bluuebunny/crossref_metadata_2025 huggingface dataset:
How well is the electronic health record supporting the clinical tasks of hospital physicians? A survey of physicians at three Norwegian hospitals
Authors: Schopf Thomas Roger , Nedrebø Bente , Hufthammer Karl Ove , Daphu Inderjit Kaur , Lærum Hallvard
Published: December 2019

Background

The electronic health record is expected to improve the quality and efficiency of health care. Many novel functionalities have been introduced in order to improve medical decision making and communication between health care personnel. There is however limited evidence on whether these new functionalities are useful. The aim of our study was to investigate how well the electronic health record system supports physicians in performing basic clinical tasks.

Methods

Physicians of three prominent Norwegian hospitals participated in the survey. They were asked, in an online questionnaire, how well the hospital’s electronic health record system DIPS supported 49 clinical tasks as well as how satisfied they were with the system in general, including the technical performance. Two hundred and eight of 402 physicians (52%) submitted a completely answered questionnaire.

Results

Seventy-two percent of the physicians had their work interrupted or delayed because the electronic health record hangs or crashes at least once a week, while 22% had experienced this problem daily. Fifty-three percent of the physicians indicated that the electronic health record is cumbersome to use and adds to their workload. The majority of physicians were satisfied with managing tests, e.g., requesting laboratory tests, reading test results and managing radiological investigations and electrocardiograms. Physicians were less satisfied with managing referrals. There was high satisfaction with some of the decision support functionalities available for prescribing drugs. This includes drug interaction alerts and drug allergy warnings, which are displayed automatically. However, physicians were less satisfied with other aspects of prescribing drugs, including getting an overview of the ongoing drug therapy.

Conclusions

In the survey physicians asked for improvements of certain electronic health record functionalities like medication, clinical workflow support including planning and better overviews. In addition, there is apparently a need to focus on system stability, number of logins, reliability and better instructions on available electronic health record features. Considerable development is needed in current electronic health record systems to improve usefulness and satisfaction.
Gametocyte clearance in children, from western Kenya, with uncomplicated Plasmodium falciparum malaria after artemether–lumefantrine or dihydroartemisinin–piperaquine treatment
Authors: Omondi Protus , Burugu Marion , Matoke-Muhia Damaris , Too Edwin , Nambati Eva A. , Chege William , Musyoka Kelvin B. , Thiongo Kelvin , Otinga Maureen , Muregi Francis , Kimani Francis
Published: December 2019

Background

The efficacy and safety of artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DP) against asexual parasites population has been documented. However, the effect of these anti-malarials on sexual parasites is still less clear. Gametocyte clearance following treatment is essential for malaria control and elimination efforts; therefore, the study sought to determine trends in gametocyte clearance after AL or DP treatment in children from a malaria-endemic site in Kenya.

Methods

Children aged between 0.5 and 12 years from Busia, western Kenya with uncomplicated Plasmodium falciparum malaria were assigned randomly to AL or DP treatment. A total of 334 children were enrolled, and dried blood spot samples were collected for up to 6 weeks after treatment during the peak malaria transmission season in 2016 and preserved. Plasmodium falciparum gametocytes were detected by qRT-PCR and gametocyte prevalence, density and mean duration of gametocyte carriage were determined.

Results

At baseline, all the 334 children had positive asexual parasites by microscopy, 12% (40/334) had detectable gametocyte by microscopy, and 83.7% (253/302) children had gametocytes by RT-qPCR. Gametocyte prevalence by RT-qPCR decreased from 85.1% (126/148) at day 0 to 7.04% (5/71) at day 42 in AL group and from 82.4% (127/154) at day 0 to 14.5% (11/74) at day 42 in DP group. The average duration of gametocyte carriage as estimated by qRT-PCR was slightly shorter in the AL group (4.5 days) than in the DP group (5.1 days) but not significantly different (p = 0.301).

Conclusion

The study identifies no significant difference between AL and DP in gametocyte clearance. Gametocytes persisted up to 42 days post treatment in minority of individuals in both treatment arms. A gametocytocidal drug, in combination with artemisinin-based combination therapy, will be useful in blocking malaria transmission more efficiently.
CT and MRI manifestations of mediastinal cavernous hemangioma and a review of the literature
Authors: Bai Yu , Zhao Guoshu , Tan Yongming
Published: December 2019

Background

The cavernous hemangioma of mediastinum (CHM) is a rare benign lesion caused by congenital vascular dysplasia. However, its incidence is extremely low, and patients often lack relevant clinical symptoms. So we analyzed retrospectively some cases to investigate the imaging features of cavernous hemangioma of mediastinum (CHM) and improve the diagnostic accuracy.

Methods

The CT/MRI imaging features and clinical information of 19 patients with CHM were analyzed retrospectively.

Results

The lesions of 18 CHM patients were single. Twelve cases in the anterior mediastinum and 8 in the posterior mediastinum. The diameter of CHM ranges from 2.0 to 7.0 cm. Thirteen cases were oval-shaped or round, 4 cases were lobulated, and 2 cases were irregular. Phleboliths or nodular calcification were identified in four cases. High signal of T2WI lipid suppression in two cases and blood vessel shadows were observed in two cases. After contrast-enhanced scan, the nodular enhancement of arteries were identified in 14 cases and contrast agent was further filled of the venous phase, where “fast in and slow out” feature was performed. One case showed inhomogeneous enhancement, one case performed “fast in and slow out” feature of multiphase-enhanced MRI. Besides, aberrant veins can be seen in or around the lesion among five cases.

