bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world treatment patterns, healthcare resource use and clinical outcomes of patients receiving second line therapy for advanced or metastatic gastric cancer
Authors: Gómez-Ulloa David , Amonkar Mayur , Kothari Smita , Cheung Winson Y. , Chau Ian , Zalcberg John R. , Lara Suriñach Núria , Falcone Alfredo
Published: May 2020

Background

Second-line (2 L) chemotherapies for advanced or metastatic gastric cancer have shown improved survival but there is no commonly accepted standard of care. This study examines real-world patient characteristics, treatment patterns, healthcare resource use (HCRU) and clinical outcomes in this setting.

Methods

Retrospective chart reviews were performed at participating institutions from Australia, Canada, Italy and UK for adult patients receiving 2 L treatment for advanced/metastatic disease from January 2013 to July 2015. Data were collected for 12 months or until death.

Results

Two hundred eighty patients were included, mean age was 60.9 years and 68.9% were male. Half (51.8%) received monotherapy in 2 L, of whom 69.0% received taxanes. Irinotecan monotherapy was common in Australia (30.0% of monotherapy patients) and Canada (43.8%), but infrequent in Italy and UK. Doublet chemotherapy was used in 36.4% of 2 L patients, most commonly fluoropyrimidine + irinotecan. Use of targeted therapies (trastuzumab, ramucirumab) was infrequent except in Italy. Estimated median real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) from the time of 2 L treatment initiation was 3.09 (95% CI: 2.76–3.68) and 6.54 (5.29–7.76) months, respectively, and estimated 12-month rwPFS and rwOS rate was 8 and 26%, respectively. Only a minority (26.8%) of patients were hospitalized during the follow-up period, with the lowest hospitalization in Italy (16.7%). Laboratory and imaging tests were performed for 93.2 and 70.4%, respectively.

Conclusions

About half of patients received monotherapy as 2 L chemotherapy for advanced/metastatic gastric cancer and a third received doublets. Real-world clinical outcomes for 2 L treatment are poor and HCRU is considerable.
Successful treatment of mycobacterial infection associated hemophagocytic lymphohistiocytosis with etoposide and anti-tuberculous therapy: a case report
Authors: Wang Yan-Hong , Ba Jun-Hui , Shi Xiao-Wei , Wu Ben-Quan
Published: May 2020

Background

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome.

Case presentation

A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide.

Conclusion

This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.
A progressive and complex clinical course in two family members with ERF-related craniosynostosis: a case report
Authors: Körberg Izabella , Nowinski Daniel , Bondeson Marie-Louise , Melin Malin , Kölby Lars , Stattin Eva-Lena
Published: May 2020

Background

ERF-related craniosynostosis are a rare, complex, premature trisutural fusion associated with a broad spectrum of clinical features and heterogeneous aetiology. Here we describe two cases with the same pathogenic variant and a detailed description of their clinical course.

Case presentation

Two subjects; a boy with a BLSS requiring repeated skull expansions and his mother who had been operated once for sagittal synostosis. Both developed intracranial hypertension at some point during the course, which was for both verified by formal invasive intracranial pressure monitoring. Exome sequencing revealed a pathogenic truncating frame shift variant in the ERF gene.

Conclusions

Here we describe a boy and his mother with different craniosynostosis patterns, but both with verified intracranial hypertension and heterozygosity for a truncating variant of ERF c.1201_1202delAA (p.Lys401Glufs*10). Our work provides supplementary evidence in support of previous phenotypic descriptions of ERF-related craniosynostosis, particularly late presentation, an evolving synostotic pattern and variable expressivity even among affected family members.
Intradialytic complications among patients on twice-weekly maintenance hemodialysis: an experience from a hemodialysis center in Eritrea
Authors: Raja Saud Mohammed , Seyoum Yemane
Published: May 2020

Background

Twice-weekly maintenance hemodialysis sessions in patients with end stage renal disease are commonly practiced due to economic constraints in developing countries including Eritrea. To ameliorate the paucity of data on the subject, our study aims to shed light on the patterns of intradialytic complications exclusively in patients undergoing twice-weekly hemodialysis in the country.

Methods

A descriptive cross-sectional study was conducted from March 01 to July 31, 2018 at Dialysis Unit of Orotta National Referral Hospital, Asmara, Eritrea in patients with end stage renal disease undergoing twice-weekly hemodialysis. Hemodialysis sessions were assessed for intradialytic complications. Data were fed into and analyzed using Epi-Info and Microsoft Excel.

Results

A total of 29 patients were included in the five-month study period. Males were 19 (65.5%) and females were 10 (34.5%). More than half of the patients had diabetes. Out of the total 573 hemodialysis sessions, 176 (30.7%) of them involved one or more intradialytic complication. Hypotension was the most common complication occurring in 10% of the sessions followed by nausea and vomiting (5.24%), hypertension (5.06%), muscle cramps (4.71%), and headache (4.54%). Other complications such as back pain, chest pain, fever, chills and itching occurred in less than 3% of the sessions. There was no death immediately associated with the complications. Half of the intradialytic complications occurred in patients with diabetes. There was a positive correlation between intradialytic hypotension and diabetes, ultrafiltration volume as well as eating during hemodialysis. Use of central line catheter as a vascular access was associated with higher complication rate.

