bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel hotspot and rare somatic mutation p.A138V, at TP53 is associated with poor survival of pancreatic ductal and periampullary adenocarcinoma patients
Authors: Saha Gourab , Singh Richa , Mandal Argha , Das Subrata , Chattopadhyay Esita , Panja Prasun , Roy Paromita , DeSarkar Navonil , Gulati Sumit , Ghatak Supriyo , Ghosh Shibajyoti , Banerjee Sudeep , Roy Bidyut , Ghosh Saurabh , Chaudhuri Dipankar , Arora Neeraj , Biswas Nidhan K. , Sikdar Nilabja
Published: June 2020

Background

Pancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary Adenocarcinoma (PAC) accounts for 0.5–2% of all gastrointestinal malignancies. Genomic observations were well concluded for PDAC and PACs in western countries but no reports are available from India till now.

Methods

Targeted Next Generation Sequencing were performed in 8 (5 PDAC and 3 PAC) tumour normal pairs, using a panel of 412 cancer related genes. Primary findings were replicated in 85 tumour samples (31 PDAC and 54 PAC) using the Sanger sequencing. Mutations were also validated by ASPCR, RFLP, and Ion Torrent sequencing. IHC along with molecular dynamics and docking studies were performed for the p.A138V mutant of TP53. Key polymorphisms at TP53 and its associated genes were genotyped by PCR-RFLP method and association with somatic mutations were evaluated. All survival analysis was done using the Kaplan-Meier survival method which revealed that the survival rates varied significantly depending on the somatic mutations the patients harboured.

Results

Among the total 114 detected somatic mutations, TP53 was the most frequently mutated (41%) gene, followed by KRAS, SMAD4, CTNNB1, and ERBB3. We identified a novel hotspot TP53 mutation (p.A138V, in 17% of all patients). Low frequency of KRAS mutation (33%) was detected in these samples compared to patients from Western counties. Molecular Dynamics (MD) simulation and DNA-protein docking analysis predicted p.A138V to have oncogenic characteristics. Patients with p.A138V mutation showed poorer overall survival (p = 0.01). So, our finding highlights elevated prevalence of the p53p.A138V somatic mutation in PDAC and pancreatobiliary PAC patients.

Conclusion

Detection of p.A138V somatic variant in TP53 might serve as a prognostic marker to classify patients. It might also have a role in determining treatment regimes. In addition, low frequency of KRAS hotspot mutation mostly in Indian PDAC patient cohort indicates presence of other early drivers in malignant transformation.
Laser capture microdissection coupled mass spectrometry (LCM-MS) for spatially resolved analysis of formalin-fixed and stained human lung tissues
Authors: Herrera Jeremy A. , Mallikarjun Venkatesh , Rosini Silvia , Montero Maria Angeles , Lawless Craig , Warwood Stacey , O’Cualain Ronan , Knight David , Schwartz Martin A. , Swift Joe
Published: June 2020

Background

Haematoxylin and eosin (H&E)—which respectively stain nuclei blue and other cellular and stromal material pink—are routinely used for clinical diagnosis based on the identification of morphological features. A richer characterization can be achieved by laser capture microdissection coupled to mass spectrometry (LCM-MS), giving an unbiased assay of the proteins that make up the tissue. However, the process of fixing and H&E staining of tissues provides challenges with standard sample preparation methods for mass spectrometry, resulting in low protein yield. Here we describe a microproteomics technique to analyse H&E-stained, formalin-fixed paraffin-embedded (FFPE) tissues.

Methods

Herein, we utilize heat extraction, physical disruption, and in column digestion for the analysis of H&E stained FFPE tissues. Micro-dissected morphologically normal human lung alveoli (0.082 mm3) and human lung blood vessels (0.094 mm3) from FFPE-fixed H&E-stained sections from Idiopathic Pulmonary Fibrosis (IPF) specimens (n = 3 IPF specimens) were then subject to a qualitative and then quantitative proteomics approach using BayesENproteomics. In addition, we tested the sensitivity of this method by processing and analysing a range of micro-dissected human lung blood vessel tissue volumes.

Results

This approach yields 1252 uniquely expressed proteins (at a protein identification threshold of 3 unique peptides) with 892 differentially expressed proteins between these regions. In accord with prior knowledge, our methodology approach confirms that human lung blood vessels are enriched with smoothelin, CNN1, ITGA7, MYH11, TAGLN, and PTGIS; whereas morphologically normal human lung alveoli are enriched with cytokeratin-7, -8, -18, -19, 14, and -17. In addition, we identify a total of 137 extracellular matrix (ECM) proteins and immunohistologically validate that laminin subunit beta-1 localizes to morphologically normal human lung alveoli and tenascin localizes to human lung blood vessels. Lastly, we show that this micro-proteomics technique can be applied to tissue volumes as low as 0.0125 mm3.

Conclusion

Herein we show that our multistep sample preparation methodology of LCM-MS can identify distinct, characteristic proteomic compositions of anatomical features within complex fixed and stained tissues.
The clinical application of microincision vein harvesting of the great saphenous vein in coronary artery bypass grafting
Authors: Zhang Shao-Zhong , Wang Guo-Xiang , Zhou Xiao-Tong
Published: June 2020

Background

The present study aimed to summarize the clinical application of microincision vein harvesting (MVH) of the great saphenous vein in coronary artery bypass grafting (CABG).

