bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Clinical Disease Recurrence Using Laboratory Data in Surgically Resected Patients From the TOPPIC Trial
Authors: Waljee Akbar K , Cohen-Mekelburg Shirley , Liu Yumu , Liu Boang , Zhu Ji , Higgins Peter D R
Published: October 2020

Background

Machine learning methodologies play an important role in predicting progression of disease or responses to medical therapy. We previously derived and validated a machine learning algorithm to predict response to thiopurines in an inflammatory bowel disease population. We aimed to apply a modified algorithm to predict postsurgical treatment response using clinical trial data.

Methods

TOPPIC was a multicenter randomized double-blinded placebo-controlled trial of 240 patients, evaluating the effectiveness of 6-mercaptopurine in preventing or delaying postsurgical Crohn disease recurrence. We adapted a well-established machine learning algorithm to predict clinical recurrence postresection using age and multiple laboratory-specific covariates, and compared this to the thiopurine metabolite, 6-thioguanine.

Results

The random forest machine learning algorithm demonstrates a mean under the receiver operator curve (AuROC) of 0.62 [95% confidence interval (CI) 0.47, 0.78]. Similar results were evident when adding thiopurine metabolite (6-thioguanine) results. Alanine aminotransferase/mean corpuscular volume (ALT/MCV) and potassium × alkaline phosphatase (POT × ALK) predicted endoscopic and biologic recurrence, respectively, with AuROCs of 0.714 (95% CI 0.601, 0.827) and 0.730 (95% CI 0.618, 0.841).

Conclusions

A machine learning algorithm with laboratory data from within the first 3 months postsurgically does not discriminate clinical recurrence well. Alternative noninvasive measures should be considered and further evaluated.
Hannah Lowe and Sarah Howe: Multicultural Heritage and Questions of Identity
Authors: Wong Jennifer
Published: October 2020

In their respective debut collections Chick and Loop of Jade, Hannah Lowe and Sarah Howe explore the questions of identity and cultural hybridity through semi-autobiographical family narratives. Conscious of their partial Chinese ancestry, their poetry reflects what it means or feels to self-perceive or be taken as ‘the Other’. In this article, I analyse and compare their poetry to shed light on the significance and representation of multicultural heritage in contemporary women’s poetry, with reference to the multiple identities of the female figure. In particular, their different writing approaches explore the questions of identity for a multicultural poet and the necessity of exoticism and self-exoticism. Through close reading of their poetry and interviews with these authors, I examine the experimentation of poetic form and language in their work, the role of imagination in connecting personal with collective history, and the complexities that underlie the relationship between poetic language, racial, and class barriers.
Evolution of the monitoring and evaluation strategies to support the World Health Organization's Global Programme to Eliminate Lymphatic Filariasis
Authors: Lammie Patrick J , Gass Katherine M , King Jonathan , Deming Michael S , Addiss David G , Biswas Gautam , Ottesen Eric A , Henderson Ralph
Published: October 2020

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was established with the ambitious goal of eliminating LF as a public health problem. The remarkable success of the GPELF over the past 2 decades in carrying out its principal strategy of scaling up and scaling down mass drug administration has relied first on the development of a rigorous monitoring and evaluation (M&E) framework and then the willingness of the World Health Organization and its community of partners to modify this framework in response to the practical experiences of national programmes. This flexibility was facilitated by the strong partnership that developed among researchers, LF programme managers and donors willing to support the necessary research agenda. This brief review summarizes the historical evolution of the GPELF M&E strategies and highlights current research needed to achieve the elimination goal.
A disparity in the number of studies related to COVID-19 and SARS-CoV-2 between low- and middle-income countries and high-income countries
Authors: Usuzaki Takuma , Chiba Shuji , Shimoyama Minoru , Ishikuro Mami , Obara Taku
Published: October 2020

Background

There may be a difference in the number of articles about COVID-19 and SARS-CoV-2 between low- and middle-income countries (LMICs) and high-income countries (HICs).

Methods

We analyzed authors’ affiliations from 36 432 articles related to COVID-19 and SARS-CoV-2. We introduced logarithmic density and compared the number of articles and logarithmic density of LMICs with those of HICs.

Results

The number of articles and the logarithmic density of LMICs were lower than those of HICs (p<0.0001 for both).

Conclusions

There was a disparity in the number of articles related to COVID-19 and SARS-CoV-2 between LMICs and HICs.
Eight weeks of resistance training with blood flow restriction improve cardiac function and vascular endothelial function in healthy young Asian males
Authors: Zhao Yan , Lin Aicui , Jiao Long
Published: October 2020

Background

Resistance training with blood flow restriction (BFR) is a physiological ischaemic training method. Before it is applied to patients with coronary artery disease, it must be proven safe and effective.

Methods

Twenty-four healthy adult males were randomly assigned to three groups: the resistance training (RT) group, low-pressure BFR and resistance training (LP-RT) group and high-pressure BFR and resistance training (HP-RT) group. The training protocol was 20 times/min/set, with a 2-min break, five sets/day and 5 d/week for 8 weeks. Cardiac function, haemodynamics and vascular endothelial function were evaluated before and after the first training and the last training.