Conclusion

Twice-weekly hemodialysis for end stage renal disease patients probably has similar intradialytic complications as the “standard” thrice-weekly frequency. Although twice-weekly hemodialysis schedule is certainly unsuitable for some patients, its advantage of preserving residual kidney function can prevent excessive interdialytic weight gain and thus lowering the risk of intradialytic hypotension related with higher ultrafiltration rate. Being the first study in the country on dialysis complications, we recommend further large scale research in the future.
Labor market exit around retirement age in Sweden and trajectories of psychotropic drugs in a context of downsizing
Authors: Blomqvist Sandra , Westerlund Hugo , Alexanderson Kristina , Magnusson Hanson Linda L.
Published: May 2020

Background

A maintained psychological wellbeing is important in order to continue working longer and remain active into older age. However, little is known about impact of different organizational factors, such as downsizing, on the mental health of older workers exiting the labor market. The aim in this study was to investigate trajectories of purchases of psychotropic drugs in relation to labor market exit later in life in a context with and without downsizing.

Method

People living in Sweden, born 1941–1951, exiting paid work via unemployment, sickness absence/disability pension, or old-age pension were followed from 2005 to 2013 regarding purchases of psychotropic drugs. Individuals employed at a workplace closing down or downsizing with ≥18% between two subsequent years were compared to employees exiting from workplaces without downsizing or workplace closure. Generalized estimating equations was applied to derive trajectories of annual prevalence of purchased antidepressants, sedatives and anxiolytics from 4 years before to 4 years after a labour market exit.

Results

During the period around the exit, old-age retirees experiencing a downsizing/workplace closure did not decrease their purchases of sedatives (OR 1.01 95% CI 0.95–1.07) while the unexposed decreased their purchases during this period (OR 0.95 95% CI 0.92–0.98). Similar differences concerning sedatives and antidepressants between exposed and unexposed were seen for those exiting via sickness absence or disability pension. Furthermore, a significant difference in purchases of anxiolytics was observed between those exposed to downsizing (OR 1.10 95% CI 0.97–1.24) and the unexposed (OR 0.98 95% CI 0.91–1.06) exiting via old-age retirement during the time before the exit.

Conclusion

Downsizing or workplace closure, although weakly, was associated with higher prevalence of psychotropic drugs certain years around the labor market exit. The results support the idea that involuntary labor market exit in mature adulthood may negatively affect the development of mental health.
The impact on selection of non-alcoholic vs alcoholic drink availability: an online experiment
Authors: Blackwell Anna K. M. , De-loyde Katie , Hollands Gareth J. , Morris Richard W. , Brocklebank Laura A. , Maynard Olivia M. , Fletcher Paul C. , Marteau Theresa M. , Munafò Marcus R.
Published: May 2020

Background

Increasing the availability of healthier food increases its selection and consumption. However, there is an absence of evidence related to alcohol. This study aimed to estimate the impact of increasing the absolute and relative availability of non-alcoholic compared to alcoholic drinks on selection. We also assessed whether effects were modified by cognitive resource.

Methods

UK adult weekly alcohol consumers (n = 808) were recruited to an online experiment with a hypothetical drink selection task. Participants were randomly assigned to one of eight conditions, in a 4 (availability) × 2 (cognitive resource) factorial design. The four availability conditions were: i. Reference 1 (two non-alcoholic, two alcoholic drinks); ii. Reference 2 (four non-alcoholic, four alcoholic drinks); iii. Increased non-alcoholic drinks (six non-alcoholic, two alcoholic drinks); iv. Increased alcoholic drinks (two non-alcoholic, six alcoholic drinks). The two cognitive resource conditions were: a. Low (high time pressure); b. High (low time pressure). Logistic regression was used to assess selection of a non-alcoholic drink.

Results

49% of participants selected a non-alcoholic drink in the Increased non-alcoholic drinks condition, compared to 36% in Reference 1, 39% in Reference 2, and 26% in the Increased alcoholic drinks condition. Non-alcoholic drink selection was similar between Reference 1 and 2 when the total number of drinks increased (absolute availability) but the proportion of non-alcoholic compared to alcoholic drinks (relative availability) was unchanged (OR = 1.15, 95% CI 0.77, 1.73). In contrast, the odds of selecting a non-alcoholic drink were 71% higher when both absolute and relative availability of non-alcoholic compared to alcoholic drinks was increased from Reference 1 to the Increased non-alcoholic drinks condition (OR: 1.71, 95% CI 1.15, 2.54), and 48% higher when increased from Reference 2 to the Increased non-alcoholic drinks condition (OR: 1.48, 95% CI 0.99, 2.19). There was no evidence of an effect of cognitive resource.