Methods

From July 2014 to October 2017, 160 patients underwent coronary artery bypass grafting. Among them, 80 patients received MVH of the great saphenous vein, and 80 received open venous harvesting (OVH). The results of the sampling operation, complications during hospitalization, and the long-term patency of the great saphenous vein were compared between the two groups.

Results

All the patients in both groups received successful operations. The difference in the length of the veins obtained and the injury of the veins was not statistically significant (P > 0.05). The difference in the long-term patency rate of the graft vessels between the two groups was not statistically significant. The in-hospital mortality rate was the same in both groups. The MVH group had noticeable advantages over the OVH group in terms of the vein collection times, the incision length, and the complications experienced when performing the leg incisions (P < 0.01). The time relating to the patients’ observed early out-of-bed activity was significantly longer in the MVH group. Furthermore, the patients’ hospitalization length was significantly shorter in the MVH group compared to the OVH group (P < 0.05). The MVH group had significant advantages in pain score and patient satisfaction, and this difference was also statistically significant (P < 0.05).

Conclusions

The MVH procedure met the requirements of CABG in vein grafting. When compared with OVH, MVH can significantly reduce leg incision complications and improve patients’ overall satisfaction with their hospital experience.
Isolation of Coxiella burnetii in patients with nonspecific febrile illness in South Korea
Authors: Lee Seung Hun , Lee Jae Hoon , Park Sungdo , Lee Hae Kyung , Do Hwang Seon , Jeong Hye Won , Heo Jung Yeon , Lee Yeong Seon
Published: June 2020

Background

The number of human Q fever cases in South Korea has been rapidly increasing since 2015. We report the first isolation of Coxiella burnetii in Korea in two patients who initially presented with non-specific febrile illness and were finally diagnosed with acute Q fever in South Korea.

Case presentation

Two adult patients with fever had serologic tests against C. burnetii initially negative, and polymerase chain reaction against 16S rRNA using whole blood was also negative. After bacterial amplification of C. burnetii in immune-depressed mice, we isolated C. burnetii from patients with acute Q fever. The isolates KZQ2 and KZQ3 were confirmed by polymerase chain reaction, nucleotide sequence analysis, and morphologic observation using a transmission electron microscope.

Conclusions

These results can help us understand the clinical and epidemiologic features of Q fever in South Korea.
Factors associated with occurrence of salmonellosis among children living in Mukuru slum, an urban informal settlement in Kenya
Authors: Mbae Cecilia , Mwangi Moses , Gitau Naomi , Irungu Tabitha , Muendo Fidelis , Wakio Zilla , Wambui Ruth , Kavai Susan , Onsare Robert , Wairimu Celestine , Ngetich Ronald , Njeru Frida , Van Puyvelde Sandra , Clemens John , Dougan Gordon , Kariuki Samuel
Published: June 2020

Background

In Kenya, typhoid fever and invasive non-typhoidal salmonellosis present a huge burden of disease, especially in poor-resource settings where clean water supply and sanitation conditions are inadequate. The epidemiology of both diseases is poorly understood in terms of severity and risk factors. The aim of the study was to determine the disease burden and spatial distribution of salmonellosis, as well as socioeconomic and environmental risk factors for these infections, in a large informal settlement near the city of Nairobi, from 2013 to 2017.

Methods

Initially, a house-to-house baseline census of 150,000 population in Mukuru informal settlement was carried out and relevant socioeconomic, demographic, and healthcare utilization information was collected using structured questionnaires. Salmonella bacteria were cultured from the blood and faeces of children < 16 years of age who reported at three outpatient facilities with fever alone or fever and diarrhea. Tests of association between specific Salmonella serotypes and risk factors were conducted using Pearson Chi-Square (χ2) test.

Results

A total of 16,236 children were recruited into the study. The prevalence of bloodstream infections by Non-Typhoidal Salmonella (NTS), consisting of Salmonella Typhimurium/ Enteriditis, was 1.3%; Salmonella Typhi was 1.4%, and this was highest among children < 16 years of age. Occurrence of Salmonella Typhimurium/ Enteriditis was not significantly associated with rearing any domestic animals. Rearing chicken was significantly associated with high prevalence of S. Typhi (2.1%; p = 0.011). The proportion of children infected with Salmonella Typhimurium/ Enteriditis was significantly higher in households that used water pots as water storage containers compared to using water directly from the tap (0.6%). Use of pit latrines and open defecation were significant risk factors for S. Typhi infection (1.6%; p = 0.048). The proportion of Salmonella Typhimurium/ Enteriditis among children eating street food 4 or more times per week was higher compared to 1 to 2 times/week on average (1.1%; p = 0.032).

Conclusion

Typhoidal and NTS are important causes of illness in children in Mukuru informal settlement, especially among children less than 16 years of age. Improving Water, Sanitation and Hygiene (WASH) including boiling water, breastfeeding, hand washing practices, and avoiding animal contact in domestic settings could contribute to reducing the risk of transmission of Salmonella disease from contaminated environments.
Malaria patterns across altitudinal zones of Mount Elgon following intensified control and prevention programs in Uganda
Authors: Siya Aggrey , Kalule Bosco John , Ssentongo Benard , Lukwa Akim Tafadzwa , Egeru Anthony
Published: June 2020

Background

Malaria remains a major tropical vector-borne disease of immense public health concern owing to its debilitating effects in sub-Saharan Africa. Over the past 30 years, the high altitude areas in Eastern Africa have been reported to experience increased cases of malaria. Governments including that of the Republic of Uganda have responded through intensifying programs that can potentially minimize malaria transmission while reducing associated fatalities. However, malaria patterns following these intensified control and prevention interventions in the changing climate remains widely unexplored in East African highland regions. This study thus analyzed malaria patterns across altitudinal zones of Mount Elgon, Uganda.

