bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness of monitoring circulating tumor cells as a therapeutic biomarker in melanoma with BRAF mutation
Authors: Kiniwa Yukiko , Nakamura Kenta , Mikoshiba Asuka , Ashida Atsuko , Akiyama Yasuyuki , Morimoto Atsushi , Okuyama Ryuhei
Published: March 2021

Background

While molecularly targeted therapies and immune checkpoint inhibitors have improved the prognosis of advanced melanoma, biomarkers are required to monitor drug responses. Circulating tumor cells (CTCs) are released from primary and/or metastatic tumors into the peripheral blood. We examined whether CTCs have potential as biomarkers by checking the number of CTCs, as well as the BRAF genotype of individual CTCs, in melanoma patients undergoing BRAF/MEK inhibitor treatment.

Methods

CTCs were isolated from peripheral blood using a high-density dielectrophoretic microwell array, followed by labeling with melanoma-specific markers (MART-1 and/or gp100) and a leukocyte marker (CD45). The numbers of CTCs were analyzed in fifteen patients with stage 0–III melanoma. Furthermore, changes in CTC numbers were assessed in five patients with stage IV melanoma at four time points during BRAF/MEK inhibitor treatment, and the BRAF genotype was analyzed in CTCs isolated from one patient.

Results

We examined CTCs in patients with stage 0–III (five samples per stage: stage 0–I, stage II, and stage III), and detected CTCs even in patients with early disease (stage 0 and I). Interestingly, recurrence occurred in the lymph nodes of one stage I patient 2 years after the detection of a high number of CTCs in the patient’s blood. The total number of CTCs in four of five patients with stage IV melanoma fluctuated in response to BRAF/MEK inhibitor treatment, suggesting that CTC number has potential for use as a drug response marker in advanced disease patients. Interestingly, one of those patients had CTCs harboring seven different BRAF genotypes, and the mutated CTCs disappeared upon BRAF/MEK inhibitor treatment, except for those harboring BRAFA598V.

Conclusions

CTCs are present even in the early stage of melanoma, and the number of CTCs seems to reflect patients’ responses to BRAF/MEK inhibitor treatment. Furthermore, genetic heterogeneity of BRAF may contribute to resistance to BRAF/MEK inhibitors. Our findings demonstrate the usefulness of CTC analysis for monitoring responses to targeted therapies in melanoma patients, and for understanding the mechanism of drug resistance.
A simple method for diagnosing gallbladder malignant tumors with subserosa invasion by endoscopic ultrasonography
Authors: Sugimoto Mitsuru , Irie Hiroki , Takasumi Mika , Hashimoto Minami , Oka Yuka , Takagi Tadayuki , Suzuki Rei , Konno Naoki , Asama Hiroyuki , Sato Yuki , Nakamura Jun , Kato Tsunetaka , Kobashi Ryoichiro , Hashimoto Yuko , Marubashi Shigeru , Hikichi Takuto , Ohira Hiromasa
Published: March 2021

Background

If the depth of gallbladder malignant tumor (GBMT) invasion is deeper than the subserosa (ss), cholecystectomy is insufficient. In past reports that used endoscopic ultrasonography (EUS) to diagnose the depth of tumor invasion, it was difficult to diagnose GMBT invasion in the ss without a narrow or disrupted lateral hyperechoic layer (LHEL). Therefore, we developed a simple preoperative method to diagnose GBMTs with ss invasion.

Methods

Forty-nine GBMT patients who underwent both EUS and surgery were enrolled: 15 patients whose tumors invaded the mucosa (m) or muscularis propria (mp) were classified as the “shallow group”, and 34 patients whose tumors invaded the ss were classified as the “deep group”. The EUS findings were compared between the two groups.

Results

An irregular (narrow or thickened) LHEL was significantly more frequently observed on EUS in the deep group than in the shallow group. The diagnosis of ss invasion based on an irregular LHEL had the highest sensitivity and accuracy among the EUS imaging parameters (sensitivity 97.1% (33/34), specificity 86.7% (13/15), accuracy 93.8% (46/49)). When the deep group was limited to patients with a tumor depth of ss, the results were similar. When an irregular LHEL was used, the diagnostic accuracy of GBMTs with ss invasion was not significantly different between EUS specialists and beginners.

Conclusions

The observation of an irregular (thickened or narrow) LHEL observed on EUS could be a reliable and simple method of diagnosing GBMTs with ss invasion and could contribute to choosing an appropriate surgical method.
Regional variation in cost of neonatal intensive care for extremely preterm infants
Authors: Rolnitsky Asaph , Urbach David , Unger Sharon , Bell Chaim M.
Published: March 2021

Background

Regional variation in cost of neonatal intensive care for extremely preterm infant is not documented. We sought to evaluate regional variation that may lead to benchmarking and cost saving.

Methods

An analysis of a Canadian national costing data from the payor perspective. We included all liveborn 23–28-week preterm infants in 2011–2015. We calculated variation in costs between provinces using non-parametric tests and a generalized linear model to evaluate cost variation after adjustment for gestational age, survival, and length of stay.