Conclusions

Greater availability of non-alcoholic drinks, compared to alcoholic drinks, increased their online selection, an effect that may be larger when changing their relative availability, i.e., increasing the proportion of non-alcoholic drinks. Naturalistic studies are needed to determine the impact of availability interventions on reducing alcohol purchasing and consumption.
Combining the use of Nuss procedure and rib fixation for severe flail chest: a case report
Authors: Guo Quanwei , Zhang Jinghui , Cai Kaican , Zhang Jianhua
Published: May 2020

Background

Severe flail chest is a life-threatening situation. The Nuss procedure is a new effective treatment for severe flail chest patients who cannot be weaned from prolonged mechanical ventilation in the last few years. However, the procedure is not suitable when there are multiple fractures in both the anterior and lateral chest walls. Here, we reported a rare case of severe flail chest in a patient who suffered multiple fractures in both the anterior and lateral chest walls in a traffic accident.

Case presentation

A 49-year-old patient suffered severe flail chest by a steering wheel in a traffic accident with multiple fractures in both the anterior and lateral chest walls. In the beginning, the patient was administrated with mechanical ventilation because of acute respiratory distress syndrome (ARDS) for more than 1 week. Then the patient suffered from a severe lung infection and decreased blood oxygen saturation. After a multidiscipline discussion (MDT), three rib fixation plates were first used to rebuild the stability of lateral chest walls, then two Nuss bars were inserted to eliminate paradoxical movement in the anterior chest wall. Finally, the patient recovered smoothly after the combining procedure.

Conclusions

Severe flail chest patients with both the anterior and lateral chest walls after trauma are in a life-threatening situation, and require an appropriate procedure to get out of danger in time. Rib fixation is an effective treatment when the fractured sites are few and the fractured area is small. The Nuss procedure is a new effective method for severe flail chest with multiple fractures in an anterior chest wall, which is also a minimally invasive and short time-consuming procedure. However, it does not suitable for the patient with multiple fractures in lateral chest walls. Combining the use of Nuss procedure and rib fixation can solve severe flail chest with multiple ribs and sternum fractures in both the anterior and lateral chest walls, and the outcome of this procedure is satisfying in the present rare case.
Missed opportunities for family planning counselling among HIV-positive women receiving HIV Care in Uganda
Authors: Nabirye Juliet , Matovu Joseph K. B. , Bwanika John Baptist , Makumbi Fredrick , Wanyenze Rhoda K.
Published: May 2020

Introduction

HIV-positive women who are still in the reproductive years need adequate sexual and reproductive health information to make informed reproductive health choices. However, many HIV-positive women who interface with the health system continue to miss out on this information. We sought to: a) determine the proportion of HIV-positive women enrolled in HIV care who missed family planning (FP) counselling; and b) assess if any association existed between receipt of FP counselling and current use of modern contraception to inform programming.

Methods

Data were drawn from a quantitative national cross-sectional survey of 5198 HIV-positive women receiving HIV care at 245 HIV clinics in Uganda; conducted between August and November 2016. Family planning counselling was defined as provision of FP information (i.e. available FP methods and choices) to an HIV-positive woman by a health provider during ANC, at the time of delivery or at the PNC visit. Analyses on receipt of FP counselling were done on 2760 HIV-positive women aged 15–49 years who were not currently pregnant and did not intend to have children in the future. We used a modified Poisson regression model to determine the Prevalence Ratio (PR) as a measure of association between receipt of any FP counselling and current use of modern contraception, controlling for potential confounders. Analyses were performed using STATA statistical software, version 14.1.

Results

Overall, 2104 (76.2%) HIV-positive women reported that they received FP counselling at any of the three critical time-points. Of the 24% (n = 656) who did not, 37.9% missed FP counselling at ANC; 41% missed FP counselling during delivery; while 54% missed FP counselling at the post-natal care visit. HIV-positive women who received any FP counselling were significantly more likely to report current use of modern contraception than those who did not (adjusted PR [adj. PR] = 1.21; 95% Confidence Interval [CI]: 1.10, 1.33).

Conclusion

Nearly one-quarter of HIV-positive women did not receive any form of FP counselling when they interfaced with the healthcare system. This presents a missed opportunity for prevention of unintended pregnancies, and suggests a need for the integration of FP counselling into HIV care at all critical time-points.
Women’s empowerment is associated with maternal nutrition and low birth weight: evidence from Bangladesh Demographic Health Survey
Authors: Kabir Alamgir , Rashid Md Mahbubur , Hossain Kamal , Khan Arifuzzaman , Sikder Shegufta Shefa , Gidding Heather F.
Published: May 2020

Background

The burden of maternal undernutrition and low birth weight (LBW) incurs enormous economic costs due to their adverse consequences. Women’s empowerment is believed to be one of the key factors for attaining maternal and child health and nutritional goals. Our objective was to investigate the association of women’s empowerment with maternal undernutrition and LBW.

Methods

We used nationally representative data from the Bangladesh Demographic Health Survey for 2011 and 2014. We analysed 27357 women and 9234 mother-child pairs. A women’s empowerment index (WEI) was constructed using principal component analysis with five groups of indicators: a) education, b) access to socio-familial decision making, c) economic contribution and access to economic decision making, d) attitudes towards domestic violence and e) mobility. We estimated odds ratios as the measure of association between the WEI and the outcome measures using generalized estimating equations to account for the cluster level correlation.

