bluuebunny/crossref_metadata_2025 huggingface dataset:
Poor Prognosis Biomolecular Factors Are Highly Frequent in Childhood Acute Leukemias From Oaxaca, Mexico
Authors: Juárez-Avendaño Gerardo , Luna-Silva Nuria Citlalli , Chargoy-Vivaldo Euler , Juárez-Martínez Laura Alicia , Martínez-Rangel Mayra Noemí , Zárate-Ortiz Noemí , Martínez-Valencia Edith , López-Martínez Briceida , Pelayo Rosana , Balandrán Juan Carlos
Published: July 2020

Objective:

To investigate the cellular and molecular epidemiology of acute leukemias in vulnerable populations of children and adolescents in Oaxaca de Juarez, Mexico.

Material and Methods:

Descriptive, cross-sectional and retrospective study, conducted from 2014 to 2018 in which profiles of molecular and immunophenotypic aberrations were investigated in children and adolescents diagnosed with acute leukemia, by evaluating 28 molecular abnormalities by HemaVision-Q28 multiplex RT-PCR kit and standardized EuroFlow Immunophenotyping of bone marrow cells.

Results:

We included 218 patients, with 82.5% younger than 14 years and 17.5% adolescents. The median age was 9 years and a main peak of incidence was recorded at age of 4 to 5 years. B-cell acute lymphoblastic leukemia was diagnosed in 70.64% of all cases, acute myeloid leukemia was in 22.48%, T-cell acute lymphoblastic leukemia in 6.42%, and mixed lineage acute leukemia in 0.46% of cases. Overall, chromosomal translocations were positive in 29.82% of cases. While 65.31% of patients with acute myeloid leukemia reported aberrancies, only in 18.83% of B-cell acute lymphoblastic leukemia cases genetic abnormalities were obvious. Surprisingly, most prevalent translocations in B-cell acute lymphoblastic leukemia were t(9;22) in 20.7%, followed by t(4;11) in 17.2% and t(6;11) in 13.8%, whereas patients with acute myeloid leukemia showed t(15;17) in 40.6% and t(8;21) in 21.9%. In contrast, an homogeneous expression of t(3;21) and t(6;11) was recorded for T-cell acute lymphoblastic leukemia and mixed lineage acute leukemia cases, respectively. Except for t(1;19), expressed only by pre-B cells, there was no association of any of the studied translocations with differentiation stages of the B-leukemic developmental pathway.

Conclusion:

Our findings identify near 50% of patients with acute lymphoblastic leukemia at debut with high-risk translocations and poor prognosis in B-cell acute lymphoblastic leukemia as well as an unexpected increase of acute myeloid leukemia cases in young children, suggesting a molecular shift that support a higher incidence of poor prognosis cases in Oaxaca.
Real-Time Fluorescence Imaging Using Indocyanine Green to Assess Therapeutic Effects of Near-Infrared Photoimmunotherapy in Tumor Model Mice
Authors: Rosenberg Adrian , Fujimura Daiki , Okada Ryuhei , Furusawa Aki , Inagaki Fuyuki , Wakiyama Hiroaki , Kato Takuya , Choyke Peter L. , Kobayashi Hisataka
Published: July 2020

Background:

Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that causes an increase in tumor perfusion, a phenomenon termed the super-enhanced permeability and retention effect. Currently, in vivo treatment efficacy of NIR-PIT is observable days after treatment, but monitoring would be improved by more acute detection of intratumor change. Fluorescence imaging may detect increased tumor perfusion immediately after treatment.

Methods:

In the first experiment, athymic nude mouse models bearing unilateral subcutaneous flank tumors were treated with either NIR-PIT or laser therapy only. In the second experiment, mice bearing bilateral flank tumors were treated with NIR-PIT only on the left-sided tumor. In both groups, immediately after treatment, indocyanine green was injected at different doses intravenously, and mice were monitored with the Shimadzu LIGHTVISION fluorescence imaging system for 1 hour.

Results:

Tumor-to-background ratio of fluorescence intensity increased over the 60 minutes of monitoring in treated mice but did not vary significantly in control mice. Tumor-to-background ratio was highest in the 1 mg kg−1 and 0.3 mg kg−1 doses. In mice with bilateral tumors, tumor-to-untreated tumor ratio increased similarly.

Conclusions:

Acute changes in tumor perfusion after NIR-PIT can be detected by real-time fluorescence imaging.
The Jewish workers in the port of Thessaloniki (1939-1943): Their war experience as workers, Greeks and Jews
Authors: Srougo Shai
Published: July 2020

This article explores the last chapter in the long history of the Jewish port workers in the waterfront of Thessaloniki—the World War II years. The Jewish blue-collar workers and white-collar workers shared a common history, and at the same time, each had a different story to tell on the drama of the war. Their everyday experience in the roles of workers, soldiers, non-combatants, and as Greek civilians reveals the Jewish role in shaping the space of the wartime port during three periods: Greek neutrality (September 1939 to September 1940), the Greek-Italian War (October 1940 to March 1941), and German occupation from April 1941 to March 1943, when the port became an ‘Aryan’ space.
Functional status as a marker of need for hospital admission following outpatient hernia repair
Authors: Reeves J Jeffery , Mannix Emily , Burton Brittany N , Gabriel Rodney A , Waterman Ruth S
Published: July 2020

Introduction

The careful selection of patients for hernia repair in ambulatory surgery centres is critical to prevent unanticipated inpatient admissions. The aim of this study was to evaluate risk factors associated with inpatient admission.

