bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia
Authors: Peiffer-Smadja Nathan , BOUADMA Lila , MATHY Vincent , ALLOUCHE Kahina , PATRIER Juliette , REBOUL Martin , MONTRAVERS Philippe , TIMSIT Jean-François , ARMAND-LEFEVRE Laurence
Published: May 2020

Background: Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 hours. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. Methods: In this prospective study we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheters (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital; the medical and infectious diseases ICU, the surgical ICU and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotics changes they would have made if the M-PCR results had been available. Results We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 hours (IQR 4.4-5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95%CI, 73-88%) and specificity of 99% (95%CI 99-100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p=0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. Conclusions: Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.
Optimized method for extraction of exosomes from human primary muscle cells
Authors: Gall Laura Le , Ouandaogo Zamalou Gisele , Anakor Ekene , Connolly Owen , Browne Gillian Butler , Laine Jeanne , Duddy William John , Duguez Stephanie
Published: May 2020

Skeletal muscle is increasingly considered as an endocrine organ secreting myokines and extracellular vesicles (exosomes and microvesicles), which can effect physiological changes with impact in different pathological conditions, including regenerative processes, aging and myopathies. Primary human myoblasts are an essential tool to study the muscle vesicle secretome. Since their differentiation in conditioned media does not induce any signs of cell death or cell stress, artefactual effects from those processes are unlikely. However, adult human primary myoblasts senesce in long-term tissue culture, so a major technical challenge is posed by the need to avoid artefactual effects resulting from pre-senescent changes. Since these cells should be studied within a strictly controlled pre-senescent division count (<21 divisions), and yields of myoblasts per muscle biopsy are low, it is difficult or impossible to amplify sufficiently large cell numbers (some 250 x 106 myoblasts) to obtain sufficient conditioned medium for the standard ultracentrifugation approach to exosome isolation.Thus an optimized strategy to extract and study secretory muscle vesicles is needed. In this study, conditions are optimized for the in vitro cultivation of human myoblasts, and the quality and yield of exosomes extracted using an ultracentrifugation protocol are compared with a modified polymer-based precipitation strategy combined with extra washing steps. Both vesicle extraction methods successfully enriched exosomes, as vesicles were positive for CD63, CD82, CD81, floated at identical density (1.15-1.27 g.ml-1), and exhibited similar size and cup-shape using electron microscopy and NanoSight tracking. However, the modified polymer-based precipitation was a more efficient strategy to extract exosomes, allowing their extraction in sufficient quantities to explore their content or to isolate a specific subpopulation, while requiring >30 times fewer differentiated myoblasts than what is required for the ultracentrifugation method. In addition, exosomes could still be integrated into recipient cells such as human myotubes or iPSC-derived motor neurons.Modified polymer-based precipitation combined with extra washing steps optimizes exosome yield from a lower number of differentiated myoblasts and less conditioned medium, avoiding senescence and allowing the execution of multiple experiments without exhausting the proliferative capacity of the myoblasts.
Epidemiological and Clinical Features of 2019 Novel Coronavirus Diseases (COVID-19) in the South of Iran
Authors: Shahriarirad Reza , Khodamoradi Zohre , Erfani Amirhossein , pour Hamid reza Hossein , Ranjbar Keivan , Emami Yasaman , Mirahmadizadeh Alireza , Lotfi Mehrzad , Yeganeh Babak Shirazi , Nejad Abolfazl Dorrani , Hemmati Abdolrasool , Ebrahimi Mostafa , Moghadami Mohsen
Published: May 2020

Background: In March 2020, the WHO declared the novel coronavirus (COVID-19) outbreak a global pandemic. Although the number of infected cases is increasing, information about its clinical characteristics in the Middle East, especially in Iran, a country which is considered to be one of the most important focal points of the disease in the world, is lacking. To date, there is no available literature on the clinical data on COVID-19 patients in Iran. Methods: In this multicenter retrospective study, 113 hospitalized confirmed cases of COVID-19 admitted to university affiliated hospitals in Shiraz, Iran from February 20 to March 20 were entered in the study. Results: The mean age was 53.75 years and 71 (62.8%) were males. The most common symptoms at onset were fatigue (75: 66.4%), cough (73: 64.6%), and fever (67: 59.3%). Laboratory data revealed significant correlation between lymphocyte count (P value= 0.003), partial thromboplastin time (P value= 0.000), international normalized ratio (P value= 0.000) with the severity of the disease. The most common abnormality in chest CT scans was ground-glass opacity (77: 93.9%), followed by consolidation (48: 58.5%). Our results revealed an overall 8% (9 out of 113 cases) mortality rate among patients, in which the majority was among patients admitted to the ICU (5: 55.6%). Conclusion: Evaluating the clinical data of COVID-19 patients and finding the source of infection and studying the behavior of the disease is crucial for understanding the pandemic.
Comparing potential drug-drug interactions in veterinary medications using two electronic databases
Authors: Boonyarattanasoonthorn Tussapon , Khemawoot Phisit , Kijtawornrat Anusak
Published: May 2020