Results

There were no significant differences among groups before and after training. After 8 weeks of training, the resting heart rate (p<0.05) of the three groups significantly decreased (p<0.05). The rate–pressure product in the LP-RT group significantly decreased (p<0.05) compared with before training. Just after the last training, heart rate (p<0.05) and cardiac output (p<0.05) in the LP-RT and HP-RT groups significantly decreased compared with those just after the first training. At the end of the experiment, vascular endothelial growth factor (VEGF; p<0.01), soluble VEGF receptor (VEGFR) (p<0.05) and interleukin-6 (p<0.01) significantly increased, except for soluble VEGFR in the RT group.

Conclusions

Low-intensity resistance training with BFR moderately alters cardiac function. The expression levels of proteins related to vascular endothelial function have significantly changed. Both findings suggest that low-intensity resistance training with BFR may be safely and effectively applied to patients with coronary artery disease.
Ancient colonialism and the economic geography of the Mediterranean
Authors: Chronopoulos Dimitris K , Kampanelis Sotiris , Oto-Peralías Daniel , Wilson John O S
Published: October 2020

This article investigates the legacy of ancient Phoenician, Greek and Etruscan colonialism in shaping the economic geography of the Mediterranean region. Utilising historical data on ancient colonies and current data on population density and night light emissions (as a proxy for economic activity), we find that geographical areas colonised by these ancient civilisations have higher population density and economic activity in the present day. We also find that ancient colonialism affected the origin and evolution of the urban system of cities and settlements prevalent in the Mediterranean region.
LectomeXplore, an update of UniLectin for the discovery of carbohydrate-binding proteins based on a new lectin classification
Authors: Bonnardel François , Mariethoz Julien , Pérez Serge , Imberty Anne , Lisacek Frédérique
Published: October 2020

Lectins are non-covalent glycan-binding proteins mediating cellular interactions but their annotation in newly sequenced organisms is lacking. The limited size of functional domains and the low level of sequence similarity challenge usual bioinformatics tools. The identification of lectin domains in proteomes requires the manual curation of sequence alignments based on structural folds. A new lectin classification is proposed. It is built on three levels: (i) 35 lectin domain folds, (ii) 109 classes of lectins sharing at least 20% sequence similarity and (iii) 350 families of lectins sharing at least 70% sequence similarity. This information is compiled in the UniLectin platform that includes the previously described UniLectin3D database of curated lectin 3D structures. Since its first release, UniLectin3D has been updated with 485 additional 3D structures. The database is now complemented by two additional modules: PropLec containing predicted β-propeller lectins and LectomeXplore including predicted lectins from sequences of the NBCI-nr and UniProt for every curated lectin class. UniLectin is accessible at https://www.unilectin.eu/
Malignant transformation of WHO grade I meningiomas after surgery or radiosurgery: systematic review and meta-analysis of observational studies
Authors: Nakasu Satoshi , Notsu Akifumi , Na Kiyong , Nakasu Yoko
Published: October 2020

Background

The incidence and clinical features of the malignant transformation of benign meningiomas are poorly understood. This study examined the risk of the malignant transformation of benign meningiomas after surgery or stereotactic radiosurgery.

Methods

We systematically reviewed studies published between 1979 and 2019 using PubMed, Scopus, and other sources. We analyzed pooled data according to the PRISMA guideline to clarify the incidence rate of malignant transformation (IMT) and factors affecting malignant transformation in surgically or radiosurgically treated benign meningiomas.

Results

IMT was 2.98/1000 patient-years (95% confidence interval [CI] = 1.9–4.3) in 13 studies in a single-arm meta-analysis. Although the evidence level of the included studies was low, the heterogeneity of the incidence was mostly explained by the tumor location. In meta-regression analysis, skull base tumors had a significantly lower IMT than non-skull base tumors, but no gender association was observed. IMT after radiosurgery in 9 studies was 0.50/1000 person-years (95% CI = 0.02–1.38). However, a higher proportion of skull base tumors, lower proportion of males, and lower salvage surgery rate were observed in the radiosurgery group than in the surgery group. The median time to malignant change was 5 years (interquartile range = 2.5–8.2), and the median survival after malignant transformation was 4.7 years (95% CI = 3.7–8) in individual case data.

Conclusion

IMT of benign meningioma was significantly affected by the tumor location. Radiosurgery did not appear to increase IMT, but exact comparisons were difficult because of differences in study populations.
Use of Smokeless Tobacco Before Conception and Its Relationship With Maternal and Fetal Outcomes of Pregnancy in Thatta, Pakistan: Findings From Women First Study
Authors: Aziz Ali Sumera , Khan Umber , Abrejo Farina , Vollmer Brandi , Saleem Sarah , Hambidge K Michael , Krebs Nancy F , Westcott Jamie E , Goldenberg Robert L , McClure Elizabeth M , Pasha Omrana
Published: October 2020

Introduction

Smokeless tobacco (SLT) consumption during pregnancy has adverse consequences for the mother and fetus. We aimed to investigate the effects of maternal pre-pregnancy SLT consumption on maternal and fetal outcomes in the district of Thatta, Pakistan.

Aims and Methods

We conducted a secondary data analysis of an individual randomized controlled trial of preconception maternal nutrition. Study participants were women of reproductive age (WRA) residing in the district of Thatta, Pakistan. Participants were asked questions regarding the usage of commonly consumed SLT known as gutka (exposure variable). Study outcomes included maternal anemia, miscarriage, preterm births, stillbirths, and low birth weight. We performed a cox-regression analysis by controlling for confounders such as maternal age, education, parity, working status, body mass index, and geographic clusters.