Conclusions

CHM is more frequently located at the anterior mediastinum than at the posterior mediastinum. The performance of phleboliths, high signal on T2WI fat suppression and DWI, the nodular enhancement of the artery, venous and delayed phase filling, enhanced “fast in and slow out,” and aberrant veins in the lesion are helpful for the diagnosis and differential diagnosis. Multiple period contrast-enhanced CT and MRI scan is helpful for the diagnosis of CHM.
Shortcomings of ultrasound-guided fine needle aspiration in the axillary management of women with breast cancer
Authors: Attieh Michel , Jamali Faek , Berjawi Ghina , Saadeldine Mothana , Boulos Fouad
Published: December 2019

Background

Ultrasound, along with ultrasound-guided fine needle aspiration, is currently used for the axillary evaluation of breast cancer patients in order to identify candidates for axillary lymph node dissection. The aim of this study is to evaluate the accuracy of this tool in correctly identifying patients who may or may not benefit from axillary clearance in light of the ACOSOG Z0011 trial recommendations.

Methods

One hundred one patients (65 with positive US-FNA with corresponding axillary lymph node dissection (ALND), and 36 with negative US-FNA with corresponding ALND/sentinel lymph node biopsy) were studied for the number of involved axillary lymph nodes, tumor clinicopathologic features, and axillary radiologic findings.

Results

From the positive US-FNA group, 43% of patients had two or fewer positive lymph nodes upon ALND pathologic examination. In the US-FNA negative group, the negative predictive value for detecting axillary disease was 72.7%. With both groups combined, the sensitivity, specificity, PPV, and NPV of US-FNA for selecting patients based on axillary disease burden were 86%, 51.7%, 57%, and 83.3%, respectively.

Conclusion

Based on Z0011 guidelines, US-FNA is not a reliable tool in triaging patients in need for ALND and leads to overtreatment of 43% patients when positive, while depriving a small but significant percentage of patients from necessary therapy, when negative.
Chronological changes and trend of breast cancer clinics and pathology among Iranian women during 22 years from the largest breast cancer registry in Iran
Authors: Tahmasebi Sedigheh , Tajali Mahsa , Akrami Majid , Arasteh Peyman , Zangouri Vahid , Nobandegani Aida Salehi , Hosseini Seyed Morteza , Safari Afsoon , Talei Abdolrasoul
Published: December 2019

Background and objective

We evaluated clinicopathological changes of breast cancer (BC) during a 22-year time period among the Iranian population.

Methods

This study is part of the largest BC registry in Iran. Patients were categorized as those diagnosed with BC during 1993–2005, 2006–2011, and 2012–2017 and compared regarding baseline characteristics and socioeconomical determinants, and obstetrical/gynecological and BC characteristics.

Results

Overall, 688, 1871, and 3020 patients entered the 1993–2005, 2006–2012, and 2012–2017 year groups, respectively. Mean (SD) age at first presentation of BC increased throughout the year groups (47.40 ± 10.34, 49.12 ± 11.70, and 49.43 ± 12.07 years, respectively;p< 0.001). Mean (SD) tumor size increased from 1993–2005 to 2006–2011 and decreased onto 2012–2017 (2.82 ± 1.69, 2.91 ± 1.49, and 2.66 ± 1.52 cm, respectively;p< 0.001). Number of individuals with stage 4 and grade 3 BC also showed an increasing pattern (p< 0.001). Tumor necrosis rates showed an increase onto 2011–2017 (43%, 47.3%, and 56%, respectively;p< 0.001). ER positive (62.4%, 73.4%, and 77.1%, respectively;p< 0.001) and PR positive individuals (59.5%, 64.3%, 72.6%, respectively;p< 0.001) showed an increasing trend. HER2 positive expression rates increased from 1993–2005 to 2005–2011 (24.5% and 31.5%, respectively) and decreased onto 2012–2017 (31.5% and 26.8%, respectively,p< 0.001). Number of involved lymph nodes increased (5.70 ± 6.56, 5.65 ± 6.00, and 5.95 ± 6.99, respectively;p< 0.001). Pattern of BC invasion and recurrence showed significant change (p< 0.001).

Conclusion

Clinical and pathological characteristics may be showing a changing pattern among the Iranian population.
Low molecular weight heparins use in pregnancy: a practice survey from Greece and a review of the literature
Authors: Papadakis E. , Pouliakis A. , Aktypi Α. , Christoforidou A. , Kotsi P. , Αnagnostou G. , Foifa A. , Grouzi E.
Published: December 2019

Background

Use of LMWH in pregnancy is not only limited to VTE management, but it extends, to the management of vascular gestational complications and the optimization of IVF pregnancies despite the lack of concrete scientific evidence. In this context, we conducted the present study aiming to gain insights regarding the use of LMWH during pregnancy and puerperium. We recorded indication for use, diagnostic work-up as well as the safety and efficacy of the treatment, trying to elucidate the clinical practice in our country.

