bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tibial Intramedullary Nail From a Suprapatellar Approach in a Semi-Extended Position
Authors: Darnley James E. , Petersen Kyle A. , Siesel Craig , Gelman Scott , Miller Eric T. 
Published: July 2020

Summary:
An intramedullary nail is a common and reliable treatment option for diaphyseal tibial fractures. One such approach for this technique is suprapatellar. This video shows the surgical technique of a tibial nail through a suprapatellar approach in a semi-extended position in a 22-year-old man with a distal third tibial shaft fracture.
Grossing Breast Cancer Specimens: A Comprehensive Review
Authors: Agarwal Apeksha N. , Ritter Jacob , Dornbluth Nella C. , Mais Daniel D. , Nazarullah Alia N. 
Published: July 2020

Abstract
Grossing breast specimens presents a unique challenge in the anatomic pathology laboratory, because the approach varies with the type of specimen received, the preoperative diagnosis, and the administration of neoadjuvant therapy. Furthermore, careful attention to preanalytic variables, such as time of fixation, is required. The specimen often lacks orienting anatomic landmarks, and accurately documenting margins in 3 dimensions requires a deliberate approach that is easily understood for future reference. This article will provide a comprehensive source for grossing commonly received breast specimens, ranging from surgical biopsies to modified radical mastectomies and will describe the proper care of preanalytical measures to avoid compromise of biomarkers, methods to ensure adequate sampling of tissue for diagnosis, and assessment of tumor burden following neoadjuvant treatment.
Favorable Outcomes of Liver Transplantation from Controlled Circulatory Death Donors Using Normothermic Regional Perfusion Compared to Brain Death Donors
Authors: Savier Eric , Lim Chetana , Rayar Michel , Orlando Francesco , Boudjema Karim , Mohkam Kayvan , Lesurtel Mickael , Mabrut Jean Yves , Pittau Gabriella , Begdadi Nassiba , Cherqui Daniel , Adam René , Dondero Federica , Sepulveda Ailton , Soubrane Olivier , Bucur Petru , Barbier Louise , Salame Ephrem , Jasseron Carine , Antoine Corinne , Riou Bruno , Scatton Olivier 
Published: July 2020

Background.
Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT.

Methods.
This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT.

Results.
A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1–4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68).

Conclusions.
This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.
Pulse-Controlled Amplification – a new powerful tool for front-line diagnostics
Authors: Müller Katharina , Daßen Sarah , Holowachuk Scott , Zwirglmaier Katrin , Stehr Joachim , Buersgens Federico , Ullerich Lars , Stoecker Kilian 
Published: July 2020

ABSTRACTMolecular diagnostics has become essential in the identification of many infectious diseases, and the detection of nucleic acids often serves as the gold standard technique for most infectious agents. However, established techniques like polymerase chain reaction (PCR) are time-consuming laboratory-bound techniques. Here we present an alternative method for the rapid identification of infectious agents using pulse-controlled amplification (PCA). PCA is a next generation nucleic acid amplification technology that uses rapid energy pulses to heat microcyclers (micro-scale metal heating elements embedded directly in the amplification reaction) for a few microseconds, thus only heating a small fraction of the reaction volume. The heated microcyclers cool off nearly instantaneously, resulting in ultra-fast heating and cooling cycles during which classic amplification of a target sequence takes place. This reduces the overall amplification time by a factor of up to 10, enabling a sample-to-result workflow in just 15 minutes, while running on a small and portable prototype device. We could demonstrate the efficacy of this technology in two assays, one for a nosocomial context targeting MecA conferred antibiotic resistance, and one for a biothreat scenario targeting Yersinia pestis. The observed limits of detection were 10 copies per reaction (purified DNA) for MecA in a methicillin resistant Staphylococcus aureus and 434 copies per reaction (purified DNA) or 9.8 cells per reaction (crude sample) of Yersinia pestis. Thus, PCA offers a decentralization of molecular diagnostics and is applicable whenever rapid, on-site detection of infectious agents is needed.
Foundational research and NIH funding enabling Emergency Use Authorization of remdesivir for COVID-19
Authors: Cleary Ekaterina Galkina , Jackson Matthew J. , Folchman-Wagner Zoë , Ledley Fred D. 
Published: July 2020