Results

The study revealed that 71.5% of the women reported using gutka, with a higher proportion residing in rural areas as compared with urban areas in the district of Thatta, Pakistan. In the multivariable analysis, we did not find a statistically significant association between gutka usage and anemia [(relative risk, RR: 1.04, 95% confidence interval, CI (0.92 to 1.16)], miscarriage [(RR: 1.08, 95% CI (0.75 to 1.54)], preterm birth [(RR: 1.37, 95% CI (0.64 to 2.93)], stillbirth [(RR: 1.02, 95% CI (0.39 to 2.61)], and low birth weight [(RR: 0.96, 95% CI (0.72 to 1.28)].

Conclusions

The study did not find an association between gutka usage before pregnancy and adverse maternal and fetal outcomes. In the future, robust epidemiological studies are required to detect true differences with a dose–response relationship between gutka usage both before and during pregnancy and adverse fetomaternal outcomes.

Implications

While most epidemiological studies conducted in Pakistan have focused on smoking and its adverse outcomes among males, none of the studies have measured the burden of SLT among WRA and its associated adverse outcomes. In addition, previously conducted studies have primarily assessed the effect of SLT usage during pregnancy rather than before pregnancy on adverse fetal and maternal outcomes. The current study is unique because it provides an insight into the usage of SLT among WRA before pregnancy and investigates the association between pre-pregnancy SLT usage and its adverse fetomaternal outcomes in rural Pakistan.
Poverty Alleviation and Interhousehold Transfers: Evidence from BRAC’s Graduation Program in Bangladesh
Authors: Gulesci Selim
Published: October 2020

Poor households often rely on transfers from their social networks for consumption smoothing, yet there is limited evidence on how antipoverty programs affect informal transfers. This paper exploits the randomized rollout of BRAC’s ultra-poor graduation program in Bangladesh and panel data covering over 21,000 households over seven years to study the program’s effects on interhousehold transfers. The program crowds out informal transfers received by the targeted households, but this is driven mainly by outside-village transfers. Treated ultra-poor households become more likely to both give and receive transfers to/from wealthier households within their village; and less likely to receive transfers from their employers. As a result, the reciprocity of their within-village transfers increases. The findings imply that, within rural communities, there is positive assortative matching by socio-economic status. A reduction in poverty enables households to engage more in reciprocal transfer arrangements and lowers the interlinkage of their labor with informal insurance.
A giant peritoneal loose body impacted in the pelvic cavity, a rare and interesting finding during laparotomy
Authors: Mohammed Ayad A.
Published: October 2020

Background:

Peritoneal loose bodies (sometimes termed as peritoneal mice) are rare findings that may be discovered incidentally during laparotomy or at autopsy. They consist of densely hyalinized, laminated, fibrous tissue which is arranged in multiple concentric layers. They arise from epiploic appendices which undergo torsion, ischemia and necrosis, saponification and then calcification. In most patients they cause no symptoms or nonspecific symptoms.

Case Presentation:

A 67-year-old male presented with lower abdominal pain and constipation for 3 months. Abdominal examination showed a fixed palpable mass in the lower abdomen arising from the pelvic cavity, the mass was firm, not tender and not mobile.

Magnetic resonance imaging of the pelvis showed a large lobulated 10×70 cm abdominal mass with no significant enhancement. During laparotomy there was a large smooth and firm intraperitoneal mass which was attached by small pedicle to the omentum. Extraction of the mass was performed. The cut surface of the mass showed multiple concentric layers with a central stone like structure. Histopathologic evaluation revealed extensive fibrous tissue with mild inflammatory cells infiltration and areas of calcifications.

Conclusion:

The most important critical step in the management of peritoneal loose bodies is to distinguish them from other intraperitoneal masses particularly tumors which is sometimes very difficult and may require some invasive procedures including surgery, surgery may also be required for large symptomatic masses.
Assessment of Cerebral Vasomotor Reactivity in Patients With Primary Open-angle Glaucoma and Ocular Hypertension Using the Breath-Holding Index
Authors: Arslan Gurcan D. , Olgun Ali , Ozcan Delil , Gökcal Elif , Guven Dilek , Asil Talip
Published: October 2020

Précis:

Patients with ocular hypertension (OHT) do not show impaired cerebral vasodilation responses to hypercapnia but patients with primary open-angle glaucoma (POAG) do. Impaired vasoreactivity in patients with POAG may have neuronal or vascular origins and increase stroke risk.

Purpose:

To investigate changes in cerebral blood flow and cerebral vasomotor reactivity using the breath-holding index in patients with POAG and OHT, to examine whether these parameters contribute to the risk of ischemic stroke.

Methods:

Thirty patients with POAG, 30 patients with OHT, and 30 age- and sex-matched healthy control subjects were included in this university hospital-based, cross-sectional, and observational study. Eyes with a greater degree of visual field loss and/or more severe optic disc damage were selected for the study in patients with POAG, whereas in patients with OHT and controls, the study eye was chosen randomly. The mean blood flow velocity and breath-holding index were measured in the middle cerebral artery ipsilaterally in patient and control groups, by using transcranial Doppler ultrasonography.