Background: One of the most common global health issues in humans and animals is drug-drug interactions (DDIs). This issue increases the risks associated with healthcare in both human and veterinary medicine, as animals live long lives and receive many medicines to treat their illnesses. Currently, many electronic databases are being used as tools for potential DDI prediction, for example, Micromedex and Drugs.com. The purpose of this study was to examine the different abilities for the identification of potential DDIs in veterinary medicines by Micromedex and Drugs.com. Results: A list of 140 drugs, mainly used for the treatment of disease in animal hospitals, was complied, but the Micromedex and Drugs.com databases could recognise only 96 of these drugs. After inputting the recognised drug list into the databases, Micromedex showed 429 pairs of potential DDIs, whilst Drugs.com showed 842 pairs of potential DDIs. The analysis comparing results between the two databases showed 139 pairs (12.28%) with the same severity and 993 pairs (87.72%) with different severities. Major mechanisms of contraindicated and major potential DDIs were cytochrome P450 induction-inhibition and QT interval prolongation.Conclusion: Although Micromedex had a lower sensitivity to identify potential DDIs than Drugs.com, Micromedex provided more informative documentation. Veterinary pharmacists should evaluate potential DDIs from several databases and communicate with both the veterinarian and animal owner to ensure an appropriate drug prescription.
Metabolic mechanism of Saccharomyces cerevisiae under different physiological conditions based on non-stationary 13C metabolic flux analysis
Authors: Li Huan , Chen Min , Liu Peng , Wang Shuai , Xia JY
Published: May 2020

Crabtree effect is well known for Saccharomyces cerevisiae, and is defined as glucose-induced repression of respiratory flux. Even though a number of hypotheses have been formulated, its triggering mechanisms are still unknown. At present, the information about intracellular metabolic flux can be obtained by the 13C isotope labeling experiments. 13C metabolic flux analysis(13C-MFA) is a traditional method for calculating metabolic flux based on isotopic steady state. Another new method (INST-13C-MFA: Isotopically nonstationary metabolic flux analysis) based on isotope non-steady state is being used by researchers. In this review, we have chemostatized S. cerevisiae at three different dilution rates (D=0.12, 0.22, 0.32 h-1) and obtained the metabolic flux distribution of the intracellular central carbon metabolic of S. cerevisiae using INST-13C-MFA. Combined with the metabolome and metabolic fluxome data, we found obvious metabolic flux shift under the three different physiological states. In this process, pyruvate decarboxylase, ethanol dehydrogenase and acetyl-CoA synthase(AcCoA) catalyzed reactions were key points. Negative correlation between relative flux of embden meyerh of pathway(EMP) and tricarboxylic acid cycle(TCA) and biomass yield, while positive correlation for pentose phosphate pathway(PPP) were observed. Yield of acetate and glycerol did not change significantly, while that of ethanol increased sharply. In the central carbon metabolism (CCM), most of the carbon flux (70%) was directed to the EMP. At the same time, the energy charge increased with dilution rate, and the cell's energy supply mode gradually shifted from oxidative respiration to substrate level phosphorylation mode.
Imbalance of circulating Tfh/Tfr cells in patients with Parkinson’s disease
Authors: Zhao Xiuzhen , Jin Tao , Zheng Chao , Ma Di , Zhang Ying
Published: May 2020

Background: Follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are essential for B cell differentiation, germinal center formation, and humoral immune responses. Immunity and inflammation have been thought to be involved in Parkinson’s disease (PD). In this study, we aimed to identify whether circulating Tfh and Tfr (cTfh and cTfr) cells contribute to PD.Methods: Thirty-nine PD patients and 26 health controls (HCs) were enrolled. The numbers of cTfh (CD4+CXCR5+PD-1+) cells and cTfr (CD4+CXCR5+CD25hiCD127low) cells were analyzed via flow cytometry. The serum concentrations of interleukin (IL)-4, IL-10, IL-21, and transforming growth factor (TGF)-β were examined by cytometric bead array.Results: The percentage of cTfh cells among CD4+ T cells in PD patients was significantly higher than that in HCs [3.68% (2.64%–5.70%) vs 1.94% (1.32%–2.99%), P<0.001], while the percentage of cTfr cells among CD4+ T cells in PD patients was slight decreased but without significance [1.05% (0.62%–1.54%) vs 1.3% (0.63%–1.90%), P>0.05]. The percentage of CD19+ B cells in peripheral blood mononuclear cells was significantly lower in PD patients than in HCs [5.35% (4.13%–9.38%) vs 8.68% (5.61%–12.93%), P=0.014]. The serum concentrations of IL-4, IL-10, IL-21, and TGF-β in PD patients did not differ significantly from those in HCs (P>0.05). However, significant positive correlations were found for the serum concentration of IL-21 with H-Y stage (r=0.356, P=0.026) and UPDRS-III score (r=0.347, P=0.030).Conclusions: These results indicate that an imbalance of cTfh and cTfr cells may be involved in the chronic progression of PD, and IL-21 may be a biomarker for monitoring the severity of this disease.
Depressive disorders in Brazil: results from the Global Burden of Disease Study 2017
Authors: Bonadiman Cecília Silva Costa , Malta Deborah Carvalho , Passos Valéria Maria de Azeredo , Naghavi Mohsen , Melo Ana Paula
Published: May 2020