ABSTRACTEmergency Use Authorization for remdesivir months after discovery of COVID-19 is unprecedented. Typically, decades of research and public-sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to remdesivir’s biological target, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research 2000–2019. There were 6,567 RdRp-related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project Years with Costs of $1,875 million. NIH support for NcAn research comprised 4,607 Project Years with Costs of $4,612 million. Research Project grants accounted for 63% and 48% of Project Years for RdRp and NcAn respectively, but only 19% and 12% of Project Costs. Analytical modeling of research maturation estimates that RdRp and NcAn research passed an established maturity threshold in 2008 and 1994 respectively. Of 97 investigational compounds targeting RdRp since 1989, the three authorized for use entered clinical trials after both thresholds. This work demonstrates the scale of foundational research on the biological target and parent chemical structure of remdesivir that supported its discovery and development for COVID-19. This work identifies $6.5 billion in NIH funding for research leading to remdesivir, underscoring the role of public sector investments in basic research and research infrastructure that underlie new drugs and the response to emergent disease.SIGNIFICANCE STATEMENTEmergency Use Authorization of remdesivir for treating COVID-19 four months after discovery of this virus was enabled by decades of research on the drug’s biological target as well as other medicines with related chemical structures. The NIH contributed 6,800 years of grant funding to this research, totaling $6.5 billion (2000–2019), including funding for both investigator-initiated research and research infrastructure. Of this, $46.5 million was for research directly related to remdesivir. This analysis demonstrates the importance of a robust body of foundational research in responding rapidly to emergent diseases, and the substantial NIH contribution to this research. It also underscores the scale and significance of the public-sector investments that enable new drug discovery and development.
Daily viral kinetics and innate and adaptive immune responses assessment in COVID-19: a case series
Authors: Vetter Pauline , Eberhardt Christiane , Meyer Benjamin , Martinez Murillo Paola Andrea , Torriani Giulia , Pigny Fiona , Lemeille Sylvain , Cordey Samuel , Laubscher Florian , Vu Diem-Lan , Calame Adrien , Schibler Manuel , Jacquerioz Frederique , Rohner Géraldine Blanchard , Siegrist Claire-Anne , Kaiser Laurent , Didierlaurent Arnaud M , Eckerle Isabella 
Published: July 2020

AbstractBackgroundViral shedding patterns and its correlation with the immune responses of mildly symptomatic COVID-19 patients are still poorly characterized.MethodsWe enrolled the first five COVID-19 patients quarantined in our institution; none received immunomodulatory treatment. We monitored shedding of viral RNA and infectious virus by RT-PCR and cell culture from the upper respiratory tract, and characterized the kinetics of systemic innate and adaptive immune responses.ResultsDespite mild clinical disease, high viral loads and shedding of infectious virus were observed from the respiratory tract, with isolation of infectious virus and prolonged positivity by PCR up to day 7 and 19 post onset of symptoms, respectively. Robust innate responses characterized by an increase in activated CD14+CD16+ monocytes and cytokine responses were observed as early as 2 days after symptoms onset. Cellular and humoral SARS-CoV-2 specific adaptive responses were detectable in all patients.ConclusionInfectious virus shedding was limited to the first week of symptom onset in mild cases. A strong innate response, characterized by the mobilization of activated monocytes during the first days of infection, as well as SARS-CoV-2 specific antibodies were detectable, even in patients with mild disease.SummaryWe describe viral and immune profiles of the first five SARS-CoV-2 patients in our institution, showing high viral loads and infectious viral shedding in early acute disease. Mild patients mount an innate response sufficient for viral control and specific immunity.
Atmosome: The Personal Atmospheric Exposome
Authors: Bhimaraju Hari , Pandey Vaibhav , Nag Nitish , Jain Ramesh 
Published: July 2020

AbstractModern health research is increasingly separated into various “omics” fields. Omics provides a quantified approach to the total collective information about the various realms of biology. One aspect of omics called the exposome relates to the collective exposures an individual is placed in throughout their life. A subset of this exposome, is the atmospheric exposome, which we name as the “atmosome”. Air surrounds individuals from the moment they are born till they take their last breath. The atmosphere is constantly changing, given our location and surroundings are always dynamic throughout life. The atmosphere inevitably plays a massive role in our health such as impact on DNA damage, metabolism, skin integrity, and lung health. In this work, we discuss the significance of the atmosome in personalized health and present our atmosome sensing system. We developed and analyzed data from our IoT, microcontroller-based system which collects real-time individual air quality data and posts it to a cloud server for immediate access. Our experimental results demonstrate the accuracy of the data we collected and the avenues our system creates for direct lifestyle to environment correlations. Quantifying the individual atmosome is a next step in advancing personalized health and medical research. Our two main goals in this paper are to present the atmosome as a concept and to explain how to track it using low-cost electronics.
Three Dimensional Multi-gene Expression Maps Reveal Cell Fate Changes Associated with Laterality Reversal of Zebrafish Habenula
Authors: Wang Guo-Tzau , Pan He-Yen , Lang Wei-Han , Yu Yuan-Ding , Hsieh Chang-Huain , Kuan Yung-Shu 
Published: July 2020