Results:

The mean blood flow velocity and breath-holding indexes were significantly lower in patients with POAG than in the control group (all P<0.05). In the OHT group, the mean blood flow velocity and breath-holding indexes were not different from those in the control group.

Conclusions:

Patients with POAG have impaired vasodilation response to hypercapnia. Presumably, the neuronal changes and deterioration of the endothelium-mediated vasodilatation in patients with glaucoma may disrupt the regulation of arteries and potentially present functional insufficiency on vasoreactivity. Moreover, impaired cerebral vascular regulation may contribute to the increased risk of stroke in patients with POAG.
Is Diabetes Mellitus a Blessing in Disguise for Primary Open-angle Glaucoma?
Authors: Hou Huiyuan , Moghimi Sasan , Baxter Sally L. , Weinreb Robert N.
Published: October 2020

Although numbers of studies have addressed this question, the relationship between diabetes mellitus and primary open-angle glaucoma is still unclear. This article discusses progress in understanding the complex relationship between these 2 entities and recent shifts in perspective that challenge the traditional dogma regarding diabetes mellitus and primary open-angle glaucoma. There are still many unanswered questions.
Thrombotic Risk of Rotor Speed Modulation Regimes of Contemporary Centrifugal Continuous-flow Left Ventricular Assist Devices
Authors: Boraschi Andrea , Bozzi Silvia , Thamsen Bente , Granegger Marcus , Wiegmann Lena , Pappalardo Federico , Slepian Marvin J. , Kurtcuoglu Vartan , Redaelli Alberto , De Zélicourt Diane , Consolo Filippo
Published: October 2020

Contemporary centrifugal continuous-flow left ventricular assist devices (LVADs) incorporate dynamic speed modulation algorithms. Hemocompatibility of these periodic unsteady pump operating conditions has been only partially explored. We evaluated whether speed modulation induces flow alterations associated with detrimental prothrombotic effects. For this aim, we evaluated the thrombogenic profile of the HeartWare ventricular assist device (HVAD) Lavare Cycle (LC) and HeartMate3 (HM3) artificial pulse (AP) via comprehensive numerical evaluation of (i) pump washout, (ii) stagnation zones, (iii) shear stress regimens, and (iv) modeling of platelet activation status via the platelet activity state (PAS) model. Data were compared between different simulated operating scenarios, including: (i) constant rotational speed and pump pressure head, used as reference; (ii) unsteady pump pressure head as induced by cardiac pulsatility; and (iii) unsteady rotor speed modulation of the LC (HVAD) and AP (HM3). Our results show that pump washout did not improve across the different simulated scenarios in neither the HVAD nor the HM3. The LC reduced but did not eliminate flow stagnation (–57%) and did not impact metrics of HVAD platelet activation (median PAS: +0.4%). The AP reduced HM3 flow stagnation by up to 91% but increased prothrombotic shear stress and simulated platelet activation (median PAS: +124%). Our study advances understanding of the pathogenesis of LVAD thrombosis, suggesting mechanistic implications of rotor speed modulation. Our data provide rationale criteria for the future design optimization of next generation LVADs to further reduce hemocompatibility-related adverse events.
Health-related Quality of Life for Children With Leukemia: Child and Parental Perceptions
Authors: Ocak Ece , Yozgat Ayca K. , Kacar Dilek , Sucakli Iclal A. , Ozbek Namik Y. , Uneri Ozden S. , Yarali Nese
Published: October 2020

Background:

The importance of health-related quality of life (HRQoL) in patients with acute lymphoblastic leukemia (ALL) has increased in recent years. This study aimed to assess HRQoL in children with ALL, affecting factors, and the relationship between parent proxy-report and child self-report HRQoL.

Materials and Methods:

A total of 59 children and their parents (both mother and father) were enrolled in this cross-sectional study. Turkish version of the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Modules were used to determine HRQoL.

Results:

According to subscales of the self-report form, nausea and operational anxiety scores differed significantly by the treatment status; communication score varied considerably by the hospitalization length of stay; pain and hurt, cognitive problems, and perceived physical appearance scores differed significantly by the maternal chronic disease status (P<0.05). The presence of maternal chronic disease was significantly related to the total score of the parent-proxy report (mother) (P<0.05). There was a moderate correlation between total scores of child and mother (P<0.05, r=0.419) but not with the father.

Conclusion:

Children on-treatment had significant problems in nausea and procedural anxiety subscales; however, children who were hospitalized more had fewer issues in the communication subscale. Also, children whose mother had chronic disease had poorer HRQoL regarding pain and hurt cognitive problems and treatment anxiety. Given the importance of assessment and monitoring HRQoL in children with ALL, health professionals should be aware of how parents’ chronic disease affects HRQoL. Psychosocial support should be provided to children and their parents, especially for those whose parents have a chronic illness.
Thyroid Metastasis From Cutaneous Melanoma on an 18F-FDG PET/CT Study
Authors: León-Asuero-Moreno Ignacio , García-Gómez Francisco Javier , Ríos-Martín Juan José , Álamo-de-la-Gala María del Carmen , Calvo-Morón María Cinta
Published: October 2020

The thyroid gland is an uncommon location for metastasis. We report a 59-year-old woman with a history of cutaneous malignant melanoma. A unique hypermetabolic mass on the left thyroid lobe was identified by control 18F-FDG PET/CT scan, leading to dysphagia and stridor clinic. Total thyroidectomy and lymphadenectomy were performed with histopathological results concordant with metastasis from melanoma. Despite its rarity, finding focal thyroid lesions in patients with an oncological history should alert us, recommending that its metastatic etiology be ruled out.
Geriatric Risk Prediction Models for Major Gastroenterological Surgery Using the National Clinical Database in Japan
Authors: Kofunato Yasuhide , Takahashi Arata , Gotoh Mitsukazu , Kakeji Yoshihiro , Seto Yasuyuki , Konno Hiroyuki , Kumamaru Hiraku , Miyata Hiroaki , Marubashi Shigeru
Published: October 2020

Objectives:

To investigate the effect of geriatric variables on 5 newly added outcomes and create risk models for predicting these outcomes.