Results

The overall prevalence of maternal undernutrition was 20% and LBW was 18%. The WEI was significantly associated with both maternal undernutrition and LBW with a dose-response relationship. The adjusted odds of having a LBW baby was 32% [AOR (95% CI): 0.68 (0.57, 0.82)] lower in the highest quartile of the WEI relative to the lowest quartile. Household wealth significantly modified the effect of the WEI on maternal nutrition; in the highest wealth quintile, the odds of maternal undernutrition was 54% [AOR (95% CI): 0.46 (0.33, 0.64)] lower while in the lowest wealth quintile the odds of undernutrition was only 18% [AOR (95% CI): 0.82 (0.67, 1.00)] lower comparing the highest WEI quartile with the lowest WEI quartile. However, the absolute differences in prevalence of undernutrition between the highest and lowest WEI quartiles were similar across wealth quintiles (6–8%).

Conclusions

This study used a comprehensive measure of women’s empowerment and provides strong evidence that low levels of women’s empowerment are associated with maternal undernutrition as well as with delivering LBW babies in Bangladesh. Therefore, policies to increase empowerment of women would contribute to improved public health.
Signaling in and out: long-noncoding RNAs in tumor hypoxia
Authors: Kuo Tse-Chun , Kung Hsing-Jien , Shih Jing-Wen
Published: May 2020

Over the past few years, long non-coding RNAs (lncRNAs) are recognized as key regulators of gene expression at chromatin, transcriptional and posttranscriptional level with pivotal roles in various biological and pathological processes, including cancer. Hypoxia, a common feature of the tumor microenvironment, profoundly affects gene expression and is tightly associated with cancer progression. Upon tumor hypoxia, the central regulator HIF (hypoxia-inducible factor) is upregulated and orchestrates transcription reprogramming, contributing to aggressive phenotypes in numerous cancers. Not surprisingly, lncRNAs are also transcriptional targets of HIF and serve as effectors of hypoxia response. Indeed, the number of hypoxia-associated lncRNAs (HALs) identified has risen sharply, illustrating the expanding roles of lncRNAs in hypoxia signaling cascade and responses. Moreover, through extra-cellular vesicles, lncRNAs could transmit hypoxia responses between cancer cells and the associated microenvironment. Notably, the aberrantly expressed cellular or exosomal HALs can serve as potential prognostic markers and therapeutic targets. In this review, we provide an update of the current knowledge about the expression, involvement and potential clinical impact of lncRNAs in tumor hypoxia, with special focus on their unique molecular regulation of HIF cascade and hypoxia-induced malignant progression.
Regulation of efferocytosis as a novel cancer therapy
Authors: Zhou Yunxiang , Yao Yihan , Deng Yongchuan , Shao Anwen
Published: May 2020

Efferocytosis is a physiologic phagocytic clearance of apoptotic cells, which modulates inflammatory responses and the immune environment and subsequently facilitates immune escape of cancer cells, thus promoting tumor development and progression. Efferocytosis is an equilibrium formed by perfect coordination among “find-me”, “eat-me” and “don’t-eat-me” signals. These signaling pathways not only affect the proliferation, invasion, metastasis, and angiogenesis of tumor cells but also regulate adaptive responses and drug resistance to antitumor therapies. Therefore, efferocytosis-related molecules and pathways are potential targets for antitumor therapy. Besides, supplementing conventional chemotherapy, radiotherapy and other immunotherapies with efferocytosis-targeted therapy could enhance the therapeutic efficacy, reduce off-target toxicity, and promote patient outcome.
A pragmatic method for costing implementation strategies using time-driven activity-based costing
Authors: Cidav Zuleyha , Mandell David , Pyne Jeffrey , Beidas Rinad , Curran Geoffrey , Marcus Steven
Published: May 2020

Background

Implementation strategies increase the adoption of evidence-based practices, but they require resources. Although information about implementation costs is critical for decision-makers with budget constraints, cost information is not typically reported in the literature. This is at least partly due to a need for clearly defined, standardized costing methods that can be integrated into implementation effectiveness evaluation efforts.

Methods

We present a pragmatic approach to systematically estimating detailed, specific resource use and costs of implementation strategies that combine time-driven activity-based costing (TDABC), a business accounting method based on process mapping and known for its practicality, with a leading implementation science framework developed by Proctor and colleagues, which guides specification and reporting of implementation strategies. We illustrate the application of this method using a case study with synthetic data.

Results

This step-by-step method produces a clear map of the implementation process by specifying the names, actions, actors, and temporality of each implementation strategy; determining the frequency and duration of each action associated with individual strategies; and assigning a dollar value to the resources that each action consumes. The method provides transparent and granular cost estimation, allowing a cost comparison of different implementation strategies. The resulting data allow researchers and stakeholders to understand how specific components of an implementation strategy influence its overall cost.