Methods

A multivariable logistic regression was performed utilising the ACS NSQIP database from 2007 to 2016. The primary outcome was same-day hospital discharge. The primary exposure variable was preoperative functional status. Additional covariates included sex, obesity, age, smoking status, steroid use, dyspnoea, diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, hypertension, bleeding disorder, dialysis-dependence and American Society of Anesthesiologists classification score.

Results

A total of 194,822 patients underwent hernia repair in the outpatient setting; 8705 (4.5%) required hospital admission. The variables with the most significantly increased odds for hospital admission were partially dependent and totally dependent preoperative functional status.

Conclusion

A non-independent baseline functional status is the strongest predictor of need for admission following outpatient hernia repair.
Comparison of two forced-air warming devices during foot and ankle surgery: a randomised controlled trial
Authors: Vecchio Jorge Javier Del , Chemes Lucas Nicolás , Ghioldi Mauricio Esteban , Dealbera Eric Daniel , Daniel Morgillo Pablo
Published: July 2020

Inadvertent perioperative hypothermia is a frequent problem associated with surgical patients which can have significant consequences during surgery and in the immediate postoperative period. We compared 35 randomised patients using over vs. under body forced air heating. There were no statistically significant differences between some demographic and surgical parameters such as: age, weight, height, body mass index, length of anaesthesia and operation. Statistically significant differences were found between the patient’s admission to the operating room and 30 minutes and the end of the procedure on the under body patients group. This study analyses a uniform population of patients (Foot and Ankle Surgery) previously not studied and supports the use of under body blankets.
Past, present, and future of the technological tracking methods to assess tactical variables in team sports: A systematic review
Authors: Rico-González Markel , Pino-Ortega José , Nakamura Fabio Y , Arruda Moura Felipe , Rojas-Valverde Daniel , Los Arcos Asier
Published: July 2020

The main aim of this work was to review the use of technological tracking methods to assess collective spatial-positioning variables in team sports. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and PICO design for systematic reviews, study identification was performed in four databases (PubMed, SPORTDiscus, ProQuest Central, and Web of Science). Articles were selected if they focused on player position and technological tracking methods. After duplicate removal, 2194 articles were identified based on the established search criteria, of which 72 articles were selected and analysed. Semi-automatic optic-based systems, Global Positioning System/Global Navigation Satellite Systems, and local positioning systems were used in 60%, 33% and 7% of the studies, respectively. All studies that measured tactical variables by local positioning system technology in team sports used local position measurement technology. Optic-based systems were used more often in the early years to analyse collective tactical behaviour during competition. Later, Global Positioning System/Global Navigation Satellite Systems became more frequent to measure behaviour in team sports during the training process. The possibility of using the same system during competition and training will facilitate the assessment of collective tactical behaviour in team sports.
Outbreak investigation of Candida auris at a tertiary care hospital in Karachi, Pakistan
Authors: Farooqi Joveria Q , Soomro Asad S , Baig Mirza A , Sajjad Shamoona F , Hamid Kamran , Jabeen Kauser , Naqvi Mohammed F , Nasir Nosheen , Roshan Rozina , Mahmood Syed F , Zafar Afia , Asghar Rana J
Published: July 2020

Background:

From September 2014, a tertiary care hospital in Karachi, Pakistan, started diagnosing 3–5 cases/month of a yeast locally identified as Saccharomyces spp. resistant to fluconazole. US Centers for Disease Control and Prevention identified the isolates as Candida auris. The Pakistan Field Epidemiology and Laboratory Training Program (FELTP) and the hospital investigated the outbreak from April 2015 to January 2016.

Objective:

The aim of the outbreak investigation was to determine the risk factors and to inform measures to limit the spread of the organism in the hospital.

Methods:

Medical records, nursing schedules and infection control practices were reviewed. Sixty-two age- and sex-matched hospital controls from the same wards were identified.

Results:

Thirty cases (17 males) were identified (mean age = 51.6 years, age range = 2–91 years), case fatality was 53%. Multivariate logistic regression showed that a history of surgery within 90 days of diagnosis, admission to the emergency department and history of chronic kidney disease were significantly associated with C. auris infection.

Discussion:

This is the report of the outbreak investigation that triggered a global exploration of C. auris as a newly identified multidrug-resistant nosocomial organism, spreading within the hospital, especially among patients with invasive procedures. Unfortunately, we could not identify any specific source of the outbreak nor stop the transmission of the organism.
The Nonoperative Instability Severity Index Score (NISIS): A Simple Tool to Guide Operative Versus Nonoperative Treatment of the Unstable Shoulder
Authors: Tokish John M. , Thigpen Charles A. , Kissenberth Michael J. , Tolan Stefan J. , Lonergan Keith T. , Tokish John M. , Dickens Jonathan F. , Hawkins Richard J. , Shanley Ellen
Published: July 2020

Background:

The management of the adolescent athlete after initial shoulder instability remains controversial.