Summary of Background Data:

Because there is a current lack of geriatric research focusing on geriatric outcomes using a national surgical database in Japan, there is a need to investigate outcomes associated with major gastro-enterological surgery using these data.

Methods:

This multicenter prospective cohort study was conducted at 26 surgery departments across 21 institutions in Japan using the NCD surgical registry. in total, 22 new geriatric variables were imported from the ACS National Surgical Quality Improvement Program geriatric pilot study. The following 5 geriatric outcomes were defined: (1) postoperative delirium, (2) physical function on postoperative day 30, (3) fall risk on discharge, (4) discharge other than home with social service, and (5) functional decline on discharge, and geriatric risk prediction models for major gastroenterological surgery were created.

Results:

Between January 2018 and December 2018, data on 3981 procedures from 7 major gastroenterological surgeries were collected and analyzed. Older age and preoperative geriatric variables (Origin status from home, History of dementia, Use of mobility aid, fall history, and not competent on admission) were strongly associated with postoperative outcomes. Geriatric risk prediction models for these outcomes were created, with C-statistic values ranging from 0.74 to 0.90, demonstrating model validity and sufficiency of fit.

Conclusions:

The risk models for the newly defined 5 geriatric outcomes that we created can be used in the decision-making process or provision of care in geriatric patients.
Cost-effectiveness of Restrictive Strategy Versus Usual Care for Cholecystectomy in Patients With Gallstones and Abdominal Pain (SECURE-trial)
Authors: Latenstein Carmen S.S. , Wennmacker Sarah Z. , van Dijk Aafke H. , Drenth Joost P.H. , Westert Gert P. , van Laarhoven Cornelis J.H.M. , Boermeester Marja A. , de Reuver Philip R. , Dijkgraaf Marcel G.W. ,   on behalf of the SECURE trial collaborators
Published: October 2020

Objective:

To perform a cost-effectiveness analysis of restrictive strategy versus usual care in patients with gallstones and abdominal pain.

Summary of Background Data:

A restrictive selection strategy for surgery in patients with gallstones reduces cholecystectomies, but the impact on overall costs and cost-effectiveness is unknown.

Methods:

Data of a multicentre, randomized-controlled trial (SECURE-trial) were used. Adult patients with gallstones and abdominal pain were included. Restrictive strategy was economically evaluated against usual care from a societal perspective. Hospital-use of resources was gathered with case-report forms and out-of-hospital consultations, out-of-pocket expenses, and productivity loss were collected with questionnaires. National unit costing was applied. The primary outcome was the cost per pain-free patient after 12 months.

Results:

All 1067 randomized patients (49.0 years, 73.7% females) were included. After 12 months, 56.2% of patients were pain-free in restrictive strategy versus 59.8% after usual care. The restrictive strategy significantly reduced the cholecystectomy rate with 7.7% and reduced surgical costs with €160 per patient, €162 was saved from a societal perspective. The cost-effectiveness plane showed that restrictive strategy was cost saving in 89.1%, but resulted in less pain-free patients in 88.5%. Overall, the restrictive strategy saved €4563 from a societal perspective per pain-free patient lost.

Conclusions:

A restrictive selection strategy for cholecystectomy saves €162 compared to usual care, but results in fewer pain-free patients. The incremental cost per pain-free patient are savings of €4563 per pain-free patient lost. The higher societal willingness to pay for 1 extra pain-free patient, the lower the probability that the restrictive strategy will be cost-effective.

Trial registration:

The Netherlands National Trial Register NTR4022. Registered on 5 June 2013.
The Surge in Deceased Liver Donors Due to the Opioid Epidemic: Is It Time to Split the Difference?
Authors: Yoeli Dor , Choudhury Rashikh A. , Nydam Trevor L. , Pomposelli James J. , Goss John A. , Pomfret Elizabeth A. , Wachs Michael E. , Adams Megan A.
Published: October 2020

Background.

This study aimed to compare trends in use of drug overdose (DO) donors in adult versus pediatric liver transplants and the utilization of split liver transplantation in this donor population.

Methods.

The United Network for Organ Sharing database was reviewed for deceased donor liver transplants from March 2002 to December 2017. Recipients were categorized by donor mechanism of death. Donor splitting criteria was defined as age <40 y, single vasopressor or less, transaminases no >3 times the normal limit, and body mass index ≤ 28 kg/m2.

Results.

Adult liver transplants from DO donors increased from 2% in 2002 to 15% in 2017, while pediatric liver transplants from DO donors only increased from <1% to 3% in the same time. While 28% of DO donors met splitting criteria, only 3% of those meeting splitting criteria were used as a split graft. Both pediatric and adult recipients of DO donor livers achieved excellent patient and graft survival.