Methods

Times-series data on malaria cases (2011–2017) from five level III local health centers occurring across three altitudinal zones; low, mid and high altitude was utilized. Inverse Distance Weighted (IDW) interpolation regression and Mann Kendall trend test were used to analyze malaria patterns. Vegetation attributes from the three altitudinal zones were analyzed using Normalized Difference Vegetation Index (NDVI) was used to determine the Autoregressive Integrated Moving Average (ARIMA) model was used to project malaria patterns for a 7 year period.

Results

Malaria across the three zones declined over the study period. The hotspots for malaria were highly variable over time in all the three zones. Rainfall played a significant role in influencing malaria burdens across the three zones. Vegetation had a significant influence on malaria in the higher altitudes. Meanwhile, in the lower altitude, human population had a significant positive correlation with malaria cases.

Conclusions

Despite observed decline in malaria cases across the three altitudinal zones, the high altitude zone became a malaria hotspot as cases variably occurred in the zone. Rainfall played the biggest role in malaria trends. Human population appeared to influence malaria incidences in the low altitude areas partly due to population concentration in this zone. Malaria control interventions ought to be strengthened and strategically designed to achieve no malaria cases across all the altitudinal zones. Integration of climate information within malaria interventions can also strengthen eradication strategies of malaria in such differentiated altitudinal zones.
Prospective evaluation of contrast-enhanced ultrasound of breast BI-RADS 3–5 lesions
Authors: Janu Eva , Krikavova Lucie , Little Jirina , Dvorak Karel , Brancikova Dagmar , Jandakova Eva , Pavlik Tomas , Kovalcikova Petra , Kazda Tomas , Valek Vlastimil
Published: June 2020

Background

To determine the benefit of contrast-enhanced ultrasound (CEUS) in the assessment of breast lesions.

Methods

A standardized contrast-enhanced ultrasound was performed in 230 breast lesions classified as BI-RADS category 3 to 5. All lesions were subjected to qualitative and quantitative analysis. MVI (MicroVascular Imaging) technique was used to derive qualitative analysis parameters; blood perfusion of the lesions was assessed (perfusion homogeneity, type of vascularization, enhancement degree). Quantitative analysis was conducted to estimate perfusion changes in the lesions within drawn regions of interest (ROI); parameters TTP (time to peak), PI (peak intensity), WIS (wash in slope), AUC (area under curve) were obtained from time intensity (TI) curves. Acquired data were statistically analyzed to assess the ability of each parameter to differentiate between malignant and benign lesions. The combination of parameters was also evaluated for the possibility of increasing the overall diagnostic accuracy. Biological nature of the lesions was verified by a pathologist. Benign lesions without histopathological verification (BI-RADS 3) were followed up for at least 24 months.

Results

Out of 230 lesions, 146 (64%) were benign, 67 (29%) were malignant, 17 (7%) lesions were eliminated. Malignant tumors showed statistically significantly lower TTP parameters (sensitivity 77.6%, specificity 52.7%) and higher WIS values (sensitivity 74.6%, specificity 66.4%) than benign tumors. Enhancement degree also proved to be statistically well discriminating as 55.2% of malignant lesions had a rich vascularity (sensitivity 89.6% and specificity 48.6%). The combination of quantitative analysis parameters (TTP, WIS) with enhancement degree did not result in higher accuracy in distinguishing between malignant and benign breast lesions.

Conclusions

We have demonstrated that contrast-enhanced breast ultrasound has the potential to distinguish between malignant and benign lesions. In particular, this method could help to differentiate lesions BI-RADS category 3 and 4 and thus reduce the number of core-cut biopsies performed in benign lesions. Qualitative analysis, despite its subjective element, appeared to be more beneficial. A combination of quantitative and qualitative analysis did not increase the predictive capability of CEUS.
Clinical characteristics and prenatal diagnosis for 22 families in Henan Province of China with X-linked agammaglobulinemia (XLA) related to Bruton’s tyrosine kinase (BTK) gene mutations
Authors: Gao Shanshan , Hu Shuang , Duan Huikun , Wang Li , Kong Xiangdong
Published: June 2020

Background

X-linked agammaglobulinaemia (XLA) is a rare immunodeficiency disease for which recurrent severe infection is the major clinical symptom. BTK is the main causative gene, with X chromosome recessive inheritance. However, the mutations reported to date do not fully explain the disorder.

Methods

We detected the percentage of CD19+ B cells and serum immunoglobulin (IgG, IgA, and IgM) levels by flow cytometry and rate scatter immunoturbidimetry, and investigated the BTK mutation profile in 22 XLA patients using Sanger sequencing and real-time PCR .