Results

We analysed 6932 infant records. The median total cost for all infants was $66,668 (Inter-Quartile Range (IQR): $4920–$125,551). Medians for the regions varied more than two-fold and ranged from $48,144 in Ontario to $122,526 in Saskatchewan. Median cost for infants who survived the first 3 days of life was $91,000 (IQR: $56,500–$188,757). Median daily cost for all infants was $1940 (IQR: $1518–$2619). Regional variation was significant after adjusting for survival more than 3 days, length of stay, gestational age, and year (pseudo-R2 = 0.9,p < 0.01). Applying the model on the second lowest-cost region to the rest of the regions resulted in a total savings of $71,768,361(95%CI: $65,527,634–$81,129,451) over the 5-year period ($14,353,672 annually), or over 11% savings for the total program cost of $643,837,303 over the study period.

Conclusion

Costs of neonatal intensive care are high. There is large regional variation that persists after adjustment for length of stay and survival. Our results can be used for benchmarking and as a target for focused cost optimization, savings, and investment in healthcare.
Maternal toxoplasmosis and the risk of childhood autism: serological and molecular small-scale studies
Authors: Al Malki Jamila S. , Hussien Nahed Ahmed , Al Malki Fuad
Published: March 2021

Background

Toxoplasmosis resulting from infection with the Toxoplasma parasite has become an endemic disease worldwide. Recently, a few studies have reported a high prevalence of Toxoplasmosis infections among Saudi Arabian women. This disease could become life threatening for pregnant women and for immunodeficient people. There is evidence that infections during pregnancy, especially in the early stages, are associated with neurodevelopmental disorders. Autism disorder represents one of the most common neurodevelopmental disorders worldwide; it is associated with delayed language development, weak communication interaction, and repetitive behavior. The relationship between prenatal toxoplasmosis and autism in childhood remains unclear. The present study aims to report a link between maternal toxoplasmosis and autistic offspring among Saudi Arabian women.

Method

Blood samples (36 maternal, 36 from their non-autistic children, and 36 from their autistic children) were collected for serological and molecular evaluation.

Results

A toxoplasmosis infection was reported for 33.34% of participants using an ELISA assay (5.56% IgG+/IgM+, 11.11% IgG−/IgM+, and 16.67% IgG+/IgM-); however, a nested PCR assay targeting B1 toxoplasmosis specific genes recorded positive tests for 80.56% of the samples. In addition, the present study detected several points of mutation of mtDNA including NADH dehydrogenase (ND1, ND4) and Cyt B genes and the nDNA pyruvate kinase (PK) gene for autistic children infected with toxoplasmosis.

Conclusion

Considering previous assumptions, we suggest that a maternal toxoplasmosis infection could have a role in the development of childhood autism linked to mtDNA and nDNA impairment.
Avoidable deaths in Sweden, 1997–2018: temporal trend and the contribution to the gender gap in life expectancy
Authors: Kiadaliri Ali
Published: March 2021

Background

Avoidable mortality is considered as a potential indicator of the influences of public health policies and healthcare quality on population health. This study aimed to examine the trend in avoidable mortality and its influence on rising life expectancy (LE) and declining gender gap in LE (GGLE) in Sweden.

Methods

We extracted data on causes of death by age, sex, and year from national registry from 1997 to 2018. The UK Office for National Statistics definition was used to divide causes of death into five mutually exclusive categories: amenable, preventable, amenable & preventable, ischemic heart disease (IHD), and non-avoidable causes. We applied Joinpoint regression to analyse temporal trends in age-standardized mortality rates. The Arriaga method was applied to decompose changes in LE and GGLE by age group and causes of death.

Results

Average annual reductions in avoidable vs. non-avoidable mortality were 2.6% (95% CI:2.5, 2.7) vs. 1.4% (95% CI:1.3, 1.5) in men, and 1.6% (95% CI:1.4, 1.9) vs. 0.9% (95% CI:0.7, 1.0) in women over the study period. LE in men rose by 4.1 years between 1997 and 2018 (from 72.8 to 76.9 years), of which 2.4 years (59.3%) were attributable to reductions in avoidable mortality. Corresponding LE gain was 2.3 years in women (from 78.0 in 1997 to 80.3 in 2018) and avoidable mortality accounted for 1.0 year (45.6%) of this gain. Between 1997 and 2018, the GGLE narrowed by 1.9 years, of which 1.4 years (77.7%) were attributable to avoidable causes. Among avoidable causes, while preventable causes had the largest contribution to the GGLE, IHD had the greatest contributions to LE gains and the narrowing GGLE.

Conclusions

Our findings showed that avoidable causes had a substantial contribution to gain in LE with more profound gain in men than in women, resulting in narrowing the GGLE. Lower pace of reductions in preventable than amenable mortality highlights the need for improving the effectiveness of inter-sectoral health policies aimed at behavioural changes.
The relationship between socioeconomic position and health literacy among urban and rural adults in regional China
Authors: Chen Wei , Ren Hongfu , Wang Na , Xiong Yaqing , Xu Fei
Published: March 2021

Background

To examine associations of socioeconomic position (SEP), separately indicated by education, monthly family average income (FAI) and occupation, with health literacy (HL) among adults in regional China.

