who underwent extended esophagectomy with two-field lymphadenectomy. These factors contributed to the RPA scoring system, which could stratify the risk of postoperative survival and may expedite the initiation of postoperative adjuvant therapy.
PH CARE COVID survey: an international patient survey on the care for pulmonary hypertension patients during the early phase of the COVID-19 pandemic
Authors: Godinas Laurent , Iyer Keerthana , Meszaros Gergely , Quarck Rozenn , Escribano-Subias Pilar , Vonk Noordegraaf Anton , Jansa Pavel , D’Alto Michele , Luknar Milan , Milutinov Ilic Senka , Belge Catharina , Sitbon Olivier , Reis Abílio , Rosenkranz Stephan , Pepke-Zaba Joanna , Humbert Marc , Delcroix Marion
Published: May 2021

Background

During the COVID-19 pandemic, most of the health care systems suspended their non-urgent activities. This included the cancellation of consultations for patients with rare diseases, such as severe pulmonary hypertension (PH), resulting in potential medication shortage and loss of follow-up. Thus, the aim of the study was to evaluate PH patient health status evolution, access to health care and mental health experience during the early phase of the pandemic.

Methods

We conducted an online patient survey, available in 16 languages, between 22/05/2020 and 28/06/2020. The survey included questions corresponding to demographic, COVID-19 and PH related information.

Results

1073 patients (or relatives, 27%) from 52 countries all over the world participated in the survey. Seventy-seven percent (77%) of responders reported a diagnosis of pulmonary arterial hypertension and 15% of chronic thromboembolic PH. The COVID-19 related events were few: only 1% of all responders reported a diagnosis of COVID-19. However, 8% of patients reported health deterioration possibly related to PH, and 4% hospitalization for PH. Besides, 11% of the patients reported difficulties to access their PH expert centre, and 3% interruption of treatment due to shortage of medication. Anxiety or depression was reported by 67% of the participants.

Conclusion

Although COVID-19 incidence in PH patients was low, PH related problems occurred frequently as the pandemic progressed, including difficulties to have access to specialized care. The importance of primary health care was emphasized. Further studies are needed to evaluate the long-term consequences of COVID-related PH care disruption.
A blood-based diagnostic test incorporating plasma Aβ42/40 ratio, ApoE proteotype, and age accurately identifies brain amyloid status: findings from a multi cohort validity analysis
Authors: West Tim , Kirmess Kristopher M. , Meyer Matthew R. , Holubasch Mary S. , Knapik Stephanie S. , Hu Yan , Contois John H. , Jackson Erin N. , Harpstrite Scott E. , Bateman Randall J. , Holtzman David M. , Verghese Philip B. , Fogelman Ilana , Braunstein Joel B. , Yarasheski Kevin E.
Published: May 2021

Background

The development of blood-based biomarker tests that are accurate and robust for Alzheimer’s disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status.

Methods

We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic curve (ROC) analyses to assess assay performance and accuracy for predicting amyloid status (positive, negative, and standard uptake value ratio; SUVR). After plasma analysis, sites shared brain amyloid status, defined using diverse, site-specific methods and cutoff values; amyloid PET imaging using various tracers or CSF Aβ42/40 ratio.

Results

Plasma Aβ42/40 ratio was significantly (p < 0.001) lower in the amyloid positive vs. negative participants in each cohort. The area under the ROC curve (AUC-ROC) was 0.81 (95% CI = 0.77–0.85) and the percent agreement between plasma Aβ42/40 and amyloid positivity was 75% at the optimal (Youden index) cutoff value. The AUC-ROC (0.86; 95% CI = 0.82–0.90) and accuracy (81%) for the plasma Aβ42/40 ratio improved after controlling for cohort heterogeneity. The AUC-ROC (0.90; 95% CI = 0.87–0.93) and accuracy (86%) improved further when Aβ42/40, ApoE4 copy number and participant age were included in the model.

Conclusions

This mass spectrometry-based plasma biomarker test: has strong diagnostic performance; can accurately distinguish brain amyloid positive from amyloid negative individuals; may aid in the diagnostic evaluation process for Alzheimer’s disease; and may enhance the efficiency of enrolling participants into Alzheimer’s disease drug trials.
A maximum flow-based network approach for identification of stable noncoding biomarkers associated with the multigenic neurological condition, autism
Authors: Varma Maya , Paskov Kelley M. , Chrisman Brianna S. , Sun Min Woo , Jung Jae-Yoon , Stockham Nate T. , Washington Peter Y. , Wall Dennis P.
Published: May 2021

Background

Machine learning approaches for predicting disease risk from high-dimensional whole genome sequence (WGS) data often result in unstable models that can be difficult to interpret, limiting the identification of putative sets of biomarkers. Here, we design and validate a graph-based methodology based on maximum flow, which leverages the presence of linkage disequilibrium (LD) to identify stable sets of variants associated with complex multigenic disorders.

Results

We apply our method to a previously published logistic regression model trained to identify variants in simple repeat sequences associated with autism spectrum disorder (ASD); this L1-regularized model exhibits high predictive accuracy yet demonstrates great variability in the features selected from over 230,000 possible variants. In order to improve model stability, we extract the variants assigned non-zero weights in each of 5 cross-validation folds and then assemble the five sets of features into a flow network subject to LD constraints. The maximum flow formulation allowed us to identify 55 variants, which we show to be more stable than the features identified by the original classifier.

Conclusion

Our method allows for the creation of machine learning models that can identify predictive variants. Our results help pave the way towards biomarker-based diagnosis methods for complex genetic disorders.