Methods

We analyzed data regarding 818 pregnant women received LMWH during 2010–2015.Our cohort had a median age of 33.9 years and a BMI of 23.6.There were 4 groups: those with a history of VTE [Group-A: 76], those with pregnancy complications [Group-B: 445], those undergoing IVF [Group-C: 132] and those carrying prothrombotic tendency (thrombophilia, family history of VTE, other) [Group-D: 165]. Mean duration of LMWH administration was 8.6 ± 1.5 months. Out of the total number, 440 received LMWH in fixed prophylactic dose, 272 in higher prophylactic-weight adjusted dose and 106 in therapeutic dose. Moreover, 152 women received in addition low-dose acetylsalicylic acid (ASA). 93.8% of pregnancies were single and 6.2% were multiple ones. Live births occurred in 98.7% of pregnancies.

Results

Anticoagulation was efficacious and well tolerated. Seventeen VTE events were recorded; 7 of them antepartum and 10 postpartum. No major bleeding events were observed while 13 clinical relevant non-major bleeding events were recorded. Regarding gestational vascular complications, 28 IUGR events were recorded, as well as 48 cases of preterm labor of which 12 were concomitant with IUGR (25%). Six early pregnancy losses were recorded; there were 3 fetal deaths and 3 cases of pre-eclampsia/eclampsia.

Conclusions

LMWHs are used extensively during pregnancy and puerperium in Greece for VTE treatment and prophylaxis and for a variety of other indications as well. Although the drug has been shown to be both safe and efficacious, its use for some indications has no proven scientific evidence. In order to clearly define the role of LMWHs in pregnancy, beyond thromboprophylaxis, large prospective studies are required, which could be based on the conclusions of this study.
The effects of maternity waiting homes on the health workforce and maternal health service delivery in rural Zambia: a qualitative analysis
Authors: Kaiser Jeanette L. , Fong Rachel M. , Ngoma Thandiwe , McGlasson Kathleen Lucile , Biemba Godfrey , Hamer Davidson H. , Bwalya Misheck , Chasaya Maynards , Scott Nancy A.
Published: December 2019

Background

Maternity waiting homes (MWHs) are a potential strategy to address low facility delivery rates resulting from access-associated barriers in resource-limited settings. Within a cluster-randomized controlled trial testing a community-generated MWH model in rural Zambia, we qualitatively assessed how MWHs affect the health workforce and maternal health service delivery at their associated rural health centers.

Methods

Four rounds of in-depth interviews with district health staff (n = 21) and health center staff (n = 73) were conducted at intervention and control sites over 24 months. We conducted a content analysis using a mixed inductive-deductive approach. Data were interpreted through the lens of the World Health Organzation Health Systems Framework.

Results

Nearly all respondents expressed challenges with understaffing and overwork and reported that increasing numbers of facility-based deliveries driven by MWHs contributed substantively to their workload. Women waiting at MWHs allow staff to monitor a woman’s final stage of pregnancy and labor onset, detect complications earlier, and either more confidently manage those complications at the health center or refer to higher level care. District, intervention, and control site respondents passionately discussed this benefit over all time points, describing it as outweighing challenges of additional work associated with MWHs. Intervention site staff repeatedly discussed the benefit of MWHs in providing a space for postpartum women to wait after the first few hours of clinical observation through the first 48 h after delivery. Additionally, intervention site staff perceived the ability to observe women for longer before and after delivery allowed them to better anticipate and plan their own work, adjust their workloads and mindset accordingly, and provide better and more timely care. When understaffing and overwork were frequently discussed, this satisfaction in providing better care was a meaningful departure.

Conclusions

MWHs may benefit staff at rural health centers and the health system more broadly, allowing for the provision of more timely and comprehensive obstetric care. We recommend future studies consider how MWHs impact the workforce, operations, and service delivery at their associated health facilities. Considering the limited numbers of skilled birth attendants available in rural Zambia, it is important to strategically select locations for new MWHs.

Trial registration

Clinicaltrials.gov, NCT02620436. Registered December 3, 2015, https://clinicaltrials.gov/ct2/show/NCT02620436
Drug utilization and cost associated with inflammatory bowel disease management in Saudi Arabia
Authors: AlRuthia Yazed , Alharbi Othman , Aljebreen Abdulrahman M. , Azzam Nahla A. , Almadi Majid A. , Bahari Ohud H. , Almalki Khalid A. , Atham Abdulaziz T. , Alanazi Ahmed S. , Saeed Maria , HajkhderMullaissa Baraa , Alsenaidy Mohammad , Balkhi Bander
Published: December 2019

Background

There has been an increase in incidence and prevalence of inflammatory bowel disease (IBD) outside the western countries. Treatment costs are an essential component for healthcare planning and priority setting. The utilization patterns and annual administration and cost of IBD medications are largely unknown in countries with an increasing incidence of disease, Saudi Arabia being an example.

Aim

To evaluate the use of non-biologic and biologic agents and their associated annual administration costs in a sample of patients with Crohn’s disease (CD) and ulcerative colitis (UC) in Saudi Arabia.