Methods

A cross-sectional survey was conducted among urban and rural adults (aged 25–69 years) who were randomly selected, using the probability proportionate to size sampling approach, from Nanjing municipality of China during October and December of 2016. HL, the outcome variable, was assessed using the Chinese Resident Health Literacy Scale. SEP, our independent variable, was separately measured with educational attainment, monthly family average income and occupation. Logistic regression models were introduced to examine SEP-HL association with odds ratio (OR) and 95% confidence interval (CI).

Results

Totally, 8698 participants completed the survey. The proportion of participants with unweighted and weighted adequate HL was 18.0% (95%CI = 17.2, 18.8%) and 19.9% (95%CI = 16.6, 23.6%), respectively, in this study. After adjustment for possible confounding factors, each SEP indicator was in significantly positive relation to both unweighted and weight HL level. Participants who obtained 13+ and 10–12 years educational attainment, respectively, had 2.41 (95%CI = 1.60, 3.64) and 1.68 (95%CI = 1.23, 2.29) times odds to record weighted adequate HL compared to their counterparts who were with 0–9 years education. Subjects within upper (OR = 1.92, 95%CI = 1.24, 2.98) and middle FAI tertile (OR = 1.59, 95%CI = 1.19, 2.13), respectively, were more likely to report weighted adequate HL relative to those who were within lower FAI tertile. White collars were more likely to have weighted adequate HL (OR = 1.33, 95%CI = 1.09, 1.61) than blue collars.

Conclusions

Each of education, FAI and occupation was positively associated with health literacy among urban and rural adults in China. The findings have important implications that different SEP indicators can be used to identify vulnerable residents in population-based health literacy promotion campaigns.
Non-obstructed supracardiac total anomalous pulmonary venous connection with giant superior vena cava aneurysm
Authors: Yan Yangbo , Yu Kai , Yang Yanlin , Gan Changping
Published: March 2021

Background

Giant superior vena cava (SVC) aneurysm in non-obstructed supracardiac total anomalous pulmonary venous connection (TAPVC) is even more rare than in obstructed one, and this combination has not been reported.

Case presentation

Here we reported a 29-year‐old young lady with non-obstructed TAPVC complicated with a giant SVC aneurysm. Routine TAPVC correction and tricuspid valve repair were done. Additionally, venoctomy was carried out to seek for its histological etiology and to avoid potential complications.

Conclusions

If confirmed by further and larger experiences, for patients with non-obstructed supracardiac TAPVC with giant SVC aneurysm, surgical treatment of SVC aneurysm could be more aggressive to prevent cardiovascular complications.
Examining public knowledge, attitudes and perceptions towards palliative care: a mixed method sequential study
Authors: McIlfatrick Sonja , Slater Paul , Beck Esther , Bamidele Olufikayo , McCloskey Sharon , Carr Karen , Muldrew Deborah , Hanna-Trainor Lisa , Hasson Felicity
Published: March 2021

Background

Palliative care is recognised as a public health issue with the need for earlier integration in the wider healthcare system. However, research indicates that it continues to be accessed late in the course of an illness, public understanding of palliative care is limited, and common misconceptions prevail. Strategies to address this are needed in order to reduce barriers to palliative care delivery and improve access.

Methods

An explanatory sequential mixed methods study, comprising a cross-sectional survey and interviews was undertaken. Sociodemographic characteristics, public awareness, knowledge and perceptions of palliative care were examined and strategies to raise awareness and overcome barriers within a public health framework were identified. Survey data were analysed using SPSS v25 with factor analysis and non-parametric statistics and qualitative data were analysed using thematic analysis.

Results

A total of 1201 participants completed the survey (58.3% female, mean age 61 years) and 25 took part in interviews. A fifth of participants (20.1%) had previously heard about palliative care and had an accurate understanding of the term. Being female, higher educated, married, and older, increased respondents’ levels of awareness. The three most commonly held misconceptions included: Palliative care is exclusively for people who are in the last 6 months of life (55.4% answered incorrectly); A goal of palliative care is to address any psychological issues brought up by serious illness (42.2% answered incorrectly); and a goal of palliative care is to improve a person’s ability to participate in daily activities (39.6% answered incorrectly). Talking about palliative and end of life care was advocated but societal taboos restricted this occurring with exposure limited to personal experience.

Conclusions

Current knowledge gaps and misconceptions derived from limited ad hoc personal experiences and fear of engaging in taboo conversations may deter people from accessing integrated palliative care services early in a disease trajectory. The results indicate the need for public education programmes that move beyond merely raising awareness but provide key messages within a public health approach, which may change attitudes to palliative care thus ultimately improving end of life outcomes.
Protective reactions of ICU nurses providing care for patients with COVID-19: a qualitative study
Authors: Moradi Yaser , Baghaei Rahim , Hosseingholipour keyvan , Mollazadeh Farzin
Published: March 2021

Background

The exponential spread of COVID-19 has caused a huge threat to public health worldwide. Providing care for patients with COVID-19 is a stressful experience for ICU nurses, which can affect their protective reactions. The present study was conducted to explore the protective reactions of ICU nurses providing care for patients with COVID-19.