Results

We evaluated the clinical symptoms of 22 XLA patients and investigated genetic mutations present, identifying six novel mutations in the BTK gene: 2 missense mutations (c.23G > T and c.112 T > C), 2 frameshift mutations (c.522_523insC and c.1060delA), 1 large deletion (deletion of exon 2 to 5), and 1 splice-site mutation (c.1631 + 2 T > C). Prenatal diagnoses were performed in six families (F10, F11, F15, F18, F20 and F21), with the following results: the male fetus in Family 10 (F10) did not carry the c.922_923delGA mutation; the male fetus in Family 15 (F15) did not carry the c.1631 + 1G > T splicing mutation; the female fetus in Family 20 (F20) did not carry the c.1931 T > C mutation; the female fetus in Family 21 (F21) did not carry the large deletion mutation. Hence, these four fetuses are not likely to develop XLA. Male fetuses with c.1060delA and c.1684C > T mutations were identified in Family 11 and Family 18, respectively. The pregnant woman in F18 chose to terminate the pregnancy, whereas the pregnant woman in F11 chose to continue the pregnancy.

Conclusion

We confirmed the diagnosis of 22 XLA patients from 22 unrelated families and detected six new pathogenic mutations. Prenatal diagnosis was performed in six families. Early genetic diagnosis and routine lifelong immunoglobulin replacement therapy can prevent and treat infections in XLA children, saving their lives.
Neutrophil-lymphocyte ratio associated with poor prognosis in oral cancer: a retrospective study
Authors: Hasegawa Takumi , Iga Tomoya , Takeda Daisuke , Amano Rika , Saito Izumi , Kakei Yasumasa , Kusumoto Junya , Kimoto Akira , Sakakibara Akiko , Akashi Masaya
Published: June 2020

Background

Prognostic biomarkers provide essential information about a patient’s overall outcome. However, existing biomarkers are limited in terms of either sample collection, such as requiring tissue specimens, or the process, such as prolonged time for analysis. In view of the need for convenient and non-invasive prognostic biomarkers for oral cancer, we aimed to investigate the prognostic values of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patient survival. We also aimed to explore the associations of these ratios with the clinicopathologic characteristics of Japanese oral squamous cell carcinoma patients.

Methods

This study was a non-randomized retrospective cohort study in a tertiary referral center. We included 433 patients (246 men, 187 women) who underwent radical surgery for oral cancers between January 2001 and December 2013. We evaluated various risk factors for poor prognosis including neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio with univariate and multivariate analyses. The disease-specific survival and overall survival rates of patients were compared among the factors and biomarkers.

Results

In multivariable Cox proportional hazards analysis, high neutrophil-to-lymphocyte ratio (hazard ratio 2.87, 95% confidence interval 1.59–5.19, P <  0.001), moderately or poorly differentiated histology (hazard ratio 2.37, 95% confidence interval 1.32–4.25, P <  0.001), and extranodal extension (hazard ratio 1.95, 95% confidence interval 1.13–3.35, P = 0.016) were independent predictors of disease-specific survival. High neutrophil-to-lymphocyte ratio (hazard ratio 2.30, 95% confidence interval 1.42–3.72, P <  0.001), moderately or poorly differentiated (hazard ratio 1.72, 95% confidence interval 1.07–2.76, P = 0.025), and extranodal extension (hazard ratio 1.79, 95% confidence interval 1.13–2.84, P = 0.013) were independent predictors of overall survival.

Conclusions

Neutrophil-to-lymphocyte ratio might be a potential independent prognostic factor in Japanese oral squamous cell carcinoma patients.
Evaluation of enhanced external counterpulsation therapy for nonarteritic anterior ischemic optic neuropathy
Authors: Lin Lixia , Zhu Wenhui , Ma Nan , Lin Xiaofeng , Yang Hui
Published: June 2020

Background

To explore the effects of enhanced external counterpulsation (EECP) and its underlying influencing factors in nonarteritic anterior ischemic optic neuropathy (NAION) patients.

Methods

Patients at Zhongshan Ophthalmic Center with recent-onset (< 8 weeks) NAION were retrospectively recruited. The patients had decided whether or not they would undergo EECP treatment, and the patients who declined were included in the control group. The effectiveness of EECP was evaluated by comparing the visual function and fellow eye involvement in patients with and without EECP treatment.

Results

In total, 61 patients (76 eyes) were included. Twenty-nine patients (37 eyes) underwent EECP treatment, while 32 patients (39 eyes) were included in the control group. Mean time from NAION onset to EECP initiation was 27.59 ± 16.70 days. In the EECP group, the mean EECP duration was 31.57 ± 18.45 days. EECP was well tolerated by all patients. However, there was no significant difference in visual function between the EECP and control groups. Furthermore, there was no evidence of the effectiveness of EECP in the subgroup analysis of patients with different systemic health conditions. Among the 42 patients with monocular NAION, the sequential attack rate was comparable between the EECP (27.78%) and control (25.00%) groups.

Conclusion

This study is the first nonrandomized controlled study to evaluate the effectiveness of EECP in NAION patients. Unfortunately, we failed to demonstrate the effectiveness of EECP in NAION at the 6-month follow-up. Any further application of EECP in NAION patients should be cautious.
Evaluation of Hydra HALT-1 as a toxin moiety for recombinant immunotoxin
Authors: Jiemy William F. , Hiew Lih Fhung , Sha Hong Xi , In Lionel L. A. , Hwang Jung Shan
Published: June 2020

Background

Immunotoxin is a hybrid protein consisting of a toxin moiety that is linked to a targeting moiety for the purpose of specific elimination of target cells. Toxins used in traditional immunotoxins are practically difficult to be produced in large amount, have poor tissue penetration and a complex internalization process. We hypothesized that the smaller HALT-1, a cytolysin derived from Hydra magnipapillata, can be used as the toxin moiety in construction of a recombinant immunotoxin.