Methods

Single-center retrospective chart review was performed to determine the use of biologic and non-biologic medications among IBD patients in a tertiary care hospital in Riyadh, Saudi Arabia. Daily and the annual acquisition cost of different IBD therapeutic agents was calculated. The utilization rates and cost of each type of medication by CD and UC patients were compared.

Results

Data of 258 CD patients and 249 UC patients were analyzed. Infliximab and adalimumab were the most commonly prescribed biologics among the study sample, however, their utilization rates were significantly higher among CD than UC patients (36.82% vs. 11.24%, and 20.54% vs. 9.64%, respectively, P < 0. 01). Azathioprine utilization rate was also higher among CD patients compared to their UC counterparts (71.71% vs. 40.16%, respectively, P < 0.01). However, the utilization rate of mesalazine in the UC patients was significantly higher than their CD counterparts (85.53% vs. 14.34% for CD, P < 0.01). The annual cost of biologics (including administration and lab test cost) ranged from 5572 USD for ustekinumab to 18,424 USD for vedolizumab. On the other hand, the annual cost of non-biologics ranged from 16 USD for prednisone to 527 USD for methotrexate.

Conclusion

Biologics are extensively used in the management of IBD, particularly CD, and their utilization costs are significantly higher than non-biologics. Future studies should examine the cost effectiveness of IBD medications especially in countries with increasing incidence such as Saudi Arabia.
Microbiota, type 2 diabetes and non-alcoholic fatty liver disease: protocol of an observational study
Authors: Motta Benedetta M. , Grander Christoph , Gögele Martin , Foco Luisa , Vukovic Vladimir , Melotti Roberto , Fuchsberger Christian , De Grandi Alessandro , Cantaloni Chiara , Picard Anne , Mascalzoni Deborah , Rossini Alessandra , Pattaro Cristian , Tilg Herbert , Pramstaller Peter P.
Published: December 2019

Background

Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the hepatocytes in the absence of alcohol overconsumption, commonly associated with insulin resistance and obesity. Both NAFLD and type 2 diabetes (T2D) are characterized by an altered microbiota composition, however the role of the microbiota in NAFLD and T2D is not well understood. To assess the relationship between alteration in the microbiota and NAFLD while dissecting the role of T2D, we established a nested study on T2D and non-T2D individuals within the Cooperative Health Research In South Tyrol (CHRIS) study, called the CHRIS-NAFLD study. Here, we present the study protocol along with baseline and follow-up characteristics of study participants.

Methods

Among the first 4979 CHRIS study participants, 227 individuals with T2D were identified and recalled, along with 227 age- and sex-matched non-T2D individuals. Participants underwent ultrasound and transient elastography examination to evaluate the presence of hepatic steatosis and liver stiffness. Additionally, sampling of saliva and faeces, biochemical measurements and clinical interviews were carried out.

Results

We recruited 173 T2D and 183 non-T2D participants (78% overall response rate). Hepatic steatosis was more common in T2D (63.7%) than non-T2D (36.3%) participants. T2D participants also had higher levels of liver stiffness (median 4.8 kPa, interquartile range (IQR) 3.7, 5.9) than non-T2D participants (median 3.9 kPa, IQR 3.3, 5.1). The non-invasive scoring systems like the NAFLD fibrosis score (NFS) suggests an increased liver fibrosis in T2D (mean − 0.55, standard deviation, SD, 1.30) than non-T2D participants (mean − 1.30, SD, 1.17).

Discussion

Given the comprehensive biochemical and clinical characterization of study participants, once the bioinformatics classification of the microbiota will be completed, the CHRIS-NAFLD study will become a useful resource to further our understanding of the relationship between microbiota, T2D and NAFLD.
Correction to: Viral integration drives multifocal HCC during the occult HBV infection
Authors: Chen Xiao-Ping , Long Xin , Jia Wen-long , Wu Han-Jie , Zhao Jing , Liang Hui-Fang , Laurence Arian , Zhu Jun , Dong Dong , Chen Yan , Lin Long , Xia Yu-Dong , Li Wei-Yang , Li Gui-Bo , Zhao Zhi-Kun , Wu Kui , Hou Yong , Yu Jing-Jing , Xiao Wei , Wang Guo-Ping , Zhu Peng-Cheng , Chen Wei , Bai Ming-Zhou , Jian Yi-Xing , Kristiansen Karsten , Chen Qian
Published: December 2019

In the original publication of this article [1], Fig. 6 is wrong and the updated figure is shown below.
PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?
Authors: Pavone Piero , Corsello Giovanni. , Cho Sung Yoon , Pappalardo Xena Giada , Ruggieri Martino , Marino Simona Domenica , Jin Dong Kyu , Marino Silvia , Falsaperla Raffaele
Published: December 2019

Background

Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders.

Case presentation

We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in PRRT2 gene (c.501C > T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing.