Methods

This qualitative descriptive study was conducted to discover the protective reactions of nurses providing care for patients with COVID-19. A total of 14 ICU nurses were selected by purposive sampling. Data were collected using individual semi-structured face-to-face interviews. All interviews were recorded, and then codes and themes were extracted using content analysis method.

Finding

Seventeen subcategories, six categories and two themes were extracted from the analysis of data. These themes include “Unbalanced self-protective reactions” and “Responsible self-protective reactions”.

Conclusion

During the COVID-19 epidemic and crisis, ICU nurses exhibit different self-protective reactions when providing care for patients with COVID-19, which include unbalanced and responsible reactions. Nursing managers can mitigate these unbalanced reactions by identifying them and their roots. Identifying the protective reactions of ICU nurses in providing care for patients with COVID-19 could assist in developing the necessary interventions to promote positive reactions and reduce unbalanced reactions by finding their root causes.
Enhanced lung inflammatory response in whole-body compared to nose-only cigarette smoke-exposed mice
Authors: Serré Jef , Tanjeko Ajime Tom , Mathyssen Carolien , Vanherwegen An-Sofie , Heigl Tobias , Janssen Rob , Verbeken Eric , Maes Karen , Vanaudenaerde Bart , Janssens Wim , Gayan-Ramirez Ghislaine
Published: March 2021

Background

Chronic obstructive pulmonary disease (COPD) is characterized by a progressive and abnormal inflammatory response in the lungs, mainly caused by cigarette smoking. Animal models exposed to cigarette smoke (CS) are used to mimic human COPD but the use of different CS protocols makes it difficult to compare the immunological and structural consequences of using a nose-only or whole-body CS exposure system. We hypothesized that when using a standardized CS exposure protocol based on particle density and CO (carbon monoxide) levels, the whole-body CS exposure system would generate a more severe inflammatory response than the nose-only system, due to possible sensitization by uptake of CS-components through the skin or via grooming.

Methods

In this study focusing on early COPD, mice were exposed twice daily 5 days a week to CS either with a nose-only or whole-body exposure system for 14 weeks to assess lung function, remodeling and inflammation.

Results

At sacrifice, serum cotinine levels were significantly higher in the whole-body (5.3 (2.3–6.9) ng/ml) compared to the nose-only ((2.0 (1.8–2.5) ng/ml) exposure system and controls (1.0 (0.9–1.0) ng/ml). Both CS exposure systems induced a similar degree of lung function impairment, while inflammation was more severe in whole body exposure system. Slightly more bronchial epithelial damage, mucus and airspace enlargement were observed with the nose-only exposure system. More lymphocytes were present in the bronchoalveolar lavage (BAL) and lymph nodes of the whole-body exposure system while enhanced IgA and IgG production was found in BAL and to a lesser extent in serum with the nose-only exposure system.

Conclusion

The current standardized CS-exposure protocol resulted in a higher internal load of serum cotinine in the whole-body exposure system, which was associated with more inflammation. However, both exposure systems resulted in a similar lung function impairment. Data also highlighted differences between the two models in terms of lung inflammation and remodelling, and potential sensitization to CS. Researchers should be aware of these differences when designing their future studies for an early intervention in COPD.
Household knowledge, perceptions and practices of mosquito larval source management for malaria prevention and control in Mwanza district, Malawi: a cross‐sectional study
Authors: Kamndaya Mphatso , Mfipa Dumisani , Lungu Kingsley
Published: March 2021

Background

Mosquito larval source management (LSM) is a key outdoor malaria vector control strategy in rural communities in sub-Saharan Africa. Knowledge of this strategy is important for optimal design and implementation of effective malaria control interventions in this region. This study assessed household knowledge, perceptions and practices of mosquito LSM methods (draining stagnant water, larviciding, clearing grass/bushes and clean environment).

Methods

A cross-sectional design was used whereby 479 households were selected using two-stage sampling in Mwanza district, Malawi. A household questionnaire was administered to an adult member of the house. Respondents were asked questions on knowledge, perceptions and practices of mosquito LSM methods. Multivariable logistic regression model was used to identify factors associated with high-level knowledge of mosquito LSM methods.

Results

Majority of the respondents (64.5%) had high-level knowledge of mosquito LSM methods. Specifically, 63.7% (200/314) had positive perceptions about draining stagnant water, whereas 95.3% (223/234) practiced clean environment for malaria control and 5.2% had knowledge about larviciding. Compared to respondents with primary education, those with secondary education were more likely, whereas those without education were less likely, to have high-level knowledge of mosquito LSM methods (AOR = 3.54, 95% CI 1.45–8.63 and AOR = 0.38, 95% CI 0.23–0.64, respectively). Compared to respondents engaged in crop farming, those engaged in mixed farming (including pastoralists) and the self-employed (including business persons) were more likely to have high-level knowledge of mosquito LSM methods (AOR = 6.95, 95% CI 3.39–14.23 and AOR = 3.61, 95% CI 1.47–8.86, respectively). Respondents living in mud-walled households were less likely to have high-knowledge of mosquito LSM methods than those living in brick-walled households (AOR = 0.50, 95% CI 0.30–0.86).