Conclusion

TDABC can serve as a pragmatic method for estimating resource use and costs associated with distinct implementation strategies and their individual components. Our use of the Proctor framework for the process mapping stage of the TDABC provides a way to incorporate cost estimation into implementation evaluation and may reduce the burden associated with economic evaluations in implementation science.
Afferents of the mouse linear nucleus
Authors: Liang Huazheng , Paxinos George
Published: May 2020

The linear nucleus (Li) was identified in 1978 from its projections to the cerebellum. However, there is no systematic study of its connections with other areas of the central nervous system possibly due to the challenge of injecting retrograde tracers into this nucleus. The present study examines its afferents from some nuclei involved in motor and cardiovascular control with anterograde tracer injections. BDA injections into the central amygdaloid nucleus result in labeled fibers to the ipsilateral Li. Bilateral projections with an ipsilateral dominance were observed after injections in a) jointly the paralemniscal nucleus, the noradrenergic group 7/ Köllike -Fuse nucleus/subcoeruleus nucleus, b) the gigantocellular reticular nucleus, c) and the solitary nucleus/the parvicellular/intermediate reticular nucleus. Retrogradely labeled neurons were observed in Li after BDA injections into all these nuclei except the central amygdaloid and the paralemniscal nuclei. Our results suggest that Li is involved in a variety of physiological functions apart from motor and balance control it may exert via its cerebellar projections.
How to select IgG subclasses in developing anti-tumor therapeutic antibodies
Authors: Yu Jifeng , Song Yongping , Tian Wenzhi
Published: May 2020

The intact antibody of human immunoglobulin (IgG) is composed of the fragment for antigen binding (Fab) and the crystallizable fragment (Fc) for binding of Fcγ receptors. Among the four subclasses of human IgG (IgG1, IgG2, IgG3, IgG4), which differ in their constant regions, particularly in their hinges and CH2 domains, IgG1 has the highest FcγR-binding affinity, followed by IgG3, IgG2, and IgG4. As a result, different subclasses have different effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Fcγ receptors include six subtypes (FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB) which differ in cellular distribution, binding affinity to Fc, and the resulting biological activity. Therefore, when developing anti-tumor therapeutic antibodies, including single-targeted antibodies, bi-specific antibodies (BsAbs), and antibody-drug conjugates (ADCs), many factors, such as target biology, cellular distribution of the targets, the environments of particular tumor types, as well as the proposed mechanism of action (MOA), must be taken into consideration. This review outlines fundamental strategies that are required to select IgG subclasses in developing anti-tumor therapeutic antibodies.
Downregulation of GLYR1 contributes to microsatellite instability colorectal cancer by targeting p21 via the p38MAPK and PI3K/AKT pathways
Authors: Hu Zhiyan , Long Ting , Ma Yidan , Zhu Jiaxian , Gao Lingfang , Zhong Yan , Wang Xia , Wang Xiaoyan , Li Zuguo
Published: May 2020

Background

GLYR1 has a high mutation frequency in microsatellite instability colorectal cancer (MSI CRC) and is presumed to be a novel tumor suppressor. However, the role of GLYR1 in tumors has never been studied. In particular, the downregulation of GLYR1 in MSI CRC is worthy of further investigation.

Methods

Western blot and immunohistochemistry analyses were used to detect GLYR1 protein expression in CRC tissues and cell lines, and the clinical significance of GLYR1 was also analyzed. The relationship between GLYR1 and MLH1 was validated by immunofluorescence, immunoprecipitation and bioinformatics analyses. Western blotting, qRT-PCR, CCK-8 assays, colony formation assays, flow cytometry and Hoechst 33258 staining assays were used to assess the effect of GLYR1 on the cell cycle progression, proliferation, differentiation and apoptosis of CRC cells in vitro. The related mechanisms were initially investigated by Western blotting.

Results

GLYR1 was significantly downregulated in MSI CRC and its expression was negatively correlated with tumor size and positively correlated with tumor differentiation in CRC patients. In addition, GLYR1 interacted with MLH1 to regulate its nuclear import and expression. Moreover, downregulation of GLYR1 accelerated G1/S phase transition, promoted proliferation and inhibited differentiation of SW480 and SW620 cells in vitro. Furthermore, downregulation of GLYR1 decreased the sensitivity to 5-fluorouracil (5-FU) by inhibiting the mitochondrial apoptosis pathway in CRC cells. Inhibition of the p38 mitogen-activated protein kinase (p38MAPK) and activation of the phosphatidyl 3-kinase/protein kinase B (PI3K/Akt) signaling pathways were involved in the mechanism by which GLYR1 downregulated p21.

Conclusions

Ours is the first study to elucidate the role of GLYR1 in tumors and provide evidence for GLYR1 as a biological marker that reflects the degree of malignancy and sensitivity to 5-FU in MSI CRC.
In utero estrogenic endocrine disruption alters the stroma to increase extracellular matrix density and mammary gland stiffness
Authors: Wormsbaecher Clarissa , Hindman Andrea R. , Avendano Alex , Cortes-Medina Marcos , Jones Caitlin E. , Bushman Andrew , Onua Lotanna , Kovalchin Claire E. , Murphy Alina R. , Helber Hannah L. , Shapiro Ali , Voytovitch Kyle , Kuang Xingyan , Aguilar-Valenzuela Renan , Leight Jennifer L. , Song Jonathan W. , Burd Craig J.
Published: May 2020

Background

In utero endocrine disruption is linked to increased risk of breast cancer later in life. Despite numerous studies establishing this linkage, the long-term molecular changes that predispose mammary cells to carcinogenic transformation are unknown. Herein, we investigated how endocrine disrupting compounds (EDCs) drive changes within the stroma that can contribute to breast cancer susceptibility.