Conclusion

Several hypotheses have been advanced on the specific role that PRRT2 gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in PRRT2 gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation.
Assessment of quality of edible vegetable oils accessed in Gondar City, Northwest Ethiopia
Authors: Negash Yonnas Adugna , Amare Dagnachew Eyachew , Bitew Bikes Destaw , Dagne Henok
Published: December 2019

Objective

Edible vegetable oils are prone to quality deterioration through oxidation and microbial degradation resulting in nutritional loss and off-flavors. Quality deterioration may contribute in the formation of oxidation products that are reactive and toxic, which ultimately pose health risks including cancer and inflammation. The objective of this study was to assess quality of both imported and locally made edible vegetable oils accessed in Gondar City, Ethiopia. Cross-sectional study design was used to collect 60 samples randomly; 30 from locally made (Niger seed at market 14, Niger seed at production center 11, sunflower at the market 5) and 30 from imported palm oil brands (Avena 11, Hayat 4, Jersey 5 and Chef 10).

Results

The mean value for: moisture content (%) (0.333 ± 0.08 while 0.089 ± 0.11), specific-gravity (0.823 ± 0.14 and 0.807 ± 0.115), peroxide value (15.09 ± 1.61 and 7.05 ± 0.102 mill-equivalents of oxygen/kg), acid value (2.43 ± 0.9 and 0.98 ± 0.23 mg KOH/g oil) and iodine value (115.63 ± 6.77 and 21.8 ± 3.4 g I2/100 g oil) for local and imported edible oils, respectively. The results highlight that all rancidity quality parameters of the locally made oil samples were not within the joint WHO/FAO standards whilst the imported oils showed a greater fatty acid saturation.
Improving selectivity of DNA–RNA binding zinc finger using directed evolution
Authors: Sulej Agata A.
Published: December 2019

Objective

Type C2H2 zinc fingers bind a variety of substrates, specific sequences in the double-stranded DNA counting among them. Engineering efforts led to the discovery of a set of general rules that enable obtaining zinc fingers modules that bind to almost any given sequence. The objective of this work was to determine an analogical set of rules for the binding of specific sequences in DNA–RNA hybrids using directed evolution of ZfQQR zinc finger. The target regions for evolution included the amino acid residues that directly interact with the substrate and linkers between the zinc finger modules.

Results

The directed evolution was performed using selection based on biopanning of phage-displayed libraries of randomized regions in the ZfQQR zinc finger. The applied strategy of randomization of the middle module of the zinc finger along with input library bias and materials used for biopanning hindered the selection of the modules with altered specificity. However, the directed evolution of the linker sequence between modules enabled selection of variants with improved selectivity towards DNA–RNA hybrids in the presence of double-stranded DNA in comparison to the original ZfQQR. This confirms the necessity of linker optimization between modules in zinc finger domains.
Chest imaging using signs, symbols, and naturalistic images: a practical guide for radiologists and non-radiologists
Authors: Chiarenza Alessandra , Esposto Ultimo Luca , Falsaperla Daniele , Travali Mario , Foti Pietro Valerio , Torrisi Sebastiano Emanuele , Schisano Matteo , Mauro Letizia Antonella , Sambataro Gianluca , Basile Antonio , Vancheri Carlo , Palmucci Stefano
Published: December 2019

Several imaging findings of thoracic diseases have been referred—on chest radiographs or CT scans—to signs, symbols, or naturalistic images. Most of these imaging findings include the air bronchogram sign, the air crescent sign, the arcade-like sign, the atoll sign, the cheerios sign, the crazy paving appearance, the comet-tail sign, the darkus bronchus sign, the doughnut sign, the pattern of eggshell calcifications, the feeding vessel sign, the finger-in-gloove sign, the galaxy sign, the ginkgo leaf sign, the Golden-S sign, the halo sign, the headcheese sign, the honeycombing appearance, the interface sign, the knuckle sign, the monod sign, the mosaic attenuation, the Oreo-cookie sign, the polo-mint sign, the presence of popcorn calcifications, the positive bronchus sign, the railway track appearance, the scimitar sign, the signet ring sign, the snowstorm sign, the sunburst sign, the tree-in-bud distribution, and the tram truck line appearance. These associations are very helpful for radiologists and non-radiologists and increase learning and assimilation of concepts.

Therefore, the aim of this pictorial review is to highlight the main thoracic imaging findings that may be associated with signs, symbols, or naturalistic images: an “iconographic” glossary of terms used for thoracic imaging is reproduced—placing side by side radiological features and naturalistic figures, symbols, and schematic drawings.
Adult human cardiac stem cell supplementation effectively increases contractile function and maturation in human engineered cardiac tissues
Authors: Murphy Jack F. , Mayourian Joshua , Stillitano Francesca , Munawar Sadek , Broughton Kathleen M. , Agullo-Pascual Esperanza , Sussman Mark A. , Hajjar Roger J. , Costa Kevin D. , Turnbull Irene C.
Published: December 2019

Background

Delivery of stem cells to the failing heart is a promising therapeutic strategy. However, the improvement in cardiac function in animal studies has not fully translated to humans. To help bridge the gap between species, we investigated the effects of adult human cardiac stem cells (hCSCs) on contractile function of human engineered cardiac tissues (hECTs) as a species-specific model of the human myocardium.