Conclusions

A high-level knowledge of mosquito LSM methods was established. However, when designing and implementing this strategy, specific attention should be paid to the uneducated, crop farmers and those living in poor households.
ZnO nanoparticle-based seed priming modulates early growth and enhances physio-biochemical and metabolic profiles of fragrant rice against cadmium toxicity
Authors: Li Yuzhan , Liang Luxin , Li Wu , Ashraf Umair , Ma Lin , Tang Xiangru , Pan Shenggang , Tian Hua , Mo Zhaowen
Published: March 2021

Background

Cadmium (Cd) is amongst the most toxic heavy metals that severely affects crop growth, whereas application of nanoparticles (NPs) to negate the toxic effects of heavy metals could be an effective management approach. In the present study, the seeds of two fragrant rice varieties i.e., Yuxiangyouzhan and Xiangyaxiangzhan under normal and Cd stress conditions i.e., 0 and 100 mg L− 1 applied with four levels of ZnO NPs i.e., 0, 25, 50, and 100 mg L− 1.

Results

Seed priming with ZnO NPs had no significant effect on the seed germination (p > 0.05) however, it substantially improved the seedling growth and other related physiological attributes under the Cd stress. The mean fresh weight of the shoot, and whole seedling was increased by 16.92–27.88% and by 16.92–27.88% after ZnO NPs application. The root fresh weight, root-shoot length was also substantially improved under ZnO NPs treatment. Moreover, application of ZnO NPs induced modulations in physiological and biochemical attributes e.g., the superoxide dismutase (SOD) activity in root and shoot, the peroxidase (POD) activity and metallothionein contents in root were increased under low levels of ZnO NPs. The α-amylase and total amylase activity were improved by ZnO NPs application under Cd Stress. Besides, modulation in Zn concentration and ZnO NPs uptake in the seedling were detected. The metabolomic analysis indicated that various pathways such as alanine, aspartate and glutamate metabolism, phenylpropanoid biosynthesis, and taurine and hypotaurine metabolism were possibly important for rice response to ZnO NPs and Cd.

Conclusion

Overall, application of ZnO NPs substantially improved the early growth and related physio-biochemical attributes in rice. Our findings provide new insights regarding the effects of ZnO NPs on seed germination, and early growth of rice, and its potential applications in developing crop resilience against Cd contaminated soils.
Sialic acid-engineered mesoporous polydopamine dual loaded with ferritin gene and SPIO for achieving endogenous and exogenous synergistic T2-weighted magnetic resonance imaging of HCC
Authors: Fan Kai , Lu Chengying , Shu Gaofeng , Lv Xiu-Ling , Qiao Enqi , Zhang Nannan , Chen Minjiang , Song Jingjing , Wu Fazong , Zhao Zhongwei , Xu Xiaoling , Xu Min , Chen Chunmiao , Yang Weibin , Sun Jihong , Du Yongzhong , Ji Jiansong
Published: March 2021

Background

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC.

Results

Herein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast.

Conclusions

The results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.
Elevated levels of inflammatory plasma biomarkers are associated with risk of HIV infection
Authors: McInally Samantha , Wall Kristin , Yu Tianwei , Tirouvanziam Rabindra , Kilembe William , Gilmour Jill , Allen Susan A. , Hunter Eric
Published: March 2021

Background

To determine if individuals, from HIV-1 serodiscordant couple cohorts from Rwanda and Zambia, who become HIV-positive have a distinct inflammatory biomarker profile compared to individuals who remain HIV-negative, we compared levels of biomarkers in plasma of HIV-negative individuals who either seroconverted (pre-infection) and became HIV-positive or remained HIV-negative (uninfected).

Results

We observed that individuals in the combined cohort, as well as those in the individual country cohorts, who later became HIV-1 infected had significantly higher baseline levels of multiple inflammatory cytokines/chemokines compared to individuals who remained HIV-negative. Genital inflammation/ulceration or schistosome infections were not associated with this elevated profile. Defined levels of ITAC and IL-7 were significant predictors of later HIV acquisition in ROC predictive analyses, whereas the classical Th1 and Th2 inflammatory cytokines such as IL-12 and interferon-γ or IL-4, IL-5 and Il-13 were not.

Conclusions

Overall, the data show a significant association between increased plasma biomarkers linked to inflammation and immune activation and HIV acquisition and suggests that pre-existing conditions that increase systemic biomarkers represent a factor for increased risk of HIV infection.
COVID-19 infection among healthcare workers: a cross-sectional study in southwest Iran
Authors: Sabetian Golnar , Moghadami Mohsen , Hashemizadeh Fard Haghighi Leila , Shahriarirad Reza , Fallahi Mohammad Javad , Asmarian Naeimehossadat , Moeini Yalda Sadat
Published: March 2021

Objective

With the novel coronavirus pandemic, the impact on the healthcare system and workers cannot be overlooked. However, studies on the infection status of medical personnel are still lacking. It is imperative to ensure the safety of health-care workers (HCWs) not only to safeguard continuous patient care but also to ensure they do not transmit the virus, therefore evaluation of infection rates in these groups are indicated.