Results

In this study, pro-inflammatory macrophage was selected as the target cell due to its major roles in numerous inflammatory and autoimmune disorders. We aimed to construct macrophage-targeted recombinant immunotoxins by combining HALT-1 with anti-CD64-scFv in two orientations, and to assess whether their cytotoxic activity and binding capability could be preserved upon molecular fusion. The recombinant immunotoxins, HALT-1-scFv and scFv-HALT-1, were successfully constructed and expressed in Escherichia coli (E. coli). Our data showed that HALT-1 still exhibited significant cytotoxicity against CD64+ and CD64− cell lines upon fusion with anti-CD64 scFv, although it had half cytotoxic activity as compared to HALT-1 alone. As positioning HALT-1 at N- or C-terminus did not affect its potency, the two constructs demonstrated comparable cytotoxic activities with IC50 lower in CD64+ cell line than in CD64− cell line. In contrast, the location of targeting moieties anti-CD64 scFv at C-terminal end was crucial in maintaining the scFv binding capability.

Conclusions

HALT-1 could be fused with anti-CD64-scFv via a fsexible polypeptide linker. Upon the successful production of this recombinant HALT-1 scFv fusion protein, HALT-1 was proven effective for killing two human cell lines. Hence, this preliminary study strongly suggested that HALT-1 holds potential as the toxin moiety in therapeutic cell targeting.
Psychometric properties of a Chinese version of the Fraboni scale of ageism: evidence from medical students sample
Authors: Fan Jun-Yao , Zhao Hui-Min , Liu Yue-Ting , Kong Ling-Lin , Mao Jing , Li Jie
Published: June 2020

Background

The increasing of older adults has led to enormous demand for medical care. However, as a group with unique needs and characteristics, older adults are often discriminated against in the medical field. In this paper, we aimed to translate the Fraboni Scale of Ageism (FSA) into Chinese and examine its construct validity, content validity, and reliability in Chinese mainland medical students. In order to evaluate the prevalence of ageism in Chinese medical students and prompt medical college to adopt necessary teaching methods to mitigate ageism in medical students.

Methods

By Brislin’s translation guidelines, FSA was translated to Chinese. The convenient sampling method was used to select samples for this survey, including 1,974 students from two medical schools in central and north China. Construct validity was verified by the exploratory and confirmatory factor analysis. The content validity index (CVI) was used to assess content validity. The Cronbach’s alpha coefficients and intraclass correlation coefficient (ICC) were used to estimate reliability.

Results

The alpha coefficients for FSA (Chinese version) was 0.81 and ICC was 0.87. The CVI was 0.93. Three factors were identified by exploratory factor analysis explaining 34.84% of the total variance and a three-factor model was confirmed to fit by confirmatory factor analysis.

Conclusions

FSA (Chinese version) is a reliable and valid scale for measuring discrimination degree against older adults in Chinese medical students.
Waiting times in emergency departments: a resource allocation or an efficiency issue?
Authors: Vainieri Milena , Panero Cinzia , Coletta Lucrezia
Published: June 2020

Background

In recent years, the flow of patients to the Emergency Departments (ED) of Western countries has steadily increased, thus generating overcrowding and extended waiting times. Scholars have identified four main causes for this phenomenon, related to: continuity of primary care services; availability of specific clinical pathways for chronic patients; ED’s personnel endowment; organization of the ED. This study aims at providing a logical diagnostic framework to support managers in investigating specific solutions to be applied to their EDs to cope with high ED waiting times. The framework is based on the ED waiting times and ED admission rate matrix. It was applied to the Tuscan EDs as illustrative example.

Methods

To provide the factors to be analyzed once the EDs are positioned into the matrix, a list of issues has been identified. The matrix was applied to Tuscan EDs. Data were collected from the Tuscan performance evaluation system, integrated with specific data on Tuscan EDs’ personnel. The Tuscan EDs matrix, the descriptive statistics for each quadrant and the Spearman’s rank correlation analysis among waiting times, admission rates and a set of performance indicators were conducted to help managers to read the phenomena that they need to investigate.

Results

The combined reading of the correlations and waiting times-admission rates matrix shows that there are no optimal rules for all the EDs in managing admission rates and waiting times, but solutions have to be found considering mixed and personalized strategies.

Conclusions

The waiting times-admission rates matrix provides a tool able to support managers in detecting the problems related to the management of ED services. In particular, using this matrix, healthcare managers could be facilitated in the identification of possible solutions for their specific situation.
Of tuberculosis and non-tuberculous mycobacterial infections – a comparative analysis of epidemiology, diagnosis and treatment
Authors: Gopalaswamy Radha , Shanmugam Sivakumar , Mondal Rajesh , Subbian Selvakumar
Published: June 2020

Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), recent epidemiological studies have shown the emergence of non-tuberculous mycobacteria (NTM) species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only a handful, primarily Mycobacterium avium complex and M. abscessus, have been implicated in pulmonary disease. While TB is transmitted through inhalation of aerosol droplets containing Mtb, generated by patients with symptomatic disease, NTM disease is mostly disseminated through aerosols originated from the environment. However, following inhalation, both Mtb and NTM are phagocytosed by alveolar macrophages in the lungs. Subsequently, various immune cells are recruited from the circulation to the site of infection, which leads to granuloma formation. Although the pathophysiology of TB and NTM diseases share several fundamental cellular and molecular events, the host-susceptibility to Mtb and NTM infections are different. Striking differences also exist in the disease presentation between TB and NTM cases. While NTM disease is primarily associated with bronchiectasis, this condition is rarely a predisposing factor for TB. Similarly, in Human Immunodeficiency Virus (HIV)-infected individuals, NTM disease presents as disseminated, extrapulmonary form rather than as a miliary, pulmonary disease, which is seen in Mtb infection. The diagnostic modalities for TB, including molecular diagnosis and drug-susceptibility testing (DST), are more advanced and possess a higher rate of sensitivity and specificity, compared to the tools available for NTM infections. In general, drug-sensitive TB is effectively treated with a standard multi-drug regimen containing well-defined first- and second-line antibiotics. However, the treatment of drug-resistant TB requires the additional, newer class of antibiotics in combination with or without the first and second-line drugs. In contrast, the NTM species display significant heterogeneity in their susceptibility to standard anti-TB drugs. Thus, the treatment for NTM diseases usually involves the use of macrolides and injectable aminoglycosides. Although well-established international guidelines are available, treatment of NTM disease is mostly empirical and not entirely successful. In general, the treatment duration is much longer for NTM diseases, compared to TB, and resection surgery of affected organ(s) is part of treatment for patients with NTM diseases that do not respond to the antibiotics treatment. Here, we discuss the epidemiology, diagnosis, and treatment modalities available for TB and NTM diseases of humans.
Segmentation of small ground glass opacity pulmonary nodules based on Markov random field energy and Bayesian probability difference
Authors: Zhang Shaorong , Chen Xiangmeng , Zhu Zhibin , Feng Bao , Chen Yehang , Long Wansheng
Published: June 2020

Background

Image segmentation is an important part of computer-aided diagnosis (CAD), the segmentation of small ground glass opacity (GGO) pulmonary nodules is beneficial for the early detection of lung cancer. For the segmentation of small GGO pulmonary nodules, an integrated active contour model based on Markov random field energy and Bayesian probability difference (IACM_MRFEBPD) is proposed in this paper.

Methods

First, the Markov random field (MRF) is constructed on the computed tomography (CT) images, then the MRF energy is calculated. The MRF energy is used to construct the region term. It can not only enhance the contrast between pulmonary nodule and the background region, but also solve the problem of intensity inhomogeneity using local spatial correlation information between neighboring pixels in the image. Second, the Gaussian mixture model is used to establish the probability model of the image, and the model parameters are estimated by the expectation maximization (EM) algorithm. So the Bayesian posterior probability difference of each pixel can be calculated. The probability difference is used to construct the boundary detection term, which is 0 at the boundary. Therefore, the blurred boundary problem can be solved. Finally, under the framework of the level set, the integrated active contour model is constructed.

Results

To verify the effectiveness of the proposed method, the public data of the lung image database consortium and image database resource initiative (LIDC-IDRI) and the clinical data of the Affiliated Jiangmen Hospital of Sun Yat-sen University are used to perform experiments, and the intersection over union (IOU) score is used to evaluate the segmentation methods. Compared with other methods, the proposed method achieves the best results with the highest average IOU of 0.7444, 0.7503, and 0.7450 for LIDC-IDRI test set, clinical test set, and all test sets, respectively.

Conclusions

The experiment results show that the proposed method can segment various small GGO pulmonary nodules more accurately and robustly, which is helpful for the accurate evaluation of medical imaging.
Image guided sacroiliac joint corticosteroid injections in children: an 18-year single-center retrospective study
Authors: Chamlati Racha , Connolly Bairbre , Laxer Ronald , Stimec Jennifer , Panwar Jyoti , Tse Shirley , Muthusami Prakash , Amaral Joao , Temple Michael , Parra Dimitri A.
Published: June 2020

Background

Sacroiliitis is commonly seen in enthesitis-related arthritis (ERA), a subtype of juvenile idiopathic arthritis (JIA). Sacroiliitis is characterized by the inflammation of the sacroiliac (SI) joints (+/− adjacent tissues). The treatment options include systemic therapy with or without corticosteroid SI joint injections. Image guided SI joint injections are frequently requested in pediatric patients with sacroiliitis.

The purpose of this study was to evaluate the feasibility and efficacy of SI joint injections in children with sacroiliitis.

Methods

A retrospective study of patients referred to Interventional Radiology (IR) for SI joint corticosteroid injections (2000–2018). Clinical information was collected from Electronic Patient Charts and procedural details from PACS. Efficacy was determined clinically, by MRI, or both when available.

Results

50 patients (13.8 years; M:F = 35:15) underwent image-guided SI joint corticosteroid injections. Most common indications were JIA (84%) and inflammatory bowel disease (14%). 80% had bilateral injections. 80% were performed under general anesthesia and 20% under sedation. The corticosteroid of choice was triamcinolone hexacetonide in 98% of patients. Needle guidance and confirmation was performed using CT and fluoroscopy (54%), Cone Beam CT (CBCT, 46%), with initial ultrasound assistance in 34%. All procedures were technically successful without any complications. 32/50 patients had long-term follow-up (2 years); 21/32 (66%) had clinical improvement within 3-months. Of 15 patients who had both pre- and post-procedure MRIs, 93% showed short-term improvement. At 2 years, 6% of patients were in remission, 44% continued the same treatment and 47% escalated treatment.