Methods

Human induced pluripotent stem cell-derived cardiomyoctes (hCMs) were mixed with Collagen/Matrigel to fabricate control hECTs, with an experimental group of hCSC-supplemented hECT fabricated using a 9:1 ratio of hCM to hCSC. Functional testing was performed starting on culture day 6, under spontaneous conditions and also during electrical pacing from 0.25 to 1.0 Hz, measurements repeated at days 8 and 10. hECTs were then frozen and processed for gene analysis using a Nanostring assay with a cardiac targeted custom panel.

Results

The hCSC-supplemented hECTs displayed a twofold higher developed force vs. hCM-only controls by day 6, with approximately threefold higher developed stress and maximum rates of contraction and relaxation during pacing at 0.75 Hz. The spontaneous beat rate characteristics were similar between groups, and hCSC supplementation did not adversely impact beat rate variability. The increased contractility persisted through days 8 and 10, albeit with some decrease in the magnitude of the difference of the force by day 10, but with developed stress still significantly higher in hCSC-supplemented hECT; these findings were confirmed with multiple hCSC and hCM cell lines. The force-frequency relationship, while negative for both, control (− 0.687 Hz− 1; p = 0.013 vs. zero) and hCSC-supplemented (− 0.233 Hz− 1;p = 0.067 vs. zero) hECTs, showed a significant rectification in the regression slope in hCSC-supplemented hECT (p = 0.011 vs. control). Targeted gene exploration (59 genes) identified a total of 14 differentially expressed genes, with increases in the ratios of MYH7/MHY6, MYL2/MYL7, and TNNI3/TNNI1 in hCSC-supplemented hECT versus controls.

Conclusions

For the first time, hCSC supplementation was shown to significantly improve human cardiac tissue contractility in vitro, without evidence of proarrhythmic effects, and was associated with increased expression of markers of cardiac maturation. These findings provide new insights about adult cardiac stem cells as contributors to functional improvement of human myocardium.
Stability of functional differential systems applied to the model of testosterone regulation
Authors: Domoshnitsky Alexander , Volinsky Irina , Pinhasov Olga , Bershadsky Marina
Published: December 2019

In this paper we propose a method for stability studies of functional differential systems. The idea of our method is to reduce the analysis of ann-dimensional system to one for an$(n+m)$(n+m)-dimensional system, wheremis a natural number, to obtain stability and then to come back and make conclusions on the stability of the givenn-dimensional system. As an example, a model describing testosterone by distributed inputs feedback control is considered. The aim of the regulation is to hold testosterone concentration above an appropriate level. The feedback control with integral term is proposed. We have to increase the testosterone level to the normal one. The control we proposed could destroy the stability of the model. That is why we have to choose the parameters of our distributed control, namely a dosage or intensity of assimilation of a medicine in a human body in such a form that the stability of our system is preserved. Thus the problem of regulation of testosterone level leads us to the stability analysis of the functional differential system describing a connection between the concentrations of hormones (GnRH), (LH), and testosterone (Te). Constructing the system, we discard the connections which seem nonessential. To estimate the effect of these connections is an important problem. We construct the Cauchy matrix of integro-differential system to estimate this influence.
FOXC2-AS1 regulates phenotypic transition, proliferation and migration of human great saphenous vein smooth muscle cells
Authors: Zhang Chuang , Li Huixiang , Guo Xueli
Published: December 2019

Objectives

In varicose veins, vascular smooth muscle cells (VSMCs) often shows phenotypic transition and abnormal proliferation and migration. Evidence suggests the FOXC2–Notch pathway may be involved in the pathogenesis of varicose veins. Here, this study aimed to explore the role of long non-coding RNA FOXC2-AS1 (FOXC2 antisense RNA 1) in phenotypic transition, proliferation, and migration of varicose vein-derived VSMCs and to explore whether the FOXC2-Notch pathway was involved in this process.

Methods

The effect of FOXC2-AS1 on the proliferation and migration of human great saphenous vein smooth muscle cells (SV-SMCs) was analyzed using MTT assay and Transwell migration assay, respectively. The levels of contractile marker SM22α and synthetic marker osteopontin were measured by immunohistochemistry and Western blot to assess the phenotypic transition.

Results

The human varicose veins showed thickened intima, media and adventitia layers, increased synthetic VSMCs, as well as upregulated FOXC2-AS1 and FOXC2 expression. In vitro assays showed that FOXC2-AS1 overexpression promoted phenotypic transition, proliferation, and migration of SV-SMCs. However, the effect of FOXC2-AS1 overexpression could be abrogated by both FOXC2 silencing and the Notch signaling inhibitor FLI-06. Furthermore, FOXC2-AS1 overexpression activated the Notch pathway by upregulating FOXC2.