Hypothesis:

Individual risk factors in athletes with shoulder instability who are managed nonoperatively can be integrated into a scoring system that can predict successful return to sport.

Study Design:

Retrospective cohort study.

Level of Evidence:

Level 4.

Methods:

A total of 57 scholastic athletes with primary anterior shoulder instability who were managed nonoperatively were reviewed. Success was defined as a return to index sport at the same level and playing at least 1 subsequent season without missed time as a result of the shoulder. Patient-specific risk factors were individually evaluated, and odds ratios were calculated. A 10-point Nonoperative Injury Severity Index Score (NISIS) incorporated the risk factors for failure. This score was then retrospectively applied with regression analysis and a chi-square analysis to determine the overall optimal score that predicted failure of nonoperative management.

Results:

In total, 6 risk factors for failure were included in the NISIS: age (>15 years), bone loss, type of instability, type of sport (contact vs noncontact), male sex, and arm dominance. Overall, 79% of patients treated nonoperatively were able to successfully return to sport. Nearly all (97%) low-risk patients (NISIS <7) successfully returned to sport, while only 59% of high-risk patients returned to sport, a relative risk of 12.2 ( P = 0.001). High-risk patients with unipolar bone loss successfully returned (100%), but 67% of high-risk patients with bipolar bone loss failed.

Conclusion:

The NISIS is a simple and effective clinical tool to determine successful nonoperative management following anterior shoulder instability and may be helpful in guiding decision making when presented with the unstable shoulder in the scholastic athlete.
Management of multivessel coronary artery disease in patients with non-ST-elevation myocardial infarction: a complex path to precision medicine
Authors: Baumann Angus A. W. , Mishra Aashka , Worthley Matthew I. , Nelson Adam J. , Psaltis Peter J.
Published: July 2020

Recent analyses suggest the incidence of acute coronary syndrome is declining in high- and middle-income countries. Despite this, overall rates of non-ST-elevation myocardial infarction (NSTEMI) continue to rise. Furthermore, NSTEMI is a greater contributor to mortality after hospital discharge than ST-elevation myocardial infarction (STEMI). Patients with NSTEMI are often older, comorbid and have a high likelihood of multivessel coronary artery disease (MVD), which is associated with worse clinical outcomes. Currently, optimal treatment strategies for MVD in NSTEMI are less well established than for STEMI or stable coronary artery disease. Specifically, in relation to percutaneous coronary intervention (PCI) there is a paucity of randomized, prospective data comparing multivessel and culprit lesion-only PCI. Given the heterogeneous pathological basis for NSTEMI with MVD, an approach of complete revascularization may not be appropriate or necessary in all patients. Recognizing this, this review summarizes the limited evidence base for the interventional management of non-culprit disease in NSTEMI by comparing culprit-only and multivessel PCI strategies. We then explore how a personalized, precise approach to investigation, therapy and follow up may be achieved based on patient-, disease- and lesion-specific factors.
Effects of exercise cessation on adipose tissue physiological markers related to fat regain: A systematic review
Authors: Del Vecchio Fabrício Boscolo , Coswig Victor Silveira , Cabistany Leo Dutra , Orcy Rafael Bueno , Gentil Paulo
Published: July 2020

Tissues usually super compensate during the period that follow physical exercise. Although this is widely accepted for muscle and glycogen, the compensatory effect is not usually applied to fat tissues. Notwithstanding, evidence for this has been present since the 1970s when it was first suggested that the increased lipogenic activity in response to training might be an adaptation that enables to restore an energy reserve that can be used in times of need. In this context, the present review aimed to summarize information about the effect of detraining on fat metabolism and the physiological responses associated with fat regain. A systematic search on PubMed and Scielo was performed using “training cessation,” “detraining,” “exercise detraining,” and “exercise cessation” combined with “fat tissue,” “adipose tissue,” “adipose metabolism,” and “fat metabolism,” as descriptors. From 377 results, 25 were included in this review, 12 humans and 13 rodents, resulting in a sample of 6772 humans and 613 animals. The analysis provided evidence for fat super compensation, as well as differences in humans and rodents, among different protocols and possible mechanisms for fat gain after exercise cessation. In summary, exercise cessation appears to increase the ability of the adipose tissue to store energy. However, caution should be taken, especially regarding conclusions based on investigations on humans, considering the multiple factors that could affect fat metabolism.
Knowledge, Attitude, and Practice in Management of Childhood Fever Among Saudi Parents
Authors: Hussain Shalam Mohamed , Al-Wutayd Osama , Aldosary Ahmed Hamad , Al-Nafeesah Abdullah , AlE’ed Ashwaq , Alyahya Modhi Saleh , Alfeneekh Anfal Saleh , AlKadi Sirin Ahmed , Alghasham Ghaida Abdulrahman , Aloyaidi Ghadah Abdulaziz
Published: July 2020