Methods

Demographic and clinical data regarding infected cases among HCWs of Fars, Iran with positive SARS‐CoV‐2 PCR tests were obtained from 10th March to 17th May 2020.

Results

Our data demonstrated a rate of 5.62% (273 out of 4854 cases) infection among HCW, with a mean age of 35 years and a dominance of female cases (146 cases: 53.5%). The majority of infected cases were among nurses (51.3%), while the most case infection rate (CIR) was among physicians (27 positive cases out of 842 performed test (3.2%)). Also, the highest rate of infection was in the emergency rooms (30.6%). Also, 35.5% of the patients were asymptomatic and the most frequent clinical features among symptomatic patients were myalgia (46%) and cough (45.5%). Although 5.5% were admitted to hospitals, there were no reports of ICU admission. Furthermore, 10.3% of the cases reported transmitting the infection to family and friends. Regarding safety precautions, 1.6% didn't wear masks and 18.7% didn't use gloves in work environments.

Conclusion

HCWs are among the highest groups at risk of infection during the COVID-19 pandemic; therefore, evaluating infection rates and associated features is necessary to improve and adjust protective measures of these vulnerable, yet highly essential group.
Early extubation is associated with improved outcomes after complete surgical repair of pulmonary atresia with ventricular septal defect and hypoplastic pulmonary arteries in pediatric patients
Authors: Li Yinan , Jia Yuan , Wang Hongbai , Wu Xie , Li Shoujun , Yan Fuxia , Yuan Su
Published: March 2021

Background

The aim of this study was to investigate the impact of an early extubation strategy on outcomes following complete repair of pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary artery.

Methods

One hundred thirteen patients undergoing complete repair surgery of pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary artery between 2016 and 2018 were included in our retrospective propensity-score matched study. Propensity score matching was conducted in 1 to 2 ratio to balance the covariables impacting on clinical outcomes between groups. The primary outcomes were defined as length of intensive care unit stay, postoperative length of hospital stay and in-hospital medical cost. The secondary outcomes included postoperative complications such as re-intubation, re-exploration, in-hospital mortality, arrhythmia and etc.. In addition, blood product consumption were also abstracted.

Results

Compared with matched controls, patients in the early extubation group were demonstrated with a significant reduced length of intensive care unit stay (Median: 1.9 d νs. 4.1 d, p = 0.039), postoperative length of hospital stay (Median: 9.0 d νs. 17.0 d, p = 0.007) and in-hospital medical cost (Median: 69.5 × 1000CNY νs. 113.6× 1000CNY, p = 0.041). As for the postoperative complications, the occurrence of re-intubation, re-exploration, in-hospital mortality, arrhythmia and renal replacement therapy was similar between groups. However, pulmonary complications (p = 0.049) were with a significantly lower rate in the early extubation group. In addition, fresh frozen plasma (p = 0.041) transfusion volume were significantly reduced in the early extubation group rather than packed red blood cells and platelets.

Conclusions

Early extubation following complete repair of pulmonary atresia improved clinical outcomes and reduced in-hospital medical cost without increasing any postoperative complications.
Bloodmeal sources and feeding behavior of anopheline mosquitoes in Bure district, northwestern Ethiopia
Authors: Adugna Tilahun , Yewhelew Delensaw , Getu Emana
Published: March 2021

Background

Mosquito bloodmeal sources determine the feeding rates, adult survival, fecundity, hatching rates, and developmental times. Only the female Anopheles mosquito takes bloodmeals from humans, birds, mammals, and other vertebrates for egg development. Studies of the host preference patterns in blood-feeding anopheline mosquitoes are crucial to determine malaria vectors. However, the human blood index, foraging ratio, and host preference index of anopheline mosquitoes are not known so far in Bure district, Ethiopia.

Methods

The origins of bloodmeals from all freshly fed and a few half-gravid exophagic and endophagic females collected using Centers for Disease Control and Prevention light traps were identified as human and bovine using enzyme-linked immunosorbent assay. The human blood index, forage ratio, and host feeding index were calculated.

Results

A total of 617 specimens belonging to An. arabiensis (n = 209), An. funestus (n = 217), An. coustani (n = 123), An. squamosus (n = 54), and An. cinereus (n = 14) were only analyzed using blood ELISA. Five hundred seventy-five of the specimens were positive for blood antigens of the host bloods. All anopheline mosquitoes assayed for a bloodmeal source had mixed- rather than single-source bloodmeals. The FR for humans was slightly > 1.0 compared to bovines for all Anopheles species. HFI for each pair of vertebrate hosts revealed that humans were the slightly preferred bloodmeal source compared to bovines for all species (except An. squamosus), but there was no marked host selection.