Conclusion

FOXC2-AS1 overexpression promotes phenotypic transition, proliferation, and migration of SV-SMCs, at least partially, by activating the FOXC2-Notch pathway.
Bacillus thuringiensis kurstaki strains produce vegetative insecticidal proteins (Vip 3) with high potential
Authors: Güney Ebru , Adıgüzel Aysun , Demirbağ Zihni , Sezen Kazım
Published: December 2019

Bacillus thuringiensis(Bt) produces vegetative insecticidal proteins (Vip) during its vegetative growth stage. Vip3 proteins have a significant role in insecticidal activity of this bacterium. Each new bacterial isolate may encode Vip with different significance. The Vip protein coding by vip genes of twoBtstrains (BnBt and MnD) with high insecticidal activity was characterized in this study. Polymerase chain reaction (PCR)-based screening for Vip genes of theseBtisolates expressed the detected Vip gene and tested the protein for insecticidal activity against the cotton leafworm,Spodoptera littoralislarvae. As a result of the screening tests, Vip3 genes were determined in MnD and BnBt isolates. Vip3 genes of both isolates were expressed and confirmed by 90 kDa proteins. Partially purified and trypsin-activated protein samples of BnBt and MnD isolates were tested against the second instar larvae ofS. littoralis.The results showed that the highest insecticidal activity of the Vip3 proteins of BnBt and MnD was 86.66% and 83.33% mortality in 10 days, respectively. The median lethal concentrations (LC50) of BnBt and MnD were determined as 41.860 and 55.154 ng/μl, respectively. The results suggest that Vip3 protein is effective for preventing resistance in various insect-pest species. The expressed proteins may be utilized as a biopesticide against nocuous insects.
In vitro evaluation of some isolated bacteria against the plant parasite nematode Meloidogyne incognita
Authors: Soliman Gaziea Mohamed , Ameen Hoda Hussein , Abdel-Aziz Shadia Mohamed , El-Sayed Ghada M.
Published: December 2019

Background

Microbial cultures are extensively used as environment friendly ways for biological control of parasitic pests, including the root-knot nematodes, alternative to the use of chemical nematicides. The present study was conducted to isolate some lytic rhizobacteria and examine their nematicidal activity againstMeloidogyne incognitaJ2mortality and egg hatching in in vitro test.

Results

Lytic Rhizobacteria were isolated from soil samples adhering to tomato plant roots from different localities at Giza governorate, Egypt. Six bacterial isolates, exhibited high efficacy against root-knot nematodes, were identified based on the analysis of the 16S rRNA gene sequence asPseudomonas aeruginosa,Paenibacillus polymyxa,Lysinibacillus sphaericus,Bacillus cereus,Bacillus subtilis, andAchromobacter xylosoxidans. These strains showed high production of chitinase, chitosanase, and protease using colloidal chitin and soluble chitosan as carbon sources. Two strains,Paenibacillus polymyxaandBacillus subtilis, produced the highest levels of chitinase in the media. Except forPseudomonas aeruginosa, all the bacterial strains produced high levels of chitosanase.

Conclusion

The results revealed that high amounts of protease were, however, secreted byPseudomonas aeruginosaas compared to the other strains. In in vitro tests, all the bacterial culture filtrates potentially displayed nematicidal effect inM. incognitaegg hatching and an obvious increase in J2mortality as compared to control.Paenibacillus polymyxacaused 100% juvenile mortality followed byBacillus subtilis97.25%,Bacillus cereus94%,Achromobacter xylosoxidans93%,Lysinibacillus sphaericus92%, andPseudomonas aeruginosa84.29% after 48 h of exposure, as compared to control.
Optimization of energy storage and system flexibility in the context of the energy transition: Germany’s power grid as a case study
Authors: K. Maia Leonardo K. , Zondervan Edwin
Published: December 2019

In this work we explore the ramifications of incoming changes brought by the energy transition, most notably the increased penetration of variable renewable energy (VRE) and phase-out of nuclear and other conventional electricity sources. The power grid will require additional flexibility capabilities to accommodate such changes, as the mismatch between generation and demand is bound to increase. Through mathematical modeling and optimization, we simulate the German power grid and investigate the requirements of on-grid large-scale storage. Different scenarios are evaluated up to 2050, when 80% of the gross electricity consumption is planned to be provided by renewable energy. Dispatchable power plants will play a key role in the transition to an energy mix with high shares of VRE. Around 120 GW of additional large-scale storage are required until 2050. Between the electrochemical technologies evaluated, lithium-ion was the best candidate. A strong reliance on dispatchables was observed, in case the commissioning of VRE plants goes slower than planned. Energy curtailment increases with VRE shares, with up to 14 TWh curtailed in high VRE scenarios in 2050.
Prevalence and Predictors of Frailty in Childhood Cancer Survivors and Siblings: A Report From the Childhood Cancer Survivor Study
Authors: Hayek Samah , Gibson Todd M. , Leisenring Wendy M. , Guida Jennifer L. , Gramatges Maria Monica , Lupo Philip J. , Howell Rebecca M. , Oeffinger Kevin C. , Bhatia Smita , Edelstein Kim , Hudson Melissa M. , Robison Leslie L. , Nathan Paul C. , Yasui Yutaka , Krull Kevin R. , Armstrong Gregory T. , Ness Kirsten K.
Published: December 2019

PURPOSE

To estimate the prevalence of frailty among childhood cancer survivors and to determine the direct and indirect effects of treatment exposures, lifestyle factors, and severe, disabling, and life-threatening chronic condition on frailty.