Fever is considered as a frequent symptom in childhood and is the cause of almost 65% to 70% of pediatric visits. Saudi Arabia has about 10% of child population (under 4 years of age), imposing a high burden of childhood illnesses including fever. A total of 1700 questionnaires were distributed to Saudi parents with children visiting pediatric clinic. Most of the participants were mothers (77.4%). A temperature of 38.0 °C was defined fever by 42% of participants. The majority of parents (80%) believed seizure is the consequence of untreated high fever. A total of 72.5% indicated that 40.7 to 43.20°C is the highest temperature that can be reached if untreated. There was a statistically significant relationship between mothers and fathers for overall knowledge, attitude, and practice scores. This study indicates that numerous misconceptions still persist regarding fever as more than 90% of parents demonstrated undue fear of consequent body damage from fever and also believed antibiotics can reduce high temperature.
The Relationship Between Environmental Hostility and Entrepreneurial Orientation of Small Businesses
Authors: Dele-Ijagbulu Oluwafemi , Moos Menisha , Eresia-Eke Chukuakadibia
Published: July 2020

Declining entrepreneurship as indicated by low total early-stage entrepreneurial activity (TEA) and high business failure is unacceptable in any economy. This predicament is indicative of South Africa’s business environment as well as the entrepreneurial disposition of firms operating within it. However, the factors precipitating entrepreneurial behaviour among small firms are yet to be fully comprehended and the environment as a motivation for entrepreneurship among these firms is yet to be examined thoroughly. Furthermore, research focus on the antecedents of entrepreneurial orientation (EO) is limited, even as EO has been considered as an aggregated construct repeatedly with inadequate attention directed at its independent constituents. In response to these concerns, this study investigates the relationships between environmental hostility (EH) and the individual components of EO among small businesses in South Africa. Using a quantitative methodological approach, the study conducts a survey, and analyses data obtained through random sampling. Through exploratory factor analysis (EFA) and partial least square structural equation modelling (PLS-SEM), it is discovered that only four components of EO are statistically recognisable, contrary to five as widely acknowledged in literature. Positive associations were also revealed between EH and each of these dimensions to varying degrees. These findings underline the necessity for entrepreneurial action along the lines of risk-taking, proactive-innovativeness, competitive aggressiveness and autonomy among small businesses in South Africa, given the hostile environment of her small business sector.
Predictors of Biologic Use and Satisfaction Among Patients With Psoriasis: An Analysis and Geographic Visualization of the 2016 and 2017 National Psoriasis Foundation Annual Surveys
Authors: Enos Clinton W. , Galadima Hadiza , Saini Arjun D. , Bell Stacie , Siegel Michael , Van Voorhees Abby S.
Published: July 2020

Background:

There are an increasing number of biologic therapies approved for the treatment of psoriasis. Previous reports have identified undertreatment as a concern in the United States. Undertreatment has been associated with decreased patient satisfaction and increased morbidity.

Objectives:

Assess biologic use and satisfaction among respondents to the 2016 and 2017 National Psoriasis Foundation (NPF) Annual Surveys.

Methods:

Retrospective data analysis of the 2016 and 2017 NPF Annual Survey responses from individuals with psoriasis. ArcGIS Pro software was utilized to generate maps and perform an optimized hot spot analysis of moderate-to-severe psoriasis and biologic use.

Results:

There were 427 patients with psoriasis involving the skin alone. Biologics were used in <23% of respondents, while nearly 69% reported body surface area (BSA) >3%. Respondents with BSA <3% and 3% to 4% were less likely to be on biologic therapy (odds ratio [OR]: 0.29, 0.11-0.78 and OR: 0.22, 0.09-0.56, respectively). Nonbiologic users were more likely to be very unsatisfied with their treatment compared to those receiving biologic therapy (OR: 5.23, 2.80-9.75). With geographic information systems (GIS), counties with increased moderate-to-severe disease were identified in the southeastern United States.

Conclusion:

Despite the increasing number of Food and Drug Administration–approved biologic medications, the proportion of respondents on biologic therapy remained small. Treatment with biologics correlated with less residual disease and increased satisfaction. Geographic variation in state legislation as well as state and federal health insurance did not impact biologic use. However, using GIS, we identify a greater burden of moderate-to-severe disease among respondents in the Southeastern United States and a lack of commensurate use of biologics in those areas.
Kiwis and COVID-19: The Aotearoa New Zealand Response to the Global Pandemic
Authors: Henrickson Mark
Published: July 2020

This fast-moving global COVID-19 pandemic caught many nations unprepared and has exposed numerous flaws in global health, public health, and economic and social welfare infrastructures. It may seem premature to write about responses, but there are lessons to be learned from the response of Aotearoa New Zealand. Although its geopolitical situation as an island nation meant that it had late exposure to COVID-19, NZ has been commended because it closed its borders (to non-nationals); lockdown; traced; tested contacts; told people to pick a ‘bubble’ (immediate and usual family or household) and stay within that bubble; and promoted clear public messages. Government assistance was available for employers to retain staff, and additional support was provided for businesses and individuals. A strong and empathetic prime minister communicated regularly with the public and developed a sense of common national purpose. However, COVID-19 still exposed the impact of social inequalities. Implications for the next steps of recovery are considered in the paper.
Social and Emergency Assistance Ex-Ante and During COVID-19 in the SADC Region
Authors: Dafuleya Gift
Published: July 2020