Conclusions.

DO donors are underutilized in pediatric liver transplantation. Increased splitting of DO donor livers could significantly decrease, if not eliminate, the pediatric liver waiting list.
Understanding the value of clinical symptoms of COVID-19. A logistic regression model
Authors: Fleitas Pedro E. , Paz Jorge A. , Simoy Mario I. , Vargas Carlos , Cimino Rubén O. , Krolewiecki Alejandro J. , Aparicio Juan P.
Published: October 2020

Background

The new coronavirus SARS-CoV-2, the causative agent of COVID-19, is responsible for the current pandemic outbreak worldwide. However, there is limited information regarding the set of specific symptoms of COVID-19. Therefore, the objective of this study was to describe the main symptoms associated with COVID-19 to aid in the clinical diagnosis for the rapid identification of cases.

Methods and findings

A cross sectional study of all those diagnosed by RT-PCR for SARS-CoV-2 between April 1 and May 24 in Argentina was conducted. The data includes clinical and demographic information from all subjects at the time of presentation, which were uploaded to the centralized national reporting system at health centers. A total of 67318 individuals were included in this study, where 12% tested positive for SARS-CoV-2. The study population was divided in two age groups, a group aged 0 to 55 years-old (<56 group), (median = 32, n=48748) and another group aged 56 to 103 years-old (≥56 group) (median =72, n=18570). Multivariate logistic regression analyses showed that out of a total of 23 symptoms, only five were found to have a positive association with COVID-19: anosmia (odds ratio [OR] 10.40, 95% confidence interval [CI] 8.20-13.10, <56 group; OR 6.09 CI 3.05-12.20, ≥56 group) dysgeusia (OR 3.67, CI 2.7-4.9, <56 group; OR 3.53 CI 1.52-8.18, ≥56 group), low grade fever (37.5-37.9° C) (OR 1.61, CI 1.20-2.05, <56 group; OR 1.80 CI 1.07-3.06, ≥56 group), cough (OR 1.20, CI 1.05-1.38, <56 group; OR 1.37 CI 1.04-1.80, ≥56 group) and headache only in <56 group (OR 1.71, CI 1.48-1.99). In turn, at the time of presentation, the symptoms associated with respiratory problems: chest pain, tachypnea, dyspnea, respiratory failure and use of accessory muscles for breathing, had a negative association with COVID-19 (OR <1) or did not present statistical relevance (OR = 1).

With the intention of helping the clinical diagnosis, we designed a model to be able to identify possible cases of COVID-19. This model included 16 symptoms, the age and sex of the individuals, and was able to detect 80% of those infected with SARS-CoV-2 with a specificity of 46%.

Conclusions

The analysis of symptoms opens the opportunity for a guidance and improved symptoms based definition of suspected cases of COVID-19, where multiple factors (age, sex, symptoms and interaction between symptoms) are considered. We present a tool to help identify COVID-19 cases to provide quick information to aid decision-making by health personnel and program managers.
Recovery of monocyte exhaustion is associated with resolution of lung injury in COVID-19 convalescence
Authors: Scott N.A. , Knight S.B. , Pearmain L. , Brand O. , Morgan D.J. , Jagger C. , Khan S. , Hackney P. , Smith L. , Menon M. , Konkel J. E. , Shuwa H. A. , Franklin M. , Kästele V. , Harbach S. , Brij S. , Ustianowski A. , Uriel A. , Lindergard G. , Bakerly N. Diar , Dark P. , Mathioudakis A.G. , Gray K.J. , Lord G.M. , Felton T. , Brightling C. , Ho L-P ,   NIHR Respiratory TRC,   CIRCO, Hanley K. Piper , Simpson A. , Grainger J.R. , Hussell T. , Mann E.R.
Published: October 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the clinical syndrome COVID-19 is associated with an exaggerated immune response and monocyte infiltrates in the lungs and other peripheral tissues. It is now increasingly recognised that chronic morbidity persists in some patients. We recently demonstrated profound alterations of monocytes in hospitalised COVID-19 patients. It is currently unclear whether these abnormalities resolve or progress following patient discharge. We show here that blood monocytes in convalescent patients at their 12 week follow up, have a greater propensity to produce pro-inflammatory cytokines TNFα and IL-6, which was consistently higher in patients with resolution of lung injury as indicated by a normal chest X-ray and no shortness of breath (a key symptom of lung injury). Furthermore, monocytes from convalescent patients also displayed enhanced levels of molecules involved in leucocyte migration, including chemokine receptor CXCR6, adhesion molecule CD31/PECAM and integrins VLA-4 and LFA-1. Expression of migration molecules on monocytes was also consistently higher in convalescent patients with a normal chest X-ray. These data suggest persistent changes in innate immune function following recovery from COVID-19 and indicate that immune modulating therapies targeting monocytes and leucocyte migration may be useful in recovering COVID-19 patients with persistent symptoms.
CTCF-binding element regulates ESC differentiation via orchestrating long-range chromatin interaction between enhancers and HoxA
Authors: Su Guangsong , Wang Wenbin , Chen Jun , Liu Man , Zheng Jian , Guo Dianhao , Bi Jinfang , Zhao Zhongfang , Shi Jiandang , Zhang Lei , Lu Wange
Published: October 2020