Conclusions

All anopheline mosquitoes assayed for bloodmeal ELISA had mixed feeds, which tends to diminish the density of gametocytes in the mosquito stomach, thereby reducing the chance of fertilization of the female gamete and reducing the chances of a malaria vector becoming infected. Moreover, An. coustani was the only species that had only human bloodmeals, meaning that this species has the potential to transmit the disease. Therefore, combination zooprophylaxis should be reinforced as a means of vector control because the study sites are mixed dwellings.

Graphical Abstract
SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models
Authors: Wang Yupeng , Jaime-Lara Rosario B. , Roy Abhrarup , Sun Ying , Liu Xinyue , Joseph Paule V.
Published: March 2021

Objective

To address the challenge of computational identification of cell type-specific regulatory elements on a genome-wide scale.

Results

We propose SeqEnhDL, a deep learning framework for classifying cell type-specific enhancers based on sequence features. DNA sequences of “strong enhancer” chromatin states in nine cell types from the ENCODE project were retrieved to build and test enhancer classifiers. For any DNA sequence, positional k-mer (k = 5, 7, 9 and 11) fold changes relative to randomly selected non-coding sequences across each nucleotide position were used as features for deep learning models. Three deep learning models were implemented, including multi-layer perceptron (MLP), Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). All models in SeqEnhDL outperform state-of-the-art enhancer classifiers (including gkm-SVM and DanQ) in distinguishing cell type-specific enhancers from randomly selected non-coding sequences. Moreover, SeqEnhDL can directly discriminate enhancers from different cell types, which has not been achieved by other enhancer classifiers. Our analysis suggests that both enhancers and their tissue-specificity can be accurately identified based on their sequence features. SeqEnhDL is publicly available at https://github.com/wyp1125/SeqEnhDL.
Process development and safety evaluation of ABCB5+ limbal stem cells as advanced-therapy medicinal product to treat limbal stem cell deficiency
Authors: Norrick Alexandra , Esterlechner Jasmina , Niebergall-Roth Elke , Dehio Ulf , Sadeghi Samar , Schröder Hannes M. , Ballikaya Seda , Stemler Nicole , Ganss Christoph , Dieter Kathrin , Dachtler Ann-Kathrin , Merz Patrick , Sel Saadettin , Chodosh James , Cursiefen Claus , Frank Natasha Y. , Auffarth Gerd U. , Ksander Bruce , Frank Markus H. , Kluth Mark A.
Published: March 2021

Background

While therapeutic success of the limbal tissue or cell transplantation to treat severe cases of limbal stem cell (LSC) deficiency (LSCD) strongly depends on the percentage of LSCs within the transplanted cells, prospective LSC enrichment has been hampered by the intranuclear localization of the previously reported LSC marker p63. The recent identification of the ATP-binding cassette transporter ABCB5 as a plasma membrane-spanning marker of LSCs that are capable of restoring the cornea and the development of an antibody directed against an extracellular loop of the ABCB5 molecule stimulated us to develop a novel treatment strategy based on the utilization of in vitro expanded allogeneic ABCB5+ LSCs derived from human cadaveric limbal tissue.

Methods

We developed and validated a Good Manufacturing Practice- and European Pharmacopeia-conform production and quality-control process, by which ABCB5+ LSCs are derived from human corneal rims, expanded ex vivo, isolated as homogenous cell population, and manufactured as an advanced-therapy medicinal product (ATMP). This product was tested in a preclinical study program investigating the cells’ engraftment potential, biodistribution behavior, and safety.

Results

ABCB5+ LSCs were reliably expanded and manufactured as an ATMP that contains comparably high percentages of cells expressing transcription factors critical for LSC stemness maintenance (p63) and corneal epithelial differentiation (PAX6). Preclinical studies confirmed local engraftment potential of the cells and gave no signals of toxicity and tumorgenicity. These findings were sufficient for the product to be approved by the German Paul Ehrlich Institute and the U.S. Food & Drug Administration to be tested in an international multicenter phase I/IIa clinical trial (NCT03549299) to evaluate the safety and therapeutic efficacy in patients with LSCD.

Conclusion

Building upon these data in conjunction with the previously shown cornea-restoring capacity of human ABCB5+ LSCs in animal models of LSCD, we provide an advanced allogeneic LSC-based treatment strategy that shows promise for replenishment of the patient’s LSC pool, recreation of a functional barrier against invading conjunctival cells and restoration of a transparent, avascular cornea.
Orchestration an extracellular lipase production from Aspergillus niger MYA 135: biomass morphology and fungal physiology
Authors: Salvatierra Hebe Natalia , Regner Erika Lucía , Baigorí Mario Domingo , Pera Licia María
Published: March 2021