METHODS

Childhood cancer survivors (≥ 5 years since diagnosis), treated between 1970 and 1999 when < 21 years old (n = 10,899; mean age, 37.6 ± 9.4 years; 48% male, 86% white) and siblings were included (n = 2,097; mean age, 42.9 ± 9.4 years). Frailty was defined as ≥ 3 of the following: low lean mass, exhaustion, low energy expenditure, walking limitations, and weakness. Generalized linear models were used to evaluate direct and indirect associations between frailty and treatment exposures, sociodemographic characteristics, lifestyle factors, and chronic condition.

RESULTS

The overall prevalence of frailty among survivors was 3 times higher compared with siblings (6.4%; 95% CI, 4.1% to 8.7%; v 2.2%; 95% CI, 1.2% to 3.2%). Survivors of CNS tumors (9.5%; 95% CI, 5.2% to 13.8%) and bone tumors (8.1%; 95% CI, 5.1% to 11.1%) had the highest prevalence of frailty. Survivors exposed to cranial radiation, pelvic radiation ≥ 34 Gy, abdominal radiation > 40 Gy, cisplatin ≥ 600 mg/m2, amputation, or lung surgery had increased risk for frailty. These associations were partially but not completely attenuated when sociodemographic characteristics, lifestyle factors, and chronic conditions were added to multivariable models. Cranial radiation (prevalence ratio [PR], 1.47; 95% CI, 1.20 to 1.76), pelvic radiation ≥ 34 Gy (PR, 1.46; 95% CI, 1.01 to 2.11), and lung surgery (PR, 1.75; 95% CI, 1.28 to 2.38) remained significant after sociodemographic, lifestyle, and chronic conditions were accounted for.

CONCLUSION

Childhood cancer survivors reported a higher prevalence of frailty compared with siblings. Radiation and lung surgery exposures were associated with increased risk for frailty. Interventions to prevent, delay onset, or remediate chronic disease and/or promote healthy lifestyle are needed to decrease the prevalence of frailty and preserve function in this at-risk population.
Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease
Authors: Abu-Sbeih Hamzah , Faleck David M. , Ricciuti Biagio , Mendelsohn Robin B. , Naqash Abdul R. , Cohen Justine V. , Sellers Maclean C. , Balaji Aanika , Ben-Betzalel Guy , Hajir Ibraheim , Zhang Jiajia , Awad Mark M. , Leonardi Giulia C. , Johnson Douglas B. , Pinato David J. , Owen Dwight H. , Weiss Sarah A. , Lamberti Giuseppe , Lythgoe Mark P. , Manuzzi Lisa , Arnold Christina , Qiao Wei , Naidoo Jarushka , Markel Gal , Powell Nick , Yeung Sai-Ching J. , Sharon Elad , Dougan Michael , Wang Yinghong
Published: December 2019

PURPOSE

The risk of immune checkpoint inhibitor therapy–related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors.

PATIENTS AND METHODS

We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events.

RESULTS

Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn’s disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event–related deaths were recorded. Anti–cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively).

CONCLUSION

Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.
Impact of Addition of Carboplatin AUC ≥ 4 to Antiemetic Guidelines for Triple Antiemetic Prophylaxis: A Gap in Quality of Care, Guideline Adoption, and Avoiding Acute Care
Authors: Navari Rudolph M. , Ruddy Kathryn J. , LeBlanc Thomas W. , Clark-Snow Rebecca , Wickham Rita J. , Binder Gary , Coberly Tammy , Potluri Ravi , Schmerold Luke M. , Roeland Eric J.
Published: December 2019

PURPOSE:

After ASCO and National Comprehensive Cancer Network guideline recommendations for triple antiemetic prophylaxis for carboplatin area under the curve (AUC) ≥ 4, and the publication of studies documenting avoidable acute care after chemotherapy involving nausea and vomiting (NV) and other toxicities, we studied clinician adherence to the guideline change and assessed avoidable acute-care use.

METHODS:

Using a large electronic health record database, we evaluated antiemetic prophylaxis as recommended in the guidelines and post-chemotherapy avoidable acute-care use (defined as involving any of NV or 8 other toxicities) for patients initiating carboplatin or other chemotherapy from October 2012 to August 2018.

RESULTS:

We identified 11,554 carboplatin courses. After the guideline change adding neurokinin-1 receptor antagonists (RAs) for carboplatin AUC ≥ 4, its use rose to 20% of courses from the prior average of 16%; virtually all courses also included a 5-HT3 RA plus dexamethasone. We found avoidable acute care in 23% of courses; one quarter of these events were associated with NV. Acute care rates after carboplatin mirrored those after other highly emetogenic chemotherapy or oxaliplatin and exceeded those after other chemotherapy regimens. The > 80% shortfall in adherence may have been caused by low awareness or acceptance of the guideline change and/or by poor awareness of avoidable acute-care use after carboplatin.

CONCLUSION:

Neurokinin-1 RA prophylaxis for carboplatin AUC ≥ 4 remains low and largely unchanged despite National Comprehensive Cancer Network and ASCO 2017 recommendations for inclusion. NV and avoidable acute care involving NV seen after carboplatin were consistent with other highly emetogenic chemotherapy. Clinician action is required to remediate incomplete prophylaxis and to no longer place patient outcomes, resources for cancer treatment, and clinician reimbursement at risk.