Proper expressions of Homeobox A cluster genes (HoxA) are essential for embryonic stem cells (ESC) differentiation and individual development. However, the mechanisms underlying controlling precise spatiotemporal expressions ofHoxAduring early ESC differentiation remain poorly understood. Herein, we identified a functional CTCF-binding element (CBE+47) closest to the 3’-end ofHoxAwithin the same topologically associated domain (TAD) in ESC. CRISPR-Cas9 mediated the CBE+47deletion significantly promotes retinoic acid (RA)-inducedHoxAexpression and early ESC abnormal differentiation. In delineating its underlying mechanisms, we find that CBE+47can precisely organize chromatin interactions between its adjacent enhancers andHoxAby using chromosome conformation capture assay (Capture-C). Furthermore, we also find that its adjacent enhancers as enhancer-enhancer interaction complex (EEIC) are required for RA-inducedHoxAactivation. Collectively, these results provide a new insight for RA-inducedHoxAexpression, also highlight the unique and precise regulatory roles of CBE in ESC differentiation.
Leveraging Sequential and Spatial Neighbors Information by Using CNNs Linked With GCNs for Paratope Prediction
Authors: Lu Shuai , Li Yuguang , Wang Fei , Nan Xiaofei , Zhang Shoutao
Published: October 2020

Antibodies consisting of variable and constant regions, are a special type of proteins playing a vital role in immune system of the vertebrate. They have the remarkable ability to bind a large range of diverse antigens with extraordinary affinity and specificity. This malleability of binding makes antibodies an important class of biological drugs and biomarkers. In this article, we propose a method to identify which amino acid residues of an antibody directly interact with its associated antigen based on the features from sequence and structure. Our algorithm uses convolution neural networks (CNNs) linked with graph convolution networks (GCNs) to make use of information from both sequential and spatial neighbors to understand more about the local environment of target amino acid residue. Furthermore, we process the antigen partner of an antibody by employing an attention layer. Our method improves on the state-of-the-art methodology.
MCM complexes are barriers that restrict cohesin-mediated loop extrusion
Authors: Dequeker Bart J. H. , Brandão Hugo B. , Scherr Matthias J. , Gassler Johanna , Powell Sean , Gaspar Imre , Flyamer Ilya M. , Tang Wen , Stocsits Roman , Davidson Iain F. , Peters Jan-Michael , Duderstadt Karl E. , Mirny Leonid A. , Tachibana Kikuё
Published: October 2020

Eukaryotic genomes are compacted into loops and topologically associating domains (TADs), which contribute to transcription, recombination and genomic stability. Cohesin extrudes DNA into loops that are thought to lengthen until CTCF boundaries are encountered. Little is known about whether loop extrusion is impeded by DNA-bound macromolecular machines. We demonstrate that the replicative helicase MCM is a barrier that restricts loop extrusion in G1 phase. Single-nucleus Hi-C of one-cell embryos revealed that MCM loading reduces CTCF-anchored loops and decreases TAD boundary insulation, suggesting loop extrusion is impeded before reaching CTCF. Single-molecule imaging shows that MCMs are physical barriers that frequently constrain cohesin translocationin vitro.Simulations are consistent with MCMs as abundant, random barriers. We conclude that distinct loop extrusion barriers contribute to shaping 3D genomes.

One Sentence Summary

MCM complexes are obstacles that impede the formation of CTCF-anchored loops.
An improved comprehensive strategy for deep and quantitative N-glycomics based on optimization of sample preparation, isotope-based data quality control and quantification, new N-glycan libraries and new algorithms
Authors: Guan Yudong , Hu Jiaxiang , Cao Weiqian , Cui Wencong , Yang Fan , Krisp Christoph , Lin Ling , Zhang Min , Voss Hannah , Schuster Raphael , Yan Guoquan , Fuh Marceline Manka , Thaysen-Andersen Morten , Packer Nicolle H. , Shen Huali , Yang Pengyuan , Schlüter Hartmut
Published: October 2020

Withdrawal statement

“The authors have withdrawn their manuscript because the authors need to re-organize the data and writing, meanwhile more experimental evidence from human cellular N-glycome will be added to support their viewpoints. In this preprint, only one human cell line, Acute Promyelocytic Leukemia (APL) cells, was deeply investigated to show the N-glycome landscape. To provide the shared features of human N-glycome, more human cells should be investigated. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.”
cognac: rapid generation of concatenated gene alignments for phylogenetic inference from large whole genome sequencing datasets
Authors: Crawford Ryan D. , Snitkin Evan S.
Published: October 2020

The quantity of genomic data is expanding at an increasing rate. Tools for phylogenetic analysis which scale to the quantity of available data are required. We present cognac, a user-friendly software package to rapidly generate concatenated gene alignments for phylogenetic analysis. We applied this tool to generate core gene alignments for very large genomic datasets, including a dataset of over 11,000 genomes from the genusEscherichiacontaining 1,353 genes, which was constructed in less than 17 hours. We have released cognac as an R package (https://github.com/rdcrawford/cognac) with customizable parameters for adaptation to diverse applications.
Quantitative glycoproteomics reveals cellular substrate selectivity of the ER protein quality control sensors UGGT1 and UGGT2
Authors: Adams Benjamin M. , Canniff Nathan P. , Guay Kevin P. , Larsen Ida Signe Bohse , Hebert Daniel N.
Published: October 2020