Social assistance is on the social development agenda of the Southern African Development Community (SADC) member states. It is not only reflected in the Code of Social Security of SADC (2007) , but is also anchored in the national legal frameworks and social protection policies of the member states. The implementation realities of social assistance in the region, however, differs. Non-state social assistance makes up for the deficits of state-run social assistance in countries with weak institutions. Countries that have institutionalised social assistance were swift to provide emergency assistance to mitigate the effects caused by the COVID-19 lockdown measures. However, the provided relief has been elusive to many migrants in the region. The implication of this is that without a clear consideration of emergency assistance as needs-based, and separate from social assistance, the region stands a little chance to assist migrants when faced with a disaster such as COVID-19.
COVID-19, Physical Distancing and Social Inequalities: Are We all Really in this Together?
Authors: Lingam Lakshmi , Suresh Sapkal Rahul
Published: July 2020

In the absence of a vaccine for combating the novel coronavirus (COVID-19), countries globally are going in for a national lockdown and are mandating all people to stay indoors, and, if out in the public domain, to maintain 2-m distance, wear masks and wash hands with soap to mitigate the spread of the virus and its community transmission. The significance of the much neglected public health measures to deal with communicable diseases has come back to haunt several countries with a large proportion of people who are poor and who live in dense settlements with low levels of public provisioning of basic amenities. This article attempts to examine the feasibility of the recommended physical distancing using data from a national level sample from India. With the aid of data on parameters such as access to water, toilet, electricity, mobile phone and secure employment from the 75th and 76th National Sample Survey Rounds of 2017–2018, a Physical Distancing Readiness Index has been constructed. The performance of 27 states and 2 union territories of India is examined using the Index. This study examines the statistical correlation of a Physical Distancing Readiness Index to the incidence rate and case fatality ratio of COVID-19. Our results show that the poorer households are unequally endowed for observing physical distancing and ensuring the effective implementation of lockdown, which leads to disproportionate increase in the incidence rate and case fatality ratio, keeping other factors constant.
Determinants of Target Victim Selection: A Case Study of Criminals from Gambaga Prisons
Authors: Azumah Francess Dufie , Nachinaab John Onzaberigu , Krampah Samuel , Ayim Pius Nzeh
Published: July 2020

The study was conducted to explore the determinants of target victim selection by criminals, mode of operations adopted by criminals and the factors considered in the selection of victims by criminals. The study adopted a qualitative approach where simple random and purposively sampling techniques were used to select a sample size of 50 inmates in the Gambaga prisons. Interview guide was the main tool used for the data collection for this study. The study found that victimization influences criminal intentions and behaviour of an individual. The inmates noted that they like to attack victims in isolation and in dark places, especially at night. The study further found that criminals operated in gangs, in areas with darkness and in the night using caps and tattered dresses that anonymized them. They also used fear to traumatize their victims, monitor their victims, as well as operated with guns and knives and under special requests of other individuals in society.
How Do Different Case Conclusions Impact on Survivors of Homicide? Developing and Applying a Conceptual Framework to Organize Current Empirical Knowledge
Authors: Baguley Chantelle , McPhedran Samara , Eriksson Li , Mazerolle Paul
Published: July 2020

Supporting families and friends of homicide victims (‘survivors’) requires understanding how homicide impacts on survivors. Although recent work has examined how the loss of a loved one and events following a homicide—such as media coverage, the criminal justice processes and the perpetrator’s sentence—affects survivors, there has been little consideration of how final ‘case conclusions’ (other than the perpetrator’s sentence)—such as homicide–suicide, cold-case homicide or perpetrator declared permanently unfit for trial or acquitted of murder or manslaughter—impacts on survivors. This article examines existing literature about how different final case conclusions, other than the perpetrator’s sentence, impact on survivors. A novel conceptual framework—the ‘Homicide Case Pathway’—is presented to organize these efforts. There are shared and diverse effects of final case conclusions on survivors, centred on five key themes—emotions and feelings, denial of justice, lack of closure, belief in the system and hope. There is a clear need to conduct further research into the effect of final case conclusions on survivors, in order to better understand survivors’ experiences, and subsequently identify and implement suitably tailored victim support strategies for survivors.
Dasatinib induces a dramatic response in a child with refractory juvenile xanthogranuloma with a novel MRC1-PDGFRB fusion
Authors: Eissa Shaimaa S. , Clay Michael R. , Santiago Teresa , Wu Gang , Wang Lu , Shulkin Barry L. , Picarsic Jennifer , Nichols Kim E. , Campbell Patrick K.
Published: July 2020

Key Points

Juvenile xanthogranuloma (JXG) usually presents with lesions isolated to the skin; however, aggressive, disseminated forms also occur. Identification of a novel MRC1-PDGFRB fusion in a child with JXG guided targeted therapy with dasatinib, leading to a dramatic response.
Doxorubicin-loaded hollow gold nanospheres for dual photothermal ablation and chemoembolization therapy
Authors: Sheth Rahul A. , Wen Xiaoxia , Li Junjie , Melancon Marites P. , Ji Xin , Andrew Wang Y. , Hsiao Cheng-Hui , Chow Diana S.-L. , Whitley Elizabeth M. , Li Chun , Gupta Sanjay
Published: July 2020