Conclusion

Image-guided SI joint injections are safe and technically feasible in children. Imaging modalities for guidance have evolved, with CBCT being the current first choice. Most patients showed short-term clinical and imaging improvement, requiring long-term maintenance or escalation of medical treatment.
Association between DRD2 and ANKK1 polymorphisms with the deficit syndrome in schizophrenia
Authors: Michalczyk Anna , Pełka-Wysiecka Justyna , Kucharska-Mazur Jolanta , Wroński Michał , Misiak Błażej , Samochowiec Jerzy
Published: June 2020

Background

The clinical course of schizophrenia varies among patients and is difficult to predict. Some patient populations present persistent negative symptoms, referred to as the deficit syndrome. Compared to relatives of non-deficit schizophrenia patients, family members of this patient population are at an increased risk of developing schizophrenia. Therefore, the aim of this study was to search for genetic underpinnings of the deficit syndrome in schizophrenia.

Methods

Three SNPs, i.e., rs1799732 and rs6276 located within DRD2, and rs1800497 within ANKK1, were identified in the DNA samples of 198 schizophrenia probands, including 103 patients with deficit (DS) and 95 patients with non-deficit schizophrenia (NDS). Results: No significant differences concerning any of the analyzed polymorphisms were found between DS and NDS patients. However, significant links were observed between family history of schizophrenia and the deficit syndrome, G/G genotype and rs6276 G allele. In a separate analysis, we identified significant differences in frequencies of rs6276 G allele between DS and NDS patients with family history of schizophrenia. No significant associations were found between DRD2 and ANKK1 SNPs and the age of onset or schizophrenia symptom severity.

Conclusions

The results of our preliminary study fail to provide evidence of associations between DRD2 and ANKK1 polymorphisms with the deficit syndrome or schizophrenia symptom severity, but suggest potential links between rs6276 in DRD2 and the deficit syndrome in patients with hereditary susceptibility to schizophrenia. However, further studies are necessary to confirm this observation.
Substance use disorders in Saudi Arabia: a scoping review
Authors: Saquib Nazmus , Rajab Ahmad Mamoun , Saquib Juliann , AlMazrou AbdulRahman
Published: June 2020

Background

Substance use disorders (SUD) are mental health conditions that arise from chronic drug use. There is an increased recognition of this problem in Saudi Arabia.

Objective

Conduct a comprehensive review of published literature on SUD to identify knowledge gaps and to guide future research.

Methods

PubMed, Embase and Cochrane databases were searched with suitable keywords for SUD publications up to June 10, 2019. Eligible studies (primary research conducted in Saudi Arabia) were organized into three broad domains: (1) risk (or protective) factors of SUD, (2) perspectives on drug use of people who use drugs, and (3) impact on family. The quality of the included studies was assessed with the Newcastle-Ottawa Scale.

Results

Of the 113 search records, 23 were eligible for analysis (19 cross-sectional and 4 case-control). All studies were conducted in clinical settings; all but two included males only. There were 4 studies about SUD risk factors, 6 studies about the perspectives of people who use drugs, and none about family impact. None of the cross-sectional studies (0%) and 25% of case-control studies were of good quality.

Conclusions

The available studies were few in number, weak in methodology, and poor in quality. Quantitative as well as qualitative studies about SUD are warranted in each domain and should represent both genders.
Surgical ligation of patent ductus arteriosus in preterm neonates weighing less than 1500g: a 9-year single center experience
Authors: Lee Jun Ho , Lee Hyun Ju , Park Hyun-Kyung , Ahn Ja-Hye , Kim Hee Sun , Jang Hyo Jun , Ro Sun Kyun , Kim Hyuck
Published: June 2020

Background

The aim of this study was to determine the feasibility and outcomes of early surgical ligation in preterm neonates with hemodynamically significant patent ductus arteriosus (HSPDA) and to investigate predictors for surgical treatment after unsuccessful medical management.

Methods

Medical records from the neonatal intensive care unit of Hanyang University Seoul Hospital from January 2010 to December 2018 were retrospectively reviewed. 233 preterm neonates weighing less than 1500g with HSPDA were enrolled in our study. Of these preterm neonates, 134 underwent surgical ligation and were subdivided into the early ligation group (n = 49; within 10 days of age) and the late ligation group (n = 85; after 10 days of age).

Results

The mean gestational age and birth weight were significantly lower in the patent ductus arteriosus (PDA) ligation group than in the Non-ligation group (p <  0.001). PDA ductal diameter > 2.0 mm (p <  0.001), low Apgar score at 5 min (p = 0.033), and chorioamnionitis (p = 0.037) were the predictors for receiving surgical treatment for PDA. Early ligation was significantly associated with a low incidence of culture-proven sepsis (p = 0.004), mechanical ventilator time > 4 weeks (p = 0.007), necrotizing enterocolitis stage (NEC) ≥ III (p = 0.022), and intraventricular hemorrhage (IVH) grade ≥ III (p = 0.035).