Methods

We utilized bisphenol A (BPA) as a model of estrogenic endocrine disruption to analyze the long-term consequences in the stroma. Deregulated genes were identified by RNA-seq transcriptional profiling of adult primary fibroblasts, isolated from female mice exposed to in utero BPA. Collagen staining, collagen imaging techniques, and permeability assays were used to characterize changes to the extracellular matrix. Finally, gland stiffness tests were performed on exposed and control mammary glands.

Results

We identified significant transcriptional deregulation of adult fibroblasts exposed to in utero BPA. Deregulated genes were associated with cancer pathways and specifically extracellular matrix composition. Multiple collagen genes were more highly expressed in the BPA-exposed fibroblasts resulting in increased collagen deposition in the adult mammary gland. This transcriptional reprogramming of BPA-exposed fibroblasts generates a less permeable extracellular matrix and a stiffer mammary gland. These phenotypes were only observed in adult 12-week-old, but not 4-week-old, mice. Additionally, diethylstilbestrol, known to increase breast cancer risk in humans, also increases gland stiffness similar to BPA, while bisphenol S does not.

Conclusions

As breast stiffness, extracellular matrix density, and collagen deposition have been directly linked to breast cancer risk, these data mechanistically connect EDC exposures to molecular alterations associated with increased disease susceptibility. These alterations develop over time and thus contribute to cancer risk in adulthood.
Does asymmetry in patient recruitment in large critical care trials follow the Pareto principle?
Authors: Ramanan Mahesh , Billot Laurent , Rajbhandari Dorrilyn , Myburgh John , Finfer Simon , Bellomo Rinaldo , Venkatesh Balasubramanian
Published: May 2020

Background

Randomised controlled trials (RCT) may be hindered by slow recruitment rates, particularly in critically ill patients. While statistical models to predict recruitment rates have been described, no systematic assessment has been conducted of the distribution of recruitment across sites, temporal trends in site participation and impact of competing trials on patient recruitment.

Methods

We used recruitment and screening logs from the SAFE, NICE-SUGAR, RENAL, CHEST and ADRENAL trials, five of the largest critical care RCTs. We quantified the extent of recruitment asymmetry between sites using Lorenz curves and Gini coefficients and assessed whether the recruitment distribution across sites follow the Pareto principle, which states that 80% of effects come from 20% of causes. Peak recruitment rates and growth in participating sites were calculated.

Results

In total, 25,412 patients were randomised in 99 intensive care units (ICUs) for the five trials. Distribution of recruitment was asymmetric, with a small number of ICUs recruiting a large proportion of the patients. The Gini coefficients ranged from 0.14 to 0.52. The time to peak recruitment rate ranged from 7 to 41 months and was variable (7, 31, 41, 10 and 40 months). Over time, the proportion of recruitment at non-tertiary ICUs increased from 15% to 34%.

Conclusions

There is asymmetry of recruitment with a small proportion of ICUs recruiting a large proportion of patients. The distributions of recruitment were not consistent with the Pareto principle. There has been increasing participation of non-tertiary ICUs in clinical trials.
Preemptive Infiltration with Betamethasone and Ropivacaine for Postoperative Pain in Laminoplasty or Laminectomy (PRE-EASE): study protocol for a randomized controlled trial
Authors: Shrestha Niti , Wu Liang , Wang Xiaodi , Jia Wenqing , Luo Fang
Published: May 2020

Background

Laminoplasty and laminectomy have been used for decades for the treatment of intraspinal space-occupying lesions, spinal stenosis, disc herniation, injuries, etc. After these procedures, patients often experience severe postoperative pain at the surgical site. Intense immediate postoperative pain after many spinal procedures makes its control of utmost importance. Preemptive injection of local anesthetics can significantly reduce postoperative pain during rest and movement; however, the analgesic effect is only maintained for a relatively short period of time. Whether betamethasone combined with local anesthetic for laminoplasty or laminectomy has better short-term and long-term effects than the local anesthetic alone has not been reported yet.

Methods

The PRE-EASE trial is a prospective, randomized, open-label, blinded endpoint, single-center clinical study including 116 participants scheduled for elective laminoplasty or laminectomy, with a 6 months’ follow-up process. Preemptive local infiltration with betamethasone and ropivacaine (treatment group) or ropivacaine alone (control group) throughout the entire thickness of the planned incision site will be performed by the surgeon prior to making the incision. The primary outcome will be the cumulative butorphanol consumption within the first 48-h postoperative period.

Discussion

This study will add significant new knowledge to the effect and feasibility of preemptive local infiltration of betamethasone for postoperative pain management in laminoplasty and laminectomy.