Background
Depression is one of the major causes of disability worldwide. The objective of this study was to analyze the results of the Global Burden of Disease Study 2017 (GBD-2017) for depressive disorders in Brazil and its Federated Units (FUs) in 1990 and 2017.
Methods
We used GBD-2017 study methodology to evaluate the prevalence estimates, the disability-adjusted life-year (DALY) and the years lived with disability (YLDs) for depressive disorders, which include major depressive disorder and dysthymia. The YLD estimates and the position of these disorders in the DALY and YLD rankings were compared to those of seven other countries. The observed versus expected YLD, based on the sociodemographic index (SDI), were compared.
Results
In GBD-2017, the prevalence of depressive disorders in Brazil was 3.30% (95% uncertainty interval [UI]: 3.08 to 3.57), ranging from 3.79% (3.53 to 4.09) in Santa Catarina to 2.78% in Pará (2.56 to 3.03), with significant differences between the Federated Units. From 1990 to 2017, there was an increase in number of YLD (55.19%, 49.57 to 60.73), but a decrease in the age-standardized rates (-9.01%, -11.66 to -6.31). The highest proportion of YLD was observed in the age range of 15–64 years and among females. These disorders rank 4th and 13th as leading causes of YLD and DALY, respectively, in Brazil. In the other countries evaluated, the ranking of these disorders in the YLD classification was close to Brazil´s, while in the DALY classification, there was higher variability. All countries had YLD rates similar to the overall rate. The observed/expected YLD ratio ranged from 0.81 in Pará to 1.16 in Santa Catarina. Morbidity of depressive disorders was not associated with SDI.
Conclusions
Depressive disorders have been responsible for a high disability burden since 1990, especially in adult women living in the Southern region of the country. The number of people affected by these disorders in the country tends to increase, requiring more investment in mental health aimed at advancements and quality of services. The epidemiological studies of these disorders throughout the national territory can contribute to this planning and to making the Brazilian health system more equitable.
Influences on catch-up growth using relative versus absolute metrics: Evidence from the MAL-ED cohort study
Authors: Richard Stephanie A , McCormick Benjamin JJ , Murray-Kolb Laura E , Bessong Pascal , Shrestha Sanjaya K , Md Estomih , Ahmed Tahmeed , Kang Gagandeep , Lee Gwyneth O , Seidman Jessica C , Svensen Erling , Kosek Margaret N , Caulfield Laura E
Published: May 2020

Background: Undernutrition in early childhood has historically been considered irreversible after 2-3 years of age and has been associated with morbidity and mortality over the short-term and poor economic and cognitive outcomes over the long-term. We used longitudinal data to determine which factors are associated with positive changes in absolute and relative differences in height and weight from the WHO Growth Standards from 24 to 60 months of age.Methods: Across six MAL-ED sites, 942 children had anthropometry data at 24 and 60 months, as well as information about socioeconomic status, maternal height, gut permeability (lactulose-mannitol z-score (LMZ)), dietary intake from 9-24 months, and micronutrient status. Anthropometric changes were categorized as positive changes in height- or weight-for-age z-score (HAZ, WAZ) or their absolute difference from the growth standard median (HAD (cm), WAD (kg)), as well as recovery from stunting/underweight. Outcomes were modeled using multivariate linear regression.Results: Forty-three/34% of the children who were stunted/underweight at 24 months were no longer stunted/underweight at 60 months, Among the sites, 64-92% of children had positive changes in their HAZ, whereas 25-60% had positive changes in HAD. Linear regression models indicate that female sex (-0.21 HAZ (95% CI -0.27, -0.15); -0.75 HAD (-1.07, -0.43)) and mean LMZ (0-24 months) (-0.10 HAZ (-0.16, -0.04); -0.47 HAD (-0.73, -0.21)) were negatively associated with change in both metrics, and maternal height was positively associated with both (0.09 HAZ (0.03, 0.15); 0.45 HAD (0.15, 0.75)). Similar relationships were identified for change in WAZ and WAD. Dietary protein density was negatively associated with change in WAZ and WAD (-0.05 WAZ (-0.09, -0.01); -0.11 WAD (-0.21, -0.01)), and mean plasma transferrin receptor concentration was positively associated with change in WAZ and WAD (0.02 WAZ (0.0, 0.04); 0.04 WAD (0.0, 0.08)).Conclusions: While children in the MAL-ED study demonstrated recovery from stunting and underweight from 24-60 months of age, they also lost additional centimeters and grams when compared to the WHO median references. Given the similarities in the factors associated with changes in HAZ and HAD (and WAZ and WAD), both can be used to characterize catch-up growth during childhood.Funding Sources: The MAL-ED study was supported by the Bill & Melinda Gates Foundation, with grants to the Foundation for the NIH and NIH/FIC.
Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: A report from the New Agents Group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP)
Authors: Rubio-San-Simon Alba , Verdú-Amorós Jaime , Hladun Raquel , Ribelles Antonio Juan , Molero Mari , Guerra-García Pilar , Pérez-Martínez Antonio , Castañeda Alicia , Cañete Adela , Rojas Teresa de , Moreno Lucas , Bautista Francisco
Published: May 2020