Conclusions

Early surgical ligation minimizes the adverse effects of HSPDA in predicted preterm neonates who subsequently require surgical treatment for PDA. This result suggests that in preterm neonates weighing less than 1500g with HSPDA that is unresponsive to medical treatment, delayed ductal closure should be avoided to reduce severe NEC, severe IVH, culture-proven sepsis, and facilitate earlier endotracheal extubation.
Experimental Investigation on the Force-Crack Quantification Model for HSRC Columns with Flexure–Shear and Shear Failure Modes
Authors: Chiu Cien-Kuo , Tandri Alexander Ivan
Published: June 2020

A total of six full-scale high strength reinforced concrete (HSRC) columns were tested under axial and cyclic lateral loading. The specified concrete compressive strength was 70 MPa and the specified yield strength was 685 MPa and 785 MPa for the longitudinal and transverse reinforcements, respectively. The main variables considered in the study are the transverse reinforcements ratio and axial load ratio. Although such HSRC columns have gradually transformed in use and scope, the damage assessment method is less understood. The main purpose of this study is to propose a damage assessment model for HSRC columns. An analytical backbone curve model for predicting force–deformation behavior of HSRC columns is described. Column stiffness is also measured from the experiment to obtain stiffness reduction factors that are necessary to calculate member deformation. Based on experiment results, a new limiting value of residual crack width is defined to determine damage level. This study uses specified residual crack width of 0.15 mm, 0.30 mm, and 1.00 mm in the damage assessment model. The new limiting value of residual crack width is also used to determine the performance points of structural members. Finally, a new drift ratio limit of each damage level is also proposed. Experiment results are presented and used to investigate the application of the proposed damage assessment model.
Analysing the quality of Swiss National Forest Inventory measurements of woody species richness
Authors: Traub Berthold , Wüest Rafael O.
Published: June 2020

Background

Under ongoing climate and land-use change, biodiversity is continuously decreasing and monitoring biodiversity is becoming increasingly important. National Forest Inventory (NFI) programmes provide valuable time-series data on biodiversity and thus contribute to assessments of the state and trends in biodiversity, as well as ecosystem functioning. Data quality in this context is of paramount relevance, particularly for ensuring a meaningful interpretation of changes. The Swiss NFI revisits about 8%–10% of its sample plots regularly in repeat surveys to supervise the quality of fieldwork.

Methods

We analysed the relevance of observer bias with equivalence tests, examined data quality objectives defined by the Swiss NFI instructors, and calculated the pseudo-turnover (PT) of species composition, that is, the percentage of species not observed by both teams. Three attributes of woody species richness from the latest Swiss NFI cycles (3 and 4) were analysed: occurrence of small tree and shrub species (1) on the sample plot and (2) at the forest edge, and (3) main shrub and trees species in the upper storey.

Results

We found equivalent results between regular and repeat surveys for all attributes. Data quality, however, was significantly below expectations in all cases, that is, as much as 20%–30% below the expected data quality limit of 70%–80% (proportion of observations that should not deviate from a predefined threshold). PT values were about 10%–20%, and the PT of two out of three attributes decreased significantly in NFI4. This type of uncertainty – typically caused by a mixture of overlooking and misidentifying species – should be considered carefully when interpreting change figures on species richness estimates from NFI data.

Conclusions

Our results provide important information on the data quality achieved in Swiss NFIs in terms of the reproducibility of the collected data. The three applied approaches proved to be effective for evaluating the quality of plot-level species richness and composition data in forest inventories and other biodiversity monitoring programmes. As such, they could also be recommended for assessing the quality of biodiversity indices derived from monitoring data.
Breast Cancer in Jamaica: Trends From 2010 to 2014—Is Mortality Increasing?
Authors: Reid Sonya , Donaldson-Davis Kayon , Willie-Tyndale Douladel , Thompson Camelia , Wharfe Gilian , Gibson Tracey , Eldemire-Shearer Denise , James Kenneth
Published: June 2020

PURPOSE

This study sought to provide a detailed analysis of breast cancer–specific mortality in Jamaica on the basis of reported deaths between 2010 and 2014.

METHODS

A cross-sectional study was done to analyze breast cancer–specific mortality data from the Registrar General’s Department, the statutory body responsible for registering all deaths across Jamaica.

RESULTS

A total of 1,634 breast cancer–related deaths were documented among Jamaican women between 2010 and 2014, which accounted for 24% of all female cancer deaths. The age-standardized breast cancer mortality rate increased from 21.8 per 100,000 in 2010 to 28 per 100,000 in 2014 for the total female population. The overall difference in breast cancer mortality rates between the 2014 and 2010 rates was not statistically significant ( P = .114). Analysis of the year-by-year trend reflected by the annual percentage of change did show, however, a statistically significant increasing trend in breast cancer mortality ( P = .028). Mortality rates varied by age, with statistically significant annual increases observed in the 35-44–, 65-74–, and ≥ 75-year age groups ( P = .04, .03, and .01, respectively).

CONCLUSION

Breast cancer remains the leading cause of cancer-related death among Jamaican women. Despite global advances in breast cancer screening and management, breast cancer remains a major public health challenge and represents a public health priority in Jamaica. The increasing breast cancer–specific mortality in Jamaica over the 5-year period contrasts with decreasing mortality rates among US women with breast cancer. This study highlights the critical need to address the implementation of a national organized breast cancer screening program in Jamaica and to focus future research efforts on the biology of breast cancer, especially among young Jamaican women.