Trial registration

ClinicalTrials.gov: NCT04153396. Registered on 6 November 2019.
Enhancing clinician and patient understanding of radiology reports: a scoping review of international guidelines
Authors: Farmer Caitlin I. , Bourne Allison M. , O’Connor Denise , Jarvik Jeffrey G. , Buchbinder Rachelle
Published: May 2020

Imaging reports are the primary method of communicating diagnostic imaging findings between the radiologist and the referring clinician. Guidelines produced by professional bodies provide guidance on content and format of imaging reports, but the extent to which they consider comprehensibility for referring clinicians and their patients is unclear. The objective of this review was to determine the extent to which radiology reporting guidelines consider comprehensibility of imaging reports for referring clinicians and patients.

We performed a scoping review of English-language diagnostic imaging reporting guidelines. We searched electronic databases (OVID MEDLINE, Embase) and websites of radiological professional organisations to identify guidelines. The extent to which the guidelines recommended essential report features such as technical information, content, format and language, as well as features to enhance comprehensibility, such as lay language summaries, was recorded.

Six guidelines from professional bodies representing radiologists from the USA, Canada, Australia and New Zealand, Hong Kong, the UK and Europe were identified from the search. Inconsistencies exist between guidelines in their recommendations, and they rarely consider that patients may read the report. No guideline made recommendations about the reporting of results considering the clinical context, and none recommended features preferred by patients such as lay language summaries. This review identifies an opportunity for future radiology reporting guidelines to give greater consideration to referring clinician and patient preferences.
Evaluating soil nutrients of Dacrydium pectinatum in China using machine learning techniques
Authors: Wu Chunyan , Chen Yongfu , Hong Xiaojiang , Liu Zelin , Peng Changhui
Published: May 2020

Background

The accurate estimation of soil nutrient content is particularly important in view of its impact on plant growth and forest regeneration. In order to investigate soil nutrient content and quality for the natural regeneration ofDacrydium pectinatumcommunities in China, designing advanced and accurate estimation methods is necessary.

Methods

This study uses machine learning techniques created a series of comprehensive and novel models from which to evaluate soil nutrient content. Soil nutrient evaluation methods were built by using six support vector machines and four artificial neural networks.

Results

The generalized regression neural network model was the best artificial neural network evaluation model with the smallest root mean square error (5.1), mean error (− 0.85), and mean square prediction error (29). The accuracy rate of the combinedk-nearest neighbors (k-NN) local support vector machines model (i.e.k-nearest neighbors -support vector machine (KNNSVM)) for soil nutrient evaluation was high, comparing to the other five partial support vector machines models investigated. The area under curve value of generalized regression neural network (0.6572) was the highest, and the cross-validation result showed that the generalized regression neural network reached 92.5%.

Conclusions

Both the KNNSVM and generalized regression neural network models can be effectively used to evaluate soil nutrient content and quality grades in conjunction with appropriate model variables. Developing a new feasible evaluation method to assess soil nutrient quality forDacrydium pectinatum, results from this study can be used as a reference for the adaptive management of rare and endangered tree species. This study, however, found some uncertainties in data acquisition and model simulations, which will be investigated in upcoming studies.
Hemobilia-a rare complication after laparoscopic cholecystectomy-
Authors: Abiko Takehiro , Ebihara Yuma , Takeuchi Motoya , Sakamoto Hiroki , Homma Hisato , Hirano Satoshi
Published: May 2020

Background

Biliary bleeding is a condition reported by Sandblom as hemobilia. The most common cause of hemobilia is iatrogenicity. But it has also been reported as a rare complication after laparoscopic cholecystectomy (LC).

Case presentation

A man in his 60s underwent a LC. He was taking a direct Xa inhibitor for paroxysmal atrial fibrillation (pAf) and had a history of thrombectomy. There was variation in the bifurcation of the hepatic artery and cystic artery. The right hepatic artery branches from the common hepatic artery by itself, and the cystic artery is double. He complained of right upper quadrant pain, nausea, and vomiting on the third postoperative day (3POD). Non-contrast computed tomography (CT) showed that a high absorption area was found to fill the common bile duct. Contrast CT showed no pseudoaneurysm formation. Ultimately, he was diagnosed with postoperative hemobilia. Angiographic examination selective for the cystic artery branching from the middle hepatic artery revealed leakage of the contrast agent and a micro-pseudoaneurysm.

Conclusions

We encountered a case of hemobilia after LC. In this case, it was presumed that in addition to the chronic inflammatory changes of the gallbladder wall, extraordinary bifurcation of the hepatic artery and the cystic arteries and easy bleeding due to resumption of a direct Xa inhibitor synergistically caused a micro-pseudoaneurysm and postoperative hemobilia. It was difficult to identify the cause of hemobilia by contrast CT alone. Angiographic examination was useful for identifying and treating the causative artery and needs to perform aggressively.
A case of hemodialysis and steroid therapy for carbamazepine-induced eosinophilic granulomatosis with polyangiitis: a case report with literature review
Authors: Abe Tetsuya , Nishiyama Keiko , Yamazaki Takuya , Miyasaka Ryoma , Honma Yukari , Tominaga Hiroshi , Hashimoto Keiko , Masaki Takanori , Kamata Fumi , Kamata Mariko , Aoyama Togo , Sano Takashi , Takeuchi Yasuo , Naito Shokichi
Published: May 2020

Background

Carbamazepine-induced acute kidney injury is mainly caused by acute tubulointerstitial nephritis. Only one case of carbamazepine-induced eosinophilic granulomatosis with polyangiitis (EGPA) with acute kidney injury has been reported. But the patient’s condition improved with the immediate discontinuation of carbamazepine. We present a case requiring hemodialysis and steroid therapy for carbamazepine-induced EGPA with acute kidney injury.