Background

Doxorubicin-loaded hollow gold nanospheres (Dox@HAuNS) are a promising technology for simultaneous trans-arterial tumor-targeted chemotherapy delivery and thermal ablation. We evaluated the efficacy of intra-arterial delivery of Dox@HAuNS followed by photothermal ablation (PTA) in a rabbit model of liver cancer. Adult New Zealand white rabbits (N = 25) were inoculated with VX2 tumors into the left lobe of the liver. The animals were then randomized to sham surgery (N = 5), PTA only (N = 3), Dox@HAuNS only (N = 5), HAuNS + PTA (N = 5), and Dox@HAuNS + PTA (N = 7). Nanoparticles were delivered as an emulsion with Lipiodol (Guerbet, France) via a trans-arterial approach. Following nanoparticle delivery, PTA was performed using an 808-nm fibered laser at 1.5 W for 3 min. Thermography during PTA demonstrated a sustained elevation in tumoral temperature in both HAuNS + laser and Dox@HAuNS + laser treatment groups relative to animals that underwent laser treatment without prior nanoparticle delivery.

Results

There was a significant decrease in tumor volumes in all three treatment arms relative to control arms (P = 0.004). Concentrations of intratumoral doxorubicin were significantly greater in animals treated with laser compared to those that were not treated with laser (P < 0.01).

Conclusions

Doxorubicin-loaded HAuNS is a promising therapeutic agent for dual ablation/chemoembolization treatment of liver cancer.
Highly efficient generation of sheep with a defined FecBB mutation via adenine base editing
Authors: Zhou Shiwei , Ding Yige , Liu Jiao , Liu Yao , Zhao Xiaoe , Li Guanwei , Zhang Chenguang , Li Chao , Wang Ying , Kalds Peter , Gao Yawei , Zong Bo , Huang Xiaoyu , Huang Shuhong , Yu Honghao , Kou Qifang , Petersen Bjoern , Huang Xingxu , Wang Xiaolong , Ma Baohua , Chen Yulin
Published: July 2020

Base editing has the potential to improve important economic traits in agriculture and can precisely convert single nucleotides in DNA or RNA sequences into minimal double-strand DNA breaks (DSB). Adenine base editors (ABE) have recently emerged as a base editing tool for the conversion of targeted A:T to G:C, but have not yet been used in sheep. ABEmax is one of the latest versions of ABE, which consists of a catalytically-impaired nuclease and a laboratory-evolved DNA-adenosine deaminase. The Booroola fecundity (FecBB) mutation (g.A746G, p.Q249R) in the bone morphogenetic protein receptor 1B (BMPR1B) gene influences fecundity in many sheep breeds. In this study, by using ABEmax we successfully obtained lambs with defined point mutations that result in an amino acid substitution (p.Gln249Arg). The efficiency of the defined point mutations was 75% in newborn lambs, since six lambs were heterozygous at the FecBB mutation site (g.A746G, p.Q249R), and two lambs were wild-type. We did not detect off-target mutations in the eight edited lambs. Here, we report the validation of the first gene-edited sheep generated by ABE and highlight its potential to improve economically important traits in livestock.
Proteus: An algorithm for proposing stabilizing mutation pairs based on interactions observed in known protein 3D structures
Authors: Barroso José Renato M. S. , Mariano Diego , Dias Sandro R. , Rocha Rafael E. O. , Santos Lucianna H. , Nagem Ronaldo A. P. , de Melo-Minardi Raquel C.
Published: July 2020

Background

Protein engineering has many applications for industry, such as the development of new drugs, vaccines, treatment therapies, food, and biofuel production. A common way to engineer a protein is to perform mutations in functionally essential residues to optimize their function. However, the discovery of beneficial mutations for proteins is a complex task, with a time-consuming and high cost for experimental validation. Hence, computational approaches have been used to propose new insights for experiments narrowing the search space and reducing the costs.

Results

In this study, we developed Proteus (an acronym for Protein Engineering Supporter), a new algorithm for proposing mutation pairs in a target 3D structure. These suggestions are based on contacts observed in other known structures from Protein Data Bank (PDB). Proteus’ basic assumption is that if a non-interacting pair of amino acid residues in the target structure is exchanged to an interacting pair, this could enhance protein stability. This trade is only allowed if the main-chain conformation of the residues involved in the contact is conserved. Furthermore, no steric impediment is expected between the proposed mutations and the surrounding protein atoms. To evaluate Proteus, we performed two case studies with proteins of industrial interests. In the first case study, we evaluated if the mutations suggested by Proteus for four protein structures enhance the number of inter-residue contacts. Our results suggest that most mutations proposed by Proteus increase the number of interactions into the protein. In the second case study, we used Proteus to suggest mutations for a lysozyme protein. Then, we compared Proteus’ outcomes to mutations with available experimental evidence reported in the ProTherm database. Four mutations, in which our results agree with the experimental data, were found. This could be initial evidence that changes in the side-chain of some residues do not cause disturbances that harm protein structure stability.