The impact of biomass morphology and culture conditions on fungal fermentation was widely reviewed in the literature. In this work, we presented three independent experiments in order to evaluate the influence of some of those input factors on a lipase production separately by using the Aspergillus niger MYA 135 and the two-stage fermentation technique. Regarding the culture modality, the biomass was pre-grown in a first reactor. Then, the washed mycelium was transferred to a second reactor to continue the study. Firstly, linear effects of fungal morphology and several physiological parameters on a lipase production were explored using the Plackett–Burman design. The dispersed fungal morphology was confirmed as a proper quality characteristic for producing an extracellular lipase activity. Concerning the impact of the carbon source on the biomass pre-growth, the sucrose (E = 9.923, p < 0.001) and the l-arabinose (E = 4.198, p = 0.009) presented positive and significant effects on the enzyme production. On the contrary, the supplementation of 0.05 g/L CaCl2 displayed a highly negative and significant effect on this process (E = − 7.390, p < 0.001). Secondly, the relationship between the enzyme production and the input variables N:C ratio, FeCl3 and olive oil was explored applying the central composite design. Among the model terms, the N:C ratio of the production medium had the most negative and significant influence on the enzyme synthesis. Thus, it was concluded that a low N:C ratio was preferable to increase its production. In addition, the bifunctional role of FeCl3 on this fungus was presented. Thirdly, a prove of concept assay was also discussed.
A study of ethnic, gender and educational differences in attitudes toward COVID-19 vaccines in Israel – implications for vaccination implementation policies
Authors: Green Manfred S. , Abdullah Rania , Vered Shiraz , Nitzan Dorit
Published: March 2021

Background

Vaccines for COVID-19 are currently available for the public in Israel. The compliance with vaccination has differed between sectors in Israel and the uptake has been substantially lower in the Arab compared with the Jewish population.

Aim

To assess ethnic and socio-demographic factors in Israel associated with attitudes towards COVID-19 vaccines prior to their introduction.

Methods

A national cross-sectional survey was carried out In Israel during October 2020 using an internet panel of around 100,000 people, supplemented by snowball sampling. A sample of 957 adults aged 30 and over were recruited of whom 606 were Jews (49% males) and 351 were Arabs (38% males).

Results

The sample of Arabs was younger than for the Jewish respondents. Among the men, 27.3% of the Jewish and 23.1% of the Arab respondents wanted to be vaccinated immediately, compared with only 13.6% of Jewish women and 12.0% of Arab women. An affirmative answer to the question as to whether they would refuse the vaccine at any stage was given by 7.7% of Jewish men and 29.9% of Arab men, and 17.2% of Jewish women and 41.0% of Arab women. Higher education was associated with less vaccine hesitancy. In multiple logistic regression analysis, the ethnic and gender differences persisted after controlling for age and education. Other factors associated with vaccine hesitancy were the belief that the government restrictions were too lenient and the frequency of socializing prior to the pandemic.

Conclusions

The study revealed a relatively high percentage reported would be reluctant to get vaccinated, prior to the introduction of the vaccine. This was more marked so for Arabs then Jews, and more so for women within the ethnic groups. While this was not a true random sample, the findings are consistent with the large ethnic differences in compliance with the vaccine, currently encountered and reinforce the policy implications for developing effective communication to increase vaccine adherence. Government policies directed at controlling the pandemic should include sector-specific information campaigns, which are tailored to ensure community engagement, using targeted messages to the suspected vaccine hesitant groups. Government ministries, health service providers and local authorities should join hands with civil society organizations to promote vaccine promotion campaigns.
External validation of an opioid misuse machine learning classifier in hospitalized adult patients
Authors: Afshar Majid , Sharma Brihat , Bhalla Sameer , Thompson Hale M. , Dligach Dmitriy , Boley Randy A. , Kishen Ekta , Simmons Alan , Perticone Kathryn , Karnik Niranjan S.
Published: March 2021

Background

Opioid misuse screening in hospitals is resource-intensive and rarely done. Many hospitalized patients are never offered opioid treatment. An automated approach leveraging routinely captured electronic health record (EHR) data may be easier for hospitals to institute. We previously derived and internally validated an opioid classifier in a separate hospital setting. The aim is to externally validate our previously published and open-source machine-learning classifier at a different hospital for identifying cases of opioid misuse.

Methods

An observational cohort of 56,227 adult hospitalizations was examined between October 2017 and December 2019 during a hospital-wide substance use screening program with manual screening. Manually completed Drug Abuse Screening Test served as the reference standard to validate a convolutional neural network (CNN) classifier with coded word embedding features from the clinical notes of the EHR. The opioid classifier utilized all notes in the EHR and sensitivity analysis was also performed on the first 24 h of notes. Calibration was performed to account for the lower prevalence than in the original cohort.

Results

Manual screening for substance misuse was completed in 67.8% (n = 56,227) with 1.1% (n = 628) identified with opioid misuse. The data for external validation included 2,482,900 notes with 67,969 unique clinical concept features. The opioid classifier had an AUC of 0.99 (95% CI 0.99–0.99) across the encounter and 0.98 (95% CI 0.98–0.99) using only the first 24 h of notes. In the calibrated classifier, the sensitivity and positive predictive value were 0.81 (95% CI 0.77–0.84) and 0.72 (95% CI 0.68–0.75). For the first 24 h, they were 0.75 (95% CI 0.71–0.78) and 0.61 (95% CI 0.57–0.64).

Conclusions

Our opioid misuse classifier had good discrimination during external validation. Our model may provide a comprehensive and automated approach to opioid misuse identification that augments current workflows and overcomes manual screening barriers.