Purpose: The COVID-19 pandemic has forced healthcare stakeholders towards challenging decisions. We analyse the impact of the pandemic on the conduct of phase I-II trials for paediatric cancer during the first month of state of alarm in Spain.Methods: A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early-Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products and legal aspects.Results: All units suffered personnel shortages and difficulties in enrolling patients, treatment continuity or performing trial assessments. Monitoring activity was frequently postponed (73%), and 49% of on-going trials interrupted recruitment. Only two patients could be recruited during this period (75% reduction in the expected rate).Conclusions: The COVID-19 crisis has significantly impacted clinical research practice and access to innovation for children with cancer. Structural and functional changes are under way to better cope with the expected future restrictions.
Role of the SDF-1/CXCR4 signaling pathway in cartilage and subchondral bone in temporomandibular joint osteoarthritis induced by overloaded functional orthopedics in rats
Authors: yang jing , Li Yazhen , Liu Ying , Zhang Qiang , Zhang Qi , Chen Junbo , Yan Xiao , Yuan Xiao
Published: May 2020

Objectives To: (i) use a mandibular-advancement appliance in rats to investigate the role of the stromal cell-derived factor/ CXC receptor 4 (SDF-1/CXCR4) signaling pathway in temporomandibular joint osteoarthritis (TMJ OA) induced by overloaded functional orthopedics (OFO); (ii) provide a cellular and molecular basis for efficacious treatment of skeletal class-II malocclusion and avoidance of TMJ OA.Method: Male Sprague–Dawley rats (6 weeks) were divided randomly into control + normal saline (NS), EXP + ADM3100 (SDF-1 antagonist), EXP + NS, and control + ADM3100 groups. Changes in articular cartilage and subchondral bone after TMJ OA in these four groups were observed by hematoxylin and eosin (H&E), Immunofluorescence double staining (IDS), Safranin-O staining, immunohistochemical (IHC) staining, real-time polymerase chain reaction, and micro-computed tomography at 2, 4, and 8 weeks.Results OFO led to increased expression of SDF-1, CXCR4, and matrix metalloproteinase (MMP)13 and decreased expression of collagen II. The thickness of the hypertrophic cartilage layer was reduced at 4 weeks in the EXP + NS group, and damage to subchondral bone was observed at 2 weeks. Using ADM3100 to inhibit SDF-1 signaling could attenuate expression of MMP13, cartilage damage, and osteoblast differentiation. IDS showed that the areas of expression of SDF-1 and OSX in subchondral bone overlapped.Conclusions The destruction of subchondral bone in TMJ OA caused by OFO occurred before damage to cartilage. An increase in expression of the SDF-1/CXCR4 signaling pathway in TMJ OA induced by OFO enabled osteoblasts in subchondral bone to up-regulate expression of SDF-1.
E-Consults: an effective way to decrease clinic wait times in Rheumatology
Authors: Patel Veena , Stewart Diana , Horstman Molly
Published: May 2020

Background To evaluate the effect of E-consults on wait times and resource utilization for positive antinuclear antibody (ANA) referrals in outpatient rheumatology.Methods We conducted a pre-post study of E-consult implementation for positive ANA referrals. We retrospectively reviewed “positive ANA” referrals from 1/2015-3/2017. A statistical process control chart was created to display monthly average wait times for in-person clinic visits and to identify special cause variation. Final Diagnoses, wait times and resource utilization were recorded and compared between E-consults and in-person referrals.Results There were 139 referrals for positive ANA with 126 occurring after E-consult implementation in August 2015. Forty-four percent (55/126) of referrals were E-consults; 76% were resolved after initial electronic rheumatology recommendation. A control chart demonstrated special cause variation in the form of a shift from June 2016 – January 2017, suggesting a temporal association between decreased wait times and the implementation of E-consults. Eleven patients were diagnosed with ANA-associated rheumatic disease; the majority of patients (73%, 86/139) did not have a rheumatologic diagnosis. Overall E-consults utilized more labs than in-person visits, but this was not statistically significant. In-person visit utilized more imaging studies, which was statistically significant.Conclusion E-consults are an effective way to address positive ANA consults without significant resource utilization and were temporally associated with decreased wait times for in-person visits.
Insights on mental health when living with r/Rheumatoid r/Thritis: A descriptive qualitative study of Reddit threads
Authors: Park Jamie Yea Eun , Howren Alyssa M. , Davidson Eileen , De Vera Mary A
Published: May 2020