Conclusion

We believe that Proteus could be used combined with other methods to give new insights into the rational development of engineered proteins. Proteus user-friendly web-based tool is available at .
Loqusdb: added value of an observations database of local genomic variation
Authors: Magnusson Måns , Eisfeldt Jesper , Nilsson Daniel , Rosenbaum Adam , Wirta Valtteri , Lindstrand Anna , Wedell Anna , Stranneheim Henrik
Published: July 2020

Background

Exome and genome sequencing is becoming the method of choice for rare disease diagnostics. One of the key challenges remaining is distinguishing the disease causing variants from the benign background variation. After analysis and annotation of the sequencing data there are typically thousands of candidate variants requiring further investigation. One of the most effective and least biased ways to reduce this number is to assess the rarity of a variant in any population. Currently, there are a number of reliable sources of information for major population frequencies when considering single nucleotide variants (SNVs) and small insertion and deletions (INDELs), with gnomAD as the most prominent public resource available. However, local variation or frequencies in sub-populations may be underrepresented in these public resources. In contrast, for structural variation (SV), the background frequency in the general population is more or less unknown mostly due to challenges in calling SVs in a consistent way. Keeping track of local variation is one way to overcome these problems and significantly reduce the number of potential disease causing variants retained for manual inspection, both for SNVs and SVs.

Results

Here, we present loqusdb, a tool to solve the challenge of keeping track of any type of variant observations from genome sequencing data. Loqusdb was designed to handle a large flow of samples and unlike other solutions, samples can be added continuously to the database without rebuilding it, facilitating improvements and additions. We assessed the added value of a local observations database using 98 samples annotated with information from a background of 888 unrelated individuals.

Conclusions

We show both how powerful SV analysis can be when filtering for population frequencies and how the number of apparently rare SNVs/INDELs can be reduced by adding local population information even after annotating the data with other large frequency databases, such as gnomAD. In conclusion, we show that a local frequency database is an attractive, and a necessary addition to the publicly available databases that facilitate the analysis of exome and genome data in a clinical setting.
Glutantβase: a database for improving the rational design of glucose-tolerant β-glucosidases
Authors: Mariano Diego , Pantuza Naiara , Santos Lucianna H. , Rocha Rafael E. O. , de Lima Leonardo H. F. , Bleicher Lucas , de Melo-Minardi Raquel Cardoso
Published: July 2020

Β-glucosidases are key enzymes used in second-generation biofuel production. They act in the last step of the lignocellulose saccharification, converting cellobiose in glucose. However, most of the β-glucosidases are inhibited by high glucose concentrations, which turns it a limiting step for industrial production. Thus, β-glucosidases have been targeted by several studies aiming to understand the mechanism of glucose tolerance, pH and thermal resistance for constructing more efficient enzymes. In this paper, we present a database of β-glucosidase structures, called Glutantβase. Our database includes 3842 GH1 β-glucosidase sequences collected from UniProt. We modeled the sequences by comparison and predicted important features in the 3D-structure of each enzyme. Glutantβase provides information about catalytic and conserved amino acids, residues of the coevolution network, protein secondary structure, and residues located in the channel that guides to the active site. We also analyzed the impact of beneficial mutations reported in the literature, predicted in analogous positions, for similar enzymes. We suggested these mutations based on six previously described mutants that showed high catalytic activity, glucose tolerance, or thermostability (A404V, E96K, H184F, H228T, L441F, and V174C). Then, we used molecular docking to verify the impact of the suggested mutations in the affinity of protein and ligands (substrate and product). Our results suggest that only mutations based on the H228T mutant can reduce the affinity for glucose (product) and increase affinity for cellobiose (substrate), which indicates an increment in the resistance to product inhibition and agrees with computational and experimental results previously reported in the literature. More resistant β-glucosidases are essential to saccharification in industrial applications. However, thermostable and glucose-tolerant β-glucosidases are rare, and their glucose tolerance mechanisms appear to be related to multiple and complex factors. We gather here, a set of information, and made predictions aiming to provide a tool for supporting the rational design of more efficient β-glucosidases. We hope that Glutantβase can help improve second-generation biofuel production. Glutantβase is available athttp://bioinfo.dcc.ufmg.br/glutantbase.
Desiccation does not drastically increase the accessibility of exogenous DNA to nuclear genomes: evidence from the frequency of endosymbiotic DNA transfer
Authors: Li Xixi , Fang Cheng , Zhao Jun-Peng , Zhou Xiao-Yu , Ni Zhihua , Niu Deng-Ke
Published: July 2020

Background

Although horizontal gene transfer (HGT) is a widely accepted force in the evolution of prokaryotic genomes, its role in the evolution of eukaryotic genomes remains hotly debated. Some bdelloid rotifers that are resistant to extreme desiccation and radiation undergo a very high level of HGT, whereas in another desiccation-resistant invertebrate, the tardigrade, the pattern does not exist. Overall, the DNA double-strand breaks (DSBs) induced by prolonged desiccation have been postulated to open a gateway to the nuclear genome for exogenous DNA integration and thus to facilitate the HGT process, thereby enhancing the rate of endosymbiotic DNA transfer (EDT).

Results

We first surveyed the abundance of nuclear mitochondrial DNAs (NUMTs) and nuclear plastid DNAs (NUPTs) in five eukaryotes that are highly resistant to desiccation: the bdelloid rotifers Adineta vaga and Adineta ricciae, the tardigrade Ramazzottius varieornatus, and the resurrection plants Dorcoceras hygrometricum and Selaginella tamariscina. Excessive NUMTs or NUPTs were not detected. Furthermore, we compared 24 groups of desiccation-tolerant organisms with their relatively less desiccation-tolerant relatives but did not find a significant difference in NUMT/NUPT contents.