UDP-glucose: glycoprotein glucosyltransferase (UGGT) 1 and 2 are central hubs in the chaperone network of the endoplasmic reticulum (ER), acting as gatekeepers to the early secretory pathway yet little is known about their cellular clients. These two quality control sensors control lectin chaperone binding and glycoprotein egress from ER. A quantitative glycoproteomics strategy was deployed to identify cellular substrates of the UGGTs at endogenous levels in CRISPR-edited HEK293 cells. The seventy-one UGGT substrates identified were mainly large multidomain and heavily glycosylated proteins when compared to the general N-glycome. UGGT1 was the dominant glucosyltransferase with a preference towards large plasma membrane proteins whereas UGGT2 favored the modification of smaller, soluble lysosomal proteins. This study sheds light on differential specificities and roles of UGGT1 and UGGT2 and provides insight into the cellular reliance on carbohydrate-dependent chaperone intervention by UGGT1 and UGGT2 to facilitate proper folding and maturation of the cellular N-glycome.
Functional repertoire convergence of distantly related eukaryotic plankton lineages revealed by genome-resolved metagenomics
Authors: Delmont Tom O. , Gaia Morgan , Hinsinger Damien D. , Fremont Paul , Vanni Chiara , Guerra Antonio Fernandez , Eren A. Murat , Kourlaiev Artem , d’Agata Leo , Clayssen Quentin , Villar Emilie , Labadie Karine , Cruaud Corinne , Poulain Julie , Da Silva Corinne , Wessner Marc , Noel Benjamin , Aury Jean-Marc ,   Tara Oceans Coordinators, de Vargas Colomban , Bowler Chris , Karsenti Eric , Pelletier Eric , Wincker Patrick , Jaillon Olivier
Published: October 2020

Marine planktonic eukaryotes play a critical role in global biogeochemical cycles and climate. However, their poor representation in culture collections limits our understanding of the evolutionary history and genomic underpinnings of planktonic ecosystems. Here, we used 280 billionTaraOceans metagenomic reads from polar, temperate, and tropical sunlit oceans to reconstruct and manually curate more than 700 abundant and widespread eukaryotic environmental genomes ranging from 10 Mbp to 1.3 Gbp. This genomic resource covers a wide range of poorly characterized eukaryotic lineages that complement long-standing contributions from culture collections while better representing plankton in the upper layer of the oceans. We performed the first comprehensive genome-wide functional classification of abundant unicellular eukaryotic plankton, revealing four major groups connecting distantly related lineages. Neither trophic modes of plankton nor its vertical evolutionary history could explain the functional repertoire convergence of major eukaryotic lineages that coexisted within oceanic currents for millions of years.

Cover

Navigating on the map of plankton genomics withTaraOceans and anvi’o: a comprehensive genome-resolved metagenomic survey dedicated to eukaryotic plankton.
Mosaic changes to the global transcriptome in response to inhibiting ribosome formation versus inhibition of ribosome function
Authors: Shamsuzzaman Md , Rahman Nusrat , Gregory Brian , Bruno Vincent M , Lindahl Lasse
Published: October 2020

Cell fate is susceptible to several internal and external stresses. Stress resulting from mutations in genes for ribosomal proteins and assembly factors leads to many congenital diseases, collectively called ribosomopathies. Even though such mutations all depress the cell’s protein synthesis capacity, they are manifested in many different phenotypes. This prompted us to useSaccharomyces cerevisiaeto explore whether reducing the protein synthesis capacity by different mechanisms result in the same or different changes to the global transcriptome. We have compared the transcriptome after abolishing the assembly of new ribosomes and inhibiting the translocation of ribosomes on the mRNA. Our results show that these alternate obstructions generate different mosaics of expression for several classes of genes, including genes for ribosomal proteins, mitotic cell cycle, cell wall synthesis, and protein transport.
Computational and experimental analyses of mitotic chromosome formation pathways in fission yeast
Authors: Gerguri Tereza , Fu Xiao , Kakui Yasutaka , Khatri Bhavin S. , Barrington Christopher , Bates Paul A. , Uhlmann Frank
Published: October 2020

Underlying higher order chromatin organization are Structural Maintenance of Chromosomes (SMC) complexes, large protein rings that entrap DNA. The molecular mechanism by which SMC complexes organize chromatin is as yet incompletely understood. Two prominent models posit that SMC complexes actively extrude DNA loops (loop extrusion), or that they sequentially entrap two DNAs that come into proximity by Brownian motion (diffusion capture). To explore the implications of these two mechanisms, we perform biophysical simulations of a 3.76 Mb-long chromatin chain, the size of the longS. pombechromosome I left arm. On it, the SMC complex condensin is modeled to perform loop extrusion or diffusion capture. We then compare computational to experimental observations of mitotic chromosome formation. Both loop extrusion and diffusion capture can result in native-like contact probability distributions. In addition, the diffusion capture model more readily recapitulates mitotic chromosome axis shortening and chromatin density enrichment. Diffusion capture can also explain why mitotic chromatin shows reduced, as well as more anisotropic, movements, features that lack support from loop extrusion. The condensin distribution within mitotic chromosomes, visualized by stochastic optical reconstruction microscopy (STORM), shows clustering predicted from diffusion capture. Our results inform the evaluation of current models of mitotic chromosome formation.