Background
Online forums, where individuals ask questions, discuss opinions and share experiences provide a valuable pool of publicly available data to better understand impacts of disease and associated complications. Our objective was to systematically search and analyze threads on the social news website, Reddit, to understand experiences of individuals with rheumatoid arthritis (RA) regarding their mental health.
Methods
We conducted a patient-oriented descriptive qualitative study. We identified threads from two subreddits, “r/Thritis” and “r/Rheumatoid”, using keywords such as “mood”, “mental health”, “stressed”, “depressed”, “anxious” over a 1-year period between June 2018 and June 2019. For included threads, we extracted the title, original post, and corresponding comments and responses. We applied thematic analysis using an inductive approach.
Results
Of 81 threads identified, we included 27. We identified four themes: 1) Navigating the management of RA explores how the physical impacts of the disease, lack of health resources/support and the complexity of medications affect mental health; 2) Experiencing impact on relationships and social isolation includes experiencing misconceptions of RA, feeling misunderstood and feeling guilt; 3) Experiencing loss, touches on the helplessness brought by challenges with performing self-defining activities such as self-care, work, and childbearing/parenting; and finally, 4) Experiencing emotional struggles captures how tension between fighting through and despair has led some to suicide ideation and thoughts of death.
Conclusions
Online forums and communities such as Reddit have created opportunities for individuals with RA to share experiences on mental health matters, which they may not necessarily be able to share with others.
Impact of the COVID-19 pandemic on stress and emotional reactions in Israel: A mixed-methods study
Authors: Levkovich Inbar , Shinan-Altman Shiri
Published: May 2020

Objectives
The COVID-19 pandemic has had a profound impact on the public worldwide. This exploratory study sought to identify the pandemic’s psychological impact on the Israeli public using a mixed-methods approach.
Methods
During the COVID-19 outbreak, Israeli adults (N = 1,407) completed a battery of measures assessing psychological variables and perceived threat related to COVID-19. Statistical analyses included tests for between-group differences and Pearson correlations. Qualitative, in-depth, semi-structured interviews (N = 38) were conducted.
Results
The findings of the quantitative study indicate that about half of the public were concerned, afraid and stressed and a fifth perceived they were liable to contract the virus. Moreover, a positive correlation emerged between these feelings and degree of perceived threat. Three major themes emerged from the qualitative study: 1) a sense of shock and chaos; 2) gradual adjustment to the new reality; 3) fears and concerns for self and family members.
Conclusions
The study provides a comprehensive picture of psychological variables and perceived threat related to COVID-19 in Israel. Social distancing is likely to make people feel safer but also to increase their feelings of isolation, stress and frustration and to cause difficulties in many life situations.The findings indicate that the public’s perceived susceptibility and emotional reactions about the COVID-19 should be addressed.
Acromegaly: a Clinical Perspective
Authors: Lawrence Lima , Alkwatli Kenda , Bena James , Prayson Richard , Kshettry Varun , Recinos Pablo , Hatipoglu Betul , Pantalone Kevin M , Weil Robert , Hamrahian Amir H , Kennedy Laurence , Yogi-Morren Divya
Published: May 2020

Background
To examine the clinical and hormonal profiles, comorbidities, treatment patterns, surgical pathology and clinical outcomes of patients diagnosed with acromegaly at the Cleveland Clinic over a 15-year period.
Methods
A retrospective chart review of patients with acromegaly who underwent surgical resection between 2003 and 2018.
Results
A total of 136 patients (62 men; mean age 48.1 years) with biochemical evidence of acromegaly were analyzed. Median insulin-like growth factor 1 (IGF-1) level at diagnosis was 769.0 ng/mL and most patients had a macroadenoma (82.2%). Immunoreactivity to growth hormone (GH) was noted in 124 adenomas, with co-staining in 89 adenomas. Complete visible tumor resection during initial surgery was achieved in 87 patients (64.0%). In this cohort, complete response to surgery alone was observed in 61 patients (70.1%), while 31 out of 65 patients (47.7%) who received additional post-surgical medications and/or radiation therapy achieved complete response. At most recent follow-up, 92 patients achieved eventual complete response by documented normalization of IGF-1 levels. Higher IGF-1 level at diagnosis (P = 0.024) and cavernous sinus invasion (P = 0.028) were predictors for failure to respond to surgery.
Conclusion
In this study, the majority of tumors were macroadenoma, plurihormonal, and treated effectively with surgery alone or surgery with adjuvant medical or radiation therapy. More studies are needed to identify additional molecular biomarkers, tumor characteristics and imaging findings to individualize treatment and better predict treatment outcomes.
Characterization of deltamethrin degradation and metabolic pathway by co-culture of Acinetobacter junii LH-1-1 and Klebsiella pneumoniae BPBA052
Authors: Tang Jie , Hu Qiong , Lei Dan , Wu Min , Zeng Chaoyi , Zhang Qing
Published: May 2020