ABSTRACTThe conserved bilateral habenular nuclei (HA) in vertebrate diencephalon develop into compartmentalized structures containing neurons derived from different cell lineages. Despite extensive studies demonstrated that zebrafish larval HA display distinct left-right (L-R) asymmetry in gene expression and connectivity, the spatial gene expression domains were mainly obtained from two-dimensional (2D) snapshots of colorimetric RNAin situhybridization staining which could not properly reflect different HA neuronal lineages constructed in three-dimension (3D). Combing the tyramide-based fluorescent mRNAin situhybridization, confocal microscopy and customized imaging processing procedures, we have created spatial distribution maps of four genes for 4 day old zebrafish and in sibling fish whose L-R asymmetry was spontaneously reversed. 3D volumetric analyses showed that ratios ofcpd2, lov, ronandnrp1aexpression in L-R reversed HA were reversed according to the parapineal positions. However, the quantitative changes of gene expression in reversed larval brains do not mirror the gene expression level in the obverse larval brains. There were a total 87.78% increase oflov+nrp1a+and a total 12.45% decrease oflov+ron+double-positive neurons when the L-R asymmetry of HA was reversed. Thus, our volumetric analyses of the 3D maps indicate that changes of HA neuronal cell fates are associated with the reversal of HA laterality. These changes likely account for the behavior changes associated with HA laterality alterations.
A model of traumatic brain injury using human iPSC-derived cortical brain organoids
Authors: Lai Jesse D. , Berlind Joshua E. , Fricklas Gabriella , Maria Naomi Sta , Jacobs Russell , Yu Violeta , Ichida Justin K. 
Published: July 2020

AbstractTraumatic brain injury confers a significant and growing public health burden and represents a major environmental risk factor for dementia. Previous efforts to model traumatic brain injury and elucidate pathologic mechanisms have been hindered by complex interactions between multiple cell types, biophysical, and degenerative properties of the human brain. Here, we use high-intensity focused ultrasound to induce mechanical injury in 3D human pluripotent stem cell-derived cortical organoids to mimic traumatic brain injuryin vitro. Our results show that mechanically injured organoids recapitulate key hallmarks of traumatic brain injury, phosphorylation of tau and TDP-43, neurodegeneration, and transcriptional programs indicative of energy deficits. We present high-intensity focused ultrasound as a novel, reproducible model of traumatic brain injury in cortical organoids with potential for scalable and temporally-defined mechanistic studies.
Validation and Long-Term Follow Up of CD33 Off-Targets Predicted In Vitro and In Silico Using Error-Corrected Sequencing in Rhesus Macaques
Authors: AlJanahi Aisha A. , Lazzarotto Cicera R. , Chen Shirley , Shin Tae-Hoon , Cordes Stefan , Jabara Isabel , Zhou Yifan , Young David , Lee Byung-Chul , Yu Kyung-Rok , Li Yuesheng , Toms Bradley , Tunc Ilker , Hong So Gun , Truitt Lauren L. , Klermund Julia , Kim Miriam Y. , Cathomen Toni , Gill Saar , Tsai Shengdar Q. , Dunbar Cynthia E. 
Published: July 2020

ABSTRACTThe programmable nuclease technology CRISPR/Cas9 has revolutionized gene editing in the last decade. Due to the risk of off-target editing, accurate and sensitive methods for off-target characterization are crucial prior to applying CRISPR/Cas9 therapeutically. Here, we utilized a rhesus macaque model to ask whether CIRCLE-Seq (CS), anin vitrooff-target prediction method, more accurately identifies off-targets compared toin silicoprediction (ISP) based solely on genomic sequence comparisons. We use AmpliSeq HD error-corrected sequencing to validate off-target sites predicted by CIRCLE-Seq and ISP for guide RNAs designed againstTET2andCD33genes. A gRNA targeting TET2 designed using modern algorithms and predicted to have low off-target risk by both ISP and CIRCLE-Seq created no detectable mutations at off-target sites in hematopoietic cells following transplantation, even when applying highly sensitive error-corrected sequencing. In contrast, aCD33gRNA designed using less robust algorithms with over 10-fold more off-targets sites predicted by both ISP and CIRCLE-Seq, however there was poor correlation between the sites predicted by the two methods. When almost 500 sites identified by each method were searched for in hematopoietic cells following transplantation, 19 detectable mutations in off-target sites were detected via error-corrected sequencing. Of these 19 sites, 8 sites were predicted in the top 500 sites by both methods, 8 by CIRCLE-Seq only, and 3 by ISP only. Cells with off-target editing exhibited no expansion or abnormal behaviorin vivoin animals followed for up to 2 years. In conclusion, neither methodology predicted all sites, and a combination of careful gRNA design, followed by screening for predicted off-target sites in target cells by multiple methods may be required for optimizing safety of clinical development.
Decoding 3D spatial location across saccades in human visual cortex
Authors: Zhang Xiaoli , Jones Christopher M , Golomb Julie D 
Published: July 2020