Case presentation

A 77-year-old man with allergic rhinitis was prescribed carbamazepine for trigeminal neuralgia 1 year ago. He developed rash and itching on the left forearm 1 month ago and was diagnosed with polymorphic exudative erythema and admitted to our hospital. Laboratory data revealed leukocytosis eosinophilia and renal failure (serum creatinine 9.2 mg/dL). Carbamazepine was discontinued, and hemodialysis was initiated because of acute uremia and oliguria. A lymphocyte stimulation test for carbamazepine was positive. Polyneuropathy in the upper and lower extremities was observed by electromyogram, and a renal biopsy indicated EGPA. The main clinical findings were allergic rhinitis, eosinophilia, and vasculitis symptoms, such as multiple mononeuritis and muscle weakness. Renal biopsy showed diffuse cellular infiltration dominated by eosinophils in the interstitium, with granulomatous changes in particular observed around the arteriole. Fibrinoid necrosis was also observed around the arteriole. We therefore made a diagnosis of carbamazepine-induced EGPA. Following steroid therapy after the discontinuation of carbamazepine, the patient was discharged from our hospital without hemodialysis. In contrast with the previous case of EGPA, the present case had the following characteristics: (1) elderly male patient, (2) hemodialysis required for acute kidney injury, and (3) improved renal function following steroid therapy after discontinuation of carbamazepine.

Conclusion

Our case report indicates that early diagnosis and appropriate therapy can improve acute kidney injury caused by carbamazepine and allow the patient to discontinue dialysis.
Medical application of exopolymers produced by marine bacteria
Authors: Abdelhamid Sayeda A. , Mohamed Sahar S. , Selim Manal S.
Published: May 2020

Background

Natural products have been viewed as essential sources that could create potential chemotherapeutic agents. In the look for new bioactive substances, examinations were extended to marine territories.

Results

Humanity has known for the last few thousand years that a marine organism contains substances fit for strong biological activity. However, the main genuine examination of marine living beings began just 50 years prior. Since then, all types of life in the marine condition (e.g., bacteria, algae, and fungi) have been researched for their bioactive content.

Conclusions

Exopolymers can be applied in a wide range of industrial applications in biomedicines.
Correction to: Open reduction and internal fixation with cables for the variant AGT Periprosthetic fracture: a case report and literature review
Authors: Fan Meng-Qiang , Chen Xiao-Lei , Huang Yong , Huang Jie-Feng
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Mental health and COVID-19: is the virus racist?
Authors: Kapilashrami Anuj , Bhui Kamaldeep
Published: May 2020

COVID-19 has changed our lives and it appears to be especially harmful for some groups more than others. Black and Asian ethnic minorities are at particular risk and have reported greater mortality and intensive care needs. Mental illnesses are more common among Black and ethnic minorities, as are crisis care pathways including compulsory admission. This editorial sets out what might underlie these two phenomena, explaining how societal structures and disadvantage generate and can escalate inequalities in crises.
Highlights from the previous volumes
Authors: Canossi D. O. , Li Y. J. , Giorgini L. T. , Cao Ye , Zhang Wei
Published: May 2020

Elastic turbulence in two-dimensional cross-slot flows Cr-based nitrides superconductor Ln3Cr10−xN11(Ln=La, Pr) Precursors to rare events in stochastic resonance Many-body localization in generalized Kondo lattice with disorder
C3G localizes to the mother centriole in a cenexin-dependent manner and regulates centrosome duplication and primary cilium length
Authors: Nayak Sanjeev Chavan , Radha Vegesna
Published: May 2020

C3G (also known as RAPGEF1) plays a role in cell differentiation and is essential for early embryonic development in mice. In this study, we identify C3G as a centrosomal protein that colocalizes with cenexin (also known as ODF2) at the mother centriole in interphase cells. C3G interacts with cenexin through its catalytic domain, and the two proteins show interdependence for localization to the centrosome. C3G depletion causes a decrease in cellular cenexin levels. Centrosomal localization of C3G is lost as myocytes differentiate to form myotubes. Depletion of C3G by CRISPR/Cas9 results in the formation of supernumerary centrioles, whereas overexpression of C3G, or expression of a catalytically active C3G deletion construct, inhibits centrosome duplication. Cilium length is increased in C3G knockout cells, and this phenotype is reverted upon reintroduction of C3G or its catalytic domain alone. Association of C3G with the basal body is dynamic, decreasing upon serum starvation and increasing upon re-entry into the cell cycle. C3G inhibits cilium formation and length, and this inhibition is dependent on C3G catalytic activity. We conclude that C3G regulates centrosome duplication and maintains ciliary homeostasis, properties that could be important for its role in embryonic development.