Deltamethrin and its major metabolite 3-phenoxybenzoic acid (3‐PBA) have caused serious threat to the environment as well as human health, yet little is known about their degradation pathways by bacterial co-cultures. In this study, the growth and degradation kinetics of Acinetobacter junii LH-1-1 and Klebsiella pneumoniae BPBA052 during deltamethrin and 3-PBA degradation were established, respectively. When the inoculum proportion of the strains LH-1-1 and BPBA052 was 7.5:2.5, and LH-1-1 was inoculated 24 h before inoculation of strain BPBA052, 94.25% deltamethrin was degraded and 9.16 mg/L of 3-PBA remained within 72 h, which was 20.36% higher and 10.25 mg/L lesser than that in monoculture of LH-1-1, respectively. And the half-life of deltamethrin was shortened from 38.40 h to 24.58 h. Based on gas chromatography–mass spectrometry, 3-phenoxybenzaldehyde, 1,2-benzenedicarboxylic butyl dacyl ester, and phenol were identified as metabolites during deltamethrin degradation in co-culture. This is the first time that a co-culture degradation pathway of deltamethrin has been proposed based on these identified metabolites. Bioremediation of deltamethrin-contaminated soils with co-culture of strains LH-1-1 and BPBA052 significantly enhanced deltamethrin degradation and 3-PBA removal. This study provides a platform for further studies on deltamethrin and 3-PBA biodegradation mechanism in co-culture, and it also proposes a promising approach for efficient bioremediation of environment contaminated by pyrethroid pesticides and their associated metabolites.
Three rare variants of SOX7 impairing its interaction with GATA4 may be a predisposing factor to complete AVSD
Authors: Li Baolei , Li Zhuoyan , Yang Jianping , Hong Nanchao , Jin Lihui , Xu Yuejuan , Fu Qihua , Sun Kun , Yu Yu , Lu Yanan , Chen Sun
Published: May 2020

Background Atrioventricular septal defects (AVSD) are a complicated subtype of congenital heart defects for which the genetic basis is poorly understood. Many evidences have demonstrated that transcription factor SOX7 which can interact with GATA4 plays a pivotal role in the cardiovascular development. The critical role of GATA4 in the morphogenesis of atrioventricular septum implies SOX7 a potential involvement of AVSD. However, whether SOX7 variants are involved in the pathogenesis of AVSD needs to be explored. Methods 100 sporadic non-syndromic AVSD Chinese Han patients were recruited and the variants of SOX7 in 100 patients were screened by target sequencing. Functional assays were performed to testify the potential pathogenicity of nonsynonymous variants of SOX7 found in these AVSD patients. Results Through target sequencing, we identified three rare variants c.40C>G, c.542G>A, and c.743C>T of SOX7 in 100 sporadic non-syndromic AVSD Chinese Han patients. All mutant sites were highly conserved in mammals. Compared to the wildtype, these variants of SOX7 increased mRNA expression and decreased protein. In the developing murine hearts, SOX7 along with GATA4 expressed highly in the region of atrioventricular cushions. Moreover, SOX7 overexpression promoted the expression of GATA4 in human umbilical vein endothelial cells. Chromatin immunoprecipitation assay uncovered that SOX7 could directly bind to the region of GATA4 promoter. Luciferase assays demonstrated that SOX7 activated GATA4 promoter and the variants impaired the transcriptional activity of SOX7. Furthermore, the variants of SOX7 altered the regulation to the activity of GATA4 on its target genes. Conclusions Our studies provide evidence that deleterious variants in SOX7 are potential contributors to human AVSD and provide novel insights into the etiology of AVSD.
Identifying novel cell glycolysis related gene signature predictive of overall survival in bladder urothelial carcinoma
Authors: Zhao Xin , Li Jia , Li Jiafeng , Xiong Wenjun , Jiang Rui
Published: May 2020

Background: Bladder urothelial carcinoma (BLCA) is the most common pathological type of bladder cancer and featured by a high risk for relapse and metastasis. Although many biomarkers have been developed by data mining and experimental studies to predict the prognosis of BLCA, a single-gene biomarker usually has poor specificity and sensitivity, leading to unsatisfactory prediction. Therefore, novel gene signatures are needed to more accurately predict the prognosis of BLCA.Methods: Data mining was performed for expression profile analysis of 433 mRNA expression data from the TCGA BLCA patients (n=412). Gene Set Enrichment Analysis (GSEA) was used to interpret the glycolysis-related gene sets. Gene signature related to the prognosis of BLCA was identified by univariate and multivariate Cox regression. A risk score was computed based on three genes by linear regression model and its relation with overall survival was investigated by Kaplan-Meier analysis.Results: Three genes (CHPF, AK3, NUP188) were found to be significantly correlated to the overall survival of BLCA patients. Based on the signature composed of these three genes, 412 BLCA patients were divided into high-risk and low-risk groups. The survival time of the high-risk group was significantly shorter than that of the low-risk group, indicating a worse prognosis.Conclusion: A signature composed of three glycolysis-related genes was developed as biomarkers to predict the prognosis of BLCA and to provide a meaningful reference for the clinical treatment of BLCA.
Evaluation of risk factors of vertebral fracture in Japanese female patients with glucocorticoid-induced osteoporosis
Authors: Mori Yu , Izumiyama Takuya , Baba Kazuyoshi , Mori Naoko , Fujii Hiroshi , Ishii Tomonori , Itoi Eiji
Published: May 2020