AbstractVisual signals are initially processed as two-dimensional images on our retina, but we live in a 3D world. Depth information needs to be reconstructed from the 2D retinal images, using cues such as binocular disparity. But in daily life, we also make frequent, rapid eye movements, which alter the 2D retinal input. How do we achieve stable 3D perception across saccades? Using fMRI pattern analysis, we investigated how 3D spatial representations in human visual cortex are influenced by saccades. Participants viewed stimuli in four possible 3D locations, defined by 2D vertical position (above or below screen center) and depth position (in front of or behind central screen plane). We compared the amount of 2D and depth information in visual cortical regions during no-saccade blocks (stationary fixation) with that during saccade blocks (series of guided saccades). On no-saccade blocks, decoding of stimulus location was highlydependenton fixation position: in later visual areas we could decode both vertical and depth information across blocks that shared the same fixation position (as previously reported), but little vertical or depth information could be decoded across blocks withdifferentfixation positions. Strikingly, the neural similarity patterns appearedtolerantto changes in fixation position during saccade blocks: despite the saccade-induced retinal and fixation changes, we could reliably decode both vertical and depth information. The findings suggest that representations of 3D spatial locations may become more tolerant of fixation positions during dynamic saccades, perhaps due to active remapping which may encourage more stable representations of the world.SignificanceThis study investigates two fundamental challenges for visual perception: how to preserve spatial information across frequent eye movements, and how to integrate binocular depth location with 2D location to form coherent 3D percepts. Aspects of these challenges have been studied in isolation, but surprisingly no studies have investigated them jointly to ask how 3D spatial representations in human visual cortex are influenced by saccades. Our fMRI pattern analysis findings highlight a potentially critical role of active, dynamic saccades on stabilizing 3D spatial representations in the brain, revealing that representations of 3D space may be modulated by eye position during sustained fixation, but could become tolerant of changes in eye position during active, dynamic saccades.
An overview of the existing problems faced by Pakistani women in agriculture: conclusion and recommendation
Authors: Muhammad Faheem , Hassan Muhammad Azher , Mehmood Tariq 
Published: July 2020

Purpose
The purpose of this paper is an attempt to cover available literature on natural resource management, which reflects the involvement of Pakistan communities living in different regions for sustainable management in agriculture, forestry and livestock sectors differentiated by women. In addition, it was also highlighted about the lack of access to productive resources for rural women farmers. The conclusion was drawn and key recommendation were suggested.

Design/methodology/approach
It is authors real-life experiences or observations in a given field to support colleagues in a variety of ways including advising, establishing best practices and noting trends.

Findings
It was concluded that there are no opportunities such as training of most advanced launched technologies for the sake of better crop production, dairy and fisheries sector sustainable development, as well as the availability of microfinance to support the women farmers in Pakistan rural areas to make them self-dependent.

Originality/value
The opinions and key recommendations are genuine and useful, which should be adopted for the more bright future of women farmers, especially in Pakistan’s rural area.
Is there transgender bias in the courtroom?
Authors: Honorée André L. , Juban Rusty 
Published: July 2020

PurposeThis study examines whether various judicial demographic and political characteristics have an influence on case outcomes in transgender employment discrimination cases. Specifically, it assesses whether the race, sex or political party of federal judges result in significantly different employment case outcomes for transgender employees in the US district courts.Design/methodology/approachUtilizing a legal database of all federal employment discrimination cases over the past five decades, the study ultimately identified 97 cases with transgender plaintiffs. Chi-square and frequency analyses were employed to test the hypotheses regarding the effect of race, sex and political party of federal judges on transgender employment case outcomes.FindingsThe results intimate that both the political party and sex of the judge have an effect on case outcomes. Specifically, the transgender plaintiffs in employment discrimination cases have a greater chance for success when such cases are presided before Democratic and female judges.Practical implicationsThe study's findings of significant differences in case outcomes suggest that characteristics of judges should be taken into account by potential plaintiffs and defendants, as they consider if/how to proceed with their cases.Social implicationsSuch research focuses more attention on the fair and equal treatment principle of the American judicial system due to the significant differences found in case outcomes as a result of judges' characteristics.Originality/valueNo research till date has examined the outcomes of transgender employment discrimination cases in the US despite national surveys indicating the pervasiveness and severity of such discrimination.