Conclusions

Desiccation may induce DSBs, but it is unlikely to dramatically increase the frequency of exogenous sequence integration in most eukaryotes. The capture of exogenous DNA sequences is possible only when DSBs are repaired through a subtype of non-homologous end joining, named alternative end joining (alt-EJ). Due to the deleterious effects of the resulting insertion mutations, alt-EJ is less frequently initiated than other mechanisms.
Fasciclin-like arabinogalactan gene family in Nicotiana benthamiana: genome-wide identification, classification and expression in response to pathogens
Authors: Wu Xinyang , Lai Yuchao , Lv Lanqing , Ji Mengfei , Han Kelei , Yan Dankan , Lu Yuwen , Peng Jiejun , Rao Shaofei , Yan Fei , Zheng Hongying , Chen Jianping
Published: July 2020

Background

Nicotiana benthamianais widely used as a model plant to study plant-pathogen interactions. Fasciclin-like arabinogalactan proteins (FLAs), a subclass of arabinogalactan proteins (AGPs), participate in mediating plant growth, development and response to abiotic stress. However, the members of FLAs inN. benthamianaand their response to plant pathogens are unknown.

Results

38NbFLAswere identified from a genome-wide study.NbFLAscould be divided into four subclasses, and their gene structure and motif composition were conserved in each subclass.NbFLAsmay be regulated by cis-acting elements such as STRE and MBS, and may be the targets of transcription factors like C2H2. Quantitative real time polymerase chain reaction (RT-qPCR) results showed that selectedNbFLAswere differentially expressed in different tissues. All of the selectedNbFLAswere significantly downregulated following infection by turnip mosaic virus (TuMV) and most of them also byPseudomonas syringae pv tomatostrain DC3000 (PstDC3000), suggesting possible roles in response to pathogenic infection.

Conclusions

This study systematically identifiedFLAsinN. benthamiana, and indicates their potential roles in response to biotic stress. The identification ofNbFLAswill facilitate further studies of their role in plant immunity inN. benthamiana.
Genome-wide identification, characterization and expression profiling of gibberellin metabolism genes in jute
Authors: Honi Ummay , Amin Md. Ruhul , Kabir Shah Md Tamim , Bashar Kazi Khayrul , Moniruzzaman Md. , Jahan Rownak , Jahan Sharmin , Haque Md. Samiul , Islam Shahidul
Published: July 2020

Background

Gibberellin (GA) is one of the most essential phytohormones that modulate plant growth and development. Jute (Corchorus sp.) is the second most important source of bast fiber. Our result has shown that exogenous GA can positively regulate jute height and related characteristics which mean increasing endogenous GA production will help to get a jute variety with improved characteristics. However, genes involved in jute GA biosynthesis have not been analyzed precisely.

Results

Genome-wide analysis identified twenty-two candidate genes involved in jute GA biosynthesis pathway. Among them, four genes- CoCPS, CoKS, CoKO and CoKAO work in early steps. Seven CoGA20oxs, three CoGA3oxs, and eight GA2oxs genes work in the later steps. These genes were characterized through phylogenetic, motif, gene structure, and promoter region analysis along with chromosomal localization. Spatial gene expression analysis revealed that 11 GA oxidases were actively related to jute GA production and four of them were marked as key regulators based on their expression level. All the biosynthesis genes both early and later steps showed tissue specificity. GA oxidase genes were under feedback regulation whereas early steps genes were not subject to such regulation.

Conclusion

Enriched knowledge about jute GA biosynthesis pathway and genes will help to increase endogenous GA production in jute by changing the expression level of key regulator genes. CoGA20ox7, CoGA3ox2, CoGA2ox3, and CoGA2ox5 may be the most important genes for GA production.
Identification of genetic loci associated with forage quality in response to water deficit in autotetraploid alfalfa (Medicago sativa L.)
Authors: Lin Sen , Medina Cesar Augusto , Boge Bill , Hu Jinguo , Fransen Steven , Norberg Steven , Yu Long-Xi
Published: July 2020

Background

Alfalfa has been cultivated in many regions around the world as an important forage crop due to its nutritive value to livestock and ability to adapt to various environments. However, the genetic basis by which plasticity of quality-relevant traits influence alfalfa adaption to different water conditions remain largely unknown.

Results

In the present study, 198 accessions of alfalfa of the core collection for drought tolerance were evaluated for 26 forage quality traits in a field trial under an imposed deficit irrigation gradient. Regression analysis between quality traits and water stress revealed that values of fiber-related traits were negatively correlated with values of energy-related traits as water deficit increased. More than one hundred significant markers associated with forage quality under different water treatments were identified using genome-wide association studies with genotyping by sequencing. Among them, 131 markers associated with multiple traits in all the water deficit treatments. Most of the associated markers were dependent to the levels of water deficit, suggesting genetic controls for forage quality traits were dependent to the stress treatment. Twenty-four loci associated with forage quality were annotated to functional genes that may play roles in cell development or in response to water stress.

Conclusions

This study addressed the genetic base of phenotypic variation of forage quality traits under water deficit. The SNP markers identified in this study will be useful in marker-assisted selection for the genetic improvement of alfalfa with enhanced drought tolerance while maintaining forage quality.