Background Glucocorticoid-induced osteoporosis and vertebral fracture are common complications in patients on glucocorticoid treatment for rheumatological diseases. The present study aimed to identify the risk factors of vertebral fracture in Japanese female patients with glucocorticoid-induced osteoporosis.Methods This study included 225 Japanese women with glucocorticoid-induced osteoporosis and 72 patients with postmenopausal osteoporosis. All participants were treated with bisphosphonate or denosumab for osteoporosis with active form of vitamin D for at least 3 years. The differences of clinical parameters, including age, disease duration, body mass index (BMI), bone mineral density (BMD), and the dose and treatment duration of glucocorticoid were assessed between patients with and without vertebral fracture. Multivariate logistic regression analysis was also performed to evaluate the association of vertebral fracture with clinical parameters.Results The significant differences related to age, BMD of the hip, disease duration, glucocorticoid treatment duration between patients with and without vertebral fractures were demonstrated. The present study indicated that disease duration, BMI, and the total hip BMD were independent risk factors for vertebral fractures in patients with glucocorticoid-induced osteoporosis.Conclusions Prolonged disease duration, low BMI, and low total hip BMD could be risk factors of vertebral fracture in patients on glucocorticoid treatment for rheumatological diseases.
Risk conditions in children hospitalized with influenza in Norway, 2017-2019
Authors: Hauge Siri Helene , Bakken Inger Johanne , de Blasio Birgitte Freiesleben , Håberg Siri Eldevik
Published: May 2020

Background
Norwegian children are more frequently hospitalized with influenza than adults. Little is known about the characteristics of these children. Our aim was to investigate the presence of pre-existing risk conditions and to determine the duration of influenza hospitalizations in children during two influenza seasons.
Methods
The Norwegian Patient Registry holds data on all hospitalized patients in Norway. We included all patients younger than 18 years hospitalized with a diagnosis of influenza during the influenza seasons 2017-18 and 2018-19. Pre-existing risk conditions for influenza were identified by ICD-10 diagnoses in the Norwegian Patient Registry. In addition, information on asthma diagnoses were also retrieved from the Norwegian Registry for Primary Health Care. To estimate the prevalence of risk conditions in the child population, we obtained diagnoses on all Norwegian children in a two-year period prior to each influenza season. We calculated age-specific rates for hospitalization and risk for being hospitalized with influenza in children with risk conditions.
Results
In total, 1013 children were hospitalized with influenza during the two influenza seasons. Children younger than 6 months had the highest rate of hospitalization, accounting for 13.5% of all admissions (137 children). Hospitalization rates decreased with increasing age. Among children hospitalized with influenza, 25% had one or more pre-existing risk conditions for severe influenza, compared to 5% in the general population under 18 years. Having one or more risk conditions significantly increased the risk of hospitalization, (Odds Ratio (OR) 6.1, 95% confidence interval (CI) 5.0-7.4 in the 2017-18 season, and OR 6.8, 95% CI 5.4–8.4 in the 2018-19 season). Immunocompromised children and children with epilepsy had the highest risk of hospitalization with influenza, followed by children with heart disease and lung disease. The average length of stay in hospital were 4.6 days, and this did not differ with age.
Conclusion
Children with pre-existing risk conditions for influenza had a higher risk of hospitalization for influenza. However, most children (75%) admitted to hospital with influenza in Norway during 2017–2019 did not have pre-existing risk conditions. Influenza vaccination should be promoted in particular for children with risk conditions and pregnant women to protect new-borns.
Are PAMAM dendrimers safe for ocular applications? -- Toxicological evaluation in ocular cells and intraocular tissues
Authors: Qin Chen , Tang Junmei , Wen Shimin , Zhu SiQing , Liu Dong , Chen Hao , Lin Quankui
Published: May 2020

Backgrounds: The human eye is a sophisticated and sensitive sensory organ. Due to its dynamic and static barriers, efficient drug therapy for eye diseases is problematic. Polymeric delivery systems have been rapidly developed to overcome this problem, where polymeric dendrimers have received much attention for their unique structures. However, there is insufficient research on whether dendrimer nanomaterials could be used in ophthalmology. Poly (amidoamine) (PAMAM) is a kind of commercialized and extensively used dendrimer. Herein the ocular cytotoxicity and biosafety of PAMAM dendrimers were deeply evaluated by conducting in vitro and in vivo experiments on ocular systems. The effects of generation (G4.0, G5.0, and G6.0) and concentration on cell metabolism, apoptosis, and oxidative damage were carried out. Ocular irritation and intravitreal injection effects were also measured. Results: The results showed that the cytotoxicity of PAMAM increased with increasing generation number. PAMAM at a concentration that below 50 μg/mL was less harmful to the ocular tissues, whereas it caused apparent damage when above 50 μg/mL in the investigated situation. Moreover, singlet oxygen generation was detected in the cells after 50 μg/mL (and above) PAMAM treatment. The in vivo results show that there is no macroscopic structural change observed from fundus and histopathological section images, whereas it shows more functional impairment according to optical coherence tomography (OCT) and electroretinogram (ERG) when treated by 100 μg/mL PAMAM. Conclusion: Overall, a higher concentration of PAMAM, such as above 50 μg/mL, may cause ocular functional damage. The concentrations that are (or lower than) 50 μg/mL showed good biocompatibility and biosafety in human ocular cells and tissues.
Extraskeletal Ewing’s sarcoma: outcomes and CT features of endoceliac lesions
Authors: Chen Zeyang , Jiao Yang , Liu Zining , Yang Jiejin , Zhang Yuyang , Sun Jiali , Zhao Kang , Pan Shaorong , Wang Pengyuan
Published: May 2020

Background To analyse the clinicopathological features and outcomes of patients with extraskeletal Ewing’s sarcoma (EES). The basic imaging characteristics of endoceliac lesions, which are always misdiagnosed preoperatively, are also summarised.Methods This study involved EES patients admitted to our centre between January 2000 and January 2020. Clinical data from patients with EES (n = 25) and computed tomography (CT) data from patients with endoceliac lesions (n = 8) were retrospectively reviewed.Results The sample comprised 18 males and 7 females with a median age of 30 years (range 1–72 years). Seven patients had EES originating from surface sites and 18 had EES originating from endoceliac sites. The median tumour size was 8.0 cm (range 2.5–17.0 cm). In total, 20% of patients had distant metastasis at diagnosis. In the univariate analyses, tumour size > 8 cm, undergoing surgery, and regional lymph nodes metastasis were risk factors for poor prognosis of EES. In the multivariate analysis, patients undergoing surgery and regional lymph node metastasis were independent predictors of overall survival (OS). Endoceliac EES cases frequently exhibited lobulated contour (87.5%), absence of calcification (75%), severe necrosis or cystic degeneration (75%), heterogeneous enhancement (100%), moderate enhancement (75%), ill-defined borderline (62.5%), and organ invasion (75%). Half of the patients with endoceliac EES had CT features of lymphadenopathy.Conclusions Comprehensive understanding of the clinicopathological and imaging features of EES is beneficial for diagnosis, development of therapeutic strategies, and accurate prediction of prognosis for this rare malignant tumour. The results suggest that evaluation of the status of regional lymph nodes is important for the treatment of EES.
Establishment and characterization of a new gastric cancer cell line, XGC-1
Authors: Peng Jigui , Xu Hao , Cai Jianchun
Published: May 2020

Background
To establish a primary human gastric cancer cell line.
Methods
Fresh gastric cancer tissue samples were separated into a cell suspension, and DMEM/F12 medium containing 10% foetal bovine serum was used for primary culture and subculture. The morphology of the cells was observed under a light microscope, and the cell growth curve was plotted. A soft agar colony formation assay was used to detect the colony formation ability of the cell line. Immunohistochemical methods were used to detect cytokeratin, vimentin and Ki-67, the chromosome G banding method was used to analyse the karyotype of the cells, and the tumourigenic ability of the cells was detected by subcutaneous inoculation of BALB/C nude mice.
Results
We established a gastric cancer cell line from a 68-year-old male patient. This gastric cancer cell line was named XGC-1 and had a doubling time of approximately 48 h. The cell line displayed strong colony formation ability and tumourigenicity in BALB/C nude mice and had complicated chromosomal abnormalities. When nutrients were insufficient, the cells shed and floated in the medium, but adherent growth was observed in nutrient-rich conditions.
Conclusions
The XGC-1 cell line will be useful for future studies of gastric cancer development, progression, metastasis and therapy.
Ipsilateral Proximal and Shaft Femoral Fractures Treated With Bridge-Link type combined fixation system
Authors: Kang Liangqi , Liu Hui , Ding Zhenqi , Ding Yiqiang , Hu Wei , Wu Jin
Published: May 2020

Background: Although many treatments for ipsilateral proximal and shaft femoral fractures have been developed, controversy exists regarding their optimal management. The purpose of this retrospective study was to discuss the effectiveness of the Bridge-Link type combined fixation system (BCFS) and evaluate functional outcomes in treating patients with these complex fractures. Patients and Methods: We retrospectively reviewed 14 cases of ipsilateral proximal and shaft femoral fractures treated from January 2012 to December 2016. All cases were treated by BCFS combined with minimally invasive percutaneous plate osteosynthesis (MIPPO). Clinical and radiographic data were collected during regular post-operative follow-up visits. Functional outcomes were determined according to the Friedman and Wyman scoring system. Results: The proximal femoral fractures were emergency diagnoses in 11 cases and delayed diagnoses in 3 cases. The delay time was 5-6 days, with an average of 5.3 days. The mean operation time was 179.6 minutes (range 135-231 minutes) with a blood loss volume that ranged from 430 to 535 ml (average 483.6 ml). Follow up was conducted in 13 cases between 9 and 30 months post-operation, with an average follow-up time of 17.3 months. The proximal femoral fractures were united in 12 cases at the final follow-up. One case had nonunion 13 months after the operation, underwent valgus intertrochanteric osteotomy, and healed 6 months later. The femoral shaft fractures obtained rigid union at the latest follow-up in 12 cases. One case endured nonunion 12 months after the operation. After the revision surgery and iliac bone grafting, the fracture healed 6 months later. Eight of the cases had good functional results, 4 had fair results, and results were poor in 1 case at the final follow-up. Conclusions: The treatment of ipsilateral proximal femoral and shaft fractures with BCFS in combination with MIPPO demonstrated a high likelihood of union for both fractures and good functional results.